Genetic markers associated with response to crth2 receptor antagonists

Patent metadata

Field	Value
Publication number	US-2021348235-A1
Application number	US-202117377514-A
Country	US
Kind code	A1
Filing date	Jul 16, 2021
Priority date	Jul 23, 2015
Publication date	Nov 11, 2021
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 asthma comprising:
administering a therapeutically effective amount of {(7R)-4-fluoro-7-[5-(4-fluorobenzyl) -1H-[1,2,3]triazol-1-y1]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-y1}-acetic acid or a pharmaceutically acceptable salt thereof to the patient, wherein said patient, prior to the administration of the {(7R)-4-fluoro-7-[5-(4-fluorobenzyl)-1H-[1,2,3]triazol-1-y1]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-y1}-acetic acid or the pharmaceutically acceptable salt thereof, has tested positive for at least one copy of the G allele of rs12118655

2 . (canceled)

3 . A method of diagnosing in a patient who is susceptible to treatment with {(7R)-4-fluoro-7-[5-(4-fluorobenzyl)-1H-[1,2,3]triazol-1-y1]-6,7,8,9-tetrahydropyrido[1,2-a]indo-10-y1}-acetic acid or a pharmaceutically acceptable salt thereof and treating asthma, said method comprising:
(a) obtaining a biological sample from a human patient; (b) detecting whether the G allele of rs12118655 is present in the biological sample; (c) diagnosing the patient as susceptible to treatment with {(7R)-4-fluoro-7-[5-(4-fluorobenzyl)-1H-[1,2,3]triazol-1-y1]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-y1}-acetic acid or the pharmaceutically acceptable salt thereof when the presence of the G allele of rs12118655 in the biological sample is detected; and (d) administering a therapeutically effective amount of {(7R)-4-fluoro-7-[5-(4-fluorobenzyl)-1H-[1,2,3]triazol-1-y1]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-y1}-acetic acid or the pharmaceutically acceptable salt thereof.

4 . The method of claim 3 , wherein step (d) further comprises administering a leukotriene receptor antagonist to the patient.

5 . (canceled)

6 . The method of claim 4 , wherein in step (d) the leukotriene receptor antagonist is montelukast.

7 - 17 . (canceled)

18 . The method of claim 1 , wherein montelukast is administered to the patient in addition to {(7R)-4-fluoro-7-[5-(4-fluorobenzyl)-1H-[1,2,3]triazol-1-y1]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-y1}-acetic acid or the pharmaceutically acceptable salt thereof.

Assignees

• Merck Sharp & Dohme

Inventors

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

Classifications

• A61P11/06

  Antiasthmatics · 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

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• A61K31/4192

  1,2,3-Triazoles · CPC title

• A61K31/47

  Quinolines; Isoquinolines · CPC title