Methods of determining efficacy of treatment in a subject having heart failure

• US 9,239,333 B2
• Filed: 05/01/2014
• Issued: 01/19/2016
• Est. Priority Date: 03/17/2011
• Status: Active Grant

• Current Assignee: Critical Care Diagnostics Inc.
• Original Assignee: Critical Care Diagnostics Inc.
• Inventors: Snider, James V.
• Primary Examiner(s): HOWARD, ZACHARY C
• Application Number:
  US14/267,487
• Publication Number:
  US 20140234875A1
• Time in Patent Office: 628 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4726 Lectins
• CPC Class Codes: C07K 14/715 for cytokines; for lymphokines; for interferons
• CPC Class Codes: G01N 2333/4724 Lectins
• CPC Class Codes: G01N 2333/7155 for interleukins [IL]
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• 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 2800/54 Determining the risk of relapse
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

Provided are methods for evaluating the risk of an adverse clinical outcome in a subject, deciding whether to discharge or continue treating a subject (e.g., treatment on an inpatient basis), or to initiate or terminate treatment, selecting a subject for participation in a clinical study, and selecting a therapeutic treatment for a subject that include determining a level of ST2 in a biological sample from the subject and determining a level of galectin-3 in a biological sample from the subject. Kits are also provided that contain an antibody that specifically binds to ST2, an antibody that specifically binds to galectin-3, and instructions for using the kit to evaluate the risk of an adverse clinical outcome in a subject, to decide whether to discharge or continue treating a subject (e.g., treatment on an inpatient basis) or to initiate or terminate treatment, to select a subject for participation in a clinical study, and/or to select treatment for a subject.

Claims

1. A method for determining the efficacy of a treatment a subject having heart failure, the method comprising:

(a) performing an assay to determine a level of galectin-3 in a biological sample from a subject having heart failure;

(b) comparing the level of galectin-3 in the biological sample of (a) to a reference level of galectin-3;

(c) selecting a subject having an elevated level of galectin-3 in the biological sample of (a) as compared to the reference level of galectin-3;

(d) performing an assay to determine a level of soluble ST2 in a biological sample obtained from the selected subject at a first time point before administration of a treatment;

(e) performing an assay to determine a level of soluble ST2 in a biological sample obtained from the selected subject at a second time point after administration of the treatment and after the first time point; and

(f) determining that the treatment was effective in a selected subject having a decrease in the level of soluble ST2 in the biological sample of (e) as compared to the level of soluble ST2 in the biological sample of (d).

2. The method of claim 1, wherein the reference level of galectin-3 is a level of galectin-3 in a subject that does not have high risk of cardiovascular disease.

3. The method of claim 1, wherein the reference level of galectin-3 is a threshold level of galectin-3.

4. The method of claim 1, wherein the treatment is selected from the group consisting of:

a nitrate, a calcium channel blocker, a diuretic, a thrombolytic agent, digitalis, a renin-angiotensin-aldosterone system (RAAS) modulating agent, and a cholesterol-lowering agent.

5. The method of claim 4, wherein the cholesterol-lowering agent is a statin.

6. The method of claim 4, wherein the RAAS modulating agent is selected from the group consisting of a beta-adrenergic blocking agent, an angiotensin-converting enzyme inhibitor, an aldosterone antagonist, a renin inhibitor, and an angiotensin II receptor blocker.

7. The method of claim 6, wherein the beta-adrenergic blocking agent is selected from the group consisting of:

alprenolol, bucindolol, carteolol, carvedilol, labetalol, nadolol, penbutolol, pindolol, propranolol, sotalol, timolol, acebutolol, atenolol, betaxolol, bisoprolol, celiprolol, esmolol, metoprolol, and nebivolol.

8. The method of claim 6, wherein the angiotensin-converting enzyme inhibitor is selected from the group consisting of:

benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril.

9. The method of claim 6, wherein the aldosterone antagonist is selected from the group consisting of:

spironolactone, eplerenone, canrenone, prorenone, and mexrenone.

10. The method of claim 6, wherein the renin inhibitor is selected from the group consisting of:

aliskiren, remikiren, and enalkiren.

11. The method of claim 6, wherein the angiotensin II receptor blocker is selected from the group consisting of:

valsartan, telmisartan, irbesartan, and olmesartan.

12. The method of claim 1, wherein the biological sample of (a), the biological sample of (d), or the biological sample of (e) comprises serum, blood, or plasma.

13. The method of claim 12, wherein the biological sample of (a), the biological sample of (d), or the biological sample of (e) comprises serum.

14. The method of claim 1, wherein the subject has a BMI of 25-29, a BMI of ≧

30, or renal insufficiency.

15. The method of claim 1, wherein the subject is human.

16. The method of claim 1, wherein the assay in (d) or (e) is an immunoassay.

17. The method of claim 16, wherein the immunoassay in (d) or (e) includes the use an antibody produced by the hybridoma deposited at the American Type Culture Collection and designated by Patent Deposit Designation PTA-10432.

18. The method of claim 16, wherein the immunoassay in (d) or (e) is an enzyme-linked immunosorbent assay (ELISA).