Immunotherapy of autoimmune disorders using antibodies which target b-cells

Abstract

Antibodies that bind with a B-cell antigen provide an effective means to treat autoimmune disorders. Antibodies and fragments, which may be conjugated or naked, are used Mono or in multimodal therapies. The antibodies may be bispecific antibodies which May be produced recombinantly as fusion proteins, or as hybrid, polyspecific antibodies.

1 - 36 . (canceled) 
     
     
         37 . A method for treating an autoimmune disorder, comprising administering to a human subject having an autoimmune disorder, a therapeutic composition comprising a pharmaceutically acceptable carrier and at least one humanized naked anti-CD20 antibody, wherein said antibody binds human or murine CD20 and said administering of said anti-CD20 antibody consists of administration of a single subcutaneous injection in a dose of 20 to 100 mg protein, said administering being in an amount effective to inactivate or kill B-cells. 
     
     
         38 . The method according to  claim 37 , wherein said autoimmune disease is selected from the group consisting of acute idiopathic thrombocytopenic purpura, chronic idiopathic thrombocytopenic purpura, dermatomyositis, Sydenham's chorea, myasthenia gravis, systemic lupus erythematosus, lupus nephritis, rheumatic fever, polyglandular syndromes, bullous pemphigoid, diabetes mellitus, Henoch-Schonlein purpura, post-streptococcal nephritis, erythema nodosum, Takayasu's arteritis, Addison's disease, rheumatoid arthritis, multiple sclerosis, sarcoidosis, ulcerative colitis, erythema multiforme, IgA nephropathy, polyarteritis nodosa, ankylosing spondylitis, Goodpasture's syndrome, thromboangitis ubiterans, Sjogren's syndrome, primary biliary cirrhosis, Hashimoto's thyroiditis, thyrotoxicosis, scleroderma, chronic active hepatitis, polymyositis/dermatomyositis, polychondritis, pemphigus vulgaris, Wegener's granulomatosis, membranous nephropathy, amyotrophic lateral sclerosis, tabes dorsalis, giant cell arteritis/polymyalgia, pernicious anemia, rapidly progressive glomerulonephritis and fibrosing alveolitis. 
     
     
         39 . The method according to  claim 37 , wherein said single subcutaneous injections are repeated. 
     
     
         40 . The method according to  claim 37 , wherein said anti-CD20 antibody is a naked humanized antibody. 
     
     
         41 . The method according to  claim 37 , wherein said therapeutic composition comprises a naked anti-CD20 antibody and a drug, wherein the antibody and the drug can be administered concurrently or in any order. 
     
     
         42 . The method according to  claim 41 , further comprising separately administering a secondary therapeutic against T-cells. 
     
     
         43 . The method according to  claim 41 , wherein said drug is administered prior to the administration of said anti-CD20 antibody. 
     
     
         44 . The method according to  claim 41 , wherein said drug is administered concurrently with the administration of said anti-CD20 antibody. 
     
     
         45 . The method according to  claim 41 , wherein said drug is administered after the administration of said anti-CD20 antibody. 
     
     
         46 . The method according to  claim 37 , comprising separate administration of a secondary therapeutic targeted against a CD4 or CD5 epitope. 
     
     
         47 . The method according to  claim 37 , wherein said autoimmune disease is autoimmune thyrotoxicosis. 
     
     
         48 . The method according to  claim 42 , wherein said autoimmune disease is autoimmune thyrotoxicosis. 
     
     
         49 . The method according to  claim 37 , wherein said single subcutaneous injection is repeated at weekly intervals. 
     
     
         50 . A method for treating an autoimmune disorder, comprising administering to a human subject having an autoimmune disorder an initial treatment with a therapeutic composition which inactivates or kills B-cells, the therapeutic composition comprising a pharmaceutically acceptable carrier and at least one humanized naked anti-CD20 antibody, wherein said antibody binds human or murine CD20 and said initial treatment consists of administration of a therapeutically effective single subcutaneous injection of said anti-CD20 antibody in a dose of 20 to 100 mg protein, followed by repeat treatments consisting of administration of therapeutically effective single subcutaneous injections of said anti-CD20 antibody in a dose of 20 to 100 mg protein. 
     
     
         51 . The method according to  claim 50 , comprising separate administration of a secondary therapeutic targeted against T-cells. 
     
     
         52 . The method according to  claim 50 , wherein said anti-CD20 antibody is a naked humanized antibody. 
     
     
         53 . The method according to  claim 50 , wherein said therapeutic composition comprises a naked anti-CD20 antibody and a drug, wherein the antibody and the drug can be administered concurrently or in any order. 
     
     
         54 . The method according to  claim 53 , further comprising separately administering a secondary therapeutic against T-cells. 
     
     
         55 . The method according to  claim 53 , wherein said drug is administered prior to the administration of said anti-CD20 antibody. 
     
     
         56 . The method according to  claim 53 , wherein said drug is administered concurrently with the administration of said anti-CD20 antibody. 
     
     
         57 . The method according to  claim 53 , wherein said drug is administered after the administration of said anti-CD20 antibody. 
     
     
         58 . The method according to  claim 50 , comprising separate administration of a secondary therapeutic targeted against a CD4 or CD5 epitope. 
     
     
         59 . The method according to  claim 50 , wherein said autoimmune disease is autoimmune thyrotoxicosis.