TNFα-neutralizing antibodies

• US 7,431,927 B2
• Filed: 03/24/2005
• Issued: 10/07/2008
• Est. Priority Date: 03/24/2005
• Status: Active Grant

• Current Assignee: Epitomics Incorporated (Abcam Plc)
• Original Assignee: Epitomics Incorporated (Abcam Plc)
• Inventors: Hendricks, Kristin Beth, Couto, Fernando Jose Rebelo Do, Wallace, Stacey Ellen
• Primary Examiner(s): Kemmerer; Elizabeth C.
• Assistant Examiner(s): Emch; Gregory S
• Application Number:
  US11/090,105
• Publication Number:
  US 20060216293A1
• Time in Patent Office: 1,293 Days
• Field of Search: None
• US Class Current: 424/145.1
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• 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 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 9/00 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 16/241 : Tumor Necrosis Factors
• CPC Class Codes: C07K 2317/20 : characterized by taxonomic origin

Abstract

The invention provides monoclonal antibodies that neutralize TNFα activity. The monoclonal antibodies may be rabbit monoclonal antibodies or monoclonal antibodies having CDR regions derived from those rabbit monoclonal antibodies. In certain embodiments, the monoclonal antibodies may be humanized. Methods of using the subject antibodies to inhibit TNFα activity, methods of treatment using those antibodies and kits containing the same are also provided. The invention finds use in a variety of research and medical applications.

Claims

1. A monoclonal antibody comprising:

a) a variable domain comprising;

i. a heavy cahin varable domain comprising a CDR1 region identical to amino acid residues 30-34 of SEQ ID NO;

31, a CDR2 region identical to amino acid residues 49-64 of SEQ ID NO;

31 and a CDR3 region identical to amino acid 97-109 of SEQ ID NO;

31; and

ii. a light chain variable domain comprising a CDR1 region identical to amino acid residues 23-33 of SEQ ID NO;

75, a CDR2 region identical to amino acid residues 49-55 of SEQ ID NO;

75 and a CDR3 region identical to amino acid residues 88-99 of SEQ ID NO;

75;

or

b) a variant of said variable domain of part a) that is otherwise identical to said variable domain except for up to 4 amino acid substitutions in said CDR regions;

wherein said monoclonal antibody neutralizes TNFα

activity.

2. The monoclonal antibody of claim 1, wherein said antibody binds TNFα

with a K_D of 10<sup>−

7</sup> M or less.

3. The monoclonal antibody of claim 1, wherein said antibody has an IC₅₀ of 1×

10<sup>−

7</sup> M or less.

5. The monoclonal antibody of claim 1, wherein said variant is otherwise identical said variable domain of part a) of said monoclonal antibody except for 1, 2 or 3 amino acid substitution in said CDR regions.

6. The monoclonal antibody of claim 1, wherein said antibody is a humanized antibody.

7. The monoclonal antibody of claim 1, wherein said antibody is a monovalent antibody.

8. The monoclonal antibody of claim 1, wherein said antibody is a bivalent antibody.

9. The monoclonal antibody of claim 1, wherein said antibody is a single chain antibody.

10. The monoclonal antibody of claim 1, wherein said antibody is a Fab, Fv, scFv, or Fd fragment.

11. The monoclonal antibody of claim 1, wherein said antibody is a chimeric antibody.

12. The monoclonal antibody of claim 1, wherein said antibody is a fusion protein.

13. The monoclonal antibody of claim 1, wherein said antibody is detectably labeled.

14. The monoclonal antibody of claim 1, wherein the antibody is conjugated to another moiety.

15. A composition comprising:

a) the antibody of claim 1; and

b) a pharmaceutically-acceptable excipient.

4. A monoclonal antibody comprising:

a heavy chain variable domain comprising a CDR1 region identical to amino acid residues 30-34 of SEQ ID NO;

31, a CDR2 region identical to amino acid residues 49-55 of SEQ ID NO;

75 and CDR3 region identical to amino acid residues 97-109 of SEQ ID NO;

31; and

a light chain varable domain comprising a CDR1 region identical to amino acid residues 23-33 of SEQ ID NO;

75, CDR2 region identical to amino acid resifues 49-55 SEQ ID NO;

75 and a CDR3 region identical to amino acid residues 88-99 of SEQ ID NO;

75;

wherein said monoclonal antibody neutralizes TNFα

activity.