Tumor Necrosis Factor-Gamma

• US 20070297977A1
• Filed: 08/10/2007
• Published: 12/27/2007
• Est. Priority Date: 11/07/1994
• Status: Active Grant

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Yu, Guo-Liang, Ni, Jian, Zhang, Jun, Rosen, Craig
• Granted Patent: US 7,820,798 B2
• Time in Patent Office: Days
• US Class Current: 424/1.49
• 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. A method of treating or preventing a disease, disorder or symptom selected from the group consisting of:

(a) an inflammatory disease or disorder;

(b) inflammation;

(c) an autoimmune disease or disorder; and

(d) graft versus host disease (GVHD);

comprising administering to an animal in which such treatment or prevention is desired an antibody or fragment thereof that specifically binds TNF-gamma-beta protein in an amount effective to treat or prevent the disease, disorder or symptom.

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

3. The method of claim 1 wherein the antibody or fragment thereof specifically binds a TNF-gamma-beta protein selected from the group consisting of:

(a) a protein whose sequence consists of amino acid residues 1 to 251 of SEQ ID NO;

20;

(b) a protein whose sequence consists of amino acid residues 62 to 251 of SEQ ID NO;

20;

(c) a protein whose sequence consists of amino acid residues 72 to 251 of SEQ ID NO;

20;

(d) a protein whose sequence consists of amino acid residues 101 to 251 of SEQ ID NO;

20;

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

Deposit Number 203055;

(f) 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 203055; and

(g) 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 203055.

4. The method of claim 3 wherein the antibody or fragment thereof is a monoclonal antibody.

5. The method of claim 3 wherein the antibody or fragment thereof is a human antibody.

6. The method of claim 3 wherein the antibody or fragment thereof is a humanized antibody.

7. The method of claim 3 wherein the disease, disorder or symptom is selected from the group consisting of:

(a) inflammatory bowel disease.

(b) encephalitis.

(c) atherosclerosis.

(d) psoriasis.

(e) systemic lupus erythematosus.

(f) arthritis.

(g) rheumatoid arthritis.

(h) multiple sclerosis.

(i) Crohn'"'"'s disease.

(j) autoimmune encephalitis.

8. A method of killing a cell of hematopoietic origin comprising contacting a TNF-gamma-beta protein with a cell of hematopoietic origin.

9. The method of claim 8, wherein said method comprises administering to an animal in which such killing of hematopoietic cells is desired, a TNF-gamma-beta protein in an amount effective to kill the cell.

10. The method of claim 9 wherein the animal is a human.

11. The method of claim 8 wherein the TNF-gamma beta protein is selected from the group consisting of:

(a) a protein whose sequence consists of amino acid residues 1 to 251 of SEQ ID NO;

20;

(b) a protein whose sequence consists of amino acid residues 62 to 251 of SEQ ID NO;

20;

(c) a protein whose sequence consists of amino acid residues 72 to 251 of SEQ ID NO;

20;

(d) a protein whose sequence consists of amino acid residues 101 to 251 of SEQ ID NO;

20;

(e) a protein whose sequence consists of a fragment of at least 30 contiguous amino acid residues of the polypeptide of SEQ ID NO;

20 that has TNF-gamma-beta functional activity.

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

Deposit Number 203055;

(g) 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 203055;

(h) 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 203055; and

(i) a protein whose sequence consists a fragment of at least 30 contiguous amino acid residues of the polypeptide encoded by the cDNA contained in ATCC™

Deposit Number 203055 that has TNF-gamma-beta functional activity.

12. The method of claim 11 wherein the TNF-gamma-beta protein is radiolabeled.

13. The method of claim 12 wherein the radiolabel is selected from the group consisting of:

(a) ¹²⁵I;

(b) ¹³¹I;

(c) ¹¹¹In;

(d) ⁹⁹Tc;

(e) ¹⁷⁷Lu;

(f) ⁹⁰Y;

(g) ¹⁶⁶Ho; and

(h) ¹⁵³Sm.

14. The method of claim 11 wherein the TNF-gamma-beta protein is conjugated to a cytotoxic agent or cytotoxic pro-drug.

15. The method of claim 11 wherein the cell of hematopoietic origin is a T cell.

16. The method of claim 15 wherein the T cell is cancerous.