Tumor Necrosis Factor-Gamma

• US 20110003399A1
• Filed: 09/10/2010
• Published: 01/06/2011
• Est. Priority Date: 11/07/1994
• Status: Active Grant

• Current Assignee: Human Genome Sciences Incorporated (GSK plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc)
• Inventors: Yu, Guo-Liang, Ni, Jian, Rosen, Craig A., Zhang, Jun
• Granted Patent: US 8,093,363 B2
• Time in Patent Office: Days
• US Class Current: 436/501
• CPC Class Codes: A61K 51/08 Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins
• 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: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 930/144 Tumor necrosis factor

Abstract

Human TNF-gamma-alpha and TNF-gamma-beta polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing such polypeptides to inhibit cellular growth, for example in a tumor or cancer, for facilitating wound-healing, to provide resistance against infection, induce inflammatory activities, and stimulating the growth of certain cell types to treat diseases, for example restenosis. Also disclosed are diagnostic methods for detecting a mutation in the TNF-gamma-alpha and TNF-gamma-beta nucleic acid sequences or overexpression of the TNF-gamma-alpha and/or TNF-gamma-beta polypeptides. Antagonists against such polypeptides and their use as a therapeutic to treat cachexia, septic shock, cerebral malaria, inflammation, arthritis and graft-rejection are also disclosed.

Claims

1. An isolated antibody or fragment thereof that specifically binds to a protein selected from the group consisting of:

(a) a protein whose amino acid sequence consists of amino acid residues −

27 to 147 of SEQ ID NO;

2;

(b) a protein whose amino acid sequence consists of amino acid residues −

26 to 147 of SEQ ID NO;

2;

(c) a protein whose amino acid sequence consists of amino acid residues 1 to 147 of SEQ ID NO;

2;

(d) a protein whose amino acid sequence consists of amino acid residues 25 to 147 of SEQ ID NO;

2;

(e) a protein whose amino acid sequence consists of a portion of SEQ ID NO;

2, wherein said portion is at least 30 contiguous amino acid residues in length;

(f) a protein whose amino acid sequence consists of a portion of SEQ ID NO;

2, wherein said portion is at least 50 contiguous amino acid residues in length;

(g) a protein whose sequence consists of the amino acid sequence of the full-length polypeptide encoded by the cDNA contained in ATCC™

Deposit Number 75927;

(h) a protein whose sequence consists of the amino acid sequence of the full-length polypeptide, excluding the N-terminal methionine residue, encoded by the cDNA contained in ATCC™

Deposit Number 75927;

(i) a protein whose sequence consists of the amino acid sequence of the extracellular domain of the polypeptide encoded by the cDNA contained in ATCC™

Deposit Number 75927; and

(j) a protein whose sequence consists of the amino acid sequence of the mature form of the polypeptide encoded by the cDNA contained in ATCC™

Deposit Number 75927.

2. The antibody or fragment thereof of claim 1 that specifically binds protein (a).

3. The antibody or fragment thereof of claim 1 that specifically binds protein (b).

4. The antibody or fragment thereof of claim 1 that specifically binds protein (c).

5. The antibody or fragment thereof of claim 1 wherein said antibody or fragment thereof is monoclonal.

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

7. The antibody or fragment thereof of claim 1 wherein said antibody or fragment thereof is human.

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

(a) a chimeric antibody or fragment thereof;

(b) a humanized antibody or fragment thereof;

(c) a single chain antibody; and

(d) a Fab fragment.

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

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

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

12. A method of detecting tumor necrosis factor-gamma protein in a biological sample comprising:

(a) contacting the biological sample with the antibody or fragment thereof of claim 1; and

(b) detecting the tumor necrosis factor-gamma protein in the biological sample.

13. An isolated antibody or fragment thereof that specifically binds a tumor necrosis factor-gamma protein purified from a cell culture wherein said tumor necrosis factor-gamma protein is encoded by a polynucleotide encoding amino acids −

27 to 147 of SEQ ID NO;

2.

14. The antibody or fragment thereof of claim 13 wherein said antibody or fragment thereof is monoclonal.

15. The antibody or fragment thereof of claim 13 wherein said antibody or fragment thereof is polyclonal.

16. The antibody or fragment thereof of claim 13 wherein said antibody or fragment thereof is human.

17. The antibody or fragment thereof of claim 13 which is selected from the group consisting of:

(a) a chimeric antibody or fragment thereof;

(b) a humanized antibody or fragment thereof;

(c) a single chain antibody; and

(d) a Fab fragment.

18. The antibody or fragment thereof of claim 13 wherein said antibody or fragment thereof specifically binds to said protein in a Western blot or an ELISA.

19. The antibody or fragment thereof of claim 13 wherein the amino acid sequence of said tumor necrosis factor-gamma protein consists of amino acid residues −

26 to 147 of SEQ ID NO;

2.

20. The antibody or fragment thereof of claim 13 wherein the amino acid sequence of said tumor necrosis factor-gamma protein consists of amino acid residues 1 to 147 of SEQ ID NO:

2.