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 alone 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 subject having an autoimmune disorder, an effective amount of a therapeutic composition comprising a pharmaceutically acceptable carrier and at least one anti-CD20 antibody.  
     
     
         38 . The method according to  claim 37 , wherein said antibody is selected from the group consisting of subhuman primate antibody, murine monoclonal antibody, chimeric antibody, humanized antibody, and human antibody.  
     
     
         39 . 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, pamphigus vulgaris, Wegener's granulomatosis, membranous nephropathy, amyotrophic lateral sclerosis, tabes dorsalis, giant cell arteritis/polymyalgia, pernicious anemia, rapidly progressive glomerulonephritis and fibrosing alveolitis.  
     
     
         40 . The method according to  claim 37 , wherein said therapeutic composition is administered parenterally in a dosage of from 20 to 2000 mg per dose.  
     
     
         41 . The method according to  claim 37 , wherein said subject receives said antibody in repeated parenteral dosages.  
     
     
         42 . The method according to  claim 37 , wherein said antibody is a naked antibody.  
     
     
         43 . The method according to  claim 37 , wherein said antibody is a bispecific antibody.  
     
     
         44 . The method according to  claim 43 , wherein said bispecific antibody targets a T-cell, plasma cell or macrophage antigen.  
     
     
         45 . The method according to  claim 37  or  43 , wherein said antibody is directed against different CD20 epitopes.  
     
     
         46 . The method according to  claim 37 , wherein said antibody is conjugated with a drug, a toxins or a therapeutic radioisotopes.  
     
     
         47 . The method according to  claim 37 , wherein said therapeutic composition comprises a naked anti-CD20 antibody and a cytokine, wherein the antibody and the cytokine can be administered concurrently or in any order.  
     
     
         48 . The method according to  claim 37 , further comprising separately administering a secondary therapeutic directed against T-cells, B-cells, plasma cells, or macrophages or inflammatory cytokines.  
     
     
         49 . The method according to claims  47  or  48 , wherein the cytokine is a TNF-αantagonist.  
     
     
         50 . The method according to  claim 47 , wherein said secondary therapeutic is administered prior to the administration of said therapeutic composition.  
     
     
         51 . The method according to  claim 47 , wherein said secondary therapeutic is administered concurrently with the administration of said therapeutic composition.  
     
     
         52 . The method according to  claim 47 , wherein said secondary therapeutic is administered after the administration of said therapeutic composition.  
     
     
         53 . The method according to  claim 47 , wherein said secondary therapeutic is selected from the group consisting of drugs, toxins, enzymes, hormones, cytokines, immunomodulators, boron compounds and therapeutic radioisotopes.  
     
     
         54 . The method according to  claim 37 , further comprising separately administering a secondary therapeutic, wherein the therapeutic is a cytokine antagonist