Inhibitory And Non-Inhibitory Antigen Binding Polypeptides Against Human P450 Enzymes
Description of Invention:
This invention concerns monoclonal antibodies (MAbs) specific for particular members of the cytochrome P450 family of enzymes. The cytochrome P450s are the metabolic interface between xenobiotics and their metabolism in human and other species as well as for the metabolism of endobiotics. A large array of drugs, mutagens, carcinogens, pesticides, environmental chemicals, fatty acids, bile acids, and steroids are metabolized by individual forms of cytochrome P450. The invention involves the construction, isolation, and production of MAbs that specifically bind to human cytochrome P450 3A3, 3A4, 3A5, and 2E1 and that specifically inhibit the enzyme activity of human cytochrome P450 3A3, 3A4, 3A5, and 2E1 (inhibitory MAbs) and MAbs that specifically bind to cytochrome P450 3A3, 3A4, 3A5, and 2E1, without inhibiting enzyme activity (non-inhibitory MAbs). Novel inhibitory MAbs to human P450 have been in development for some time. These MAbs can be used to assess adverse reactions in patients to compounds and to identify populations that would exhibit different sensitivities to the therapeutic or toxic effects of compounds. Cytochrome P450 3A4 and 3A3 are very important members of the P450 family of enzymes. The human P450 3A4 and 3A3 metabolize a large variety of drugs, steroids, and carcinogens. Cytochromes P450 3A3 and 3A4 are considered the most important P450s for a wide range of high molecular weight substrates which include many of the known clinically useful drugs, such as tranquilizers, antidepressants, immunosuppressants, and anticancer drugs. Cytochrome P450 2E1 is important because it metabolizes low molecular weight compounds susceptible to environmental hazards and carcinogens. The human P450 2E1 also metabolizes clinically useful drugs such as the anesthetic chlorzoxazone and the analgesic acetaminophen as well as caffeine. Issuance of a patent for this invention is currently pending.
Inventors:
HV Gelboin (NCI) FJ Gonzalez (NCI)
Patent Status:
DHHS Reference No. E-185-1995/0 --
U.S. Patent No. 5,939,530 issued 17 Aug 1999
Cancer -Diagnostics-In Vitro-MAb Based Cancer -Diagnostics Cancer -Research Materials Internal Medicine-Diagnostics Internal Medicine-Other
For Additional Information Please Contact: Fatima Sayyid M.H.P.M.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4521
Email: sayyidf@mail.nih.gov
Fax: (301) 402-0220
