# US 2014/0154259 A1 · Method for the treatment of inflammatory disorders

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2014/0154259 A1
- Document ID: US20140154259A1
- Status: Published application
- Kind: A1
- Application number: 14/021,547
- Filed: 2013-09-09
- Published: 2014-06-05
- Earliest claimed: 1999-06-01
- Assignees: Biogen Idec MA Inc.
- Inventors: ANTONIN DE FOUGEROLLES; Philip Gotwals; Roy R. Lobb; Victor E. Kotelianski
- Web page: https://patentgrep.com/patent/US20140154259A1

## CPC

- C07K 16/2842: {against integrin beta1-subunit-containing molecules, e.g. CD29, CD49}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/06: Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/06: Antianaemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/06: Antimigraine agents
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 27/16: Otologicals
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 39/02: Antidotes
- C07K 16/2821: {against ICAM molecules, e.g. CD50, CD54, CD102}
- C07K 16/2839: {against the integrin superfamily}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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

A method for the treatment of inflammatory disorders is disclosed, particularly the treatment of arthritis. The method comprises the administration of a function blocking antibody which is capable of binding an epitope of VLA-1.

## Claims

### Claim at position 1

1-7. (canceled)

### Claim 8

An antibody or antigen binding fragment thereof that binds to VLA-1, wherein the antibody or antigen binding fragment thereof
(i) binds to a cation-dependent epitope of VLA-1,
(ii) is capable of binding to a human α1-I domain but is not capable of binding to a rat α1-I domain, and
(iii) is capable of binding to an RΔH α1-I domain which is a rat α1-I domain in which rat residues G91, R92, Q93, and L96 are replaced with residues V, Q, R, and R respectively.

### Claim 9 (depends on 8)

The antibody or antigen binding fragment thereof of claim 8, wherein the capability of the antibody or antigen binding fragment thereof to bind to the human α1-I domain, the rat α1-I domain, and the RΔH α1-I domain is assessed using ELISA.

### Claim 10 (depends on 8)

The antibody or antigen binding fragment thereof of claim 8, wherein the antibody is monoclonal.

### Claim 11 (depends on 8)

The antibody or antigen binding fragment thereof of claim 8, wherein the antibody or antigen binding fragment thereof inhibits binding of K562-α1 cells to collagen IV coated plates as assessed using ELISA.

### Claim 12 (depends on 11)

The antibody or antigen binding fragment thereof of claim 11, wherein the inhibitory activity plateaus at about 0.6 μg/ml of the antibody or antigen binding fragment.

### Claim 13 (depends on 8)

The antibody or antigen binding fragment thereof of claim 8, wherein the antibody or antigen binding fragment thereof inhibits binding of a human α1-I domain to collagen W coated plates as assessed using ELISA.

### Claim 14 (depends on 13)

The antibody or antigen binding fragment thereof of claim 13, wherein the inhibition of binding of the human α1-I domain to collagen W coated plates is observed at concentrations of about 2.5 μg/ml or more of the antibody or antigen binding fragment.

### Claim 15 (depends on 8)

The antibody or antigen binding fragment of claim 8, wherein the antibody or antigen binding fragment thereof when administered to a subject having arthritis is capable of decreasing the arthritic score in said subject by about 65% or greater.

### Claim 16 (depends on 15)

The antibody or antigen binding fragment of claim 15, wherein the antibody or antigen binding fragment thereof is capable of decreasing the arthritic score in said subject by about 79% or greater.

### Claim 17 (depends on 16)

The antibody or antigen binding fragment thereof of claim 16, wherein the antibody or antigen binding fragment is capable of decreasing the arthritic score in said subject by about 85% or greater.

### Claim 18 (depends on 17)

The antibody or antigen binding fragment thereof of claim 17, wherein the antibody or antigen binding fragment is capable of decreasing the arthritic score in said subject by about 90% or greater.

### Claim 19 (depends on 8)

A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 8 and a pharmaceutically acceptable carrier.

### Claim 20

A method of treating an inflammatory disorder, the method comprising administering to a subject suffering from an inflammatory disorder an antibody or antigen binding fragment thereof that binds to VLA-1, wherein the antibody or antigen binding fragment thereof
(i) binds to a cation-dependent epitope of VLA-1,
(ii) is capable of binding to a human α1-I domain but is not capable of binding to a rat α1-I domain, and
(iii) is capable of binding to an RΔH α1-I domain which is a rat α1-I domain in which rat residues G91, R92, Q93, and L96 are respectively replaced with residues V, Q, R, and R, thereby treating said disorder.

### Claim 21 (depends on 20)

The method of claim 20, wherein the capability of the antibody or antigen binding fragment thereof to bind to the human α1-I domain, the rat α1-I domain, and the RΔH α1-I domain is assessed using ELISA.

### Claim 22 (depends on 20)

The method of claim 20, wherein said disorder is arthritis.

### Claim 23 (depends on 22)

The method of claim 22, wherein said disorder is rheumatoid arthritis.

### Claim 24 (depends on 20)

The method of claim 20, wherein said disorder is an inflammatory bowel disease.

### Claim 25 (depends on 24)

The method of claim 24, wherein said disorder is Crohn's disease or ulcerative colitis.

### Claim 26 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof is administered parenterally.

### Claim 27 (depends on 26)

The method of claim 26, wherein the antibody or antigen binding fragment thereof is administered subcutaneously, intravenously, intramuscularly, intra-articularly, intra-synovially, intrastemally, intrathecally, intrahepatically, intralesionally, or intracranially.

### Claim 28 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof is administered subcutaneously.

### Claim 29 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof is administered to the subject in an amount between 0.1 mg to 50 mg of the antibody or antigen binding fragment thereof per kilogram of the subject per day.

### Claim 30 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof is administered to the subject in an amount between 0.1 mg to 20 mg of the antibody or antigen binding fragment thereof per kilogram of the subject per day.

### Claim 31 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof is administered to the subject in an amount between 0.1 mg to 10 mg of the antibody or antigen binding fragment thereof per kilogram of the subject per day.

### Claim 32 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof is administered to the subject at intervals of every one to 14 days.

### Claim 33 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof is administered to the subject in an amount effective to provide a plasma level of at least 1 μg/ml of the antibody or antigen binding fragment thereof in the plasma of said subject.

### Claim 34 (depends on 33)

The method of claim 33, wherein the antibody or antigen binding fragment thereof is administered to the subject in an amount effective to provide a plasma level of at least 1 μg/ml of the antibody or antigen binding fragment thereof in the plasma of said subject.

### Claim 35 (depends on 20)

The method of claim 20, wherein the antibody is monoclonal.

### Claim 36 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof inhibits binding of K562-α1 cells to collagen IV coated plates as assessed using ELISA.

### Claim 37 (depends on 36)

The method of claim 36, wherein the inhibitory activity plateaus at about 0.6 μg/ml of the antibody or antigen binding fragment thereof.

### Claim 38 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof inhibits binding of a human α1-I domain to collagen W coated plates as assessed using ELISA.

### Claim 39 (depends on 38)

The method of claim 38, wherein the inhibition of binding of the human α1-I domain to collagen W coated plates is observed at concentrations of about 2.5 μg/ml or more of the antibody or antigen binding fragment thereof.

### Claim 40 (depends on 20)

The method of claim 20, wherein the antibody or antigen binding fragment thereof is capable of decreasing arthritic score in said subject by about 65% or greater.

### Claim 41 (depends on 40)

The method of claim 40, wherein the antibody or antigen binding fragment thereof is capable of decreasing arthritic score in said subject by about 79% or greater.

### Claim 42 (depends on 41)

The method of claim 41, wherein the antibody or antigen binding fragment thereof is capable of decreasing arthritic score in said subject by about 85% or greater.

### Claim 43 (depends on 42)

The method of claim 42, wherein the antibody or antigen binding fragment thereof is capable of decreasing arthritic score in said subject by about 90% or greater.

### Claim 44 (depends on 20)

The method of claim 20, wherein said subject is a human.