Use of an antibody that binds human tumor necrosis factor receptor-like 2

• US 7,824,675 B2
• Filed: 09/30/2008
• Issued: 11/02/2010
• Est. Priority Date: 04/27/1995
• 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:
  US12/241,203
• Publication Number:
  US 20090092608A1
• Time in Patent Office: 763 Days
• Field of Search: None
• US Class Current: 424/130.1
• 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 expression of TR2 receptors. Further provided are therapeutic methods for treating disease states related to aberrant proliferation and differentiation of cells which express the TR2 receptors.

Claims

1. A method for inhibiting T-cell proliferation in an individual comprising administering to said individual a therapeutically effective amount of an antibody or fragment thereof which specifically binds to a polypeptide consisting of amino acids −

38 to 162 of SEQ ID NO;

26, wherein said antibody or fragment thereof inhibits T-cell proliferation.

2. The method of claim 1, wherein said antibody or fragment thereof is administered in combination with a pharmaceutically acceptable carrier.

3. The method of claim 1, wherein said antibody or fragment thereof is administered in conjunction with a therapeutically effective amount of another therapeutic compound.

4. The method of claim 1, wherein said antibody or fragment thereof is a monoclonal antibody.

5. The method of claim 1, wherein said antibody or fragment thereof is selected from the group consisting of:

(a) a polyclonal antibody;

(b) a whole immunoglobulin;

(c) a chimeric antibody;

(d) a human antibody;

(e) a humanized antibody;

(f) a Fab fragment;

(g) a Fab′

fragment;

(h) a F(ab′

)₂ fragment;

(i) a Fv;

(j) a disulfide linked Fv; and

(k) a scFv fragment.

6. The method of claim 1, wherein said individual has a T-cell mediated autoimmune disease.

7. The method of claim 6, wherein said T-cell mediated autoimmune disease is selected from the group consisting of:

(a) multiple sclerosis;

(b) ulcerative colitis; and

(c) rheumatoid arthritis.

8. The method of claim 1, wherein said antibody or fragment thereof is labeled.

9. The method of claim 8, wherein said label is selected from the group consisting of:

(a) an enzyme;

(b) a fluorescent label; and

(c) a radioisotope.

10. A method for inhibiting T-cell proliferation in an individual comprising administering to said individual a therapeutically effective amount of an antibody or fragment thereof which specifically binds to a polypeptide consisting of amino acids 1 to 162 of SEQ ID NO:

26, wherein said antibody or fragment thereof inhibits T-cell proliferation.

11. The method of claim 10, wherein said antibody or fragment thereof is administered in combination with a pharmaceutically acceptable carrier.

12. The method of claim 10, wherein said antibody or fragment thereof is administered in conjunction with a therapeutically effective amount of another therapeutic compound.

13. The method of claim 10, wherein said antibody or fragment thereof is a monoclonal antibody.

14. The method of claim 10, wherein said antibody or fragment thereof is a polyclonal antibody.

15. The method of claim 10, wherein said antibody or fragment thereof is selected from the group consisting of:

(a) a whole immunoglobulin;

(b) a chimeric antibody;

(c) a human antibody;

(d) a humanized antibody;

(e) a Fab fragment;

(f) a Fab′

fragment;

(g) a F(ab′

)₂ fragment;

(h) a Fv;

(i) a disulfide linked Fv; and

(j) a scFv fragment.

16. The method of claim 10, wherein said individual has a T-cell mediated autoimmune disease.

17. The method of claim 16, wherein said T-cell mediated autoimmune disease is selected from the group consisting of:

(a) multiple sclerosis;

(b) ulcerative colitis; and

(c) rheumatoid arthritis.

18. The method of claim 10, wherein said antibody or fragment thereof is labeled.

19. The method of claim 18, wherein said label is selected from the group consisting of:

(a) an enzyme;

(b) a fluorescent label; and

(c) a radioisotope.