Methods of Treatment Using Antibodies to Neutrokine-alpha

• US 20060193859A1
• Filed: 05/11/2006
• Published: 08/31/2006
• Est. Priority Date: 10/25/1996
• Status: Abandoned Application

• Current Assignee: Human Genome Sciences Incorporated (GSK plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc)
• Inventors: Yu, Guo-Liang, Ni, Jian, Ebner, Reinhard
• Application Number:
  US11/382,837
• Publication Number:
  US 20060193859A1
• Time in Patent Office: Days
• US Class Current: 424/145.1
• 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 disease in an animal comprising administering a therapeutically effective amount of an anti-Neutrokine-alpha antibody that binds to a human Neutrokine-alpha polypeptide having SEQ ID NO:

2.

2. The method of claim 1, wherein the anti-Neutrokine-alpha antibody is a monoclonal antibody.

3. The method of claim 1, wherein the antibody is recombinantly produced.

4. The method of claim 1, wherein the antibody is a chimeric antibody.

5. The method of claim 1, wherein the antibody is a humanized antibody.

6. The method of claim 1, wherein the antibody comprises human constant domains.

7. The method of claim 1, wherein the antibody is a F(ab′

)2 fragment.

8. The method of claim 1, wherein the animal is human.

9. The method of claim 1, further comprising detecting the level of B cell growth in the animal.

10. The method of claim 1, further comprising detecting the level of immunoglobulin production in the animal.

11. The method of claim 1, further comprising detecting the levels of B cell growth and immunoglobulin production in the animal.

12. The method of claim 1, further comprising detecting circulating levels of a rheumatoid factor in the animal.

13. The method of claim 1, further comprising detecting circulating levels of anti-DNA autoantibody in the animal.

14. A method of treating an autoimmune disease comprising the step of administering a therapeutically effective amount of an anti-Neutrokine-alpha antibody that binds to a murine Neutrokine-alpha polypeptide.

15. The method of claim 14, wherein the anti-Neutrokine-alpha antibody is a monoclonal antibody.

16. The method of claim 14, wherein the antibody is recombinantly produced.

17. The method of claim 14, wherein the antibody is a chimeric antibody.

18. The method of claim 14, wherein the antibody is a humanized antibody.

19. The method of claim 14, wherein the antibody comprises human constant domains.

20. The method of claim 14, wherein the antibody is a F(ab′

)2 fragment.

21. The method of claim 14, wherein the animal is human.

22. The method of claim 14, further comprising detecting the level of B cell growth in the animal.

23. The method of claim 14, further comprising detecting the level of immunoglobulin production in the animal.

24. The method of claim 14, further comprising detecting the levels of B cell growth and immunoglobulin production in the animal.

25. The method of claim 14, further comprising detecting circulating levels of a rheumatoid factor in the animal.

26. The method of claim 14, further comprising detecting circulating levels of anti-DNA autoantibody in the animal.

27. The method of claim 14, wherein the murine Neutrokine-alpha polypeptide has the amino acid sequence of SEQ ID NO:

22.