Anti-IL-12/IL-23 antibodies

• US 8,563,697 B2
• Filed: 08/14/2009
• Issued: 10/22/2013
• Est. Priority Date: 08/14/2008
• Status: Expired due to Fees

• Current Assignee: Teva Pharmaceuticals Australia, Pty. Ltd. (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cephalon Australia Pty., Ltd. (Teva Pharmaceutical Industries Limited)
• Inventors: Clarke, Adam William, Doyle, Anthony Gerard, Poulton, Lynn Dorothy, Wai, Bernadette, Kopsidas, George, Jennings, Philip Anthony, Pow, Andrew James
• Primary Examiner(s): Jiang, Dong
• Application Number:
  US13/058,914
• Publication Number:
  US 20110262445A1
• Time in Patent Office: 1,530 Days
• Field of Search: None
• US Class Current: 530/388.23
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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 14/5434 : IL-12
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention provides an antibody comprising an antigen binding domain which binds to human IL-12 and human IL-23. The antibody binds human IL-12p40 existing as a monomer (human IL-12p40) and as a homodimer (human IL-12p80) and the antibody inhibits the binding of human IL-12 to human IL-12R β2 and human IL-23 to human IL-23R but does not inhibit the binding of human IL-12 or human IL-23 or human IL-12p40 or human IL-12p80 to human IL-12Rβ1.

Claims

1. An isolated antibody which binds human IL-12p40, said antibody comprising an immunoglobulin heavy chain variable region selected from the group consisting of SEQ ID NO:

6, SEQ ID NO;

115, SEQ ID NO;

119, SEQ ID NO;

158, SEQ ID NO;

159, SEQ ID NO;

162, and SEQ ID NO;

112.

2. The antibody as claimed in claim 1 in which the antibody comprises a human or non-human primate heavy chain immunoglobulin constant region selected from a group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA.

3. An isolated antibody which binds human IL-12p40, said antibody comprising an immunoglobulin light chain variable region selected from the group consisting of SEQ ID NO:

7, SEQ ID NO;

169, SEQ ID NO;

189, and SEQ ID NO;

179.

4. The antibody as claimed in claim 3 in which the antibody comprises a human or non-human primate light chain immunoglobulin constant region selected from a group consisting of kappa or lambda.

5. An isolated antibody which binds human IL-12p40, said antibody comprising two immunoglobulin variable regions, wherein said two immunoglobulin variable regions are selected from a group consisting of:

SEQ ID NO;

6 and SEQ ID NO;

7;

SEQ ID NO;

119 and SEQ ID NO;

179;

SEQ ID NO;

112 and SEQ ID NO;

169;

SEQ ID NO;

158 and SEQ ID NO;

189;

SEQ ID NO;

159 and SEQ ID NO;

189;

SEQ ID NO;

162 and SEQ ID NO;

189; and

SEQ ID NO;

115 and SEQ ID NO;

189.

6. The antibody as claimed in claim 5 in which the antibody comprises a human or non-human primate heavy chain immunoglobulin constant region selected from a group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA.

7. The antibody as claimed in claim 5 in which the antibody comprises a human or non-human primate light chain immunoglobulin constant region selected from a group consisting of kappa or lambda.

8. The antibody as claimed in claim 5 in which the antibody is modified by the covalent attachment of an organic moiety.

9. The antibody as claimed in claim 8 in which the organic moiety is a linear or branched hydrophilic polymeric group, fatty acid group, or fatty acid ester group.

10. The antibody as claimed in claim 5 in which the antibody is modified to modulate a functional characteristic selected from the group consisting of antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, serum half-life, biodistribution and binding to Fc receptors.

11. The antibody as claimed in claim 10 in which the modification is by protein engineering, glycoengineering or chemical methods.