# US 7,608,416 B2 · Targeting mPGES-1 as a treatment for inflammation which avoids cardiovascular risk

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,608,416 B2
- Document ID: US7608416B2
- Status: Granted
- Kind: B2
- Application number: 11/296,979
- Filed: 2005-12-07
- Published: 2006-06-22
- Granted: 2009-10-27
- Earliest claimed: 2004-12-07
- Assignees: The Trustees of the University of Pennsylvania
- Inventors: Garret A. Fitzgerald
- Web page: https://patentgrep.com/patent/US7608416B2

## CPC

- A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure}
- A61K 31/415: 1,2-Diazoles
- A61K 31/60: Salicylic acid; Derivatives thereof
- C12Q 1/25: involving enzymes not classifiable in groups C12Q1/26 {- C12Q1/66}
- G01N 2500/00: Screening for compounds of potential therapeutic value
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to methods for the treatment of inflammation and pain without increasing cardiovascular risk by administration of an inhibitor of mPGES-1. The invention further is related to identifying inhibitors of mPGES-1 that do not increase cardiovascular risk when administered to an individual.

## Claims

### Claim 1

A method of identifying an inhibitor of microsomal prostaglandin E synthase (mPGES-1) in a cell that does not increase risk of a cardiovascular event in an individual comprising said cell, the method comprising:
a. measuring a first level of prostacyclin and a first level of prostaglandin E2 (PGE2) produced by a cell that expresses mPGES-1,
b. administering a test compound to the cell, and
c. measuring a second level of prostacyclin and a second level of PGE2 produced by the cell, wherein a test compound that reduces the second level of PGE2 compared to the first level of PGE2 and wherein the second level of prostacyclin is greater than the first level of prostacyclin is identified as an inhibitor of mPGES-1 that does not increase the risk of a cardiovascular event in an individual when administered to the individual.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cell is an endothelial cell.

### Claim 3 (depends on 2)

The method of claim 2, wherein the endothelial cell is a murine endothelial cell or a human endothelial cell.

### Claim 4 (depends on 2)

The method of claim 2, wherein the murine endothelial cell comprises a human mPGES-1 gene.

### Claim 5

A method of identifying an inhibitor of microsomal prostaglandin E synthase (mPGES-1) that does not increase the risk of a cardiovascular event in an organism, the method comprising:
a. measuring a first level of prostacyclin and a first level of prostaglandin E2 (PGE2) in a biological sample derived from an organism that expresses mPGES-1,
b. administering a test compound to the organism, and
c. measuring a second level of prostacyclin and a second level of PGE2 in a biological sample derived from the organism, wherein a test compound that reduces the second level of PGE2 compared to the first level of PGE2, and wherein the second level of prostacyclin is greater than the first level of prostacyclin, is identified as an inhibitor of mPGES-1 that does not increase the risk of a cardiovascular event in the organism when administered to the organism.

### Claim 6 (depends on 5)

The method of claim 5, wherein the first and second levels of PGE2 and prostacyclin are measured in urine samples obtained from the organism.

### Claim 7 (depends on 5)

The method of claim 5, wherein the organism is a mouse.

### Claim 8 (depends on 7)

The method of claim 7, wherein the mouse expresses human mPGES-1.