Antibodies to human tumor necrosis factor receptor-like 2

• US 7,429,646 B1
• Filed: 03/22/2000
• Issued: 09/30/2008
• Est. Priority Date: 06/05/1995
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GSK plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc)
• Inventors: Gentz, Reiner L., Ni, Jian, Rosen, Craig A.
• Primary Examiner(s): Kemmerer; Elizabeth C.
• Application Number:
  US09/533,262
• Time in Patent Office: 3,114 Days
• Field of Search: 530/388.1, 530/388.23, 530/387.3, 530/351, 424/145.5, 424/192.1
• US Class Current: 530/388.22
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The present invention relates to novel members of the Tumor Necrosis Factor family of receptors. The invention provides isolated nucleic acid molecules encoding a human TR2 receptor and two splice variants thereof. TR2 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of TR2 receptor activity. Also provided are diagnostic methods for detecting disease states related to the aberrant states related to aberrant proliferation and differentiation of cells which express the TR2 receptors.

Claims

1. An isolated antibody which specifically binds to a polypeptide consisting of amino acids −

38 to 245 of SEQ ID NO;

26.

2. The isolated antibody of claim 1, wherein said antibody is a monoclonal antibody.

3. The isolated antibody of claim 1, wherein said antibody is a polyclonal antibody.

4. The isolated antibody of claim 1, wherein said antibody is a chimeric antibody.

5. The isolated antibody of claim 1, wherein said antibody is a humanized antibody.

6. The isolated antibody of claim 1, wherein said antibody is a single-chain Fv antibody.

7. The isolated antibody of claim 1, wherein said antibody is a Fab antibody.

8. A composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

12. The isolated antibody of claim 1, wherein said antibody is the product of an Fab expression library.

13. A method of producing the isolated antibody of claim 1, comprising:

(a) immunizing an animal with a polypeptide comprising amino acids −

38 to 245 of SEQ ID NO;

26; and

(b) recovering an antibody, which specifically binds, said polypeptide.

14. A hybridoma which produces the monoclonal antibody of claim 2.

15. A method of producing a monoclonal antibody which comprises:

(a) culturing the hybridoma of claim 14 under appropriate conditions; and

(b) isolating monoclonal antibody therefrom.

9. An isolated antibody which binds to a polypeptide consisting of amino acids −

38 to 162 of SEQ ID NO;

26.

10. The isolated antibody of claim 9 which binds to a polypeptide consisting of amino acids 1 to 162 of SEQ ID NO:

26.

11. A composition comprising the antibody of claim 9 and a pharmaceutically acceptable carrier.

16. An isolated antibody which specifically binds to a polypeptide consisting of amino acids −

38 to 162 of SEQ ID NO;

26.

17. The isolated antibody of claim 16, wherein said antibody is a monoclonal antibody.

18. The isolated antibody of claim 16, wherein said antibody is a polyclonal antibody.

19. The isolated antibody of claim 16, wherein said antibody is a chimeric antibody.

20. The isolated antibody of claim 16, wherein said antibody is a humanized antibody.

21. The isolated antibody of claim 16, wherein said antibody is a single-chain Fv antibody.

22. The isolated antibody of claim 16, wherein said antibody is an Fab antibody fragment.

23. The isolated antibody of claim 16, wherein said antibody is a product of an Fab expression library.

24. A composition comprising the antibody of claim 16 and a pharmaceutically acceptable carrier.

25. A method of producing the isolated antibody of claim 16, comprising:

(a) immunizing an animal with a polypeptide comprising amino acids −

38 to 162 of SEQ ID NO;

26; and

(b) recovering an antibody which specifically binds said polypeptide.

26. A hybridoma which produces the monoclonal antibody of claim 17.

27. A method of producing a monoclonal antibody which comprises:

(a) culturing the hybridoma of claim 26 under appropriate conditions; and

(b) isolating monoclonal antibody therefrom.

28. An isolated antibody which specifically binds to a polypeptide consisting of amino acids 1 to 162 of SEQ ID NO:

26.

29. The isolated antibody of claim 28, wherein said antibody is a monoclonal antibody.

30. The isolated antibody of claim 28, wherein said antibody is a polyclonal antibody.

31. The isolated antibody of claim 28, wherein said antibody is a chimeric antibody.

32. The isolated antibody of claim 28, wherein said antibody is a humanized antibody.

33. The isolated antibody of claim 28, wherein said antibody is a single-chain Fv antibody.

34. The isolated antibody of claim 28, wherein said antibody is an Fab antibody fragment.

35. The isolated antibody of claim 28, wherein said antibody is the product of an Fab expression library.

36. A composition comprising the antibody of claim 28 and a pharmaceutically acceptable carrier.

37. A method of producing the isolated antibody of claim 28, comprising:

(a) immunizing an animal with a polypeptide comprising amino acids 1 to 162 of SEQ ID NO;

26; and

(b) recovering an antibody, which specifically binds, said polypeptide.

38. A hybridoma which produces the monoclonal antibody of claim 29.

39. A method of producing a monoclonal antibody which comprises:

(a) culturing the hybridoma of claim 38 under appropriate conditions; and

(b) isolating monoclonal antibody therefrom.

40. An isolated antibody which binds to a polypeptide having the sequence of SEQ ID NO:

26.

41. An isolated antibody that immunospecifically binds a tumor necrosis factor receptor, wherein said receptor comprises a polypeptide having the sequence of SEQ ID NO:

26.