Prediction of QT prolongation based on SNP genotype

• US 8,652,776 B2
• Filed: 09/10/2008
• Issued: 02/18/2014
• Est. Priority Date: 09/10/2007
• Status: Active Grant

• Current Assignee: Vanda Pharmaceuticals Incorporated
• Original Assignee: Vanda Pharmaceuticals Incorporated
• Inventors: Lavedan, Christian, Volpi, Simona, Licamele, Louis, Mack, Kendra Tomino, Heaton, Callie Michelle
• Primary Examiner(s): SITTON, JEHANNE SOUAYA
• Application Number:
  US12/675,607
• Publication Number:
  US 20100249188A1
• Time in Patent Office: 1,987 Days
• Field of Search: None
• US Class Current: 435/6.1
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• 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

Abstract

The present invention relates to the prediction of QT prolongation following administration of a compound capable of increasing an individual'"'"'s QT interval based on the individual'"'"'s genotype at one or more single nucleotide polymorphism (SNP) loci and to the treatment of a patient based on such prediction.

Claims

1. A method of treating a human patient for one or more symptoms of a psychotic disorder, the method comprising:

determining, from a biological sample of the patient, the patient'"'"'s genotype in both copies of the single nucleotide polymorphism (SNP) locus rs3924426; and

treating the patient based upon whether the patient'"'"'s genotype at the rs3924426 SNP locus is associated with increased QT prolongation,

wherein treating includes;

in the case that the patient has a TT genotype at the rs3924426 SNP locus, administering to the patient an effective amount of iloperidone or a pharmaceutically-acceptable salt thereof, the effective amount being less than would be administered to a patient who does not have a TT genotype at the rs3924426 SNP locus;

or

in the case that the patient does not have a TT genotype at the rs3924426 SNP locus, administering to the patient an increased amount of iloperidone, the increased amount being more than would be administered to a patient who has a TT genotype at the rs3924426 SNP locus.

2. The method of claim 1, wherein the effective amount is between about 2 mg/day and about 24 mg/day.

3. The method of claim 2, wherein the effective amount is between about 5 mg/day and about 20 mg/day.

4. The method of claim 3, wherein the effective amount is between about 10 mg/day and about 15 mg/day.

5. The method of claim 1, wherein the increased amount is between about 24 mg/day and about 50 mg/day.

6. The method of claim 5, wherein the increased amount is between about 30 mg/day and about 50 mg/day.

7. The method of claim 6, wherein the increased amount is between about 40 mg/day and about 50 mg/day.

8. The method of claim 1, wherein treating the patient includes monitoring the patient for QT prolongation.