Antipsychotic treatment based on SNP genotype

Patent metadata

Field	Value
Publication number	US-9328387-B2
Application number	US-67559808-A
Country	US
Kind code	B2
Filing date	Sep 10, 2008
Priority date	Sep 10, 2007
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

The present invention relates to the prediction of antipsychotic treatment efficacy based on a patient's genotype at one or more single nucleotide polymorphism (SNP) loci and to the treatment of a patient based on such prediction.

First claim

What is claimed is:

1. A method of treating a human individual with at least one psychotic symptom comprising:
a) determining the individual's genotype at the single nucleotide polymorphism (SNP) locus rs4528226; and
b) administering to the individual a first effective amount of between about 2 mg/day and about 24 mg/day of iloperidone, a pharmaceutically-acceptable salt thereof, a metabolite thereof, or a pharmaceutically-acceptable salt of a metabolite thereof in the case that the individual's genotype at rs4528226 is GT; or administering to the individual a second effective amount of iloperidone, a pharmaceutically-acceptable salt thereof, a metabolite thereof, or a pharmaceutically-acceptable salt of a metabolite thereof in the case that the individual's genotype at rs4528226 is not GT, wherein the second effective amount is between about 24 mg/day and about 50 mg/day and greater than the amount administered to an individual that has a GT genotype at the rs4528226 locus.

2. The method of claim 1 , wherein the iloperidone metabolite is selected from a group consisting of: 4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-α-methylbenzene methanol, 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-hydroxyphenyl]ethanone, 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]-2-hydroxyethanone, 4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-hydroxy-α-methylbenzene methanol, 4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxyl-2-hydroxy-5-methoxy-α-methylbenzene methanol, 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-2-hydroxy-5-methoxyphenyl]ethanone, and 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-2,5-dihydroxyphenyl]ethanone.

3. The method of claim 1 , wherein the first effective amount is between about 5 mg/day and about 20 mg/day.

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

5. The method of claim 1 , wherein the second effective amount is between about 30 mg/day and about 50 mg/day.

6. The method of claim 5 , wherein the second effective amount is between about 40 mg/day and 50 mg/day.

7. A method of treating a human individual with at least one psychotic symptom comprising:
a) obtaining a biological sample from the individual, wherein the sample comprises nucleic acids;
b) performing a PCR and sequencing assay on the nucleic acid sample, wherein the primers in the PCR assay are SEQ ID NOS: 11 and 12,
c) detecting the individual's genotype at the single nucleotide polymorphism (SNP) locus rs4528226; and
d) administering to the individual a first effective amount of between about 2 mg/day and about 24 mg/day of iloperidone, a pharmaceutically-acceptable salt thereof, a metabolite thereof, or a pharmaceutically-acceptable salt of a metabolite thereof in the case that the individual's genotype at rs4528226 is GT; or administering to the individual a second effective amount of iloperidone, a pharmaceutically-acceptable salt thereof, a metabolite thereof, or a pharmaceutically-acceptable salt of a metabolite thereof in the case that the individual's genotype at rs4528226 is not GT, wherein the second effective amount is between about 24 mg/day and about 50 mg/day and greater than the amount administered to an individual that has a GT genotype at the rs4528226 locus.

8. The method of claim 7 , wherein the iloperidone metabolite is selected from a group consisting of: 4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-α-methylbenzene methanol, 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-hydroxyphenyl]ethanone, 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]-2-hydroxyethanone, 4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]3-hydroxy-α-methylbenzene methanol, 4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxyl-2-hydroxy-5-methoxy-α-methylbenzene methanol, 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-2-hydroxy-5-methoxyphenyl]ethanone, and 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-2,5-dihydroxyphenyl]ethanone.

9. The method of claim 7 , wherein the first effective amount is between about 5 mg/day and about 20 mg/day.

10. The method of claim 9 , wherein the first effective amount is between about 5 mg/day and 15 mg/day.

11. The method of claim 7 , wherein the second effective amount is between about 30 mg/day and about 50 mg/day.

12. The method of claim 11 , wherein the second effective amount is between about 40 mg/day and about 50 mg/day.

Assignees

• Lavedan Christian
• Volpi Simona
• Licamele Louis
• Polymeropoulos Mihael H
• Vanda Pharmaceuticals Inc

Inventors

• Lavedan Christian
• Volpi Simona
• Licamele Louis
• Polymeropoulos Mihael H

Classifications

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• C12Q2600/106

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

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title