Polymorphisms in ABCB1 associated with a lack of clinical response to medicaments

Patent metadata

Field	Value
Publication number	US-9901582-B2
Application number	US-201514800848-A
Country	US
Kind code	B2
Filing date	Jul 16, 2015
Priority date	Jun 12, 2007
Publication date	Feb 27, 2018
Grant date	Feb 27, 2018

Abstract

The present invention relates to methods, compositions, kits and reagents for determining the prognosis of a clinical response in a human patient to a medicament which acts in the central nervous system (CNS) and which is a substrate of the ABCB1 protein. Further, the invention relates to a combination of medicaments for the treatment of human patients having specific polymorphisms in the ABCB1 gene.

First claim

The invention claimed is:

1. A method for detecting the minor C allele of the rs4148740 polymorphism in a patient, comprising:
a) obtaining a blood sample from a patient suffering from depressive disorder, dysthymia, or bipolar disorder;
b) extracting DNA from the blood sample to provide a DNA sample;
c) contacting the DNA sample with at least one probe or primer capable of hybridizing with ABCB1 gene polymorphism rs4148740, and
d) carrying out genotyping analysis to detect the minor C allele of the rs4148740 polymorphism.

2. The method according to claim 1 , further comprising contacting the DNA sample with at least one additional probe or primer capable of determining the presence of a ABCB1 gene polymorphism in linkage disequilibrium with polymorphism rs4148740, wherein said ABCB1 gene polymorphism in linkage disequilibrium with polymorphism rs4148740 is selected from the group consisting of rs2235067, rs2032583, rs4148739, rs11983225, rs2235040, rs12720067, rs7787082, rs10248420, and combinations thereof.

3. The method of claim 1 , wherein the genotyping analysis comprises the use of polymorphism-specific primers and/or probes.

4. The method of claim 1 , wherein the genotyping analysis comprises a primer extension reaction.

5. The method of claim 1 , wherein the genotyping analysis comprises a microarray analysis.

6. The method of claim 1 , wherein the genotyping analysis comprises a mass-spectrometric analysis.

7. The method of claim 1 , further comprising detecting a change in the function of the ABCB1 gene.

8. The method of claim 7 , wherein detecting a change in the function of the ABCB1 gene comprises detecting the transport of specific substances at the blood-brain barrier.

Assignees

• Max Planck Ges Zur Foerderung Der Wisenschaften E V
• Max Planck Gesellschaft

Inventors

• Uhr Manfred
• Holsboer Florian
• Mueller Myhsok Bertram

Classifications

• A61P25/24

  Antidepressants · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K31/137

  Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q1/6883

  for diseases caused by alterations of genetic material · CPC title