Antibodies selective for cells presenting erbb2 at high density

An antibody or a bivalent fragment thereof that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density, the antibody comprising:

• a heavy chain (HC) comprising a complementarity determining region (CDR)1 comprising the sequence GFNIKDTYIH (SEQ ID NO:
• 1);
• a CDR2 comprising the sequence RIYPTNGY57TR59YADSVKG (SEQ ID NO:
• 2);
• and a CDR3 comprising the sequence WGGDGFYAMDY (SEQ ID NO:
• 3);
• and
• a light chain (LC) comprising a CDR1 comprising the sequence RASQDVN30TAVA (SEQ ID NO:
• 4);
• a CDR2 comprising the sequence SASF53LYS (SEQ ID NO:
• 5);
• and a CDR3 comprising the sequence QQHY92TTPPT (SEQ ID NO. 6),
• wherein the heavy chain and the light chain contain substitutions consisting of HC Y57A, LC F53N, and LC Y92A.

An antibody or a bivalent fragment thereof comprising a heavy chain and a light chain, each chain having a constant region and a variable region, each variable region comprising framework regions and complementarity determining regions (CDRs), wherein:

• the heavy chain (HC) comprises a CDR1 comprising the sequence GFNIKDTYIH (SEQ ID NO:
• 1);
• a CDR2 comprising the sequence RIYPTNGY57TR59YADSVKG (SEQ ID NO:
• 2);
• and a CDR3 comprising the sequence WGGDGFYAMDY (SEQ ID NO:
• 3);
• and
• the light chain (LC) comprises a CDR1 comprising the sequence RASQDVN30TAVA (SEQ ID NO:
• 4);
• a CDR2 comprising the sequence SASF53LYS (SEQ ID NO:
• 5);
• and a CDR3 comprising the sequence QQHY92TTPPT (SEQ ID NO. 6),
• wherein the heavy chain and the light chain contain substitutions consisting of HC Y57A, LC F53N, and LC Y92A, and wherein the antibody further comprises the framework region sequences of trastuzumab.