Monospecific and bispecific anti-igf-1r and anti-erbb3 antibodies

Patent metadata

Field	Value
Publication number	US-2017051063-A1
Application number	US-201615248562-A
Country	US
Kind code	A1
Filing date	Aug 26, 2016
Priority date	Apr 19, 2011
Publication date	Feb 23, 2017
Grant date	—

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

1 . A binding agent 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, 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 binding agent of claim 1 , which is an antibody.

3 . The binding agent of claim 2 , wherein the antibody is a monoclonal antibody.

4 . The binding agent of claim 2 , wherein the antibody is a bispecific antibody.

5 . The binding agent of claim 4 , wherein the bispecific antibody further comprises an ErbB3 binding site.

6 . The binding agent of claim 5 , 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.

7 . A binding agent 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.

8 . The binding agent of claim 7 , which is an antibody.

9 . The binding agent of claim 8 , wherein the antibody is a monoclonal antibody.

10 . The binding agent of claim 8 , wherein the antibody is a bispecific antibody.

11 . The binding agent of claim 10 , wherein the bispecific antibody further comprises an IGF-1R binding site.

12 . The binding agent of claim 11 , 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, 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.

13 . The binding agent of claim 1 , wherein the antibody is an IgG, IgE, IgGM, IgD, IgA, or IgY antibody.

14 . The binding agent of claim 13 , wherein the antibody is an IgG antibody.

15 . The binding agent of claim 14 , wherein the antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

16 . A composition comprising the binding agent of claim 1 and a pharmaceutically acceptable carrier.

17 . The composition of claim 16 , wherein the carrier is suitable for injection or infusion.

18 . A method of treating a cancer comprising administering to a subject in need thereof a therapeutically effective amount of the binding agent of claim 1 .

19 . A kit comprising the binding agent of claim 1 .

20 . The binding agent of claim 7 , wherein the antibody is an IgG, IgE, IgGM, IgD, IgA, or IgY antibody.

21 . The binding agent of claim 20 , wherein the antibody is an IgG antibody.

22 . The binding agent of claim 21 , wherein the antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

23 . A composition comprising the binding agent of claim 7 and a pharmaceutically acceptable carrier.

24 . The composition of claim 23 , wherein the carrier is suitable for injection or infusion.

25 . A method of treating a cancer comprising administering to a subject in need thereof a therapeutically effective amount of the binding agent of claim 7 .

26 . A kit comprising the binding agent of claim 7 .

Assignees

• Merrimack Pharmaceuticals Inc

Inventors

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

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• C07K16/2869

  against hormone receptors (for antibodies against neuromediator receptors C07K16/286) · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/92

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