The United States of America, as Represented by the Secretary, Department of Health and Human Services

The United States of America as Represented by the Department of Health

The United States of America as Represented by the Secretary of

Other

Nestec S.a.

Gentest Corporation

Harry V Gelboin

Frank J Gonzalez

Kristopher W Krausz

Curtis C Harris

Andrea M Pfeifer

Bernard Moss

Katharine C Mace

Narayana Battula

Bruce W Penman

James P Hardwick

Tian J Yang

Urs A Meyer

Talia Sher

Charles L Chrespi

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.

Agents that bind to and inhibit human cytochrome P450 2C19

The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 2C8, 2C9, 2C18, and 2C19 having advantageous properties, including capacity substantially to inhibit enzyme activity of the various human cytochrome P450 2C family members and lack of specific binding to other human cytochromes P450. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 2C family members, and in methods of screening individuals for a poor metabolizing individual human P450 2C family phenotypes.

Antibodies that bind to and inhibit human cytochrome P450 2C9*1, 2C9*2, and 2C9*3

The invention provides monoclonal antibodies to human cytochrome P450 2C8, 2C9, 2C18, and 2C19 having advantageous properties, including capacity substantially to inhibit enzyme activity of the various human cytochrome P450 2C family members and lack of specific binding to other human cytochromes P450. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 2C family members, and in methods of screening individuals for a poor metabolizing individual human P450 2C family phenotypes.

Agents that bind to and inhibit human cytochrome P450 2C8, 2C9, 2C18 and 2C19

The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 1A2 having advantageous properties, including capacity substantially to inhibit enzyme activity of human cytochrome P450 1A2 and lack of specific binding to other human cytochromes P450. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 1A2, and in methods of measuring p450 1A2 levels in individuals relative to p450 1A2 levels in a control population.

Agents that bind to and inhibit human cytochrome P450 1A2

The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 2A6 having advantageous properties, including capacity substantially to inhibit enzyme activity of human cytochrome P450 2A6 and lack of specific binding to other human cytochromes P450. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 2A6, and in methods of measuring p450 2A6 levels in an individual relative to p450 2A6 levels in a control population.

Agents that bind to and inhibit human cytochrome P450 2A6

The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 2D6 having advantageous properties, including capacity substantially to inhibit enzyme activity of human cytochrome P450 2D6 and lack of specific binding to other human cytochromes P450. The binding agents of the invention are useful in methods for screening drugs for metabolism by cytochrome P450 2D6, and in methods of screening individuals for a poor metabolizing human P450 2D6 phenotype.

Agents that bind to and inhibit human cytochrome P450 2D6

Antigen binding polypeptides that specifically bind human cytochrome P450 3A3, 3A4, and 3A5 and that specifically inhibit the enzyme activity of human cytochrome P450 3A3, 3A4, and 3A5 are described. Antigen binding polypeptides that specifically bind to human cytochrome P450 3A3 and 3A4 are also described. Antigen binding polypeptides which specifically bind to human cytochrome P450 2E1 and which specifically inhibit the enzyme activity of human cytochrome P450 2E1 are described. Antigen binding polypeptides which specifically bind to human cytochrome P450 2E1 are also described. Methods of determining the contribution of human cytochrome P450s to the metabolism of compounds, using the antigen binding polypeptides of the invention, are also described.

Inhibitory and non-inhibitory antigen binding polypeptides against human

An improved method for measuring the activity of a promoter sequence in a mammalian cell using a reporter gene is provided. The improvement involves using a reporter cassette containing a DNA sequence encoding a cytochrome P450 with a polyadenylation signal sequence as the reporter gene. Compositions containing the cytochrome P450 reporter cassette also are provided.

Method for detecting a receptor-ligand complex using a cytochrome P450

Non-tumorigenic, stable, human bronchial and liver epithelial cell lines are provided wherein the cell lines are capable of expressing human cytochrome P450 genes which have been inserted into the cell lines. Also provided are methods and kits for identifying potential mutagens, cytotoxins, carcinogens, chemotherapeutic and chemo-preventive agents utilizing these cell lines.

Immortalized human cell lines containing exogenous cytochrome P450 genes

A cloned cDNA encoding debrisoquine 4-hydroxylase gene and a probe for identifying humans having a genetic defect in the metabolism of a certain class of drugs of which debrisoquine is a model, have been prepared. Testing of new drugs and of humans by a simple assay has also been described.

P450db1 clones for identifying humans with genetic defect in drug

The present invention is related to the construction and application of vaccinia virus containing DNA sequences for encoding and efficient expression of enzymatically active cytochrome P-450 polypeptides in mammalian cells. Preparation and use of pure P1-450 and P3-450 cytochromes have been described.

Recombinant vaccinia virus encoding cytochromes P-450

Non-tumorigenic, human bronchial epithelial cell lines are provided wherein the cell lines are capable of expressing cytochrome P450 genes which have been inserted into the cell lines. Also provided are methods and kits for identifying potential mutagens, cytotoxins, carcinogens, and chemotherapeutic agents utilizing these cell lines.

Growing community of inventors

Chevy Chase, MD, United States of America

Harry V Gelboin