Antibodies that immunospecifically bind to B lymphocyte stimulator protein

• US 8,101,181 B2
• Filed: 09/02/2009
• Issued: 01/24/2012
• Est. Priority Date: 06/16/2000
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Ruben, Steven M., Choi, Gil H., Vaughan, Tristan, Hilbert, David
• Primary Examiner(s): Duffy, Patricia A
• Application Number:
  US12/552,915
• Publication Number:
  US 20100003259A1
• Time in Patent Office: 874 Days
• Field of Search: None
• US Class Current: 424/139.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• 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 16/2875 against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 against NGF C07K16/22, against TNF C07K16/241
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• 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

Abstract

The present invention relates to antibodies and related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention also relates to methods and compositions for detecting or diagnosing a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate function of B Lymphocyte Stimulator comprising antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention further relates to methods and compositions for preventing, treating or ameliorating a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate B Lymphocyte Stimulator function comprising administering to an animal an effective amount of one or more antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator.

Claims

1. A method of reducing B cell proliferation comprising administering an antibody to an animal so as to reduce B cell proliferation,

wherein the antibody comprises a first amino acid sequence that is at least 85% identical to amino acid residues 1-123 of SEQ ID NO:

327 and a second amino acid sequence that is at least 85% identical to amino acid residues 141-249 of SEQ ID NO;

327, and

wherein the antibody binds B Lymphocyte Stimulator selected from the group consisting of;

(a) amino acid residues 1-285 of SEQ ID NO;

3228;

(b) amino acid residues 134-285 of SEQ ID NO;

3228; and

(c) a trimer comprising amino acid residues 134-285 of SEQ ID NO;

3228.

2. The method of claim 1, wherein the antibody is administered by a route selected from the group consisting of intravenous and subcutaneous.

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

4. The method of claim 3, wherein the antibody is administered by a route selected from the group consisting of intravenous and subcutaneous.

5. The method of claim 3, wherein the human has been diagnosed with an autoimmune disease or cancer.

6. The method of claim 5, wherein the autoimmune disease or cancer is selected from the group consisting of:

(a) Systemic Lupus Erythematosus;

(b) Rheumatoid Arthritis;

(c) Multiple Sclerosis;

(d) Idiopathic Thrombocytopenic Purpura;

(e) Sjö

gren'"'"'s syndrome;

(f) Diabetes;

(g) Waldenstrom'"'"'s macroglobulinaemia;

(h) acute lymphocytic leukemia;

(i) chronic lymphocytic leukemia;

(j) non-Hodgkin'"'"'s lymphoma;

(k) multiple myeloma;

(l) vasculitis; and

(m) graft or transplant rejection.

7. The method of claim 1 further comprising administering one or more agents selected from the group consisting of:

(a) a non-steroidal anti-inflammatory drug;

(b) an anti-malarial agent;

(c) a steroid;

(d) a cytotoxic agent;

(e) an immunosuppressive agent; and

(f) an anti-angiogenic factor.

8. The method of claim 7, wherein the agent is a non-steroidal anti-inflammatory drug.

9. The method of claim 7, wherein the agent is an anti-malarial agent.

10. The method of claim 7, wherein the agent is a steroid.

11. The method of claim 7, wherein the agent is a cytotoxic agent.

12. The method of claim 7, wherein the agent is an immunosuppressive agent.

13. The method of claim 7, wherein the agent is an anti-angiogenic factor.

14. The method of claim 1 further comprising administering one or more agents selected from the group consisting of:

(a) a TNF antagonist;

(b) an anti-CD20 antibody;

(c) an interleukin-1 antagonist;

(d) CTLA4-Ig;

(e) methotrexate;

(f) leflunomide;

(g) sulfasalazine;

(h) auranofin;

(i) gold;

(j) azathioprine;

(k) penicillamine;

(l) cyclophosphamide; and

(m) cyclosporine.

15. The method of claim 1, wherein the first amino acid sequence is at least 95% identical to amino acid residues 1-123 of SEQ ID NO:

327 and the second amino acid sequence is at least 95% identical to amino acid residues 141-249 of SEQ ID NO;

327.

16. The method of claim 1, wherein the first amino acid sequence comprises amino acid residues 1-123 of SEQ ID NO:

327 and the second amino acid sequence comprises amino acid residues 141-249 of SEQ ID NO;

327.

17. The method of claim 1, wherein the antibody also comprises a heavy chain immunoglobulin constant domain selected from the group consisting of:

(a) a human IgM constant domain;

(b) a human IgG1 constant domain;

(c) a human IgG2 constant domain;

(d) a human IgG3 constant domain;

(e) a human IgG4 constant domain; and

(f) a human IgA constant domain.

18. The method of claim 1, wherein the antibody also comprises a light chain immunoglobulin constant domain selected from the group consisting of:

(a) a human Ig kappa constant domain; and

(b) a human Ig lambda constant domain.

19. The method of claim 6, wherein the autoimmune disease or cancer is Systemic Lupus Erythematosus.

20. The method of claim 6, wherein the autoimmune disease or cancer is Rheumatoid Arthritis.

21. A method of reducing B cell proliferation comprising administering an antibody to an animal so as to reduce B cell proliferation,

wherein the antibody comprises amino acid residues 26-35, 50-66, 99-112, 163-173, 189-195, and 228-238 of SEQ ID NO:

327, and

wherein the antibody binds B Lymphocyte Stimulator selected from the group consisting of;

(a) amino acid residues 1-285 of SEQ ID NO;

3228;

(b) amino acid residues 134-285 of SEQ ID NO;

3228; and

(c) a trimer comprising amino acid residues 134-285 of SEQ ID NO;

3228.

22. The method of claim 21, wherein the antibody is administered by a route selected from the group consisting of intravenous and subcutaneous.

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

24. The method of claim 23, wherein the antibody is administered by a route selected from the group consisting of intravenous and subcutaneous.

25. The method of claim 23, wherein the human has been diagnosed with an autoimmune disease or cancer.

26. The method of claim 25, wherein the autoimmune disease or cancer is selected from the group consisting of:

(a) Systemic Lupus Erythematosus;

(b) Rheumatoid Arthritis;

(c) Multiple Sclerosis;

(d) Idiopathic Thrombocytopenic Purpura;

(e) Sjö

gren'"'"'s syndrome;

(f) Diabetes;

(g) Waldenstrom'"'"'s macroglobulinaemia;

(h) acute lymphocytic leukemia;

(i) chronic lymphocytic leukemia;

(j) non-Hodgkin'"'"'s lymphoma;

(k) multiple myeloma

(l) vasculitis; and

(m) graft or transplant rejection.

27. The method of claim 26, wherein the autoimmune disease or cancer is Systemic Lupus Erythematosus.

28. The method of claim 26, wherein the autoimmune disease or cancer is Rheumatoid Arthritis.

29. The method of claim 21 further comprising administering one or more agents selected from the group consisting of:

(a) a TNF antagonist;

(b) an anti-CD20 antibody;

(c) an interleukin-1 antagonist;

(d) CTLA4-Ig;

(e) methotrexate;

(f) leflunomide;

(g) sulfasalazine;

(h) auranofin;

(i) gold;

(j) azathioprine;

(k) penicillamine;

(l) cyclophosphamide; and

(m) cyclosporine.

30. The method of claim 21, wherein the antibody also comprises a heavy chain immunoglobulin constant domain selected from the group consisting of:

(a) a human IgM constant domain;

(b) a human IgG1 constant domain;

(c) a human IgG2 constant domain;

(d) a human IgG3 constant domain;

(e) a human IgG4 constant domain; and

(f) a human IgA constant domain.

31. The method of claim 21, wherein the antibody also comprises a light chain immunoglobulin constant domain selected from the group consisting of:

(a) a human Ig kappa constant domain; and

(b) a human Ig lambda constant domain.