Antibody molecules having specificity for human IL-1β

• US 7,608,694 B2
• Filed: 02/06/2004
• Issued: 10/27/2009
• Est. Priority Date: 02/13/2003
• Status: Expired due to Fees

• Current Assignee: Ucb Biopharma Sprl (UCB SA)
• Original Assignee: UCB Pharma SA (UCB SA)
• Inventors: Popplewell, Andrew George, Lawson, Alastair David Griffiths
• Primary Examiner(s): Blanchard; David J.
• Application Number:
  US10/544,911
• Publication Number:
  US 20060228358A1
• Time in Patent Office: 2,090 Days
• Field of Search: None
• US Class Current: 530/388.23
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: 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
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/245 IL-1
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]

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

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.

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

3. 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.

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

15).

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

20).

6. 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).

8. 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.

9. 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.

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

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

12. 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.

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

14. 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.

19. 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.

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

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.

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.

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.

18. 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.

21. A compound comprising the antibody molecule of claim 16 or claim 17 having the formula:

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.