Anti-brdu antibodies and methods of use

Abstract

The invention provides anti-BRDU antibodies and methods of using the same.

1 . A humanized anti-BRDU antibody, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 01, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 04, and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 05, further comprising (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 06, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 07, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 08,
 wherein the antibody comprises
 P at position 30 of the heavy chain variable domain, and 
 F at position 58 of the heavy chain variable domain, and 
 T at position 108 of the heavy chain variable domain, and 
 K at position 49 of the light chain variable domain, and 
 L at position 98 of the light chain variable domain (all positions according to Kabat). 
   
     
     
         2 - 4 . (canceled) 
     
     
         5 . A humanized anti-BRDU antibody, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 01, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 13, and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 05, further comprising (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 06, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 07, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 08,
 wherein the antibody comprises
 P at position 30 of the heavy chain variable domain, and 
 F at position 58 of the heavy chain variable domain, and 
 T at position 108 of the heavy chain variable domain, and 
 K at position 49 of the light chain variable domain, and 
 L at position 98 of the light chain variable domain (all positions according to Kabat). 
   
     
     
         6 - 13 . (canceled) 
     
     
         14 . The humanized anti-BRDU antibody according to  claim 1  or  5 , wherein the antibody comprises a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 09 and a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10. 
     
     
         15 . (canceled) 
     
     
         16 . The humanized anti-BRDU antibody according to  claim 1  or  5 , wherein the antibody is a humanized variant of a non-human anti-BRDU antibody comprising the heavy chain variable domain of SEQ ID NO: 11 and the light chain variable domain of SEQ ID NO: 12. 
     
     
         17 . The humanized anti-BRDU antibody according to any one of  claims 1 ,  5 ,  14  or  16 , wherein the antibody comprises a VH with the amino acid sequence of SEQ ID NO: 09. 
     
     
         18 . The humanized anti-BRDU antibody according to any one of  claims 1 ,  5 ,  14 ,  16  or  17 , wherein the antibody comprises a VL with the amino acid sequence of SEQ ID NO: 10. 
     
     
         19 . A complex comprising the humanized anti-BRDU antibody according to any one of  claims 1 ,  5 ,  14 ,  16 ,  17  or  18  and a nucleic acid comprising BRDU. 
     
     
         20 . A covalent complex comprising the humanized anti-BRDU antibody according to any one of claims 5, 14, 16, 17, or 18 and a BRDU conjugated to a cysteine residue. 
     
     
         21 . A pharmaceutical formulation comprising the humanized anti-BRDU antibody according to any one of  claims 1 ,  5 ,  14 ,  16 ,  17 , or  18  or a complex according to any one of  claim 19  or  20  and a pharmaceutically acceptable carrier. 
     
     
         22 . Use of an antibody comprising
 a) the light chain of a first antibody that specifically binds to a first antigen, and   b) the heavy chain of the first antibody that specifically binds to the first antigen conjugated at its C-terminus to a scFv or a scFab derived from a second antibody that specifically binds to a second antigen,   whereby either the first antibody or the second antibody is an anti-BRDU antibody according to any one of  claim 1 ,  5 ,  14 ,  16 ,  17 , or  18 ,   for the delivery of a BRDU containing nucleic acid to a cell.   
     
     
         23 - 31 . (canceled) 
     
     
         32 . The use according to  claim 22  wherein the anti-BRDU antibody comprises a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 09 and a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10. 
     
     
         33 . (canceled) 
     
     
         34 . The use according to any one of  claim 22  or  32  wherein the anti-BRDU antibody is a humanized variant of a non-human anti-BRDU antibody comprising the heavy chain variable domain of SEQ ID NO: 11 and the light chain variable domain of SEQ ID NO: 12.