# US 11,079,394 B2 · Detection of angiopoietin-2 and thrombospondin-2 in connection with diagnosing acute heart failure

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- Number: US 11,079,394 B2
- Document ID: US11079394B2
- Status: Granted
- Kind: B2
- Application number: 16/045,465
- Filed: 2018-07-25
- Published: 2019-01-31
- Granted: 2021-08-03
- Earliest claimed: 2017-07-25
- Assignees: Vanderbilt University; Beth Israel Deaconess Medical Center, Inc.
- Applicants: Vanderbilt University; Beth Israel Deaconess Medical Center, Inc.
- Inventors: Thomas J. Wang; Deepak K. Gupta; Quinn S. Wells; Robert E. Gerszten
- Web page: https://patentgrep.com/patent/US11079394B2

## CPC

- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2333/4704: Inhibitors; Supressors
- G01N 2333/515: Angiogenesic factors; Angiogenin
- G01N 2800/325: Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N 2800/7014: (Neo)vascularisation - Angiogenesis
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Methods for detecting angiopoietin-2 (Angpt-2) and/or thrombospondin-2 (Tsp-2) in a sample involve obtaining or having obtained a blood or plasma sample from a subject; and detecting Angpt-2 and Tsp-2 in the sample. Detecting can involve performing an assay to determine whether the sample includes Angpt-2 and/or Tsp-2 or elevated levels of Angpt-2 and/or Tsp-2. Elevated levels are indicative of acute heart failure.

## Claims

### Claim 1

A method for treating a subject, comprising:
(a) determining whether there is angiopoietin-2 (Angpt-2) and/or thrombospondin-2 (Tsp-2) in a blood or plasma sample from the subject by:
(i) obtaining or having obtained the blood or plasma sample from the subject;
(ii) performing or having performed an assay to determine whether the sample includes an elevated level of Angpt-2 and/or Tsp-2, wherein it is determined that there is elevated Angpt-2 in the sample when the level of Angpt-2 is above about 220 pg/ml and that there is elevated Tsp-2 in the sample when the level of Tsp-2 is above about 30 ng/ml; and
(b) if there is an elevated level of Angpt-2 and/or Tsp-2 in the sample, then administering treatment for acute heart failure comprising administering diuretics to the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject has dyspnea.

### Claim 3 (depends on 1)

The method of claim 1, and further comprising detecting or having detected natriuretic peptides in the sample.

### Claim 4

A method of diagnosing and treating acute heart failure in a subject, said method comprising:
(a) obtaining or having obtained a blood or plasma sample from the subject to detect levels in the sample of one or both of angiopoietin-2 (Angpt-2) and thrombospondin-2 (Tsp-2);
(c) diagnosing the subject with acute heart failure when there is an elevated level of Angpt-2 and/or Tsp-2 in the sample, wherein it is determined that there is elevated Angpt-2 in the sample when the level of Angpt-2 is above about 220 pg/ml and that there is elevated Tsp-2 in the sample when the level of Tsp-2 is above about 30 ng/ml; and
(d) administering treatment for acute heart failure comprising administering diuretics to the diagnosed subject.

### Claim 5 (depends on 4)

The method of claim 4, wherein the subject has dyspnea.

### Claim 6 (depends on 4)

The method of claim 4, and further comprising detecting or having detected natriuretic peptides in the sample.

### Claim 7

A method of detecting a combination of angiopoietin-2 (Angpt-2) and thrombospondin-2 (Tsp-2) in a sample from a subject, comprising:
(a) obtaining or having obtained a blood or plasma sample from the subject;
(b) detecting or having detected Angpt-2 and Tsp-2 in the sample;
(c) diagnosing the subject with acute heart failure when there is an elevated level of Angpt-2 and/or Tsp-2 in the sample as compared to a non-heart failure control; and
d) administering treatment for acute heart failure to the subject, said treatment comprising administering diuretics to the subject.

### Claim 8 (depends on 7)

The method of claim 7, wherein the subject has dyspnea.

### Claim 9 (depends on 7)

The method of claim 7, and further comprising determining that there is an elevated level of Angpt-2 in the sample when the level of Angpt-2 is above about 220 pg/ml and determining that there is an elevated level of Tsp-2 in the sample when the level of Tsp-2 is above about 30 ng/ml.

### Claim 10 (depends on 7)

The method of claim 7, and further comprising detecting or having detected natriuretic peptide levels in the sample, and diagnosing the subject with acute heart failure when there is an elevated level of Angpt-2 and/or Tsp-2 as compared to a non-heart failure control, and when the natriuretic peptide levels are above a threshold level for excluding acute heart failure.

### Claim 11 (depends on 7)

The method of claim 7, and further comprising identifying the subject as having an increased risk of developing heart failure if there is an elevated level of Angpt-2 and/or Tsp-2 in the sample relative to a non-heart failure control.

### Claim 12 (depends on 11)

The method of claim 11, wherein said increased risk is due to the subject having coronary artery disease, myocardial infarction, hypertension, diabetes mellitus, or obesity.

### Claim 13 (depends on 11)

The method of claim 11, wherein the treatment further comprises preventing or delaying onset of heart failure when there is an elevated level of Angpt-2 and/or Tsp-2 in the sample as compared to a non-heart failure control.

### Claim 14 (depends on 7)

The method of claim 7, and further comprising detecting or having detected natriuretic peptides in the sample, and administering treatment to the subject to prevent or delay onset of heart failure when there is an elevated level of Angpt-2 and/or Tsp-2 relative to a non-heart failure control, and natriuretic peptide levels are above a threshold level for excluding acute heart failure.
