1L1RL-1 as a cardiovascular disease marker and therapeutic target

• US 8,734,769 B2
• Filed: 03/08/2013
• Issued: 05/27/2014
• Est. Priority Date: 05/09/2002
• Status: Expired due to Term

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Lee, Richard T.
• Primary Examiner(s): STANFIELD, CHERIE MICHELLE
• Application Number:
  US13/789,941
• Publication Number:
  US 20130251664A1
• Time in Patent Office: 445 Days
• Field of Search: None
• US Class Current: 424/78.01
• CPC Class Codes: A61K 39/00112 Receptors for interferons [IFN]
• 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 9/10 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: G01N 2333/7155 for interleukins [IL]
• CPC Class Codes: G01N 2800/2871 Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/324 Coronary artery diseases, e.g. angina pectoris, myocardial infarction
• 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 33/6869 Interleukin
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

This invention pertains to methods and compositions for the diagnosis and treatment of cardiovascular conditions. More specifically, the invention relates to isolated molecules that can be used to diagnose and/or treat cardiovascular conditions including cardiac hypertrophy, myocardial infarction, stroke, arteriosclerosis, and heart failure.

Claims

1. A method for evaluating the likelihood that a subject will benefit from treatment with an agent for reducing the risk of a cardiovascular condition and treating the subject, the method comprising:

(a) performing an assay to determine a level of soluble ST2 in a sample from a subject having or suspected of having a cardiovascular condition;

(b) comparing the level of soluble ST2 in the sample to a predetermined value;

(c) identifying a subject having an elevated level of soluble ST2 compared to the predetermined value as having an increased likelihood of benefiting from treatment with an agent for reducing the risk of a cardiovascular condition; and

(d) administering an agent for reducing the risk of a cardiovascular condition to the subject identified in (c).

2. The method of claim 1, wherein the agent is selected from the group consisting of:

an anti-inflammatory agent, an anti-thrombotic agent, an anti-platelet agent, a fibrinolytic agent, a lipid-reducing agent, a direct thrombin inhibitor, a glycoprotein IIb/IIIa receptor inhibitor, a calcium channel blocker, a beta-adrenergic receptor blocker, a cyclooxygenase-2 inhibitor, and a renin-angiotensin system (RAS) inhibitor.

3. The method of claim 2, wherein the agent is a lipid-reducing agent.

4. The method of claim 3, wherein the lipid-reducing agent is selected from the group consisting of:

gemfibrozil, cholystyramine, colestipol, nicotinic acid, probucol, lovastatin, fluvastatin, simvastatin, atorvastatin, pravastatin, and cerivastatin.

5. The method of claim 2, wherein the renin-angiotensin system (RAS) inhibitor is selected from the group consisting of:

an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), an angiotensin II receptor antagonist, an agent that activates the catabolism of angiotensin II, and an agent that prevents the synthesis of angiotensin I.

6. The method of claim 1, wherein the cardiovascular condition is selected from the group consisting of:

cardiac hypertrophy, myocardial infarction, stroke, and heart failure.

7. The method of claim 1, wherein the assay in (a) is performed using an antibody that specifically binds to soluble ST2.

8. The method of claim 1, wherein the predetermined value is a plurality of predetermined marker level ranges and said comparing in (b) comprises determining in which of said predetermined marker ranges the subject'"'"'s level falls.

9. The method of claim 1, wherein the sample comprises a biological fluid.

10. The method of claim 9, wherein the biological fluid is blood or serum.

11. The method of claim 1, further comprising determining the level of at least one other marker related to a cardiovascular condition.

12. The method of claim 11, wherein the at least one marker is selected from the group consisting of:

a circulating catecholamine, angiotensin II, creatine, creatine kinase MB isoenzyme, C-reactive protein, a troponin, a natriuretic peptide, and a marker of oxidative stress.

13. The method of claim 12, wherein the at least one marker is a troponin or a brain natriuretic peptide.

14. The method of claim 12, wherein the troponin is cardiac troponin I.

15. The method of claim 12, wherein the circulating catecholamine is norephinephrine, domaine, or epinephrine.

16. The method of claim 12, wherein the natriuretic peptide is a brain natriuretic peptide (BNP) or pro-atrial natriuretic peptide (ProANP).

17. The method of claim 16, wherein the natriuretic peptide is a BNP.

18. The method of claim 12, wherein the marker of oxidative stress is adrenolutin or malondialdehyde.

19. The method of claim 1, wherein the subject is suspected of having a cardiovascular condition.