# US 2014/0155499 A1 · Biomarkers of osteoarthritis

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- Number: US 2014/0155499 A1
- Document ID: US20140155499A1
- Status: Published application
- Kind: A1
- Application number: 14/175,254
- Filed: 2014-02-07
- Published: 2014-06-05
- Earliest claimed: 2010-03-05
- Assignees: The Curators of the University of Missouri
- Applicants: The Curators of the University of Missouri
- Inventors: James L. Cook; Cristi R. Cook; Aaron M. Stoker; Keiichi Kuroki; Bridget Colleen Garner; Richard Evans; Brandon Lee Roller; Prakash Sidha Jayabalan
- Web page: https://patentgrep.com/patent/US20140155499A1

## CPC

- G01N 33/6887: {from muscle, cartilage or connective tissue}
- C12Q 1/6883: for diseases caused by alterations of genetic material
- G01N 33/5308: {for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites}
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/136: Screening for pharmacological compounds
- G01N 2333/52: Assays involving cytokines
- G01N 2333/5421: IL-8
- G01N 2800/105: Osteoarthritis, e.g. cartilage alteration, hypertrophy of bone
- G01N 2800/56: Staging of a disease; Further complications associated with the disease
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

Biomarkers, biomarker panels and methods for diagnosing osteoarthritis (OA) and determining treatment are disclosed, using measurement of the expression level of certain polypeptides in a test sample from a subject, including MCP1, IL8, KC, MMP2, MMP3, Apolipoprotein A1, and Apolipoprotein E. Related methods for monitoring OA treatment efficacy, diagnostic reagents, and kits are also described.

## Claims

### Claim 1

A method for treating osteoarthritis in a canine subject comprising: (i) requesting the results of a first biomarker profile analysis of a test biological fluid sample from the subject and (ii) administering a treatment for OA to the subject when the results of the biomarker profile analysis are indicative of the presence of OA in the subject, wherein the biomarker profile analysis comprises:
(a) measuring an expression level of at least two osteoarthritis marker polypeptides in the test sample using a protein detection method to determine a first OA biomarker profile, wherein the osteoarthritis marker polypeptides are selected from the group consisting of: MCP1, IL8, and KC;
(b) measuring an expression level of each osteoarthritis marker polypeptide used in (a) in a control biological fluid sample from a control canine subject in which OA is not present using the protein detection method used in (a) to determine a second OA biomarker profile; and
(c) comparing the first OA biomarker profile from (a) to the second OA biomarker profile from (b),
wherein a difference between the first OA biomarker profile and the second OA biomarker profile is indicative of the presence of osteoarthritis in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the biological fluid sample comprises any one of synovial fluid, whole blood, blood plasma, serum, urine, and saliva.

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

The method of claim 1, wherein the level of expression of MCP1, IL8, and KC is measured.

### Claim 5 (depends on 4)

The method of claim 4, wherein the level of expression of at least one additional osteoarthritis marker polypeptide is measured.

### Claim 6 (depends on 5)

The method of claim 5, wherein the at least one additional osteoarthritis marker polypeptide is selected from the group consisting of MMP2 and MMP3.

### Claim 7 (depends on 5)

The method of claim 5, comprising measuring in the biological fluid samples from the canine test and control subjects the level of expression of MCP1, IL8, KC, MMP2 and MMP3.

### Claim 8 (depends on 7)

The method of claim 7, further comprising measuring in the biological fluid samples from the canine test and control subjects the level of expression of at least one additional osteoarthritis marker selected from Apolipoprotein A1 and Apolipoprotein E.

### Claim 9 (depends on 8)

The method of claim 8, wherein the level of expression of at least seven osteoarthritis marker polypeptides is measured.

### Claim 10 (depends on 9)

The method of claim 9, wherein the selected osteoarthritis marker polypeptides comprise MCP-1, IL8, KC, MMP2, MMP3, Apolipoprotein A1 and Apolipoprotein E.

### Claim 11 (depends on 1)

The method of claim 1, further comprising monitoring the effect of the treatment of osteoarthritis in the subject by obtaining the results of a second biomarker profile analysis and comprising the results to the first biomarker profile analysis.

### Claim 12 (depends on 1)

The method of claim 1, wherein the subject is at risk of having or is suspected of having osteoarthritis.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the protein detection method is selected from the group consisting of: LUMINEX, ELISA, immunoassay, mass spectrometry, high performance liquid chromatography, two-dimensional electrophoresis, Western blotting, protein microarray, and antibody microarray.

### Claim 14 (depends on 13)

The method of claim 13, wherein the protein detection method is an immunoassay.
