Monospecific and bispecific anti-IGF-1R and anti-ErbB3 antibodies

Patent metadata

Field	Value
Publication number	US-9938346-B2
Application number	US-201615248562-A
Country	US
Kind code	B2
Filing date	Aug 26, 2016
Priority date	Apr 19, 2011
Publication date	Apr 10, 2018
Grant date	Apr 10, 2018

Abstract

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.

First claim

The invention claimed is:

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 .

Assignees

• Merrimack Pharmaceuticals Inc

Inventors

• Baum Jason
• Johnson Bryan
• Lugovskoy Alexey Alexandrovich
• Xu Lihui
• Kohli Neeraj
• Fitzgerald Jonathan Basil
• Adams Sharlene

Classifications

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• C07K16/468

  Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title