Antibodies that immunospecifically bind to b lymphocyte stimulator protein

Abstract

The present invention relates to antibodies and related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention also relates to methods and compositions for detecting or diagnosing a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate function of B Lymphocyte Stimulator comprising antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention further relates to methods and compositions for preventing, treating or ameliorating a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate B Lymphocyte Stimulator function comprising administering to an animal an effective amount of one or more antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator.

1 . A method of treating an individual clinically diagnosed with an autoimmune disease, comprising:
 analyzing a biological sample from an individual clinically diagnosed with autoimmune disease for the presence or absence of elevated BCMA protein expression levels on their B cells, wherein the presence of elevated BCMA protein expression levels is associated with the clinical diagnosis of autoimmune disease; and   selecting a treatment plan that is most effective for individuals clinically diagnosed as having a condition associated with an increased BCMA protein expression level.   
     
     
         2 . The method of  claim 1  wherein said treatment plan involves administration of a BLyS antagonist. 
     
     
         3 . The method of  claim 2  wherein said BLyS antagonist is also an APRIL antagonist. 
     
     
         4 . The method of  claim 1 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         5 . The method of  claim 1  wherein said autoimmune disease is SLE. 
     
     
         6 . A method for predicting a patient's likelihood to respond to a drug treatment for an autoimmune disease, comprising determining the level of BCMA protein expression on the patient's B cells, wherein the presence of elevated BCMA protein expression levels is predictive of the patient's likelihood to respond to a drug treatment for the condition. 
     
     
         7 . The method of  claim 6  wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         8 . The method of  claim 6  wherein said autoimmune disease is SLE. 
     
     
         9 . The method of  claim 6  wherein said drug treatment involves administration of a BLyS antagonist. 
     
     
         10 . The method of  claim 9  wherein said BLyS antagonist is also an APRIL antagonist. 
     
     
         11 . An in vitro method of selecting a treatment plan that is most effective for treating an individual clinically diagnosed with an autoimmune disease, comprising: analyzing in vitro a biological sample from an individual clinically diagnosed with autoimmune disease for the presence or absence of elevated BCMA levels on their B cells, wherein the presence of elevated BCMA levels is associated with the clinical diagnosis of autoimmune disease. 
     
     
         12 . The method of  claim 11  wherein said treatment plan involves the use of a BLyS antagonist. 
     
     
         13 . The method of  claim 12  wherein said BLyS antagonist is also an APRIL antagonist. 
     
     
         14 . The method of  claim 11 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         15 . The method of  claim 11  wherein said autoimmune disease is SLE. 
     
     
         16 . An in vitro method for predicting a patient's likelihood to respond to a drug treatment for an autoimmune disease, comprising determining the level of BCMA expression on the surface of B cells in a sample from the patient; wherein the presence of elevated B cell levels is predictive of the patient's likelihood to respond to a drug treatment for the condition. 
     
     
         17 . The method of  claim 16  wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener's disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         18 . The method of  claim 16  wherein said autoimmune disease is SLE. 
     
     
         19 . The method of  claim 16  wherein said drug treatment comprises a BLyS antagonist. 
     
     
         20 . The method of  claim 19  wherein said BLyS antagonist is also an APRIL antagonist. 
     
     
         21 . A BLyS antagonist for use in the treatment of an autoimmune disease in a patient, wherein said patient has elevated levels of BCMA expression on the surface of B cells. 
     
     
         22 . The antagonist of  claim 21  wherein the autoimmune disease is SLE. 
     
     
         23 . The antagonist of  claim 21  wherein said antagonist is a BLyS antibody. 
     
     
         24 . The antagonist of  claim 23  wherein said BLyS antibody is Lymphostat-B. 
     
     
         25 . The antagonist of  claim 23  wherein said antagonist is a receptor-extracellular domain/Fc domain fusion protein selected from the group consisting of TACI-Ig, BCMA-Ig, and BAFF-R-Ig. 
     
     
         26 . The antagonist of  claim 25  wherein said receptor-extracellular domain/Fc domain fusion protein is TACI-Ig. 
     
     
         27 . The antagonist of  claim 26  wherein said TACI-Ig is atacicept. 
     
     
         28 . A method of treating an individual diagnosed with an autoimmune disease, comprising:
 analyzing a biological sample from an individual diagnosed with an autoimmune disease for the presence or absence of elevated B Lymphocyte Stimulator receptor protein expression levels, wherein the presence of elevated B Lymphocyte Stimulator receptor protein expression levels is associated with the diagnosis of autoimmune disease; and   treating the individual.   
     
     
         29 . The method of  claim 28 , wherein the method further comprises selecting a treatment plan that is most effective for individuals diagnosed as having a condition associated with an increased B Lymphocyte Stimulator receptor protein expression level prior to treating the individual 
     
     
         30 . The method of  claim 28 , wherein the B Lymphocyte Stimulator receptor is BCMA. 
     
     
         31 . The method of  claim 29 , wherein the B Lymphocyte Stimulator receptor is BCMA. 
     
     
         32 . The method of  claim 28 , wherein treating the individual comprises administering a BLyS antagonist. 
     
     
         33 . The method of  claim 29 , wherein the treatment plan involves administration of a BLyS antagonist. 
     
     
         34 . The method of  claim 28 , wherein the BLyS antagonist is also an APRIL antagonist. 
     
     
         35 . The method of  claim 29 , wherein the BLyS antagonist is also an APRIL antagonist. 
     
     
         36 . The method of  claim 28 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune throbocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         37 . The method of  claim 29 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune throbocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         38 . The method of  claim 28 , wherein the autoimmune disease is SLE. 
     
     
         39 . The method of  claim 29 , wherein the autoimmune disease is SLE. 
     
     
         40 . A method for determining whether or not a patient diagnosed with an autoimmune disease will respond to treatment with a BLyS antagonist, comprising determining the level of B Lymphocyte Stimulator receptor protein expression on the patient's cells, wherein the presence of elevated B Lymphocyte Stimulator receptor protein expression levels is indicative of whether or not the patient will respond to the treatment. 
     
     
         41 . The method of  claim 40 , wherein the B Lymphocyte Stimulator receptor is BCMA. 
     
     
         42 . The method of  claim 40 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune thrombocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         43 . The method of  claim 40 , wherein the autoimmune disease is SLE. 
     
     
         44 . The method of  claim 40 , wherein the BLyS antagonist is also an APRIL antagonist. 
     
     
         45 . An in vitro method of selecting a treatment that is most effective for treating an individual diagnosed with an autoimmune disease, comprising analyzing in vitro a biological sample from an individual diagnosed with an autoimmune disease for the presence or absence of elevated B Lymphocyte Stimulator receptor levels on their cells, wherein the presence of elevated B Lymphocyte Stimulator receptor levels is associated with the diagnosis of the autoimmune disease. 
     
     
         46 . The method of  claim 45 , wherein the B Lymphocyte Stimulator receptor is BCMA. 
     
     
         47 . The method of  claim 45 , wherein the treatment involves the use of a BLyS antagonist. 
     
     
         48 . The method of  claim 47 , wherein the BLyS antagonist is also an APRIL antagonist. 
     
     
         49 . The method of  claim 45 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune thrombocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         50 . The method of  claim 45 , wherein the autoimmune disease is SLE. 
     
     
         51 . An in vitro method for determining whether or not a patient diagnosed with an autoimmune disease will respond to treatment with a BLyS antagonist, comprising determining the level of B Lymphocyte Stimulator receptor expression on the surface of cells in a sample from the patient; wherein the presence of elevated B Lymphocyte Stimulator receptor levels is indicative of whether or not the patient will respond to the treatment. 
     
     
         52 . The method of  claim 51 , wherein the B Lymphocyte Stimulator receptor is BCMA. 
     
     
         53 . The method of  claim 51 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune thrombocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud's syndrome, Sjorgen's syndrome and glomerulonephritis. 
     
     
         54 . The method of  claim 51 , wherein the autoimmune disease is SLE. 
     
     
         55 . The method of  claim 51 , wherein the BLyS antagonist is also an APRIL antagonist. 
     
     
         56 . A BLyS antagonist for use in the treatment of an autoimmune disease in a patient, wherein the patient has elevated levels of B Lymphocyte Stimulator receptor expression on the surface of cells. 
     
     
         57 . The antagonist of  claim 56 , wherein the B Lymphocyte Stimulator receptor is BCMA. 
     
     
         58 . The antagonist of  claim 56 , wherein the autoimmune disease is SLE. 
     
     
         59 . The antagonist of  claim 56 , wherein the antagonist is a BLyS antibody. 
     
     
         60 . The antagonist of  claim 59 , wherein the BLyS antibody comprises amino acid residues 1-123 of SEQ ID NO: 327 and amino acid residues 141-249 of SEQ ID NO: 327. 
     
     
         61 . The antagonist of  claim 56 , wherein the antagonist is a receptor-extracellular domain/Fc domain fusion protein selected from the group consisting of TACI-Ig, BCMA-Ig, and BAFF-R-Ig. 
     
     
         62 . The antagonist of  claim 56 , wherein the receptor-extracellular domain/Fc domain fusion protein is TACI-Ig.