Monospecific and bispecific anti-IGF-1R and anti-ErbB3 antibodies
Provided are monospecific and bispecific antibodies that are useful as anti-neoplastic agents and that bind specifically to human IGF-1R and human ErbB3. Exemplary antibodies inhibit signal transduction through either or both of IGF-1R and ErbB3. Exemplary polyvalent proteins comprise at least one anti-IGF-1R binding site and at least one anti-ErbB3 binding site. In certain embodiments the binding sites may be linked through an immunoglobulin constant region. AntiErbB3 and anti-IGF-1R antibodies (e.g., monoclonal antibodies) are also provided.
1. A bispecific antibody comprising:
a) an IGF-1R binding site comprising heavy and light chain variable regions, wherein the heavy chain variable region comprises a CDR1 comprising amino acid numbers 26-35 of SEQ ID NO: 226, a CDR2 comprising amino acid numbers 51-66 of SEQ ID NO: 226, a CDR3 comprising amino acid numbers 99-111 of SEQ ID NO: 226, and the light chain variable region comprises a CDR1 comprising amino acid numbers 24-34 of SEQ ID NO: 204, a CDR2 comprising amino acid numbers 50-56 of SEQ ID NO: 204, and a CDR3 comprising amino acid numbers 89-97 of SEQ ID NO: 204; and
b) an ErbB3 binding site comprising heavy and light chain variable regions, wherein the heavy chain variable region comprises a CDR1 comprising amino acid numbers 492-501 of SEQ ID NO: 226, a CDR2 comprising amino acid numbers 517-532 of SEQ ID NO: 226, and a CDR3 comprising amino acid numbers 565-577 of SEQ ID NO: 226, and the light chain variable region comprises a CDR1 comprising amino acid numbers 634-644 of SEQ ID NO: 226, a CDR2 comprising amino acid numbers 660-666 of SEQ ID NO: 226, and a CDR3 comprising amino acid numbers 699-709 of SEQ ID NO: 226.
2. A composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
3. The composition of claim 2 wherein the carrier is suitable for injection or infusion.
4. The bispecific antibody of claim 1 , wherein the antibody contains 2 IGF-1R binding sites and 2 ErbB3 binding sites.
5. A composition comprising the antibody of claim 4 and a pharmaceutically acceptable carrier.
6. The composition of claim 5 wherein the carrier is suitable for injection or infusion.