Human tumor necrosis factor receptor-like proteins TR11, TR11SV1 and TR11SV2

• US 6,503,184 B1
• Filed: 02/23/2000
• Issued: 01/07/2003
• Est. Priority Date: 10/21/1997
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GSK plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc)
• Inventors: Ni, Jian, Ruben, Steven M.
• Primary Examiner(s): HUFF, SHEELA JITENDRA
• Application Number:
  US09/512,363
• Time in Patent Office: 1,049 Days
• Field of Search: 514/2, 514/12, 424/278.1, 424/283.1, 424/178.1, 424/184.1, 424/185.1, 424/192.1, 424/198.1
• US Class Current: 424/134.1
• 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: 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]

Abstract

The present invention relates to novel members of the Tumor Necrosis Factor family of receptors. The invention provides isolated nucleic acid molecules encoding human TR11, TR11SV1, and TR11SV2 receptors. TR11, TR11SV1, and TR11SV2 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 TR11, TR11SV1, and TR11SV2 receptor activity. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of TR11, TR11SV1, and TR11SV2 receptors. Further provided are therapeutic methods for treating disease states related to aberrant proliferation and differentiation of cells which express the TR11, TR11SV1, and TR11SV2 receptors.

Claims

1. A method of inhibiting binding of Endokine-alpha to endogenous Endokine-alpha receptors in a mammal comprising administering to said mammal an effective amount of TR11 polypeptide selected from the group consisting of:

(a) a polypeptide whose amino acid sequence comprises amino acid residues −

25-137 of SEQ ID NO;

2;

(b) a polypeptide whose amino acid sequence comprises amino acid residues 1-137 of SEQ ID NO;

2;

(c) a polypeptide whose amino acid sequence comprises amino acid residues 1-114 SEQ ID NO;

2; and

(d) a polypeptide fragment of the polypeptide of SEQ ID NO;

2, wherein said fragment binds endokine-alpha;

in a pharmaceutically acceptable carrier.

2. The method of claim 1 wherein the mammal is a human.

3. The method of claim 1 wherein the TR11 polypeptide is fused to a heterologous polypeptide.

4. The method of claim 3 wherein the heterologous polypeptide is an immunoglobulin constant domain.

5. The method of claim 4 wherein the immunoglobulin constant domain is an IgG1 constant domain.

6. The method of claim 4 wherein the immunoglobulin constant domain is an IgG3 constant domain.

7. The method of claim 3 wherein the heterologous polypeptide is human albumin.

8. The method of claim 2 wherein the pharmaceutically acceptable carrier is water.

9. The method of claim 1 wherein the pharmaceutically acceptable carrier is saline.

10. The method of claim 1 wherein the pharmaceutically acceptable carrier is Ringer'"'"'s solution.

11. The method of claim 1 wherein the pharmaceutically acceptable carrier in dextrose solution.

12. The method of claim 1 wherein the pharmaceutically acceptable carrier is ethyl oleate.

13. The method of claim 1 wherein the pharmaceutically acceptable carrier is a liposome.

14. The method of claim 1 wherein the TR11 polypeptide inhibits T cell migration across endothelial cells.

15. A method of inhibition binding of Endokine-alpha to endogenous Endokine-alpha receptors in a mammal comprising administering to said mammal an effective amount of TR11 polypeptide selected from the group consisting of:

(a) a polypeptide whose amino acid sequence comprises the signal sequence and the extracellular domain of the polypeptide encoded by the cDNA contained in ATCC Deposit Number 209341;

(b) a polypeptide whose amino acid sequence comprises the extracellular domain of the polypeptide encoded by the cDNA contained in ATCC Deposit Number 209341; and

(c) a polypeptide fragment of the polypeptide encoded by the cDNA contained in ATCC Deposit Number 209341;

wherein said fragment binds endokine-alpha;

in a pharmaceutically acceptable carrier.

16. The method of claim 15 wherein the mammal is a human.

17. The method of claim 15 wherein the TR11 polypeptide is fused to a heterologous polypeptide.

18. The method of claim 17 wherein the heterologous polypeptide is an immunoglobulin constant domain.

19. The method of claim 18 wherein the immunoglobulin constant domain is an IgG1 constant domain.

20. The method of claim 18 wherein the immunoglobulin constant domain is an IgG3 constant domain.

21. The method of claim 17 wherein the heterologous polypeptide is human albumin.

22. The method of claim 15 wherein the pharmaceutically acceptable carrier is water.

23. The method of claim 15 wherein the pharmaceutically acceptable carrier is saline.

24. The method of claim 15 wherein the pharmaceutically acceptable carrier is Ringer'"'"'s solution.

25. The method of claim 15 wherein the pharmaceutically acceptable carrier is dextrose solution.

26. The method of claim 15 wherein the pharmaceutically acceptable carrier is ethyl oleate.

27. The method of claim 15 wherein the pharmaceutically acceptable carrier is liposome.

28. The method of claim 15 wherein the TR11 polypeptide inhibits T cell migration across endothelial cells.