Claims for Patent: 7,198,789

Summary for Patent: 7,198,789

Title:	Methods and compositions for modulating interleukin-21 receptor activity
Abstract:	Methods and compositions for modulating interleukin-21 (IL-21)/IL-21 receptor (MU-1) activity using agonists or antagonists of IL-21 or IL-21 receptor (\"IL-21R\" or \"MU-1\"), are disclosed. IL-21/IL-21R antagonists can be used to induce immune suppression in vivo, e.g., for treating or preventing immune cell-associated pathologies (e.g., pathologies associated with aberrant activity of one or more of mature T cells (mature CD8+, mature CD4+ T cells), mature NK cells, B cells, macrophages and megakaryocytes, including transplant rejection and autoimmune disorders). IL-21/IL-21R agonists can be used by themselves or in combination with an antigen, e.g., as an adjuvant (e.g., a vaccine adjuvant), to up-regulate an immune response in vivo, e.g., for example, for use in treating cancer and infectious disorders.
Inventor(s):	Carter; Laura (Medford, MA), Carreno; Beatriz (Acton, MA), Lowe; Leslie D. (Sudbury, MA), Whitters; Matthew J. (Hudson, MA), Dunussi; Kyri (Belmont, MA), Collins; Mary (Natick, MA), Ma; Margery (W. Roxbury, MA), Young; Deborah A. (Melrose, MA), Witek; JoAnn S. (Acton, MA), Larsen; Glenn (Sudbury, MA), Kasaian; Marion T. (Charlestown, MA), Donaldson; Debra D. (Medford, MA), Unger; Michelle (Chapel Hill, NC)
Assignee:	Genetics Institute, LLC (Cambridge, MA)
Application Number:	10/264,634
Patent Claims:	1. A method of treating an arthritic disorder in a subject, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to IL-21R in an amount sufficient to inhibit or reduce immune cell activity in the subject, thereby treating the arthritic disorder, wherein said IL-21R has a sequence at least about 90% identical to the amino acid sequence of SEQ ID NO:2 and is capable of binding to an IL-21 polypeptide. 2. The method of claim 1, further comprising administering to the subject a therapeutic agent selected from the group consisting of cytokine inhibitors, growth factor inhibitors, immunosuppressants, anti-inflammatory agents, metabolic inhibitors, enzyme inhibitors, cytotoxic agents, and cytostatic agents. 3. The method of claim 2, wherein the therapeutic agent is selected from the group consisting of TNF antagonists, anti-TNF agents, IL-12 antagonists, IL-15 antagonists, IL-17 antagonists, IL-18 antagonists, IL-22 antagonists, T cell-depleting agents, B cell-depleting agents, cyclosporin, FK506, CCI-779. etanercept, infliximab, rituximab, adalimumab, prednisolone, azathioprine, gold, sulphasalazine, hydroxychloroquine, minocycline, anakinra, atabacept, methotrexate, leflunomide, rapamycin, rapamycin analogs, Cox-2 inhibitors, cPLA2 inhibitors, NSAIDs, p38 inhibitors, antagonists of B7.1, B7.2, ICOSL, ICOS, and CD28, and CTLA4 agonists. 4. The method of claim 1, wherein the arthritic disorder is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and ankylosing spondylitis. 5. The method of claim 4, wherein the arthritic disorder is rheumatoid arthritis. 6. The method of claim 4, wherein said arthritic disorder is psoriatic arthritis. 7. The method of claim 4, wherein said arthritic disorder is osteoarthritis. 8. The method of claim 4, wherein said arthritic disorder is juvenile rheumatoid arthritis. 9. The method of claim 4, wherein said arthritic disorder is ankylosing spondylitis. 10. The method of claim 1, wherein the subject is a mammal. 11. The method of claim 1, wherein said IL-21R comprises the sequence of SEQ ID NO:2. 12. The method of either claim 1 or 4, wherein said antibody or antigen-binding fragment thereof is administered subcutaneously or intravenously. 13. The method of either claim 1 or 4, wherein said subject is a human. 14. The method of either claim 1 or 4, wherein said IL-21R has a sequence at least about 95% identical to the amino acid sequence of SEQ ID NO:2 and is capable of binding to an IL-21 polypeptide. 15. The method of either claim 1 or 4, wherein said IL-21R comprises the sequence of SEQ ID NO:2 from about amino acids 20 538. 16. The method of either claim 1 or 4, wherein said antibody, or antigen-binding fragment thereof, binds to an epitope found in the extracellular domain of IL-21R. 17. The method of either claim 1 or 4, wherein said antibody, or antigen-binding fragment thereof, is a neutralizing antibody. 18. The method of either claim 1 or 4, wherein said antibody, or antigen-binding fragment thereof, is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a chimeric antibody, a single-chain antibody, a CDR-grafted antibody and a humanized antibody. 19. The method of either claim 1 or 4, wherein said antibody, or antigen-binding fragment thereof, is a human antibody. 20. A method of ameliorating a symptom associated with arthritis in a subject, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to IL-21R in an amount sufficient to ameliorate the symptom in the subject, wherein the IL-21R has a sequence at least about 90% identical to the amino acid sequence of SEQ ID NO:2 and is capable of binding to an IL-21 polypeptide. 21. The method of claim 20, wherein said antibody, or antigen-binding fragment thereof, is administered therapeutically. 22. The method of claim 20, wherein said antibody, or antigen-binding fragment thereof, is administered prophylactically. 23. The method of claim 20, wherein said IL-21R has a sequence at least about 95% identical to the amino acid sequence of SEQ ID NO:2 and is capable of binding to an IL-21 polypeptide. 24. The method of claim 20, wherein said IL-21R comprises the sequence of SEQ ID NO:2 from about amino acids 20 538. 25. The method of claim 20, wherein said IL-21R comprises the sequence of SEQ ID NO:2. 26. The method of claim 20, wherein said antibody, or antigen-binding fragment thereof, binds to an epitope found in the extracellular domain of IL-21R. 27. The method of claim 26, wherein said arthritic symptom is associated with a disorder selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and ankylosing spondylitis. 28. The method of claim 27, wherein said disorder is rheumatoid arthritis. 29. The method of claim 27, wherein said disorder is psoriatic arthritis. 30. The method of claim 27, wherein said disorder is osteoarthritis. 31. The method of claim 27, wherein said disorder is juvenile rheumatoid arthritis. 32. The method of claim 27, wherein said disorder is ankylosing spondylitis. 33. The method of claim 20, further comprising administering to the subject a therapeutic agent selected from the group consisting of cytokine inhibitors, growth factor inhibitors, immunosuppressants, anti-inflammatory agents, metabolic inhibitors, enzyme inhibitors, cytotoxic agents, and cytostatic agents. 34. The method of claim 33, wherein said therapeutic agent is selected from the group consisting of TNF antagonists, anti-TNF agents, IL-12 antagonists, IL-15 antagonists, IL-17 antagonists, IL-18 antagonists, IL-22 antagonists, T cell-depleting agents, B cell-depleting agents, cyclosporin, FK506, CCI-779, etanercept, infliximab, rituximab, adalimumab, prednisolone, azathioprine, gold, sulphasalazine, hydroxychloroquine, minocycline, anakinra, atabacept, methotrexate, leflunomide, rapamycin, rapamycin analogs, Cox-2 inhibitors, cPLA2 inhibitors, NSAIDs, p38 inhibitors, antagonists of B7.1, B7.2, ICOSL, ICOS, and CD28, and CTLA4 agonists. 35. The method of either claim 20 or 26, wherein said antibody or antigen-binding fragment thereof is administered subcutaneously or intravenously. 36. The method of either claim 20 or 26, wherein said subject is a human. 37. The method of either claim 20 or 26, wherein said antibody, or antigen-binding fragment thereof, is a neutralizing antibody. 38. The method of either claim 20 or 26, wherein said antibody, or antigen-binding fragment thereof, is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a chimeric antibody, a single-chain antibody, a CDR-grafted antibody and a humanized antibody. 39. The method of either claim 20 or 26, wherein said antibody, or antigen-binding fragment thereof, is a human antibody. 40. A method of treating rheumatoid arthritis in a subject, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to IL-21R in an amount sufficient to treat rheumatoid arthritis in the subject, wherein the IL-21R has a sequence at least about 90% identical to the amino acid sequence of SEQ ID NO:2 and is capable of binding to an IL-21 polypeptide. 41. The method of claim 40, wherein said IL-21R has a sequence at least about 95% identical to the amino acid sequence of SEQ ID NO:2 and is capable of binding to an IL-21 polypeptide. 42. The method of claim 40, wherein said IL-21R comprises the sequence of SEQ ID NO:2 from about amino acids 20 538. 43. The method of claim 40, wherein said IL-21R comprises the sequence of SEQ ID NO:2. 44. The method of claim 40, wherein said antibody, or antigen-binding fragment thereof, binds to an epitope found in the extracellular domain of IL-21R. 45. The method of claim 40, further comprising administering to the subject a therapeutic agent selected from the group consisting of cytokine inhibitors, growth factor inhibitors, immunosuppressants, anti-inflammatory agents, metabolic inhibitors, enzyme inhibitors, cytotoxic agents, and cytostatic agents. 46. The method of claim 45, wherein said therapeutic agent is selected from the group consisting of TNF antagonists, anti-TNF agents, IL-12 antagonists, IL-15 antagonists, IL-17 antagonists, IL-18 antagonists, IL-22 antagonists, T cell-depleting agents, B cell-depleting agents, cyclosporin, FK506, CCI-779, etanercept, infliximab, rituximab, adalimumab, prednisolone, azathioprine, gold, sulphasalazine, hydroxychloroquine, minocycline, anakinra, atabacept, methotrexate, leflunomide, rapamycin, rapamycin analogs, Cox-2 inhibitors, cPLA2 inhibitors, NSAIDs, p38 inhibitors, antagonists of B7.1, B7.2, ICOSL, ICOS, and CD28, and CTLA4 agonists. 47. The method of either claim 40 or 44, wherein said antibody or antigen-binding fragment thereof is administered subcutaneously or intravenously. 48. The method of either claim 40 or 44, wherein said subject is a human. 49. The method of either claim 40 or 44, wherein said antibody, or antigen-binding fragment thereof, is a neutralizing antibody. 50. The method of either claim 40 or 44, wherein said antibody, or antigen-binding fragment thereof, is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a chimeric antibody, a single-chain antibody, a CDR-grafted antibody and a humanized antibody. 51. The method of either claim 40 or 44, wherein said antibody, or antigen-binding fragment thereof, is a human antibody. 52. A method of treating an immune cell-associated pathology selected from the group consisting of an arthritic disorder, psoriasis, systemic lupus erythematosus, Crohn's disease, inflammatory bowel disease (IBD) and transplant rejection, in a subject, comprising administering to the subject an antibody against IL-21R, or an antigen-binding fragment thereof, in an amount sufficient to treat said pathology, wherein said IL-21R has a sequence at least about 90% identical to the amino acid sequence of SEQ ID NO:2 and is capable of binding to an IL-21 polypeptide. 53. The method of claim 52, wherein said IL-21R has a sequence at least about 95% identical to the amino acid sequence of SEQ ID NO:2 and is capable of binding to an IL-21 polypeptide. 54. The method of claim 52, wherein said IL-21R comprises the sequence of SEQ ID NO:2 from about amino acids 20 538. 55. The method of claim 52, wherein said IL-21R comprises the sequence of SEQ ID NO:2. 56. The method of claim 52, wherein said antibody, or antigen-binding fragment thereof, binds to an epitope found in the extracellular domain of IL-21 R. 57. The method of claim 52, wherein said pathology is psoriasis. 58. The method of claim 52, wherein said pathology is systemic lupus erythematosus. 59. The method of claim 52, wherein said pathology is IBD. 60. The method of claim 52, wherein said pathology is Crohn's disease. 61. The method of claim 52, wherein said pathology is transplant rejection. 62. The method of claim 52, wherein said antibody or antigen-binding fragment thereof is administered subcutaneously or intravenously. 63. The method of claim 52, wherein said subject is a human. 64. The method of claim 52, wherein said antibody, or antigen-binding fragment thereof, is a neutralizing antibody. 65. The method of claim 52, wherein said antibody, or antigen-binding fragment thereof, is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a chimeric antibody, a single-chain antibody, a CDR-grafted antibody and a humanized antibody. 66. The method of claim 52, wherein said antibody, or antigen-binding fragment thereof, is a human antibody.

Details for Patent 7,198,789

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
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