Claims for Patent: 9,987,356

Summary for Patent: 9,987,356

Title:	Anti-CD40 antibodies and methods of administering thereof
Abstract:	The present invention relates to antibodies specific for a particular epitope on CD40 and antibodies that bind CD40 and have particular functional characteristics. The present invention also relates to fragments of these antibodies, uses of the antibodies for reduction or treatment of transplant rejection and graft-versus-host disease, and methods for making the antibodies.
Inventor(s):	Reimann; Keith A. (Marblehead, MA), Wang; Rijian (Saugus, MA), Larsen; Christian P. (Atlanta, GA)
Assignee:	Beth Israel Deaconess Medical Center, Inc. (Boston, MA) Emory University (Atlanta, GA)
Application Number:	14/004,552
Patent Claims:	1. An isolated antibody, or antigen-binding fragment thereof, that specifically binds to CD40, wherein the heavy chain variable region of said antibody comprises the hypervariable regions set forth in amino acids 20-132 of SEQ ID NO:2, and the light chain variable sequence of said antibody comprises the hypervariable regions set forth in amino acids 23-128 of SEQ ID NO:4. 2. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein said antibody or said antigen-binding fragment thereof blocks B lymphocyte activation by CD154-expressing Jurkat cells in vitro or said antibody inhibits B lymphocyte CD23, CD80, or CD86expression. 3. The isolated antibody or antigen-binding fragment thereof of claim 2, wherein said B lymphocyte is a rhesus or human B lymphocyte. 4. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the constant regions of said antibody or said antigen-binding fragment thereof are human constant regions. 5. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein said antibody or said antigen-binding fragment thereof is a humanized antibody, a human antibody, or a monoclonal antibody. 6. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein said antigen-binding fragment is an antibody that lacks the Fc portion or is a F(ab').sub.2, a Fab, an Fv, or an scFv structure. 7. A method of suppressing the immune system in a subject in need thereof, said method comprising administering to said subject an effective amount of an antibody, or antigen-binding fragment thereof of claim 1 to said subject. 8. The method of claim 7, wherein said subject has received, or is in need of, an organ transplant. 9. The method of claim 8, wherein said organ is selected from the group consisting of heart, kidney, lung, liver, pancreas, intestine, and thymus, or a portion thereof. 10. The method of claim 7, wherein said subject has received, or is in need of a tissue transplant. 11. The method of claim 10, wherein said tissue is bone, tendon, cornea, skin, heart valve, vein, or bone marrow. 12. The method of claim 7, wherein said administration is commenced prior to said transplantation or said graft. 13. The method of claim 7, wherein said administration continues for at least one month following transplantation of a graft in said subject. 14. A method of blocking the ability of CD40 to interact with CD154 in a subject, said method comprising administering an effective amount of an antibody, or an antigen-binding fragment thereof of claim 1 to said subject. 15. The method of claim 14, wherein said subject has a disorder selected from the group consisting of systemic lupus erythematosus (SLE), CREST syndrome (calcinosis, Raynaud's syndrome, esophageal dysmotility, sclerodactyl, and telangiectasia), opsoclonus, inflammatory myopathy, systemic scleroderma, primary biliary cirrhosis, celiac disease, dermatitis herpetiformis, Miller-Fisher Syndrome, acute motor axonal neuropathy (AMAN), multifocal motor neuropathy with conduction block, autoimmune hepatitis, antiphospholipid syndrome, Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, rheumatoid arthritis, chronic autoimmune hepatitis, scleromyositis, myasthenia gravis, Lambert-Eaton myasthenic syndrome, Hashimoto's thyroiditis, Graves' disease, Paraneoplastic cerebellar degeneration, Stiff person syndrome, limbic encephalitis, Isaacs Syndrome, Sydenham's chorea, pediatric autoimmune neuropsychiatric disease associated with Streptococcus (PANDAS), encephalitis, diabetes mellitus type 1, neuromyelitis optica, pernicious anemia, Addison's disease, psoriasis, inflammatory bowel disease, psoriatic arthritis, Sjogren's syndrome, lupus erythematosus, multiple sclerosis, reactive arthritis, polymyositis, dermatomyositis, multiple endocrine failure, Schmidt's syndrome, autoimmune uveitis, adrenalitis, thyroiditis, autoimmune thyroid disease, gastric atrophy, chronic hepatitis, lupoid hepatitis, atherosclerosis, presenile dementia, demyelinating diseases, subacute cutaneous lupus erythematosus, hypoparathyroidism, Dressler's syndrome, autoimmune thrombocytopenia, idiopathic thrombocytopenic purpura, hemolytic anemia, pemphigus vulgaris, pemphigus, alopecia arcata, pemphigoid, scleroderma, progressive systemic sclerosis, adult-onset diabetes mellitus, male and female autoimmune infertility, ankylosing spondolytis, ulcerative colitis, Crohn's disease, mixed connective tissue disease, polyarteritis nedosa, systemic necrotizing vasculitis, juvenile onset rheumatoid arthritis, glomerulonephritis, atopic dermatitis, atopic rhinitis, Goodpasture's syndrome, Chagas' disease, sarcoidosis, rheumatic fever, asthma, recurrent abortion, anti-phospholipid syndrome, farmer's lung, erythema multiforme, post cardiotomy syndrome, Cushing's syndrome, autoimmune chronic active hepatitis, bird-fancier's lung, allergic disease, allergic encephalomyelitis, toxic epidermal necrolysis, alopecia, Alport's syndrome, alveolitis, allergic alveolitis, fibrosing alveolitis, interstitial lung disease, erythema nodosum, pyoderma gangrenosum, transfusion reaction, leprosy, malaria, leishmaniasis, trypanosomiasis, Takayasu's arteritis, polymyalgia rheumatica, temporal arteritis, schistosomiasis, giant cell arteritis, ascariasis, aspergillosis, Sampter's syndrome, eczema, lymphomatoid granulomatosis, Behcet's disease, Caplan's syndrome, Kawasaki's disease, dengue, endocarditis, endomyocardial fibrosis, endophthalmitis, erythema elevatum et diutinum, erythroblastosis fetalis, eosinophilic fasciitis, Shulman's syndrome, Felty's syndrome, filariasis, cyclitis, chronic cyclitis, heterochronic cyclitis, Fuch's cyclitis, IgA nephropathy, Henoch-Schonlein purpura, graft versus host disease, transplantation rejection, human immunodeficiency virus infection, echovirus infection, cardiomyopathy, Alzheimer's disease, parvovirus infection, rubella virus infection, post vaccination syndromes, congenital rubella infection, Hodgkin's and non-Hodgkin's lymphoma, renal cell carcinoma, multiple myeloma, Eaton-Lambert syndrome, relapsing polychondritis, malignant melanoma, cryoglobulinemia, Waldenstrom's macroglobulemia, Epstein-Barr virus infection, mumps, Evan's syndrome, and autoimmune gonadal failure. 16. The method of claim 7, wherein said subject is a mammal. 17. The method of claim 16, wherein said subject is a human. 18. The method of claim 7, wherein said administration is parenteral, intravenous, subcutaneous, oral, topical, intrathecal, or local. 19. The method of claim 7, wherein said method further comprises administering a second agent within six months of said antibody, wherein said second agent is an immunosuppressant. 20. The method of claim 19, wherein said second agent is selected from the group consisting of a calcineurin inhibitor selected from the group consisting of cyclosporin A and cyclosporine G, tacrolimus, an mTor inhibitor, fingolimod, myriocin, alemtuzumab, rituximab, an anti-CD4 monoclonal antibody, an anti-LFA1 monoclonal antibody, an anti-LFA3 monoclonal antibody, an anti-CD45 antibody, an anti-CD19 antibody, monabatacept, belatacept, indolyl-ASC; azathioprine, lymphocyte immune globulin and anti-thymocyte globulin, mycophenolate mofetil, mycophenolate sodium, daclizumab, basiliximab, cyclophosphamide, prednisone, prednisolone, leflunomide, FK778, FK779, 15-deoxyspergualin, busulfan, fludarabine, methotrexate, 6-mercaptopurine, 15-deoxyspergualin, LF15-0195, bredinin, brequinar, and muromonab-CD3. 21. The method of claim 20, wherein said mTor inhibitor is sirolimus, temsirolimus, zotarolimus, or everolimus. 22. The method of claim 19, wherein said antibody and said second agent are administered within one month of each other. 23. The method of claim 21, wherein said antibody and said second agent are administered within one week of each other. 24. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein said heavy chain variable region comprises of amino acids 20-132 of SEQ ID NO:2 and said light chain variable region comprises of amino acids 23-128 of SEQ ID NO:4. 25. The method of claim 7, wherein said subject has transplant rejection. 26. The method of claim 7, wherein said method increases the duration of time before transplant rejection occurs in said subject. 27. The method of claim 7, wherein said subject has graft-versus-host disease. 28. The method of claim 13, wherein said administration continues for at least six months following transplantation of said graft. 29. The method of claim 15, wherein said inflammatory myopathy is selected from the group consisting of polymyositis, dermatomyositis, and inclusion-body myositis. 30. The method of claim 15, wherein said celiac disease is gluten-sensitive enteropathy. 31. The method of claim 15, wherein said lupus erythematosus is selected from the group consisting of discoid lupus erythematosus, drug-induced lupus erythematosus, and neonatal lupus erythematosus. 32. The method of claim 15, wherein said adult-onset diabetes mellitus is type II diabetes. 33. The method of claim 20, wherein said anti-CD45 antibody is an anti-CD45RB antibody. 34. The method of claim 20, wherein said second agent is belatacept.

Details for Patent 9,987,356

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2031-03-11
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	05/12/1998		2031-03-11
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	01/02/2003		2031-03-11
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	05/07/2001		2031-03-11
Genzyme Corporation	LEMTRADA	alemtuzumab	Injection	103948	11/14/2014		2031-03-11
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	10/12/2004		2031-03-11