Agents That Bind To And Inhibit Human Cytochrome P450 2D6
Description of Invention:
This invention concerns monoclonal antibodies (MAbs) and other binding agents specific for the 2D6 subgroup of cytochrome P450 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 2D6 and that specifically inhibit the enzyme activity of human cytochrome P450 and lack specific binding to other human cytochrome P450s. 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 2D6, also known as debrisoquine hydroxylase, is the best characterized polymorphic P450 in the human population. Genetic differences in cytochrome P450 2D6 may be associated with increased risk of developing environmental and occupational based diseases. In addition, several drugs for treating cardiovascular and psychiatric disorders are known substrates of cytochrome P450 2D6, and these compounds could be more readily prescribed to normal metabolizers as assessed using the MAbs described in the invention. The list of compounds includes beta-blockers and antiarrhythmics, psychoactive drugs including tricyclic antidepressants, and a variety of other commonly used drugs including codeine and dextromethorphan.
An adjunct technology to this invention that is available for licensing involves two inhibitory monoclonal antibodies to human P450 3A4 and human P450 2E1 that have been developed (U.S. Patent No. 5,939,530). The P450 3A4 has likely the largest number of known drug substrates than any other P450. The P450 2E1 also metabolizes some drugs and has high activity towards smaller molecules which are found in the environment and which may be toxic.
Cancer -Diagnostics-In Vitro-MAb Based Cancer -Diagnostics Cancer -Research Materials Internal Medicine-Diagnostics Internal Medicine-Research Materials
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
