# US 11,442,068 B2 · Method for diagnosing and treating fibromyalgia

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- Number: US 11,442,068 B2
- Document ID: US11442068B2
- Status: Granted
- Kind: B2
- Application number: 16/002,689
- Filed: 2018-06-07
- Published: 2018-12-06
- Granted: 2022-09-13
- Earliest claimed: 2010-10-12
- Assignees: Epicgenetics, Inc.
- Applicants: Epicgenetics, Inc.
- Inventors: Bruce S. Gillis
- Web page: https://patentgrep.com/patent/US11442068B2

## CPC

- G01N 33/6863: {Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors}
- G01N 33/6866: {Interferon}
- G01N 33/6869: {Interleukin}
- G01N 2333/523: Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1or LDCF-2
- G01N 2333/5409: IL-5
- G01N 2333/5412: IL-6
- G01N 2333/5421: IL-8
- G01N 2333/5428: IL-10
- G01N 2333/57: IFN-gamma
- G01N 2800/10: Musculoskeletal or connective tissue disorders
- G01N 2800/2842: Pain, e.g. neuropathic pain, psychogenic pain
- G01N 2800/50: Determining the risk of developing a disease
- 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 2800/60: Complex ways of combining multiple protein biomarkers for diagnosis
- G01N 2800/7095: Inflammation
- 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 invention provides methods, kits and reagents for diagnosing fibromyalgia (FM) in an individual by determining whether the levels of one or more cytokines in the individual are altered, as compared to control levels. The altered level(s) or patterns of expression of the cytokines measured in the affected individual compared to the level from the control is predictive/indicative of FM in the individual.

## Claims

### Claim 1

A method of treating fibromyalgia (FM) in an individual, the method comprising:
(a) stimulating a peripheral blood mononuclear cell (PBMC) sample obtained from an individual previously diagnosed with FM with one or more mitogens;
(b) determining expression levels in the PBMC sample of at least four cytokines selected from the group consisting of interleukin 5 (IL5), interleukin 6 (IL6), interleukin 8 (IL8), interleukin 10 (IL 10), interferon-γ (IFN-γ), monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and macrophage inflammatory protein-1β (MIP-1β) at the protein level by an antibody bead-based capture assay, wherein the bead-based capture assay comprises beads derivatized with antibodies specific to the at least four cytokines;
(c) comparing the determined levels of protein expression to the expression levels of the at least four cytokines in a control sample;
(d) identifying the individual as having the at least four cytokines expression levels decreased by at least about 1.5 times in the PBMC sample obtained from the individual previously diagnosed with FM as compared to the expression levels of the control sample; and
(e) administering to the identified individual an effective amount of a FM standard of care selected from the group consisting of duloxetine, pregabalin, gabapentin and milnacipran.

### Claim 2 (depends on 1)

The method of claim 1, wherein determining the protein expression levels in the PBMC sample comprises determining the protein expression levels of at least five cytokines selected from the group consisting of IL5, IL6, IL8, IL 10, IFN-γ, MCP-1, MIP-1α and MIP-1β.

### Claim 3 (depends on 1)

The method of claim 1, wherein determining the protein expression levels in the PBMC sample comprises determining the protein expression levels of at least six cytokines selected from the group consisting of IL5, IL6, IL8, IL 10, IFN-γ, MCP-1, MIP-1α and MIP-1β.

### Claim 4 (depends on 1)

The method of claim 1, wherein determining the protein expression levels in the PBMC sample comprises determining the protein expression levels of at least seven cytokines selected from the group consisting of IL5, IL6, IL8, IL 10, IFN-γ, MCP-1, MIP-1α and MIP-1β.

### Claim 5 (depends on 1)

The method of claim 1, wherein determining the protein expression levels in the PBMC sample comprises determining the protein expression levels of IL5, IL6, IL8, IL 10, IFN-γ, MCP-1, MIP-1α and MIP-1β.

### Claim 6 (depends on 1)

The method of claim 1, wherein the at least four cytokines are IL6, IL8, MIP-1α and MIP-1β.

### Claim 7 (depends on 1)

The method of claim 1, wherein the one or more mitogens is selected from a T-cell mitogen, lipopolysaccharide (LPS), phorbol ester, phorbol myristate acetate (PMA) and PMA plus ionomycin.

### Claim 8 (depends on 7)

The method of claim 7, wherein the T cell mitogen is selected from phytohemagglutinin (PHA), pokeweed mitogen (PWM) and concavalin A (Con-A).

### Claim 9 (depends on 1)

The method of claim 1, wherein the decreased expression levels are characterized by a decrease in expression level of each of the at least four cytokines by at least about 2 times, at least about 2.5 times, at least about 3 times, at least about 4 times or at least about 5 times.

### Claim 10 (depends on 1)

The method of claim 1, wherein the bead-based assay is a fluorescence-based assay.

### Claim 11 (depends on 1)

The method of claim 1, wherein the bead-based capture assay is an enzyme-linked immunoassay (ELISA) assay.

### Claim 12 (depends on 1)

The method of claim 1, wherein the beads derivatized with antibodies specific to the at least four cytokines are magnetic beads.

### Claim 13 (depends on 2)

The method of claim 2, wherein the at least five cytokines comprise IL6, IL8, MIP-1α and MIP-1β and one or more cytokines selected from IL5, IL10, IFN-γ and MCP-1.

### Claim 14 (depends on 3)

The method of claim 3, wherein the at least six cytokines comprise IL6, IL8, MIP-1α and MIP-1β and two or more cytokines selected from IL5, IL10, IFN-γ and MCP-1.

### Claim 15 (depends on 4)

The method of claim 4, wherein the at least seven cytokines comprise IL6, IL8, MIP-1α and MIP-1β and three or more cytokines selected from IL5, IL10, IFN-γ and MCP-1.

### Claim 16 (depends on 1)

The method of claim 1, wherein the control sample is obtained from an individual known not to have fibromyalgia.

### Claim 17 (depends on 1)

The method of claim 1, wherein the control sample is obtained from an individual diagnosed with a disease of widespread pain selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjogren Syndrome and multiple sclerosis.