Methods For Identifying Patients With An Increased Likelihood Of Responding To DPP-IV Inhibitors

• US 20110020797A1
• Filed: 02/11/2008
• Published: 01/27/2011
• Est. Priority Date: 02/09/2007
• Status: Abandoned Application

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Koustubh, Ranade
• Application Number:
  US12/526,320
• Publication Number:
  US 20110020797A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

The invention provides novel in vitro diagnostic methods for identifying patients who may have an increased likelihood of responding to DPP-IV inhibitor therapy. The invention also provides novel polynucleotides associated with increased responsiveness of a patient to DPP-IV inhibition. Polynucleotide fragments corresponding to the genomic and/or coding regions of these polynucleotides, which comprise at least one polymorphic locus per fragment, are also provided. Allele-specific primers and probes which hybridize to these polymorphic regions, and/or which comprise at least one polymorphic locus are also provided. The polynucleotides, primers, and probes of the present invention are useful in phenotype correlations, medicine, and genetic analysis.

Claims

1. A method of identifying an individual having an increased likelihood of achieving a favorable response to the administration of a pharmaceutically acceptable amount of a DPP-IV inhibitor comprising the step of determining whether said individual has a reference or variant allele at one or more polymorphic loci of the human CYP3A5 gene, wherein the presence of a reference allele at said one or more polymorphic loci indicates a decreased likelihood of achieving a favorable response to a DPP-IV inhibitor relative to an individual harboring the variant allele at that locus.

3. The method according to claim 1 or 2, wherein said polymorphic locus is at nucleotide position 7068 of SEQ ID NO:

1 or SEQ ID NO;

2.

4. The method according to claim 3, wherein said reference allele at the polymorphic locus is “

G”

.

5. The method according to claim 3, wherein said variant allele at the polymorphic locus is “

A”

.

7. The method of claim 1, 2, or 6, wherein the subject is of Hispanic descent.

8. The method according to 1, 2, 6, or 7, wherein said DPP-IV inhibitor is saxagliptin.

2. A method of identifying an individual having an increased likelihood of achieving a favorable response to the administration of a pharmaceutically acceptable amount of a DPP-IV inhibitor comprising the step of determining whether said individual has a reference or variant allele at one or more polymorphic loci of the human CYP3A5 gene, wherein the presence of a variant allele at said one or more polymorphic loci indicates an increased likelihood of achieving a favorable response to a DPP-IV inhibitor relative to an individual harboring the reference allele at that locus.

6. A method of identifying a subject who may benefit from the administration of a pharmaceutically acceptable amount of a DPP-IV inhibitor comprising the step of determining whether said subject has a reference or variant allele at one or more polymorphic loci of the human CYP3A5 gene, wherein the presence of a variant allele at said one or more polymorphic loci indicates an increased likelihood that said subject will benefit from the administration of said DPP-IV inhibitor relative to a subject harboring the reference allele at that locus.

9. A method of identifying an individual who may have an increased likelihood of achieving a favorable response to the administration of a pharmaceutically acceptable amount of a DPP-IV inhibitor comprising the step of determining whether said individual has a reference or variant allele at one or more polymorphic loci of the human Insulin Promoter Factor-1 (IPF-1) gene, wherein the presence of a reference allele at said one or more polymorphic loci indicates a decreased likelihood of achieving a favorable response to a DPP-IV inhibitor relative to an individual harboring the variant allele at that locus.

10. A method of identifying an individual who may have an increased likelihood of achieving a favorable response to the administration of a pharmaceutically acceptable amount of a DPP-IV inhibitor comprising the step of determining whether said individual has a reference or variant allele at one or more polymorphic loci of the human IPF-1 gene, wherein the presence of a variant allele at said one or more polymorphic loci indicates an increased likelihood of achieving a favorable response to a DPP-IV inhibitor relative to an individual harboring the reference allele at that locus.

11. The method according to claim 9 or 10, wherein said polymorphic locus is at nucleotide position 4445 of SEQ ID NO:

11 or SEQ ID NO;

12.

12. The method according to claim 11, wherein said reference allele at the polymorphic locus is “

C”

.

13. The method according to claim 11, wherein said variant allele at the polymorphic locus is “

T”

.

15. The method according to claim 9, 10, or 14, wherein said DPP-IV inhibitor is saxagliptin.

14. A method of identifying a subject who may benefit from the administration of a pharmaceutically acceptable amount of a DPP-IV inhibitor comprising the step of determining whether said subject has a reference or variant allele at one or more polymorphic loci of the human IPF-1 gene, wherein the presence of a variant allele at said one or more polymorphic loci indicates an increased likelihood said individual will benefit from the administration of said DPP-IV inhibitor relative to a subject harboring the reference allele.