Agents that bind to and inhibit human cytochrome P450 2C19
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsHarry V. Gelboin, Kristopher W. Krausz, Frank J. Gonzalez
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Abstract
The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 2C19 having advantageous properties, including capacity substantially to inhibit enzyme activity of human cytochrome P450 2C19 and lack of specific binding to other human cytochrome P450s. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 2C19, and in methods of measuring P450 2C19 levels in individuals relative to P450 2C19 levels in a control population.
Claims19
A method of detecting cytochrome P450 2C19, comprising:
- contacting a sample suspected of containing cytochrome P450 2C19 with a first monoclonal antibody or a binding fragment thereof;
- and
- determining whether the first monoclonal antibody or the binding fragment thereof specifically binds to the sample, specific binding indicating the presence of cytochrome P450 2C19 in the sample,
- wherein the first monoclonal antibody or the binding fragment thereof competes with a second monoclonal antibody selected from the group consisting of MAb 1-7-4-8 (ATCC PTA-3970) or a binding fragment thereof, MAb 1-5-1-3 (ATCC PTA-3969) or a binding fragment thereof, and MAb 1-1-11-1 (ATCC PTA-3971) or a binding fragment thereof, and
- wherein the first monoclonal antibody or the binding fragment thereof comprises a member selected from the group consisting of:
- MAb 1-7-4-8 (ATCC PTA-3970) or a binding fragment thereof,
- MAb 1-5-1-3 (ATCC PTA-3969) or a binding fragment thereof, and
- MAb 1-1-11-1 (ATCC PTA-3971) or a binding fragment thereof.
A method of measuring P450 2C19 levels in an individual relative to P450 2C19 levels in a control population, the method comprising:
- contacting a sample suspected of containing cytochrome P450 2C19 from the individual with a first monoclonal antibody or a binding fragment thereof specific for P450 2C19, and
- determining the P450 2C19 levels in the individual relative to P450 2C19 levels in the control population,
- wherein the first monoclonal antibody or the binding fragment thereof competes with a second monoclonal antibody selected from the group consisting of MAb 1-7-4-8 (ATCC PTA-3970) or a binding fragment thereof, MAb 1-5-1-3 (ATCC PTA-3969) or a binding fragment thereof, and MAb 1-1-11-1 (ATCC PTA-3971) or a binding fragment thereof, and
- wherein the first monoclonal antibody or the binding fragment thereof comprises a member selected from the group consisting of:
- MAb 1-7-4-8 (ATCC PTA-3970) or a binding fragment thereof,
- MAb 1-5-1-3 (ATCC PTA-3969) or a binding fragment thereof, and
- MAb 1-1-11-1 (ATCC PTA-3971) or a binding fragment thereof.
A method of detecting cytochrome P450 2C19, comprising:
- contacting a sample suspected of containing cytochrome P450 2C19 with a first monoclonal antibody or a binding fragment thereof specific for P450 2C19;
- and
- determining whether the first monoclonal antibody or the binding fragment thereof specifically inhibits the activity of cytochrome P450 2C19, specific inhibition indicating the presence of cytochrome P450 2C19 in the sample,
- wherein the first monoclonal antibody or the binding fragment thereof competes with a second monoclonal antibody selected from the group consisting of MAb 1-7-4-8 (ATCC PTA-3970) or a binding fragment thereof, MAb 1-5-1-3 (ATCC PTA-3969) or a binding fragment thereof, and MAb 1-1-11-1 (ATCC PTA-3971) or a binding fragment thereof, and
- wherein the first monoclonal antibody or the binding fragment thereof comprises a member selected from the group consisting of:
- MAb 1-7-4-8 (ATCC PTA-3970) or a binding fragment thereof,
- MAb 1-5-1-3 (ATCC PTA-3969) or a binding fragment thereof, and
- MAb 1-1-11-1 (ATCC PTA-3971) or a binding fragment thereof.
Dependencies are inferred from the claim text.