# US 8,541,182 B2 · Biological marker for inflammation

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- Number: US 8,541,182 B2
- Document ID: US8541182B2
- Status: Granted
- Kind: B2
- Application number: 12/819,945
- Filed: 2010-06-21
- Published: 2010-10-07
- Granted: 2013-09-24
- Earliest claimed: 2004-12-02
- Assignees: Can-Fite Biopharma Ltd.
- Applicants: Pnina Fishman; Sara Bar-Yehuda; Lea Madi
- Inventors: Pnina Fishman; Sara Bar-Yehuda; Lea Madi
- Web page: https://patentgrep.com/patent/US8541182B2

## CPC

- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels}
- A61K 31/7076: containing purines, e.g. adenosine, adenylic acid
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/564: for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9}
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- 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)

## Abstract

Inflammatory state in a subject is assayed by determining the level of expression of A3 adenosine receptor (A3AR) in white blood cells (WBC), e.g. circulating WBCs, from the subject. A high level of expression of A3AR is indicative of an inflammatory state in the subject. This assay can be used for determining the severity of inflammation in a subject and monitoring the efficacy of anti-inflammatory treatment. Also, the level of expression may be used for selecting patients to receive an anti-inflammatory treatment that comprises an A3AR agonist.

## Claims

### Claim 1

A therapeutic method, comprising:
a. determining the level of A3 adenosine receptor (A3AR) in a sample of white blood cells (WBCs) of a subject; and
b. treating the subject only if said level is above a predefined threshold which is about twice the level of A3AR in WBC of healthy subjects; wherein
(i) the subject is one that is known to have an inflammatory state,
(ii) the treating comprises administering an anti-inflammatory agent to the subject, and
(iii) the anti-inflammatory agent is N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA); wherein the treating step comprises treating the subject with an amount of IB-MECA that is effective to reduce the inflammatory state in said subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the sample of WBC is taken from a subject before receiving the anti-inflammatory treatment.

### Claim 3 (depends on 1)

The method of claim 1, wherein the autoimmune disease is rheumatoid arthritis (RA).

### Claim 4

A method for anti-inflammatory therapeutic treatment of a subject known to have an inflammatory state that is the result of an autoimmune disease, the method comprising:
a. determining the level of A3 adenosine receptor (A3AR) in a sample of white blood cells (WBCs) of the subject; and
b. treating the subject with an anti-inflammatory agent only if the level is above a predefined threshold which is about twice the level of A3AR in WBC of healthy subjects;
wherein the anti-inflammatory agent is N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA) and the amount of the A3AR agonist is effective to reduce the inflammatory state in said subject.

### Claim 5 (depends on 4)

The method of claim 4, wherein the sample of WBC is taken from the subject before receiving the anti-inflammatory treatment.

### Claim 6

In a method for anti-inflammatory therapeutic treatment of a subject known to have an inflammatory state that is the result of an autoimmune disease, the method comprising treating the subject with an effective amount of N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA),
wherein the improvement comprises selecting the subject to receive the anti-inflammatory therapeutic treatment if determined to have a level of A3 adenosine receptor (A3AR), in a sample of white blood cells (WBCs) of the subject, above a predefined threshold that is about twice the level of A3AR in WBC of healthy subjects, and withholding said treatment if determined to have a level of A3AR, in a sample of WBCs of the subject, below the predefined threshold.

### Claim 7 (depends on 6)

The method of claim 6, wherein the sample of WBCs is taken from a subject before receiving the anti-inflammatory treatment.

### Claim 8 (depends on 6)

The method of claim 6, wherein the autoimmune disease is rheumatoid arthritis (RA).

### Claim 9

A therapeutic method, comprising:
a. determining the level of A3 adenosine receptor (A3AR) in a sample of white blood cells (WBCs) of a subject; and
b. treating the subject only if said level is above a predefined threshold which is about twice the level of A3AR in WBC of healthy subjects; wherein
(i) the subject is one that is known to have rheumatoid arthritis,
(ii) the treating comprises administering an anti-inflammatory agent to the subject, and
(iii) the anti-inflammatory agent is an A3AR agonist;
wherein the A3AR agonist is N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA), and the amount of the A3AR agonist administered is effective to reduce the inflammatory state in said subject.

### Claim 10

A method for anti-inflammatory therapeutic treatment of a subject known to have rheumatoid arthritis, the method comprising:
a. determining the level of A3 adenosine receptor (A3AR) in a sample of white blood cells (WBCs) of the subject; and
b. treating the subject with an anti-inflammatory agent only if the level is above a predefined threshold which is about twice the level of A3AR in WBC of healthy subjects;
wherein the anti-inflammatory agent is an A3AR agonist N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA), and the amount of said A3AR agonist is effective to reduce the inflammatory state in said subject.

### Claim 11

In a method for anti-inflammatory therapeutic treatment of a subject known to have rheumatoid arthritis, the method comprising treating the subject with an A3 adenosine receptor (A3AR) agonist,
wherein the improvement comprises selecting the subject to receive the anti-inflammatory therapeutic treatment if determined to have a level of A3AR, in a sample of white blood cells (WBCs) of the subject, above a predefined threshold that is about twice the level of A3AR in WBC of healthy subjects, and withholding said treatment if determined to have a level of A3AR, in a sample of WBCs of the subject, below said predefined threshold;
wherein the A3AR agonist is N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA) and the amount of the A3AR agonist is effective to reduce the inflammatory state in said subject.
