# US 2014/0193845 A1 · Use of sfrp-3 in the assessment of heart failure

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- Number: US 2014/0193845 A1
- Document ID: US20140193845A1
- Status: Published application
- Kind: A1
- Application number: 14/180,384
- Filed: 2014-02-14
- Published: 2014-07-10
- Earliest claimed: 2008-04-30
- Assignees: The Governing Council of the University of Toronto; Roche Diagnostics Operations, Inc.
- Applicants: The Governing Council of the University of Toronto; Roche Diagnostics Operations, Inc.
- Inventors: Ursula-Henrike Wienhues-Thelen; Sara Arab; Dirk Block; Andrew Emili; Anthony Gramolini; Georg Hess; Hendrik Huedig; Peter Liu; David MacLennan
- Web page: https://patentgrep.com/patent/US20140193845A1

## CPC

- G01N 33/566: using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2800/325: Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
- 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

Disclosed is a method for assessing heart failure in vitro including the steps of measuring in a sample the concentration of the marker SFRP-3, of optionally measuring in the sample the concentration of one or more other marker(s) of heart failure, and of assessing heart failure by comparing the concentration determined in for SFRP-3 and the concentration(s) determined for the optionally one or more other marker to the concentration of this marker or these markers as established in a reference population. Also disclosed are the use of SFRP-3 as a marker protein in the assessment of heart failure, a marker combination comprising SFRP-3 and a kit for measuring SFRP-3.

## Claims

### Claim 1

(canceled)

### Claim 2

A method of diagnosing heart failure in an individual at risk for heart failure, the method comprising the steps of:
contacting, in vitro, a portion of a sample obtained from the individual with an antibody having specific binding affinity for secreted frizzled related protein 3 (SFRP-3), thereby forming a complex of the antibody and the SFRP-3, the antibody having a detectable label, the sample being one of serum, plasma or whole blood;
separating the complex formed in said step of contacting from antibody not comprising the complex of the antibody and the SFRP-3;
quantifying a signal from the detectable label of the antibody comprising the complex of the antibody and the SFRP-3 formed in said step of contacting, the signal being proportional to an amount of SFRP-3 in the sample from the individual, whereby a concentration of SFRP-3 in the sample is calculated;
comparing the concentration of SFRP-3 calculated in said step of quantifying to a SFRP-3 reference value; and
diagnosing heart failure in the individual if the concentration of SFRP-3 calculated in said step of quantifying is greater than the SFRP-3 reference value.

### Claim 3 (depends on 2)

The method according to claim 2, wherein said step of quantifying a signal comprises the use of a computing device.

### Claim 4 (depends on 2)

The method according to claim 2, wherein the individual at risk for heart failure is classified in stage B according to the ACC/AHA guidelines.

### Claim 5 (depends on 2)

The method according to claim 2, wherein the individual at risk for heart failure has been diagnosed as having at least one of obesity, diabetes, metabolic syndrome and hypertension.

### Claim 6 (depends on 2)

The method according to claim 2, wherein the detectable label comprises one of a peroxidase conjugate and digoxigenin.

### Claim 7 (depends on 2)

The method according to claim 2, wherein the SFRP-3 reference value is set at a specificity of at least 90%.

### Claim 8 (depends on 2)

The method according to claim 2, wherein the SFRP-3 reference value is derived from a control population of samples known to not suffer from heart failure.

### Claim 9 (depends on 2)

The method according to claim 2 further comprising coupling the complex to a solid support prior to said step of separating.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the solid support is a microwell

### Claim 11

A method for diagnosing heart failure in an individual at risk for heart failure, the method comprising the steps of:
contacting a portion of a serum, blood or plasma sample obtained from the individual with a capture antibody having specific binding affinity for secreted frizzled related protein 3 (SFRP-3), thereby forming a complex of the capture antibody and SFRP-3, the capture antibody being one of coupled to a solid support or comprising a component configured for coupling the capture antibody to a solid support;
contacting the portion of the sample with a detection antibody having specific binding affinity for SFRP-3, thereby forming a complex of the capture antibody, SFRP-3, and the detection antibody, the detection antibody having a detectable label;
contacting the complex of the capture antibody, SFRP-3 and the detection antibody with a solid support, whereby the complex of the capture antibody, SFRP-3 and the detection antibody couples to the solid support;
separating the complex of the capture antibody, SFRP-3 and the detection antibody coupled to the solid support from detection antibody, capture antibody and SFRP-3 not coupled to the solid support;
exposing the complex of the capture antibody, SFRP-3 and the detection antibody to a substrate, thereby producing a signal from the detectable label of the detection antibody comprising the complex of the capture antibody, SFRP-3 and the detection antibody which couples to the solid support in said step of contacting;
quantifying the signal produced in said step of exposing the complex of the capture antibody, SFRP-3 and the detection antibody, the signal being proportional to an amount of SFRP-3 in the sample from the individual, whereby a concentration of SFRP-3 in the sample is calculated;
comparing the concentration of SFRP-3 calculated in said step of quantifying to a SFRP-3 reference value; and
providing a diagnosis of heart failure in the individual if the concentration of SFRP-3 in the sample calculated in said step of quantifying is greater than the SFRP-3 reference concentration.

### Claim 12 (depends on 11)

The method according to claim 11, wherein said step of quantifying the signal comprises the use of a computing device.

### Claim 13 (depends on 11)

The method according to claim 11, wherein the individual at risk for heart failure is classified in stage B according to the ACC/AHA guidelines.

### Claim 14 (depends on 11)

The method according to claim 11, wherein the individual at risk for heart failure has been diagnosed as having at least one of obesity, diabetes, metabolic syndrome and hypertension.

### Claim 15 (depends on 11)

The method according to claim 11, wherein the detectable label comprises one of a peroxidase conjugate and digoxigenin.

### Claim 16 (depends on 11)

The method according to claim 11 wherein the SFRP-3 reference value is set at a specificity of at least 90%.

### Claim 17 (depends on 11)

The method according to claim 11, wherein the SFRP-3 reference value is derived from a control population of samples known to not suffer from heart failure.

### Claim 18 (depends on 11)

The method according to claim 11, wherein the second epitope is different than the first epitope.

### Claim 19 (depends on 11)

The method of claim 11, wherein said step of contacting the portion of the sample with the capture antibody and said step of contacting the portion of the sample with the detection antibody occur at substantially the same time.

### Claim 20 (depends on 11)

The method of claim 11, wherein the solid support is a microwell.
