Genetic markers associated with response to crth2 receptor antagonists

Patent metadata

Field	Value
Publication number	US-2018237856-A1
Application number	US-201615745926-A
Country	US
Kind code	A1
Filing date	Jul 21, 2016
Priority date	Jul 23, 2015
Publication date	Aug 23, 2018
Grant date	—

Abstract

The present invention provides genetic markers on human chromosome 1 that are associated with a beneficial response to CRTH2 receptor antagonists. These CRTH2 receptor antagonist response markers are useful, inter alia, to identify patients who are most likely to benefit from treatment with CRTH2 receptor antagonist compositions and drug products, in methods of treating patients having a disease susceptible to treatment with a CRTH2 receptor antagonist, and in methods for selecting the most appropriate therapy for such patients.

First claim

1 . A method of treating a patient with a disorder susceptible to treatment with a CRTH2 receptor antagonist comprising:
administering a therapeutically effective amount of the CRTH2 receptor antagonist to the patient, wherein said patient, prior to the administration of the CRTH2 receptor antagonist, has tested positive for at least one copy of a better response allele selected from a CRTH2 receptor antagonist marker in the table below:

Polymorphic

Better

Site

Response

(PS)
Alleles
Allele

rs12748961
T/C
C

rs12118655
A/G
G

rs6679073
C/A
A

rs12564209
C/G
G

rs3805
T/G/A
G

rs71633561
G/C
C

rs71970505
ATGCAGACTGT/-
-

rs12132270
C/T
T

rs67625805
T/-
-

rs3747972
A/G
A

rs11557080
G/A
A

rs71633563
C/T
T

rs34848415
A/-
-

rs1891091
A/G
A

2 . The method of claim 1 , wherein the CRTH2 receptor antagonist response marker is the rs12748961 SNP, and
said patient, prior to the administration of the CRTH2 receptor antagonist, has tested positive for at least one copy of the C allele of the rs12748961 SNP.

3 . A method of diagnosing in a patient who is susceptible to treatment with a CRTH2 receptor antagonist and treating asthma, said method comprising:
(a) obtaining a biological sample from a human patient; (b) detecting whether a better response allele of at least one of the CRTH2 receptor antagonist markers in the table below is present in the biological sample;

Polymorphic

Better

Site

Response

(PS)
Alleles
Allele

rs12748961
T/C
C

rs12118655
A/G
G

rs6679073
C/A
A

rs12564209
C/G
G

rs3805
T/G/A
G

rs71633561
G/C
C

rs71970505
ATGCAGACTGT/-
-

rs12132270
C/T
T

rs67625805
T/-
-

rs3747972
A/G
A

rs11557080
G/A
A

rs71633563
C/T
T

rs34848415
A/-
-

rs1891091
A/G
A

Assignees

• Merck Sharp & Dohme

Inventors

• Opiteck Gregory J
• Wong Peggy H
• Mcelwee Joshua
• Mehrotra Devan V
• Greenberg Steven
• Guo Zifang

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• A61K31/47

  Quinolines; Isoquinolines · CPC title

• A61K31/437 Primary

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title