# US 2010/0166757 A1 · Antibodies against monocyte chemotactic proteins

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- Number: US 2010/0166757 A1
- Document ID: US20100166757A1
- Status: Published application
- Kind: A1
- Application number: 12/612,087
- Filed: 2009-11-04
- Published: 2010-07-01
- Earliest claimed: 2001-11-30
- Assignees: Biogen Idec MA Inc.
- Inventors: Antonin R. De Fougerolles; Victor E. Kotelianski; Carl Reid; Ellen Garber
- Web page: https://patentgrep.com/patent/US20100166757A1

## CPC

- C07K 16/24: against cytokines, lymphokines or interferons
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- 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 17/00: Drugs for dermatological disorders
- 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 25/00: Drugs for disorders of the nervous system
- 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 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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

The invention provides antibodies that bind to a plurality of β-chemokines, particularly monocyte chemotactic proteins MCP-1, MCP-2 and MCP-3. The invention also provides cells producing the antibodies, and methods of making and using the same.

## Claims

### Claim at position 1

1-55. (canceled)

### Claim 56

A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or fragment thereof, wherein said antibody or fragment thereof binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprise MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment comprises:
a) a heavy chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:29, a CDR2 domain comprising the sequence set forth in SEQ ID NO:30, and a CDR3 domain comprising the sequence set forth in SEQ ID NO: 31; and
b) a light chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:32, a CDR2 domain comprising the sequence set forth in SEQ ID NO:33, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:34.

### Claim at position 3

57-75. (canceled)

### Claim 76 (depends on 56)

The method of claim 56, wherein the at least one other β-chemokine is MCP-2.

### Claim 77 (depends on 56)

The method of claim 56, wherein the antibody is a chimeric antibody.

### Claim 78 (depends on 56)

The method of claim 56, wherein the antibody is a humanized antibody.

### Claim 79 (depends on 56)

The method of claim 56, wherein the fragment is an Fab fragment.

### Claim 80 (depends on 56)

The method of claim 56, wherein the antibody is modified by reducing or eliminating at least one potential glycosylation site.

### Claim 81 (depends on 56)

The method of claim 56, wherein the antibody is modified by conjugation to a carrier selected from polyethylene glycol and albumen.

### Claim 82 (depends on 56)

The method of claim 56, wherein the constant region of the antibody is modified to reduce at least one constant region-mediated biological effector function relative to an unmodified antibody selected from the group of binding to an Fc receptor, opsonization, phagocytosis, and antigen-dependent cellular cytotoxicity.

### Claim 83

A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody heavy chain, wherein said antibody heavy chain comprises a variable region complementarity determining region (CDR) from an antibody heavy chain variable region set forth in SEQ ID NO:27.

### Claim 84

A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody light chain, wherein said antibody light chain comprises a variable region complementarity determining region (CDR) from an antibody light chain variable region as set forth in SEQ ID NO:28.

### Claim 85

A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a variable heavy chain region as set forth in SEQ ID NO:27 and a variable light chain region as set forth in SEQ ID NO:28

### Claim 86

A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment thereof comprises a variable region complementarity determining region (CDR) from a heavy chain variable region set forth in SEQ ID NO:27.

### Claim 87 (depends on 86)

The method of claim 86, wherein the at least one other β-chemokine includes MCP-2.

### Claim 88

A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment thereof comprises a variable region complementarity determining region (CDR) from a light chain variable region set forth in SEQ ID NO:28.

### Claim 89 (depends on 88)

The method of claim 88, wherein the at least one other β-chemokine includes MCP-2.

### Claim 90

A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated single-chain antibody antigen-binding fragment, wherein said single-chain antibody antigen-binding fragment specifically binds MCP-1 and at least one other monocyte chemotactic protein, wherein said single-chain antibody antigen-binding fragment comprises a heavy chain variable region complementarity determining region (CDR) from an antibody heavy chain variable region set forth in SEQ ID NO:27 or a light chain variable region complementarity determining region (CDR) from an antibody light chain variable region set forth in SEQ ID NO:28, wherein said antibody fragment does not have agonistic activity for MCP-2.

### Claim 91 (depends on 90)

The method of claim 90, wherein the antibody antigen-binding fragment comprises a variable heavy chain region as set forth in SEQ ID NO: 27 and a variable light chain region as set forth in SEQ ID NO:28.

### Claim 92 (depends on 90)

The method of claim 90, wherein the antibody antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said antibody antigen-binding fragment comprises:
i. a heavy chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:29, a CDR2 domain comprising the sequence set forth in SEQ ID NO:30, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:31; and
ii. a light chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:32 a CDR2 domain comprising the sequence set forth in SEQ ID NO:33, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:34.

### Claim 93 (depends on 90)

The method of claim 90, wherein the antibody antigen-binding fragment specifically binds to MCP-1, MCP-2, and MCP-3.

### Claim 94 (depends on 90)

The method of claim 90, wherein the antibody antigen-binding fragment is a monoclonal or antigen-binding fragment.

### Claim 95 (depends on 90)

The method of claim 90, wherein the antibody antigen-binding fragment is a humanized antibody.

### Claim 96 (depends on 90)

The method of claim 90, wherein the antibody antigen-binding fragment is selected from the group consisting of an Fab fragment, an Fab′ fragment, an F(ab)2 fragment, and an Fv fragment.

### Claim 97 (depends on 90)

The method of claim 90, wherein the antibody antigen-binding fragment is an Fab fragment.

### Claim 98 (depends on 90)

The method of claim 90, wherein the antibody antigen-binding fragment is conjugated to polyethylene glycol or albumen.

### Claim 99 (depends on 90)

The method of claim 90, wherein the antibody antigen-binding fragment has a Kd for binding affinity to MCP-1 of 1 pM or less or 0.4 pM to about 0.7 pM.