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 and also offer highly specific, novel b-lactamase inhibitors for clinical development.BACKGROUND: b-lactams, including penicillin and the cephalosporins, are the most prescribed class of antibiotics. With increased use of these antibiotics, increased resistance has developed. For example, about 70% of bacteria that cause infections in hospitals are believed to be resistant to at least one of the most commonly used antibiotics. The total market for antibiotics was estimated at $22.4 billion and the segment for 'new antibiotics' was estimated at approximately $960 million in 2001. The total market is expected to grow at an average annual growth rate of 9.1% to reach $34.5 billion by 2006. Bacteria have evolved resistance to the commonly prescribed antibiotics by expressing b-lactamase enzymes that hydrolyze the lactam ring of the antibiotic and render it inactive. To identify new, novel clinically useful inhibitors against class C b-lactamases, investigators at Northwestern University have undertaken several approaches including compound synthesis, library screening, and molecular docking. The compounds identified using these approaches have been tested in vivo in bacteria expressing AmpC b-lactamase and clinically obtained pathogenic bacteria that express class C b-lactamases. These compounds fall into several different categories: some interact with b-lactamase covalently, while others interact with the enzyme in a non-covalent manner. Some of the compounds are loosely based on known b-lactam ring containing compounds (e.g. penicillin and loracarbef), while others share no obvious similarity in structure to known antibiotics. However, these inhibitors are able to inhibit b-lactamase with high specificity and affinity.
Several patents have issued, and several patent applications are still pending. Northwestern University is interested in further developing and licensing this technology.
Patents and published patent applications: U.S. Patent 6,075,014; U.S. Patent 6,417,174; 6,184,363; 6,448,230; 7,271,186
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Tondi, et. al., Chem Biol 2001 Jun;8(6):593-611 Caselli, et. al., Chem Biol 2001 Jan;8(1):17-31 Weston et. al., J Med Chem. 1998 Nov 5;41(23):4577-86.
Type of Offer: Licensing
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