Methods for treatment with bucindolol based on genetic targeting

• US 8,080,578 B2
• Filed: 08/13/2007
• Issued: 12/20/2011
• 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
• Application Number:
  US11/838,131
• Publication Number:
  US 20080096982A1
• Time in Patent Office: 1,590 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 a human patient for heart failure, cardiac arrhythmia, or hypertension with bucindolol comprising:

administering bucindolol to the patient if the patient is determined to be homozygous wildtype for Del322-325 in the α

2c andrenergic receptor (AR) gene based on a test of a biological sample from the patient.

2. The method of claim 1, wherein the results are obtained by receiving a report containing the information or taking a patient history that reveals the results.

3. The method of claim 1, wherein bucindolol is formulated for oral administration.

4. The method of claim 1, wherein the patient is also treated with ACE inhibitors, digoxin or a diuretic.

5. The method of claim 1, wherein bucindolol is administered every 12 hours.

6. The method of claim 1, further comprising ordering a test from a sample from the patient that determines the patient'"'"'s genotype.

7. A method for treating a human patient with symptoms of or a diagnosis of heart failure, cardiac arrhythmia, or hypertension with bucindolol comprising:

treating the patient with bucindolol if the patient is tested and determined not to be a Del322-325 carrier in the α

2c andrenergic receptor (AR) gene based on results of a test of a biological sample from the patient.

8. The method of claim 7, wherein the results are obtained by receiving a report containing the information or taking a patient history that reveals the results.

9. The method of claim 7, wherein bucindolol is formulated for oral administration.

10. The method of claim 7, wherein the patient is also treated with ACE inhibitors, digoxin or a diuretic.

11. The method of claim 7, wherein bucindolol is administered or prescribed for administration every 12 hours.

12. The method of claim 7, further comprising ordering a test from a sample from the patient that determines the patient'"'"'s genotype.

13. A method for administering bucindolol to a human patient with symptoms of or a diagnosis of heart failure, cardiac arrhythmia, or hypertension comprising:

a) obtaining information about whether the patient'"'"'s genotype is homozygous wildtype for Del322-325 in the α

_2c AR gene; and

b) then administering bucindolol to the patient if the patient'"'"'s genotype is homozygous wildtype for Del322-325 in the α

_2c AR gene.

14. The method of claim 13, wherein the results are obtained by receiving a report containing the information or taking a patient history that reveals the results.

15. The method of claim 13, wherein bucindolol is formulated for oral administration.

16. The method of claim 13, wherein the patient is also treated with ACE inhibitors, digoxin or a diuretic.

17. The method of claim 13, wherein bucindolol is administered every 12 hours.

18. The method of claim 13, wherein the information is obtained by ordering a test from a sample from the patient that determines the patient'"'"'s genotype.

19. A method for treating a human patient for heart failure, cardiac arrhythmia, or hypertension with bucindolol comprising:

a) obtaining results from a test that determines whether the patient'"'"'s genotype is homozygous wildtype for Del322-325 in the α

_2c AR gene; and

,

b) then treating the patient with bucindolol if the test indicates that the patient'"'"'s genotype is homozygous wildtype for Del322-325 in the α

_2c AR gene.

20. The method of claim 19, wherein the results are obtained by receiving a report containing the information or taking a patient history that reveals the results.

21. The method of claim 19, wherein bucindolol is formulated for oral administration.

22. The method of claim 19, wherein the patient is also treated with ACE inhibitors, digoxin or a diuretic.

23. The method of claim 19, further comprising ordering a test from a sample from the patient that determines the patient'"'"'s genotype.

24. A method for treating heart failure or cardiac arrhythmia comprising administering bucindolol to a heart failure or cardiac arrhythmia human patient who has been determined to be homozygous wildtype for Del322-325 in the α

2c andrenergic receptor (AR) gene based on a test of a biological sample from the patient.

25. The method of claim 24, wherein bucindolol is formulated for oral administration.

26. The method of claim 24, wherein the patient is also treated with ACE inhibitors, digoxin or a diuretic.

27. The method of claim 24, wherein bucindolol is administered every 12 hours.

28. The method of claim 24, further comprising ordering a test using a sample from the patient that determines the patient'"'"'s genotype.