NEUTROKINE-ALPHA ANTIBODIES AND METHODS OF USE THEREOF

• US 20090169565A1
• Filed: 02/26/2009
• Published: 07/02/2009
• Est. Priority Date: 10/25/1996
• 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, Rosen, Craig A., Ebner, Reinhard
• Granted Patent: US 8,303,951 B2
• Time in Patent Office: Days
• US Class Current: 424/152.100
• 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 Neutrokine-alpha antibody and a process for producing a Neutrokine-alpha antibody. The invention further relates to screening methods for identifying compounds that inhibit or enhance the action of Neutrokine-alpha. Also provided are diagnostic methods for detecting autoimmune disorders and therapeutic methods for treating autoimmune disorders using a Neutrokine-alpha antibody.

Claims

1. An antibody that binds an amino acid sequence comprising residues 134-146 of human Neutrokine-alpha protein (SEQ ID NO:

2).

2. The antibody according to claim 1, wherein the antibody is a monoclonal antibody.

7. A pharmaceutical composition comprising the antibody according to claim 1 or 2 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition prevents and/or treats an autoimmune disease.

9. The pharmaceutical composition according to claim 8, wherein the autoimmune disease is systemic lupus erythematosus, rheumatoid arthritis, Sjogren'"'"'s syndrome, autoimmune diabetes, AIDS, or an autoimmune disease associated with B-cell proliferation and immunoglobulin secretion.

10. A diagnostic agent for an autoimmune disease, which comprises the antibody according to claim 1 or 2.

11. The diagnostic agent according to claim 10, wherein the autoimmune disease is systemic lupus erythematosus, rheumatoid arthritis, Sjogren'"'"'s syndrome, autoimmune diabetes, AIDS, or an autoimmune disease associated with B-cell proliferation and immunoglobulin secretion.

12. The diagnostic agent according to claim 10, which diagnostic agent can be used to conduct a diagnosis by ELISA.

13. A method of diagnosing an autoimmune disease, which method comprises the use of the antibody according to claim 1 or 2 to diagnose an autoimmune diease in a mammal.

14. The method according to claim 13, wherein the autoimmune disease is systemic lupus erythematosus, rheumatoid arthritis, Sjogren'"'"'s syndrome, autoimmune diabetes, AIDS, or an autoimmune disease associated with B-cell proliferation and immunoglobulin secretion.

15. The method according to claim 13, wherein the diagnosis is carried out by ELISA.

16. A method of detecting or quantifying Neutrokine-alpha in a sample, which comprises contacting a sample with the antibody of claim 1 or 2 and detecting or quantifying Neutrokine-alpha bound to the antibody.

17. The method according to claim 16, wherein the Neutrokine-alpha is human Neutrokine-alpha.

18. The method according to claim 16, wherein the detecting or quantifying of Neutrokine-alpha bound to the antibody is carried out by ELISA.

19. A method of screening for compounds that inhibit or enhance the action of Neutrokine-alpha in a sample comprising contacting a sample with a candidate compound, and quantitatively measuring Neutrokine-alpha level in the sample using the antibody of claim 1 or 2, as compared to the Neutrokine-alpha level in the sample in the absence of the candidate compound.

20. The method according to claim 19, wherein the Neutrokine-alpha is human Neutrokine-alpha.

21. The method according to claim 19, wherein the method of screening for compounds that inhibit the action of Neutrokine-alpha comprises screening for compounds that block the interaction of Neutrokine-alpha with Neutrokine-alpha binding molecules.

22. Use of the antibody of claim 1 or 2 for producing a pharmaceutical composition for the prophylaxis/therapy of autoimmune diseases.

23. Use of the antibody of claim 22, wherein the autoimmune disease is systemic lupus erythematosus, rheumatoid arthritis, Sjogren'"'"'s syndrome, autoimmune diabetes, AIDS, or an autoimmune disease associated with B-cell proliferation and immunoglobulin secretion.

24. Use of the antibody of claim 1 or 2 for producing a composition for diagnosis of autoimmune diseases.

25. A method of preventing or treating an autoimmune disease, comprising administering an effective amount of the antibody of claim 1 or 2 to a patient, thereby treating or preventing an autoimmune disease in the patient.

26. The method of claim 25, wherein the autoimmune disease is systemic lupus erythematosus, rheumatoid arthritis, Sjogren'"'"'s syndrome, autoimmune diabetes, AIDS, or an autoimmune disease associated with B-cell proliferation and immunoglobulin secretion.

3. A process for producing an antibody comprising immunizing an animal with an antigen comprising an amino acid sequence comprising at least residues 134-146 of SEQ ID NO:

2 so that an antibody-producing cell in the animal produces an antibody that binds an amino acid sequence comprising at least residues 134-146 of SEQ ID NO;

2.

4. The process according to claim 3, wherein the amino acid sequence consists of residues 134-146 of SEQ ID NO:

2.

5. The process according to claim 3 or 4, wherein the antigen further comprises a molecule selected from the list consisting of (a) keyhole limpet hemacyanin (KLH), (b) tetanus toxoid, and (c) albumin.

6. The process according to claim 3 or 4, wherein the animal is a mouse, rat, hamster, guinea pig, chicken, or rabbit.