B cell surface reactive antibodies

Abstract

The invention relates to antibodies that are reactive to the cell surface of CD19+ B cells, including B-cell chronic lymphocytic leukemia (B-CLL) cells, and compositions and methods for using such antibodies, including in the diagnosis and treatment of disorders associated with CD19+ B cells, such as B-CLL.

1 . An isolated antibody having B-cell chronic lymphocytic leukemia (B-CLL) cell surface reactivity, wherein the antibody comprises:
 (a) a light chain variable domain having at least 95% identity to a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:12, and SEQ ID NO:14; and   (b) a heavy chain variable domain having at least 95% identity to a sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:26, SEQ ID NO:31, and SEQ ID NO:33.   
     
     
         2 . The antibody of  claim 1 , wherein the light chain variable domain has at least 96% identity to a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:12, and SEQ ID NO:14. 
     
     
         3 . The antibody of  claim 2 , wherein the light chain variable domain has at least 97% identity to a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:12, and SEQ ID NO:14. 
     
     
         4 . The antibody of  claim 3 , wherein the light chain variable domain has at least 98% identity to a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:12, and SEQ ID NO:14. 
     
     
         5 . The antibody of  claim 1 , wherein the heavy chain variable domain has at least 96% identity to a sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:26, SEQ ID NO:31, or SEQ ID NO:33. 
     
     
         6 . The antibody of  claim 5 , wherein the heavy chain variable domain has at least 97% identity to a sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:26, SEQ ID NO:31, or SEQ ID NO:33. 
     
     
         7 . The antibody of  claim 6 , wherein the heavy chain variable domain has at least 98% identity to a sequence selected from the group consisting of SEQ ID NO:18, SEQ ID NO:26, SEQ ID NO:31, or SEQ ID NO:33. 
     
     
         8 .- 14 . (canceled) 
     
     
         15 . The antibody of  claim 1 , wherein the antibody is selected from the group consisting of IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, IgM, Fab2, Fv, scFV, IgGΔACH 2 , F(ab′)2, Fab, dsFv, Fv, scFV-Fc, a non-depleting IgG, a diabody, a T-body, a bispecific antibody, and a bivalent antibody. 
     
     
         16 . The antibody of  claim 15 , wherein the antibody is an IgG selected from the group consisting of IgG1, IgG2, IgG3, IgG4, and synthetic IgG. 
     
     
         17 . The antibody of  claim 15 , wherein the antibody is an Fab. 
     
     
         18 . The antibody of  claim 15 , wherein the antibody is a dsFv. 
     
     
         19 . The antibody of  claim 1 , wherein the antibody is conjugated to a synthetic molecule. 
     
     
         20 . The antibody of  claim 19 , wherein the antibody is a T-body, and the synthetic molecule comprises a transmembrane region and an intracellular T-cell receptor (TCR) signaling domain. 
     
     
         21 . The antibody of  claim 19 , wherein the synthetic molecule is a label. 
     
     
         22 . The antibody of  claim 19 , wherein the synthetic molecule is a cytotoxic agent or a therapeutic radioisotope. 
     
     
         23 . The antibody of  claim 1 , wherein the antibody is a fully human antibody. 
     
     
         24 . A pharmaceutical composition comprising a therapeutically effective amount of an isolated antibody of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         25 . A kit comprising the isolated antibody of  claim 1 . 
     
     
         26 . The kit of  claim 25 , further comprising one or more immunoassay buffers. 
     
     
         27 . The kit of  claim 25 , wherein the antibody is conjugated to a label. 
     
     
         28 .- 45 . (canceled)