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The following Pharmaceutical patents, intellectual property and technologies are offered for sale or license. Viewing these patents and technologies for sale is a free service of IdeaConnection.com. You can post as many patented technologies as you like at no charge. Click on the headings below for more information on each patent.



Oxygen Sensors and their Uses

Brief description Novel oxygen sensors for use in product packaging for storing products under oxygen-free conditions. Basic principle Our novel sensors are based upon a unique synthetic platform technology that enables specific manipulation of oxo-hydroxide materials modified with organic ligands. The sensors consist of redox metal-containing materials that change colour in response to changing oxygen or oxidative environment. These materials may be used as a film, powder, in suspension
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Cytotoxin compounds and methods of isolation

The present invention concerns groups of compounds derived from tunicates of the Synoicum species, as well as to pharmaceutical compositions comprising these compounds, and uses thereof. Extracts from tunicates show selective toxicity against several different cancer cell lines in the NCI 60 cell line panel. These compounds are useful in the effective treatment of cancers, particularly malignant melanomas, colon cancer, and renal cancer cell lines.
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Oral Antidepressant Formulation

TriRima® Product Profile Summary TriRima® is an optimized, specific, high affinity, reversible inhibitor of monoamine oxidase-A (RIMA) potentially useful as monotherapy in the treatment of major depressive disorder. TriRima was designed and developed specifically to maximize RIMA efficacy while minimizing traditional MAOI-class tolerability issues. There is a clear unmet medical need for a robust, well tolerated alternative antidepressant with a proven mechanism of action for non-responder
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Metadichol ® Nano particle and applications ( patent pending)

Metadichol®*(anagram METHODICAL) is a product produced from the waste of our agricultural industry and is present in small amounts in our foods we consume on a daily basis as most of it is lost in our food processing. We suffer from diseases because our immune system gets weakened over time and  leads to death. A enhanced immunity is the key to a longer life. All diseases are reducible to passive or active disturbances of cells. One can mitigate diseases by correcting and manipulating the
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Hydroxy Ceramides and analogs thereof and their use for Preventing or Treating Cancer

Disclosed are compounds, compositions, methods of treatment and synthetic methods for making compounds related to stereoisomers of 2-hydroxy-ceramides and the use of 2-hydroxy-ceramides and their analogs.
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Intelligent Temperature Indicator Label and Method

Our Smart Labels or Time Temperature Indicators (TTI) are researched and designed for use in Cold Chain . The labels provide information regarding the Products Integrity. They monitor whether or not the products have been stored or maintained at the proper temperature and time limits. These smart labels will indicate unsafe storage temperatures and/or expiration dates of food, medical and pharmaceutical products which are no longer safe to be used. Benefi
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Intelligent Temperature Indicator Label and Method

Our Smart Labels or Time Temperature Indicators (TTI) are researched and designed for use in Cold Chain . The labels provide information regarding the Products Integrity. They monitor whether or not the products have been stored or maintained at the proper temperature and time limits. These smart labels will indicate unsafe storage temperatures and/or expiration dates of food, medical and pharmaceutical products which are no longer safe to be used. Benefi
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Biodegradable Self-Expanding Drug-Eluting Prosthesis

Implantable radially expandable medical prostheses for treatment of vascular diseases through percutaneous deployment.
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Indole compounds and their use as radiation sensitizing agents and chemotherapeutic agents

Radiotherapy is the treatment of cancer and other diseases with ionizing radiation. Radiotherapy is used in curative therapy, palliative therapy, adjuvant therapy after or before surgery, simultaneous radio-chemotherapy, etc. Radiotherapy is successful because ionizing radiation kills dividing cells and is thus slightly more toxic to fast growing cancer cells. Radiotherapy may be used to treat localized solid tumors, such as cancers of the skin, tongue, larynx, brain, breast, or uterine cervix.
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Device for Organizing the Administration of Pills At Predetermined Time Intervals

A device for organizing the administration of pills at predetermined time intervals, characterized in that it has a main body used as an individual tissue ring with an opening, through which tissues can be inserted, and that the main body includes at least one compartment (4,4',4''), which can hold at least one pill, covered by at least one lid (5,5',5'').
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Unit Dosage of Apadenoson

The present invention provides a unit dosage of Apadenoson, a pharmacological stress agent, and use of the same as a pharmacologic agent for myocardial perfusion imaging.
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Pyridinone Diketo Acids: Inhibitors of HIV Replication in Combination Therapy.

A new class of diketo acids constructed on pyridinone scaffolds, designed as inhibitors of HTV replication through inhibition of HIV integrase, is described. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents,
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2'-fluoro-6'-methylene Carbocyclic Nucleosides and Methods of Treating Viral Infections

The present invention relates to 2'-Fluoro-6'-methylene carbocyclic nucleosides, pharmaceutical compositions containing these nucleosides and their use in the treatment or prophylaxis of a number of viral infections and secondary disease states and conditions thereof, especially including Hepatitis B virus (HBV) and secondary disease states and conditions thereof (cirrhosis and liver cancer), Heptatitis C virus (HCV), Herpes Simplex virus I and II (HSV-1 and HSV-2), cytomegalovirus (CMV), Varice
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Antimicrobial Composition and Use

Antimicrobial compositions are provided comprising a pharmaceutically acceptable organic acid and a pharmaceutically acceptable surfactant. This synergistic combination allows compositions to be formulated at low concentrations that have efficacy in reducing bacterial counts by greater than 3 log within 5 minutes of contact while preserving the organoleptic properties of treated foods, including fresh produce. As shown in Fig. 1C the efficacy of six different compositions (A. 3% levulinic acid p
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Vaccine for Runting-stunting Syndrome

The present invention includes polypeptides, polynucleotides, antibodies, and vaccines associated with Runting Stunting Syndrome (RSS) in poultry. The present invention also includes methods of protecting poultry, including chickens, against RSS by immunization with such polypeptides and vaccines.
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Composition À Base De Mycoplasma Gallisepticum

The present invention provides a formulation that prevents virulent Mycoplasma galHsepticum infection in birds of the order GaIHf ormes. The formulation comprises live Mycoplasma galHsepticum strain K5831 or derivatives thereof in a pharmaceutically acceptable carrier. A vaccine that prevents virulent Mycoplasma galHsepticum infection in birds of the order Galliformes is also presented. Methods for administering the formulation and vaccine are also presented.
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Methods and Compositions for Ophthalmic Treatment of Fungal and Bacterial Infections

The present invention provides methods and compositions for use in the methods for contacting an eye of a patient with an effective amount of therapeutic composition comprising a pharmaceutically acceptable chelating agent, a pharmaceutically acceptable pH buffering agent, and an antimicrobial agent.
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Dose of an Angiogenic Factor and Method of Administering to Improve Myocardial Blood Flow

The present invention has multiple aspects. In one aspect, the present invention is directed to a unit dose pharmaceutical composition comprising from about 5 ng/dose to less than 135,000 ng of an angiogenic agent, typically from 5 ng to 67,500 ng. Preferably, the angiogenic agent is FGF, more preferably it is basic FGF (FGF-2). In its second aspect, the present invention is directed to a method for inducing angiogenesis, or increasing myocardial perfusion or vascular density in a patient's hear
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Aptamer Inhibitors of Osteopontin and Methods of Use Thereof

The present invention polynucleotide aptamers that selectively bind to and inhibit the function of osteopontin, pharmaceutical compositions comprising the same, and methods of use for diagnostics and treatment of diseases and disorders associated with osteopontin.
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Anti-CD19 Antibodies and Uses in Oncology

The invention relates to immunotherapeutic compositions and methods for the treatment of B cell diseases and disorders in human subjects, such as, but not limited to, B cell malignancies, using therapeutic antibodies that bind to the human CD19 antigen and that preferably mediate human ADCC. The present invention relates to pharmaceutical compositions comprising human or humanized anti-CD19 antibodies of the IgG1 or IgG3 human isotype. The present invention relates to pharmaceutical compositions
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Use of Ranolazine for Non-cardiovascular Disorders

Disclosed is a method of treating a non-cardiovascular disorder characterized by an abnormal persistent sodium current in a subject in need of treatment thereof, said method comprising administering to the subject an effective amount of a compound of Formula (I): wherein: m is 1 or 2; R1, R2, R3, R4, and R5 are each independently selected from the group consisting of hydrogen, halo, CF3, CN, OR22, SR22, N(R22)2, S(=O)R22, SO2N(R22)2, C(-O)R22, alkylamido, alkyl, alkenyl, morpholino, and pyrrolyl
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Geranylgeranyl Transferase Inhibitors and Methods of Making and Using the Same

The present invention is directed to compounds useful in the treatment of diseases associated with prenylation of proteins and pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising same, and to methods for inhibiting protein prenylation in an organism using the same.
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Indoles, Derivatives, and Analogs Thereof and Uses Thereof

Indole derivatives and analog compounds and pharmaceutical compositions comprising the same are provided. Also provided are methods of using these compounds to inhibit tubulin polymerization in a cell associated with a proliferative disease or to treat a cancer.
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Methods and Compositions for Modulating Drug-polymer Architecture, Pharmacokinetics and Biodistribution

Drug-polymer chemotherapeutics are provided having improved therapeutic efficacy and reduced dose-limiting toxicity. Methods are also provided for modulating the architecture, pharmacokinetics and biodistribution of drug-polymers and for reducing the dependence of transition temperature on concentration for drug-polymers.
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Method of modulating the activity of a nucleic acid molecule

The present invention relates, in general, to agents that modulate the pharmacological activity of nucleic acid molecules and, in particular, to agents that bind therapeutic or diagnostic nucleic acid molecules in a sequence independent manner and modulate (e.g., inhibit or reverse) their activity. The invention also relates to compositions comprising such agents and to methods of using same.
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Substituted Porphyrins

Discloses are compounds according to Formula I. Further provided are methods of reducing oxidative stress in a cell, methods of treating a disease including cancer, and methods of treating a subject with a disorder associated with oxidative stress, the methods including administering a compound according to the invention. Also disclosed are methods of potentiating a cancer cell for treatment with ionizing radiation or chemotherapeutics including contacting the cell with an effective amount of a
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Manassantin Compounds and Methods of Making and Using Same

Provided are manassantin compounds and methods of using the compounds. Provided are methods of treating a disease, the method comprising administering a compound according to Formula I. Further provided are pharmaceutical compositions comprising compounds according to Formula I. Also provided are methods of inhibiting HIF-1 in a cell, the methods comprising administering to the cell a compound according to Formula I.
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Aromatic C16-C20 Substituted Tetrahydro Prostaglandins Useful As FP Agonists

PROBLEM TO BE SOLVED: To provide a new PGF analogs, particularly compounds useful for the treatment of various diseases and conditions such as bone disorders and glaucoma, to provide pharmaceutical compositions comprising these compounds, and further to provide the methods for treatment of bone disorders and glaucoma using these compounds or the compositions containing them. ; SOLUTION: One example of chemical formulas of the compounds is disclosed here. The invention also includes optical isome
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TRPC6 Involved in Glomerulonephritis

Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology and up to 20% of patients on dialysis have this diagnosis. A large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion channel protein Transient Receptor Potential Cation Channel 6. The missense mutation is a P112Q substitution, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such
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Inhibiting Eph B-3 Kinase

EphB3 kinase inhibitor compounds, including certain pyrazolo[1,5-a]pyridine and imidazo[1,2-a]pyridine compounds, inhibit EphB3 kinase. The EphB3 kinase inhibitor compounds can have greater potency for the inhibition of EphB3 kinase than general kinase inhibitors. Pharmaceutical compositions, such as neuroprotective agents, comprising the EphB3 kinase inhibitor compounds are also provided. The EphB3 kinase inhibitor compounds and pharmaceutical compositions are useful, for example, to provide ne
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Methods and Systems for Treating Cell Proliferation Disorders with Psoralen Derivatives

Psoralen compounds of Formula (I): wherein (N+Aryl) is a member selected from the group consisting of nitrogen containing aromatic heterocycles of formulae (i)-(iii): wherein Z is a group of formula: (iv), wherein R is C1-C30 hydrocarbyl, which may be linear, branched or cyclic and contains from 1 to 15 carbon-carbon double bonds, which may be conjugated or unconjugated with one another or may include an aryl ring, and may contain one or more substituents; R1 is hydrogen, aryl, heteroaryl, alkyl
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Substituted Porphyrins

PROBLEM TO BE SOLVED: To provide a method for modulating physiological and pathological processes, and in particular, to provide a method for modulating the intracellular levels of oxidants and thereby modulating the processes in which such oxidants are a participant, and to provide a compound and composition suitable for use in the methods. ; SOLUTION: There is provided the compound of formula I or formula II or a pharmaceutically acceptable salts thereof äwherein, each R is independently 1-8C
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Biomolecule Polymer Conjugates and Methods for Making the Same

Methods for producing biomolecule-polymer conjugates, such as polypeptide-polymer conjugates, include attachment of an initiator agent to a biomolecule and in situ polymerization of a polymer from defined sites on the biomolecule. The conjugates may have desirable pharmacological properties and may be used therapeutically.
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Peptide Adjuvants, Vaccines, and Methods of Use

Provided herein are peptides that have activity as mast cell activating proteins (MCAP), as well as compositions, adjuvant compositions, vaccines, and pharmaceutical formulations that include the peptides. Also provided are methods of using the peptides, including methods for eliciting an immune response to an immunogen in a mammal upon administration.
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Prochelators Useful for Inhibiting Metal-associated Toxicity

Prochelator compounds of Formula (I) or Formula (II) are described, along with methods of using the same and pharmaceutical formulations or compositions containing the same.
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CD20-specific Antibody and Method of Employing the Same

The present invention provides monoclonal antibodies and antigen-binding fragments thereof that specifically bind to CD20, as well as pharmaceutical compositions comprising the same. The invention further provides methods of using the monoclonal antibodies, antigen-binding fragments, and pharmaceutical compositions, for example, in methods of depleting B cells or in treating B cell disorders. Also provided are cells, nucleic acids and methods for producing the monoclonal antibodies.
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Compositions, Methods, and Kits for Determining an Alkyl Transferase

The present invention relates to novel compounds as well as to compositions, methods, and kits comprising the compounds for determining an alkyltransferase (ATase), in particular an alkylguanine-DNA alkyl transferase (AGT). In general, the novel compounds provide for determining ATase levels, in particular for in vivo applications including, but not limited to, theranostic applications, in particular to cancer- related applications.
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Bisphosphonate Compositions and Methods for Treating Heart Failure

The present invention provides for methods and compositions for treating and/or preventing cardiac dysfunction by administering to subject a therapeutically effective amount of a bisphosphonate, functional analogue or a pharmaceutically effective salt thereof.
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Betulinic Acid Derivatives As Anti-HIV Agents

The present invention provides compounds of the general structure: which are substituted at the 3 and 28 positions, along with pharmaceutical formulations containing the same and methods of treating viral infections employing the same.
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Polyvalent Vaccine

The present invention relates, in general, to an immunogenic composition (e.g., a vaccine) and, in particular, to a polyvalent immunogenic composition, such as a polyvalent HIV vaccine, and to methods of using same. The invention further relates to methods that use a genetic algorithm to create sets of polyvalent antigens suitable for use, for example, in vaccination strategies.
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Compositions and Methods Relating to Heat Shock Transcription Factor Activating Compounds and Targets Thereof

The present invention relates to HSF activating compounds, methods for their discovery, and their research and therapeutic uses, as well as pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs, mixtures (including both R and S enantiomeric forms and racemic mixtures thereof), and pharmaceutical Formulations thereof. In particular, the present invention provides compounds capable of facilitating HSF1 homotrimerization, and methods of using such compounds as ther
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Derivative N-thiolated 2-oxazolidinone Antibiotics

This invention describes the discovery and synthesis of N-thiolated 2-oxazolidinones as a new class of anti bacterial agents. These compounds can be synthesized from 2-oxazolidinones by Ndeprotection and N-sulfenylation. These new substances were found to exhibit potent anti-bacterial activity, including bacteriostatic properties against Staphylococcus spp., including methicillin resistant Staphylococcus aureus (MRSA), and Bacillus spp., including Bacillus anthracis.
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Polyphenol proteasome inhibitors, synthesis, and methods of use

The present invention relates to synthetic green tea derived polyphenolic compounds, their modes of syntheses, and their use in inhibiting proteasomal activity and in treating cancers. The present invention is also directed to pharmaceutical compositions useful in methods of inhibiting proteasomes and of treating cancers.
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Novel Polymorph of Acetylsalicylic Acid, and Methods of Making and Using the Same

A polymorph of aspirin is provided by the present invention. Methods of making and using the same are also provided.
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Compositions Comprising Anti-icam-1 Antibodies

There is provided a method of preventing a respiratory infection by administering an effective amount of an agent for regulating ICAM-1 expression. Also provided is a composition for the prevention of respiratory infection including an agent which regulates ICAM expression. method of preventing RSV infection by administering an effective amount of an agent that interferes with the binding of RSV to ICAM-1. A method of preventing RSV infection by administering an effective amount of an agent that
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Antibacterial S-heterosubstituted Disulfides

Synthetically-derived S,S-heterodisubstituted disulfides that exhibit potent in vitro antibacterial activity against a variety of bacteria, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Francisella tularensis. The present invention provides compounds, methods and compositions effective to treat microbial/bacterial infections, and, especially, infections arising from bacteria which have developed resistance to conventional antibiotics.
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Pharmaceutical Co-Crystal Compositions

A pharmaceutical composition comprising a co-crystal of an API and a co-crystal former; wherein the API has at least one functional group selected from ether, thioether, alcohol, thiol, aldehyde, ketone, thioketone, nitrate ester, phosphate ester, thiophosphate ester, ester, thioester, sulfate ester, carboxylic acid, phosphonic acid, phosphinic acid, sulfonic acid, amide, primary amine, secondary amine, ammonia, tertiary amine, imine, thiocyanate, cyanamide, oxime, nitrile diazo, organohalide, n
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Fish-ribosyn for antibiotic susceptibility testing

The subject invention concerns materials and methods for evaluating the susceptibility of bacterial cells to an antibiotic or other antimicrobial compound or agent. In one embodiment, a sample comprising a microbial population is exposed to an antibiotic of interest. The sample is then processed using FISH-RiboSyn methods to determine the specific growth rate of the antibiotic-exposed microbes as compared to an untreated control. The subject invention also concerns materials and methods for dete
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Broad Spectrum Vaccine Against Non-typhoidal Salmonella

The present invention is drawn to attenuated Salmonella serovar strains S. Typhimurium and S. Enteritidis, conjugate vaccines derived from these attenuated strains of S. Typhimurium and S. Enteritidis, comprising an O polysaccharide covalently linked to a flagellin protein, and methods for inducing an immune response in a subject comprising administering the attenuated strains and/or the conjugate vaccines of the invention.
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Mutual Prodrugs and Methods to Treat Cancer.

Mutual prodrugs comprising retinoids and histone deacetylase inhibitors, methods for production of the mutual prodnigs, and methods of treatment comprising administration of the mutual prodrugs. The retinoids include all-trans retinoic acid, 13-cis retinoic acid, and retinoic acid analogs that have a substitution at C-4. Further, the mutual prodrugs of the present invention can be used as therapeutic agents for the treatment of cancer and dermatological diseases and conditions. Pharmaceutical co
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P53 Activator Peptides

The present invention relates to novel polypeptides that activate p53, and the polynucleotides encoding these p53 activator peptides. The present invention also relates to pharmaceutical compositions comprising the p53 activator peptides as well as methods of treating abnormal conditions, such as malignant tumors, with the methods comprising administering the pharmaceutical compositions of the present invention to a subject in need of treatment thereof.
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Kynurenine-aminotransferase Inhibitors

Compounds of formula (I) : prodrug derivatives and/or pharmaceutically acceptable salt thereof, selectively inhibit the enzyme kynurenine aminotransferase, thereby reducing the synthesis of kynurenic acid. The compounds are used for the treatment of psychiatric and neurological diseases which benefit from an increase in glutamatergic and/or cholinergic neurotransmission, such as schizophrenia, depression, bipolar illness, anxiety and Alzheimer's disease. Furthermore, the compounds of the inventi
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Attenuated Salmonella Enterica Serovar Paratyphi a and Uses Thereof

The present invention is drawn to a live, attenuated S. Paratyphi A strain, a live, attenuated S. Paratyphi A strain comprising a stabilized plasmid expression system, an S. Paratyphi conjugate vaccine, and methods of using these strains and conjugate vaccine.
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Protective Vaccine Against Staphylococcus Aureus Biofilms Comprising Cell Wall-associated Immunogens

Vaccine formulations effective against Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) are disclosed, as well as methods of using the vaccine formulations in the treatment, prevention and prophylaxis of Staphylococcus aureus infections in a subject.
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Multivalent Live Vector Vaccine Against Clostridium Difficile-associated Disease

The invention relates to a multivalent Clostridium difficile vaccine comprising a Salmonella Typhi live vector comprising the cell binding domain of TcdA toxin (CBD/A) of Clostridium difficile or an antigenic fragment thereof and the cell binding domain of TcdB toxin (CBD/B) of Clostridium difficile or an antigenic fragment thereof and optionally the cell-binding subunit component (CdtB) of binary toxin of Clostridium difficile or an antigenic fragment thereof. The invention further provides met
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Sulfated Psyllium Derivative for Reducing the Risk of Chronic Human Diseases and Method for Preparing the Same

The invention is directed to a method for preparing sulfated psyllium derivatives for use to reduce the risk of chronic human diseases. The sulfation of psyllium was carried out with sulfur, trioxide, pyridine, dimethylformamide and chlorosulfonic acid in pyridine. Six total sulfated psyllium derivatives named SP1, SP2, SP3, SPR1, SPR2, and SPR3 were prepared and evaluated for their morphological and rheological properties, and bile acid-binding abilities. The invention offers a novel approach t
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Substituted Phenyl Aziridine Precursor Analogs as Modulators of Steroid Receptor Activities

Disclosed are methods and pharmaceutical compositions for modulating one or more steroidal receptor activities. The methods typically utilize and the pharmaceutical compositions typically include one or more substituted phenyl aziridine precursors, their respective aziridines, analogs thereof, derivatives thereof, or pharmaceutically acceptable salts thereof such as CpdA. The methods and compositions may be used for treating diseases, disorders, and conditions associated with glucocorticoid rece
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Kainate Receptor-Selective Epimeric Analogs of Dysiherbaine

Disclosed are compounds, pharmaceutical compositions, methods of treatment, and methods for selectively antagonizing a GluR5 receptor, a GluR6 receptor, or both receptors. The pharmaceutical compositions include and the methods utilize compounds that are analogs and stereoisomers of dysiherbaine and neodysiherbaine which have specificity for kainate receptors.
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Selective Poly-n-substituted Glycine Antibiotics

Antimicrobial peptoid compounds and related compositions as can be used against bacteria effectively and selectively.
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Vaccine Compositons for Inducing Immune Responses Against Components of Drusen

Disclosed are compositions and methods for treating or preventing the formation of drusen in a patient in need thereof. The compositions include an effective amount of at least one polypeptide present in drusen, or an immunogenic fragment or variant thereof that induces an immune response against the polypeptide, together with a pharmaceutical carrier, excipient, or diluent. The compositions are suitable as vaccines for treating or preventing drusen and diseases associated with drusen.
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Treatment of Amyotrophic Lateral Sclerosis

The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided compounds.
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Compositions and Methods of Vitamin E Administration

The present invention relates to compositions and methods of vitamin E administration. In particular, the present invention provides opposing effects, relative to inflammation, from the administration of two major forms of vitamin E ([alpha]-tocopherol and [gamma]-tocopherol).
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Targeted Schiff Base Complexes

The present invention provides targeted Schiff base complexes. In particular the present invention provides biopolymer targeted transition metal complexes configured to inhibit the activity of targeted proteins, methods of synthesis thereof, and pharmaceutical compositions and uses thereof.
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Pyrimidine-2,4,6-triones for Use in the Treatment of Amyotrophic Lateral Sclerosis

The present invention relates to the identification of inventive pyrimidine-2,4,6- triones (PYT compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the inventive PYT compounds.
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Cyclohexane-1,3-diones for Use in the Treatment of Amyotrophic Lateral Sclerosis

The present invention relates to the identification of provided cyclohexane-1,3-diones (CHD compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided CHD compounds.
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Vaccine Compositions and Uses Thereof

The present invention relates to vaccine compositions and uses thereof. Embodiments of the present invention provide oral bacterial (e.g., probiotic lactic acid bacteria) vaccine delivery systems comprising an antigen and a dendritic cell-targeting peptide. Such compositions target vaccines to dendritic cells, resulting in a high level of humoral and acquired immunity, including both mucosal and systemic immunity. Such delivery systems find use in the specific delivery of a wide variety of oral
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Pharmacological Treatment for Sleep Apnea

The present invention relates generally to pharmacological methods for the prevention of amelioration of sleep-related breathing disorders via administration of agents or combinations of agents that possess serotonin-related pharmacological activity.
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Use of Specifically Engineered Enzymes to Enhance the Efficacy of Prodrugs

The invention provides methods for enhancing efficiency of prodrugs by specifically engineered enzymes with altered or enhanced activity and broader substrate specificity towards nucleoside analogs used in cancer chemotherapy, and delivering the enzymes to specific target cells in a patient. The invention also provides modified deoxycytidine kinase (dCK) mutants with such enhanced activities. Furthermore, the invention provides antibody-conjugated enzymes, pharmaceutical composition and kit cont
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Ecteinascidins

The present invention is directed to several newly discovered ecteinascidin (Et) species, designated herein as Et 731, Et 815, Et 808, and Et 594. The physical properties of these compounds, their preparation and therapeutic properties are also reported.
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Non-simian Cells for Growth of Porcine Reproductive and Respiratory Syndrome (PRRS) Virus.

Disclosed are compositions and methods relating to growth of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) using non-simian cells. In a particular example, porcine alveolar macrophage cells are described as having a capability of supporting infectivity and reproduction by PRRSV. Cells and cell lines of the invention are disclosed in connection with applications relating to PRRS disease, including vaccine technologies.
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Liposome Formulation Having Hydrophilic and Hydrophobic Pharmaceutical Compounds Co-encapsulated Therein

The present invention features liposomal formulations composed of at least one hydrophilic pharmaceutical compound loaded in the aqueous core of the liposome and at least one hydrophobic pharmaceutical compound in the bilayer of the liposome; and a method for producing the same. In so far as the pharmaceutical compounds are chemotherapeutic agents, the present invention also embraces a method for preventing the development of chemotherapeutic drug resistance.
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Enzyme Inhibiting Compounds and Methods

The invention provides compounds, compositions, and methods for studying the Rohmer pathway and for treating bacterial infections or parasitic infections. The parasitic infection can be a protozoan infection, such as malaria. The compounds and compositions can also be used as antibiotics, for example, to kill bacteria or parasites, or to inhibit bacterial or parasite growth. The invention further provides inhibitors of isoprenoid biosynthesis enzymes, and methods of inhibiting the activity of is
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Portable Active Fluid Powered Ankle-foot Orthosis

A portable active pneumatically-powered ankle foot orthosis. A lower leg mount and a foot bed are pivotally coupled at or proximate to an ankle position. A pneumatically powered rotary actuator is configured to receive power from a wearable fluid power source and provide controlled force and resistance to aid or inhibit relative rotation of the foot bed and the lower leg mount. Embedded sensors provide feedback from the device.
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Method of Regulating Cell Growth Using a Proteasome Inhibitor

This invention provides methods and pharmaceutical compositions for regulating cell growth or inducing apoptosis in a cell, particularly a mammalian tumor cell. Specifically, the invention provides methods for inducing apoptosis in a tumor cell comprising contacting the tumor cell with a proteasome inhibitor and a thiazole antibiotic, particularly each in a suboptimal amount.
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Compositions and Methods for Treating Neurodegenerating Diseases

This invention provides agents, compositions, pharmaceutical compositions and methods for treating or slowing the progression of a neurodegenerating disease, such as Alzheimer's disease and a demyelinating disease.
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Synergistic Antibiotic Combinations and Derivatives

Improved antibiotic analogs, and synergistic combinations of antibiotics designed based on structural crystallographic analysis, are provided as well as pharmaceutical compositions comprising the improved analogs and the synergistic combinations, and methods for their production and use. The synergistic combinations target neighboring sites in the ribosome demonstrating the importance of the corresponding ribosomal sites for development of clinically-relevant synergistic antibiotics.
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Methods and Compositions for Affecting Cyclophilin a Regulation of Kinases in Modulating Cellular Activities

The present invention relates to drug screening assays, therapeutic protocols and pharmaceutical compositions designed to target non-receptor tyrosine family kinases and components of the tyrosine kinase family signal transduction pathways. It has been previously reported by the inventors that a substrate SH2 domain docking mechanism apart from the kinase active site is required for appropriate tyrosine phosphorylation by these tyrosine kinases. According to the invention, it has been discovered
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Agr-mediated Inhibition of Methicillin Resistant Staphylococcus Aureus

The present invention involves the use of activators of bacterial Agrquoroum-sensing systems to prevent or reverse biofilm formation in methicillin resistant Staphylococcus aureus (MRSA), or to restore sensitivity of MRSA bio films to antibiotics.
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2,4,6-trisubstituted Phenols Having Anesthetic Properties

Trisubstituted phenol compounds and methods of using the compounds, e.g., for anesthetizing a subject, are disclosed.
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Cellulose Capsules and Methods for Making Them

Disclosed are cellulose capsules, methods for preparing a cellulose capsule, and compositions comprising cellulose capsules, including sustained- or controlled-release dosage forms comprising cellulose capsules.
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Methods of Improving Vaccine Immunogenicity

The present invention provides a process called "Immune Banking" that enhances vaccine efficacy by exploiting existing humoral responses. The process involves tagging new antigens with molecular markers recognized by an existing antibody response. This recognition of the tagged vaccine components enhances adaptive immune responses to the new vaccine.
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Inhibitors of Phosphodiesterase Type 5A for Treating or Preventing Muscle Disease or the Symptoms Thereof in a Patient

Disclosed are pharmaceutical compositions and methods for treating or preventing muscle diseases or the symptoms thereof. The compositions typically include and the methods typically utilize phosphodiesterase type 5A inhibitors.
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Capped Mesoporous Silicates

The invention provides an article comprising, a mesoporous silicate matrix, such as a particle, having one or more pores; and one or more releasable caps obstructing one or more of the pores. The articles are useful as delivery vehicles for encapsulated agents such as therapeutic agents, polynucleotides, polypeptides and the like.
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Novel Antibiotic Alternatives

The present invention relates to two recombinant colicin expression systems, one utilizing a yeast expression system that produces a protein that is inexpensive to purify, and the other utilizing a plasmid expression system to be used as a probiotic culture. The recombinant colicins provide effective alternatives to conventional antibiotics and may be used to improve the efficiency of pork production, and the safety of its products.
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Neuroprotective Compounds and their Use

Apocynin derivative compounds, active pharmaceutical ingredients, dosage forms, and methods of use thereof as neuroprotectants in the brain of mammals.
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COMPOSITION COMPRISING beta -HYDROXY- beta -METHYLBUTYRIC ACID AND AT LEAST ONE AMINO ACID AND METHODS OF USE

The present invention provides a composition comprising HMB and at least one amino acid. The present invention also provides a method for the treatment of disease-associated wasting of an animal, a method for decreasing the serum-level of triglycerides of an animal, a method for decreasing the serum viral load of an animal, a method for redistributing fat in an animal having a visceral region and a subcutaneous region, a method for increasing the lean tissue mass of an animal without substantial
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Producing polyelectrolyte hydrogel bodies, useful e.g. as soft tissue implants, comprises filling a semi-permeable membrane-forming liquid and a coagulation medium in a hollow template to form hollow

Producing dimensionally stable polyelectrolyte hydrogel bodies (2) with defined three-dimensional shape, comprises: filling a semi-permeable membrane-forming liquid in a hollow template (1); separating a liquid film adhered on the template; filling a coagulation medium, preferably water or alcohol in the template to form a hollow semipermeable membrane body from the liquid film; and subjecting the hollow semipermeable membrane body (4) to dialysis bath treatment after it is filled with a polyele
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PKCdelta REGULATES NEUROINFLAMMATORY EVENTS

This invention relates to methods and pharmaceutical compositions for regulating the levels of proinflammatory substances released from activated microglia using a protein kinase C delta (PKCd) inhibitor. In particular, it relates to decreasing the levels of proinflammatory substances produced within the microglial cells or released from activated microglical cells or both. Accordingly, the invention provides for the treatment of diseases, disorders, and conditions where neuroinflammation is imp
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Analgesic Agents

he invention provides a compound of formula (I) or a salt thereof, as well as compositions comprising such compounds. The compounds and compositions are useful as analgesics.
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Triptolide Prodrugs

The invention provides compounds of formula (I): or a salt thereof. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods using the compounds of formula I.
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STREPTOCOCCAL C5a PEPTIDASE VACCINE

Novel vaccines for use against beta -hemolytic Streptococcus colonization or infection are disclosed. The vaccines contain an immunogenic amount of a variant of streptococcal C5a peptidase (SCP). Also disclosed is a method of protecting a susceptible mammal against beta -hemolytic Streptococcus colonization or infection by administering such a vaccine. Enzymatically inactive SCP, and polynucleotides encoding these SCP proteins are further disclosed.
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Methods of Administering Porcine B-domainless FVIII

The present invention provides a method of administering porcine B-domainless factor VIII (OBI-1) to a patient having factor VIII deficiency to provide more rapid and effective protection against bleeding episodes, compared to formerly available methods, or to provide more effective protection to such patients during non-bleeding periods. This invention is based on the discovery that the recombinant B-domainless porcine fVIII, termed OBI-1, has greater bioavailability compared to the natural por
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Nucleoside Derivatives for Treatment of Caliciviridae Infections, Including Norovirus Infections

A method and composition for treating a host infected with a Caliciviridae virus, such as a Norovirus, comprising administering an effective treatment amount of a described modified nucleoside or a pharmaceutically acceptable salt thereof, is provided.
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Non-myelosuppressive Compounds, Pharmaceutical Compositions Thereof, and Methods of Treatment

The present invention provides microtubule targeting compounds that are myelo-sparing. Particularly, the MTCs of the invention are structurally designed to exhibit specificity for inhibiting ss-tubulin isotypes that are not related to the myelosuppression associated with other known MTCs. The invention further provides pharmaceutical compositions incorporating the inventive MTCs and methods of treating cancer using the MTCs. The invention still further provides various assays for identifying mye
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Steroid Analogues for Neuroprotection

Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.
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2'-fluoronucleosides

The 2'-fluoronucleoside is provided to treat hepatitis type B, hepatitis type C, HIV(human immunodeficiency virus), and abnormal cell proliferation including tumor and cancer. The pharmaceutical composition for treating hepatitis type B in human comprises the 2'-fluoro-beta-D-nucleoside represented by the chemical formula or pharmaceutically acceptable salts thereof, wherein the base is purine; R^1 is OH, H, OR^3, N3, CN, halogen, CF3, C1-C4 alkyl, amino, C1-C4 alkyl amino or di(C1-C4) alkyl ami
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Branched Diepoxide Compounds for the Treatment of Inflammatory Disorders

The present invention provides certain diepoxide carbocyclic compounds wherein at least one carbocyclic ring carbon includes two non-epoxide substituents, and pharmaceutical compositions containing the same, for the treatment or prophylaxis of inflammatory, autoimmune and hyper- or abnormally proliferative diseases and disorders.
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Cyanine-containing Compounds for Cancer Imaging and Treatment

This invention relates generally to cyanine-containing compounds; pharmaceutical compositions comprising cyanine-containing compounds; and methods of using cyanine-containing compounds for cancer cell imaging, cancer cell growth inhibition, and detecting cancer cells, for example. Compounds of the invention are preferentially taken up by cancer cells as compared to normal cells. This allows many uses in the cancer treatment, diagnosis, tracking and imaging fields.
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Methods and Compositions for Improved Delivery of Therapeutic and Diagnostic Agents

Among other things, this disclosure provides for compounds having a targeting moiety linked to a therapeutic moiety and/or a diagnostic moiety; the synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and, methods for treating or diagnosing disorders. Some of the compounds include a linker which can be cleaved under physiological conditions, including linkers comprising an amide or disulfide bond. Examples of targeting moieties are derivatives of DNA
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Catecholamine Derivatives for Obesity and Neurological Disorders

Novel compounds, compositions, and methods related to the activation of the TrkB receptor are provided. The methods include administering in vivo or in vitro a therapeutically effective amount of a compound containing a catecholamine backbone and pharmaceutically acceptable salts, prodrugs, and derivatives thereof. Specifically, methods, compositions, and compounds for the treatment of disorders including neurological disorders, neuropsychiatric disorders, and metabolic disorders are provided. F
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Compounds, Compositions, Methods of Synthesis, and Methods of Treatment

Briefly described, embodiments of this disclosure include compounds as described herein, labeled compounds as described herein, pharmaceutical composition including compounds described herein, methods of imaging, method of forming a compound as described herein, and the like. In particular, embodiments of the disclosure include a series of triamino-pyridine derivatives and labeled triamino-pyridine derivatives, methods of synthesizing these compounds, intermediate compounds, methods of treatment
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Subunit Selective NMDA Receptor Potentiators for the Treatment of Neurological Conditions

Provided are compounds, pharmaceutical compositions and methods of treating or preventing disorders associated with NMDA receptor activity, including schizophrenia, Parkinson's disease, cognitive disorders, depression, neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds of the general Formulas A-J, and pharmaceutically acceptable salts, esters, prodrugs or derivatives thereof are disclosed.
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Methods of Neuroprotection Using Neuroprotective Steroids and a Vitamin D

Described herein are compositions and methods for treating or preventing nervous system injury. In particular, the methods and compositions relate to the use of at least one neuroprotective steroid, such as progesterone, and vitamin D.
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ENANTIOMERICALLY PURE beta -D-DIOXOLANE-NUCLEOSIDES

A method and composition for the treatment of humans infected with HIV that includes the administration of an HIV treatment amount of an enantiomerically pure (beta)-D-dioxolanyl purine nucleoside of formula (I), wherein R is OH, Cl, NH2, or H, or a pharmaceutically acceptable salt or derivative of the compound, optionally in a pharmaceutically acceptable carrier or diluent.
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MVA Expressing Modified HIV Envelope, Gag, and Pol Gene

PROBLEM TO BE SOLVED: To control pathogenic immunodeficiency virus. ; SOLUTION: There is provided a pharmaceutical composition comprising a recombinant MVA virus expressing an HIV env, gag, and pol gene or modified gene thereof for production of an HIV Env, Gag, and Pol antigen by expression from the virus, and a pharmaceutically acceptable carrier, wherein the HIV env gene is modified to encode an HIV Env protein which is composed of gp120 and the membrane-spanning domain and ectodomain of gp41
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Conjugates of Noscapine and Folic Acid and their Use in Treating Cancer

The present invention is directed to compounds which are conjugates of two non-toxic natural products, noscapine (and various noscapine analogs) and folic acid (and various folic acid analogs), where the folic acid is conjugated to noscapine or the noscapine analog at the 9-position on the isoquinoline ring on the noscapine framework. Pharmaceutical compositions including the compounds, and methods of treating various tumors using the compounds and compositions, are also disclosed. The conjugate
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Small-molecule Inhibitors of HIF and Angiogenesis

Inhibitors of Hypoxia Inducible Factor (HIF) and angiogenesis, for example 2,2-dimethylbenzopyran compounds and derivatives thereof, and methods of their use including treatment of cancer, disorders leading to ischemia (e.g., stroke and ischemic heart disease), and non-cancerous angiogenic diseases are provided.
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NMDA Receptor Antagonists for Neuroprotection.

Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: Formula I wherein: each (L)k-Ar1 is a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl
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Use of Imipramine Blue and Analogs Thereof in Treating Cancers

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are triphenyl methane analogs. The compounds and compositions can be used to treat and/or prevent a wide variety of cancers, including drug resistant cancers, inflammatory, degenerative and vascular diseases, and parasitic infections. The compounds are triphenyl methane analogs of imipramine blue and analogs thereof, as defined herein. The compounds are believed
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Treating Various Disorders Using TrkB Agonists

Novel compounds and methods for activating the TrkB receptor are provided. The methods include administering in vivo or in vitro a therapeutically effective amount of a compound containing four six-membered rings and a substituted or unsubstituted C5 or C6 heteroaryl or hetero-cycloalkyl ring and pharmaceutically acceptable salts, prodrugs, and derivatives thereof. Specifically, methods and compounds for the treatment of disorders including neurologic, neuropsychiatric, and metabolic disorders a
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Noscapine and Noscapine Analogs and their Use in Treating Infectious Diseases By Tubulin Binding Inhibition

Compositions and methods for treating or preventing infectious diseases, and inhibiting the ability of microbes to travel within mammalian cells, and inhibiting microbial replication, are disclosed. The compositions include various noscapine analogs, which are capable of blocking the movement of viruses and other microbes within mammalian and other cells by inhibiting the cytoplasmic transport mechanisms within the cells. The compositions described herein include an effective amount of the nosca
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NMDA Receptor Antagonists for the Treatment of Neuropsychiatric Disorders.

Provided are pharmaceutical compositions and methods of treatment or prophylaxis of certain neuropsychiatric conditions, in particular mood disorders. The compounds are of the general Formula I-V as described herein.
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Systems Biology Approach Predicts Immunogenicity of Vaccines

A major challenge in vaccinology is to prospectively determine vaccine efficacy. Disclosed herein are methods and compositions for identifying early expression "signatures" that predicted immune responses in humans vaccinated with a vaccine.
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Synergistic Induction of Humoral and Cellular Immunity By Combinatorial Activation of Toll-like Receptors

Described herein are compositions that include a selected antigen, a TLR4 ligand and a TLR7/TLR8 ligand, wherein the antigen and TLR ligands are encapsulated in nanoparticles. Co-administration of both a TLR4 ligand and a TLR7/TLR8 ligand results in the synergistic induction of humor and cellular immunity as evidenced by an increase in pro-inflammatory cytokine production, an increase in the number of CD8+ T effector and T memory cells, an increase in titer of antigen-specific antibodies, an inc
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Compositions and Methods for Treating MIV-infection, and Preventing and Treating Mlv-initiated Diseases

Compositions and methods for inhibiting infection by XMRV or other MLV are disclosed. Also disclosed are methods for treating cancers resulting from infection by XMRV or other MLV, and for preventing such cancers. The anti- XMRV/anti-MLV compounds are predominantly integrase inhibitors, such as globoidnan A, L-000870812, S/GSK1349572, S/GSK1265744, Raltegravir and Elvitegravir, and also reverse transcriptase inhibitors AZT, tenofovir, and tenofovir DF. The compounds are also useful for treating
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Recombinant Antibodies Against H1N1 Influenza

Antibodies that bind with high affinity to swine H1N1 virus are described. In vivo experiments showed that one such antibody is able to fully protect mice challenged with a lethal dose of swine H1N1 virus. The antibody is also able to cure mice in a therapeutic setting when treated as late as up to 60 hours (2.5 days) after infection with swine H1N1 virus. Also described are recombinant forms of this antibody.
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Polymers for Delivering a Substance Into a Cell

Disclosed herein are polymers that can be made cationic and used to deliver a substance into a cell. Also disclosed are pharmaceutical compositions comprising the polymers and methods of using the polymers.
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Anti-cancer Vaccine Composition

Combinations of anti-cancer vaccines and inhibitory antibodies to CD223 overcome immune suppression in cancer patients. The vaccines may be isolated antigens, groups of antigens, or whole tumor cells. The inhibitory antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.
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Spiperone Derivatives and Methods of Treating Disorders

Described herein are spiperone derivative compounds which have been found to be useful in methods of stimulating CaCC and treating disorders (or symptoms thereof) associated with CaCC including cystic fibrosis, wherein a compound of the invention is administered to a subject.
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Compositions and Methods for Treatment of Neurodegenerative Disease

Compounds, compositions, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed.
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Thermostabilization of Proteins.

Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Addition
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Inhibitors of Mre11, Rad50 And/or Nbs1

The invention provides, inter alia, compositions comprising an inhibitor of MRE11, RAD50 and/or NBSl and methods of using such inhibitor for modulating the cellular response to DNA damage, arresting the cell cycle, and/or treatment of cancer. The inhibitor is, e.g., a compound of formula I:
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Pharmaceutical Composition Comprising a Proton Pump Inhibitor and Protein Component

The present disclosure relates to, inter alia, pharmaceutical compositions comprising a H+,K+-ATPase proton pump inhibitor and a protein component; to methods for manufacture of such compositions, and to use of such compositions in treating and preventing diseases and/or disorders.
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Compounds for Treatment of Copper Overload

The present invention provides compounds, pharmaceutical compositions, and methods that can be used to treat pathologies that are due to copper overload or to the presence of reactive oxygen species.
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Novel substituted benzimidazole dosage forms and method of using same

The invention provides a solid oral pharmaceutical composition in capsule or powder dosage form comprising: a) omeprazole or a single enantiomer thereof, including a salt or other derivative thereof; and b) sodium bicarbonate; wherein the dosage form is not enteric coated or time-released, and the composition comprises from 7 to 25 mEq sodium bicarbonate per 20 mg omeprazole.
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E3 Ligase Inhibitors

The present invention provides, e.g., compounds having the structure of formula (I): The present invention also provides pharmaceutical compositions that include such compounds, and methods for modulating murine double minute 2 protein (Mdm2) E3 ligase activity, particularly the Mdm2-MdmX hetero-complex E3 ligase activity, using such compounds.
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Compounds that Inhibit Production of sAPPB and AB and Uses Thereof

The present invention relates to compounds with activity as inhibitors of sAPP[beta] and A[beta] production, and methods for treating, preventing, or ameliorating neurodegenerative diseases, such as Alzheimer's disease and pharmaceutical compositions containing such candidate compounds.
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Rage Fusion Proteins and Methods of Use

Disclosed are RAGE fusion proteins comprising RAGE polypeptide of soluble human sRAGE fragment with the certain amino acid sequence and non-RAGE polypeptide linked thereto. Said protein is used for treatment of diabetes and complications connected with diabetes.
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Agents for preventing and treating disorders involving modulation of the RyR receptors

The present invention provides novel compounds of Formula I and salts, hydrates, solvates, complexes, and prodrugs thereof. The present invention further provides methods for synthesizing compounds of Formula I. The invention additionally provides pharmaceutical compositions comprising the compounds of Formula I and methods of using the pharmaceutical compositions of Formula I to treat and prevent disorders and diseases associated with the RyR receptors that regulate calcium channel functioning
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Novel Curcumin Derivatives and their Pharmaeutical Uses Thereof

Disclosed are methods relating to analogues, derivatives, and metabolites of curcumin. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention
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Vaccine Against Botulism

The invention relates to novel DNA and protein vaccines against Clostridium botulinum. The DNA vaccine includes a DNA molecule that includes a first segment encoding a fragment of a heavy chain region of a Clostridium botulinum neurotoxin, wherein the first segment is codon-enhanced to improve expression of the isolated DNA molecule in a mammalian host, and preferably a second segment that encodes a secretion signal peptide. The chimeric protein of the present invention includes the secretion si
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Method and Compositions for Treatment Or Prevention of Inflammatory Conditions

Pharmaceutical compositions and methods for treating or preventing an inflammatory condition in a patient are disclosed. The pharmaceutical compositions and methods include the use of vincamine or a vincamine derivative, either alone or in combination with one or more additional therapeutic agents, including a steroid (preferably a corticosteroid), an angiotensin II receptor (type 1) antagonist, an angiotensin-converting enzyme (ACE) inhibitor, and a non-steroidal anti-inflammatory drug.
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Respiratory Syncytial Virus Vaccine Based on Chimeric Papillomavirus Virus-like Particles Or Capsomeres

The present invention is directed to a chimeric papillomavirus virus- like particle (VLP) or capsomere including an Ll polypeptide and, optionally, an L2 polypeptide, and a respiratory syncytial virus (RSV) protein or polypeptide fragment thereof comprising a first epitope, where the RSV protein or polypeptide fragment thereof is attached to one or both of the Ll and L2 polypeptides. Chimeric proteins, genetic constructions, and recombinant vectors and host cells suitable for expression of the c
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Use of Electrophilic Compounds for Inducing Platelet Production Or Maintaining Platelet Function

The present invention is directed to a method of inducing platelet production that includes contacting a megakaryocyte with an electrophilic compound under conditions effective to induce platelet production by the contacting megakaryocyte. Methods of treating a patient for low platelet levels, increasing the circulating half- life of platelets, and improving the quality (activity) of platelets are also disclosed herein, which involve administering the electrophilic compound to a patient an effec
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Systems and Methods for Enhancing Vaccine Efficacy

Pharmaceutical compositions of the invention include an antigen or a nucleic acid molecule encoding the antigen; one or both of a PPAR ligand and an RxR ligand; and a pharmaceutically suitable carrier. The pharmaceutical composition can optionally include a mitogen or other additives. Also disclosed are methods of inducing B cell differentiation and promoting an immune response against an antigen.
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Compounds and Methods for Altering Lifespan of Eukaryotic Organisms

Provided are compounds which generally have a triketone structure. Examples of the compounds include derivatives of 1,3-cyclohexanedione, such as: 1,3-cyclohexanedione, 2-propanoyl-5-cyclohexyl-; 1,3-cyclohexanedione, 2-propanoyl-5-[4-fluorophenyl]-; 1,3-cyclohexanedione, 2-acetyl-5-[thien-2-yl]-; 1,3-cyclohexanedione, 2-acetyl-5 -butyl-; and 1,3-cyclohexanedione, 2-propanoyl-5-[bicyclo[2.2.1]hept-2-en-5-yl]-. The compounds can be used to alter the lifespan of eukaryotic organisms and treat infl
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Phenazine Derivatives and Uses Thereof

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
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Biocompatible Polysaccharide-based Hydrogels

Modified polysaccharides and crosslinked modified polysaccharide compositions are described. Methods of using the crosslinked modified polysaccharide compositions to deliver proteins, oligonucleotides, or pharmaceutical agents are also disclosed.
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Phosphopeptides As Melanoma Vaccines

We characterized a total of 175 HLA-DR-associated phosphopeptides using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing and comparative analysis. Many were derived from source proteins which may have roles in cancer development, growth and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome "fingerprints". We generated HLA-DRss1*0101-restricted CD4+ T cells s
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Antifungal Agents As Neuroprotectants

Provided herein are compounds, compositions and methods for protecting neuronal and glial cells.
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Vaccines Targeting Cellular Death Receptors

The invention provides therapeutics and methods to induce a mammalian host, including a human, to produce antibodies, which agonize death receptors and cause the apoptotic death of target cells within the host's body. The therapeutics are vaccine compositions, including genetic vaccines encoding death receptor antigens of the tumor necrosis factor receptor family. Also provided are means and methods for overcoming host immunological tolerance to death receptors. The vaccines are useful against c
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Antitumor Agents

The invention provides compounds of formula I as described herein wherein Y is F, Cl or Br; or a pharmaceutically acceptable salt thereof. The compounds are effective antitumor agents. The invention also provides pharmaceutical compositions comprising a compound of formula I or a salt thereof, intermediates useful for preparing a compound of formula I, and therapeutic methods comprising administering a compound of formula I or a salt thereof to a mammal in need thereof.
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Dendrimers for Sustained Release of Compounds

Dendrimer-based compositions and methods are provided, that are useful for administering pharmaceutical compositions to target cells and tissues for treatment of ocular diseases including macular degeneration, diabetic retinopathy, and retinitis pigmentosa.
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Topical Steroidal Formulations

The present invention relates to formulations of poorly water soluble pharmaceutical agents of Formula I and II. The present invention also relates to compositions containing compounds of Formula I or II, and glucocorticoids, and methods for reducing side effects from glucocorticoid treatment by co-administration of compounds of Formula I and II. The compositions herein are useful for the treatment of diabetes and obesity related diseases including metabolic syndrome.
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Substituted Styryl Benzylsulfones for Treating Proliferative Disorders

Styryl benzylsulfones of formula (I) are useful as antiproliferative agents, including, for example, anticancer agents. In said formula, (a) (i) at least three of R1, R2, R3, R4 and R5 are independently selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, cyano, carboxyl, hydroxyl, phosphonato, amino, sulfamyl, acetoxy, dimethylamino(C2-C6 alkoxy) and trifluoromethyl, and the balance of said R1, R2, R3, R4 and R5 are independently selected from the group consisting of
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Manipulating Sp1 Activity to Improve Therapeutic Cloning

The observed over-expression of Sp1 target genes has inspired inventors to formulate a specific strategy for correcting many gene expression defects, and thus improve clone development. The invention is based on the belief that manipulating Sp1 activity can improve cloning. Inventors believe that cloning is inefficient in large part because of the continued expression of Sp1 target genes in the early cloned embryos, which causes clones to be very unlike normal embryos, and so makes them very unh
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Suppression of Postoperative Ileus

The invention provides a method for suppressing postoperative ileus in connection with the performance of a surgical procedure on a patient. In accordance with the inventive method, interleukin-10 (IL-10), glycine, a COX-2 inhibitor and a mast cell stabilizer are administered to the patient undergoing the surgical procedure in an amount and at a location sufficient to therapeutically or prophylactically suppress postoperative ileus in the patient. The invention further provides a pharmaceuticall
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Cyclic Adenosine Monophosphates for Reducing the Formation of Adhesions

Provided herein are methods of reducing adhesion formation in a subject, for example, post-surgical abdominal and pelvic adhesions. The methods comprise administering to the subject a compound chosen from one or both of 2',3' cyclic adenosine monophosphate, or an analogue or pharmaceutically acceptable salt thereof, able to reduce the formation of adhesions in a subject as compared to adenosine monophosphate, wherein the 2',3' cyclic adenosine monophosphate, or analogue or pharmaceutically accep
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Compounds for the Treatment of Pathologies Associated with Aging and Degenerative Disorders

The present invention relates to methods of inhibiting one or more signs of aging and/or degenerative disorder in a subject in need of such treatment, which comprise administering, to the subject, an effective amount of one or more of the compounds as set forth herein. "Inhibiting a sign of aging or degenerative disorder" means reducing the risk of occurrence, delaying the onset, slowing the progression, and/or reducing the severity and/or manifestation, of a sign of aging or degenerative disord
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Prediction and Prevention of Preeclampsia

The present disclosure relates to methods for assessing increased risk of preeclampsia in a pregnant woman. The methods described herein employ measuring relaxin levels, and optionally measuring C-reactive protein levels in a biological sample of a pregnant woman. The disclosure further encompasses methods of reducing risk of preeclampsia through administration of a pharmaceutical formulation of relaxin to a pregnant woman.
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Anticancer Vaccine and Diagnostic Methods and Reagents

The invention provides a method for vaccinating a patient against a malignancy comprising introducing a protein or peptide comprising of all or an immunogenic fragment of a cyclin protein into the patient. The invention further provides a method of identifying tumor antigens.
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Bicyclic Compounds Having Antimitotic And/or Antitumor Activity and Methods of Use Thereof

The present invention provides bicyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.
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Tricyclic Compounds Having Antimitotic And/or Antitumor Activity and Methods of Use Thereof

The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.
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Novel Compunds, Pharmaceutical Compositions Containing Same, and Methods of Use for Same

A pharmaceutical composition comprising a phamaceurtical diluent and a compound of formula IV wherein R21= H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, -CH2OR25, -C(O)R25, -CO(O)R25, -C(O)NR25R26, -CH2C(O)R25, or ûCH2C(O)NHR25, where R25 and R26 are each independently H, C1-C10 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms. R22= -OH, -OR27, -OCH2C(O)R27, -OCH2C(O)NHR27, -OC(O)R27, - OC(O)OR27, -OC(O)NHNH-R5, or
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Method for Treatment of Tumors Using Nordihydrogualaretic Acid Derivatives

Pharmaceutical compositions comprising nordihydroguaiaretic derivatives and uses thereof to suppress Spl regulated promoter activity, arrest cell growth, stimulate apoptosis, and treat tumors.
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Chimeric Vaccines

The invention provides chimeric proteins and nucleic acids encoding these which can be used to generate vaccines against selected antigens. In one aspect, a chimeric protein comprises an antigen sequence and a domain for trafficking the protein to an endosomal compartment, irrespective of whether the antigen is derived from a membrane or non-membrane protein. In one preferred aspect, the trafficking domain comprises a lumenal domain of a LAMP polypeptide. Alternatively, or additionally, the chim
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Antithrombotic Agents and Methods of Use Thereof

The instant invention provides methods and compositions for the treatment, prevention and diagnosis of for example, platelet aggregation or clot formation in a subject. The invention inhibits the activity of decreases the amount of neutrophils in the subject by inhibiting the activity or production of IL-6, interferon-gamma, STAT1, or cathepsin D. The invention addresses decreasing the amount of neutrophils in an attempt to treat subjects that have or are at risk of developing a vascular occlusi
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Fused Diimidazodiazepine Compounds and Methods of Use and Manufacture Thereof

he invention encompasses novel compounds and pharmaceutically acceptable salts thereof and compositions including therapeutically or prophylactically effective amounts of such compounds or pharmaceutically acceptable salts thereof. The invention also encompasses methods for treating or preventing diseases and disorders associated abnormal cell growth, for example, treating or preventing cancer or tumor growth, which methods include administering to a mammal in need thereof a composition comprisi
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Inhibitors of Human Methionine Aminopeptidase 1 and Methods of Treating Disorders

Described herein are novel pyrimidine-pyridine compounds, methods of inhibiting methionine aminopeptidase and treating disorders (or symptoms thereof) associated with methionine aminopeptidase, wherein a compound of the invention is administered to a subject.
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N-acyloxysulfonamide and N-hydroxy-n-acylsulfonamide Derivatives

The invention provides certain N-acyloxysulfonamide and N-hydroxy-N-acylsulfonamide derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the invention provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or develop of a disease or condition. In some embodiments, the disease or condition is selected from cardiova
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Bis-acylated Hydroxylamine Derivatives

The invention provides certain bis-acylated hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the invention provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or develop of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia,
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Trioxane Dimer Sulfur Compounds

The disclosure provides novel trioxane sulfur dimers having Formula I: methods for their preparation, pharmaceutical compositions containing these compounds, and methods for treating cancer, proliferative disorders, and/or malaria using these compounds and/or compositions.
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Pharmaceutical Formulation for Regulating the Timed Release of Biologically Active Compounds Based on a Polymer Matrix

A formulation containing a biologically active compound having a structure with hydrogen bonding sites is blended with a polymer having a structure with complementary hydrogen bonding sites, the polymer forming hydrolytic degradation products that promote the release of the biologically active compound from the polymer.
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Soybean Oil Based Oxygen Carrying Emulsion for Massive Blood Loss

VivaSure is a new treatment for shock from massive blood loss. It is based on soybean oil and is therefore biodegradable. It refills lost vascular volume, protects from free radicals, absorbs toxins and provides nutrition to cells. Also it can deliver oxygen, nitric oxide or other gases to tissues. Efficacy has been demonstrated in mouse and rat models of severe hemorrhagic shock. In these tests VivaSure was superior to Ringer's Lactate and equal to blood. The market is 25 Billion dollars/year.
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Therapeutic Compounds.

he invention provides compounds of formula (I) wherein A, B, R<1>, F, G, n, n' and the dotted line have any values defined herein, as well as salts thereof. The compounds have activity as anti-proliferative agents.
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Solubilized Topoisomerase Poison Agents

The invention provides compounds of formula I: wherein A, B, W, Y, Z, and R1 have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I, and therapeutic methods for treating cancer using compounds of formula I.
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Multiple Phase Cross-linked Compositions and Uses Thereof

The present invention is directed to pharmaceutical compositions, and method for preparing pharmaceutical compositions, comprising a cross-linked matrix physically entrapping at least one therapeutic agent. The matrix may comprise one or more phases in addition to an aqueous phase, such as a solid and/or oil phase. The matrix of the invention has at least one controlled release in-vivo kinetic profile, and may have additional profiles for the same agent. The matrix may also comprise more than on
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Pharmaceutical Preparations Having Individualized Dosage and Structure

A manufacturing device capable of creating individualized dosages of pharmaceutical preparations in which a metering system and a means of performing non-destructive chemical analysis of individual manufactured units are controlled by a microprocessor to precisely control the content and structure of each individual unit.
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Methylenedioxybenzo [i] Phenanthridine Derivatives Used to Treat Cancer

The invention provides compounds of formula I: wherein A, B, X, and Y have any of the values defined in the specification, as well as pharmaceutical compositions comprising such compounds, processes for preparing such compounds, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.
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Type 5 Adenylyl Cyclase Inhibitors for Providing Cardiac Protection

The invention provides a method of treating a cardiac disease by administering a pharmaceutically effective amount of at least one compound capable of inhibiting AC5 to a patient. The compound capable of inhibiting AC5 may be administered singly or in combination with another agent, such as, for instance a ss-blocker. In some embodiments, the AC5 inhibiting compound is 9-ss-D-arabinofuranosyladenine (AraAde). The compound may be administered in an amount of about 1 to about 200 mg/kg/day, about
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Therapeutic Compounds

The invention provides compounds of formula (I) wherein u, d, v, m, n, R1, W, X, Y, and Z have any values defined herein, as well as salts thereof. The compounds have activity as anti-proliferative agents.
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Compositions and Methods Modulating Mg29 for the Treatment of Diabetes

Disclosed herein are compositions and methods for treatment of muscle dysfunction, including diabetes. In addition, the invention relates to therapeutic compositions comprising nucleotides and/or polypeptides of the invention in combination with a pharmaceutically acceptable carrier, wherein the composition facilitates the treatment of skeletal musle disorders. Moreover, the invention relates to the treatment and/or prevention of pathological conditions associated with altered intracellular Ca2+
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Antimicrobial Agents

The invention provides a compound of formula (I): or a salt or prodrug thereof, wherein Y, W, Z, Z1, Z2, Z3, Z4, and R1- R12 have any of the values described in the specification, as well as compositions comprising a compound of formula (I). The compounds are useful as antibacterial agents.
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Cytomegalovirus Vaccines and Methods of Production.

Methods of increasing diversity in cytomegalovirus vaccines through the selection of cell type in which the virus is propagated, and the use of cytomegalovirus produced by those methods in the development of vaccine compositions, are disclosed. Vaccine compositions comprising CMV isolated from epithelial cells are also disclosed.
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Inhibition of Glycerol-3-phosphate Acyltransferase (gpat) and Associated Enzymes for Treatment of Viral Infections

A method of treating or preventing a viral infection in a mammal by administering a compound or pharmaceutically acceptable derivative thereof that inhibits a phosphatidic acid synthesis enzyme
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Antibiotic Compounds

Methods for identifying prodrug antibiotic compounds and direct inhibitory antibiotic compounds utilizing various screens are provided. Also provided are methods for treating infections using these compounds.
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Compositions for Treating Bacterial Infections

The present invention is antibiotic compositions having the ability to disrupt a MazEF complex in S. aureus. The compositions also have the ability to inhibit growth of S. aureus and as such are useful as antibiotic compounds.
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Inhibitors of Fructose 1,6-bisphosphatase and Methods of Use Thereof

The invention is directed to a compound according to formula (I). The compounds of formula (I) include prodrugs, pharmaceutically acceptable salts, stereoisomer mixtures, and enantiomers thereof. The invention is also directed to a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier and to methods for treating diabetes by administering such a pharmaceutical composition alone or in combination with other therapeutic agents. The inven
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Novel Hetero Pyrrole Analogs Acting on Cannapinoid Receptors

Disclosed are biologically active hetero pyrrole analogs such as imidazoles, thiazoles, oxazoles and pyrazoles capable of interacting with the CB1 and/or CB2 cannabinoid receptors. Aspects disclose hetero pyrrole analogs acting as CB1 and/or CB 1 receptor antagonists, having selectivity for the CB 1 or CB2 receptor, acting as neutral antagonists, acting preferentially on CB 1 receptors located in the peripheral nervous system, and/or acting as nitric oxide donors. Pharmaceutical preparations emp
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Methods and Compositions for Inhibiting Atherosclerosis and Vascular Inflammation

Disclosed herein are compositions and methods for reducing inflammation associated with atherosclerosis and/or vascular inflammatory disease. The methods include administering to a subject in need of treatment for atherosclerosis and/or vascular inflammation a pharmaceutically effective amount of an inhibitor of the receptor activity of the S1P2 receptor. Also included are compositions including an S1P2 receptor antagonist and a pharmaceutically acceptable excipient.
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Cholera Vaccines

The methods and compositions of the present invention are directed to a vaccine against Vibrio cholerae comprised of V. cholerae outer membrane vesicles (OMVs). Such vaccines are relatively stable, facilitating distribution. Inventive methods generally include administration of a vaccine against Vibrio cholerae by intranasal, intraperitoneal, oral or intragastric routes. Such vaccines confer immunity to the individual, and when administered to pregnant subjects, can be conferred to the offspring
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Small Molecule Antagonists of Phosphatidylinositol-3, 4, 5-triphosphate (pip3) and Uses Thereof

Disclosed are a new class of non-lipid small molecule inhibitors which interfere with the interaction between PIP3 and pleckstrin homology domains. These molecules target a broad range of PIP3 -dependent signaling events in vitro and exert significant anti-tumor activity in vivo. The small molecule inhibitors of the invention can be used alone or together with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or other cancer medicament to treat cancer. Small molecule inhibito
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Method and Composition for Inhibiting Multi-drug Resistance By Hyaluronan Oligomer

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition for treating multi-drug resistant cell. ; SOLUTION: The pharmaceutical composition includes a competing agent of hyaluronan interaction with an effective dosage in order to reduce the cellular tolerance against a pharmacologic agent. As the competing agent of hyaluronan interaction, hyaluronan binding protein is exemplified, more specifically hyaluronidase which digests a hyaluronan polymer to a hyaluronan oligomer is cited. The compo
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Methods and Compositions for Spore-based Vaccines

Methods for immunizing a subject to an infectious agent are provided, using vegetative cytoplasmic expression of an antigen encoding an infectious agent or spore surface display of the antigen, and contacting the subject with a composition including a spore or a vegetative cell or both with or without an adjuvant. Also included are a thermally- stable vaccine composition using the method described above and a kit for its use.
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Indole Compounds and Methods of Use Thereof

Novel indole compounds are disclosed. Also disclosed are methods for using the compounds to treat human and animal disease, pharmaceutical compositions of the compounds, and kits including the compounds.
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Antifungal Formulation and Method of Preparation

A pharmaceutical preparation for treating a microbial infection such as a fungal or bacterial infection in an individual comprises a peptide or a pharmaceutically acceptable salt thereof, wherein said peptide has an amino acid sequence of at least 8 amino acids selected from the group of amino acid sequences consisting of the amino acid sequence of peptide P-1 13 as set forth in SEQ ID NO: 18 and various modifications thereof, wherein the buffer molarity of the pharmaceutical preparation is suit
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Compositions and Methods for the Treatment of Cystic Fibrosis

The invention is directed to novel pharmaceutical compositions comprising chemicals agents that are useful in the treatment and prevention of cystic fibrosis and the prevention of signs and symptoms of this disease. These pharmaceutical compositions are surprisingly successful in the treatment disorders related to cystic fibrosis including disorders of blood production. Many of these compositions of the invention are even more effective when administered to a patient in pulses. Pulse therapy is
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Tetrahydropyranonaphthyridines Derivatives, Pharmaceutical Compositions and Therapeutic Treatment Thereof

This invention relates to tetrahydropyranonaphthyridines derivatives having formula (III) or IV: and analogues of the tetrahydropyranonaphthyridines derivatives. The invention also relates to pharmaceutical compositions comprising these compounds and methods for treatment of tuberculosis using these compounds.
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Human Antibodies Against Hepatitis C Virus (hcv) Uses Thereof.

Isolated human monoclonal antibodies which bind to hepatitis C virus (HCV), and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced in a transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals,
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Reagents for Recombinogenic Engineering and Use Thereof

The present invention features homologous recombination methods and systems. The methods and systems promote highly efficient homologous recombination in cells (e.g., in prokaryotic cells). The methods and systems are useful, for example, in pharmaceutical drug development, vaccine development and cloning.
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Antibodies to Treat Cancer

Compositions and methods for the treatment of cancer, particularly melanoma, myeloma, small cell lung cancer, thymic lymphoma, T-cell lymphoma, B-cell lymphoma, osteosarcoma, and acute T-cell leukemia, are disclosed. Illustrative compositions include one or more anti-ganglioside antibodies and polynucleotides that encode such anti-ganglioside antibodies. These antibodies may be for example, hamster antibodies, chimeric human/hamster antibodies, or humanized antibodies. The disclosed compositions
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Espfu Nucleic Acids and Proteins and Uses Thereof

Disclosed are EspFU (EspF-like polypeptide encoded by a gene of the cryptic prophage CP-933U of enterohemorrhagic E. coli) polypeptides, fragments thereof, nucleic acids that encode EspFU polypeptides, or fragments thereof, and cells including the polypeptides, fragments, and/or nucleic acids. Also disclosed are model systems, kits, and methods for screening that use, for example, EspFU polypeptides and nucleic acids. Also included are pharmaceutical and diagnostic compositions and methods of di
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Compounds and Methods for Treating Mammalian Gastrointestinal Microbial Infections

Described herein are compounds, and pharmaceutically acceptable salts and prodrugs thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound of the invention selectively inhibits a parasitic IMPDH versus a host IMPDH. Further, the invention provides pharmaceutical compositions comprising one or more compounds of the invention. The invention also relates to methods of treating various parasitic and bacterial infections in mammals. Moreover, the compounds may be used alo
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Compositions with Enhanced Bioavailability and Fast Acting Inhibitor of Gastric Acid Secretion

The present invention relates to the use of pharmaceutically acceptable zinc salts, preferably water soluble zinc salts alone or optionally, in combination with one or more of a protein pump inhibitor (PPI), H2 blocker, anti-H. pylori antibiotic/antimicrobial, cytoprotective agent or a combination agent as otherwise described herein for providing fast action with optional long duration effect in reducing gastric acid secretion, raising the p? of the stomach during resting phase as well as decrea
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Methods of Treating Cancer and Other Conditions Or Disease States Using Lfmau and Ldt

The present invention relates to the use of the compound according to formula (I), below for the treatment of tumors, cancer and hyperproliferative diseases, among other conditions or disease states: Where X is H or F; R1 and R2 are independently H, an acyl group, a C1-C20 alkyl or ether group, a phosphate, diphosphate, triphosphate or a phosphodiester group, a (A) or (B) group; Where Nu is a radical of a biologically active compound such as an anticancer, antiviral or antihyperproliferative com
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Anti-inflammatory compounds and uses thereof

The present invention provides anti-inflammatory compounds, pharmaceutical compositions thereof, and methods of use thereof for treating inflammatory disorders. The present invention also provides methods of identifying anti-inflammatory compounds and methods of inhibiting NF- B-dependent target gene expression in a cell.
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Immunogenic Epitopes As Targets for Universal Cancer Vaccines

The present invention provides a peptide having an amino acid sequence as set forth in SEQ ID NOs: 1 through 95 and any combination there of. The peptide or combination of peptides possess 0CT4 specific inducibility. The peptide or combination of peptides can further be used as a vaccine.
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Anti-inflammatory Compounds and Uses Thereof

The present invention provides anti-inflammatory compounds, pharmaceutical compositions thereof, and methods of use thereof for treating inflammatory disorders. The present invention also provides methods of identifying anti-inflammatory compounds and methods of inhibiting NF-[kappa]B-dependent target gene expression in a cell.
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Anti-hepatitis C Activity of Meso-tetrakis-porphyrin Analogues

The present invention relates to porphyrin analogues, their use in pharmaceutical compositions alone, or combination with other agents and in the treatment and/or prophylaxis of flaviviridae viral infections, especially hepatitis C viral infection, and secondary disease states and/or conditions associated with same.
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Mif Modulators

The invention provides novel heterocyclic compounds, pharmaceutical compositions and methods of treatment that modulate levels of MIF expression and treat disorders associated with high or low levels of MIF expression.
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Use of Hsp90 Protein Inhibiting Compounds and Pharmaceutical Composition Intended for Anti-tumour Therapy

The invention relates to a method for designing an individual anti-tumour therapy for a patient based on the detection of the levels of the Hsp90 protein responsible for resistance to a drug or a mixture of anti-tumour drugs that inhibit receptors IGF1R/KIT. The invention also relates to the use of Hsp90 protein inhibitors for the production of drugs for the treatment of tumours resistant to IGF1R/KIT inhibitors, the resulting pharmaceutical compositions and the use thereof on Ewing's sarcoma tu
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Method for Marking and Identifying Manufactured Articles, Substances and Organisms, and Uses Thereof

The present invention comprises a method for marking and identifying manufactured articles, substances and organisms (referred to below as "products"), based on the addition to the product to be marked of a known mixture of two or more isotropic profiles of a single chemical element that are enriched in different stable isotopes. Identification thereof may be performed by measuring the ratio of molar fractions between those isotropic profiles present in the product using mass spectrometry. The p
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Spiropiperidyl Rifamycins for the Treatment of Microbacterial Infections

The compounds of formula (1), their pharmaceutically acceptable salts and their solvates, wherein R 1 is a radical selected between hydrogen and alkyl; R 2 is selected from hydroxyalkyl, phenyl, phenyl mono-substituted and phenyl di-substituted in positions 3 and 4; R 3 is selected from phenyl, phenyl mono-substituted and phenyl di-substituted in positions 3 and 4; the substituents of the phenyl of R 2 and R 3 selected from halogen, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxyl and R 4 is selected f
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Deuterated Tapazole and Derivatives, Preparation Method Therefor and Use of Same

The invention relates to deuterated compounds having formula (I) in which R1, R2 and R3 represent independently a hydrogen atom or a C1-C4alkyl group, optionally substituted with: a -OR4 group, R4 representing a hydrogen atom or a C1-C3 alkyl group optionally substituted with phenyl; a -NR5R6 group, R5 and R6 representing independently a hydrogen atom or a C1-C3alkyl group, tosyl or mesyl; a -SR7 group, R7 representing a hydrogen atom or a C1-C3 alkyl group; a -OCOR8 group, R8 representing a C1-
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Recombinant Antigen

The invention relates to a recombinant peptide of the catalytic subunit of the serine/threonine protein phosphatase of Angiostrongylus costaricensis and active peptides used in the production of an intranasal anthelmintic vaccine.
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Peptides for the Treatment of Ocular Hypertension And/or Glaucoma

The invention relates to peptide compounds with the amino acid sequence having formula (I): Tyr-Ala-Arg-Ala-Ala-Ala-Arg-Gln-Ala-Arg-Ala-(X)-Ser-Asp-Gly-Gly-pTyr-Met- Asp-Met-Ser (I), wherein (X) is none, one or more amino acid spacer residues and pTyr is a phosphorylated tyrosine, and variants and derivatives of said compounds, which can be used in medicine to reduce intraocular pressure. The peptides or the pharmaceutical compositions containing same can be used for the treatment and/or prevent
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Bisthiazole Compounds That Can Be Used to Treat Cancer

The invention relates to compounds having formula (I), the pharmaceutically acceptable salts thereof, or the solvates of same, wherein: Ri is selected from phenyl, optionally mono-, di- or tri-substituted with a radical independently selected from F, Cl, Br, I, (C1C4)-alkyl, N,N-(C1,C4)-alkylamino, hydroxy, (C1C4)-alkoxy, phenoxy, methylenedioxy, trifluoromethoxy, trifluoromethyl, carboxyl, 4-phenoxyphenyl and (C1C4)-alkoxycarbonyl; 2-thiazolyl; 2-pyridinyl; 2,2'-bipyridinyl; 2,2'-bisthiazole; n
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Triterpenoid Derivatives Useful As Antiproliferative Agents

Formule (I) and (II). The present invention relates to the use of a new lupane derivative of general formula (I) or (II), or a pharmaceutically acceptable salt, crystal form, complex, hydrate, or hydrolysable ester thereof, for preventing and/or inhibiting tumor growth and for treating cancer and other proliferative diseases, more particularly for treating leukemia, liver, cervical, colon and prostate cancer. The present invention also relates to the synthesis of these compounds and to pharmaceu
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Method for Screening Compounds for the Treatment Or Prevention of Colon Cancer

The invention is in the field of molecular medicine, more in particular in the field of identifying new compounds for the treatment or prevention of colorectal cancer. The invention provides a method for the screening and/or identification of compounds that are capable of preventing or ameliorating the adverse effects of reactive oxygen species on eukaryotic cells. More in particular, the invention provides a method for the identification of an active therapeutic compound for preventing or ameli
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Antagonistic Peptides for Frizzled-1 and Frizzled-2

The invention is in the field of molecular medicine. It provides antagonistic compounds for frizzled-1and/or frizzled-2 receptors which may be useful in molecular imaging of the wound healing process after myocardial infarction and in therapeutic intervention into wound healing after remodeling of the heart, thereby ameliorating the consequences of myocardial infarction. The invention provides a method for antagonizing frizzled-1 or frizzled-2 receptors wherein the receptor is contacted with a c
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Method for the Treatment of Ischemia Reperfusion Injury

The invention is in the field of thrombosis, haemostasis, cardiology, medicinal chemistry and/or pharmacology. More particularly, it relates to the use of a mutant activated protein C (APC) for the treatment of ischemia reperfusion injury. A method is provided for treating or preventing reperfusion injury following an ischemic event that comprises administering to a subject a pharmaceutical preparation comprising a mutant APC or a precursor thereof. Compositions for use in the present invention
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A3 Adenosine Receptor Allosteric Modulators

The present invention relates to allosteric modulation of A3 adenosine receptor (A3AR) and provides for the use of an A3 adenosine receptor modulator (A3RM),for the preparation of pharmaceutical compositions for modulating the A3AR in a subject, as well as pharmaceutical compositions comprising the same and therapeutic methods comprising administering to a subject an amount of an A3RM, the amount being effective to modulate A3AR activity. The A3RM according to the invention are 1H-Imidazo-[4,5-c
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Compounds and Uses

The invention relates to a compound having the formula of structure (I): or a pharmaceutically acceptable salt thereof, for use in treating a LH receptor-related condition.
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Novel Antimalarial 3-azabicyclo[3.2.2]nonane Derivatives

The present invention relates to novel 3-azabicyclo[3.2.2]nonane derivatives of the general formula (I) or a pharmaceutically acceptable salt thereof wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are as defined in the specification. The novel 3-azabicyclo[3.2.2]nonane derivatives are particularly useful for treatment and prevention of malaria and trypanosomiasis.
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Tryptamine-derived Compounds As Antibacterial Agents

The present invention relates to a compound according to formula I, a pharmaceutically acceptable salt and/or N-oxide thereof for use as an antibacterial agent.
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Water Soluble Curcumin Compositions for Use in Anti-cancer and Anti-inflammatory Therapy

The present invention relates to the medical field. In a first aspect the present invention relates to novel water soluble cyclodextrin-curcumin complexes having a pharmacological activity, in particular an anti-tumour and/or anti-inflammatory activity, and improved physico-chemical properties. In a second aspect, the present invention relates to a method for preparation of said water soluble curcumin derivatives. The invention further relates in a third aspect to a pharmaceutical composition co
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Method for Generating Islet Beta Cells from Dedifferentiated Exocrine Pancreatic Cells

The present invention relates to an in vitro method for generating insulin-producing beta cells from a population of mammalian cells comprising dedifferentiated exocrine pancreatic cells. The method comprises the step of culturing said dedifferentiated exocrine pancreatic cells in a culture medium in the presence of at least one agent that is able to inhibit the Notch 1 signaling pathway in said dedifferentiated exocrine pancreatic cells, and at least one ligand of the gp130 receptor and/or at l
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In Vitro Cultivation of Helicobacter Species.

The present invention relates to media and methods for the isolation and cultivation of "Candidatus Helicobacter suis" and isolates of "Candidatus Helicobacter suis" obtainable by these methods. The present invention further relates to the use of these bacteria for the manufacture of antigen preparations and vaccines.
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Novel Vaccine Against Trypanosoma Cruzi Infection

The present invention relates to a vaccine against Trypanosoma cruzi infection, useful in the prevention and/or treatment of the Chagas disease. More specifically, the present invention relates to a recombinant mutant trans-sialidase enzyme that can be used as an efficient vaccine, without side effects.
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Immediate Release Pharmaceutical Granule Compositions and a Continuous Process for Making Them

A pharmaceutical or veterinary granule composition in the form of a mixture consisting essentially of: (i) at least one drug classifiable as Class II or Class IV of the Biopharmaceutical Classification System, wherein said drug (i) constitutes from 0.5% to 20% by weight of the composition, and excipients, said pharmaceutical or veterinary granule composition providing a drug release of at least 70% within 10 minutes in water, (ii) a first excipient being a maltodextrin representing from 40% by w
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Vitamin D3 Analogues for the Prevention and Treatment of Bone Disorders

Novel vitamin D analogues are useful for making pharmaceutical compositions for the prevention or treatment of bone disorders such as osteoporosis
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Streptococcus Pneumoniae Vaccines

Streptococcus pneumoniae is a major cause of pneumoniae, meningitis, and major cause of morbidity and mortality throughout the world by bacterial otitis media, pneumoniae, meningitis, and bacteraemia. It is an important agent of disease in man especially among infants, the elderly and immunocompromised persons. The present invention provides a solution to this problem by providing a substantially pure or isolated disease related antigen selected from the group consisting of the isolated, recombi
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Novel Bicyclic Heterocycles

The present invention relates to compound of formula I, II, III, or IV, and/or a pharmaceutical acceptable addition salt thereof and/or a stereoisomer thereof and/or a solvate thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R11, and R12 are as defined in the claim 1. The present invention also relates to a method for their preparation, as well as to pharmaceutical compositions thereof. The present invention further relates to the use of said compounds as biologically active ingredients, mor
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Morpholine Derivatives Used As Antifungal Compounds

The present invention relates to a series of novel compounds (I) which have been shown to possess antifungal activity. The invention therefore relates to the new compounds, methods for their preparation, pharmaceutical compositions comprising them and to the compounds for use as a medicament, more in particular antifungal medicament.
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Indole Amide Derivatives and Related Compounds for Use in the Treatment of Neurodegenerative Diseases

This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic a-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders
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Anti-viral Pyrimidine Nucleoside Derivatives

A compound for use in the treatment or prophylaxis of viral infections such, for example as chicken pox or shingles caused by the Varicella Zoster virus, said compound having the general formula (II): wherein X is O, S, NH or CH2, Y is O, S or NH, Z is O, S or CH2, R1 is C1-6 alkyl, preferably n-alkyl, e.g., n-pentyl or n-hexyl, and one of R2 and R3 is OH, and the other of R3 and R2 is a neutral, non-polar amino acid moiety, or a pharmaceutically acceptable salt or hydrate thereof. Said neutral,
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Synthesis of Resorcylic Acid Lactones Useful As Therapeutic Agents.

Disclosed are macrocyclic compounds of formulae I, I', II, II', III, III', IV, and V, which are analogs of the pochonin resorcylic acid lactones, pharmaceutical compositions comprising the compounds, and methods and uses comprising the compounds for the treatment of diseases mediated by kinases and Heat Shock Protein 90 HSP90.
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Oral Galenic Form, Polymer Production Method and Use of Same

The polymers according to the invention comprise a polysaccharide block (17) and several hydrophobic polyacrylic blocks (18) enabling the polymer to remain intact until it reaches the colon. The polysaccharide block is degraded by the colonic microflora irrespective of the pH, while the polyacrylic blocks are solubilized at neutral pH. Colon-specific release of the active ingredients is thus provided in all cases. These polymers may serve as a coating in particular for tablets, gel capsules, gra
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Hydroxy-bisphosphonic Acid Derivatives As Vector for Targeting Bone Tissue

The present invention relates to hydroxy-bisphosphonic acid derivatives corresponding to general formula (I): in which: - n and m denote, independently of one another, an integer ranging from 1 to 4, - X denotes an oxygen atom or an N-R3 group, - R1 and R3 denote, independently of one another, a linear or branched C1 to C6 alkyl group, and - R2 denotes a residue of a molecule of therapeutic or diagnostic interest, or pharmaceutically acceptable salts of said derivatives, and also the method for
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Piperidine derivatives, process for their preparation and pharmaceutical compositions containing them

Phenyl-carbamic acid piperidin-3-yl ester compounds (I) and their enantiomers, and addition salts with an acid or a base are new. Phenyl-carbamic acid piperidin-3-yl ester compounds of formula (I) and their enantiomers, and addition salts with an acid or a base are new. R 1> : H or methyl group; and R 2> : Br, F or CF 3. An independent claim is included for the preparation of (I). [Image] - ACTIVITY : Nootropic. - MECHANISM OF ACTION : None given.
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ANXIOLYTIC COMPOSITION CONTAINING ALPHAs-CASEIN -DERIVED PEPTIDES

The invention relates to pharmaceutical compositions and food products containing peptides derived from the as1-casein in milk and having benzodiazepine-type activity and particularly, anxiolytic activity.
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Stambomycin and Derivatives, their Production and their Use As Drugs

The present invention relates to Stambomycin compounds, their derivatives and their pharmaceutically acceptable salt thereof.
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Casein-Derived Peptides having Anxiolytic Activity

The invention relates to peptides and, in particular, heptapeptides derived from milk casein [alpha]s1 and having anxiolytic activity. The invention also relates to pharmaceutical and food compositions containing said peptides and to the preparation methods thereof.
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Peptides Modulating the Activity of IGF-1 and the Applications of Said Peptides

The invention relates to peptides that can modulate the activity of IGF-1, to a pharmaceutical composition containing said peptides, and to the applications thereof as medicaments and agents for the in vitro modulation of cellular proliferation.
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Analogs of Temporin-sha, and Uses Thereof

The present invention relates to novel antimicrobial peptides, to pharmaceutical compositions including said peptides, and to the uses thereof, in particular as antimicrobial drugs, disinfectants, pesticides or preservatives. The present invention also relates to a transgenic plant expressing said novel peptides.
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Nitrogen Heterocycle Derivatives As Proteasome Modulators

The instant invention relates to the use of at least one nitrogen heterocycle derivative of formula (I): as proteasome activity modulator in the manufacture of a pharmaceutical composition intended to prevent and/or treat a disease condition mediated by the proteasome activity.
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Viral Encoded Pellino Protein and Its Uses

This invention relates to a pharmaceutical composition. In particular, it relates to a virally encoded form of a Pellino protein and its use in the regulation of signalling pathways that are associated with immune disorders.
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Guanidine Based Compounds

The adrenergic receptors or adrenoceptors are a family of G-protein coupled receptors split into a and ss subclasses. The adrenoceptors have important roles in regulating a myriad of physiological conditions and their malfunction has been implicated in the pathophysiology of anumber of diseases. Disclosed herein are a series of novel guanidine and 2-aminoimidazoline compounds which are ligands of the alpha2- adrenoceptor (a2-ARs) subclass of adrenergic receptors. The invention also provides for
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Modified Helicobacter Protein

A vaccine comprising a structurally modified AhpC protein for inducing immunoreactivity against Helicobacter pylori. The structurally modified AhpC protein may have a molecular weight of between about 3OkDa to about 5OkDa. A modified AhpC protein with enhanced immunogenicity and antibodies raised against a structurally modified AhpC protein are also described.
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Treatment of Microbial Infections

The present invention is directed to improved microbial antigen vaccines, pharmaceutical compositions, immunogenic compositions and antibodies and their use in the treatment of microbial infections, particularly those of bacterial origin, including Staphylococcal origin. Ideally, the present invention is directed to a recombinant staphylococcal MSCRAMM or MSCRAMM-like proteins, or fragment thereof, with reduced binding to its host ligand, for use in therapy.
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Efficient Aspirin Prodrugs

Aspirin is one of the most widely used drugs in the treatment of inflammation, pain and fever. It has more recently found application in the prevention of heart attacks and stroke and is being studied as a cancer chemopreventative agent. Despite its value aspirin continues to be underutilized because it causes gastric bleeding. The technology under development potentially removes this problem. It is designed to reduce contact between the drug and the intestinal lining. An isosorbide aspirinate p
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Soluble Influenza Vaccine

The invention provides fusion proteins comprising: (i) a first portion comprising an influenza A M2e polypeptide, and (ii) a second portion comprising a rotaviral NSP4 polypeptide. The fusion proteins mimics the native tetrameric structure of native M2 protein. Additionally it is highly soluble and as disclosed herein can be produced and isolated in large quantities extremely quickly and efficiently. Also provided are related materials and methods, including use of the fusion proteins as vaccine
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PDZ Domain Modulators

This invention relates to compounds useful as PDZ domain modulators, in particular the PDZ domain of PICK1. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions.
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Vaccine

The invention provides a vaccine comprising secreted protein derived from Mycobacterium avium subsp paratuberculosis (M. ptb) substantially free of whole organisms of that species either dead or alive. The secreted protein may be obtained from a culture of M. ptb with the microorganisms being removed by centrifugation and subsequent filtration. The vaccine may be used for vaccination against Johne's disease.
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Multi-component Compositions and Methods for Delivery of Anti-cancer Agents

The present invention relates to a composition for the treatment or prevention of cancer, the composition comprising 5-fluorouracil, or a pharmaceutically acceptable salt or analogue thereof; folinic acid, or a pharmaceutically acceptable salt thereof, oxaliplatin and a cyclodextrin or a pharmaceutically acceptable salt or derivative thereof.
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Group a Streptococcus Pharmaceutical Compositions and Methods Thereof

Isolated proteins and immunogenic fragments thereof, for use in the treatment and prevention of a Group A Streptococcus infection are provided. In particular, the invention provides pharmaceutical compositions and methods of prophylactic and/or therapeutic treatment of a Group A Streptococcus infection.
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Compositions and Methods for Delivery of Anti-cancer Agents

The present invention relates to compositions comprising 5-fluorouracil, or a pharmaceutically acceptable salt or analogue thereof, folinic acid, or a pharmaceutically acceptable salt thereof and a cyclodextrin, or a pharmace utically acceptable salt or derivative thereof. The invention also relates t o methods for the treatment of cancer using such compositions.
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Antimicrobial Compounds

The present invention relates to antimicrobial compounds and their uses, and in particular to peptide antibiotics which may be used in the treatment of Gram-negative bacterial infections.
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Compositions and Methods for the Treatment of Disease

The present invention relates to pharmaceutical compositions for the treatment and/or prophylaxis of disease associated with fibrosis in a vertebrate, said composition comprising at least one activin antagonist, and optionally a pharmaceutically acceptable carrier, adjuvant and/or diluent. The invention also relates to methods of treatment of disease associated with fibrosis in a vertebrate, as well as methods for diagnosing such conditions, and kits therefor.
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A Method for Treating Obesity

A method and pharmaceutical composition for treating a disease or condition associated with elevated hypothalamic T cell protein tyrosine phosphatase (TCPTP) such as obesity, weight gain, type 2 diabetes mellitus, insulin sensitivity, impaired glucose tolerance, and inflammation is disclosed. The method involves administering a subject with an agent which inhibits the activity or expression of TCPTP, wherein the agent is administered, adapted and/or formulated in a manner ensuring that an effect
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2-ARYLPYRAZOLO[L,5-alpha]PYRIMIDIN-3-YL ACETAMIDE DERIVATIVES AS LIGANDS FOR TRANSLOCATOR PROTEIN(18 KDA)

The invention provides compounds of formula (I) radiolabelled with 18F, 123I, 76Br, 124I or75Br and salts thereof, and a method of imaging translocator protein (18kDa) (TSPO) in a subject comprising administering a compound of formula (I) radiolabelled with 18F, 123I, 76Br, 124I or 75Br or a pharmaceutically acceptable salt thereof. The invention further provides fluoro-substituted compounds of formula (II) and salts thereof, and a method of treating a neurodegenerative disorder, inflammation or
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Administrable Compositions

The present invention relates to a composition suitable for administration to a subject, the composition comprising pharmacologically acceptable particulate material dispersed throughout a pharmacologically acceptable liquid carrier, the particulate material being maintained in the dispersed state by a steric stabiliser, wherein the steric stabiliser is a polymeric material comprising a steric stabilising polymeric segment and an anchoring polymeric segment, one or both of which are derived from
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Halogenated Analogues of Anti-fibrotic Agents

The present invention relates to halogenated compounds of formula (I) with the substituents as described within the specification. The compounds may be useful as anti-fibrqtic agents. The present invention also relates to methods for their preparation.
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Porous Silica Shell-mediated Assembly of Macromolecular Capsules

The present invention relates to a process of preparing macromolecular capsules. In particular, the invention relates to the use of a template with a permeable shell and an impermeable core for preparing macromolecular capsules. The process of the present invention relates to infiltrating macromolecules such as polymers into a permeable shell and then crosslinking the macromolecules to form a macromolecular network within the pores of the permeable shell. In some cases, the permeable shell and i
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A Temperature Sensitive Vaccine Strain of Mycoplasma Hyopneumoniae and Uses Thereof

The present invention relates to a Mycoplasma hyopneumoniae vaccine strain comprising a mutation in at least one of the genes listed or as deposited with the National Measurements Institute (Australia) under accession number NM04/41259, which strain is temperature sensitive and attenuated, a vaccine comprising such strains and methods and uses thereof.
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Polypeptides et polynucleotides de phorphorymonas gingivalis

The present invention relates to isolated Porphorymonas gingivalis polypeptides and nucleotides. The polypeptides include; an amino acid sequence selected from the group consisting of SEQ. ID. NO. 265 to SEQ. ID. NO. 528, SEQ. ID. NO. 531 and SEQ. ID. NO. 532; or an amino acid sequence at least 85%, preferably at least 95%, identical to an amino acid sequence selected from the group consisting of SEQ. ID. NO. 265 to SEQ. ID. NO. 528, SEQ. ID. NO. 531 and SEQ. ID. NO. 532; or at least 40 amino ac
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A Synthetic Vaccine Component

The present invention relates generally to the field of synthetic vaccines, components thereof and methods for producing same. More particularly, the present invention provides a component of synthetic vaccines and its use in a modular approach to vaccine production.
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Dinuclear, Quadruply-stranded Compounds Comprising Palladium Or Platinum

The invention relates to a compound of formula (M2L4 where: M = a palladium or platinum metal ion; L = X = -O-, -S-, -NH-, or (-CH2-)n, where n = 1, 2 or 3; R2, R4, R5, R6 are each independently selected from -H, -F, -Cl, -Br, -I, -methyl, -ethyl, -propyl, -O-methyl, -OH, -CH2OH, and - CH2CH2OH, R7, R8, R9, R10 are each independently selected from -H, -F, -Cl, -Br, -I, - methyl, -ethyl, -propyl and -O-methyl; a pharmaceutically acceptable salt, complex thereof, compositions comprising the compou
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Anti-cancer Composition Comprising Alginate

The present invention relates to a biologically acceptable composition for the prophylaxis and/or treatment of colorectal cancer comprising an iron chelator, wherein the composition is adapted for the selective targeting of the iron chelator to the colon.
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Use of Pharmaceutical Compound Containing Crotoxin for the Treatment of Muscle Dystonias

The present invention is related to the use of a pharmaceutical compound containing a toxin extracted from the rattlesnake (Crotalus durissus terrificus) venom, known as crotoxin, which can act as an agent provoking muscular paralysis. Medical uses of this invention formulation are described, which was developed for muscular pathological conditions whose muscular paralysis is desired, such as strabismus, blepharospams, and nystagmus, among others.
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Methods for Synthesizing Glycinols, Glyceollins I and Ii, Compositions of Selected Intermediates, and Therapeutic Uses Thereof

Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, di
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Therapeutic Aryl-am I Do-aryl Compounds and their Use

The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-amido-aryl compounds of the following formula (for convenience, collectively referred to herein as "AAA compounds"), which, inter alia, are (selective) retinoic acid receptor a (RARa) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) ac
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Hot-melt Extrusion of Modified Release Multi-particulates

The present invention includes compositions and methods of making a modified release pharmaceutical formulation and a method of preparation for the embedding of modified release multi-particulates into a polymeric or wax-like matrix. The modified release multi-particulates comprise an effective amount of a therapeutic compound having a known or desired drug-release profile. Modified release multi-particulates may include a polymeric coat or may be incorporated into particle or core material. The
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Use of Riboflavin in the Treatment of Hypertension.

The invention provides the use of riboflavin in the manufacture of a medicament for the treatment or prophylaxis of elevated blood pressure in a subject homozygous or heterozygous for the MTHFR C677T polymorphism. The invention also provides a pharmaceutical product for the treatment or prophylaxis of elevated blood pressure in a subject homozygous or heterozygous for the MTHFR C677T polymorphism, comprising a pharmaceutically effective amount of an anti-hypertensive agent and riboflavin, and th
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Combinations Comprising Epothilone Derivatives and Alkylating Agents and Pharmaceutical Compositions Comprising Them

The invention relates to a pharmaceutical combination which comprises (a) an alkylating agent and (b) an epothilone derivative of formula (I) wherein A represents O or NRN, wherein RN is hydrogen or lower alkyl, R is hydrogen or lower alkyl, and Z is O or a bond. Said combination can be useful for the treatment of a proliferative disease, especially a tumor disease.
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P53 Tumor Suppressor Protein Activating

The invention provides a compound of formula (I), wherein X, L1-4 and R1-4 are as defined herein, with the proviso that the compound is not (i) 4-benzoyl-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester; (ii) 4-(2,5-difluorobenzoyl)-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester); (iii) 4-acetyl-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester; or (iv) 4-(3-dimethylamino-acryloyl)-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester, or a pharmaceutically acceptable derivative
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Pyrimide Derivatives and their Pharmaceutical Use

The invention provides a compound according to formula (I): wherein: X is O or S; Y is O or S; each Ar and Ar' is independently a mono-, bi- or tricyclic aryl or heteroaryl group optionally substituted with one or more substituents selected from halo, alkyl, aryl, heteroaryl, hydroxyl, nitro, amino, alkoxy, alkylthio, cyano, thio, ester, acyl and amido; each R2 is independently hydrogen, halo, alkyl, aryl, heteroaryl, hydroxyl, nitro, amino, alkoxy, alkylthio, cyano and thio; and R1 is as define
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SingleC-9 Binding Agents

The present invention relates to agents capable of binding sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) and their use in the treatment of cell proliferation and differentiation disorders. Furthermore, the present invention provides associated pharmaceutical formulations and methods.
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Use of Tiamulin As an Antiviral Agent

The invention relates to an antiviral medicament produced using an antibiotic. The invention relates to the use of an antibiotic in the preparation an antiviral medicament. The invention also relates to a method of treating a viral infection comprising administering an antibiotic to a subject having a viral infection. Tiamulin is a diterpene antibiotic with a pleuromutilin structure similar to valnemulm. Tiamulin has the following structure:
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Methods for Identification

The invention relates to methods for the discovery of new chemical entities and pharmaceutical compositions with broad-spectrum chemokine inhibitor (BSCI) activity, together with the use of such agents as anti-inflammatory medicaments. In one aspect the method for the identification of a compound or agent with BSCI activity comprises the steps of : (a) firstly one or more candidate compounds or agents are screened for binding to a GPCR neuroreceptor known to be expressed on leukocytes; then (b)
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Improved Methods for Identification

The invention relates to methods for the discovery of new chemical entities and pharmaceutical compositions with broad-spectrum chemokine inhibitor (BSCI) activity, together with the use of such agents as anti-inflammatory medicaments. In one aspect, there is provided a method for the identification of a compound or agent with BSCI activity comprising the steps of (a) firstly one or more candidate compounds or agents are screened for binding to a somatostatin receptor such as the type 2 somatost
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Fusion Polypeptide Comprising S-antigen Repeat Units

The present invention relates to a fusion polypeptide comprising a) at least one fragment of the Plasmodium falciparum S-antigen or a variant thereof, wherein the fragment comprises one or a plurality of Plasmodium falciparum S-antigen repeat unit(s) or variant(s) thereof and b) at least one antigen different from the S-antigen. The present invention also relates to a pharmaceutical composition comprising that fusion polypeptide as well as to the use thereof for the treatment or prevention of an
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Anti-inflammatory Compositions and Combinations

Use of broad-spectrum chemokine inhibitors (BSCIs), and in particular members of the acylaminolactam class of pharmaceutical agents, for the prevention, prophylaxis, treatment or amelioration of symptoms of inflammatory diseases. In particular, improved compositions consisting of BSCI agents combined with one or more additional active pharmaceutical agents in order to achieve improved anti-inflammatory efficacy with a reduced side-effect profile are described and claimed.
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Anti-inflammatory composition

The invention relates to 3-(2',2'-dimethylpropanoylamino)-tetrahydropyridin-2-one, and its pharmaceutical compositions and its use for preparing a medicament intended to prevent or treat inflammatory disorders.
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Dimethylthiofoxins and azafoxins which may be useful as ligands for G-protein coupled receptors

The invention provides compounds of general formulae (II) or (III), or pharmaceutically acceptable salts thereof. X is -CO-(Y)k-(Z)nor -SO2-(Y)k-(Z)nwherein k is 0 or 1, each Y is a cycloalkyl, polycycloalkyl, cycloalkenyl or polycycloalkenyl group, n is an integer from 1 to the maximum number of substitutions permissible on the cyclo group Y, each Z is H or various residues or Z may be a peptide radical. R2, R3and R4are independently any substitutent.; The invention also provides methods for pr
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Novel Antibiotic Compositions

This invention is directed to antibiotic compositions comprising a targeting moiety covalently linked to an antibiotic moiety. This invention is also directed to pharmaceutical compositions comprising the antibiotic compositions of the invention and methods of making and using the antibiotic compositions of the invention.
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Anti-inflammatory agents

The invention provides compounds, pharmaceutical compositions and uses of compounds and salts thereof of general formula (I), for the preparation of a medicament for treatment of an inflammatory disorder, <PC>but excluding (S)-3-(1'-methylcyclohexylcarbonylamino)-caprolactam; wherein z is 1,2,3 or 4; A is -CO- or -SO2-; Q is alkyl, alkenyl, alkynyl, alkoxy, oxyalkyl, aminoalkyl, alkylamino, alkylaminoalkyl haloalkyl, optionally substituted aryl or tert-butoxycarbonylamino; T<1> and T<2> together
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Magnetically-controlled micro-fluid system for e.g. 'lab-on-chip' system for determination of presence of bio-molecules, virus, biological cells

A micro-fluid system transports tiny particulate quantities of a biological or pharmaceutical liquid sample through a channel exposed to the effect of a magnetic force generated nearby. The channel is exposed to two or more magnetic sources, each separated from the other. - The magnetic force is generated by an electro-magnet by a spiral micro-coil. The coil longitudinal axis runs along or is transverse to the micro-channel. The coil has a core whose tip is directed at the micro-channel. The mag
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Quantitative Screening Assay for Protein Surface Changes

Isis Project No 3849 A new Quantitative Profiling Of biotinylation Patterns (Q-POP) assay, to enable screening for protein surface changes following protein-protein interaction. Potential applications include normal, cancer or pathogen cell function research; enabling identification of new treatment targets. Marketing Opportunity Many biological functions are performed by multimers of different protein subunits so investigation of protein-protein interactions is of great interest in many di
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High-throughput Screening of Membrane Proteins

Isis Project No 3329 A novel method for producing synthetic biological membranes has potential in new high-throughput screens of membrane protein function and drug interactions. Marketing Opportunity Membrane proteins such as G-protein coupled receptors and ion-channels represent around 60% of known pharmaceutical targets. Despite this importance, development is limited by the lack of techniques capable of screening membrane protein function. For example, ion channels; the defective functio
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Improved Physical Methods for Increasing Stereoselectivity

BACKGROUND: Since 1988, the Food & Drug Administration has required that the enantiomeric composition of all drugs be known, making stereoselective reactions essential for the pharmaceuticals industry. However, the reactions used to establish chirality at one or more stereocenters often are not sufficiently stereoselective to warrant asymmetric synthesis, thus necessitating the addition of costly stereoisomer resolution steps. Chiral pool resolution strategies have two significant limitations th
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Bifunctional Catalysts and Methods for Synthesis of Impermeable and Semipermeable Coatings

BACKGROUND: Fields that involve the handling of sensitive materials, such as electronics, chemicals, and biological agents need a means of safely isolating these items to protect them or the outside environment from contamination. Current methods for coating, sealing, or encapsulating these materials may involve exposure to heat or other chemicals, which can be detrimental to both the substance and the environment. DESCRIPTION: Scientists at the University of California have developed metho
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One-Pot Organocopper Chemistry and Stereospecific Nucleoside Formation

A researcher at the University of California has made several inventions related to organic syntheses involving higher-order cuprates. Higher-order organocuprates are reagents containing copper atoms to which are bound multiple negatively-charged ligands in ethereal solvents, and have been successfully exploited as highly selective and efficient means of making carbon-carbon bonds. The use of cuprates in 1,4-conjugate addition reactions for introduction of unsaturated carbanions is particularly
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DNA Binding Compounds for Genetic Regulation and Medical Diagnosis and Therapy

Compounds that bind to DNA could be used to target drugs to DNA and to regulate expression of genes. Indeed, many compounds have been discovered (e.g. Distamycin) which bind to the minor groove of DNA, but the bond is too weak for reliable medical application. Scientists at the University of California have discovered a class of novel compounds that have a high binding affinity for DNA (Keq>=109 M-1). The compounds bind in the minor grooves of the double helix and extend into the major groov
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RNA Nano-Constructions for Cell Detection and Drug Delivery

BACKGROUND: RNA has been previously demonstrated to assemble into nanoparticles of various shapes and sizes. These nanoparticles are able to carry various non-RNA components, including molecules for specific cell recognition, image detection and therapeutic treatment, making them ideal drug delivery particles. Engineered RNA nanoparticles have been used to target and attack hepatitis B virus, as well as enabling apoptosis in cancer cells. DESCRIPTION: Researchers at UCSB have developed novel
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Multiplexing Protein Binding Microarrays for Genetic Analysis

BACKGROUND: Our ability to understand and practically benefit from the control logic encoded in the human genome is currently limited by a lack of accurate information regarding promoter regulation. Gene regulatory proteins play critical roles in converting the genome into the complex ensemble of expressed genes which define variations in cell types and human health. Currently available antibody and surface Plasmon resonance-based methods have provided unprecedented insights into the promoter-sp
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Novel Agents that act in Steroid-like signaling pathways in Medicine and Agriculture

BACKGROUND: The END-2 protein of the nematode Caenorhabditis elegans is a member of the nuclear hormone receptor family. Classically, nuclear hormone receptors are thought to be localized in the cytoplasm and nucleus of the cell. Steroids or steroid-like molecules, such as retinoids, diffuse across membranes, bind to the appropriate nuclear hormone receptors and cause them to become transcriptional activators. DESCRIPTION: UC researchers have developed new evidence showing that steroid recep
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Methods for Identifying Novel Therapeutics and Diagnostics in the p53 Pathway

BACKGROUND: Current non-surgical cancer therapies rely on the use of compounds or radiation doses that are non-specific for the tumor cells and are highly toxic to humans. Although these treatments are particularly effective against tumor cells, they are also destructive to the surrounding normal cells, which leads to severe side effects. In addition, the non-specificity of these therapies limits their efficacy. Efforts to develop more specific treatments have focused on targeting the defect
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Safe and Potent Synthetic Lung Surfactant for Treating RDS and Acute Asthma

BACKGROUND: The use of lung surfactant dispersions, based on lipid and protein components extracted from animal lung tissue, has significantly reduced mortality and morbidity from respiratory distress syndrome (RDS) in premature infants in the past decade. However, existing lung surfactants are not potent enough or cost effective enough to treat adult RDS and acute asthma, both of which represent far larger indications than neonatal RDS. Growing concerns of possible viral and prion contamination
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Enzyme for Antimicrobial and Vaccine Development

Scientists at the University of California have shown that a specific enzyme is an essential regulator of Salmonella virulence. This enzyme is prevalent in many organisms including most enterobacteria, certain gram negative and gram positive bacteria, as well as archaebacteria. It is expected that this enzyme will be a major virulence factor for many types of infection, including cholera (Vibrio cholerae), the plague (Yersinia), brain infections (Haemophilus influenzae), typhoid fever (Salmonell
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Initiators for Block-Copolypeptide Synthesis

BACKGROUND: Amino acid-N-carboxyanhydride (NCA) polymerizations employing conventional initiators (e.g. hexylamine or sodium methoxide) are plagued by chain-breaking transfer and termination reactions which prevent the formation of block copolymers. The mechanisms of NCA polymerization have been under intensive study to find a method for enhancing control over chain growth in these reactions. These investigations have been severely hindered by the complexity of the polymerizations, which can pro
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Tools for the Genetic Manipulation of Fusobacterium Nucleatum

BACKGROUND: Fusobatcerium nucleatum is an anaerobic Gram-negative microorganism that is commonly found in the mouth. For example, Fusobacterium nucleatum is the most frequently isolated pathogen from periodontal disease sites and is believed to be an initiator of periodontal diseases. Moreover, this bacterium is commonly found in abscesses and other infections in the abdomen, blood, chest, lung, sinuses, and female genital tract. Several F. nucleatum proteins that are believed to be associated
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BPM-3, a Negataive Determinant of Bone Density

BACKGROUND: Bone morphogenetic proteins (BMPs) are members of the TGFb superfamily, a large family of growth factors with varied functions. BMPs induce the formation of cartilage and bone by influencing cell proliferation, differentiation, morphogenesis and apoptosis. BMP signaling activity is regulated by the relative amounts of different BMP family members, and of BMP antagonists, in a given tissue. This regulation in turn controls the development and maintenance of bone, including peak bone d
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EPLIN, a marker for human Cancer

BACKGROUND: EPLIN, a novel gene not previously described encodes a protein expressed in human epithelial cells. EPLIN is of significant importance because its expression is diminished in many forms of human cancers including breast and prostate cancer. Restoring the expression of EPLIN in cancer cells antagonizes oncogenic transformation. DESCRIPTION: UC researchers have discovered a gene encoding EPLIN. EPLIN cDNA has been cloned, completely sequenced, and tested to detect its expression in
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A Novel Tumor Suppressor Gene

BACKGROUND: Tumor suppressor genes are genes that, when damaged, fail to suppress tumorigenesis. Typically, tumor suppressor genes are genes that, in their wild-type alleles, express proteins that suppress abnormal cellular proliferation. When the gene coding for a tumor suppressor protein is mutated or deleted, the resulting mutant protein or the complete lack of tumor suppressor protein expression may fail to correctly regulate cellular proliferation, and abnormal cellular proliferation may t
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Antibody Fusion Proteins for treating Cancer

University of California researchers have developed a family of antibody fusion proteins with a potential for various therapeutic applications. These inventions represent both novel technologies and products with novel applications. These UC fusion proteins combine an antibody with various cytokines. While these cytokines have been used previously as direct antitumor agents, these antibody-cytokine fusion proteins can be employed in a novel therapeutic strategy. In this role, the fusion prote
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High-Speed, High-Resolution Impedance Sensor

BACKGROUND: While there has been extensive work in developing radio-frequency probes for measuring proximal impedances in air, these probes have been limited to applications using good conductors as their proximal impedance source. For electrolytic and biological samples, lower frequency probes have generally been employed, but they are limited to a relatively low signal-to-noise ratio and slow signal response due to the stray capacitances and large resistances often encountered in such samples.
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A Novel Mechanism and Target for Asthma Intervention

The Challenge Asthma is a chronic inflammatory disorder of the airways characterized by an obstruction of airflow, usually caused by mucus overproduction. Currently, most treatments for mucus hyper secretion (corticosteroids) have limited efficacy and are largely non-specific, indicating a clear need for new therapeutic strategies. Furthermore, morbidity and mortality rates associated with asthma have risen globally over the last 20 years. This increase is largely attributed to an increas
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Linker Microemulsions as a Transdermal Drug Delivery Vehicle

The Challenge A key challenge in developing an effective transdermal delivery system for hydrophobic compounds, involves the creation of formulations that balance high permeability of the stratum corneum barrier with minimal skin irritation. Because of their small droplet size, high oil solubilization capacity and large interfacial area, microemulsions have demonstrated a greater adsorption/penetration of hydrophobic actives when compared to conventional emulsions. Unfortunately, toxicity i
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Rapid Protection from Neuronal Failure following Heat-stroke and Hyperthermia

The Technology We have identified that the down-regulation and reduced activity of certain protein kinase signaling molecules by pharmacological intervention allows the central nervous system to both function at much higher temperatures and recover RAPIDLY following heat-induced neural trauma. This observation of thermo-tolerance and thermo-protection of neural circuits in two divergent insect species raises the possibility that this function may be conserved in mammals. Hence, these sig
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Rim 3F4 Hybridoma Cell Line

The University of British Columbia have developed a cell line for the Rim 3F4 antibody and have isolated and characterized the epitope sequence in the Rim 3F4 protein. The epitope sequence is amenable to recombinant protein expression and the binding characteristics of the Rim 3F4 antibody are ideal for protein purification. The monoclonal antibody Rim 3F4 directed against the bovine 220-kDa disc rim protein was generated from a BALB/c mouse that had been repeatedly immunized with a partially pu
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Rho 1D4 Antibody

Dr. Robert Molday and coworkers at The University of British Columbia, have developed a cell line for the Rho 1D4 antibody and have isolated and characterized the epitope sequence in Rho 1D4 (9 amino acids). The antibody can be covalently bound to affinity gels directly using cyanogen bromide or indirectly using any of the common immobilization linkers. The antibody specifically binds to the C- terminal epitope -T-E-T-S-Q-V-A-P-A- (COOH) of rhodopsin. Proteins containing the epitope tag can be s
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The Ocean Surface Wave Identification and Tracking System (WITS)

APL-WAVES is a set of integrated software tools for the analysis and display of ocean surface directional wave data and related information. Custom wave partitioning and tracking tools provide comprehensive analyses and display of evolving wind sea and swell systems. APL-WAVES can be applied to directional wave spectra from any source including surface buoys, remote sensors, and computer simulations. Features: * A wide variety of wave data plotting options * Wave partitioning for quantifying win
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Advantages of Insulin Delivered as an Aerosol Through the Lungs

A method of delivering a protein, in particular insulin, to the lungs. The method is characterized in that an aerosolized mist of small particles is produced in an associated medicament delivery chamber, the distance from the chamber to the patient's mouth is set to slow the speed of aerosol particles entering the mouth and the flow rate through the chamber is regulated to a low rate of less than about 30 liters per minute. It has been found that administering insulin in accordance with the inve
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A New Potent Irreversible Inhibitor of y-Aminobutyric Acid Aminotransferase (21058/23058)

A promising new candidate inhibitor of the enzyme gamma-aminobutyric acid aminotransferase, critical to central nervous system disorders, has been prepared. Therapeutic potential in the treatment of epilepsy, drug addiction, pain control and neurological disorders is indicated. ADVANTAGES: In vitro studies indicate enhanced inhibition and selectivity toward the GABA-AT enzyme than present day drugs. SUMMARY: A low level of gamma-amino butyric acid (GABA) in the brain is associated with epi
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Inhibitors of B-Lactamases and Uses Therefor (22090, et al)

Over 100 novel inhibitors to b-lactamase, an enzyme that hydrolyzes the lactam ring of the b-lactam containing antibiotics to render the antibiotic inactive, have been identified and developed at Northwestern. These novel inhibitors have affinity for class C b-lactamases as low as 1 nM. As bacterial resistance to antibiotics is widespread, these newly identified inhibitors of b-lactamase activity offer new compounds to be used in combination with antibiotics to treat antibiotic resistant strains
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Protein Kinase Targeted Therapeutics (26087)

A validated novel compound and medicinal chemistry refinement for bioavailable small molecule inhibitors of protein kinases or protein kinase-mediated cellular stress response pathways. ADVANTAGES: A small molecule p38α MAPK inhibitor presents significant therapy potential for neurodegenerative diseases and other CNS disorders where proinflammatory cytokine overproduction is a component, such as Alzheimers (AD) and related indications, Parkinson’s, multiple sclerosis, and traumatic brain
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Clock Gene and Gene Product

Pharmaceutical control of circadian rhythms, whether directly through CLOCK or through other components of the pathway, has a wide range of applications. U. S. Patent Nos. 5,874,241 ,6,057,125, 6,291,429
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Formulation of Toll-like Receptor Ligand with Whole Cell Tumor Vaccine to Enhance Anti-tumor Responses

Established reports in literature have shown that the innate immune system can modulate immune responses against cancer. Lipopolysaccharide (LPS), a Toll-like receptor ligand 4 (TLR4), was absorbed onto whole cell tumor vaccine using a liposome formulation. The liposome reagent was titrated with LPS for greater than 95% complex formulation onto whole tumor cells. The LPS absorbed whole tumor cells had been previously modified to secrete genetically modified cerebrospinal fluid (GM-CSF). After ab
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Use of High-dose Oxazaphosphorine Drugs in Combination with Monoclonal Antibodies for Treating Immune Disorders

(Set) Autoimmune diseases afflict more than 8 million people in the U.S alone. Autoimmunity usually occurs when lymphocytes, which are designed to defend the body against infections and foreign agents, start attacking one or more of the body's tissues or organs. The conventional treatment for many autoimmune diseases includes the systemic use of anti-inflammatory drugs and potent immunomodulatory agents, such as steroids and inhibitors of inflammatory cytokines, and in certain circumstances, cy
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Use of High Dose Cyclophosphamide in Combination with Immune Therapeutics in Anti-Cancer Therapy

Cyclophosphamide and especially high-dose cyclophosphamide has been used for the treatment of certain autoimmune diseases such as severe aplastic anemia. Low to intermediate doses of cyclophosphamide have also been used in combination chemotherapy for treating certain cancers and appears to work either by stopping the growth of cancer cells or by killing the cancer cells. However, remaining cancer cells, especially cancer stem cells, are able to divide and lead to relapse. More recently, immune-
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Emission Ratiometric Kinase Activity Reports in High Throughput Drug Screening and Analysis

Protein phosphorylation is one of the major regulatory mechanisms controlling cellular functions and aberrant kinase activities are found to form the molecular basis for many disease phenotyes. As a result, protein kinases are well recognized as important drug targets and are a focus of small molecule drug discovery efforts. JHU inventors have developed improved emission ratiometric reporters as research tools for monitoring the activation and deactivation of a prototype kinase, cAMP-dependent k
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PS-341 Rescues Cystic Fibrosis Transmembrane Regulator (CFTR) from Endoplasmic Reticulum Mediated Degradation

Endoplasmic reticulum (ER)-associated protein degradation (ERAD) eliminates misfolded, damaged, or mutant proteins with abnormal conformation from the cell. The most common disease-causing protein folding mutation is deletion of phenylalanine at position 508 of the cystic fibrosis transmembrane regulator (�508-CFTR). This mutation results in a temperature-sensitive folding defect and premature degradation by ERAD, which ultimately leads to cystic fibrosis. JHU researchers have demonstrated tha
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Valosin Containing Protein (VCP)/p97 Gene Inhibition Rescues cystic Fibrosis Transmembrane Regulator (CFTR) from Endoplasmic Reticulum Mediated Degradation

Endoplasmic reticulum (ER)-associated protein degradation (ERAD) eliminates misfolded, damaged, or mutant proteins with abnormal conformation from the cell. The most common disease-causing protein folding mutation is deletion of phenylalanine at position 508 of the cystic fibrosis transmembrane regulator (delta F508-CFTR). This mutation results in a temperature-sensitive folding defect and premature degradation by ERAD, which ultimately leads to cystic fibrosis. The p97/valosin-containing protei
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Nrf2 as a Target for Intervening Pulmonary and Systemic Inflammation

Sustained inflammation is critical in the development of several pathophysiological diseases such as Chronic Obstructive Pulmonary Disease (COPD), asthma, sepsis, acute lung injury, cardiovascular disease, in addition to cancer. Research suggests that controlling inflammation is an effective mechanism for intervention but the current inflammation reducers, such as cox-2 inhibitors, are being proscribed due to negative long term side-effects. Researchers at JHU have discovered a novel gene targe
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Inhibiting Binding of Inducible Nitric Oxide Synthase to Cyclooxygenase-2 to Treat Inflammation

Cyclooxygenase (C0X2) and inducible nitric oxide synthase (iNOS) are two major inflammatory mediators. Inducible NOS specifically binds to C0X2 and S-nitrosylates it, enhancing C0X2 catalytic activity. Selectively disrupting iN0S-C0X2 binding prevents NO-mediated activation of C0X2. The synergistic molecular interaction between two inflammatory systems permits assays for developing anti-inflammatory drugs. Patent (Set) WO 2006/116702
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Selectively Targeted Histone Deacetylase Inhibitors

Inhibitors of histone deacetylases (HDAC) are regarded as an important approach to cancer chemotherapy, since they disrupt the aberrant cellular metabolism that occurs in many tumor types. The HDAC inhibitors currently in clinical trials and typified by compounds such as trichostatin (TSA) and MS-275, are effective antitumor agents, but also produce significant toxicity to cells and whole animals. JHU researchers have designed and synthesized 16 compounds which are hybrids including structural a
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Use of Consensus Sequence as Vaccine Antigen to Enhance Recognition of Virulent Viral Variants

Vaccines for diverse viruses will be most effective when they direct the recipient?s response to recognize the most virulent form of the organism. Scientists at JHU have found that circulating strains of hepatitis C virus (HCV) contain substitutions that render the virus less fit. Therefore, the use of a consensus sequence as a vaccine for HCV would stimulate responses that drive the virus to mutate to a less-fit state, thereby rendering it less able to replicate and easier to eradicate. Further
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Method for Targeting Motor Neurons

Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy are disorders of motor neurons for which there is presently no effective treatment. As understanding of the mechanisms of these conditions increases, the possibility for therapy involving delivery of genes to the motor nerve cell bodies is becoming attractive. For example, anti-apoptotic agents, growth factors, free radical scavengers, etc. are thought to show promise for treatment of ALS. However, it is difficult to deliver vectors speci
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Immune Modulation Through Targeting of the MINOR Gene

this gene will induce apoptosis in dendritic cells, thereby limiting immune responses. Inhibition of the gene will prevent dendritic cell death, thereby enhancing immune responses. Dendritic cells are critical to the initiation of the immune response, thus this will provide a central tool to manipulate immune function. Description (Set) Proposed Use (Set) In addition to therapeutic uses, dendritic cells are used as diagnostic tools to monitor or test the ability of immune cells to generate
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Molecular Switches and Methods for Making and Using the Same Involving the Circular Permutation of DNA

The invention provides molecular switches which couple external signals to functionality and to methods of making and using the same. The switches according to the invention can be used, for example, to regulate gene transcription, target drug delivery to specific cells, transport drugs intracellularly, control drug release, provide conditionally active proteins, perform metabolic engineering, create molecular sensors, and modulate cell signaling pathways. Libraries comprising the switches and e
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Suppression of HIV Replication and Prevention/Treatment of HIV-Associated Dementia by Minocycline

This invention describes the addition of a tetracycline derviative to existing combinations of antiretroviral drugs for treatment of HIV-infected individuals. JHU researchers have determined that the tetracycline derivative, which is a potent anti-inflammatory and neuroprotective drug, also inhibits SIV replication in macrophages, the major target cell for HIV/SIV replication in the brain. This invention provides for the use of a tetracycline derviative in combination with currently existing ant
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Antitumor Effects Generated by pNGVL4a-Sig/E7 (detox)/HSP70 DNA Vaccine Administered Through Gene Gun, Biojector and Syringe

DNA vaccines have emerged as an attractive approach for antigen-specific cancer immunotherapy. We have previously linked Mycobacterium tuberculosis heat shock protein 70 (HSP70) to human papillomavirus type 16 (HPV-16) E7 in the context of a DNA vaccine. Vaccination with DNA encoding E7/HSP70 has generated a dramatic increase of E7-specific CD8+ T cell precursors and a strong anti-tumor effect against E7-expressing tumor (TC-1) in vaccinated mice. The success of our strategy has led to two Phase
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Use of Hedgehog Pathway Inhibitors in Small Cell Lung Cancer

We have shown that small cell lung cancer (SCLC), a highly aggressive and frequently lethal tumor, uses an embryonic signaling pathway to promote its growth. This signaling pathway is known as the Hedgehog pathway, and its normal function is to regulate organ formation and regulate progenitor cells in embryos and in some adult tissues. SCLC is characterized by abnormal activation of this pathway which can be specifically inhibited by cyclopamine, a naturally occurring compound. Use of cyclopamin
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Method for producing diverse libraries of encoded polymers

With our reagents, libraries of drug-like molecules are rendered in a format where they can be subjected to evolution. This enables processing of libraries that are about 10 orders of magnitude more diverse than those typically used in high-throughput screens. Such diversity makes it probable that libraries will contain lead compounds for virtually any target, while a library's ability to undergo evolution makes it trivial to identify lead compounds. In addition, simple techniques within the ca
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Inhibitors of N-ethylmaleimide Sensitive Factor

JHU researchers have discovered that a previously described protein N-ethylmaleimide Sensitive Factor (NSF) regulates thrombosis. Inhibition of NSF, by certain cell permeable peptides, has been discovered as a novel method of anticoagulation. It has also discovered that these cell permeable NSF peptides inhibitors inhibit exocytosis. Description (Set) Proposed Use (Set) This invention is a novel treatment for thrombotic disorders, such as myocardial infarction, stroke, deep venous thrombo
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Comparison of HPV DNA Vaccines Employing Intracellular Targeting Strategies

Human papillomavirus (HPV) E6 and E7 are consistently expressed and are responsible for the malignant transformation of HPV-associated lesions. Thus, E6 and E7 represent ideal targets for therapeutic HPV vaccine development. Scientists at JHU previously used a gene gun approach to test several intracellular targeting strategies that are able to route model antigen, HPV-16 E7 to desired subcellular compartments and enhance antigen processing and presentation to T-cells in a context of DNA vaccin
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A Molecular Mechanism for Action of Immunophilins and a Method to Identify Novel Pharmaceuticals

The immunophilins are a family of proteins that are functionally related by their rotamase activity (ie they are peptidylprolyl isomerases, PPIase) and their ability to bind immunosuppressive drugs such as FK-506, rapamycin, and cyclosporin A. Immunophilin ligands also hold great promise for the treatment of nerve injuries and neurological diseases. While their mechanism of immunosuppressive activity is understood, the mechanism by which PPIase antagonists exert their neuroprotective activities
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Enhancement of Adenoviral Oncolytic Activity by Modification of the E1A Gene Product

The present invention relates to compositions and methods for enhancing the oncolytic activity of replication-competent, target cell-specific adenovirus vectors by modification of the E1A gene product. The target cell-specific replication-competent adenovirus vectors comprise a chimera of an adenovirus gene essential for replication, preferably an early gene, and the Androgen receptor (or a portion thereof) under the transcriptional control of a cell type-specific transcriptional regulatory elem
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inhibition of Tumor Growth Through Reduction of Peroxiredoxin 3 levels

The primary transforming activity of MYC is thought to arise through transcriptional regulation of numerous target genes. Scientists at Johns Hopkins have demonstrated that PRDX3, which encodes a mitochondrial protein of the peroxiredoxin gene family, is a direct target of MYC and is required for MYC-mediated transformation. These observations are consistent with the finding that PRDX3 protein levels are frequently elevated in breast cancer cells. Importantly, Hopkins researchers found that redu
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3-BROMOPYRUVIC ACID As a Potent Anticancer Agent Delivered Intraarterially

Liver cancer is one of the most common fatal cancers in the world and may reach epidemic levels in the future due to increased viral hepatitis. Current treatment options are rarely successful indicating a real need for alternative therapies. We have developed a new approach based on delivering the chemical agent 3-bromopyruvate intraarterially directly into liver tumors that are fed primarily by arteries. Significantly, 3-bromopyruvate is a strong alkylating agent that inhibits both sources of e
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Use of Proaerolysin Toxins Modified to Contain Tissue Specific Protease Activation Sequences as Targeted Therapy for Cancer

Proaerolysin is a bacterial toxin that is normally activated by furin protease to produce the pore forming toxin aerolysin which is toxic to prostate cancer cells at picomolar concentrations. We have removed the furin activation site and replaced it with a site that is recognized by the serine protease prostate-specific antigen (PSA) to produce a protoxin that is selectively activated within sites of prostate cancer Description (Set) Proposed Use (Set) Therapy for prostate cancer
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Modulation of systemic Immune Responses by Transplantation of Hemotopoietic Stem Cells Transduced with Genes Encoding Antigens and Antigen Presenting Cell Regulatory Molecules

The initiation of T cell-dependent immune responses depends on presentation of antigens by bone marrow-derived antigen-presenting cells such as dendritic cells. Tolerance induction depends on expression of antigens by tolerizing antigen presenting cells. Immunotherapy approaches are aimed at introducing antigen into various populations of APCs such as dendritic cells. However, the efficiency with which standard immunotherapy and vaccine approaches introduces antigens into APCs is relatively low.
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Oncogenic Osteomalacia-Related Gene 1: MEPE

This invention provides isolated polynucleotides encoding an oncogenic osteomalacia-related factor and polypeptides encoded by this polynucleotide. Expression systems, including gene delivery vehicles such as liposomes and vectors, and host cells containing the polynucleotides are further provided by this invention. The present invention also provides proteins encoded by the polynucleotides and antibodies that specifically recognize and bind to these proteins. In one embodiment the proteins that
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Phosphatonin-Related Gene: FRP - 4

This invention provides methods for modulating phosphate homeostasis and renal phosphate transport by delivering agents that alter the expression of the FRP-4 gene or alter the activity of the FRP-4 protein. The methods of the invention are useful for modulating bone mineralization, renal phosphate transport, alleviating oncogenic osteomalacia-associated symptoms and treating phosphate homeostasis-related disease. The invention further provides methods for reducing phosphate re-absorption by del
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Enhancement of Suicidal DNA Vaccine Potency by Linkage Mycobacterium Tuberculosis Heat Shock Protein 70 to an Antigen

Naked DNA vaccines represent an attractive approach for generating antigen-specific immunity because of their stability and simplicity of delivery. There are particular concerns, however, such as potential integration into the host genome, cell transformation, and limited potency. The usage of DNA-based alpha viral RNA replicons (suicidal DNA vectors) may alleviate the concerns of integration or transformation since suicidal DNA vectors eventually cause lysis of transfected cells. To further imp
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A Method for Generating Constitutively Active Transmembrane Proteins

The present invention related to methods and reagents for generating and using activating mutations of receptors and ion channels.
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Enhancement of Nucleic Acid Vaccine Potency by Intercellular Spreading and Enhancement of MHC Class I Presentation of Antigen Linked to Herpesvirus VP22 Protein

The potency of naked DNA vaccines is limited by their inability to amplify and spread in vivo. VP22, a herpes simplex virus type 1 (HSV-1) protein, has demonstrated the remarkable property of intercellular transport and may thus provide a unique approach for enhancing vaccine potency. We therefore created a novel fusion of VP22 with a model antigen, human papillomavirus type 16 (HPV-16) E7, in a DNA vaccine which generated enhanced spreading and MHC class I presentation of antigen. These proper
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Gene Responsible for Stargardt-like Dominant Macular Dystrophy

The gene responsible for Stargardt-like macular dystrophy has been identified, along with its normal allelic form. The mutant gene encodes a mutant protein containing a frameshift mutation, resulting in abnormal fatty acid synthesis and transport in the retina. Also disclosed are assays for Stargardt-like macular dystrophy and therapies.
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Oral Gene Delivery for Hemophilia

This invention is a non-viral trans gene delivery system developed for the long-term treatment of genetic disease. A recombinant plasmid construct with a cDNA of the gene implicated in hemophilia B was used to form nanospheres. Complex coacervation of the recombinant constrct with chitosan, a bioploymer found in the shells of crustaceans, under specific conditions led to the formation of nanospheres. Chitosan is a non-toxic compound used frequently in biomedical applications such as surgical gau
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The Analgesic and Anesthetic Effects of Inhibiting the Interaction of the NMDA Receptor Subunits 2A/2B with Neuronal Nitric Oxide via PDZ Domain of PSD95/SAP90

PSD-95/SAP90 is a molecular scaffold protein that, through interactions involving its PDZ domains, couples the NMDA receptor to cellular signaling pathways at neuronal synapses. PSD-95/SAP90?s mRNA and protein are enriched in the spinal cord and selectively distributed in the superficial dorsal horn, where PSD-95/SAP90 overlapped with the NMDA receptor and neuronal NOS. In spinal cord neurons, PSD-95/SAP90 interacted with the NMDA receptor subunits 2A/2B and neuronal NOS. JHU researchers have de
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Enhancement of Sindbis Virus Self-Replicating RNA Vaccine Potency by Linkage of Mycobacterium Tuberculosis Heat Shock Protein 70 Gene to an Antigen Gene

Self-replicating RNA vaccines (RNA replicons) have emerged as an effective strategy for nucleic acid vaccine development. Unlike naked DNA vaccines, RNA replicons eventually cause lysis of transfected cells and therefore do not raise the concern of integration into the host genome. We evaluated the effect of linking human papillomavirus type 16 (HPV-16) E7 as a model antigen to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of antigen-specific immunity generated by a Sin
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Enhancement of DNA Vaccine Potency by Linkage of Antigen Gene to the Extracellular Domain of FLT3-Ligand Gene

professional antigen presenting cells (APCs), particularly dendritic cells (DCs). A recombinant chimera of the extracellular domain of Flt3-ligand (FL) linked to a model antigen may potentially target the antigen to DCs and their precursor cells. Using HPV-16 E7 as a model antigen, we evaluated the effect of linkage to the FL on the potency of antigen-specific immunity generated by naked DNA vaccines administered intradermally via gene gun. We found that vaccines containing chimeric FL-E7 fusion
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Fusion of Calreticulun (CRT) to Antigens Enhances the Potency of DNA Vaccines

Antigen-specific cancer immunotherapy and anti-angiogenesis have emerged as two attractive strategies for cancer treatment. An innovative approach that combines both mechanisms will likely generate the most potent anti-tumor effect. In this study, we tested this notion using calreticulin (CRT) since it has been shown to be able to enhance MHC class I presentation and exhibit an anti-angiogenic effect. We explored the linkage of CRT to a model tumor antigen, human papillomavirus type-16 (HPV-16)
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Genetic Engineering of Autologous Vein Grafts with thrombomodulin-Expressing Vectors to Resist thrombosis, Neointimal Hyperplasia and Atherosclerosis

Autologous vein grafts are the most widely used conduits for coronary and peripheral arterial bypass surgery. Compared to arterial grafts, vein grafts suffer significantly higher failure rates that limit their clinical efficacy. The pathophysiology of graft occlusion varies with graft age, with acute graft occlusion due to thrombosis, subacute graft failure due to hyperplasia, and late graft failure due to atherosclerosis. Thrombin has been implicated in the pathogenesis of all three phases of v
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Human BARX2 Gene

Surprisingly, it has been found that the Barx2 gene is mutated in ovarian cancer. The invention provides methods of diagnosis, prognosis and treatment of cancer related to the Barx2 gene. Description (Set) Proposed Use (Set) This technology could be commercialized as diagnostic and prognostic kits and therapeutics for cancer related to the Barx2 gene.
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Biodegradable and Biocompatible Lactide-Phosphate Copolymers, Compositions, Articles and Methods for Making the Same

The growing need for new polymer-based drug delivery materials continues to stimulate polymer research. Although several classes of synthetic polymers have been studied for controlled drug delivery and tissue engineering, polylactide (PLA) and poly (lactide-co-glycolide) (PLGA) still remain the most popular and well characterized biodegradable polymers. Due to the wide range of applications for polymer-based drug delivery, polymers often require varied physiochemical properties. Besides physical
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Phenylalkenoic Acid-Mediated Corection of Aberant Protein Trafficking

This discovery encompasses the compound 4-phenyl-delta3-transbutenoic acid, which restores normal biosynthetic trafficking to the CFTR mutation deltaF508 The mechanism centers on butyrate-mediated down-regulation of the chaperone protein Hsc70. The compound 4-phenyl-delta3-transbutenoic acid is related to the compound biphenyl, which is currently approved for inherited urea cycle disorders where it functions to scavenge excess ammonia and has exhibited little toxicity.
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Biosynthetic Engineering of Cell Surface Sialic Acids

Surrounding every cell is a halo of glycoproteins, glycolipids and proteoglycans termed the glycocalyx. On these structures, the most common terminus is the sugar sialic acid which is unique in its 9-carbon structure and tissue specific derivatization. Because of its location and potential for diversity by derivatization, this sugar is often involved in cell to cell communication events, viral adhesion, and bacterial pathogenesis. Description (Set) Proposed Use (Set) Treatment of viral or
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A New Human p53 Homologue (p46)

Since its identification as a tumor suppressor gene, p53 has become one of the most studied genes in human cancer. Inactivation of p53 is though to represent the most common genetic event in all neoplasms and may contribute to the development of 50% of all human cancers. Because of p53?s role in DNA repair and apoptosis, an extensive search has been conducted for other members of the p53 family and other components of the p53 signaling pathway. Johns Hopkins researchers have designed degenerate
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Cloning of a Novel Telomerase Associated Protein from Human Cells

Telomerase activity is associated with human cancer and is often associated with the selection of cells that grow well after immortalization. Since cancer cells have high levels of telomerase, some tumors may require telomerase for growth. However, cells grown from a telomerase knockout mouse form tumors suggesting that not all tumors require telomerase. These knockout mice show an increase in aneuploidy and problems with cell division. The RNA component of telomerase has been the subject of stu
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Human Smad3 and Smad4 are Sequence-Specific Transcription Activators

Mounting evidence suggests that Smad proteins are required for TGFbeta signaling, but the way(s) in which Smad proteins propagate this signal is unclear. It was found that two human Smad proteins (Smad3 and Smad4) could specifically recognize an identical 9 bp palindromic sequence (GTCTAGAC). Tandem repeats of this palindrome conferred striking TGFbeta responsiveness to a minimal promoter. This responsiveness was abrogated by targeted deletion of the cellular Smad4 gene. These results define a n
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SynGAP

The PSD-95/SAP90 family of proteins have recently been implicated in the organization of synaptic structure. Here we describe the isolation of a novel ras-GTPase activating protein, GAPSYN, that specifically interacts with the PDZ domains of PSD-95 and SAP102 in vitro and in vivo. GAPSYN is selectively expressed in brain and is highly enriched at excitatory synapses where it is present in a large macromolecular complex with PSD-95 and the NMDA receptor. GAPSYN stimulates the GTPase activity of R
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Oral Delivery of Nucleic Acid Vaccines by Particulate Complexes

Nanoparticle coacervates of nucleic acids and polycations serve as effective vaccines when administered orally. They can induce immunity to a variety of disease causing agents and raise a protective response to allergens. This invention is related to the field of immunology and allergic diseases. In particular it relates to the area of food allergies. Patent (Set) 1045700; 749625; 505877; 6,475,995
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A Simplified System for Generating Recombinant Adenoviruses

Recombinant adenoviruses provide a versatile system for gene expression studies and therapeutic applications. A strategy, which simplifies the generation and production of such viruses is reported here. A recombinant adenoviral plasmid is generated with a minimum of enzymatic manipulation, employing homologous recombination in bacteria rather than in eukaryotic cells. Following transfections of such plasmids into a mammalian packaging cell line, viral production is conveniently followed with the
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Therapeutic Nanospheres

4-Phenylbutyrate exerts many beneficial biological effects. It appears to induce the transcription of certain promoters, as well as having a remedial effect on proteins which are aberrantly localized within the cell. In addition, it appears to cause cells to developmentally differentiate. The present invention provides nanosphere formulations of 4-phenylbutyrate and other drugs which remediate defective protein localization intracellularly. These formulations permit lower concentrations of drugs
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Semaphorins

The semaphorin gene family consists of a large family of conserved proteins several members of which have been shown to function in inhibitory and repulsive axon guidance. In addition, semaphorins may influence neural regeneration in vertebrates. It is herein reported that neuropilin a type 1 transmembrane protein implicated in neurodevelopment is a Sema III receptor. Neuropilin was previously identified as a membrane-associated protein expressed in many populations of neuron, but its function h
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Arachadonic Acid/Ceramide-Based Screens for Colorectal Cancer Chemopreventive Agents

Nonsteroidal antiinflammatory drugs (NSAIDS) can inhibit colorectal tumorigenesis and are one of the few agents known to be useful for the chemoprevention of neoplasia. It is shown that NSAID treatment of colon tumor cells induces apoptosis and a dramatic increase in ceramide, a known mediator of apoptosis. The ceramide increase is likely to be mediated by the elevated arachidonic acid resulting form cyclooxygenase inhibition, which in turn stimulates sphingomyelinase. These results have signifi
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Autologous GVHD

Portions of the MHC class II invariant chain peptide, termed CLIP, exhibit immunomodulatory properties and can skew the cytokine response. In particular, the flanking regions of CLIP interact with receptors on the T lymphocyte surface. Polypeptides engineered to comprise different sub-sequences of the CLIP molecule can be used to modulate immune responses to specific targets including tumor-associated antigens. Depending upon the particular subsequence of CLIP chosen for the polypeptide construc
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Isolation of GRIP

The invention concerns the discovery of a novel family of proteins named as glutamate receptor interacting proteins (GRIPs). GRIPs interact with non-NMDA glutamate receptors and, in particular, interact selectively with the C-termini of AMPA glutamate receptors. A novel gene that encodes GRIP has been isolated and equenced. GRIPs appear to be involved in the targeting of membrane proteins that may have a critical role in neurotransmitter receptor functions, such as the formation and maintenance
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Reversal of Loss of Imprinting in Tumor Cells by 5-aza-2"-deoycytidine

In order to determine whether loss of imprinting (LOI) in cancer might be reversed by altering DNA methylation, tumor cells were treated with 5-aza-2?deoxycytidine, a specific inhibitor of cytosine DNA methyltransferase. Treated cells showed several significant and reproducible changes: equal expression of maternal and paternal alleles of IGF2 switched to predominant expression of a single parental allele; H19 expression was reactivated; biallelic H19 expression switched to monoallelic expressio
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Therapeutic use of Ligands for CD46 for treatment of patients with disorders associate patheogenetically w/inappropriate or excess production of IL-12.

The present invention provides a method of treating a variety of disorders in a mammal characterized by dysregulated, physiologically abnormal, aberrant IL-12 production and/or overproduction of IL-12. The mammal is preferably a human. As discussed herein, IL-12 is critical for the generation of cell mediated immune (CMI) responses, which in some instances are critical for clearance of and immunity to a wide variety of pathogens. Thus, the method of the invention is useful for the treatment of a
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Use of Recombinant Bacteriophages to Monitor Ion Channel Receptor Expression im Mammalian Cells

The present invention concerns a novel method for detecting cell surface proteins utilizing a modified virus. This method combines peptide display technology and traditional immuno-amplification strategy to provide an economical detection system. In contrast to traditional approaches, both specificity and affinity can be either coarsely modified or subtly tuned to achieve more resistance to changes of temperature and pH. These physical properties allow the viral or nonviral peptides to register
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Discovery of Human Mad-related Genes

Resistance to the growth inhibitory effects of TGF-beta is common in human cancers. However the mechanism(s) by which tumour cells become restistant to TGF-beta are generally unknown. We have identified five novel human genes related to a Drosophila gene called Mad which is thought to transduce signals from TGF-beta family members. One of these genes was found to be somatically mutated in two of eighteen colorectal cancers, and three of the other genes were located at chromosomal positions previ
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Generation of Soluble Divalent Heterodimeric Analogs of Proteins involved in Immune Responses

This invention is directed to compositions comprising soluble divalent and multivalent heterodimeric analogs of proteins that are involved in immune regulation and methods of making and using the same. The high affinity that these complexes have for their cognate ligands enables them to be effective competitors to T cell receptors and MHC molecules normally involved in transplant rejection and autoimmune disease. Molecules such as divalent T cell receptors may also have an impact on the diagnosi
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Interferon Gamma-Gene-Based Therapy in Allergic Diseases

In vivo delivery of an interferon-y gene to mucosal cells of the lung is an effective means to treat and prevent the development of allergen-induced diseases Description (Set) Proposed Use (Set) Therapeutic for treatment and prevention of allergic diseases Patent (Set) 6,121,247
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Gdf -14

The present invention provides a growth and differentiation factor, GDF-14, and a polynucleotide sequence encoding GDF-14. GDF-14 is expressed at highest levels in muscle, brain, uterus, spleen, and thymus and at lower levels in other tissues. In one embodiment, the invention provides a method for detection of a cell proliferative or immunologic disorder which is associated with GDF-14 expression or function. In another embodiment, the invention provides a method for treating a cell proliferativ
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4.0 Demethyl Perclomedine

Substantially pure 3,5-dichloro-2-nethoxy-4-hydroxy-6-(trichloromethyl)pyridine or 4-demethylpenclomedine (formula I), acid addition salts thereof, pharmaceutical compositions containing the aforesaid compound, and a method of using the compound in the treatment of cancer in a mammal are disclosed. ##STR1## Description (Set) Proposed Use (Set) Patent (Set) 6,235,761
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Enhancing Nerve Regeneration

Compounds have been identified which can stimulate neuronal growth by inhibiting the neuronal inhibitory activity of myelin-associated glycoprotein (MAG). Specifically, complex carbohydrates have been identified which will bind to MAG, thereby inhibiting the MAG-mediated inhibiting mechanism so that nerve cell axons may regenerate after injury. This invention also provides a method to identify molecules or compounds which inhibit MAG inhibition of axonal outgrowth of injured nerve cells. Descr
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cDNA Cloning and Sequencing of Peptidyl-Glycine Alpha-Amidating Monooxygenasse

The sequence of bovine PAM is taught as well as new forms of PAM not known before. One new form is membrane bound and provides the basis and methods for alpha-amidating inactive precursors of peptide hormones. Patent (Set) 6,255,067;
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Therapeutic Suppression of Specific Immune Responses by Administration of Oligomeric Forms of Antigen of Controlled Chemistry

The method and construct used to reduce undesired antibody response in a mammal by administering a non-immunogenic construct of which contains at least two copies of a B cell membrane immunoglobulin receptor epitope bound to a pharmaceutically acceptable non-immunogenic carrier. This directly binds to the B cell membrane immunoglobulin receptors but fails to form an immunon. Description (Set) Proposed Use (Set) This invention is available for licensing for use in treatment of all diseases
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Methods and Compositions for Creating Biopolymers with Modulatable or Novel Functionalities by Insertional Mutagenesis

The invention provides molecular switches which couple external signals to functionality and to methods of making and using the same. The switches according to the invention can be used, for example, to regulate gene transcription, target drug delivery to specific cells, transport drugs intracellularly, control drug release, provide conditionally active proteins, perform metabolic engineering, create molecular sensors, and modulate cell signaling pathways. Libraries comprising the switches and e
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O2-Benzyl-substituted Dizeniumdiolates that Release Nitric Oxide at Controlled Rates Upon Photolysis

Nitric oxide (NO) is a critically important bioregulator, involved in a wide range of processes including neurotransmission, blood clotting, and blood pressure control. In addition, macrophages have been shown to kill cancerous tumor cells and intercellular parasites by releasing large amounts of NO. Deficiencies in these processes caused by a poor endogenous supply of NO are often treatable with NO-releasing drugs. This invention describes novel photochemical precursors to NO based on the photo
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Inhibitors of Plasmepsin II, an Anti-Malarial target

Compounds and methods for the inhibition of anti-malarial target aspartyl protease plasmepsins (e.g. Plasmepsin I, Plasmepsin II, Plasmepsin IV and HAP) are provided. The compounds are based on allophenylnorstatine substituted at positions R1-R4, such that R1 is isoquinoline, carboxyl, naphtalene, phenyl, phenol, benzene, an amino acid, and derivatives thereof; R2 and R3 are aliphatic groups; and R4 is indan, naphthalene, benzylamine, phenyl, phenol, cyclopentane, tert-butylamine, or derivatives
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Modulation of Cell Survival Using E1B and Aven

The present invention relates to preventing or delaying programmed cell death by expressing one or more anti-apoptotic polypeptides in a cell such that programmed cell death in the cell is prevented or delayed. The present invention also relates to increasing production of a cell-related product by expressing one or more anti-apoptotic polypeptides in a cell such that production of the cell-related product by the cell is increased. Recombinant cells useful for producing cell-related product or c
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Structural Prediction of Allosterism

During the course of biological function, proteins interact with other proteins, ligands, substrates, inhibitors, etc. These interactions occur at precisely defined locations with the protein but their effects are sometimes propagated to distal regions triggering highly specific responses. These effects can be used as signals directed to activate or inhibit other sites, modulate interactions with other molecules and /or establish inter-molecular communication networks. It has become evident hat
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Antiproliferative Vitamin D3 Hybrids

The present invention is based on the unexpected finding that certain modifications to the A-ring portion of vitamin D.sub.3 analogues produce compounds of superior biological activity. In its broadest aspects, the invention provides vitamin D.sub.3 analogues which include a 1-hydroxyalkyl group or 1-fluoroalkyl group in a trans- configuration with a 3-hydroxyl group on the A ring. Thus, the invention includes analogues in which a fluorine or hydroxyl group is substituted at one or more position
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Formation of Oligonucleotide Triplexes with Selectively Modified Cytosines

The present invention is based on the finding that it is possible to use the bisulfite-catalyzed transamination reaction to selectively introduce aminoalkyl or carboxyalkyl linker arms at a specific deoxycytidine site within oligonucleotides or analogs thereof which also contain one or more 5-methyldeoxycytidine residues. This enables the provision of oligonucleotides and analogs thereof which contain a single amine or carboxylic acid functionality at a desired deoxycytidine site, which can serv
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1, 2, 4 - Trioxanes Having Antimalarial Activity

Because of the widespread incidence of malaria in certain parts of the world and because of the increasing parasite resistance to standard anti-malarial drugs, there is an urgent need for new and effective anti-malarial drugs. A wide variety of anti-malarial compounds have been proposed for use. One such compound is qinghaosu (also called QHS or antemisinin). See Klayman, Science (1985) 228 1049-1055. This compound is a sesquiterpene lactone which bears a peroxide group and, unlike most other an
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Vitamin D3 Analogues

The present invention is based on the unexpected finding that the A-ring portion of vitamin D.sub.3 analogues can be modified without negatively affecting the biological activity of the resulting compounds. In its broadest aspects, the invention provides vitamin D.sub.3 analogues which include at least one hydroxyalkyl substituent on the ring-A. It is contemplated that this hydroxyalkyl substituent may be placed on the 1, 2, 3- and/or 4- positions of the A-ring. However, the preferred embodiment
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Identification of a new Type II Heat-labile Enterotoxin

One of the factors limiting the commercial development of mucosal vaccines is the availability of appropriate, safe and effective adjuvants and antigen delivery systems that promote the desired kinds of immune responses. In addition, many of the new subunit vaccine candidates lack sufficient immunogenicity to be clinically effective. Microbiologists at the University at Buffalo have designed a variety of novel vaccine adjuvants that demonstrate an ability to stimulate mucosal and systemic immune
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Calcium Sulfate (sulphate)-Based Nanoparticles: Synthesis and Modification Methods and Application in Bone Regenerative Therapy

Bone regeneration within critical size defects, both in the oral cavity and throughout the rest of the body, occurs very slowly in the absence of bone stabilizing agents to act as scaffolds. Though autogenous and allogenic bone grafts have been used to address this limitation, each faces its own set of issues which limit their widespread use. Autogenous bone grafts must be harvested from the patient’s donor site, thus requiring a painful and more complex procedure. Allogenic bone grafts serve
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Methods for Preparing Multivalent RNA-Targeting Ligands with Specific Application Towards Targeting the (CUG)n Oligomers that Cause Myotonic Dystrophy

Trinucleotide repeat disorders are genetic disorders caused by extended stretches of DNA encoded with the same trinucleotide sequence repeated many times. Some of the most notable trinucleotide repeat disorders include Myotonic Dystrophy, Fragile X, Huntington’s, and Friedreich’s ataxia. Myotonic Dystrophy (DM) is the most common form of Muscular Dystrophy, an inherited condition estimated to affect 1 in 8,000 individuals. DM is characterized as a multi-system disorder with clinical feat
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Using Selection to Define Rules for Small Molecule Targeting of RNA

Information needed to design nucleic acid-based compounds which target RNA can be as limited as knowing the Watson-Crick base pairing “code”. However, to date, the clinical success of such compounds (e.g. antisense and RNAi) has been elusive. Unlike nucleic acid-based drug candidates, delivery and stability of small molecules is not as significant an issue, making them more likely to progress through the development path, but designing them to target RNA is far more complicated due to the la
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Inhibition of Mechanical Ion Channels by Peptide Enantiomers

Stretch-activated cation channels (SAC) are wide-spread in the body and trigger cellular responses to mechanical stresses. They mediate the senses of touch and hearing and help to regulate organ functions. GsMTx4, a tarantula venom peptide, and its enantiomer selectively block SAC channels. By blocking the SAC channels, GsMTx4 offers a potentially powerful therapy for arrhythmia, congestive heart failure, incontinence, muscular dystrophy and other possibilities. Categories: Research Tool, Th
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Transgenic mouse model for neurodegenerative diseases

The study of neurodegenerative diseases such as Parkinson’s Disease (PD) and the subsequent development of therapeutic agents to combat these diseases rely upon accurate non-human models that mimic the pathogenesis of their human counterparts. As th e current PD models fail to simulate all of the pathogenic, histological, biochemical and clinical features of the disease, their value remains limited. A researcher at the University at Buffalo has developed transgenic mice that mimic not only
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Composition of Liposomal GM-CSF

Pharmaceutical and immunological scientists at the University at Buffalo have developed novel formulations for cytokine and growth factor drugs, including recombinant interleukin-12 (rhIL-12), GM-CSF and VEGF-C. Depending on the preferred method of a dministration, these formulations can be customized to either remain localized at the site of injection or prolong circulation time, and in either case with minimal or no loss of biological activity. One of these formulations, liposomal rhIL-12, app
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Method for Inhibiting Proteases in the Oral Cavity

Sensitive teeth, a condition which affects more than 45 million Americans each year, likely results from exposed dentinal tubules. A number of products have been developed that either occlude the exposed dentinal tubules or desensitize the nerves r esponsible for transmitting signals that the brain interprets as pain. Unfortunately, these products suffer from a number of drawbacks including but not limited to low pH, increased risk for developing kidney stones with long-term use, and/or are kn o
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Composition and method of preparation of liposomal microparticulate IL-12 for immunotherapy

Pharmaceutical and immunological scientists at the University at Buffalo have developed novel formulations for cytokine and growth factor drugs, including recombinant interleukin-12 (rhIL-12), GM-CSF and VEGF-C. Depending on the preferred method of a dministration, these formulations can be customized to either remain localized at the site of injection or prolong circulation time, and in either case with minimal or no loss of biological activity. One of these formulations, liposomal rhIL-12, app
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Composition of the reconstitution medium for protein and peptide formulations

Pharmaceutical scientists at the University at Buffalo have developed a rational strategy to design compositions for the reconstitution of freeze-dried protein/peptide formulations. These compositions confer stability to otherwise unstable protein p roducts such as replacement therapies (i.e. factor VIII, interferon-beta, etc.) and vaccines. Other applications include use as a delivery vehicle or as adjuvants for therapeutic and prophylactic vaccines. The strategy allows for the selection of ap
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Gene silencing of human c-myc oncogene by poly-DNP-RNA

Overexpression of the c-myc proto-oncogene has been implicated in the onset and progression of a wide range of cancers; in restenosis following arterial injury or intervention; and in the loss and dysfunction of insulin-producing ??cells in diabetes. UB researchers have synthesized a new compound, DNP002, that triggers cleavage of c-myc mRNA, thereby leading to growth inhibition and apoptosis of cells which overexpress the c-myc gene. Compared to other antisense compounds that have been develo p
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Novel Human Gene with Immunoregulatory and Antiproliferative Properties

Abnormal or unregulated control of the body’s immune system can contribute to a variety of disorders, including but not limited to autoimmune disease and cancer. Standard treatments for autoimmune disease involve administration of non-steroidal anti- inflammatory drugs, corticosteroids, and disease modifying anti-rheumatic drugs. Unfortunately, long-term treatment with these drugs can cause unwanted side effects and toxicity. The newest and most promising class of drugs includes proteins that
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Poly-DNP-RNA-21

The RIa/PKA gene is often overexpressed in cancers of the breast, lung, colon, prostate and ovary. UB researchers have synthesized a new compound, DNP-ssRNA-21, that triggers cleavage of the mRNA of RIa/PKA, thereby leading to growth inhibition and apoptosis of these cancer cells but with no effect on normal cell lines without RIa/PKA gene overexpression. Compared to GEM 231, an antisense therapeutic currently in Phase I/II clinical trials, DNP-ssRNA-21 is 30- to 900-fold more potent in vi t
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Use of hair follicle cells for tissue engineering of artificial organs or cell therapy

Many different tissues have been identified as stem cell sources for cell-based tissue engineering and cell therapies. However, the procurement of such cells is limited by ethical issues or the accessibility of donor sites. A definite need exists for an alternative, easily accessible stem cell source to facilitate cell-based tissue engineering. Chemical and biological engineers at the University at Buffalo have isolated a population of multipotent stem cells from the human hair follicle. These c
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Isolation of Functional Smooth Muscle Cells using Tissue Specific Promoters

Chemical engineers at the University at Buffalo have developed a method for isolating a patient’s own functional smooth muscle cells from hair follicles, bone marrow, cord blood or peripheral blood cells. The cells isolated via this method have shown utility in at least one tissue engineering application: tissue engineered vasculature (TEV). TEVs developed using these cells demonstrate all the functional characteristics of normal vasculature,including but not limited to mechanical strength and
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Biological Vaccine Delivery System

This invention relates to methods and compositions for producing a fusion protein comprised of Haemophilus influenae P2 amino acid sequences, wherein in place of loop 5, or a portion thereof, is displayed a heterologous or homologous peptide sequence having biological activity. The protrusion of loop 5 from the P2 sequence allows for proper presentation of the fused antigen, and hence an enhanced immune response. The fusion protein may be expressed on the surface of the host cell, such as in H.
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Use of RNA inhibitors based on IL-14 and antibodies to IL-14 for the treatment of autoimmune diseases and lymphomas

Autoimmune disorders and B cell derived lymphomas cause life-long suffering or premature death. Often the treatment for these diseases is symptomatic at best with severe side effects. An effective new treatment would be life saving for those patie nts. The cytokine interleukin-14 (IL-14) also known as high molecular weight B-cell growth factor (HMW-BCGF) plays an important role in both inflammation and B-cell memory formation. Recent research, including work with transgenic animals, highligh ts
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Monoclonal antibody 3F5-5E5 and P107 diagnostic markers and putative vaccine antigen for Moraxella catarrhalis and supplemental Mab 4G5

This invention includes monoclonal antibodies, proteins, nucleic acid seqeunces and lipoologosaccharides (LOS) which are specific to Moraxella catarrhalis. These materials are useful for designing a much-needed diagnostic test. The ability to diagn osis this form of otitis media would be very valuable for pediatric applications. Further, compositions and methods useful for distinguishing between M. catarrhalis serotypes are also available. Categories: Therapeutic and Vaccines, Diagnostic
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HIV antisense ORF(s) and putative protein(s)

The current invention is a gene comprising an open reading frame on the plus strand of the pro-viral DNA, and located in the region of HIV-1 long terminal repeat. The gene encodes a protein that is related to, and has a structural motif resembling t hat of chemokine proteins. Depending upon the ribosomal frameshift, a plurality of proteins may be translated from the antisense RNA. The protein has similarity with chemokine SDF-1 and may play a role as a cofactor with gp120 in the binding to and e
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Outer Membrane Protein B1 of Moraxella Catarrhalis

The present invention includes a method for the isolation and purification of outer membrane protein B1 as well as B1 peptides from Moraxella catarrhalis, and the resulting compositions. The method involves growing the bacteria in iron-depleted medi um to enhance the expression of the B1 protein, harvesting the bacteria from the culture, extracting from the harvested bacteria a preparation substantially comprising an outer membrane preparation with an affinity matrix containing immobilized trans
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Novel 4-Substituted Indole compounds and methods for making same

The basic indole structure has been a structure of great interest to synthetic and medicinal chemists because of its presence in a large number of biologically active agents. For the most part, the current methods for producing substituted indole mo lecules rely upon cyclization of a suitably substituted precursor. More recently, research has been investigating asymmetric functionalization of the indole core itself by taking advantage of the relatively nucleophilic 3-position. While the 3- p
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Erogorgiaene derivatives and method for making

Marine-derived bioactive compounds hold great promise as therapeutics in the treatment of human disease. One particular family of marine-derived diterpene compounds has demonstrated anti-cancer, anti-tubercular and anti-inflammatory activities. How ever, the complete evaluation of such compounds and the development of new medications derived from them have been restricted by limited supplies, low yields and inefficient methods for synthesis. Using a patented chiral catalyst, a method has been de
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Novel Chalcogenoxanthylium Dyes for Purging Blood Pathogens

Researchers at the University at Buffalo and the American Red Cross have developed a suite of chemical compounds to be used to purge pathogens found in the blood supply. There is a dire need to increase the blood supply. At current rates of donat ion, there is barely a three-day supply in many areas of the country, which restricts most types of blood to the “transfuse only” status thus effectively limiting much elective surgery. Concomitant with low donation rates, with each new pathogen
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21,23-Core-Modified Porphyrins as Sensitizers for Photodynamic Therapy

Photodynamic Therapy (PDT) is a unique approach to the treatment of cancer and other diseases. Able to differentiate cancerous and normal tissue while minimizing or eliminating many of the side effects associated with conventional chemotherapy and r adiation, PDT offers an appealing and cost-effective treatment alternative. Current limitations of PDT include depth of penetration, selectivity, and photosensitization. Researchers at the University at Buffalo have developed new compounds that overc
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Use of hair follicle cells for tissue engineering of artificial organs or cell therapy

Many different tissues have been identified as stem cell sources for cell-based tissue engineering and cell therapies. However, the procurement of such cells is limited by ethical issues or the accessibility of donor sites. A definite need exists for an alternative, easily accessible stem cell source to facilitate cell-based tissue engineering. Chemical and biological engineers at the University at Buffalo have isolated a population of multipotent stem cells from the human hair follicle. These c
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Composition and Method of preparation of Lipidic particles containing VEGF for lymphadema

Pharmaceutical and immunological scientists at the University at Buffalo have developed novel formulations for cytokine and growth factor drugs, including recombinant interleukin-12 (rhIL-12), GM-CSF and VEGF-C. Depending on the preferred method of a dministration, these formulations can be customized to either remain localized at the site of injection or prolong circulation time, and in either case with minimal or no loss of biological activity. One of these formulations, liposomal rhIL-12, app
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Identification of a new Type II Heat-labile Enterotoxin

One of the factors limiting the commercial development of mucosal vaccines is the availability of appropriate, safe and effective adjuvants and antigen delivery systems that promote the desired kinds of immune responses. In addition, many of the new subunit vaccine candidates lack sufficient immunogenicity to be clinically effective. Microbiologists at the University at Buffalo have designed a variety of novel vaccine adjuvants that demonstrate an ability to stimulate mucosal and systemic immune
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Method of treating bacterial infection in humans using antimicrobial nanoparticles applied in vivo and ex vivo

Method of treating bacterial infection in humans using antimicrobial nanoparticles applied in vivo and ex vivo Categories: Environment, Therapeutic and Vaccines
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Composition of Liposomal GM-CSF

Pharmaceutical and immunological scientists at the University at Buffalo have developed novel formulations for cytokine and growth factor drugs, including recombinant interleukin-12 (rhIL-12), GM-CSF and VEGF-C. Depending on the preferred method of a dministration, these formulations can be customized to either remain localized at the site of injection or prolong circulation time, and in either case with minimal or no loss of biological activity. One of these formulations, liposomal rhIL-12, app
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Methods for Preparing Multivalent RNA-Targeting Ligands with Specific Application Towards Targeting the (CUG)n Oligomers that Cause Myotonic Dystrophy

Trinucleotide repeat disorders are genetic disorders caused by extended stretches of DNA encoded with the same trinucleotide sequence repeated many times. Some of the most notable trinucleotide repeat disorders include Myotonic Dystrophy, Fragile X, Huntington’s, and Friedreich’s ataxia. Myotonic Dystrophy (DM) is the most common form of Muscular Dystrophy, an inherited condition estimated to affect 1 in 8,000 individuals. DM is characterized as a multi-system disorder with clinical feat
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Anti-tumor compounds

Members of the inhibitor of apoptosis protein (IAP) protein family are often expressed at high levels in cancer cells. It is thought that high expression of IAP proteins leads to a disruption in the apoptotic pathway (programmed cell death). This d isruption allows for continuation of the cell cycle and thus proliferation of tumor cells. XIAP and survivin are two members of the IAP protein family. It is thought that drugs or compounds that inhibit such proteins will allow for the cell to retu rn
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Method and Composition of Less Immunogenic, Long Circulating EPO

Over one million patients in the U.S. are prescribed a therapeutic erythropoietin to treat anemia caused by kidney failure or cancer chemotherapy. It is estimated that over 80% of cancer patients and 87% of patients with severe kidney disease devel op this condition. Treatment is critical considering the high mortality rate associated with the presence of anemia in these patient groups. Currently available therapies suffer from several problems including the production of neutralizing antibod ie
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Using Selection to Define Rules for Small Molecule Targeting of RNA

Information needed to design nucleic acid-based compounds which target RNA can be as limited as knowing the Watson-Crick base pairing “code”. However, to date, the clinical success of such compounds (e.g. antisense and RNAi) has been elusive. Unlike nucleic acid-based drug candidates, delivery and stability of small molecules is not as significant an issue, making them more likely to progress through the development path, but designing them to target RNA is far more complicated due to the la
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Calcium Sulfate (sulphate)-Based Nanoparticles: Synthesis and Modification Methods and Application in Bone Regenerative Therapy

Bone regeneration within critical size defects, both in the oral cavity and throughout the rest of the body, occurs very slowly in the absence of bone stabilizing agents to act as scaffolds. Though autogenous and allogenic bone grafts have been used to address this limitation, each faces its own set of issues which limit their widespread use. Autogenous bone grafts must be harvested from the patient’s donor site, thus requiring a painful and more complex procedure. Allogenic bone grafts serve
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Method for Delivering Hydrophobic Drugs Via Nanocrystal Formulations

This technology explains the formulation of a nanosized drug delivery carrier and the method of delivering photodynamic drugs, which are free from the external agents. From the results obtained for significant photosensitizing efficacy in vitro and in vivo conditions, it is believed that upon administration for photodynamic therapy use in humans, the drug will interact with human serum albumin or other intracellular molecules for allowing the recovery of fluorescence Categories: Nanotechnol
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Organically Modified Silica Nanoparticles Coencapsulating Photosensitizing Drug and Two-Photon Absorber for Two-photon Activated Photodynamic Therapy

Photodynamic therapy (PDT), following health agency approvals throughout the world for various cancers and other diseases, is slowly being accepted as a standard treatment for the treatment of obstructive esophageal and lung cancers as well as e arly stage lung cancer, and actinic keratoses. However, the hydrophobic nature of most photosensitizing drugs makes the preparation of pharmaceutical formulations for parenteral administration very difficult. This technology explains the for mulation
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Method for Inhibiting Proteases in the Oral Cavity

Sensitive teeth, a condition which affects more than 45 million Americans each year, likely results from exposed dentinal tubules. A number of products have been developed that either occlude the exposed dentinal tubules or desensitize the nerves r esponsible for transmitting signals that the brain interprets as pain. Unfortunately, these products suffer from a number of drawbacks including but not limited to low pH, increased risk for developing kidney stones with long-term use, and/or are kn o
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Chimeric TBP-Toxin Proteins as Mucosal Antigens for Vaccination against Neisseriae

Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, has been a burden to mankind from antiquity. Central to this bacteria's prolific nature, is its antigenic avariability of surface structures, as well as abilit y to avoid initiating host immune responses. Its cousin, Neisseria meningitidisis responsible for bacterial menigococcal meningitis, a disease that is invariabley fatal if untreated. Vaccines have developed against several N. meningitidis groups. Unf
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Method and Composition of Less Immunogenic, Long- Circulating Protein- Lipid Complexes

These novel compositions provide for enhanced delivery of protein therapeutics. Proteins (e.g. recombinant or full-length Factor VIII) associated with LIPRO-FORM (see R-6031 as well) exhibited markedly improved pharmacokinetic profiles and higher e fficacies in animal models. With characteristics such as lowered immunogenicity and increased circulation time, LIPRO-FORM provides significant potential advantages including a reduction in the frequency of administration, an abatement of inhibitor de
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Isolation of Functional Smooth Muscle Cells using Tissue Specific Promoters

Chemical engineers at the University at Buffalo have developed a method for isolating a patient’s own functional smooth muscle cells from hair follicles, bone marrow, cord blood or peripheral blood cells. The cells isolated via this method have shown utility in at least one tissue engineering application: tissue engineered vasculature (TEV). TEVs developed using these cells demonstrate all the functional characteristics of normal vasculature,including but not limited to mechanical strength and
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Method and composition of Pegylated protein (FVIII)-Phosphoserine complex

These novel compositions provide for enhanced delivery of protein therapeutics. Proteins (e.g. recombinant Factor VIII) associated with LIPRO-FORM exhibited improved pharmacokinetic profiles and higher efficacies in animal models. With characterist ics such as lowered immunogenicity and increased circulation time, LIPRO-FORM provides significant potential advantages including a reduction in the frequency of administration, an abatement of inhibitor development and an extension of patent life.
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Composition and method of preparation of liposomal microparticulate IL-12 for immunotherapy

Pharmaceutical and immunological scientists at the University at Buffalo have developed novel formulations for cytokine and growth factor drugs, including recombinant interleukin-12 (rhIL-12), GM-CSF and VEGF-C. Depending on the preferred method of a dministration, these formulations can be customized to either remain localized at the site of injection or prolong circulation time, and in either case with minimal or no loss of biological activity. One of these formulations, liposomal rhIL-12, app
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Novel 4-Substituted Indole compounds and methods for making same

The basic indole structure has been a structure of great interest to synthetic and medicinal chemists because of its presence in a large number of biologically active agents. For the most part, the current methods for producing substituted indole mo lecules rely upon cyclization of a suitably substituted precursor. More recently, research has been investigating asymmetric functionalization of the indole core itself by taking advantage of the relatively nucleophilic 3-position. While the 3- p
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Erogorgiaene derivatives and method for making

Marine-derived bioactive compounds hold great promise as therapeutics in the treatment of human disease. One particular family of marine-derived diterpene compounds has demonstrated anti-cancer, anti-tubercular and anti-inflammatory activities. How ever, the complete evaluation of such compounds and the development of new medications derived from them have been restricted by limited supplies, low yields and inefficient methods for synthesis. Using a patented chiral catalyst, a method has been de
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TLR2-mediated adjuvant activities of LT-II B subunits

The present invention deals with heat-labile enterotoxins (LT-IIs) in which the toxic A-subunits are absent, leaving only the nontoxic B pentamers. Researchers found that despite the absence of toxic A-subunits, the B-subunits alone are immunostimula tory and that their ability to activate NF-?B and induce proinflammatory cytokine release is dependent upon Toll-like Receptor 2 (TLR2) activity. TLR2-dependent activation of mononuclear cells by LT-II B-subunits appears to be a novel mechanism
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Gene silencing of human c-myc oncogene by poly-DNP-RNA

Overexpression of the c-myc proto-oncogene has been implicated in the onset and progression of a wide range of cancers; in restenosis following arterial injury or intervention; and in the loss and dysfunction of insulin-producing ??cells in diabetes. UB researchers have synthesized a new compound, DNP002, that triggers cleavage of c-myc mRNA, thereby leading to growth inhibition and apoptosis of cells which overexpress the c-myc gene. Compared to other antisense compounds that have been develo p
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Inhibition of Mechanical Ion Channels by Peptide Enantiomers

Stretch-activated cation channels (SAC) are wide-spread in the body and trigger cellular responses to mechanical stresses. They mediate the senses of touch and hearing and help to regulate organ functions. GsMTx4, a tarantula venom peptide, and its enantiomer selectively block SAC channels. By blocking the SAC channels, GsMTx4 offers a potentially powerful therapy for arrhythmia, congestive heart failure, incontinence, muscular dystrophy and other possibilities. Categories: Research Tool, Th
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Use of anti-T antibody to block metastasis of T antigen bearing tumors

Many cancer cells contain a carbohydrate structure on their surface known as the Thomsen-Friedenreich Antigen (TF-Ag). This antigen, which is not detectable on normal cells, plays a pivotal role in metastasis. An antibody which binds strongly to TF -Ag would be extremely useful in imaging cancer in vivo, blocking metastasis, and treating tumors with radioimmunotherapy. Unfortunately, this antibody has been difficult to isolate. Dr. Kate Rittenhouse-Olson has developed a monoclonal IgG3 antibo dy
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Monoclonal antibody 3F5-5E5 and P107 diagnostic markers and putative vaccine antigen for Moraxella catarrhalis and supplemental Mab 4G5

This invention includes monoclonal antibodies, proteins, nucleic acid seqeunces and lipoologosaccharides (LOS) which are specific to Moraxella catarrhalis. These materials are useful for designing a much-needed diagnostic test. The ability to diagn osis this form of otitis media would be very valuable for pediatric applications. Further, compositions and methods useful for distinguishing between M. catarrhalis serotypes are also available. Categories: Therapeutic and Vaccines, Diagnostic
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MUC7 12-mer-D isomer: novel and promising antimicrobial agent

This invention encompasses isomeric peptide derivatives of a naturally occurring protein found within the human body. These isomeric derivatives have been shown to possess potent antifungal activity comparable to that of currently used antifungal ag ents but with far less toxicity. The microbes used within those studies include but are not limited to C. albicans, C.glabrata, and C. krusei. These derivatives have been optimized for both size and charge and were specifically designed to resist t h
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Novel Chalcogenoxanthylium Dyes for Purging Blood Pathogens

Researchers at the University at Buffalo and the American Red Cross have developed a suite of chemical compounds to be used to purge pathogens found in the blood supply. There is a dire need to increase the blood supply. At current rates of donat ion, there is barely a three-day supply in many areas of the country, which restricts most types of blood to the “transfuse only” status thus effectively limiting much elective surgery. Concomitant with low donation rates, with each new pathogen
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Adjuvant activities of a mutant LT-IIb enterotoxin lacking binding to ganglioside GD1a

UB microbiologists have developed a mutant heat-labile enterotoxin (LT-IIb) that demonstrates promising adjuvant activity and appears to overcome the limitations and concerns related to various mucosal adjuvants currently under investigation. The abi lity of the mutant LT-IIb to stimulate mucosal and systemic immune responses against co-administered vaccine antigens in the absence of ganglioside binding is certainly advantageous, as it offers the potential to develop a safe and effective mucosal
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Novel Human Gene with Immunoregulatory and Antiproliferative Properties

Abnormal or unregulated control of the body’s immune system can contribute to a variety of disorders, including but not limited to autoimmune disease and cancer. Standard treatments for autoimmune disease involve administration of non-steroidal anti- inflammatory drugs, corticosteroids, and disease modifying anti-rheumatic drugs. Unfortunately, long-term treatment with these drugs can cause unwanted side effects and toxicity. The newest and most promising class of drugs includes proteins that
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Composition of the reconstitution medium for protein and peptide formulations

Pharmaceutical scientists at the University at Buffalo have developed a rational strategy to design compositions for the reconstitution of freeze-dried protein/peptide formulations. These compositions confer stability to otherwise unstable protein p roducts such as replacement therapies (i.e. factor VIII, interferon-beta, etc.) and vaccines. Other applications include use as a delivery vehicle or as adjuvants for therapeutic and prophylactic vaccines. The strategy allows for the selection of ap
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A vaccine to prevent infection by nontypeable Haemophilus influenzae infection

Currently, there is no effective vaccine to prevent infection by non-typeable Haemophilus influenzae (NTHi), a leading cause of otitis media as well as a number of other upper respiratory tract infections that affect both pediatric and adult populati ons. The most common treatment for OM is antibiotic therapy. In the U.S. alone, nearly 30 million antibiotic prescriptions are written for this condition each year. The widespread use of antibiotics has contributed to the fact that more than half of
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Poly-DNP-RNA-21

The RIa/PKA gene is often overexpressed in cancers of the breast, lung, colon, prostate and ovary. UB researchers have synthesized a new compound, DNP-ssRNA-21, that triggers cleavage of the mRNA of RIa/PKA, thereby leading to growth inhibition and apoptosis of these cancer cells but with no effect on normal cell lines without RIa/PKA gene overexpression. Compared to GEM 231, an antisense therapeutic currently in Phase I/II clinical trials, DNP-ssRNA-21 is 30- to 900-fold more potent in vi t
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Method for preparing less-immunogenic protein-lipid complexes

A novel method has been developed for preparing less immunogenic protein formulations. One composition derived from this method has demonstrated promising results in the delivery and efficacy of protein therapeutics (Factor VIII) involved in hemophi lia. By shielding the most immunogenic portion of the Factor VIII protein, UB researchers have created a complex that exhibits improved pharmaceutical properties. This technology can be applied to virtually any protein or peptide therapeutic includin
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Organic Mixtures for the Encapsulation of Proteins in Dispersed Systems

Liposome technologies were developed to circumvent the problems associated with delivering therapeutic proteins into the human body. By encapsulating the protein of interest, the liposome allows the protein to remain in the circulation long enough t o have a pharmacological effect. While liposomes can increase the protein’s half-life, improve its stability and minimize its immunogenicity, they are not without limitations. A remaining problem in the liposome field is that there is a limitation
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Novel Antihemophilic (AHF) Formulations: Surface Coated Dispersion Systems as a Delivery Vehicle for AHF and its Fragments

Liposome technologies were developed to circumvent the problems associated with delivering therapeutic proteins into the human body. By encapsulating the protein of interest, the liposome allows the protein to remain in the circulation long enough t o have a pharmacological effect. While liposomes can increase the protein’s half-life, improve its stability and minimize its immunogenicity, they are not without limitations. A remaining problem in the liposome field is that there is a limitation
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Chimeric LT-II toxins as adjuvant-carrier molecules

One of the factors limiting the commercial development of mucosal vaccines is the availability of appropriate, safe and effective adjuvants, or delivery systems that promote the desired kinds of immune responses. The present invention provides m ethods of inducing immune responses by recombinant antigen-enterotoxin chimeric mucosal immunogens that contain the A2/B subunits of cholera toxin or heat-labile type II toxins. Adjuvants based on these subunits (A2/B) are likely to be safe, because
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Protein Components of Streptococcus Pneumonae That Bind to Mucin Glycoproteins of Human Nasal and Middle Ear Secretions

Currently, there is no effective vaccine to prevent infections by Streptococcus pneumoniae, a leading cause of otitis media (OM) as well as a number of other upper respiratory tract infections that affect both pediatric and adult populations. A prer equisite for infection is bacterial colonization of the nasopharynx. From the site of colonization, pathogens may spread locally, either upward into the eustachian tube and into the middle ear resulting in OM or downward into the alveoli of the lowe
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Outer Membrane Protein B1 as a Vaccine for Branhamella Catarrhalis

The present invention encompasses nucleotide sequences derived from Moraxella catarrhalis which encode one or more epitopes of its outer membrane protein B1. Recombinant B1 protein or B1 peptides may be produced from genetically engineered host cells that contain and express these nucleotide sequences. The nucleotide sequences can be used in diagnostic assays for detecting M. catarrhalis genetic material. These sequences may also be used in antigenic compositions to produce B1-specific amino a c
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HIV antisense ORF(s) and putative protein(s)

The current invention is a gene comprising an open reading frame on the plus strand of the pro-viral DNA, and located in the region of HIV-1 long terminal repeat. The gene encodes a protein that is related to, and has a structural motif resembling t hat of chemokine proteins. Depending upon the ribosomal frameshift, a plurality of proteins may be translated from the antisense RNA. The protein has similarity with chemokine SDF-1 and may play a role as a cofactor with gp120 in the binding to and e
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Stabilization of Taxane Formulations

The clinical development of taxanes has been hampered by poor aqueous solubility, which necessitates administration of the drug in a vehicle such as Cremophor EL mixed with ethanol. Unfortunately, the formulation vehicle causes a variety of adverse r eactions, including anaphylactic hypersensitivity reactions This invention provides a method of stabilizing a taxane (e.g., paclitaxel) in a dispersed system by exposing the taxane to a molecule which improves the physical stability of the taxane
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Biological Vaccine Delivery System

This invention relates to methods and compositions for producing a fusion protein comprised of Haemophilus influenae P2 amino acid sequences, wherein in place of loop 5, or a portion thereof, is displayed a heterologous or homologous peptide sequence having biological activity. The protrusion of loop 5 from the P2 sequence allows for proper presentation of the fused antigen, and hence an enhanced immune response. The fusion protein may be expressed on the surface of the host cell, such as in H.
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Specific glycan-modified HIV envelope proteins as vaccine immunogens against

Introduction A major obstacle in current AIDS/HIV vaccine development is the failure to induce broadly neutralizing antibodies against primary isolates of human immunodeficiency virus. Standard vaccination approaches prime the adaptive immune system to recognize viral envelope proteins. However, these methods have failed in the case of HIV-1, as the epitopes of the viral envelope are too variable and the functionally important epitopes of the gp120 envelope protein are masked by glycosylation. A
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BCRP expressing cell lines

Introduction The breast cancer resistance protein (BCRP) is an ATP-binding cassette efflux transporter originally identified by its ability to confer multidrug resistance in cancer cells. BCRP mediates the efflux transport of a broad spectrum of substrates, including many drugs routinely administered to pregnant women to treat various diseases. Given its tissue localization pattern, BCRP is expected to play an important role in absorption, distribution, and elimination of drugs. Indeed, the impo
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Alteration of Surface Affinities

Summary This invention claims a method for using a pulse of current in an electrochemical microdevice to change a surface from one that resists the adsorption of proteins and cells to one that promotes that adsorption. This invention allows the preparation of surfaces that adsorb eucaryotic cells and presents them in patterns, and then the controlled release of these cells from those patterns. The movement of the cells across the surface following the current pulse provides the basis for bioche
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Bead-based polymerase colony microarrays and nucleic acid sequencing ("Polony-FISSEQ Beads")

Summary Foundational work of Dr. George Church has enabled the production and use of replicable arrays of polymerase-amplified nucleic acid colonies (so-called "polonies") on semisolid support matrices (see Harvard Case No. 1438). The present invention extends the polony technology to provided miniaturized, high-density, bead-based nucleic acid arrays and improved methods for array-based sequencing of nucleic acids. High feature resolution enables identification and isolation of clonal sequences
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Synthesis of Compounds with Peptide Characteristics

Summary Although peptides have shown some promise in clinical trials as therapeutic agents, its success has largely been limited by several factors, including rapid degradation by peptidases, poor cell permeability, and a lack of binding specificity resulting from conformational inflexibility. Over the years research has overcome some of these limitations with peptidomimetics-a system for the production of modified chemical compounds capable of mimicking the structural and or functional properti
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High-Throughput Synthetic Platform for Natural Product Analog Libraries

Summary Background: In small molecule drug development, researchers typically develop biased libraries in which all members share a particular characteristic, such as an ability to interact with a particular target ligand or structural features designed to mimic a particular aspect of a class of natural compounds. For example, a number of libraries have been designed to mimic one or more features of natural peptides. Although these libraries have provided reliable synthetic strategies for compou
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Calcipressins: Lead Targets for Autoimmune, Inflammatory, and Cardiovascular Disease

Summary The development of more selective immunosuppressive agents to mitigate transplant rejection and autoimmune diseases requires effective strategies of blocking signaling pathways in T cells. Current immunosuppressive strategies use cyclosporin A (CsA) or FK506 to inhibit calcineurin, which dephosphorylates and promotes the nuclear import of nuclear factor of activated T cells (NFAT) transcription factors. These nuclear NFATs then transactivate cytokine genes that regulate proliferative res
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Toxin-Phage Bacteriocide Antibiotic and Uses Thereof

Summary The rise of antibiotic resistant bacterial strains will necessitate the development of new strategies for treating bacterial infections. One potential alternative to conventional antibiotics is phage therapy - the use of bacteriophage viruses to specifically target and destroy disease-causing bacteria. This invention is based in part on the development of intracellular peptide and peptide-like toxins that are toxic to a cell when internalized, but non-toxic when outside the cell. Such to
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Mu Opioid Peptidomimetics: Lead Compounds for the Treatment of Pain

Summary Background: Although peptides have shown some promise in clinical trials as therapeutic agents, their success has largely been limited by several factors, including rapid degradation by peptidases, poor cell permeability, and a lack of binding specificity resulting from conformational inflexibility. Science has overcome these limitations with the advance of peptidomimetics--a system for the production of modified chemical compounds capable of mimicking the structural and or functional pr
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Liposome- Based, Intracellular Delivery of Drugs into Phagocytes, B- and T- cells and their tumor cells.

Summary Liposomes are man-made spheres, or vesicles, with an aqueous interior enclosed by one or more phospholipid bilayers. Liposomes can enhance the pharmacokinetics and efficacy of therapeutics by allowing slow diffusion of a drug through the liposomal membrane, so that the concentration of the drug in the bloodstream remains high for a longer duration as compared to normal intravenous injection. While liposomes can improve the pharmacokinetics of a drug in the bloodstream, they typically can
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Antisense Inhibition of Angiogenin Expression in Cancer

Summary Antisense oligonucleotides targeted to anigogenin and designed based on the known sequence of the ANG gene have been synthesized. Angiogenin is a potent positive mediator of neovascularization, a process required for both primary tumor growth and metastasis. Initial immoassay studies showed that antisense sequences inhibited the synthesis of ANG in three tumor cell lines of prostate and colon origin. Since then, in-vivo testing of ANG antisense in athymic mice have demonstrated a potent
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Methods and Reagents for Modulating TGF-beta Superfamily Signalling

Summary Harvard Medical School researchers have developed compositions and methods for modulating TGF-b signalling. TGF-b superfamily members regulate a wide range of normal and pathological biological processes, and have been implicated in a variety of developmental and immunological disorders, as well as cancer. TGF-b signals are mediated intracellularly by Smad proteins. Multiple Smad proteins form a complex with the DNA-binding protein FAST-1 to activate transcription of target genes.
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Novel Chemistry and Method to make Compounds Active Against Picornaviruses

Summary Picornaviruses are a large family of viruses responsible for many serious human and animal diseases, including hepatitis A, meningitis, diarrhea, summer flu, the common cold and polio. Several candidate antivirals have been shown to bind and inactivate picornaviruses. Current drugs active against these viruses are all derived from the same parent compound, identified via large scale random screening for activity against viral replication in vivo. Most of these are active against a limite
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Synthesis of Compounds with Peptide Characteristics

Summary Although peptides have shown some promise in clinical trials as therapeutic agents, its success has largely been limited by several factors, including rapid degradation by peptidases, poor cell permeability, and a lack of binding specificity resulting from conformational inflexibility. Over the years research has overcome some of these limitations with peptidomimetics-a system for the production of modified chemical compounds capable of mimicking the structural and or functional properti
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Compositions and Methods for Treating Papillomavirus-Infected Cells

Summary Human papillomaviruses have been linked to widespread, serious human diseases, especially cervical carcinoma. Researchers estimate that over 90% of the 500,000 cases of cervical cancer that arise worldwide each year may be linked to HPV. In addition to cervical cancer, papillomaviruses commonly induce benigh, dysplastic and malignant hyperproliferations of skin and mucosal epithelium, causing warts, plantar warts, venereal warts and others. These skin growths are unsightly, irritat
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High-Throughput Synthetic Platform for Natural Product Analog Libraries

Summary Background: In small molecule drug development, researchers typically develop biased libraries in which all members share a particular characteristic, such as an ability to interact with a particular target ligand or structural features designed to mimic a particular aspect of a class of natural compounds. For example, a number of libraries have been designed to mimic one or more features of natural peptides. Although these libraries have provided reliable synthetic strategies for compou
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Small Molecule Arrays: a New Forefront in Drug Discovery

Summary Scientists from the laboratory of Professor Stuart Schreiber at Harvard University have developed a novel method of printing small molecule libraries on glass microscope slides. This method represents a next-generation platform for drug discovery. Small Molecule Printing is simple and efficient: Bioactive small molecules, natural products, and small molecules originating from several diversity-oriented syntheses (DOS) beads are dissolved in a small volume of suitable solvent. A high
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Drug candidate for neurological stroke and septic shock

Summary Apoptosis is a genetically regulated cellular suicide mechanism that plays an important role in regulating normal development and tissue homeostasis as well as pathogenesis of diseases. This process is mediated by one of at least 14 members of the Ced-3/ICE (caspase) family of cysteine proteases. Regulation of these activities may have therapeutic potential in the treatment of a wide range of diseases, from degenerative diseases such as Alzheimer's and Parkinson's to proliferative disord
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Next Generation Diagnostics for Breast Cancer, Prostate Cancer, and Melanoma

Summary From the labs of Professor Alun Jones (inventor of CardioliteTM) and Professor Ashfaq Mahmood, comes a series of small molecule imaging probes, capable of conjugation to both SPECT-based and PET-based imaging agents. Lead candidates include sigma-1 and selective sigma-2 receptor probes in the low nanomolar sensitivity range (relevant to a wide variety of cancers, e.g., breast cancer), an advanced pre-clinical malignant melanoma diagnostic probe conjugated to technetium, and probes sensit
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Techniques for high yield synthesis of macrocyclic compounds

Summary Many useful pharmaceuticals, including natural products, have a macrocyclic structure that can be a challenge when exploring synthesis methods. The Walsh Laboratory has discovered a new process using of a solid-phase resin to synthesize macrocycle compounds, including polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS) and fatty acid synthase (FAS). The peptidic precursor molecules are connected to the solid-phase resin using a specific linker, and macrocyclization is achi
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Method of Creating Self-Assembled, Selectively-Permeable Colloidosome Structures

Summary Colloidosomes are spherical shells of micron-sized particles made by the simple technique of self-assembly onto emulsion droplets. These hollow, elastic capsules are ideal for efficiently encapsulating active agents for selective and timed release because they are highly controllable in strength, permeability and elasticity. Colloidosomes are an enabling technology with a variety of applications from functional foods to drug delivery to biotech and metallurgy. Capsules are composed o
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Aminoglycosides Scaffolding Targeting Antibiotic-Resistant Bacteria

Summary This invention encompasses key modifications to the chemistry of aminoglycosides to overcome bacterial resistance. The novel chemistry leverages: (a) the weak stereospecificity of aminoglycoside binding to rRNA, and (b) the stereospecific binding of extrinsic enzymes shown to inactivate aminoglycosides. These distinct properties are used to generate aminoglycoside enantiomers and diastereomers able to escape enzyme-mediated resistance and also reduce future resistance generation. Experim
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Novel Peptide Therapeutic for Multiple Sclerosis

Summary Background: In Multiple Sclerosis, the host’s immune system (lead by T cells) attacks and destroys myelin basic protein, the principle component necessary for nerve transmission. Part and parcel of this immune response pathway are the so-called Major Histocompatibility Complex (MHC) molecules. MHC molecules interact with myelin basic protein and bring it to the cell surface for interaction with T cells, which in turn proliferate and dispose lethal inflammatory cytokines to the cel
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Targeting FtsZ Activity Using Novel Antibacterials: Screening Assays, Small Molecule Hits, and Synthetic Pathways to Potent Natural Products

Summary Inhibition of bacterial septation machinery represents a promising approach for countering antibiotic-resistant bacteria. One such approach targets FtsZ, an essential protein and key mediator of bacterial cell division, which is highly conserved in prokaryotes, yet absent in the mitochondria of higher eukaryotes. Since FtsZ consumes GTP during the cytokinetic FtsZ ring (Z-ring) assembly, much like its eukaryotic analog tubulin during microtubule dynamics in mitosis, it is susceptible to
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Ephrins as Novel Targets in Neuronal Regeneration

Summary Chemokines play an intrinsic role in immunity and neural trafficking through their interactions with GPCRs. A reverse signaling mechanism of Ephrin B/EphB receptor has been discovered to inhibit GPCR sensitivity to chemokine binding. Reduced GPCR sensitivity is mediated by a novel cytoplasmic protein, PDZ-RGS3. Results in a Xenopus adhesion assay indicate that attraction of the SDF-1 chemokine to its GPCR receptor, CXCR4 (BDNF), was inhibited by PDZ-RGS3 binding with Ephrin B. The invent
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TreeDock protein docking software

Summary Predicting protein-protein and protein-ligand docking remains one of the challenging topics of structural biology. The main problems are (i) to reliably estimate the binding free energies of docked states, (ii) to enumerate possible docking orientations at a high resolution, and (iii) to consider mobility of the docking surfaces and structural rearrangements upon interaction. The invention provides a novel algorithm, TreeDock, that addresses the enumeration problem in a rigid-body dockin
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Techniques for high yield synthesis of macrocyclic compounds

Summary Many useful pharmaceuticals, including natural products, have a macrocyclic structure that can be a challenge when exploring synthesis methods. The Walsh Laboratory has discovered a new process using of a solid-phase resin to synthesize macrocycle compounds, including polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS) and fatty acid synthase (FAS). The peptidic precursor molecules are connected to the solid-phase resin using a specific linker, and macrocyclization is achi
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Toxin-Phage Bacteriocide Antibiotic and Uses Thereof

Summary The rise of antibiotic resistant bacterial strains will necessitate the development of new strategies for treating bacterial infections. One potential alternative to conventional antibiotics is phage therapy - the use of bacteriophage viruses to specifically target and destroy disease-causing bacteria. This invention is based in part on the development of intracellular peptide and peptide-like toxins that are toxic to a cell when internalized, but non-toxic when outside the cell. Such to
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Treatment of alcoholism and substance abuse using selective inhibition of alpha 2 adrenergic receptors and dopamine D2 receptors

Summary To date, most alcohol and substance-abuse drugs have been plagued by moderate efficacy and a lack of specific target mechanisms. A new approach is proposed involving weighted inhibition of the brain’s alpha 2 noradrenergic receptors (A2) and dopamine D2 receptors (D2). Lowered dependency on alcohol has been observed in alcoholic schizophrenics using clozapine, an anti-psychotic that represents an A2/D2 dual inhibitor balance. The unexpected effects of clozapine on alcohol abuse we
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Mu Opioid Peptidomimetics: Lead Compounds for the Treatment of Pain

Summary Background: Although peptides have shown some promise in clinical trials as therapeutic agents, their success has largely been limited by several factors, including rapid degradation by peptidases, poor cell permeability, and a lack of binding specificity resulting from conformational inflexibility. Science has overcome these limitations with the advance of peptidomimetics--a system for the production of modified chemical compounds capable of mimicking the structural and or functional pr
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In Vivo Evolution of an RNA-Based Transcriptional Activator

Summary This invention claims a method of evolving potent RNA transcriptional regulators using a combination of directed evolution and site directed mutagenesis. Also described are specifically evolved RNA aptamers and their structures. The potency of the evolved RNA based transcriptional activators is comparable to that of the most active naturally occurring protein transcriptional activation domains. RNA aptamers offer several advantages over peptamers: i) random RNA pools will form relativ
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Manipulating Stem Cells for Repair and Drug Delivery at Various Anatomic Sites

Summary Cellular and gene therapy for chronic drug delivery and tissue repair have been explored in a range of anatomic sites including the heart, brain, bone marrow, and skeletal muscle. Mashimo and colleagues present a new approach using modified embryonic stem (ES) cells to deliver drugs to the gastrointestinal system and to repair gastrointestinal tissue using somatic stem cells. A preliminary application of the embryonic stem cell delivery technology targets NO deficiency. NO deficiency
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Novel Avrainvillamide-like Compounds with Anti-proliferative Properties

Summary Avrainvillamide and stephacidin B, (a dimer of avrainvillamide) have been identified in culture media from various strains of the fungus Aspergillus. Both compounds demonstrate anti-proliferative activity, and avrainvillamide is reported to exhibit antimicrobial activity against multidrug-resistant bacteria. A common barrier to the use of avrainvillamide and stephacidin in the clinic is the inability to produce sufficient quantities of the compounds in bulk. This problem stems, in part,
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Targeting FtsZ Activity Using Novel Antibacterials: Screening Assays, Small Molecule Hits, and Synthetic Pathways to Potent Natural Products

Summary The emergence of bacterial strains resistant to current drugs has prompted a renewed effort to discover new methods for fighting infectious disease. A promising new target is FtsZ, a key mediator of bacterial cell division that is highly conserved among bacteria. Because FtsZ, much like its eukaryotic analog tubulin, consumes GTP during Z-ring assembly in mitosis, it is susceptible to both antagonists and agonists that interfere with its GTPase activity. Discoveries from two multidiscipl
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Novel Urazole Epoxyquinol Inhibitors of Hepatitis C Virus Replication

Summary Background: Hepatitis C virus (HCV) infects about 200 million people worldwide and frequently leads to cirrhosis, liver failure, and hepatocellular carcinoma. Currently, the best therapy for the treatment of chronic hepatitis C is a combination of pegylated interferon (PEG-IFN) and ribavirin. While the sustained virologic response (SVR) rate approaches 80% for patients with genotypes 2 and 3, the SVR rate is limited to about 45% for those with HCV genotype 1, which accounts for about 75%
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Clinical Stage HIV Vaccine Candidate and Other Vaccine Vectors

Summary Replication-defective viruses integrate the safety advantages of a killed virus vaccine and the immunogenicity of a live virus vaccine. Professor David Knipe and his research team present a novel replication-defective HSV-1 virus for the delivery of heterologous immunogens and nucleic acids relevant to vaccine applications. Viral replication is inhibited through the mutation of multiple early immediate genes of the HSV-1 virus, including ICP27 and ICP8. The mutation of multiple genes (e.
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Hydroxapatite -Antigen Conjugates AMPERSAND Methods for Generating a Poly-IG Immune Resp

Summary Issued patents 5,443,832: SUMMARY OF THE INVENTION We have discovered that hydroxylated calcium phosphate (HCP) particulate is a particularly useful carrier for antigens to be applied to mucosal surfaces. The antigen-HCP conjugate is transported across epithelium where it raises a poly Ig immune response. One aspect of the invention generally features a method for generating antigen-sensitized Ig-A-producing lymphoblasts in a mammal. In that method, an immunogen comprising an an
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Treating Diseases Associated with Oxidative Stress through the Metalothioneine System

Summary Since its initial discovery and characterization over 40 years ago by Vallee and colleagues, metallothionein has attracted a remarkable level of scientific attention due to its unique structural characteristics, its ubiquitous expression in eukaryotes, and its impressive metal binding and redox capabilities. Through years of studies, metallothionein has been associated with biological events ranging from protection against metal toxicity to involvement in inflammatory processes. However,
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Genetically Attenuated Microbial Vaccines

Summary The invention, covered by U.S. Patent No. 6,254,874, provides vaccines that comprise attenuated pathogens. It also encompasses methods for the creation of attenuated microorganisms useful in such vaccines. As claimed, attenuation of the organism against which the vaccine is to be directed in a recipient host is attributable to a combination of mutations. The first such mutation produces an auxotrophic condition, such that the microorganism requires a nutrient to proliferate, while a seco
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Novel Surfactants for Stabilizing Emulsions of Water or Hydrocarbon Oil-Based Droplets in a Fluorocarbon Oil Continuous Phase

Summary Emulsions—dispersions of two immiscible fluids—have many applications in industry and everyday life. These range from paints, to crop protection, chemical synthesis, and production of latices. They are also increasingly attractive for analytical applications. Traditional emulsions consist of water and hydrocarbon oil. However, this combination does not allow for a wide variety of applications. It is therefore of advantage to replace one of these liquids with a third class o
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High-throughput hydrogels for cell culture in realistic tissue stiffness environments

Summary Markets/ Needs Addressed: The physical environment surrounding a living cell influences its ability to proliferate, metabolize, differentiate and survive. In particular, the stiffness of the underlying matrix greatly affects cell fate and behavior. For example, cultured stem cells undergo neurogenic differentiation on soft substrates (which mimic soft brain tissue), whereas on hard substrates (which mimic bone) they differentiate into bone-like cells. It is becoming increasingly clear t
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Targeting MEF-2 for the Treatment of Neurodegenerative Disease

Summary Post-synaptic differentiation of dendrites is an essential step in synapse formation and is intrinsic to neural reprogramming following CNS trauma or neurodegenerative disease. Investigators from Harvard Medical School have discovered an important molecular switch of the transcription factor known as Mef-2 (myocyte enhancer factor 2A), which is able to modulate dendritic plasticity in CNS granule neurons. Functional analysis has pinpointed this switch to lysine-403, where sumoylation enh
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Genetic Test for Periodontal Disease

Summary Peridontitis is a serious oral disease characterized by highly painful loss of tissue between the tooth and the gingival tissue. In the US, it is estimated that dentists perform upwards of 28.5 million periodontal procedures each year, accounting for a multibillion dollar treatment market. Leading oral disease research conducted at the Harvard School of Dental Medicine has elucidated a panel of diagnostic and prognostic gene markers for periodontitis. Current surgical intervention is
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Brainbow Mice: a Technicolor Approach to map the Neuronal Circuits

Summary Understanding how the precise interconnections of neurons account for brain functions has been a preoccupation of neuroscientists for over a century. The primary obstacle that researchers have faced when attempting to map the neural circuitry of the brain has been their inability to clearly resolve the cellular elements involved. Scientists have tried a number of approaches, from simple histological stains (developed generations ago) that allow them to distinguish small subsets of neuron
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Array of Micro Differential Scanning Calorimeters for Combinatorial Studies

Summary Differential scanning calorimetry (DSC) is a primary technique for measuring the thermal properties of materials. A typical DSC system requires relatively large amounts of test material, making thermal measurements on nano-scale samples difficult if not impossible. Thus, while traditional DSC has proved a very useful technique, its application in nanotechnology is rather limited. Since the properties of materials on the nano-scale may differ significantly from their bulk counterparts, a
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Microfluidic Platform for Constructing Tunable 3D Cellular Microenvironments for Performing Biologically Relevant Cell-Based Assays

Summary Markets/Needs Addressed: In vitro studies of living cells are commonly carried out in 2-dimensional (2D) systems involving cells grown in monolayers in glass or polystyrene Petri dishes. The limitations of these systems, and their differences from native three-dimensional (3D) in vivo biology, are well accepted. Indeed, the sometimes drastic changes in phenotype and/or gene expression that cells (e.g. primary human cells) may undergo when cultured in 2D systems limit the biological rele
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Brainbow Mice: a Technicolor Approach to map the Neuronal Circuits

Summary Understanding how the precise interconnections of neurons account for brain functions has been a preoccupation of neuroscientists for over a century. The primary obstacle that researchers have faced when attempting to map the neural circuitry of the brain has been their inability to clearly resolve the cellular elements involved. Scientists have tried a number of approaches, from simple histological stains (developed generations ago) that allow them to distinguish small subsets of neuron
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AlignAce motif searching software

Summary Developed by genomics researchers at Harvard Medical School, AlignAce employs an algorithm that scans non-coding nucleic acid sequences at high resolution for motifs that occur with non-random frequency. This algorithm is built into a multi-level sequence analysis program that highlights gene-specific regulatory elements for further analysis. AlignAce offers both efficiency and convenience. Its high signal-to-noise ratio preferentially reduces false positives in the program output, w
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Time and concentration warping software for RNA and protein expression data

Summary The predominant strategies for drug discovery today employ high-throughput screens and microarray-based methods that generate large data sets. Increasingly, these techniques are being used to study biological processes as a function of time and/or chemical concentration. Functionally-related processes may vary in timecourse or strength in different experiments or individuals. Current clustering methods do not highlight their similarities, because while their expression- or reaction profi
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TreeDock protein docking software

Summary Predicting protein-protein and protein-ligand docking remains one of the challenging topics of structural biology. The main problems are (i) to reliably estimate the binding free energies of docked states, (ii) to enumerate possible docking orientations at a high resolution, and (iii) to consider mobility of the docking surfaces and structural rearrangements upon interaction. The invention provides a novel algorithm, TreeDock, that addresses the enumeration problem in a rigid-body dockin
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Microfluidic Arrays for Multiplex Detection of Analyts

Summary This invention is a microfluidic array apparatus and a method of performing multiple analyses on multiple samples simultaneously, utilizing nanoliter volumes of reagents. It has two embodiments, the first consists of N microfluidic channels, perhaps in a parallel array, in fluidic contact with N' microfluidic channels, perhaps parallel and orthogonal to the N channels, making NxN' contact points where analyses can occur. Contact is controlled by use of membranes, or other dividers, at th
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Algorithm for Haplotype Construction of Single Nucleotide Polymorphism

Summary The Haplotyper software program utilizes a novel algorithm called Partition-Ligation to reconstruct individual haplotype phase information from unphased genoptype data. The Partition-Ligation method uses an ingenious Markov chain Monte Carlo approach both to construct the partial haplotypes of each segment and to assemble all the segments together. It has the ability to deal with ambiguous or missing genotypes, it has the ability to handle hundreds or thousands of single nucleotide polym
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GoFish gene annotation and database query software

Summary GoFish, a genomics software tool developed at Harvard Medical School, provides methods for improved gene annotation and query of gene annotation databases. The software enables efficient analysis of large genomics data sets by allowing the user to search for genes that possess investigator-defined combinations of characteristics or, alternatively, of features that approximate those characteristics. GoFish is useful both for basic research applications (e.g., pathway analysis) and pharmac
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Phenotype Drug Screening Platform ; Based on Quantitative Morphometric Analysis of Cells

Summary A new platform has been developed for rapid phenotypic drug screening and cytological profiling. Recent studies demonstrate the platform’s efficacy for rapidly discovering and characterizing novel pharmaceutical compounds using morphometric analysis. This is achieved using a proprietary imaging and analytical system to measure samples based on a variety of parameters (e.g. cell shape, size, number of centrosomes, size of centrosomes, pattern of staining, perimeter of nucleus, etc
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Method and Apparatus for Fluid Dispersion

Summary The invention is a microfluidic device for focusing and/or breaking fluid sections and drops. The subject fluid flows in the device's central channel as the dispersing fluid flows in the two outer channels. The outer fluid exerts pressure and viscous stresses that focus the inner fluid into a narrow thread that then breaks at, or just after, the orifice via capillary instability. The invention also covers "passive breakup" and "flow focusing" techniques to control the size and size di
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Calcipressins: Lead Targets for Autoimmune, Inflammatory, and Cardiovascular Disease

Summary The development of more selective immunosuppressive agents to mitigate transplant rejection and autoimmune diseases requires effective strategies of blocking signaling pathways in T cells. Current immunosuppressive strategies use cyclosporin A (CsA) or FK506 to inhibit calcineurin, which dephosphorylates and promotes the nuclear import of nuclear factor of activated T cells (NFAT) transcription factors. These nuclear NFATs then transactivate cytokine genes that regulate proliferative res
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Methods to Regulate the Duration of Th2 Activation

Summary TID1 encodes two human mitochondrial matrix localized splice variants. Expression of each of two splice variants has opposing effects on the cell's ability to respond to exogenous apoptotic stimuli. TNF and mitomycin c both trigger apoptosis via hTID1(L) expression. Both forms affect cytochrome c release, as well as caspase 3 activation; neither affect caspase 8 activation. The accumulation of hTID1(s) in Th2 cells following activation represents a novel mechanism that may contribute to
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A Novel Class of Phospholipase A2 Preferentially Expressed in Th2 Cells

Summary This invention describes the identification of a novel, low molecular weight class of Phospholipase A2 enzyme, PLA2 Group XII, that is involved in Type 2 T helper (Th2) cell differentiation and activity. This enzyme provides a potential target for therapeutic modification of Th2 activity, including prostaglandin production and Th2-mediated immune response. Applications This invention encompasses the isolation and use of PLA2 GXII nucleic acids and proteins, including transgenic animal
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Novel Peptide Therapeutic for Multiple Sclerosis

Summary Background: In Multiple Sclerosis, the host’s immune system (lead by T cells) attacks and destroys myelin basic protein, the principle component necessary for nerve transmission. Part and parcel of this immune response pathway are the so-called Major Histocompatibility Complex (MHC) molecules. MHC molecules interact with myelin basic protein and bring it to the cell surface for interaction with T cells, which in turn proliferate and dispose lethal inflammatory cytokines to the cel
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Ephrins as Novel Targets in Neuronal Regeneration

Summary Chemokines play an intrinsic role in immunity and neural trafficking through their interactions with GPCRs. A reverse signaling mechanism of Ephrin B/EphB receptor has been discovered to inhibit GPCR sensitivity to chemokine binding. Reduced GPCR sensitivity is mediated by a novel cytoplasmic protein, PDZ-RGS3. Results in a Xenopus adhesion assay indicate that attraction of the SDF-1 chemokine to its GPCR receptor, CXCR4 (BDNF), was inhibited by PDZ-RGS3 binding with Ephrin B. The invent
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A Sensitive Assay to Identify Inhibitors of HSV DNA Polymerase

Summary Investigators from Harvard Medical School have developed a novel in vitro screening assay for small molecule inhibitors of viral DNA polymerase subunits. A number of hit have been identified with this assay that show antiviral effect in the low micromolar range, and the activity profiles of the in vitro assay itself correspond well to the antiviral effect. Applications This high throughput antiviral screening assay has utility in identification of small molecule candidates for DNA vir
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Anti-Mitotic Eg5 Inhibitors for Treatment of Cancer and Inflammatory Disease

Summary Background: Molecules targeting mitosis and microtubule stability are important for the treatment of cancer. Unfortunately, the mechanism of action of these agents can cause undesirable toxicities For example, antimitotic agents such as taxol, epothilone, and vinca alkaloids produce toxicity in peripheral neurons, leading to chronic neuropathy. In addition, many of these agents are subject to acquired resistance. As such, researchers often look to new targets for development of antimitot
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Saframycin Assay

Summary Background: Chemotherapeutic DNA-binding compounds exert their effects, in part, by preventing DNA synthesis and initiating events that leads to apoptotic death. Despite the excellent antiproliferative activity of these compounds, though, elucidating their particular modes of action (i.e. their biological targets) has been difficult. Given this uncertainty, there is a high demand for the development of assays that can identify these essential drug effectors. Novel Technology: A novel
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Small Molecule Approaches to the Management of Macular Degeneration by Short-Circuiting the Visual Cycle

Summary Age related macular degeneration (AMD) affects millions of persons worldwide and is a leading cause of vision loss and blindness in ageing populations. In this disease, daytime vision (cone dominated vision) degrades with time because cone photoreceptors, which are concentrated in the foveal region of the retina, die. The incidence of this disease increases from less than 10% of the population 50 years of age to over 30% at 75 and continues upwards past this age. Dr. Robert Rando at H
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Novel Avrainvillamide-like Compounds with Anti-proliferative Properties

Summary Avrainvillamide and stephacidin B, (a dimer of avrainvillamide) have been identified in culture media from various strains of the fungus Aspergillus. Both compounds demonstrate anti-proliferative activity, and avrainvillamide is reported to exhibit antimicrobial activity against multidrug-resistant bacteria. A common barrier to the use of avrainvillamide and stephacidin in the clinic is the inability to produce sufficient quantities of the compounds in bulk. This problem stems, in part,
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Brainbow Mice: a Technicolor Approach to map the Neuronal Circuits

Summary Understanding how the precise interconnections of neurons account for brain functions has been a preoccupation of neuroscientists for over a century. The primary obstacle that researchers have faced when attempting to map the neural circuitry of the brain has been their inability to clearly resolve the cellular elements involved. Scientists have tried a number of approaches, from simple histological stains (developed generations ago) that allow them to distinguish small subsets of neuron
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Method of Creating Self-Assembled, Selectively-Permeable Colloidosome Structures

Summary Colloidosomes are spherical shells of micron-sized particles made by the simple technique of self-assembly onto emulsion droplets. These hollow, elastic capsules are ideal for efficiently encapsulating active agents for selective and timed release because they are highly controllable in strength, permeability and elasticity. Colloidosomes are an enabling technology with a variety of applications from functional foods to drug delivery to biotech and metallurgy. Capsules are composed o
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Nonhomologous Random Recombination of Nucleic Acids (Nucleic Acid Shuffling)

Summary This invention comprises methods for non-homologous random recombination (NRR) of nucleic acids, and their use to develop and select nucleic acids or polypeptides with novel structure and function. This technology is distinct from previous DNA shuffling methods in that it provides more comprehensive recombination of nucleic acid sequences for non-natural evolution. Background: In vitro DNA mutagenesis and shuffling enable the non-natural "molecular evolution" of nucleic acid sequen
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Nonhomologous Random Recombination of Nucleic Acids (Nucleic Acid Shuffling)

Summary This invention comprises methods for non-homologous random recombination (NRR) of nucleic acids, and their use to develop and select nucleic acids or polypeptides with novel structure and function. This technology is distinct from previous DNA shuffling methods in that it provides more comprehensive recombination of nucleic acid sequences for non-natural evolution. Background: In vitro DNA mutagenesis and shuffling enable the non-natural "molecular evolution" of nucleic acid sequen
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Novel Surfactants for Stabilizing Emulsions of Water or Hydrocarbon Oil-Based Droplets in a Fluorocarbon Oil Continuous Phase

Summary Emulsions—dispersions of two immiscible fluids—have many applications in industry and everyday life. These range from paints, to crop protection, chemical synthesis, and production of latices. They are also increasingly attractive for analytical applications. Traditional emulsions consist of water and hydrocarbon oil. However, this combination does not allow for a wide variety of applications. It is therefore of advantage to replace one of these liquids with a third class o
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Animal Model for Benign Prostate Hyperplasia

Summary The invention provides transgenic mouse models of benign prostate hyperplasia. These animals are useful in toxicity screens, as well as in assays aimed at the development of drugs to prevent prostate hyperplasia in mammals, including humans. References: Muller et al., 1990, "The int-2 gene product acts as an epithelial growth factor in transgenic mice", EMBO J. 9(3): 907-13. Tutrone et al., 1993, "Benign prostatic hyperplasia in a transgenic mouse: a new hormonally sensitive in
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Targeting MEF-2 for the Treatment of Neurodegenerative Disease

Summary Post-synaptic differentiation of dendrites is an essential step in synapse formation and is intrinsic to neural reprogramming following CNS trauma or neurodegenerative disease. Investigators from Harvard Medical School have discovered an important molecular switch of the transcription factor known as Mef-2 (myocyte enhancer factor 2A), which is able to modulate dendritic plasticity in CNS granule neurons. Functional analysis has pinpointed this switch to lysine-403, where sumoylation enh
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Purification of a Smooth Muscle Cell Mitogen from Beta Tumor Cell Conditioned Me

Summary This invention describes a novel human growth factor, sometimes referred to as "BTC-GF". BTC-GF is a mitogen for smooth muscle cells, 3T3 fibroblasts, and retinal pigment epithelial cells, but has no such effect on endothelial cells. Applications -smooth muscle replication in hypertension -competitive antibodies to receptors for factors -markers for diabetic retinopathy For Further Information Please Contact the Director of Business Development Laura Brass Email: laura_brass@harvard.
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A New p53 Cell-Based Assay

Summary Harvard researchers developed a reliable, high-throughput screening assay to identify activators and inhibitors of p53. This cell-based luminescence assay measures the level of a reporter gene product under the control of a promoter containing a p53-binding site. P53 is a transcription factor that can activate multiple genes involved in cell cycle regulation, DNA repair and programmed cell-death. It is often described as the "gatekeeper" of cellular integrity and plays a central role
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Dominant negative inhibitor of anthrax toxin

Summary The invention enables prevention and emergency treatment of anthrax. It provides a dominant negative inhibitor (DNI) of an essential infectivity factor of B. anthracis, a potentially lethal pathogen. Animal testing has been performed, and an IND has been filed for human therapeutic use. The DNI technology is protected by U.S. and international patent applications (see international patent application WO 01/082788). It is available for exclusive- or non-exclusive license in the field o
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ras Oncogene Inhibitors

Summary Activated ras genes have been associated with a number of human cancers. An activated ras gene, H-ras-1, was the first non-viral oncogene discovered. Several other human ras proto-onco genes have subsequently been identified including H-ras-2, K-ras-1, K-ras-2, and N-ras. Activated K-ras genes have been detected in pre-malignant neoplasms of the human colon and in human pre-leukemia. The ras proteins and ras-like proteins, including R-ras, RAS2, rap-2, and phoB, have a conserved carb
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Deglycosylating gp120

Summary This invention describes a method for producing partially deglycosylated HIV-1 envelope glycoproteins through site-directed mutagenesis. Removal of multiple carbohydrate residues by mutation of their consensus N-linkage sites exposes gp160/gp120 protein domains to the host immune system and may lead to enhanced immune response. Such mutated derivations of gp160/gp120 retain normal structure and function, as measured by infectivity of virions bearing the mutated proteins. The invention pr
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Selective Deposition of Cells in Microwells

Summary This invention is a method of selectively functionalizing indentations (such as wells or channels in microfluidic systems) or protrusions on a substrate such that, for example, cells selectively bind to the indentations or the protrusions. The ability to control the placement of cells on a surface is useful in making arrays of cells, which in turn make possible analytical systems for the detection of toxic substances, systems for high throughput screening for drug discovery and new metho
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Methods for Treating Arteriosclerosis

Summary Scientists at Harvard Medical School have identified imidazoles that inhibit endothelial cell, vascular smooth muscle cell and fibroblast proliferation. These imidazoles can be used to beneficially treat a variety of arteriosclerotic conditions. U.S. Patent No. 5,358,959 protects the use of chlotrimzole and derivatives for the treatment of arteriosclerosis in general and, in particular, for the prevention of restenosis after angioplasty (see, in particular, claim 3). Applications A
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Mediators of Chronic Allograft Rejection and DNA Molecules Encoding Them

Summary This invention provides methods of detecting and treating arterial inflammatory disease, including chronic allograft rejection subsequent to organ transplantation or chronic vascular Chlamydia pnuemonii infection, that results in atherosclerosis or restenosis. A major limiting factor for survival after organ transplantation is the development of chronic rejection due to obliterative arteriosclerosis in the transplanted blood vessels. The factors responsible for the intimal thickening
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NF-X1: Novel Target for Inhibition of MHC Class II Transcription and Autoimmune Disease

Summary The class II MHC molecules function in the presentation of processed peptides to helper T cells during an immune response. Dysregulated expression of class II major histocompatibility complex (MHC) molecules is hypothesized to contribute to the pathogenesis of a severe combined immunodeficiency syndrome and certain autoimmune diseases. Due to the central role these molecules play in the initiation of the immune response and disease, considerable effort is focused on elucidating the mecha
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EPH Receptor Ligands, and Uses Related Thereto

Summary The EPH kinases constitute the largest family of receptor tyrosine kinases. EPH receptors and their ligands (ephrins) play a central role in embryonic development and increasing evidence also implicates EPH and ephrins in cancer progression and metastasis. Harvard's researchers have identified a membrane bound protein, Elf-1 (EPH ligand family-1) as an EPH receptor ligand, isolated and sequenced Elf-1 cDNA and generated fusion proteins. Elf-1, also known as Ephrin-A2, Cek7-L and LER
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Novel Synthetic Mechanism to b-Lactone and Analogs: Lead Compounds for the Treatment of Proteasome-Related Diseases

Summary Background: Proteasome inhibition offers considerable promise in the therapy of a number of types of diseases, such as cancer and neurodegenerative diseases. One such proteasome inhibtor, Velcade, is currently marketed for treatment of multiple myeloma by Millennium Pharmaceuticals. Despite the success of Velcade, there still exist many issues to resolve. For example, animal studies indicated that bortezomib injected intravenously leaves the vascular compartment within minutes, rendering
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Liposome- Based, Intracellular Delivery of Drugs into Phagocytes, B- and T- cells and their tumor cells.

Summary Liposomes are man-made spheres, or vesicles, with an aqueous interior enclosed by one or more phospholipid bilayers. Liposomes can enhance the pharmacokinetics and efficacy of therapeutics by allowing slow diffusion of a drug through the liposomal membrane, so that the concentration of the drug in the bloodstream remains high for a longer duration as compared to normal intravenous injection. While liposomes can improve the pharmacokinetics of a drug in the bloodstream, they typically can
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Improved Method of Expression Cloning

Summary The human genome will soon be completely sequenced, presenting a vast new array of targets against which pharmaceutical agents can potentially be designed. However, to capitalize on this new information, the cellular function and medical significance of each of these genes will need to be determined. Here we describe a new cell-free expression cloning method that can rapidly identify novel proteins based on their function. Whereas traditional expression cloning methods have been used to
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Assay and Reagents for Detecting Inhibitors of Ubiquitin-dependent Degredation o

Summary Issued US patent 5,726,025 : SUMMARY OF THE INVENTION The present invention provides a systematic and practical approach for the identification of candidate agents able to inhibit ubiquitin-mediated degradation of a cell-cycle regulatory protein in cells from vertebrate organism, especially mammals, preferably humans. For instance, the assays permit identification of agents which inhibit ubiquitination of the cyclin proteins, e.g., B-type cyclins. One aspect of the present inventio
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In Vitro Differentiation of CD34+ Progenitor Cells into T-Lymphocytes (formerly

Summary Harvard Medical School researchers have developed a method for the production of large quantities of T lymphocytes in vitro. A monolayer of non-human primate thymic stromal cells is cocultured in vitro with human hematopoietic T cell progenitor cells, resulting in the differentiation and growth of mature human T cells. The T cells may be isolated from the stromal monolayer at any stage of differentiation and further expanded, allowing the production of large quantities of cells at a sele
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High Lead Expression of Soluble CMV UL97 and Development of an Assay to Screen Inhibitors

Summary The Coen Lab has expressed UL97 and UL97 fusion proteins and developed an assay to identify agents that inhibit or activate UL97 to be used in the treatment of human cytomegalovirus (HCMV) infection. HCMV is a beta herpes virus that causes significant pathology in individuals who are immunosuppressed (cancer patients, HIV patients, transplant patients) and in children born with primary HCMV infection. UL97 is a HCMV gene which encodes a protein kinase. UL97 kinase can phosphorylate n
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A Novel Tumor Suppressor Protein and Gene

Summary A novel tumor suppressor gene, doc-1, has been discovered which is structurally altered during oral carcinogenesis and which is expressed by normal and not transformed human tissues, and not by oral carcinoma. The expression of this gene as a tumor suppressor protein is inducible in cells with tumor necrosis factor (TNF). This discovery could be used to develop treatments of carcinoma, by administering a therapeutic amount of TNF-alpha to the site of the carcinoma, eventually in comb
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Herpesvirus Antiviral Drug Screen

Summary Herpesviruses continue to be a significant medical problem, causing painful chronic genital infections as well as devastating neonatal infections. To address these problems, Harvard Medical School faculty member Dr. David Knipe has looked at factors that control the replication of HSV. ICP-4 is the herpes protein most involved in HSV transcriptional regulation, and the activity of ICP-4 itself is modified by phosphorylation. As a result, compounds that affect the phosphorylation of ICP-4
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Smooth Muscle Cell Lim Protein

Summary Summary Issued patents claim DNA encoding the SmLIM polypeptide and/or promoter sequence, and the SmLIM polypeptide. Background and Significance Cardiovascular disease is the leading cause of death in the United States and other Western countries, responsible for twice as many deaths per year as cancer. In arteriosclerosis, a form of vascular disease, arterial walls become thickened and their internal diameters constrict. This constriction leads to increased blood pressure and redu
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Identification and Characterization of Class II HDACs: Lead Targets for Treatment of Cancer and Neurodegenerative Diseases

Summary Background: One promising target of recent cancer therapy research involves a family of proteins primarily involved in gene regulation known as histone deacetylases or HDACs. Currently there are over 15 separate clinical trials ongoing with HDAC inhibitors. A major drawback with the use of present HDAC inhibitors in clinical trials is their toxicity. HDAC inhibitors target specific classes of HDACs (HDACs consist of three classes and a total of at least eighteen known isoforms) rather th
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Antisense Inhibition of Angiogenin Expression in Cancer

Summary Antisense oligonucleotides targeted to anigogenin and designed based on the known sequence of the ANG gene have been synthesized. Angiogenin is a potent positive mediator of neovascularization, a process required for both primary tumor growth and metastasis. Initial immoassay studies showed that antisense sequences inhibited the synthesis of ANG in three tumor cell lines of prostate and colon origin. Since then, in-vivo testing of ANG antisense in athymic mice have demonstrated a potent
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Methods and Reagents for Modulating TGF-beta Superfamily Signalling

Summary Harvard Medical School researchers have developed compositions and methods for modulating TGF-b signalling. TGF-b superfamily members regulate a wide range of normal and pathological biological processes, and have been implicated in a variety of developmental and immunological disorders, as well as cancer. TGF-b signals are mediated intracellularly by Smad proteins. Multiple Smad proteins form a complex with the DNA-binding protein FAST-1 to activate transcription of target genes.
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Cell Based Assay for Discovery of Glycogen Synthase Kinase Inhibitors

Summary Background: Lithium exhibits numerous physiological effects in animals. For example, lithium mimics insulin action by stimulating glycogen synthesis and is remarkably effective for the treatment of mania in many human patients. Research over the years has demonstrated that lithium administers these effects, in part, through the inhibition of glycogen synthase kinase 3 beta (GSK3b), an enzyme involved in the regulation of glycogen synthesis and cell fate determination in diverse organisms
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Method for Cloning Secreted Proteins

Summary Many biologically important molecules, including many used therapeutically, are secreted proteins, such as interferons, erythropoietin and insulin. Secreted proteins have a hydrophobic signal peptide at the amino terminus of the protein. This hydrophobic signal sequence is typically about 16 to 30 amino acids long and contains one or more positively charged amino acid residues near its N-terminus, followed by a continuous stretch of hydrophobic residues. This signal peptide is recognized
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Novel Chemistry and Method to make Compounds Active Against Picornaviruses

Summary Picornaviruses are a large family of viruses responsible for many serious human and animal diseases, including hepatitis A, meningitis, diarrhea, summer flu, the common cold and polio. Several candidate antivirals have been shown to bind and inactivate picornaviruses. Current drugs active against these viruses are all derived from the same parent compound, identified via large scale random screening for activity against viral replication in vivo. Most of these are active against a limite
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Surface-Bound, Bimolecular, Double-Stranded DNA Arrays

Summary The invention, developed at Harvard Medical School, achieves high array feature density and accurate feature production through enzymatic second-strand synthesis of immobilized single-stranded DNA on one or more solid- or semi-solid support structures. Efficient, high-fidelity production of surface-bound nucleic acid arrays and microarrays is desirable both in commercial manufacturing and in the research laboratory. Selected advantages: - Utilizes natural or synthetic first-stran
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A Rapid and Inducible Method for Repressing Gene Function

Summary The Struhl lab has developed a rapid and effective mean to inactivate a target gene, including genes involved in essential pathways. This invention allows the inducible degradation of the polypeptide product in addition to the repression of a targeted gene. In combination, this double shut-off provides for a thorough block to continued target gene function. References: Z. Moqtaderi, Y. Bai, D. Poon, P.A. Weil, K. Struhl, Nature 1996, 383, 188-191. Harvard's intellectual property port
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Production and uses of polymerase colony ("polony") arrays

Summary The invention provides methods for rapid fabrication and use of replicable, high-density nucleic acid arrays. Array features are produced through amplification on a support matrix of nucleic acid templates of interest. A significant advance over conventional DNA array technologies, the so-called polymerase colony ("polony") technology requires no prior characterization or isolation of sequences to be placed on an array, and so is ideally suited to the analysis of unfractionated nucleic a
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Surface-Bound Double-Stranded DNA Protein Arrays

Summary Developed at Harvard Medical School, this invention provides nucleic acid arrays specifically designed for the assay of DNA-dependent protein:protein binding and/or physical interactions between proteins and nucleic acid molecules. Intermolecular analyses enabled by this technology are advantageously performed in massively-parallel fashion under uniform reaction conditions. This technology enables researchers to: - Screen for polypeptides that bind nucleic acid sequences of interest.
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AlignAce motif searching software

Summary Developed by genomics researchers at Harvard Medical School, AlignAce employs an algorithm that scans non-coding nucleic acid sequences at high resolution for motifs that occur with non-random frequency. This algorithm is built into a multi-level sequence analysis program that highlights gene-specific regulatory elements for further analysis. AlignAce offers both efficiency and convenience. Its high signal-to-noise ratio preferentially reduces false positives in the program output, w
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Cellular Basis of Vascular-Graft Stenosis

Summary The invention features a mouse model of vascular graft stenosis in which the stenosis develops rapidly and closely mimics the development of vascular graft stenosis in humans. Methods of surgically modifying a mouse artery to obtain the desired model are detailed. About 400,000 patients undergo aorta-coronary bypass graft surgery annually in the United States. Two years after surgery, up to 30% of vein grafts develop significant occlusion, known as stenosis. The incidence of stenosis
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Synthesis of Compounds with Peptide Characteristics

Summary Although peptides have shown some promise in clinical trials as therapeutic agents, its success has largely been limited by several factors, including rapid degradation by peptidases, poor cell permeability, and a lack of binding specificity resulting from conformational inflexibility. Over the years research has overcome some of these limitations with peptidomimetics-a system for the production of modified chemical compounds capable of mimicking the structural and or functional properti
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Systematic, condition-independent identification of essential genes of microorganisms

Summary Traditional antibiotics have been aimed at a small subset of cellular processes (such as cell wall synthesis, protein synthesis and mRNA synthesis) and targets (including DNA gyrase and the cell membrane). Linkage of additional genes, proteins and pathways with functions essential to microbial infectivity is highly desirable, as it may lead to the development of new classes of useful antibiotics. This invention identifies new antimicrobial targets though high-density mutagenesis of a
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Compositions and Methods for Treating Papillomavirus-Infected Cells

Summary Human papillomaviruses have been linked to widespread, serious human diseases, especially cervical carcinoma. Researchers estimate that over 90% of the 500,000 cases of cervical cancer that arise worldwide each year may be linked to HPV. In addition to cervical cancer, papillomaviruses commonly induce benigh, dysplastic and malignant hyperproliferations of skin and mucosal epithelium, causing warts, plantar warts, venereal warts and others. These skin growths are unsightly, irritat
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Monoclonal Antibody 2F12, Anti-ITK

Summary Monoclonal antibody to the T cell signaling protein ITK (Tyrosine kinase), developed by Heather Wilcox in Dr. Leslie Berg's lab, in the department of Molecular and Cell Biology, Harvard. These monoclonal antibodies were raised against a GST fusion protein comprising the first 26 amino acids of murine ITK. The clone is 2F12, an IgG1, and it works for immunoprecipitation and Western blot. It apparently works for intracellular staining. It recognizes a single protein of 72kDa. The clone has
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Geminin: a Biomarker with Significant Prognostic Potential in Cancer and Neuronal Differentiation

Summary A nuclear protein known as geminin is proposed as a broadly applicable cancer biomarker. The geminin protein was initially discovered by Kirchner et al. as an inhibitor of DNA synthesis and as a key regulator of genetic stability during chromosomal replication. Recent studies have pointed out a novel, and as of yet unelucidated, role for geminin as an oncogene. These studies have shown consistent upregulation of geminin in a variety of cancers, and have further suggested that geminin has
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Polo-Like Kinase Polo Box: Lead Target for Cancer Therapeutics

Summary Elevated expression of mammalian polo-like kinase (Plk) 1 occurs in many different types of cancers, such as head and neck, squamous cell carcinomas, oropharyngeal carcinomas, non-small cell lung cancer, melanomas, and ovarian and endometrial carcinomas. Plk1 has also been proposed as a novel diagnostic marker for several tumors. Polo kinases affect diverse cellular events during M-phase, such as centrosome maturation and bipolar spindle formation. Polo kinases also affect steps in the t
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Methods and Compositions Relating to Modulation of Cartilage Growth by Modulatio

Summary Dr. Laurie Glimcher at Harvard University has recently discovered that the transcription factor NFATp plays a critical role in regulating the formation of cartilage. Mice that lack NFATp display uncontrolled proliferation of cartilage over time as well as the capacity to regenerate cartilage after surgical injury. Once destroyed, articular cartilage cannot normally regenerate, leading to osteoarthitis. Applications For Further Information Please Contact the Director of Business Develo
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The Cytoblot: a Miniaturized High-Throughput Immunodetection Screening Assay Kit

Summary Background: A major goal of drug discovery efforts is to develop successful high throughput assays. Current assays either detect specific protein-ligand interactions using recombinant proteins or study the effects of small molecules on cell proliferation. The detection of cell proliferation has traditionally been performed by tedious and labor intensive methods, such as direct cell count, mitotic index, and clonogenic assays. Although these methods are useful, they are not practical for
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A Tool for the Linkage and Presentation of Multiple Protein Functional Domains

Summary Recent molecular biology research is moving beyond genetics to look at protein - protein interactions and how cells interact or communicate. These exciting areas are in need of improved tools that allow these interactions to be identified and studied. Harvard Medical School researchers have developed a novel approach that allows investigators to quickly generate platforms for the multivalent display of protein domains. By the use of a cassette expression system, researchers can quick
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A Method to Target the Degradation of Specific Cellular Proteins

Summary In order to study the role of specific proteins in cellular processes, researchers use a variety of techniques, including gene knockout, antisense, and RNA interference technologies. These technologies are limited in their all or nothing nature - they do not permit a low level of expression. Harvard Medical School researchers have developed a novel method to control the level of expression of proteins. This method uses the SCF ubiquitin-protolytic machinery within a cell to target
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On Bead Tagging and Decoding for Combinatorial Synthesis

Summary Pharmaceutical drug discovery has been greatly impacted by the development of novel approaches to the rapid synthesis of novel compounds, including combinatorial synthesis approaches. A common problem in combinatorial synthesis is that the compounds are frequently produced as mixed pools attached to solid state supports. From these, it is necessary to identify the specific compound of interest by deconvoluting or using encoding techniques during synthesis. Harvard Medical School resea
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Drug screening tool for herpes antivirals

Summary Harvard Medical School researchers have developed a genetically modified herpes simplex virus that has utility as a drug screening tool. To develop this tool, Harvard researchers engineered a replication competent herpes virus that contains green fluorescent protein (GFP) fused to a viral replication protein. During replication, this modified protein is transcribed and translated such that its expression can be detected by fluorescence of the GFP. As a result, drug candidates that affect
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Small Molecule Therapeutic and Screening Assays for Drugs Active Against Chronic Neural Degenerative Diseases.

Summary Huntington's disease, as well as other ataxias, are caused by the abnormal expansion of nucleic acid CAG repeats that code a glutamine stretch. These repeats are found within several otherwise non related proteins. The abnormally long polyglutamine tracts are believed to trigger programmed cell death (apoptosis), neuronal death, and subsequent neural degenerative disease. As part of an ongoing research effort at Harvard University, Harvard Medical School researchers have been investig
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Direct and Practical Synthetic Route to Pseudopterosins: Important Anti-Inflammatory, Anti-Pain, and Anti-Irritant Compounds

Summary Background: The pseudopterosins are a group of diterpene glycosides isolated from the Caribbean sea whip, Pseudopterogorgia elisabethae. The pseudopterosins represent an important structural class of anti-inflammatory and analgesic metabolites, and exhibit superior analgesic activity compared to industrial standards such as indomethacin. They appear to work by inhibiting the synthesis of eicosanoids in specific white blood cells called polymorphonuclear leukocytes. This potency and the f
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Bilins as anticancer agents

Summary A remarkable discovery at Harvard Medical School has led to the recognition that a naturally-occurring small molecule and analogs thereof possess potent anticancer properties through their ability to control cell differentiation. According to the invention, bilins are administered to induce terminal differentiation of dividing mammalian cells and thereby halt uncontrolled cell proliferation. This invention represents a major conceptual departure from traditional, signaling pathway-target
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Inhibitors of Protein-Processivity Factor

Summary Harvard investigators have discovered that Pol interacts with a processivity factor at a site that is distinct from sites of normal interaction between known Pol family members and other cellular factors. Unlike most protein-protein interactions, the target site is uniquely suited to small molecule drug discovery. Structure-based methods of designing and screening candidate drugs aimed at disrupting Pol processivity factor binding at this target site are fully disclosed. Treatment of vir
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Drug candidate for neurological stroke and septic shock

Summary Apoptosis is a genetically regulated cellular suicide mechanism that plays an important role in regulating normal development and tissue homeostasis as well as pathogenesis of diseases. This process is mediated by one of at least 14 members of the Ced-3/ICE (caspase) family of cysteine proteases. Regulation of these activities may have therapeutic potential in the treatment of a wide range of diseases, from degenerative diseases such as Alzheimer's and Parkinson's to proliferative disord
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Small Molecule Arrays: a New Forefront in Drug Discovery

Summary Scientists from the laboratory of Professor Stuart Schreiber at Harvard University have developed a novel method of printing small molecule libraries on glass microscope slides. This method represents a next-generation platform for drug discovery. Small Molecule Printing is simple and efficient: Bioactive small molecules, natural products, and small molecules originating from several diversity-oriented syntheses (DOS) beads are dissolved in a small volume of suitable solvent. A high
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Method of Detecting Compounds Utilizing Genetically Modified Lambdoid Bacterioph

Summary This invention describes a method to detet a molecule of interest in a given solution, and a method of selecting or screening for cell lines that can continuously produce desired compounds. This method uses a genetically and chemically modified lambdoid bacteriophage that has a target molecule chemically linked to its gpV gene product. Applications Some examples of target molecules include: -protein -peptide -hormone -nucleic acid -carbohydrate -lipid -glycoprotein -proteoglycan -l
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Identification and Characterization of Class II HDACs: Lead Targets for Treatment of Cancer and Neurodegenerative Diseases

Summary Background: One promising target of recent cancer therapy research involves a family of proteins primarily involved in gene regulation known as histone deacetylases or HDACs. Currently there are over 15 separate clinical trials ongoing with HDAC inhibitors. A major drawback with the use of present HDAC inhibitors in clinical trials is their toxicity. HDAC inhibitors target specific classes of HDACs (HDACs consist of three classes and a total of at least eighteen known isoforms) rather th
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Reaction Microarrays: Ultra Fast Method for Chiral Catalyst Discovery

Summary Background: While combinatorial chemistry has been successfully applied to the problem of chiral catalyst discovery, its utility is severely hampered by the lack of rapid, high-throughput screens for enantiomeric purity. Current methods require weeks to screen the products of 10,000 reactions. As a consequence, chemical companies face an increasing need for high throughput methods capable of efficiently producing enantiomerically pure products. Invention: A novel method for determinin
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Dominant negative inhibitor of anthrax toxin

Summary The invention enables prevention and emergency treatment of anthrax. It provides a dominant negative inhibitor (DNI) of an essential infectivity factor of B. anthracis, a potentially lethal pathogen. Animal testing has been performed, and an IND has been filed for human therapeutic use. The DNI technology is protected by U.S. and international patent applications (see international patent application WO 01/082788). It is available for exclusive- or non-exclusive license in the field o
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"Teabag" Processing: an Automated, High Throughput Method for Affinity Purification

Summary A high throughput system for protein purification has been developed, whereby a “tea-bag” structure is used to house microspheres for targeted protein binding and elution. The microspheres are compatible with any solid-phase protein purification, which includes coupling of Ni++/Histidine, Glutathione/Glutathione-S-transferase, avidin/biotin, and immunoprecipitation (beads with either protein A or G). From an efficacy perspective, the system has demonstrated equivalent purifie
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Methods to Regulate the Duration of Th2 Activation

Summary TID1 encodes two human mitochondrial matrix localized splice variants. Expression of each of two splice variants has opposing effects on the cell's ability to respond to exogenous apoptotic stimuli. TNF and mitomycin c both trigger apoptosis via hTID1(L) expression. Both forms affect cytochrome c release, as well as caspase 3 activation; neither affect caspase 8 activation. The accumulation of hTID1(s) in Th2 cells following activation represents a novel mechanism that may contribute to
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Aminoglycosides Scaffolding Targeting Antibiotic-Resistant Bacteria

Summary This invention encompasses key modifications to the chemistry of aminoglycosides to overcome bacterial resistance. The novel chemistry leverages: (a) the weak stereospecificity of aminoglycoside binding to rRNA, and (b) the stereospecific binding of extrinsic enzymes shown to inactivate aminoglycosides. These distinct properties are used to generate aminoglycoside enantiomers and diastereomers able to escape enzyme-mediated resistance and also reduce future resistance generation. Experim
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Targeting FtsZ Activity Using Novel Antibacterials: Screening Assays, Small Molecule Hits, and Synthetic Pathways to Potent Natural Products

Summary Inhibition of bacterial septation machinery represents a promising approach for countering antibiotic-resistant bacteria. One such approach targets FtsZ, an essential protein and key mediator of bacterial cell division, which is highly conserved in prokaryotes, yet absent in the mitochondria of higher eukaryotes. Since FtsZ consumes GTP during the cytokinetic FtsZ ring (Z-ring) assembly, much like its eukaryotic analog tubulin during microtubule dynamics in mitosis, it is susceptible to
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A Drug Discovery Platform Using Novel Labeled Uridine Analogs: Unique moieties contribute to molecular biology research

Summary Background: Uracil is a nucleic acid base that, when bound to ribose or deoxyribose, forms uridine or deoxyuridine, respectively. Certain analogs of uridine and deoxyuridine have been synthesized and used in a variety of applications. For example, deoxyribouridine analogs containing a 5-amino group have been prepared and used as anticancer, antiviral, and antibacterial agents. In other cases, 5-amino deoxyribouridine analogs have been made with fluorescent compounds for use in DNA sequen
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A Versatile Method for Accelerated Chromosome Walking and DNA Fingerprinting

Summary Background: A variety of DNA amplification methods deal with sequence analysis of an uncharacterized region adjacent to a known element. These methods include inverse PCR (iPCR), panhandle PCR, cassette ligation-anchored, and Thermal Asymmetric Interlaced PCR. Despite various degrees of success, a number of drawbacks reduce the accuracy and efficiency of each of these methods. Unsequenceable domains are frequently poor in restriction enzyme sites or contain heterochromatic DNA, which has
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Nonhomologous Random Recombination of Nucleic Acids (Nucleic Acid Shuffling)

Summary This invention comprises methods for non-homologous random recombination (NRR) of nucleic acids, and their use to develop and select nucleic acids or polypeptides with novel structure and function. This technology is distinct from previous DNA shuffling methods in that it provides more comprehensive recombination of nucleic acid sequences for non-natural evolution. Background: In vitro DNA mutagenesis and shuffling enable the non-natural "molecular evolution" of nucleic acid sequen
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HDAC Inhibitors

HDAC Inhibitors Laura Brass Email: laura_brass@harvard.edu Telephone: (617) 495-3067
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Absolute Quantification of Proteins (AQUA)

Summary This invention provides methods, reagents and kits for obtaining absolute quantification of proteins and their modifications directly from cell lysates. In particular, the invention provides peptide internal standards for use in high performance liquid chromatography (HPLC) with online detection by multistage mass spectrometry (MSn). Applications The invention provides reagents, kits, and methods for accurate quantification of proteins and methods for use. The reagents, kits, and meth
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Tome-1, a novel cell-cycle gene required for mitotic entry

Summary This invention, out of Marc Kirschner's research group, concerns the discovery of a novel protein required for mititic entry. Harvard researchers have isolated and identified the protein and the gene encoding the protein. Further work has shown Tome-1's key role in the activation of cdk1/Cyclin B, in turn required for mitotic entry. Further details are available in Cell, Vol. 113, 1-20, April 4, 2003 Applications antimitotic antiproliferative oncology autoimmune For Further Inform
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Saframycin Assay

Summary Background: Chemotherapeutic DNA-binding compounds exert their effects, in part, by preventing DNA synthesis and initiating events that leads to apoptotic death. Despite the excellent antiproliferative activity of these compounds, though, elucidating their particular modes of action (i.e. their biological targets) has been difficult. Given this uncertainty, there is a high demand for the development of assays that can identify these essential drug effectors. Novel Technology: A novel
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Susceptibility to Tuberculosis 1 (sst1): Novel Target for Diagnosis and Treatment of Mycobacterium tuberculosis

Summary Background: Tuberculosis is the seventh most important cause of global premature mortality and disability. Currently there are 8 million new cases and 3 million deaths annually from tuberculosis, and it is projected that a total of 225 million new cases and 79 million deaths will occur between now and 2030. Despite the prevalence and incidence of tuberculosis, host populations are heterogeneous in terms of their susceptibility to infection, and only 10% of the individuals infected with T
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Monoclonal IgE anti-ovalbumin antibody

Summary A laboratory from the Harvard School of Public Health has developed a monoclonal Ig E mouse anti-ovalbumin. This antibody is useful as a positive control in ELISA assays used to measure the level of IgE anti-ovalbumin antibodies in mouse models of asthma. Currently there is no commercial IgE anti-ova available. Most investigators use a pool of positive serum as the positive control and express their results as an index. This reagent could be of interest to many asthma and immunology inve
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Transgenic GFP-Rhodopsin Zebrafish Model System for Study of Retinal Disease

Summary Background: Rhodopsin is a G-protein coupled receptor that initiates the light response upon absorption of a photon in the outer segment of the retina (ROS). Rhodopsin constitutes at least 90% of the total protein in the outer segment and as a consequence the efficient transport of this molecule is essential for the proper functioning of rod photoreceptors. More than 70 mutations in the rhodopsin gene have been identified as leading to inherited retinal disease retinitis pigmentosa and f
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Method and Apparatus for Fluid Dispersion

Summary The invention is a microfluidic device for focusing and/or breaking fluid sections and drops. The subject fluid flows in the device's central channel as the dispersing fluid flows in the two outer channels. The outer fluid exerts pressure and viscous stresses that focus the inner fluid into a narrow thread that then breaks at, or just after, the orifice via capillary instability. The invention also covers "passive breakup" and "flow focusing" techniques to control the size and size di
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A Novel Class of Proteosome Inhibitors

Summary Harvard Medical School investigators has discovered a number of anticancer small molecules, termed ubistatins, that inhibit cell cycle machinery through interference with the ubiquitin-proteasome system. Lead ubistatins were able to arrest cyclin B proteolysis in Xenopus extract assays, and were found to prevent proteasome recognition by attaching to Lys-48-linked ubiquitinated chains. The ubistatins were discovered in a rapid miniaturized assay measuring cyclin B in Xenopus cell cycle e
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Small Molecule Approaches to the Management of Macular Degeneration by Short-Circuiting the Visual Cycle

Summary Age related macular degeneration (AMD) affects millions of persons worldwide and is a leading cause of vision loss and blindness in ageing populations. In this disease, daytime vision (cone dominated vision) degrades with time because cone photoreceptors, which are concentrated in the foveal region of the retina, die. The incidence of this disease increases from less than 10% of the population 50 years of age to over 30% at 75 and continues upwards past this age. Dr. Robert Rando at H
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Novel Candidates for Tuberculosis Therapy

Summary There is a need for new antibiotics that are useful against tuberculosis. Proteasomes of Mycobacterium tuberculosium are essential in enabling these bacteria to evade killing by macrophages of the infected host. Proteasome inhibitors, an emerging class of drugs, enhance the ability of host macrophages to kill M. tuberculosium; however, known inhibitors also block mammalian proteasomes. While one such composition has been approved for cancer therapy, these inhibitors likely are too toxic
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Fully-integrated 2D microelectromagnet coil arrays in silicon for magnetic manipulation and RF imaging of cells and magnetic particles

Summary The invention comprises a novel method and an apparatus to manipulate, segregate, detect and analyze biological samples on a microfluidic CMOS chip. This technique offers sub-micrometer precision and fast processing speeds for a cheap, easily accessible lab-on-a-chip system. The technology is based on a microcoil array, built into the front end of the CMOS chip, which creates varying electric and/or magnetic fields that can be used to manipulate the system. A microfluidic chamber is phot
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Genetic Test for Periodontal Disease

Summary Peridontitis is a serious oral disease characterized by highly painful loss of tissue between the tooth and the gingival tissue. In the US, it is estimated that dentists perform upwards of 28.5 million periodontal procedures each year, accounting for a multibillion dollar treatment market. Leading oral disease research conducted at the Harvard School of Dental Medicine has elucidated a panel of diagnostic and prognostic gene markers for periodontitis. Current surgical intervention is
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Deteremination of intracellular protein-protein interactions by colocalization with cytoplasmic inclusions

Summary Viral inclusion bodies are formed in transfected mammalian cells to enable an endogenous assay for protein-protein or nucleic acid-protein interactions. Inclusion bodies are generated by transfecting a cell with a vector encoding a protein fused with a modified reovirus protein/GFP hybrid. A second protein is expressed in the cell and interaction with the first protein is observed if the second protein is recruited to the viral inclusion body. Through this method, libraries of small mole
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Simultaneous Study of Multiple Genetic Interactions Using Multi-mutant Yeast

Summary While the Saccharomyces Genome Deletion Project succeeded in deleting many open reading frames in the S. cerevisiae genome, the possibility of multiple deletions in the same strain still represents an unmet challenge. A method has been discovered to precisely delete large numbers of genes in a single S. cerevisiae strain. Current methods have produced strains with approximately 20 engineered deletions, however these methods also induce undesirable genome rearrangement. The invention may
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Novel Cancer Target Following HDAC Track: First Histone Demethylase offers opportunity in treating resistant cancers

Summary The invention encompasses a novel target representing a potential new avenue in the treatment of cancer and other diseases, based on interference with gene regulation. The target, LSD1 (lysine-sepcific demethylase 1), the first example of histone demethylase, is responsible for trimming methyl groups from histones. While previously it was thought that histone methylation was irreversible, the Shi group discovered both positive and negative regulators of LSD1. Histone demethylase is t
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A Novel Class of HIV Therapeutics: Monoclonal Antibodies that Neutralize Previously Resistant HIV Primary Isolates

Summary Background: Molecular studies of the genomic organization of HIV-1 show that it encodes a number of genes common to all retroviruses, such as the gag, pol, and env genes. The env gene of HIV-1 produces a cleaved envelope glycoprotein (gp120) that is expressed on the exterior viral envelope surface. The binding and fusion of HIV-1 viruses with cells is mediated by specific interactions between the external subunit of gp120 and the CD4 receptor on the target cell surface. Studies have show
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Correlated Mutation Analysis-assisted Chimeric-Engineering/Directed-Evolution of Novel Portein/Enzyme Function

Summary Chimeric protein engineering and directed-evolution are increasingly popular methods to obtain enzymes with desired activities and substrate specificities. Chimeric-engineering goes about this by grafting select components of two homologous enzymes together (preserving activity while combinatorially affecting substrate specificity), whereas directed-evolution mutagenizes ligand-binding pockets to perturb substrate specificity and/or catalytic sites to modify activity. The major experimen
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Novel Avrainvillamide-like Compounds with Anti-proliferative Properties

Summary Avrainvillamide and stephacidin B, (a dimer of avrainvillamide) have been identified in culture media from various strains of the fungus Aspergillus. Both compounds demonstrate anti-proliferative activity, and avrainvillamide is reported to exhibit antimicrobial activity against multidrug-resistant bacteria. A common barrier to the use of avrainvillamide and stephacidin in the clinic is the inability to produce sufficient quantities of the compounds in bulk. This problem stems, in part,
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Targeting the Par-4 Protein as a Novel Approach in Depression Treatment

Summary Harvard researchers have discovered methods for identifying agents that modulate the interaction between Par-4 and the dopamine D2 receptor (D2DR). The ability to screen for this interaction may provide researchers with the ability to identify specific small molecule inhibitors of this interaction, providing a novel class of depression therapeutics. Applications A target for the development of treatments for depression. For Further Information Please Contact the Director of Business
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Proteasome-Mediated Degradation of RISC: Lead Target for Treatment of Long-Term Memory Disorders

Summary Background: Breakthrough research by Professor Sam Kunes and colleagues at Harvard University demonstrates that degradative control of the miRNA RISC pathway underlies the synaptic pattern of protein synthesis associated with the establishment of a stable long-memory. Manipulation of this pathway has implications not only for long-term memory, but also additional neurological disorders such as Parkinson’s and Huntington’s disease. This pathway includes several proteins that
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Single Cell mAB Discovery: ; Discovering Therapeutic Antibodies Invisible to Current Screening Platforms

Summary Monoclonal antibodies, including the epitope specific antibodies, represent a rapidly growing pharmaceutical segment, driven by the need for targeted therapeutics and growing knowledge of disease pathways. However, despite the high value of therapeutic mABs, discovery techniques have not advanced accordingly. For example, discovering a mAB with desired specificity is a time-consuming process often using inefficient serial dilution methods to isolate the desired mAB from a polyclonal mixt
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Wnt1-Cre transgenic mouse model

Summary Background: The ability to generate specific genetic modifications in mice provides a powerful approach to assess gene function. As such systems allowing conditional genetic modification have been developed; for example, inducible forms of the Cre recombinase from P1 phage have been generated that can catalyze intramolecular recombination between target recognition sequences (loxP sites) in response to ligand. However, when genetic modifications have been generated in the germ line, the
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Attenuated RNA Viruses for Vacine and Drug Delivery

Summary Research in the lab of Prof. Sean Whelan has revealed new compositions to attenuate non-segmented negative-sense RNA (nsNS) viruses. Successful attenuation was demonstrated on vesicular stomatitis virus (VSV) and involved specific residue modifications that impair methylation capping in new viral mRNA. Single-step growth assays showed that modified viruses yielded pin-point plaque morphologies and 10- to 1,000 fold replication defects compared to wild type viruses. The unique nature of t
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Brainbow Mice: a Technicolor Approach to map the Neuronal Circuits

Summary Understanding how the precise interconnections of neurons account for brain functions has been a preoccupation of neuroscientists for over a century. The primary obstacle that researchers have faced when attempting to map the neural circuitry of the brain has been their inability to clearly resolve the cellular elements involved. Scientists have tried a number of approaches, from simple histological stains (developed generations ago) that allow them to distinguish small subsets of neuron
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Transgenic Mice with Fluorescently Tagged Neuronal Mitochondria as a New Tool to Study Axonal Transport

Summary Background: Axonal transport supplies organelles to axons and synapses but little is known about how organelles are distributed among the branches of an axon to insure adequate supply of resources. This problem applies to axonal mitochondria, which play the central role in the energy metabolism of axons and synapses despite their origination in the soma. Because mitochondria are typically sparsely distributed and large enough to be imaged with optical techniques, their means of distribut
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Targeting MEF-2 for the Treatment of Neurodegenerative Disease

Summary Post-synaptic differentiation of dendrites is an essential step in synapse formation and is intrinsic to neural reprogramming following CNS trauma or neurodegenerative disease. Investigators from Harvard Medical School have discovered an important molecular switch of the transcription factor known as Mef-2 (myocyte enhancer factor 2A), which is able to modulate dendritic plasticity in CNS granule neurons. Functional analysis has pinpointed this switch to lysine-403, where sumoylation enh
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Smaller and faster biocalorimeter for ultra-sensitive temperature sensing that helps reduce drug-development cost and risk

Summary Innovation and Advantages: We have developed a novel calorimetry device for ultra-sensitive temperature sensing associated with a chemical reaction using surface plasmon-enhanced radiation. Radiation is directed at a thin electrically conductive film having one or more small apertures. The incident radiation excites surface plasmons on a first surface of the electrically conductive film, and energy associated with the surface plasmons couples to an opposite surface of the electrically co
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Small Molecule Microarrays: a New Forefront in Drug Discovery

Summary Scientists from the laboratory of Professor Stuart Schreiber at Harvard University have developed a novel method of printing small molecule libraries on glass microscope slides. This method represents a next-generation platform for drug discovery. Small molecule arrays can be utilized in all facets of a drug discovery platform—from targeted libraries to bioassay development and screening. Additionally, the arrays can be prepackaged and sold as focused libraries, such as an ion cha
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Nanobioelectronics: Building functional hybrid nanoelectronic/cell circuit elements

Summary Background: The determination of electrophysiological properties is important for understanding signal propagation through individual neurons and neuronal networks as well as muscle tissue. However, previously existing technologies are relatively crude: micropipette electrodes poked into cells are invasive and harmful, and microfabricated electrode arrays are too bulky to detect activity at the level of individual cells or in the case of neurons, discrete axons and dendrites. Novel T
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Treating Diseases Associated with Oxidative Stress through the Metalothioneine System

Summary Since its initial discovery and characterization over 40 years ago by Vallee and colleagues, metallothionein has attracted a remarkable level of scientific attention due to its unique structural characteristics, its ubiquitous expression in eukaryotes, and its impressive metal binding and redox capabilities. Through years of studies, metallothionein has been associated with biological events ranging from protection against metal toxicity to involvement in inflammatory processes. However,
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HEK293T cells stably expressing Divalent Metal Transporter-1 (DMT1-1): Model System to Screen for Inhibitors of Iron Uptake

Summary A HEK293T cell line that stably expresses Divalent Metal Transporter-1 (DMT-1). DMT1 functions in transport of ferrous iron across the plasma membrane and/or out of the endosomal compartment. Thus, the cell line is an ideal tool to screen for potential iron transport inhibitors. In one example, the cell line was used to screen two bioactives libraries for DMT-1 iron uptake inhibitors. Several potential hits were found, including one that may be specific for the DMT1 iron uptake pathway.
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Generating transgenic models via in-vitro selection of embryonic stem clones:; an accelerated route to in-vivo disease models and target validation

Summary Techniques to customize and predict transgenic animal phenotype through in-vitro pre-screening would be highly advantageous. Research from the lab of Professor David Sinclair presents a new platform for generating transgenic animals using a series of in-vitro screening techniques and a library of embryonic stem (ES) cell clones. Key improvements over the prior art include methods for exposing ES cell clones to various conditions and agents, screening for specific ES cell phenotypes, and
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High-throughput hydrogels for cell culture in realistic tissue stiffness environments

Summary Markets/ Needs Addressed: The physical environment surrounding a living cell influences its ability to proliferate, metabolize, differentiate and survive. In particular, the stiffness of the underlying matrix greatly affects cell fate and behavior. For example, cultured stem cells undergo neurogenic differentiation on soft substrates (which mimic soft brain tissue), whereas on hard substrates (which mimic bone) they differentiate into bone-like cells. It is becoming increasingly clear t
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Magnetic Resonance Force Microscope

Introduction Magnetic resonance force microscopy (MRFM) is a variant of scanning probe microscopy that combines the sensitivity and spatial resolution of atomic force microscopy with the threedimensional and nondestructive imaging capabilities of magnetic resonance imaging. Technology description Molecular imaging through magnetic resonance force microscopy (MRFM), was conceived in 1991 as a means for achieving 3D molecular imaging. MRFM combines three technologies: threedimensional magnetic res
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Preparative-Scale Microfabricated Capillary Electrophoresis

Introduction The demand for precise, high throughput protein separation is increasing due to both the growing number of protein based therapeutics being developed and the emphasis on proteomic analysis in research and drug discovery applications. The established technologies are electrophoresis and liquid chromatography (LC). Electrophoresis enables a sharp separation of individual proteins from complex mixtures but it is restricted to small sample volumes. This precision of separation can’t b
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Droplet Compartmentalization for Chemical Separations and On-Line Sampling

Introduction The ability to separate complex mixtures of chemicals and biomolecules is an important component of any chemical synthesis or biological processing. To date, there is no technology available to combine the high resolution of analytical separations with monodisperse droplet generation. Integrating these two technologies will allow for the detailed analysis of extremely low concentration analytes, such as are found in single cells, sub-cellular organelles, or low concentration synthet
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BCRP expressing cell lines

Introduction The breast cancer resistance protein (BCRP) is an ATP-binding cassette efflux transporter originally identified by its ability to confer multidrug resistance in cancer cells. BCRP mediates the efflux transport of a broad spectrum of substrates, including many drugs routinely administered to pregnant women to treat various diseases. Given its tissue localization pattern, BCRP is expected to play an important role in absorption, distribution, and elimination of drugs. Indeed, the impo
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In Vivo Drug Discovery Assay for Otoprotective Compounds

Introduction A number of commonly used drugs are known to kill hair cells in the mammalian inner ear and cause dose-dependent sensorineural hearing loss. Most notably, aminoglycoside antibiotics and platinum-based chemotherapeutic agents are known to cause irreversible hearing damage. While these drugs are clinically effective, their use is limited by this adverse effect and, as such, there is a need for the identification of compounds which could prevent or reduce the amount of hearing loss ind
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Fabrication of Gold Nanocages and Cubic Nanoframes for Biomedical Treatment through Etching Nanoboxes

Introduction Because of their small sizes and unique properties, nanomaterials are finding widespread use in studying complex biological systems. Gold nanostructures have been the subject of intensive research because of their unique and tunable surface plasmon resonance (SPR) properties. Because of their biocompatibility and easy surface modification (i.e., using the well-established Au-thiolate chemistry to attach antibodies, polymers or other ligands), Au nanostructures are also being conside
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The Multiple Drug Resistance Gene, Polymorphisms, and uses Thereof

Introduction Multiple drug resistance is a well-documented phenomenon and critical problem in the treatment of various diseases including cancer and HIV. While there are many mechanisms leading to multiple drug resistance, one area of focus is the MDR1 gene and its protein product P-glycoprotein (Pgp). Pgp functions as a membrane channel that removes drugs from cells. By increasing Pgp activity, removal of drugs from diseased cells is accelerated, making the drugs ineffective. Pgp is able to exp
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A Yeast Ligand Sensor

Introduction The yeast ligand sensor is a novel approach for the detection and quantification of ligandbinding, an issue of great interest in drug discovery and other areas. The approach is a protein-derived biosensor in which the readout is a change in growth of temperaturesensitive yeast. The yeast lack dihydrofolate reductase (DHFR) and are complemented by mouse DHFR containing a ligand-binding domain inserted in a flexible loop. The yeast grow poorly and are temperature-sensitive, due in lar
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Delivery of PEGylated Drugs from Bioadhesive Formulations

Introduction While significant advances have been made in the field of PEGylated drug delivery, there is still a need for novel and improved PEGylated drug delivery formulations, particularly those that are useful in the area of sustained drug delivery. Technology description Researchers at the University of Washington have developed a novel drug delivery formulation consisting of a PEGylated drug complexed with a bioadhesive polymer wherein the PEGylated drug comprises a polyethylene glycol cov
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Use of Adhesion Molecules as Shear-Induced Nanoscale Binding Switches

Introduction Methods, compositions, and devices for using shear-dependent binding switches in a variety of applications would be extremely useful in biomedical and other fields. Applications for this technology include the following: 1) as a non-invasive probe for force fields; 2) to control the aggregation of ionic and molecular scavengers; 3) to fabricate devices for particle and cell sorting; 4) to allow for the assembly of molecules, particles, and micro- or nanosystems into novel materials
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Solubility Enhancing Fusion Proteins

Introduction Recombinant proteins having therapeutic, diagnostic or any other commercial or research applications are produced by expression in a host cell. However these proteins of interest are often misfolded and form insoluble aggregates known as inclusion bodies. Inclusion bodies are difficult to purify and are not suitable for work such as x-ray crystallography and enzymology which require the use of properly folded, soluble proteins. A number of methods to solve this problem have been dev
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Novel Synthesis of Iduronate a Heparan Sulphate Subunit

BACKGROUND Heparan sulphate and heparin play a central role in a large number of processes including anti-coagulation, angiogenesis, cell growth and migration. A new class of medicinal drugs can be envisaged that would either promote or inhibit the function of heparan sulfate/heparin by mimicking or competitively inhibiting the function of heparan sulphate/heparin. These types of complex heparan sulphate molecules have historically been difficult to synthesise and the majority could be obtained
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A Functional Food with Indications for Peptic Ulcers

BACKGROUND 1 in 10 people are affected by peptic ulcers over the course of their lifetime. Incidence of the condition is set to increase as the population ages. Current treatment relies on combination antibiotic therapy. However, a 20% failure rate and increasing antibiotic resistance highlight the need for a new therapeutic paradigm. THE TECHNOLOGY Prof Ian Roberts’ group at the University of Manchester are developing natural extracts for the treatment and prevention of peptic ulcers that spe
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Novel Antimicrobial Peptides

BACKGROUND Ai2 Limited is a University of Manchester spinout company that aims to become a significant player in the global anti-infectives market. The company’s focus is on developing novel anti-microbial products, for out-licensing to healthcare companies across a range of sectors. THE TECHNOLOGY The core technology stems from research into a class of human proteins involved in innate immunity, whose role in fighting infection had not previously been identified. Specific regions of these pro
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A novel antibiotic for the control of biofilm formation

Invention TA is a broad spectrum antibiotic differing from known antibiotics by virtue of its adhesiveness to synthetic materials and to biological tissues, whilst retaining its bactericidal activity in the bound form. TA may be topically administered to the implanted device or infected zone without spreading to other parts of the body. The Need Infections due to biofilms are often the cause of implant failure. Indeed, catheter-associated urinary tract infection is the most common nosocomia
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Identification and Isolation of Osteogenic Progenitor Cells

Invention A novel gene, termed chromatin remodeling protein (ChroM1), from osteoblast progenitor cells has been cloned and sequenced. ChroM1 functions as a transcriptional regulator of genes involved in osteoblast differentiation and is differentially expressed on osteogenic progenitor cells. It can serve as a marker with which to enrich isolated populations of osteogenic progenitor cells and may server as a novel drug target for the development of therapies for the treatment of bone diseases
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Modulation of sperm activity in fertility and contraception

Invention Prof. Naor’s team has recently discovered that two Mitogen-Activated Protein Kinases (MAPKs) play a role in human sperm functions. The team discovered that human sperm progressive and hyperactivated motility is maintained by the ratio of these kinases, by either stimulating or inhibiting motility. These kinases are present in human spermatozoa in patches along the mid, principal and end pieces of the tail. Known inhibitors of these kinases were effective in modulating sperm motili
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Novel Anti Bacterial Drug

The Invention Two non-toxic short peptides were conjugated to form a novel drug candidate. One of the peptides is a polymyxin-B or polymyxin-E analog (PMBN or PMEN, respectively) while the other is an immune cell chemotactic peptide (fMLF). The resultant new drug candidates (PMBN-fMLF or PMEN-fMLF) exhibit dual antimicrobial activities: it binds specifically to gram negative bacteria, thus enhancing penetration of antibiotics into the bacteria and at the same time it promotes bacterial killin
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Topical Therapy for Fungal Nail Infections (Onychomycosis)

Invention The invention comprises a two-step topical treatment for fungal nail infections combining (a) enzymatic digestion of dermatophyte hyphae by lysing enzymes to expose the growing tips and (b) application of a new highly effective fungicide (a derivative of the non-specific protease inhibitor Phenyl Boronic Acid (PBA). The Need Onychomycosis is a stubborn, progressive, recurring fungal nail infection that, although superficial, can cause significant health problems. Its prevalence
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Improved Calcitonin-based Therapeutics

Invention The aggregation site on human calcitonin has been identified, paving the way for development of specific inhibitors of calcitonin amyloid fibril formation. Such inhibitors will enable development of improved calcitonin therapeutics as well as greatly facilitate in vitro calcitonin manipulations. The Need The therapeutic use of human calcitonin is severely limited by its tendency to associate and form fibrils. Salmon calcitonin, which is used in the clinic, causes immunogenic react
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An inhibitor to the ß-secretase pathway of Aß generation in Alzheimer´s Disease

Invention Antibodies have been raised against the β-secretase cleavage site in Amyloid β precursor protein (AβPP). These antibodies can prevent the processing of AβPP and the subsequent formation of amyloid deposits, a central event in the pathogenesis of Alzheimer’s Disease. This approach will not interfere with 'house keeping' activities associated with β-secretase, likely to be a problem with direct β-secretase inhibitors. Therapy may be active, inducing the patient's immune system t
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Collagomers - Widely Applicable Drug Delivery Technology

Invention Collagomers are bioadhesive micro and macro particles generated by linking a phospholipid to collagen. Collagomers entrap a wide range of molecules and release them slowly over long periods of time. They bind with high affinity to cells providing an efficient, widely applicable drug delivery system. The Need Current particulate systems for drug delivery such as cell microspheres, viral envelopes and liposomes suffer from disadvantages such as stability and biocompatibility proble
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Single-Trigger Molecular Amplifiers

Invention Dendrimers were synthesized, whereby a single specific cleavage event releases all the functional groups at the tips of the dendrimer, via spontaneous fragmentation of the dendrimer to its building blocks. These dendrimers, with the capacity to self destruct, have been termed Self-Immolative Dendrimers (SIDs). SIDs can be used to amplify chemical or biological signals depending upon the specific trigger, which may be cleavage by a specific enzyme, specific photo-activation of a phot
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Targeted Nanoparticles for Drug Delivery

Invention Novel particulate drug delivery technology comprises of lipidated Glycosaminoglycan, that form micro or nano particles in a controlled manner. The particles (neither a liposome nor a microsphere/nanosphere) can encapsulate DNA, proteins and small molecules with high efficiency and perform in vivo as targeted, site-adherent, site retaind, sustained-release drug depots. In vivo studies with encapsulated chemotherapeutics have demonstrated that these particles are long-circulating, activ
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GSK-3 inhibitors for the Treatment of Insulin Resistance-Related Diseases

Invention Novel inhibitors of GSK-3 were identified. These inhibitors represent substrate competitors that interact specifically with the GSK-3 substrate binding site. GSK-3 modulates insulin action by controlling the activity of two other proteins in the insulin-signaling pathway, and its activity is elevated in insulin resistant and type II diabetic tissues. Reducing GSK-3 activity should, therefore, alleviate the deleterious effect and restore insulin responses including glucose uptake and
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Inhibitors of Amyloid Fibril Formation for the Treatment of Type II Diabetes

Invention Novel inhibitors directed against a newly identified sequence, aimed to prevent amyloid plaque formation and beta cell death are currently being developed. These inhibitors present a novel approach to the treatment of Type II Diabetes and prevention of disease progression. They are based on a novel domain in islet amyloid polypeptide (IAPP), the shortest sequence that best mediates the molecular recognition process that leads to the formation of amyloid fibrils. The Need Type II
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Immunotherapy for the prevention and treatment of osseous metastasis

Invention A gene encoding a novel cell adhesion protein whose expression is associated with bone metastases has been identified. The gene is termed SEL-OB and codes for a selectin type protein. SEL-OB is expressed in human breast cancer cell lines and invasive pleomorphic lobular carcinoma. The SEL-OB protein is involved in cell adhesion, hence therapies to interfere with SEL-OB are expected to prevent cell adhesion and the establishment of bone metastases. SEL-OB may also serve as a diagnostic
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Novel Peptides for Therapeutic Angiogenesis and lschemic Cardiovascular Diseases

Invention Novel peptides were identified that bind endothelial cells and induce angiogenesis. The peptides were demonstrated to induce proliferation, migration and vascularization of endothelial cells under hypoxic conditions and completely restored blood perfusion in ischemic tissues in an ischemic hind limb mouse model. The peptides were shown to operate by binding to membrane GRP78 (glucose regulated heat shock protein) inducing inhibition of hypoxia induced apoptosis in endothelial cells a
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Novel anti-cancer drugs with improved potency and acitivity against drug resistant cells

Invention Antimetabolites and antineoplastic agents have been chemically modified to render them active against resistant as well as sensitive cancer cells The Need The major reason for chemotherapy failure in cancer treatment is the emergence of cells that are resistant to therapeutic agents Potential Applications Cancer Chemotherapy Advantages These new chemical entities have a substantial therapeutic advantage over existing anti-cancer agents as they are active against resistant cancer
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New Application for Vitamin D

Invention A new application / Use for Calcitriol - It was demonstrated, in vitro, that calcitriol and some of its synthetic analogs have the potential to reduce the damage inflicted to normal tissue by accepted anti-cancer therapy. Vitamin D offers protection from programmed cell death to cells in culture, reduces the synthesis and secretion of metalloproteinases (proteolytic enzymes that cause damage to tissues when in excess) and decreased the secretion of chemokines (pro-inflammatory mediat
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Genetic Screen for Hepatitis C virus (HCV) Protease Inhibitors

Invention A novel in vivo genetic screen for Hepatitis C virus (HCV) Protease Inhibitors has been developed based on the concerted co-expression of a reporter gene, recombinant Hepatitis C virus (HCV) non-structural 3 (NS3) protease and a potential inhibitor within a bacterial host. Potential inhibitors may be selected from a library of stabilized peptides or from a library of recombinant antibodies. The assay affords simple blue/white selection coupled with enrichment of cells expressing prot
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Cell Replacement Therapy for Diabetes

Invention A novel source of surrogate insulin producing beta cells has been developed. Genetic and epigenetic manipulations are employed to induce differentiation of a number of human progenitor cell types into mature, functional beta cells for treatment of diabetes. The Need Type 1 (insulin-dependent) diabetes mellitus, which results from the autoimmune destruction of the insulin-producing pancreatic islet beta cells, afflicts about 1 in 200 people. Treatment of type 1 diabetes by insulin
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Cell THerapy for Diabetes: Expansion and re-differentiation of adult human pancreatic islet cells for transplantation

Invention Conditions have been discovered for efficient expansion of adult human islet cells expressing normal beta-cell function (beta-cell gene expression and insulin content) The Need Type 1 (insulin-dependent) diabetes mellitus, which results from the autoimmune destruction of the insulin-producing pancreatic islet beta cells, afflicts about 1 in 200 people. Treatment of type 1 diabetes by insulin administration can not prevent the long-term complications of the disease. Type 2 diabetes i
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Adamantyl-OEG-fullerene Hybrids as potential therapeutic agents

The Invention A series of novel soluble adamantyl-oligoethyleneglycol-fullerene hybrids was prepared via Bingel-Hirsch functionalization of C60 fullerene with various adamantyl-oligoethyleneglycol malonates. As NMDA-targeted antioxidants, these compounds have potential as therapeutic agents for the treatment of neurological disorders The Need NMDA receptor contributes importantly to the etiology and progression of many neurological diseases such as Multiple Sclerosis, Parkinson's and Alzheime
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Macrolid Induced Correction of Premature Stop Codons: a novel Treatment for Colorectal Cancer

The Invention An antibiotic of the Macrolid family was demonstrated as a new treatment for colorectal cancer and other genetic human diseases that arise from pre-mature stop codons in important coding sequences. The Need Around one third of all genetic disorders as well as most cases of sporadic and hereditary colorectal cancer occur as a result of premature stop codons (termed nonsense mutations) in an individual’s DNA. For a significant proportion of these cases, if the cell can be ‘p
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TAR-1: a human single chain antibody for the treatment of cancer related to mutations in p53

The Invention TAR-1, a human single chain antibody, which recognizes the common epitope exposed in mutant p53, but not in wild type p53, has been isolated. Binding of TAR-1 to the mutant p53 common epitope restores both the wt conformation and function of p53, and thus restores its ability to bind specifically to DNA and/or abolishes the distinct oncogenic properties of the p53 mutant protein. TAR-1 binds the mutant p53 either in the cytoplasm or in the nucleus of tumor cells and serve as a “
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Novel psychotropic agents for the treatment of both negative and positive symptoms of Schizophrenia

The Invention New Chemical Entities (NCE's) psychotropic agents have been developed, possessing anti-dopaminergic activity, along with positive modulatory glutamate NMDA receptor activity. These agents are aimed at the treatment of schizophrenia and bipolar disorder affecting positive symptoms as well as negative symptoms and cognitive deficits, and possibly mood disorders. PGW4, the lead compound, has been assayed both in vitro and in vivo demonstrating anti-psychotic activity and anti-depress
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Serotonin Reuptake Inhibitors as Novel Anti-Platelet Drugs

The Invention Serotonin-selective reuptake inhibitors (SSRIs) were chemically modified to produce novel quaternary nitrogen derivatives having a peripheral-restricted serotonin reuptake inhibitory activity. The lead compound GR-101 was demonstrated as a novel anti-platelet drug (for reducing platelet aggregation). Such compounds have a clinical potential similarly to aspirin or clopidogrel (Plavix) for reducing the risk of thrombosis and the related risks of ischemia, including ischemic heart
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ASSNAC: a novel treatment of oxidative stress induced by reactive oxygen

The Invention ASSNAC, S-allymercapto-N-acetylcysteine, is a small bi-functional molecule that up-regulates cellular glutathione levels, the major cellular anti-oxidant. ASSNAC dissociates in peripheral tissues, slowly releasing s-allylmercaptan and NAC. s-allylmercaptan, the thiol-active component of allicin, induces the expression of oxidative stress-related genes and glutathione biosynthesis. NAC, N-acetylcysteine is a food supplement aimed to supply cells with cysteine, a precursor for glu
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Novel Hapatatis C Virus NS3 serine protease inhibitor

The Invention Novel single chain and single domain antibodies and peptide aptamers which inhibit NS3 protease, have been isolated The Need Hepatitis C virus (HCV) infection is a major world-wide health problem, causing chronic hepatitis, liver cirrhosis and primary liver cancer (HCC). Currently there is no anti HCV vaccine, and even the most effective HCV therapy with PEGylated interferon in combination with ribavirin, a nucleoside analog with antiviral activity, is effective in <50% of inf
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Gagomers - Novel drug delivery system for the delivery of proteins to the brain

The Invention Gagomers are novel particles (neither liposomes nor microspheres/nanospheres) composed of hyaluronan shell which is crossed linked via phospholipids. Gagomers could be generated either as micro or nano particles. The research team at Tel Aviv University has demonstrated the ability of Gagomers to encapsulate various proteins ranging from ~ 11,000 KDa (Insulin) to ~50,000 KDa (BSA). Gagomers encapsulating a specific protein in the size of ~50,000 KDa were tested in vivo showing p
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Novel oral formulation of Insulin

The Invention Gagomers are novel particles (neither liposomes nor microspheres/nanospheres) composed of hyaluronan shell which is crossed linked to phospholipids and can be generated either as micro or nano particles. The research team at Tel Aviv University has demonstrated that: (1) Gagomers efficiently encapsulate fibrillar Insulin (2) gagomers are protecting the insulin in the GIT (3) Due to the hyaluronan shell Gagomers are targeting the Insulin to intestinal mucosa and show muco-adhesiv
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Targeting Cancer and Bone Metastases with Novel Anti Angiogenic Polymer Therapeutics

The Invention A new strategy for cancer and bone metastases therapy was developed using combined targeted polymeric drug delivery system with angiogenesis inhibitors. The novel compounds are composed of three elements: 1. Water soluble synthetic copolymer (HPMA) as specific carrier enabling the molecules to internalize into the tumor leaky vessels. 2. The aminobisphosphonate alendronate (ALN) as a specific bone targeting moiety, that was demonstrated as an excellent candidate for targeting tu
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Cell Permeable Peptides for the Treatment of Allergy, Asthma and Inflammatory Related Diseases

The Invention Novel cell permeable peptides that fuse a membrane permeation sequence to a functional sequence were developed. These cell-permeable peptides are capable of blocking signal transduction pathways in mast cells, preventing mediator release and the subsequent inflammatory reactions. The cell-permeable peptides comprising the C-terminal end of Galpha i3 could serve as a potent inhibitors of both IgE dependent and IgE independent signaling pathways and therefore as a potent
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Silencing of Mortalin with siRNA as Adjuvant for Cancer Immunotherapy

The Invention We suggest a novel mode of treatment by inhibition of mortalin or mortalin synthesis as an adjuvant to antibody-based immunotherapy. Novel siRNA was designed as blocker of Mortalin expression. The anti-mortalin siRNA binds specifically to mortalin mRNA and leads to its destruction. Upon transfection into cells, this siRNA reduced the level of expression of mortalin by 60-90%. This was shown with several cancer cells. Mortalin specific siRNA was demonstrated to augment sensitivit
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HDACIvir´s- Novel anticancer agents

The Invention The research teams at Tel Aviv and Bar Ilan Universities have developed novel compounds derived from known histone deacetylase inhibitory (HDACI) molecules linked to acyclovir and its analogs. The new compounds (HDACIvir's) demonstrated potent anticancer activity both in vitro and in vivo and were well tolerated in initial safety studies The Need According to WHO reports, cancer is the leading cause of death worldwide - it accounts for 7.6 million (or 13%) from all deaths world
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Production of Novel Human Collagens

BACKGROUND A powerful new platform technology for the production of human collagens is being developed in the Kadler Centre for Cell-Matrix Research within the Department of Life Sciences at the University of Manchester. The collagens most closely mimic human collagen structure, giving a far superior product to that produced by the harsh conditions necessary to extract animal collagens and can be tailored to incorporate binding sites for growth factors and cell attachment to promote integration
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Advanced 3d Flexible Fibre Material for Wound Management, Orthopaedic, Sports & Personal Protective Equipment Applications

BACKGROUND Spacer structures find applications is many areas. These include automotive, sports wear, medical, mattresses and protective clothing such as gloves and body armour. Spacer structures could provide a replacement for foam. These structures can be specifically tailored to meet the needs of unique applications. THE TECHNOLOGY Research in the William Lee Innovation Centre (School of Materials, University of Manchester) has lead to the formulation of a 3D knitted spacer fabric with a high
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Collaboration/Licence Opportunity PAEDIATRIC ANAESTHESIA RE-BREATHING APPARATUS

BACKGROUND In the normal Jackson-Rees system that is used to provide anaesthetic gas to a patient, one part of the apparatus connects to an open tailed reservoir bag. This bag expands and contracts in unison with the patients breathing and allows the anaesthetist to ventilate the patient by partial occlusion of the tail and squeezing the bag. A major drawback of this system is that when exhaust gases leave the reservoir bag they vent into the operating theatre. This poses a healthcare risk to th
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Novel Antimicrobial Peptides

BACKGROUND Ai2 Limited is a University of Manchester spinout company that aims to become a significant player in the global anti-infectives market. The company’s focus is on developing novel anti-microbial products, for out-licensing to healthcare companies across a range of sectors. THE TECHNOLOGY The core technology stems from research into a class of human proteins involved in innate immunity, whose role in fighting infection had not previously been identified. Specific regions of these pro
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Corticosteroids with Reduced Side Effects

BACKGROUND Glucocorticoids (GCs) have been used therapeutically for many years to treat a range of inflammatory conditions as immunosuppressants and in the treatment of certain cancers. These compounds are the most potent and effective anti-inflammatory agents known. Their use has been limited however by their multiple and often devastating side effects. As anti-inflammatory agents, GCs have two primary modes of action. One is responsible for the unwanted side effects and the other for the desir
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Opticin a Treatment for Cancer and Angiogenesis

BACKGROUND Opticin is a protein present in the eye (in the vitreous humour) and was discovered at University of Manchester by Dr Paul Bishop. Uniquely Opticin has been found to exhibit both cytotoxic AND anti-angiogenic (blood vessel formation) effects on a range of cell lines from different cancers. Currently there is considerable interest in developing drugs derived from natural endogenous molecules with cytotoxic/anti-proliferative effects for treating cancer, as these are less likely to have
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Novel Synthesis of Iduronate a Heparan Sulphate Subunit

BACKGROUND Heparan sulphate and heparin play a central role in a large number of processes including anti-coagulation, angiogenesis, cell growth and migration. A new class of medicinal drugs can be envisaged that would either promote or inhibit the function of heparan sulfate/heparin by mimicking or competitively inhibiting the function of heparan sulphate/heparin. These types of complex heparan sulphate molecules have historically been difficult to synthesise and the majority could be obtained
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A Functional Food with Indications for Peptic Ulcers

BACKGROUND 1 in 10 people are affected by peptic ulcers over the course of their lifetime. Incidence of the condition is set to increase as the population ages. Current treatment relies on combination antibiotic therapy. However, a 20% failure rate and increasing antibiotic resistance highlight the need for a new therapeutic paradigm. THE TECHNOLOGY Prof Ian Roberts’ group at the University of Manchester are developing natural extracts for the treatment and prevention of peptic ulcers that spe
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Tumour Vascular Targeting Agents

A new pharmacophore for selective targeting of tumour blood-supply BACKGROUND Cancer is a huge killer, responsible for more than 500,000 deaths in the US and 150,000 in the UK each year, thus making new anti-cancer drugs a key driver in the pharmaceutical industry. Most cancer treatments are poorly targeted and inherently toxic to the patient. Anti-vascular drugs for cancer treatment offer a potential solution to these problems, since they specifically target the tumour vasculature which is non-
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Opticin a Treatment for Cancer and Angiogenesis

BACKGROUND Opticin is a protein present in the eye (in the vitreous humour) and was discovered at University of Manchester by Dr Paul Bishop. Uniquely Opticin has been found to exhibit both cytotoxic AND anti-angiogenic (blood vessel formation) effects on a range of cell lines from different cancers. Currently there is considerable interest in developing drugs derived from natural endogenous molecules with cytotoxic/anti-proliferative effects for treating cancer, as these are less likely to have
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Novel Drugs for the Treatment & Prevention of Allergy

BACKGROUND There is a high and increasing incidence of allergic disorders such as asthma and hay fever. It is expected that some 300m people in the western world will suffer from allergic diseases by 2010. Upwards of 60% of asthma cases are triggered by allergic responses and up to 1 in 4 urban children suffer from asthma. . Pioneering research by Prof David Garrod (University of Manchester) and Dr Clive Robinson (St. Georges Hospital Medical School) into cell junction processes and the mechanis
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Zebra Fish Models for Drug Discovery

THE TECHNOLOGY Transgenic zebrafish are becoming increasing important as models for human disease. This organism offers the drug discovery industry a number of advantages including rapid reproductive cycle and large numbers of offspring, ethical preference over other animal models, cost effectiveness and strong correlations with the genetic and phenotypic characteristics of human disease. Researchers at the University of Manchester have developed a number of exciting phenotypic models of human d
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Mitochondrial DNA Variants Associated with Metabolic Syndrome

Background: Over the past 25 years, the Wallace's laboratory discovered that the variation in the maternally-inherited human mtDNA forms a single mtDNA tree in which the branches of the tree are region specific. The mtDNAs in each major branch of the tree are thus a group of related haplotypes, called a haplogroup. These regional branches contain functional mtDNA mutations that permitted ancestral humans to adapt to different environments, and it is Dr. Wallace's belief that these "adaptive" va
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Energy-Saving Technological Method for Long-Term Storage of Bio-Degradable Tissue

Background: Currently the critical storage of bio-degradable tissue for long periods of time is done at -70" C. This temperature does provide nearly unlimited storage time. Storage at -70' C is substantially more expensive as compared with that at -40" C Technology: The crucial part of this proposal is based on the idea that while the initial cooling to the temperature where the flip-flop will be accomplished (to or below approx. -70" C) is obligatory, this low temperature is not obligatory
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Compound to Aid in Smoking Cessation

Background: Clinical studies have illustrated that tobacco is highly addictive. Paradoxically, nicotine, the psychoactive component in tobacco, is weakly reinforcing in animals. This phenomenon has led researchers to hypothesize that nicotine may interact with other constituents in tobacco smoke to produce its addictive effects. One such constituent is known to be an irreversible, nonselective, monoamine oxidase (MAO) inhibitor, a compound yet to be structurally characterized. Technology: Re
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A Chemical Compound with Possible p53 Cancer Mutant Rescue Activity

Background: Mutants of the tumor suppressor protein are frequently found in human cancers. About three quarters of them have a single amino acid change in the core domain of p53 that is needed to bind to p53 DNA binding cites. There is great interest for identifying chemical compounds that can restore function to p53 cancer mutants because 1) the patient pool that would benefit from such drugs enormous and 2) cancers with p53 mutations have worse prognosis. One of the challenge is the remarkabl
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Mouse Model of Cardiac and Muscle Disease and Cancer Caused by a Mitochondrial DNA Point Mutation

Background: It is becoming increasingly clear that mitochondrial DNA (mtDNA) base substitution mutations are a common cause of age-related degenerative diseases as well as cancer. However, no mouse model has been generated in which a mtDNA base substitution has been stably introduced into the mouse germline and resulted in an inherited predisposition to and age-related disease or cancer. Technology: UCI researchers report the introduction of a mtDNA harboring a missense mutation in the COI g
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CPET Laboratory

Technology: UCI clinic developed a novel algorithm to analyze the results of stress tests done in patients having a new pulmonary valve implant. Application: Analysis of exercise stress tests
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Chronic Sequential Sensorimotor Neural Probe Array

Background: The Chronic Sequential Neural Probe Array is designed for patients with an axonal injury in the peripheral nerves or spinal cord who require chronic intervention where stimulation of and/or recording from the axonal bundles is desired. There are two major categories of potential patients: those dealing with paralysis and those dealing with spinal cord injury (SCI) or amputation. The useable life of currently employed neural probes is typically less than one year due to a variety
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Novel Inhibitors of N-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA)

Background: Ethanoloamides of long-chain fatty acids, termed N-acylethanolamines (NAEs) have been reported to have a variety of biological activities. NAEs are a substrate of N-acylethanolamine-hydrolyzing acid amidase (NAAA) that catalytically hydrolyze NAEs to ethanolamine and the corresponding fatty acid. The catalytic activity of NAAA is distinct from that of fatty acid amide hydrolase (FAAH) and NAAA exhibits a preference for N-palmitoylethanolamine (PEA) over other NAEs. PEA has anti-infl
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Antigens for Borrelia Infection Diagnosis and Prevention

Background: Lvme disease is the most frequently reported arthropod-borne disease in the United States and Europe. Serological assays are the most common laboratory tests used to confirm or support a diagnosis based on clinical features and epidemiological circumstances. Direct detection of the organism by cultivation, histology of biopsy, or by an approved and validated polymerase chain reaction assay is uncommonly used. These direct detection methods, while generally preferable to serological
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Prokineticin 2 and Prokineticin Receptor 2 as a Target to Treat Epilepsy and Seizures

Background: PK2 belongs to a family of secreted peptides that regulate diverse biological functions including serving as a regulatory molecule for circadian rhythms. The signaling of PK2 is mediated through two cognate G-protein coupled receptors Prokineticin Receptor 1 and Prokineticin Receptor 2 (PKR1 and PKR2). Technology: Researchers at the University of California have found that PK2 is an important regulator of seizure onset and epilepsy. A PKR2 modulator would thus help treat epilepti
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Method for Making and Using Vascularized Tumor Spheroid to Predict Response to Antiangiogenesis Agents

Background: Angiogenesis drugs act to inhibit survival of newly formed blood vessels required for tumor growth and progression. These drugs have recently shown good activity in the clinic for breast, lung, colon and kidney cancer. However, these drugs can be toxic and even cause death. Only about half of patients benefit from this treatment approach. It would therefore be of value to be able to predict in advance if a patient has a better or worse probability of responding in order to avoid thi
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A New Mouse Model of Sjogren's Syndrome

Background: Sjogren's Syndrome is a grave autoimmune disease in which destruction of the exocrine glands leads to severe dryness of the eyes and mouth, with additional systemic complications. The pathogenesis of Sjogren's Syndrome is unclear, and treatment options are limited. Development of good animal models of the disease might lead to effective treatments for human patients, as well as a greater understanding of the cellular and molecular alterations that underlie disease progression. Tec
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A Novel 7 Base Deletion in the Gene on Chromosome 21 for Diagnostic of Keratoconus

Background: Keratoconus is a noninflammatory progressive corneal thinning disorder leading to mixed myopic and irregular astigmatism and is implicated as a major cause of cornea transplants in the Western world. Genetic factors have been suggested as a cause of keratoconus. The stromal thinning of keratoconus corneas is related to increase in degradative enzyme activities. In addition, keratoconus corneas have an abnormal accumulation of cytotoxic byproducts. This may be due to alterations in t
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Hybrid Binding Proteins Against Pathological Protein Aggregates in the Central

Background: The pathological protein aggregates such as beta-amyloids, alpha-synuclein and prion protein deposits in the CNS can be removed by vaccination, i.e., immunization using specific antibodies andlor synthesized antigens. Studies have demonstrated that clearance of these pathological protein aggregates in brain can attenuate brain cell loss and ameliorate brain function recovery. The disadvantage of existing methods is causing severe inflammatory response in host and involved in complic
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Methods and Reagents for Screening New Drugs and Treating Ion Pump Associated Disorders

Background: Sodium/potassium ATPases (Na+/K+-ATPases), a family of multi-subunit ion pumps, are the most important active transporters in animal cells. They are required for maintaining the electrochemical gradient responsible for resting membrane potentials in neuronal cells and for the function of other transport proteins in a variety of cell types. The important regulatory activities of Na+/K+-ATPases make them an attractive therapeutic target for the treatment of neurodegenerative, cardiac,
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Biomarker-Guided Prediction of Patient Adherence to Medications

Background: Adherence is one of the pivotal determinants of treatment outcomes for many medical disorders. It is estimated that 50% or more of patients with chronic conditions are noncompliant with medications at some time during their illness. Although there have been numerous attempts to develop approaches to evaluate adherence to drug therapy, including electronic dosing monitors, quantitative assessment of adherence remains a formidable challenge. Quantification of adherence to drug adminis
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Treatment of Retinal Disorders by Transforming Growth Factor-Beta (TFG-beta ) Superfamily Proteins and their Antagonists

Background: Retinal disorders often turn into debilitating diseases, and in most cases only few treatment options are available. With available treatment options, vision is usually not restored and treatments are often limited to delaying disease progression. Recent developments using implanted devices suggest that a limited degree of vision can be restored, but such devices have been problematic and are suboptimal for improving or restoring ocular function. The development and/or regeneration
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Rapid Multiplex Gene and mRNA Detection in Picoliter Droplets by Molecular Beacons

Background: Breast cancer is a world wide public health concern and the estimated death toll in the U.S. in 2001 was 20,000 and it also ranked first as the cause of cancer death for women between the ages of 20 to 59. People carrying a mutation in the BRCA1and BRCA2 genes are prone to breast cancer and ovarian cancer. The conventional DNA detection method which involves a heterogeneous solid-liquid hybridization process requires probe immobilization. Stringent rinsing to remove specific DNA bon
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New Therapy to Inhibit Plasma Cells in Autoimmune Diseases

Background: In patients suffering from multiple sclerosis (MS) B cells, stimulated by axon antigens, infiltrate central nervous system. Technology: The inventors discovered a new class of antibodies that specifically binds to axons in early stage of acute lesions in multiple sclerosis (MS) brains. Further the inventors engineered a single chain-variable domain antibody fragment (scFv) from clonally expanded B cells from MS patients. This scFv antibody specifically binds to axons in acute
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A New PET Radiotracer for Serotonin 5HT1A Receptors

Background: Serotonin 5-HT1A receptors are implicated in Alzheimers disease, dementia, anxiety, schizophrenia, and depression, and significant efforts have been undertaken to develop various compounds that bind to these receptors for potential use in diagnosis and therapy of disorders associated with serotonin 5-HT1A receptors. Among other proposed approaches, particularly desirable compounds include those suitable for selective positron emission tomography (PET) analysis. While currently known
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Methods of Improving Memory and Cognition

Technology: University of California, Irvine researchers have discovered a new method of improving memory by selectively modulating nuclear receptor cell signaling. The technology has been validated in several animal models of memory in both rats and mice. Application: This technology provides a drug discovery platform for new methods of treating memory or cognitive impairment.
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Methods and Compostions for the Treatment of Immune Disorders and Regulation of Cytokine and Growth Factor Signaling

Categories: Pharmaceuticals: Central Nervous System Disorders, Immune and Inflammatory Disorders Biotechnology: Assays, Diagnostics, Model Systems Background: Mgat5 is an enzyme that glycosylates T-cell receptors to modulate T-cell activation and autoimmune response. Mgat5 Null PL/J Mice were developed as part of a study performed by scientists at Mount Sinai Hospital and the University of California, Irvine to establish an understanding of the role of Mgat5 modified glycans in the regula
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Phage-displayed Peptide Library with Affinity for Bacterial Elongation Factor Tu

Background: The highly abundant GTP binding protein elongation factor Tu (EF-Tu) fulfills multiple roles in bacterial protein biosynthesis. EF-Tu also binds other ligands, including four structurally distinct families of antibiotics. The lack of sequence homology among the identified EF-Tu ligands demonstate promiscuous peptide binding by EF-Tu. Technology: A peptide library with a diversity of ~ 4.7X1011 different peptides was constructed containing both linear and disulfide-constrained pep
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Selective Inhibitors of Monoacylglycerol Lipase as a Treatment for Neurological Disorders

Background: Acute stress elicits the rapid formation of two endocanabinoid ligands, 2-arachidonoylglycerol (2-AG) and anandamide (AEA). These endogenous lipids bind to the CB1 cannabinoid receptor and inhibit pain sensation by acting as non-opioid stress-induced analgesics. AEA and 2-AG are metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol (MGL) respectively. Technology: University of California, Irvine researchers have developed a novel class of compounds that selectivel
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New Polymeric Biomaterials

Technology: The invention is on new polymeric biomaterials. The new biomaterials were created by chemical synthesis with carbohydrates and amino acids as building blocks. The biopolymers have a specific alternating structure between carbohydrate and peptide units. Application: The new biomaterials can also be used for many other biomedical and biotechnology applications such as: implants, prosthesis, tissue engineering, drug delivery, sensors, substrates for enzyme-linked immunosorbent assay
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Somatic Mitochondrial DNA (mtDNA) Control Region (CR) Mutations Associated with Alzheimer's Disease: the Cause and Diagnosis

Background: Sporadic Alzheimer's Disease (AD) has been associated with defects in mitochondrial oxidative phosphorylation (OXPHOS) as well as inherited and somatic mitochondrial DNA (mtDNA) mutations. To determine if mtDNA mutations contribute more generally to the etiology of AD, we have investigated the mtDNA control region (CR) from AD brains for possible disease causing mutations. Technology: We discoved that sporadic Alzheimer's Disease is associated with high frequencies of CONFIDENTIA
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Antibodies that Bind and Detect Acute Lesions in MS Brains

Background: In patients suffering from multiple sclerosis (MS) B cells, stimulated by axon antigens, infiltrate central nervous system. Technology: The inventors discovered a new class of antibodies that specifically binds to axons in early stage of acute lesions in multiple sclerosis (MS) brains. Further the inventors engineered a single chain-variable domain antibody fragment (scFv) from clonally expanded B cells from MS patients. This scFv antibody specifically binds to axons in acute
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Using Female Endocrine Hormones to Improve Psoriasis

Background: The most commonly prescribed medications for severe psoriasis are methotrexate and cyclosporine. Both these medications have serious side effects. The next line of treatment includes phototherapy but this is limited by the availability of light boxes in the dermatologist's office. Biologic treatments which include Infliximab and Etanercept are costly, administered by IV or injection and their side effects are not yet well documented. Technology: University of California, Irvine r
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Neuropeptide S (NPS) as a Treatment for Anxiety, Sleep Disorders, Attention Deficit Hyperactivity Disorder, Attention Deficit Disorder, and Asthma

Background: Patent "WO02/31145" discloses a newly deorphanized GPCR system, Neuropeptide S (NPS), the endogenous ligand, and its cognate GPCR. However this patent does not detail the pharmacological or physiological function of NPS and its GPCR. University of California, Irvine researchers have characterized NPS's function in the CNS. Technology: University of California, Irvine researchers have shown that central administration of NPS increases locomotor activity in mice and decreases parad
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Melanin Concentrating Hormone Receptor Small Molecule Antagonists for the Treatment of Obesity and Related Metabolic Disorders

In mammals, Melanin Concentrating Hormone (MCH), a GPCR, has been shown to regulate food consumption and energy metabolism. Central administration of MCH has been shown to promote feeding while mRNA levels of the MCH Receptor 1 (MCHR1) rise as a result of starvation and leptin deficiency. MCH also stimulates insulin and leptin relase in insulinoma cell lines and adipose cells respectively and regulates pituitary hormones. Mice devoid of MCH are lean and hypophagic, while mice over-expressing MCH
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Design and Synthesis of PET Radioligands for alpha 4 beta 2 Nicotinic Acetylcholine Receptors

Background: Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of ligand-gated ion channels and are distributed widely in the human and nonhuman brain. Several nAChRs have been identified and characterized pharmacologically and have distinct patterns of distribution in the brain. The nicotine alpha 4 beta 2 receptor subtypes are thought to play a role in various diseases, including various brain disorders (e.g., Alzheimer's disease), behavioral disorders (e.g., schizophrenia o
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Treatment of Bladder and Urinary Tract Cancers Using Chalcone and Flavone Derivatives

Background: About 56,000 new cases of bladder cancer are diagnosed in the United States each year and approximately 12,000 Americans will die of the disease. Drawbacks of older cisplatin based therapies, such as MVAC, include toxicity and poor patient tolerance. Newer therapies such as paclitaxel do not demonstrate the ability to improve patient survival or the ability to prolong response duration. Thus the search for improved therapies is imperative. Technology: Researchers at the Universit
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R6G9 Treatment Improves Viral-Induced Neurological Disease

Background: Multiple Sclerosis (MS) is a devastating neurological disease. MS patients often experience neurologic dysfunction believed to be the result of infiltration of immune cells, inflammation of the central nervous system and eventual nerve damage. Technology: Researchers at the University of California, Irvine have identified a monoclonal antibody-based method that decreases immune cell infiltration into the CNS and improves neurological function in a mouse model of MS. Application
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An Antibody-based Method for Reducing Ocular Inflammation which Can Aid in Corneal Transplantation

HSV keratinitis is characterized, in part, by scarring of the eye as a result of HSV reactivation. To date, corneal transplantation is the standard treatment method. A significant obstacle preventing successful corneal transplantation is inflammation that occurs within the eye (ocular inflammation). Researchers at University of California, Irvine and the University of Oklahoma have identified an antibody that prolongs survival in HSV infected mice and reduces inflammation within the eyes of infe
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A Reduction in Sumoylation of Cellular Proteins Reduces Polyglutamine Toxicity in Vivo in a Drosophila Fruit Fly Model of Huntington's Disease

Background: Huntington's disease (HD) is a fatal, autosomal dominant, progressive neurodegenerative disorder. Clinical symptoms are progressive and include chorea, impaired voluntary movement, behavioral changes and dementia. Present therapies are limited to alleviating these symptoms without any influence on the course of the disease. HD is caused by a mutant protein, Huntingtin, which contains an expansion of a polyglutamine repeat in the amino-terminal domain of the protein. In transgenic mo
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Triple Transgenic Mouse Model of Alzheimer's Disease

University of California, Irvine researchers have developed a novel transgenic mouse model that contains the three major genes that contribute to the hallmark pathological features of Alzheimer's disease. These mice are exceedingly valuable for therapeutic investigations and for basic research aimed at understanding the behavioral, physiological, molecular/cell biological, and pharmacological processes leading to dementia in an animal model. Even though these mice contain three transgenes, the m
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Screening and Therapeutic Methods for Promoting Wakefulness and Sleep

Background: Current drugs used to modulate sleep and wakefulness cause a number of undesirable side-effects such as anxiety, addiction, and continued sedation. AMPA and PrRP receptors are found in the reticular thalamic nuclear (RTN) region of the brain that has been implicated in sleep rhythms, attention processing, and absence seizures. The AMPA receptor plays a role in synaptic plasticity and has been implicated in Alzheimer's disease, schizophrenia, and epilepsy. Technology: University o
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Novel Retinoblastoma Binding Protein-Related Gene and Potential Use As Cancer Vaccine

Background: The central objective in the development of an effective immunotherapy is the identification of tumor antigens that can elicit antibody and cellular immune responses in humans. Human autologous or allogeneic antibodies from cancer patients are an alternative to the use of monoclonal antibodies. Though not as specific as monoclonal antibodies, serum antibodies are useful probes to identify tumor-associated antigen epitopes relevant to immune responses in cancer patients. Technology
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DRD4, ADHD

Background: Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent disorder of early childhood. It affects an estimated 3-6% of elementary school children. ADHD individuals may have abnormal release of dopamine resulting in a "dopamine deficit" that leads to cognitive as well as behavioral problems. Technology: University of California, Irvine researchers have done molecular genetic work on the Dopamine Receptor D4 (DRD4). Their work suggests that the DRD4 7R "risk allele" may
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Her2/neu Vaccine Protects Against Tumor Growth

Background: Her2/neu is over-expressed in various types of tumor cells, including 20-30% of breast cancers, adenocarcinomas of the ovary, salivary gland, stomach and kidney, colon cancer, and non-small cell lung cancer. Passive immunotherapeutics like Herceptin control and prevent further tumor cell growth. Unlike active immunotherapeutics, Herceptin does not mediate the immunological cellular destruction. Active immunotherapeutics such as vaccines elicit T helper-1 (Th1) and Cytotoxic T ly
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Platelet Aggregation Inhibitors

Thrombin is an enzyme in the blood that plays a key role in platelet formation during injury. While blood coagulation is essential for a surface wound, platelet activation underlies various pathological situations such as unstable angina pectoris, myocardial infarction and stroke. Thrombin is mediated by protease activated receptor-1 (PAR-1) which is expressed in the nervous system and in platelets. Once activated by thrombin, PAR-1 induces rapid and dramatic changes in cell morphology that is c
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ADP Glucose Receptor as a Target for Disorders Involving Platelet Aggregation

Background: Recently, activation of the P2Y12 G-protein coupled receptor (GPCRs) has been shown to be central to platelet aggregation. Drugs preventing platelet aggregation are being tested, but one that would be specific to the P2Y12 receptor would capture a large market share. Developing drugs for the P1Y12 receptor is difficult, because it is a receptor that is naturally activated by ADP. Since practically every cell expresses ADP-activatable receptors, developing a drug screening program di
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Treatment for Prostate Cancer

Background: Polyamines are naturally synthesized by the body and are involved in many biochemical processes, including cellular proliferation, cell cycle regulation, and protein synthesis. The prostate epithelium synthesizes plyamines at a high rate making the prostate gland having one of the highest level of polyamines in the body . Elevated levels of polyamines lead to excessive cellular proliferation and cancer. Polyamines have become a potential target for therapeutic intervention against c
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A Novel Treatment for Upper Respiratory Tract Irritation and Cough

Background: Traditional cough suppression therapy has included palliatives in the form of herbal remedies, narcotics such as codeine, and local anesthetics such as benzonatate. The anesthetic compounds have limited efficacy, while the narcotics cause severe side effects because they work through the activation of opioid receptors in the central nervous system. Technology: Researchers at the University of California, Irvine, have discovered a naturally occurring compound that suppresses the c
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A New Process of Adding Alkyl Groups to Organic Substrates Using TmI2(MeOCH2CH2OMe)3

Background: In the pharmaceutical industry, synthetic chemists often alkylate starting compounds to generate compounds that have more desirable properties. However, the current reagents used in this modification process can be expensive or harmful to the chemist. Technology: Researchers at the University of California, Irvine, have discovered a compound that allows a variety of important chemical transformations to be accomplished using cheaper materials and eliminates the use of some carcin
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Donor Organ Preservation for Transplantation Using a Hemoglobin Based Solution

During heart transplantation, the heart must be preserved while it is transported from donor to recipient. Standard techniques call for the heart to be immersed and cooled in cardioplegia or saline solution. Unfortunately, this method does not deliver necessary oxygen, nutrients, and electrolytes to the heart. Newer methods of preservation have focused on creating blood-like substitutes. At the University of California, Irvine, researchers have formulated a solution that significantly lengthens
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Use of Perillyl Alcohol in Organ Transplantation

Background: Current state of the art in the field of organ transplantation employs various immunosuppressive agents to prevent post-surgical allograft rejection by the host. However, these pharmacological agents often result in many adverse side effects due to the quantities of medication that are required following transplantation. Cyclosporins, tacrilomus, mycophenclate mofetil and rapamycin are among the drugs commonly used today. The efficacy of these drugs can be attributed to their ab
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Treatment for Circadian Performance Deficits By Upmodulation of Central Glutamate Receptors

Background: Alertness and general physical and mental performance are impaired during normal sleep periods compared to those during normal waking periods. Unlike stimulants such as caffeine or methamphetamine, certain glutamatergic enhancer compounds have been shown to improve memory and performace in tests conducted during normal sleep periods for both rats and humans. Technology: Researchers at the University of California, Irvine, have tested certain compounds on rats that were subjected
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Novel and Selective Inhibitors of HIV-1 Integrase

In the ongoing battle against the human immunodeficiency virus (HIV), researchers at the University of California, Irvine, have synthesized novel compounds that inhibit the protein HIV Integrase and prevent the virus from replicating, thus providing an alternative to currently available AIDS therapy. Current therapies target the HIV proteins Reverse Transcriptase and Protease, but both these therapies have toxic side effects. Application: These novel, proprietary compounds are potent HIV Inte
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Diagnostic Marker and Novel Therapeutic Target for Neurodegenerative Disorders

Scientists at the University of California, Irvine, have isolated a candidate gene that may be responsible for increasing the risk of schizophrenia and bipolar disorder. This elusive gene encodes for a potassium ion channel that acts like an "off switch" by dampening electrical activity in neurons. It has been known that street drugs such as PCP create schizophrenia-like symptoms by blocking NMDA receptors in neurons. Over-activity of this potassium ion channel blocks the same NMDA receptors, wh
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Drugs to Improve Synaptic Transmission

About 5% of the general population over the age of 65 suffers from Alzheimer's disease for which there is no known treatment. Synaptic connections in the hippocampus, a brain region known to be important for learning and memory are especially vulnerable to Alzheimer's disease. This presumably reflects the loss of memory that is a characteristic of early stages of Alzheimer's disease. Therefore, one strategy for reducing the memory loss would be to enhance synaptic efficacy at the synapses remain
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Silica Nanoboxes

Microporous crystalline materials (e.g. zeolites, aluminophosphates), also called molecular sieves, are widely used as catalysts, adsorbents, and membranes. Two factors largely determine the utility of such materials: their regular nanoscaled size of pores and cavities, and their structural rigidity and stability under quite harsh working conditions. However, the maximum pore size of these materials is about 0.8 nm. Extending the application of porous crystalline materials to encompass the contr
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A library containing more than 3000 new enzymes produced by 14 Fungi

Solution / invention summary : 14 fungi have been grown in various harsh conditions in order to produce a variety of enzymes. A high throughput platform is then used to isolate some 3000 new enzymes. A few of them are being tested by industrial partners. Advantages / benefits : The isolated enzymes are novel and can make enzyme economically viable in selected industrial processes. Potential applications : Enzymes can replace chemicals in industrial processes in industries such as Pulp &
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Novel Targets for Preterm Labour

New Market Opportunity Over 4 million births occur annually in the US, between 0.5-1 million women are treated annually with tocolytic drugs to halt early preterm labour contractions, while annual tocolytic drug sales of in the USA are estimated at up to $500 million. With over 8 million births in Europe as a whole, an estimated total of 2-3 million patients are treated annually for preterm labour in these two major global markets. This represents a total tocolytic therapeutic market of well o
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Live-Cell based assay for DNA Damage Response

New Market Opportunity Cell-based assays play a decisive role in the current drug screening process, yielding safer drugs in a cost effective manner. Such assays offer the potential to screen out compound failure earlier in the discovery and development lifecycle, delivering increased productivity. Globally, the total cell-based assay market is expected to rise to $720 million by 2009 with a CAGR of approximately 10% over the next 5 years. Background Cell-based assays are screening proce
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Novel Sirtuin Activating Compounds

An improved method of synthesizing stilbene analogs, specifically resveratrol, that can activate sirtuins with increased efficiency, activity, and stability. General Information Sirtuins are NAD+ - dependent deacetylases that regulate many cellular processes that promote cell survival in response to environmental stress. An example of this in humans is the SIRT1 enzyme which deacetylases p53, a ubiquitous tumor suppressor protein, in order to promote cell longevity. It is supposed that one c
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Use of Equol for Treating Skin, Hair, Brain and Prostate Health and Obesity/Weight Control

General Information Dihydrotestosterone (DHT) is a metabolite of the principal male hormone testosterone. However, it is more powerful than testosterone because of its increased affinity for the androgen receptor. DHT’s function is to promote male secondary sex characteristics, such as growth of facial and body hair and deepening of the voice. Equol, a metabolite of the phytoestrogen daidzein, has been found to bind and sequester DHT thus preventing it from binding to the androgen receptor.
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