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

Patent metadata

Field	Value
Publication number	US-9527914-B2
Application number	US-201514857344-A
Country	US
Kind code	B2
Filing date	Sep 17, 2015
Priority date	Apr 19, 2011
Publication date	Dec 27, 2016
Grant date	Dec 27, 2016

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. 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.

Assignees

• Merrimack Pharmaceuticals Inc

Inventors

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

Classifications

• C07K2317/33

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

• C07K16/468

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

• C07K2317/60

  characterized by non-natural combinations of immunoglobulin fragments · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/32

  against translation products of oncogenes · CPC title