Tumor necrosis factor-gamma

• US 7,597,886 B2
• Filed: 07/06/2001
• Issued: 10/06/2009
• Est. Priority Date: 11/07/1994
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Zhang, Jun, Yu, Guo-Liang, Ni, Jian, Rosen, Craig A.
• Primary Examiner(s): Romeo; David S
• Application Number:
  US09/899,059
• Publication Number:
  US 20020150534A1
• Time in Patent Office: 3,014 Days
• Field of Search: None
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• 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 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• 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 an inflammatory disease or disorder comprising administering to an animal in which such treatment is desired an antibody or fragment thereof that specifically binds and antagonizes a TNF-gamma-beta protein comprising SEQ ID NO:

20 in an amount effective to treat or ameliorate an inflammatory disease or disorder,

wherein the inflammatory disease or disorder is selected from the group consisting of inflammatory bowel disease and Crohn'"'"'s disease.

2. The method of claim 1 wherein the animal is 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 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 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 inflammatory disease or disorder is inflammatory bowel disease.

8. A method of treating inflammation comprising administering to an animal in which such treatment is desired an antibody or fragment thereof that specifically binds and antagonizes a TNF-gamma-beta protein comprising SEQ ID NO:

20 in an amount effective to treat or ameliorate an inflammation associated with tissue-specific inflammatory disorders,

wherein the tissue-specific inflammatory disorder is colitis.

9. The method of claim 8 wherein the animal is a human.

10. The method of claim 8 wherein the antibody 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.

11. The method of claim 10 wherein the antibody or fragment thereof is a monoclonal antibody.

12. The method of claim 10 wherein the antibody or fragment thereof is a human antibody.

13. The method of claim 10 wherein the antibody or fragment thereof is a humanized antibody.

14. A method of treating an autoimmune disease or disorder comprising administering to an animal in which such treatment is desired an antibody or fragment thereof that specifically binds and antagonizes a TNF-gamma-beta protein comprising SEQ ID NO:

20 in an amount effective to treat or ameliorate an inflammation associated with Crohn'"'"'s disease.