Antibodies directed to tumor necrosis factor

• US 7,285,269 B2
• Filed: 12/02/2003
• Issued: 10/23/2007
• Est. Priority Date: 12/02/2002
• Status: Active Grant

• Current Assignee: Amgen Fremont Inc. (Amgen Inc.)
• Original Assignee: Amgen Fremont Inc. (Amgen Inc.)
• Inventors: Haak-Frendscho, Mary, Green, Larry, Foord, Orit, Feng, Xiao, Manchulenko, Kathy, Liang, Meina, Rathanaswami, Palaniswami, Senaldi, Giorgio, Klakamp, Scott, Kang, Jaspal S., Faggioni, Raffaella, Babcook, John S., Su, Qiaojuan Jane, Pigott, Craig, Lee, Yen-Wah
• Primary Examiner(s): Gambel; Phillip
• Assistant Examiner(s): SKELDING, ZACHARY S
• Application Number:
  US10/727,155
• Publication Number:
  US 20050049402A1
• Time in Patent Office: 1,421 Days
• Field of Search: None
• US Class Current: 424/142.1
• 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 13/12 of the kidneys
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• 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 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• 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

Antibodies directed to the antigen TNFα and uses of such antibodies. In particular, fully human monoclonal antibodies directed to the antigen TNFα. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR'"'"'s), specifically from FR1 through FR4 or CDR1 through CDR3. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies.

Claims

1. A fully human monoclonal antibody, or binding fragment thereof, comprising a light chain comprising the amino acid sequence of SEQ ID NO:

72 and a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO;

74 and wherein said antibody or said binding fragment thereof binds to human Tumor Necrosis Factor-α

.

2. A composition comprising the antibody;

or binding fragment of claim 1 and a pharmaceutically acceptable carrier.

3. A conjugate comprising the antibody or binding fragment of claim 1 and a therapeutic agent.

4. The conjugate of claim 3, wherein the therapeutic agent is a toxin.

5. The conjugate of claim 3, wherein the therapeutic agent is a radioisotope.

20. The fully human monoclonal antibody or binding fragment of claim 1, wherein said binding fragment comprises a Fab, Fab′

, F(ab′

)₂, or Fv fragment.

21. The fully human monoclonal antibody or binding fragment of claim 1, wherein said antibody has an IgG2 isotype.

6. A fully human monoclonal antibody, or binding fragment thereof, comprising a light chain comprising the amino acid sequence of SEQ ID NO:

72 and a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO;

70 and wherein said antibody or said binding fragment thereof binds to human Tumor Necrosis Factor-α

.

7. A composition comprising the antibody or binding fragment of claim 6, and a pharmaceutically acceptable carrier.

15. A conjugate comprising the antibody or binding fragment of claim 6 and a therapeutic agent.

16. The conjugate of claim 15, wherein the therapeutic agent comprises a toxin.

17. The conjugate of claim 15, wherein the therapeutic agent comprises a radioistope.

18. The fully human monoclonal antibody or binding fragment of claim 6, wherein said binding fragment comprises a Fab, Fab′

, F(ab′

)₂, or Fv fragment.

19. The fully human monoclonal antibody or binding fragment of claim 6, wherein said antibody has an IgG2 isotype.

8. A fully human monoclonal antibody, or bindivg fragment thereof comprising a light chain comprising the amino acid sequence of SEQ ID NO:

50 and a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO;

52 and wherein said antibody or said binding fragment thereof binds to human Tumor Necrosis Factor-α

.

9. A composition comprising the antibody or binding fragment of claim 8, and a pharmaceutically acceptable carrier.

10. A conjugate comprising the antibody or binding fragment of claim 8, and a therapeutic agent.

11. The conjugate of claim 10, wherein the therapeutic agent is a toxin.

12. The conjugate of claim 10, wherein the therapeutic agent is a radioisotope.

22. The fully human monoclonal antibody or binding fragment of claim 8, wherein said binding fragment comprises a Fab, Fab′

, F(ab′

)₂, or Fv fragment.

23. The fully human monoclonal antibody or binding fragment of claim 8, wherein said antibody has an IgG2 isotype.

35. The conjugate according to claim 3, 10, 15 or 32, admixed with a pharmaceutically acceptable carrier.

13. A fully human monoclonal antibody, or binding fragment thereof, comprising a light chain comprising the amino acid sequence of SEQ ID NO:

54 and a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO;

56 and wherein, said antibody or said binding fragment thereof binds to human Tumor Necrosis Factor-α

.

14. A composition comprising the antibody or binding fragment of claim 13, and a pharmaceutically acceptable carrier.

24. The fully human monoclonal antibody or binding fragment of claim 13, wherein said binding fragment comprises a Fab, Fab′

, F(ab′

)₂, or Fv fragment.

25. The fully human monoclonal antibody or binding fragment of claim 13 wherein said antibody has an IgG2 isotype.

26. A fully human monoclonal antibody, or binding fragment thereof, that binds to Tumor Necrosis Factor-α

, wherein the antibody, or binding fragment thereof, comprises;

a heavy chain complementarity determining region 1 (CDR1) comprising the amino acid sequence of “

Ser Tyr Asp Met His”

(SEQ ID NO;

     321);

a heavy chain complementarity determining region 2 (CDR2) comprising the amino acid sequence of “

Val Ile Trp Ser Asp Gly Ser Ile Lys Tyr Tyr Ala Asp Ser Val Lys Gly”

(SEQ ID NO;

     322);

a heavy chain complementarity determining region 3 (CDR3) the amino acid sequence of “

Glu Val Glu Ser Ala Met Gly Gly Phe Tyr Tyr Asn Gly Met Asp Val”

(SEQ ID NO;

     323);

a light chain complementarity determining region 1 (CDR1) comprising the amino acid sequence of “

Arg Ala Ser Gln Gly Ile Arg Ile Asp Len Gly”

(SEQ ID NO;

     324);

a light chain complementarity determining region 2 (CDR2) comprising the amino acid sequence of “

Ala Ala Ser Thr Leu Gln Ser”

(SEQ ID NO;

     325); and

a light chain complementarity determining region 3 (CDR3) the amino acid sequence of “

Leu Gin His Lys Ser Tyr Pro Leu Thr”

(SEQ ID NO;

     326).

27. The antibody, or binding fragment thereof of claim 26, wherein the antibody, or binding fragment thereof, comprises a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:

70 and a light chain polypeptide comprising the amino acid sequence of SEQ ID NO;

72.

28. The antibody, or binding fragment thereof, of claim 26, wherein the antibody, or binding fragment thereof, comprises a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:

74 and a light chain polypeptide comprising the amino acid sequence of SEQ ID NO;

72.

29. The fully human monoclonal antibody or binding fragment of claim 26, wherein said binding fragment comprises a Fab, Fab′

, F(ab′

)₂, or Fv fragment.

30. The fully human monoclonal antibody or binding fragment of claim 26, wherein said antibody has an IgG2 isotype.

31. A composition comprising the antibody or binding fragment of claim 30, and a pharmaceutically acceptable carrier.

32. A conjugate comprising the antibody or binding fragment of claim 30, and a therapeutic agent.

33. The conjugate of claim 32, wherein the therapeutic agent is a toxin.

34. The conjugate of claim 32, wherein the therapeutic agent is a radioisotope.