Levels of bcma protein expression on b cells and use in diagnostic methods of treating systemic lupus erythematosus

Abstract

The present invention provides a method of measuring the levels of BCMA in a biological sample, specifically upon the B cell surface. The diagnostic assays are useful in predicting an individual's likelihood of developing or currently suffering from an autoimmune disease, such as SLE, and for methods for treating an individual clinically diagnosed with an autoimmune disease. This diagnostic test serves to predict a patient's likelihood to respond to a specific drug treatment, in particular treatment with BLyS antagonists, either singly or in combination with other immune suppressive drugs

That which is claimed: 
     
         1 . A bispecific antibody comprising:
 (a) a first antigen binding moiety that binds to CD3; and   (b) a second antigen binding moiety that binds to B cell maturation agent (BCMA).   
     
     
         2 . The bispecific antibody of  claim 1 , wherein second antigen binding moiety binds the extracellular domain of BCMA. 
     
     
         3 . The bispecific antibody of  claim 2 , wherein said extracellular domain of BCMA comprises amino acids 1-48 of SEQ ID NO: 6, amino acids 1-41 of SEQ ID NO: 6, amino acids 8-41 of SEQ ID NO: 6, amino acids 8-37 of SEQ ID NO: 6, amino acids 8-88 of SEQ ID NO: 6, amino acids 41-88 of SEQ ID NO: 6, amino acids 1-54 of SEQ ID NO:6, amino acids 4-55 of SEQ ID NO:6, amino acids 4-51 of SEQ ID NO:6, amino acids 21-53 of SEQ ID NO:6, or amino acids 1-150 of SEQ ID NO: 6. 
     
     
         4 . The bispecific antibody of  claim 1 , wherein said first antigen binding moiety binds an extracellular epitope of CD3. 
     
     
         5 . A polynucleotide encoding the bispecific antibody of  claim 1 . 
     
     
         6 . A vector comprising the polynucleotide of  claim 5 . 
     
     
         7 . A host cell transformed or transfected with the polynucleotide of  claim 5 . 
     
     
         8 . A method for treating or delaying progression of a proliferative disease or autoimmune disease in a subject, wherein the method comprises administering to the subject an effective amount of a bispecific antibody comprising:
 (a) a first antigen binding moiety that binds to CD3; and   (b) a second antigen binding moiety that binds to B cell maturation agent (BCMA).   
     
     
         9 . The method of  claim 8 , wherein said second antigen binding moiety binds the extracellular domain of BCMA. 
     
     
         10 . The method of  claim 9 , wherein said extracellular domain of BCMA comprises amino acids 1-48 of SEQ ID NO: 6, amino acids 1-41 of SEQ ID NO: 6, amino acids 8-41 of SEQ ID NO: 6, amino acids 8-37 of SEQ ID NO: 6, amino acids 8-88 of SEQ ID NO: 6, amino acids 41-88 of SEQ ID NO: 6, amino acids 1-54 of SEQ ID NO:6, amino acids 4-55 of SEQ ID NO:6, amino acids 4-51 of SEQ ID NO:6, amino acids 21-53 of SEQ ID NO:6, or amino acids 1-150 of SEQ ID NO: 6. 
     
     
         11 . The method of  claim 8 , wherein said first antigen binding moiety binds an extracellular epitope of CD3. 
     
     
         12 . The method of  claim 8 , wherein said subject is further administered an effective amount of a TACI-Ig fusion protein. 
     
     
         13 . The method of  claim 12 , wherein said TACI-Ig fusion protein is atacicept. 
     
     
         14 . The method of  claim 13 , wherein said bispecific antibody and atacicept are administered together in a single composition. 
     
     
         15 . The method of  claim 13 , wherein said bispecific antibody and atacicept are administered separately in two different compositions. 
     
     
         16 . The method of  claim 13 , wherein said bispecific antibody and atacicept are administered intravenously or subcutaneously. 
     
     
         17 . The method of  claim 8 , wherein the proliferative disease is a B cell proliferative disorder. 
     
     
         18 . The method of  claim 8 , wherein the autoimmune disease is 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, or glomerulonephritis. 
     
     
         19 . A method for localizing CD3 to B cells, said method comprising administering a bispecific antibody comprising:
 (a) a first antigen binding moiety that binds to CD3; and   (b) a second antigen binding moiety that binds to B cell maturation agent (BCMA),   
       wherein said bispecific antibody is administered to a biological sample comprising at least one B cell and at least on CD3 molecule. 
     
     
         20 . The method of  claim 19 , wherein said biological sample is an in vitro biological sample. 
     
     
         21 . The method of  claim 19 , wherein second antigen binding moiety binds the extracellular domain of BCMA 
     
     
         22 . The method of  claim 21 , wherein said extracellular domain of BCMA comprises amino acids 1-48 of SEQ ID NO: 6, amino acids 1-41 of SEQ ID NO: 6, amino acids 8-41 of SEQ ID NO: 6, amino acids 8-37 of SEQ ID NO: 6, amino acids 8-88 of SEQ ID NO: 6, amino acids 41-88 of SEQ ID NO: 6, amino acids 1-54 of SEQ ID NO:6, amino acids 4-55 of SEQ ID NO:6, amino acids 4-51 of SEQ ID NO:6, amino acids 21-53 of SEQ ID NO:6, or amino acids 1-150 of SEQ ID NO: 6. 
     
     
         23 . The method of  claim 19 , wherein said first antigen binding moiety binds an extracellular epitope of CD3. 
     
     
         24 . A composition comprising a bispecific antibody comprising:
 (a) a first antigen binding moiety that binds to CD3; and   (b) a second antigen binding moiety that binds to B cell maturation agent (BCMA) wherein said bispecific antibody is bound to BCMA.   
     
     
         25 . The composition of  claim 24 , wherein second antigen binding moiety is bound to the extracellular domain of BCMA. 
     
     
         26 . The composition of  claim 25 , wherein said extracellular domain of BCMA comprises amino acids 1-48 of SEQ ID NO: 6, amino acids 1-41 of SEQ ID NO: 6, amino acids 8-41 of SEQ ID NO: 6, amino acids 8-37 of SEQ ID NO: 6, amino acids 8-88 of SEQ ID NO: 6, amino acids 41-88 of SEQ ID NO: 6, amino acids 1-54 of SEQ ID NO:6, amino acids 4-55 of SEQ ID NO:6, amino acids 4-51 of SEQ ID NO:6, amino acids 21-53 of SEQ ID NO:6, or amino acids 1-150 of SEQ ID NO: 6. 
     
     
         27 . The composition of  claim 25 , wherein said composition is further bound to CD3. 
     
     
         28 . The composition of  claim 27 , wherein said first antigen binding moiety is bound to an extracellular epitope of CD3.