Death domain containing receptor 5 antibodies

• US 6,872,568 B1
• Filed: 05/04/2000
• Issued: 03/29/2005
• Est. Priority Date: 03/17/1997
• Status: Expired due to Term

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Gentz, Reiner L., Yu, Guo-Liang, Ni, Jian, Rosen, Craig A.
• Primary Examiner(s): Caputa, Anthony C.
• Assistant Examiner(s): Kaufman, Claire M.
• Application Number:
  US09/565,009
• Time in Patent Office: 1,790 Days
• Field of Search: 530/350, 530/387.1, 530/388.1, 530/388.2, 530/388.8, 530/389.1, 530/389.7, 530/391.3, 530/388.22, 530/391.1, 530/300, 435/326, 435/7.1, 435/330, 435/331, 435/344, 536/23.5
• US Class Current: 435/326
• 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 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 14/7151 for tumor necrosis factor [TNF], for lymphotoxin [LT]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• 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 Death Domain Containing Receptor-5 (DR5) proteins which are members of the tumor necrosis factor (TNF) receptor family, and have now been shown to bind TRAIL. In particular, isolated nucleic acid molecules are provided encoding the human DR5 proteins. DR5 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 antagonists and antagonists of DR5 activity.

Claims

1. An isolated antibody or fragment thereof that specifically binds to a protein consisting of amino acid residues 1 to 133 of SEQ ID NO:

2.

2. The antibody or fragment thereof of claim 1 wherein said protein bound by said antibody or fragment thereof is glycosylated.

3. The antibody or fragment thereof of claim 1 which is a polyclonal antibody.

4. The antibody or fragment thereof of claim 1 which is selected from the group consisting of:

(a) an F(ab′

)₂ fragment; and

(b) an Fab fragment.

5. The antibody or fragment thereof of claim 1 which is labeled.

6. The antibody or fragment thereof of claim 5 wherein the label is selected from the group consisting of:

(a) an enzyme;

(b) a fluorescent label; and

(c) a radioisotope.

7. The antibody or fragment thereof of claim 1 wherein said antibody or fragment thereof is an agonist of the protein of SEQ ID NO:

2.

8. The antibody or fragment thereof of claim 1 wherein said antibody or fragment thereof is an antagonist of the protein of SEQ ID NO:

2.

9. The antibody or fragment thereof of claim 1 wherein said antibody or fragment thereof specifically binds to said protein in a Western blot.

10. The antibody or fragment thereof of claim 1 wherein said antibody or fragment thereof specifically binds to said protein in an ELISA.

11. An isolated cell that produces the antibody or fragment thereof of claim 1.

12. A hybridoma that produces the antibody or fragment thereof of claim 1.

13. A method of detecting DR5 protein in a biological sample comprising:

(a) contacting the biological sample with the antibody or fragment thereof of claim 1 under conditions wherein said antibody or fragment thereof binds to and forms a complex with a DR5 protein; and

(b) detecting said complex, thereby detecting DR5 protein in the biological sample.

14. The method of claim 13 wherein the antibody or fragment thereof is a polyclonal antibody.

15. An isolated monoclonal antibody or fragment thereof that specifically binds to a protein consisting of amino acid residues 1 to 133 of SEQ ID NO:

2.

16. The antibody or fragment thereof of claim 15 wherein said protein bound by said antibody or fragment thereof is glycosylated.

17. The antibody or fragment thereof of claim 15 which is selected from the group consisting of:

(a) an F(ab′

)₂ fragment; and

(b) an Fab fragment.

18. The antibody or fragment thereof of claim 15 which is labeled.

19. The antibody or fragment thereof of claim 18 wherein the label is selected from the group consisting of:

(a) an enzyme;

(b) a fluorescent label; and

(c) a radioisotope.

20. The antibody or fragment thereof of claim 15 wherein said antibody or fragment thereof is an agonist of the protein of SEQ ID NO:

2.

21. The antibody or fragment thereof of claim 15 wherein said antibody or fragment thereof is an antagonist of the protein of SEQ ID NO:

2.

22. The antibody or fragment thereof of claim 15 wherein said antibody or fragment thereof specifically binds to said protein in a Western blot.

23. The antibody or fragment thereof of claim 15 wherein said antibody or fragment thereof specifically binds to said protein in an ELISA.

24. An isolated cell that produces the antibody or fragment thereof of claim 15.

25. A hybridoma that produces the antibody or fragment thereof of claim 15.

26. A method of detecting DR5 protein in a biological sample comprising:

(a) contacting the biological sample with the antibody or fragment thereof of claim 15 under conditions wherein said antibody fragment thereof binds to and forms a complex with a DR5 protein; and

(b) detecting said complex, thereby detecting DR5 protein in the biological sample.

27. An isolated antibody or fragment thereof that specifically binds to the extracellular domain of the protein encoded by the cDNA contained in ATCC Deposit No. 97920.

28. The antibody or fragment thereof of claim 27 wherein said protein bound by said antibody or fragment thereof is glycosylated.

29. The antibody or fragment thereof of claim 27 which is a polyclonal antibody.

30. The antibody or fragment thereof of claim 27 which is selected from the group consisting of:

(a) an F(ab′

)₂ fragment; and

(b) an Fab fragment.

31. The antibody or fragment thereof of claim 27 which is labeled.

32. The antibody or fragment thereof of claim 31 wherein the label is selected from the group consisting of:

(a) an enzyme;

(b) a fluorescent label; and

(c) a radioisotope.

33. The antibody or fragment thereof of claim 27 wherein said antibody or fragment thereof is an agonist of the protein encoded by the cDNA contained in ATCC Deposit No. 97920.

34. The antibody or fragment thereof of claim 27 wherein said antibody or fragment thereof is an antagonist of the protein encoded by the cDNA contained in ATCC Deposit No. 97920.

35. The antibody or fragment thereof of claim 27 wherein said antibody or fragment thereof specifically binds to said protein in a Western blot.

36. The antibody or fragment thereof of claim 27 wherein said antibody or fragment thereof specifically binds to said protein in an ELISA.

37. An isolated cell that produces the antibody or fragment thereof of claim 27.

38. A hybridoma that produces the antibody or fragment thereof of claim 27.

39. A method of detecting DR5 protein in a biological sample comprising:

(a) contacting the biological sample with the antibody or fragment thereof of claim 27 under conditions wherein said antibody or fragment thereof binds to and forms a complex with a DR5 protein; and

(b) detecting said complex, thereby detecting DR5 protein in the biological sample.

40. The method of claim 39 wherein the antibody or fragment thereof is a polyclonal antibody.

41. An isolated monoclonal antibody or fragment thereof that specifically binds to the extracellular domain of the protein encoded by the cDNA contained in ATCC Deposit No. 97920.

42. The antibody or fragment thereof of claim 41 wherein said protein bound by said antibody or fragment thereof is glycosylated.

43. The antibody or fragment thereof of claim 41 which is selected from the group consisting of:

(a) an F(ab′

)₂ fragment; and

(b) a Fab fragment.

44. The antibody or fragment thereof of claim 41 which is labeled.

45. The antibody or fragment thereof of claim 44 wherein the label is selected from the group consisting of:

(a) an enzyme;

(b) a fluorescent label; and

(c) a radioisotope.

46. The antibody or fragment thereof of claim 41 wherein said antibody or fragment thereof is an agonist of the protein encoded by the cDNA contained in ATCC Deposit No. 97920.

47. The antibody or fragment thereof of claim 41 wherein said antibody or fragment thereof is an antagonist of the protein encoded by the cDNA contained in ATCC Deposit No. 97920.

48. The antibody or fragment thereof of claim 41 wherein said antibody or fragment thereof specifically binds to said protein in a Western blot.

49. The antibody or fragment thereof of claim 41 wherein said antibody or fragment thereof specifically binds to said protein in an ELISA.

50. An isolated cell that produces the antibody or fragment thereof of claim 41.

51. A hybridoma that produces the antibody or fragment thereof of claim 41.

52. A method of detecting DR5 protein in a biological sample comprising:

(a) contacting the biological sample with the antibody or fragment thereof of claim 41 under conditions wherein said antibody or fragment thereof binds to and forms a complex with a DR5 protein; and

(b) detecting said complex thereby detecting DR5 protein in the biological sample.