Anti-ifnar1 antibodies with reduced fc ligand affinity

Abstract

The invention provides anti-IFNAR1 antibodies with reduced affinity for Fc receptors and/or ligands and methods of making and using such antibodies.

1 - 31 . (canceled) 
     
     
         31 . A method of treating a condition or a disease associated with an immune disorder, comprising administering to a subject in need thereof an effective amount of the composition of a pharmaceutical composition comprising an a modified IgG class monoclonal antibody specific for IFNAR1, wherein said antibody comprises in the Fc region at least one amino acid substitution selected from the group consisting of L234F, L235E, and P331 S, as numbered by the EU index as set forth in Kabat and wherein said antibody exhibits reduced affinity for at least one Fc ligand compared to an unmodified antibody. 
     
     
         32 . The method of  claim 31  wherein said disease is a type I interferon mediated disease. 
     
     
         33 . The method of  claim 32  wherein said type I interferon is interferon alpha. 
     
     
         34 . The method of  claim 33  wherein said type I interferon mediated disease is associated with the type I interferon receptor. 
     
     
         35 . The method of  claim 31 , wherein said disease or disorder is HIV infection of AIDS. 
     
     
         36 . The method of  claim 31 , wherein said disease or disorder is systemic lupus erythematosus. 
     
     
         37 . The method of  claim 31 , wherein said disease or disorder is Sjogren's syndrome. 
     
     
         38 . The method of  claim 31 , wherein said disease or disorder is myositis. 
     
     
         39 . The method of  claim 31 , wherein said disease or disorder is inflammatory myositis. 
     
     
         40 . The method of  claim 31 , wherein said disease or disorder is polymyositis. 
     
     
         41 . The method of  claim 31 , wherein said disease or disorder is dermatomyositis. 
     
     
         42 . The method of  claim 31 , wherein said disease or disorder is inclusion body myositis. 
     
     
         43 . The method of  claim 31 , wherein said disease or disorder is juvenile myositis. 
     
     
         44 . The method of  claim 31 , wherein said disease or disorder is idiopathic inflammatory myositis. 
     
     
         45 . The method of  claim 31 , wherein said disease or disorder is vasculitis. 
     
     
         46 . The method of  claim 31 , wherein said disease or disorder is sarcoidosis. 
     
     
         47 . The method of  claim 31 , wherein said disease or disorder is selected from the group consisting of: inflammatory bowel disease, multiple sclerosis, autoimmune thyroiditis, rheumatoid arthritis, insulin dependent diabetes mellitus, glomerulonephritis, and graft versus host disease. 
     
     
         48 . The method of  claim 31 , wherein said disease or disorder is psoriasis or conditions resulting thereof. 
     
     
         49 . The method of  claim 31 , wherein said disease or disorder is transplant rejection or graft versus host disease. 
     
     
         50 . The method of  claim 31  wherein said disease or disorder is selected from the group consisting of: Grave's disease, Hashimoto's thyroiditis, Crohn's disease, psoriasis, psoriatic arthritis, sympathetic opthalmitis, autoimmune oophoritis, autoimmune orchitis, autoimmune lymphoproliferative syndrome, antiphospholipid syndrome, Sjogren's syndrome, scleroderma, Addison's disease, polyendocrine deficiency syndrome, Guillan-Barre syndrome, immune thrombocytopenic purpura, pernicious anemia, myasthenia gravis, primary biliary cirrhosis, mixed connective tissue disease, vitiligo, autoimmune uveitis, autoimmune hemolytic anemia, autoimmune thrombopocytopenia, celiac disease, dermatitis herpetiformis, autoimmune hepatitis, pemphigus, pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, autoimmune myocarditis, autoimmune vasculitis, alopecia areata, autoimmune artherosclerosis, Behcet's disease, autoimmune myelopathy, autoimmune hemophelia, autoimmune interstitial cystitis, autoimmune diabetes isipidus, autoimmune endometriosis, relapsing polychondritis, ankylosing spondylitis, autoimmune urticaria, dermatomyositis, Miller-Fisher syndrome, IgA nephropathy, goodpastures syndrome, and herpes gestationis. 
     
     
         51 . The method of any of  claim 31 , further comprising administering at least one agent selected from the group consisting of: phototherapy, corticosteroids, prednisone, NSAIDS, plasmapheresis, immunosuppressants, methotrexate, retinoic acid, tioguanine, mycophenolate mofetil, fumaric esters, cyclophosphamide, azathioprine, cyclosporine, and immunoglobulins. 
     
     
         52 . The method of any of  claim 31  further comprising administering at least one agent selected from the group consisting of: alefacept (AMEVIVE™), etanercept (ENBREL<®>), adalimumab (HUMIRA<®>), inflixinab (REMICADE<®>), belimumab (LYMPHOSTATB™), rituxumab (RITUXAN<®>), and efalizumab (RAPTIV A<®>). 
     
     
         53 - 67 . (canceled)