ANTI-BRDU ANTIBODIES AND METHODS OF USE
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.