Antibodies that immunospecifically bind to B lymphocyte stimulator

• US 7,879,328 B2
• Filed: 02/10/2005
• Issued: 02/01/2011
• Est. Priority Date: 06/16/2000
• Status: Expired due to Term

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Vaughan, Tristan, Choi, Gil H., Hilbert, David, Ruben, Steven M.
• Primary Examiner(s): DUFFY, PATRICIA ANN
• Application Number:
  US11/054,515
• Publication Number:
  US 20050255532A1
• Time in Patent Office: 2,182 Days
• Field of Search: 424/130.1, 424/135.1, 424/141.1, 424/145.1, 424/153.1, 424/156.1, 424/158.1
• US Class Current: 424/145.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• 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 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• 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 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5011 : for testing antineoplastic activity
• CPC Class Codes: G01N 33/5052 : involving B-cells
• CPC Class Codes: G01N 33/5091 : for testing the pathological state of an organism
• 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 33/574 : for cancer
• CPC Class Codes: G01N 33/68 : involving proteins, peptides or amino acids involving lipoproteins G01N33/92

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 antagonizing B Lymphocyte Stimulator activity in an animal having systemic lupus erythematosus or rheumatoid arthritis comprising administering to the animal an antibody comprising 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.

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

30. 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.

33. 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.

2. A method of antagonizing B Lymphocyte Stimulator activity in a human patient having rheumatoid arthritis comprising administering to the human patient an antibody comprising 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, 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.

3. The method of claim 2 further comprising administering one or more agents employed for treating rheumatoid arthritis 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.

4. The method of claim 2 further comprising administering one or more agents employed for treating rheumatoid arthritis 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.

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

11. The method of claim 3, wherein the agent employed for treating rheumatoid arthritis is a non-steroidal anti-inflammatory drug.

12. The method of claim 3, wherein the agent employed for treating rheumatoid arthritis is an anti-malarial agent.

13. The method of claim 3, wherein the agent employed for treating rheumatoid arthritis is a steroid.

14. The method of claim 3, wherein the agent employed for treating rheumatoid arthritis is a cytotoxic agent.

15. The method of claim 3, wherein the agent employed for treating rheumatoid arthritis is an immunosuppressive agent.

16. The method of claim 3, wherein the agent employed for treating rheumatoid arthritis is an anti-angiogenic factor.

31. The method of claim 2, 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.

34. The method of claim 2, wherein the first amino acid sequence is 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.

5. A method of antagonizing B Lymphocyte Stimulator activity in a human patient having systemic lupus erythematosus comprising administering to the human patient an antibody comprising 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, 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.

6. The method of claim 5 further comprising administering one or more agents employed for treating systemic lupus erythematosus 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.

7. The method of claim 5 further comprising administering one or more agents employed for treating systemic lupus erythematosus 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.

10. The method of claim 5, wherein the antibody is administered by a route selected from the group consisting of intravenous and subcutaneous.

17. The method of claim 6, wherein the agent employed for treating systemic lupus erythematosus is a non-steroidal anti-inflammatory drug.

18. The method of claim 6, wherein the agent employed for treating systemic lupus erythematosus is an anti-malarial agent.

19. The method of claim 6, wherein the agent employed for treating systemic lupus erythematosus is a steroid.

20. The method of claim 6, wherein the agent employed for treating systemic lupus erythematosus is a cytotoxic agent.

21. The method of claim 6, wherein the agent employed for treating systemic lupus erythematosus is an immunosuppressive agent.

22. The method of claim 6, wherein the agent employed for treating systemic lupus erythematosus is an anti-angiogenic factor.

23. The method of claim 7, wherein the agent employed for treating systemic lupus erythematosus is a TNF antagonist.

24. The method of claim 7, wherein the agent employed for treating systemic lupus erythematosus is an anti-CD20 antibody.

25. The method of claim 7, wherein the agent employed for treating systemic lupus erythematosus is an interleukin-1 antagonist.

26. The method of claim 7, wherein the agent employed for treating systemic lupus erythematosus is CTLA4-Ig.

27. The method of claim 7, wherein the agent employed for treating systemic lupus erythematosus is methotrexate.

28. The method of claim 7, wherein the agent employed for treating systemic lupus erythematosus is leflunomide.

29. The method of claim 7, wherein the agent employed for treating systemic lupus erythematosus is cyclosporine.

32. The method of claim 5, 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.

35. The method of claim 5, 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.

36. The method of claim 17, 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.

37. The method of claim 18, 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.

38. The method of claim 19, 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.

39. The method of claim 20, 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.

40. The method of claim 21, 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.

41. The method of claim 22, 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.

42. The method of claim 23, 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.

43. The method of claim 24, 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.

44. The method of claim 25, 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.

45. The method of claim 26, 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.

46. The method of claim 27, 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.

47. The method of claim 28, 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.

48. The method of claim 29, 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.

49. A method of antagonizing B Lymphocyte Stimulator activity in a patient having systemic lupus erythematosus or rheumatoid arthritis comprising administering an antibody to the patient,

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.

50. The method of claim 49, wherein the patient has systemic lupus erythematosus.

51. The method of claim 50, wherein the antibody is administered by a route selected from the group consisting of intravenous and subcutaneous.

52. The method of claim 50 further comprising administering one or more agents employed for treating systemic lupus erythematosus 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.

53. The method of claim 50 further comprising administering one or more agents employed for treating systemic lupus erythematosus 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.

54. The method of claim 49, wherein the patient has rheumatoid arthritis.

55. The method of claim 54, wherein the antibody is administered by a route selected from the group consisting of intravenous and subcutaneous.

56. The method of claim 54 further comprising administering one or more agents employed for treating rheumatoid arthritis 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.

57. The method of claim 54 further comprising administering one or more agents employed for treating rheumatoid arthritis 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.