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. An antibody or antigen-binding portion thereof having an IGF-1R binding site comprising heavy and light chain variable regions, wherein the heavy chain variable region comprises a CDR1 comprising amino acids 26-35 of SEQ ID NO: 226, a CDR2 comprising amino acids 51-66 of SEQ ID NO: 226, and a CDR3 comprising amino acids 99-111 of SEQ ID NO: 226, and the light chain variable region comprises a CDR1 comprising amino acids 24-34 of SEQ ID NO: 204, a CDR2 comprising amino acids 50-56 of SEQ ID NO: 204, and a CDR3 comprising amino acids 89-97 of SEQ ID NO: 204.
2. The antibody or antigen-binding portion thereof of claim 1 , wherein the antibody or antigen-binding portion thereof is a monoclonal antibody.
3. The antibody or antigen-binding portion thereof of claim 1 , wherein the antibody or antigen-binding portion thereof is a bispecific antibody.
4. The antibody or antigen-binding portion thereof of claim 3 , wherein the bispecific antibody further comprises an ErbB3 binding site.
5. The antibody or antigen-binding portion thereof of claim 4 , wherein the ErbB3 binding site comprises heavy and light chain variable regions, wherein the heavy chain variable region comprises a CDR1 comprising amino acids 492-501 of SEQ ID NO: 226, a CDR2 comprising amino acids 517-532 of SEQ ID NO: 226, and a CDR3 comprising amino acids 565-577 of SEQ ID NO: 226, and the light chain variable region comprises a CDR1 comprising amino acids 634-644 of SEQ ID NO: 226, a CDR2 comprising amino acids 660-666 of SEQ ID NO: 226, and a CDR3 comprising amino acids 699-709 of SEQ ID NO: 226.
6. An antibody or antigen-binding portion thereof having an ErbB3 binding site comprising heavy and light chain variable regions, wherein the heavy chain variable region comprises a CDR1 comprising amino acids 492-501 of SEQ ID NO: 226, a CDR2 comprising amino acids 517-532 of SEQ ID NO: 226, and a CDR3 comprising amino acids 565-577 of SEQ ID NO: 226, and the light chain variable region comprises a CDR1 comprising amino acids 634-644 of SEQ ID NO: 226, a CDR2 comprising amino acids 660-666 of SEQ ID NO: 226, and a CDR3 comprising amino acids 699-709 of SEQ ID NO: 226.
7. The antibody or antigen-binding portion thereof of claim 6 , wherein the antibody or antigen-binding portion thereof is a monoclonal antibody.
8. The antibody or antigen-binding portion thereof of claim 6 , wherein the antibody or antigen-binding portion thereof is a bispecific antibody.
9. The antibody or antigen-binding portion thereof of claim 8 , wherein the bispecific antibody further comprises an IGF-1R binding site.
10. The antibody or antigen-binding portion thereof of claim 9 , wherein the IGF-1R binding site comprises heavy and light chain variable regions, wherein the heavy chain variable region comprises a CDR1 comprising amino acids 26-35 of SEQ ID NO: 226, a CDR2 comprising amino acids 51-66 of SEQ ID NO: 226, and a CDR3 comprising amino acids 99-111 of SEQ ID NO: 226, and the light chain variable region comprises a CDR1 comprising amino acids 24-34 of SEQ ID NO: 204, a CDR2 comprising amino acids 50-56 of SEQ ID NO: 204, and a CDR3 comprising amino acids 89-97 of SEQ ID NO: 204.
11. The antibody or antigen-binding portion thereof of claim 1 , wherein the antibody is an IgG, IgE, IgM, IgD, IgA, or IgY antibody.
12. The antibody or antigen-binding portion thereof of claim 11 , wherein the antibody is an IgG antibody.
13. The antibody or antigen-binding portion thereof of claim 12 , wherein the antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.
14. A composition comprising the antibody or antigen-binding portion thereof of claim 1 and a pharmaceutically acceptable carrier.
15. The composition of claim 14 , wherein the carrier is suitable for injection or infusion.
16. A method of treating a cancer comprising administering to a subject in need thereof a therapeutically effective amount of the antibody or antigen-binding portion thereof of claim 1 .
17. A kit comprising the antibody or antigen-binding portion thereof of claim 1 .
18. The antibody or antigen-binding portion thereof of claim 6 , wherein the antibody is an IgG, IgE, IgM, IgD, IgA, or IgY antibody.
19. The antibody or antigen-binding portion thereof of claim 18 , wherein the antibody is an IgG antibody.
20. The antibody or antigen-binding portion thereof of claim 19 , wherein the antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.
21. A composition comprising the antibody or antigen-binding portion thereof of claim 6 and a pharmaceutically acceptable carrier.
22. The composition of claim 21 , wherein the carrier is suitable for injection or infusion.
23. A method of treating a cancer comprising administering to a subject in need thereof a therapeutically effective amount of the antibody or antigen-binding portion thereof of claim 6 .
24. A kit comprising the antibody or antigen-binding portion thereof of claim 6 .