PAR4 inhibitor therapy for patients with PAR4 polymorphism

• US 9,789,087 B2
• Filed: 08/02/2016
• Issued: 10/17/2017
• Est. Priority Date: 08/03/2015
• Status: Active Grant

• Current Assignee: Thomas Jefferson University (Main Line Health System)
• Original Assignee: Thomas Jefferson University (Main Line Health System)
• Inventors: Bray, Paul, Holinstat, Michael, Edelstein, Leonard
• Primary Examiner(s): HEARD, THOMAS SWEENEY
• Application Number:
  US15/226,425
• Publication Number:
  US 20170035734A1
• Time in Patent Office: 441 Days
• Field of Search: None
• CPC Class Codes: A61K 31/416 condensed with carbocyclic ring systems, e.g. indazole
• CPC Class Codes: A61K 31/429 condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C12Q 1/6827 for detection of mutation or polymorphism
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers

Abstract

Disclosed herein are methods for determining whether a PAR4 inhibitor should be administered to a human subject, the methods comprising administering a PAR4 inhibitor to a subject determined to have a “G” allele for a single-nucleotide polymorphism (SNP) at rs773902, and not administering a PAR4 inhibitor to a subject determined to have an “A” allele for the SNP at rs773902. A genotyping assay can be used to determine the SNP.

Claims

1. A method of preventing or treating thrombosis in a human subject in need thereof, the method comprising administering a therapeutically effective amount of a PAR4 inhibitor to a human subject determined to have a “

G”

allele for a single-nucleotide polymorphism (SNP) at rs773902.

2. The method of claim 1 wherein the method of preventing or treating thrombosis in a human subject further comprises, wherein (a) the human subject is being administered a PAR1 inhibitor and (b) has a “

G”

allele for a single-nucleotide polymorphism (SNP) at rs773902;

the method comprising (a) stopping administration of the PAR1 inhibitor and (b) administering a therapeutically effective amount of a PAR4 inhibitor.

3. The method of claim 1, wherein the PAR4 inhibitor is selected from the group consisting of ethyl 4-(1-benzyl-1H-indazol-3-yl)benzoate (YD-3), trans-cinnamoyl-YPGKF-amide, P4pal-i1, and palmitoyl-SGRRYGHALR-amide (P4pal-10).

4. The method of claim 1, wherein the thrombosis is associated with coronary artery disease, stroke, vascular thrombosis, arterial thrombosis, atherothrombosis, deep vein thrombosis, peripheral vascular disease, peripheral arterial disease, or an inflammatory disease.

5. The method of claim 1, further comprising testing a sample from the human subject to determine the genotype of the SNP at rs773902.

6. The method of claim 5, wherein the sample is a blood sample, a urine sample, a buccal sample, a saliva sample, or a hair sample.

7. The method of claim 1, further comprising administering a therapeutically effective amount of a P2Y12 inhibitor to the subject selected from the group consist of:

clopidogrel, prasugrel, ticagrelor, or cangrelor, a salt thereof, or a combination thereof.