Methods of treating or selecting a treatment for a subject having heart failure that include detecting levels of galectin-3 and soluble ST2

• US 9,823,257 B2
• Filed: 01/12/2016
• Issued: 11/21/2017
• 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:
  US14/993,196
• Publication Number:
  US 20160299153A1
• Time in Patent Office: 679 Days
• Field of Search: None
• 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 of treating 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) identifying 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 the level of soluble ST2 in a biological sample from the identified subject;

(e) comparing the level of soluble ST2 in the biological sample of (d) to a reference level of soluble ST2; and

(f) administering inpatient treatment to an identified subject having an elevated level of soluble ST2 in the biological sample of (d) as compared to the reference level of soluble ST2;

or

administering outpatient treatment to an identified subject having a non-elevated level of soluble ST2 in the biological sample of (d) as compared to a reference level of soluble ST2.

2. The method of claim 1, wherein (f) comprises administering inpatient treatment to an identified subject having an elevated level of soluble ST2 in the biological sample of (d) as compared to the reference level of soluble ST2.

3. The method of claim 1, wherein (f) comprises administering outpatient treatment to an identified subject having a non-elevated level of soluble ST2 in the biological sample of (d) as compared to a reference level of soluble ST2.

4. The method of claim 3, wherein outpatient treatment comprises administration of a therapeutic agent selected from the group consisting of:

nitrates, calcium channel blockers, diuretics, thrombolytic agents, digitalis, renin-angiotensin-aldosterone system (RAAS) modulating agents, and cholesterol-lowering agents.

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

6. The method of claim 1, wherein the biological samples of (a) and (d) comprise serum, blood, or plasma.

7. The method of claim 1, wherein the biological samples of (a) and (d) are obtained from the subject at the same time.

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

30, or renal insufficiency.

9. The method of claim 1, wherein the reference level of soluble ST2 is a level of soluble ST2 in a subject that does not have high risk of cardiovascular disease, or the reference level of galectin-3 is a level of galectin-3 in a subject that does not have a high risk of cardiovascular disease.

10. The method of claim 1, wherein the reference level of soluble ST2 or the reference level of galectin-3 is a threshold level of soluble ST2 or galectin-3.

11. A method for treating a subject having heart failure, the method comprising:

(a) identifying a subject having heart failure and an elevated level of galectin-3 as compared to a reference level of galectin-3;

(b) performing an assay to determine the level of soluble ST2 in a biological sample from the identified subject;

(c) comparing the level of soluble ST2 in the biological sample to a reference level of soluble ST2; and

(d) administering inpatient treatment to an identified subject having an elevated level of soluble ST2 as compared to the reference level of soluble ST2, or

administering outpatient treatment to an identified subject having a non-elevated level of soluble ST2 as compared to the reference level of soluble ST2.

12. The method of claim 11, wherein (d) comprises administering inpatient treatment to an identified subject having an elevated level of soluble ST2 in the biological sample of (b) as compared to the reference level of soluble ST2.

13. The method of claim 11, wherein (d) comprises administering outpatient treatment to an identified subject having a non-elevated level of soluble ST2 in the biological sample of (b) as compared to a reference level of soluble ST2.

14. The method of claim 13, wherein outpatient treatment comprises administration of a therapeutic agent selected from the group consisting of:

nitrates, calcium channel blockers, diuretics, thrombolytic agents, digitalis, renin-angiotensin-aldosterone system (RAAS) modulating agents, and cholesterol-lowering agents.

15. The method of claim 14, wherein the cholesterol-lowering agent is a statin.

16. The method of claim 11, wherein the biological sample of (b) comprises serum, blood, or plasma.

17. The method of claim 11, wherein the subject has a BMI of 25-29, a BMI of ≧

30, or renal insufficiency.

18. The method of claim 11, wherein the reference level of soluble ST2 is a level of soluble ST2 in a subject that does not have high risk of cardiovascular disease, or the reference level of galectin-3 is a level of galectin-3 in a subject that does not have a high risk of cardiovascular disease.

19. The method of claim 11, wherein the reference level of soluble ST2 or the reference level of galectin-3 is a threshold level of soluble ST2 or galectin-3.

20. A method of selecting a treatment for 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) identifying 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 the level of soluble ST2 in a biological sample from the identified subject;

(e) comparing the level of soluble ST2 in the biological sample of (d) to a reference level of soluble ST2; and

(f) selecting a treatment including heart transplant or heart surgery for an identified subject having an elevated level of soluble ST2 in the biological sample of (d) as compared to the reference level of soluble ST2.

21. The method of claim 20, wherein the biological samples of (a) and (d) comprise serum, blood, or plasma.

22. The method of claim 20, wherein the subject has a BMI of 25-29, a BMI of ≧

30, or renal insufficiency.

23. The method of claim 20, wherein the reference level of soluble ST2 is a level of soluble ST2 in a subject that does not have high risk of cardiovascular disease, or the reference level of galectin-3 is a level of galectin-3 in a subject that does not have a high risk of cardiovascular disease.

24. The method of claim 20, wherein the reference level of soluble ST2 or the reference level of galectin-3 is a threshold level of soluble ST2 or galectin-3.

25. The method of claim 20, further comprising administering a treatment including heart transplant or heart surgery to the subject.

26. The method of claim 20, wherein the biological sample of (a) and (d) are obtained from the subject at the same time.

27. A method of selecting a treatment for a subject having heart failure, the method comprising:

(a) identifying a subject having heart failure and an elevated level of galectin-3 as compared to a reference level of galectin-3;

(b) performing an assay to determine the level of soluble ST2 in a biological sample from the identified subject;

(c) comparing the level of soluble ST2 in the biological sample to a reference level of soluble ST2; and

(d) selecting a treatment including heart transplant or heart surgery for an identified subject having an elevated level of soluble ST2 as compared to the reference level of soluble ST2.

28. The method of claim 27, wherein the biological sample of (b) comprises serum, blood, or plasma.

29. The method of claim 27, wherein the subject has a BMI of 25-29, a BMI of ≧

30, or renal insufficiency.

30. The method of claim 27, wherein the reference level of soluble ST2 is a level of soluble ST2 in a subject that does not have high risk of cardiovascular disease, or the reference level of galectin-3 is a level of galectin-3 in a subject that does not have a high risk of cardiovascular disease.

31. The method of claim 27, wherein the reference level of soluble ST2 or the reference level of galectin-3 is a threshold level of soluble ST2 or galectin-3.

32. The method of claim 27, further comprising administering a treatment including heart transplant or heart surgery to the subject.