Anti-IL-6 antibodies, compositions, methods and uses

• US 7,291,721 B2
• Filed: 10/26/2002
• Issued: 11/06/2007
• Est. Priority Date: 11/14/2001
• Status: Active Grant

• Current Assignee: Eusa Pharma (USA) Incorporated (Jazz Pharmaceuticals Plc)
• Original Assignee: Centocor Incorporated (Johnson & Johnson)
• Inventors: Knight, David, Giles-Komar, Jill, Peritt, David, Trikha, Mohit
• Primary Examiner(s): Yu; Misook
• Assistant Examiner(s): Halvorson; Mark
• Application Number:
  US10/280,716
• Publication Number:
  US 20060188502A1
• Time in Patent Office: 1,837 Days
• Field of Search: None
• US Class Current: 536/23.53
• CPC Class Codes: A01K 2267/0331 Animal model for proliferative diseases
• CPC Class Codes: A01K 67/0271 Chimeric vertebrates, e.g. comprising exogenous cells
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/04 for throat disorders
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 : Antipruritics
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 17/12 : Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 17/14 : for baldness or alopecia
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• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 21/04 : for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 25/32 : Alcohol-abuse
• 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 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/08 : for leprosy
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• 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 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• 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 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 7/08 : Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 16/248 : IL-6
• CPC Class Codes: C07K 16/4241 : against anti-human or anti-animal Ig
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• 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 relates to at least one novel chimeric, humanized or CDR-grafted anti-IL-6 antibodies derived from the murine CLB-8 antibody, including isolated nucleic acids that encode at least one such anti-IL-6 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Claims

1. Isolated nucleic acid molecules encoding an antibody or antigen-binding fragment thereof that binds and inhibits the activity of human IL-6, wherein said antibody or antigen-binding fragment comprise:

a human antibody heavy chain constant region and a heavy chain variable region comprising CDR1, CDR2 and CDR3, which comprise the amino acid sequences SEQ ID NO;

1, SEQ ID NO;

2 and SEQ ID NO;

3, respectively; and

a human antibody light chain constant region and a light chain variable region comprising CDR1, CDR2 and CDR3, which comprise the amino acid sequences SEQ ID NO;

4, SEQ ID NO;

5 and SEQ ID NO;

6, respectively.

2. The isolated nucleic acid molecules of claim 1, wherein said isolated nucleic acid molecules comprise:

a nucleotide sequence that encodes a human antibody heavy chain constant region and a heavy chain variable region comprising SEQ ID NO;

7; and

a nucleotide sequence that encodes a human antibody light chain constant region and a light chain variable region comprising SEQ ID NO;

8.

3. A method for producing an IL-6 antibody or antigen-binding fragment, therof, comprising translating the nucleic acid molecules according to claim 1 under conditions in vitro, in vivo or in situ, such that the IL-6 antibody or antibody fragment is expressed in detectable or recoverable amounts.

4. A composition, comprising the nucleic acid molecules according to claim 1 and a carrier or diluent.

5. A method for producing an IL-6 antibody or antigen-binding fragment comprising transforming a host cell capable of expressing said antibody or antigen-binding fragment therof in recoverable amounts with the nucleic acid molecules according to claim 1 and expressing said antibody or antigen-binding fragment therof from said host cell.

6. The method according to claim 5 wherein said host cell is a mammalian cell, a plant cell or a yeast cell.

7. A vector, comprising the nucleic acid molecule according to claim 1.

8. The vector according to claim 7, wherein said vector comprises at least one promoter selected from the group consisting of a late or early SV490 promoter, a CMV promoter, an HSV tk promoter, a pgk (phosphoglycerate kinase) promoter, a human immunoglobulin promoter and an F-1 alpha promoter.

9. The vector according to claim 7, wherein said vector comprises at least one gene or portion thereof selected from the group consisting of methotrexate (MTX), green fluorescent prototein (GFP), dihydrofolate reductase (DHFR), neomycin (G418), and glutamine synthestase (GS).