Assays to detect Cox-2 activity for determining treatment effectiveness for a variety of inflammatory and cancerous diseases

Summary

This invention identifies COX-2 metabolites as markers for a variety of inflammatory, neurodegenerative and cancerous diseases, and it provides a means for determining and monitoring levels of metabolites of COX-2 from patient samples. It may also be used to augment information from imaging and other diagnostic and disease progression monitoring modalities. In addition, the technology provides a means for testing activity of agonists or antagonists that can aid in the design of drugs that reduce effects of harmful prostaglandins with reduced side effects.

Description

COX-2 activity detection and measurement is accomplished by detecting and/or measuring the COX-2 specific enzymatic glyceryl-prostaglandin products, anandamide and 2-arachidonyl glycerol (2-AG). Certain changes in COX-2 activity are associated with a variety of human inflammatory diseases. These diseases include, but are not limited to, acute appendicitis, asthma, myocardial infarction, certain immunological disease processes, infection, malignancy, endotoxemia and reperfusion injury. In addition, COX-2 inappropriate expression or overexpression is associated with certain types of cancers, including, but not limited to, carcinoma of the colon, rectum, cervix, stomach, esophagus, lung and skin. The amount of COX-2 expression is related to the stage or progression of cancer. COX-2 has become a major pharmaceutical target for developing treatments for these and other diseases.

In addition to their roles as endogenous arachidonic acid derivatives, 2-AG has been shown to be a high affinity agonist of the cannabinoid receptors, CB1 and CB2, and is termed an endocannabinoid. Recent studies have shown a role of the 2-AG as a modulator of the immune system due to its detection in a variety of different cellular elements of the immune system, including dendritic cells, macrophages, microglia and lymphocytes.

Potential Market Size

The in vitro cancer diagnostic market is estimated at $1.3 billion in the U.S. alone.

Scope of Opportunity

Statistics show that over half the population, 51% of Americans, is taking one or more prescription drugs for a chronic condition. The ability to detect and accurately measure COX-2 specific activity is important for patients with a variety of inflammatory and cancerous diseases. The present invention provides novel compositions and methods for diagnosing and monitoring these disease processes, for staging of disease non-invasively, for evaluating the effectiveness of therapy and for developing new treatment regiments.

Current Expectations

The technology has the potential for providing a simple and accurate test method to allow physicians to track the presence and rate of growth of a wide variety of diseases. The test methods are simple and will be easy to use. Following the progression of an illness is an essential part of treatment for determining preventive, therapeutic or prophylactic measures. The testing sample is selected from a group consisting of urine, plasma, cerebrospinal fluid, saliva, sputum, bile, joint fluid, biopsy and conditioned media from a cell culture.

Partnering Opportunity

A licensing partner is sought to support the development of assays for testing and quantifying metabolite activity in relation to regulation of COX-2 activity in pathogenesis of inflammatory related diseases, cancer, pain, and neurodegenerative diseases.

Intellectual Property Status

2 U.S. patents, 1 C.I.P., 1 divisional and 2 nationalized PCT's:
US: 7,314,709
US: 7,189,504
EP: 01963833.7, allowed claims in Europe
EP: 01963827.9, allowed claims in Europe

Publications

See http://bret.mc.vanderbilt.edu/marnett/recentpublications-2008.htm