# US 2014/0194364 A1 · Biomarkers for Painful Intervertebral Discs and Methods of Use Thereof

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- Number: US 2014/0194364 A1
- Document ID: US20140194364A1
- Status: Published application
- Kind: A1
- Application number: 14/103,248
- Filed: 2013-12-11
- Published: 2014-07-10
- Earliest claimed: 2008-05-29
- Assignees: The Regents of the University of California
- Inventors: Zorica Buser; Jeffrey Charles Lotz
- Web page: https://patentgrep.com/patent/US20140194364A1

## CPC

- A61K 38/1709: {from mammals}
- A61K 31/565: not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C12Q 1/6876: Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q 1/6883: for diseases caused by alterations of genetic material
- G01N 33/6893: {related to diseases not provided for elsewhere}
- C12Q 2600/158: Expression markers
- G01N 2800/2842: Pain, e.g. neuropathic pain, psychogenic pain
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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

The present disclosure provides methods of diagnosing painful intervertebral discs. The present disclosure also provides methods of treating a painful intervertebral disc.

## Claims

### Claim 1

A method of identifying a painful intervertebral disc, the method comprising assaying for an expression level of a gene product of at least one pain indicator gene selected from COL2A, COL9A3, AGC1, DCN, MMP3, MMP13, TIMP1, TIMP3, CD44, HIF1, IL8, IL1R, PLA2, TSG6, MMP9, Col1A1, Col3, BMP7, TNF-α, IL1β, PGE2, HIF1A, and ADAMTS5,
wherein a decreased expression level of a gene product selected from COL2A, COL9A3, AGC1, DCN, MMP3, MMP13, TIMP1, TIMP3, CD44, HIF1, IL8, IL1R, PLA2, TSG6, MMP9, Col1A1, and Col3 in an intervertebral disc tissue, compared to a normal control value, indicates that the intervertebral disc is painful, and wherein an increased expression level of a gene product selected from BMP7, TNF-α, IL1β, PGE2, HIF1A, and ADAMTS5 in an intervertebral disc tissue, compared to a normal control value, indicates that the intervertebral disc is painful.

### Claim 2 (depends on 1)

The method of claim 1, wherein the intervertebral disc tissue is annulus fibrosus.

### Claim 3 (depends on 1)

The method of claim 1, wherein the intervertebral disc tissue is nucleus pulposus.

### Claim 4 (depends on 1)

The method of claim 1, wherein the gene product is a nucleic acid.

### Claim 5 (depends on 1)

The method of claim 1, wherein the gene product is a polypeptide.

### Claim 6 (depends on 5)

The method of claim 5, wherein the method comprises contacting the intervertebral disc tissue with an antibody specific for the polypeptide.

### Claim 7 (depends on 6)

The method of claim 6, wherein the antibody is detectably labeled.

### Claim 8 (depends on 7)

The method of claim 7, wherein binding of the detectably labeled antibody to the polypeptide is detected using an imaging method selected from magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography.

### Claim 9 (depends on 1)

The method of claim 1, wherein the pain indicator gene product is a TSG6 gene product.

### Claim 10 (depends on 1)

The method of claim 1, further comprising administering a therapy for treatment of the painful intervertebral disc.

### Claim 11 (depends on 10)

The method of claim 10, wherein the therapy comprises surgery.

### Claim 12 (depends on 10)

The method of claim 10, wherein the therapy comprises administration of an agent.

### Claim 13 (depends on 1)

The method of claim 1, further comprising generating a report comprising information and/or a statement regarding the presence of a painful intervertebral disc in the individual.

### Claim 14 (depends on 13)

The method of claim 13, wherein the report is provided in an electronic medium.

### Claim 15 (depends on 13)

The method of claim 13, wherein the report is provided in a tangible medium.

### Claim 16

A method of treating intervertebral disc pain, the method comprising administering to an individual having intervertebral disc pain an effective amount of a tumor necrosis factor-alpha-induced protein 6 (TSG6) polypeptide, a polynucleotide comprising a nucleotide sequence encoding a TSG6 polypeptide, or a small molecule agent that increases the level of a TSG6 polypeptide in a cell.

### Claim 17 (depends on 16)

The method of claim 16, wherein said administering is local administration.

### Claim 18 (depends on 17)

The method of claim 17, wherein said administering is via bolus injection.

### Claim 19 (depends on 17)

The method of claim 17, wherein said administering is carried out using a device that provides for sustained release.

### Claim 20 (depends on 19)

The method of claim 19, wherein the device is a depot.

### Claim 21 (depends on 19)

The method of claim 19, wherein the device is a pump.

### Claim 22 (depends on 16)

The method of claim 16, wherein the TSG6 polypeptide comprises an amino acid sequence having at least about 75% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:1.

### Claim 23 (depends on 16)

The method of claim 16, wherein the agent comprises 2-methoxyestradiol.