Methods of treatment using antibodies to Neutrokine-alpha

• US 20060198784A1
• Filed: 03/17/2006
• Published: 09/07/2006
• Est. Priority Date: 10/25/1996
• Status: Abandoned Application

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Yu, Guo-Liang, Ni, Jian, Rosen, Craig A., Ebner, Reinhard
• Application Number:
  US11/377,165
• Publication Number:
  US 20060198784A1
• Time in Patent Office: Days
• US Class Current: 424/1.49
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 14/715 for cytokines; for lymphokines; for interferons
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons
• CPC Class Codes: C07K 16/2875 against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 against NGF C07K16/22, against TNF C07K16/241
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2333/52 Assays involving cytokines
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 2800/245 : Transplantation related diseases, e.g. graft versus host disease
• CPC Class Codes: G01N 33/564 : for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/6863 : Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• 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

Abstract

The present invention relates to a novel Neutrokine-alpha, and a splice variant thereof designated Neutrokine-alphaSV, polynucleotides and polypeptides which are members of the TNF family. In particular, isolated nucleic acid molecules are provided encoding the human Neutrokine-alpha and/or Neutrokine-alphaSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-alpha and/or Neutrokine-alphaSV 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 Neutrokine-alpha and/or Neutrokine-alphaSV activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

Claims

1. A method of treating an autoimmune system disease or disorder comprising administering to an individual, an effective amount of an antagonistic antibody or portion thereof that specifically binds a protein consisting of an amino acid sequence of amino acid residues 134-285 of SEQ ID NO:

2.

2. The method of claim 1 wherein the antibody or portion thereof is a monoclonal antibody.

3. The method of claim 1 wherein the antibody or portion thereof is a polyclonal antibody.

4. The method of claim 1 wherein the antibody or portion thereof is a Fab fragment.

5. The method of claim 1 wherein the antibody or portion thereof is labeled.

6. The method of claim 5 wherein the label is selected from the group consisting of:

(a) an enzyme label;

(b) a radioisotope;

(c) a fluorescent label; and

(d) biotin.

7. The method of claim 6 wherein the label is a radioisotope selected from the group consisting of:

(a) ¹²⁵I;

(b) ¹²¹I;

(c) ¹³¹I;

(d) ¹¹²In; and

(e) ^99mTc.

15. The method of claim 1 wherein the autoimmune disease or disorder is systemic lupus erythematosus.

31. The method of claim 1 wherein said antibody or portion thereof is administered intravenously.

32. The method of claim 1 which comprises administering between 0.1 and 20 mg/kg of the patient'"'"'s body weight of said antibody or portion thereof.

8. A method of treating rheumatoid arthritis comprising administering to an individual, an effective amount of an antagonistic antibody or portion thereof that specifically binds a protein consisting of the amino acid sequence of amino acid residues 134-285 of SEQ ID NO:

2.

9. The method of claim 8 wherein the antibody or portion thereof is a monoclonal antibody.

10. The method of claim 8 wherein the antibody or portion thereof is a polyclonal antibody.

11. The method of claim 8 wherein the antibody or portion thereof is a Fab fragment.

12. The method of claim 8 wherein the antibody or portion thereof is labeled.

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

(a) an enzyme label;

(b) a radioisotope;

(c) a fluorescent label; and

(d) biotin.

14. The method of claim 13 wherein the label is a radioisotope selected from the group consisting of:

(a) ¹²⁵I;

(b) ¹²¹I;

(c) ¹³¹I;

(d) ¹¹²In; and

(e) ^99mTc.

33. The method of claim 8 wherein said antibody or portion thereof is administered intravenously.

34. The method of claim 8 which comprises administering between 0.1 and 20 mg/kg of the patient'"'"'s body weight of said antibody or portion thereof.

16. A method of treating an autoimmune disease or disorder comprising administering to an individual, an effective amount of an antagonistic antibody or portion thereof that specifically binds to an isolated recombinant Neutrokine-α

protein purified from a cell culture wherein the cells in said cell culture comprise a polynucleotide encoding amino acids 1-285 of SEQ ID NO;

2 operably associated with a regulatory sequence that controls gene expression.

17. The method of claim 16 wherein the antibody or portion thereof is a monoclonal antibody.

18. The method of claim 16 wherein the antibody or portion thereof is a polyclonal antibody.

19. The method of claim 16 wherein the antibody or portion thereof is a Fab fragment.

20. The method of claim 16 wherein the antibody or portion thereof is labeled.

21. The method of claim 20 wherein the label is selected from the group consisting of:

(a) an enzyme label;

(b) a radioisotope;

(c) a fluorescent label; and

(d) biotin.

22. The method of claim 21 wherein the label is a radioisotope selected from the group consisting of:

(a) ¹²⁵I;

(c) ¹³¹I;

(d) ¹¹²In; and

(e) ^99mTc.

23. The method of claim 16 wherein the autoimmune disease or disorder is systemic lupus erythematosus.

35. The method of claim 16 wherein said antibody or portion thereof is administered intravenously.

36. The method of claim 16 which comprises administering between 0.1 and 20 mg/kg of the patient'"'"'s body weight of said antibody or portion thereof.

24. A method of treating rheumatoid arthritis comprising administering to an individual, an effective amount of an antagonistic antibody or portion thereof that specifically binds to an isolated recombinant Neutrokine-α

protein purified from a cell culture wherein the cells in said cell culture comprise a polynucleotide encoding amino acids 1-285 of SEQ ID NO;

2 operably associated with a regulatory sequence that controls gene expression.

25. The method of claim 24 wherein the antibody or portion thereof is a monoclonal antibody.

26. The method of claim 24 wherein the antibody or portion thereof is a polyclonal antibody.

27. The method of claim 24 wherein the antibody or portion thereof is a Fab fragment.

28. The method of claim 24 wherein the antibody or portion thereof is labeled.

29. The method of claim 28 wherein the label is selected from the group consisting of:

(a) an enzyme label;

(b) a radioisotope;

(c) a fluorescent label; and

(d) biotin.

30. The method of claim 29 wherein the label is a radioisotope selected from the group consisting of:

(a) ¹²⁵I;

(b) ¹²¹I;

(c) ¹³¹I;

(d) ¹¹²In; and

(e) ^99mTc.

37. The method of claim 24 wherein said antibody or portion thereof is administered intravenously.

38. The method of claim 24 which comprises administering between 0.1 and 20 mg/kg of the patient'"'"'s body weight of said antibody or portion thereof.