Methods for treatment with bucindolol based on genetic targeting

• US 8,916,603 B2
• Filed: 12/01/2011
• Issued: 12/23/2014
• Est. Priority Date: 09/14/2004
• Status: Active Grant

• Current Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Liggett, Stephen B., Bristow, Michael
• Primary Examiner(s): MYERS, CARLA J
• Application Number:
  US13/309,114
• Publication Number:
  US 20120289573A1
• Time in Patent Office: 1,118 Days
• Field of Search: None
• US Class Current: 514/415
• CPC Class Codes: A61B 5/021 Measuring pressure in heart or blood vessels A61B5/0205 takes precedence
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/172 Haplotypes
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/5041 involving analysis of members of signalling pathways
• CPC Class Codes: G01N 33/6887 from muscle, cartilage or connective tissue

Abstract

The present invention concerns the use of methods for evaluating bucindolol treatment for a patient, particularly one with heart failure. It concerns methods for determining whether to administer or prescribe bucindolol to a patient based on whether the patient is homozygous for the Arg 389 polymorphism in the β1-adrenergic receptor (AR).

Claims

1. A method for treating heart failure, cardiac arrhythmia, or hypertension in a human patient with bucindolol comprising administering bucindolol to a patient after a sample from the patient has been genotyped and determined to be homozygous for a cytosine at position 1165 in the nucleotide coding sequence of β

₁AR gene.

2. The method of claim 1, wherein position 1165 in the nucleotide coding sequence of β

₁AR has been sequenced.

3. The method of claim 1, wherein sequencing comprises amplifying a nucleic acid sequence complementary or identical to a region of the β

₁AR coding sequence that comprises position 1165.

4. The method of claim 3, wherein amplifying comprises using polymerase chain reaction (PCR).

5. A method for treating heart failure, cardiac arrhythmia, or hypertension in a human patient with bucindolol comprising administering bucindolol to a patient after a sample from the patient has been determined to have β

₁AR polypeptides comprising Arg389 and not Gly 389 based on assaying β

₁AR polypeptides.