# US 7,608,694 B2 · Antibody molecules having specificity for human IL-1β

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- Number: US 7,608,694 B2
- Document ID: US7608694B2
- Status: Granted
- Kind: B2
- Application number: 10/544,911
- Filed: 2004-02-06
- Published: 2006-10-12
- Granted: 2009-10-27
- Earliest claimed: 2003-02-13
- Assignees: UCB Pharma S.A.
- Inventors: Alastair David Griffiths Lawson; Andrew George Popplewell
- Web page: https://patentgrep.com/patent/US7608694B2

## CPC

- C07K 16/245: {IL-1}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- 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 19/10: for osteoporosis
- A61P 25/02: for peripheral neuropathies
- 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 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- 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
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- 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)
- 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

## Abstract

The invention relates to an antibody molecule having specificity for antigenic determinants of IL-1β, therapeutic uses of the antibody molecule and methods for producing said antibody molecule.

## Claims

### Claim 1

A neutralising antibody having specificity for human IL-1β, the antibody comprising a heavy chain and a light chain, wherein the variable domain of the heavy chain comprises the sequence given in SEQ ID NO:5 for CDR-H1, the sequence given in SEQ ID NO:6 for CDR-H2 and the sequence given in SEQ ID NO:7 for CDR-H3 and wherein the variable domain of the light chain comprises the sequence given in SEQ ID NO:8 for CDR-L1, the sequence given in SEQ ID NO:9 for CDR-L2 and the sequence given in SEQ ID NO:10 for CDR-L3.

### Claim 2 (depends on 1)

A neutralising antibody according to claim 1, wherein said neutralising antibody is a CDR-grafted antibody molecule.

### Claim 3 (depends on 2)

The antibody molecule of claim 2, wherein the variable domain of either the heavy chain, the light chain, or both the heavy chain and the light chain comprises human acceptor framework regions and non-human donor CDRs.

### Claim 4 (depends on 2)

A CDR-grafted antibody according to claim 2, wherein the heavy chain comprises the sequence gH3 (SEQ ID NO: 15).

### Claim 5 (depends on 2)

A CDR-grafted antibody according to claim 2, wherein the light chain comprises the sequence gL3 (SEQ ID NO:20).

### Claim 6 (depends on 2)

A CDR-grafted antibody according to claim 2, wherein the heavy chain comprises the sequence gH3 (SEQ ID NO: 15) and the light chain comprises the sequence gL3 (SEQ ID NO:20).

### Claim 7

A neutralising antibody having specificity for human IL-1β, having a heavy chain comprising the sequence given in SEQ ID NO:3 and a light chain comprising the sequence given in SEQ ID NO:4.

### Claim 8 (depends on 1)

A neutralising antibody molecule according to claim 1, wherein the antibody molecule is selected from the group consisting of: a complete antibody molecule having full length heavy and light chains, a Fab, Fab′, F(ab′)2, Fv fragment, scFv fragment, and Fab that has been modified to enable an effector or reporter molecule to be attached to it, wherein the modification is the addition to the C-terminal end of its heavy chain of one or more amino acids to allow the attachment of an effector or reporter molecule.

### Claim 9 (depends on 8)

The antibody molecule of claim 8, wherein the additional amino acids form a modified hinge region containing one or two cysteine residues to which the effector or reporter molecule may be attached.

### Claim 10 (depends on 8)

A neutralising antibody molecule according to claim 8, having an effector or a reporter molecule attached to it.

### Claim 11 (depends on 10)

A neutralising antibody molecule according to claim 10, wherein the effector molecule comprises one or more polymers.

### Claim 12 (depends on 11)

A neutralising antibody molecule according to claim 11, wherein the one or more polymers is/are optionally substituted straight or branched chain polyalkylene, polyalkenylene or polyoxyalkylene polymer or a branched or unbranched polysaccharide.

### Claim 13 (depends on 11)

A neutralising antibody molecule according to claim 11, wherein the one or more polymers is/are a methoxypoly(ethyleneglycol) or poly(ethyleneglycol).

### Claim 14 (depends on 10)

A neutralising antibody molecule according to claim 10, having attached to one of the cysteine residues at the C-terminal end of the heavy chain a lysyl-maleimide or lysyl bis-maleimide group wherein each amino group of the lysyl residue has covalently linked to it a methoxypoly(ethyleneglycol) residue having a molecular weight of about 20,000 Da.

### Claim 15

A neutralising antibody molecule having specificity for human IL-1β, which is a modified Fab fragment having a heavy chain comprising the sequence given in SEQ ID NO: 15 and a light chain comprising the sequence given in SEQ ID NO:20 and having at the C-terminal end of its heavy chain a modified hinge region containing one cysteine residue to which an effector or reporter molecule may be attached.

### Claim 16

A neutralising antibody molecule having specificity for human IL-1β, which is a modified Fab fragment having a heavy chain comprising the sequence given in SEQ ID NO:15 and a light chain comprising the sequence given in SEQ ID NO:20 and having at the C-terminal end of its heavy chain a modified hinge region containing one cysteine residue to which an effector or reporter molecule is attached.

### Claim 17

A neutralising antibody having specificity for human IL-1β having a heavy chain comprising amino acid residue numbers 22 to 251 of the sequence given in SEQ ID NO:71 and a light chain comprising amino acid residue numbers 22 to 235 of the sequence given in SEQ ID NO:70 and having an effector or reporter molecule attached to the cysteine residue at the C-terminal end of the heavy chain.

### Claim 18 (depends on 16, 17)

A neutralising antibody molecule according to claim 16 or claim 17, having attached to the cysteine residue at the C-terminal end of the heavy chain a lysyl-maleimide group, wherein each amino group of the lysyl residue has covalently linked to it a methoxypoly(ethyleneglycol) residue having a molecular weight of about 20,000 Da.

### Claim 19 (depends on 1, 17)

A pharmaceutical composition comprising an antibody molecule according to any one of claims 1 or 17, in combination with one or more of a pharmaceutically acceptable excipient, diluent or carrier.

### Claim 20 (depends on 19)

A pharmaceutical composition according to claim 19, additionally comprising other active ingredients.

### Claim 21 (depends on 16, 17)

A compound comprising the antibody molecule of claim 16 or claim 17 having the formula:
wherein n is about 420.