Method of combination therapy using an EGFR antagonist and anti-c-Met antibody

Patent metadata

Field	Value
Publication number	US-9572878-B2
Application number	US-201414227759-A
Country	US
Kind code	B2
Filing date	Mar 27, 2014
Priority date	Mar 27, 2013
Publication date	Feb 21, 2017
Grant date	Feb 21, 2017

Abstract

A method of combination therapy for prevention and/or treatment of c-Met- and/or EGFR-induced diseases including co-administering a pharmaceutically effective amount of an EGFR antagonist and a pharmaceutically effective amount of an anti-c-Met antibody to a subject in need thereof is provided.

First claim

What is claimed is:

1. A method for the treatment of a c-Met-induced or EGFR-induced cancer, comprising co-administering a pharmaceutically effective amount of (a) a small-molecule EGFR inhibitor and (b) an anti-c-Met antibody or antigen-binding fragment thereof to a subject in need thereof,
wherein the anti c-Met antibody or the antigen-binding fragment thereof comprises
a complementarity determining region H1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 1,
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2,
a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3,
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10,
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 13.

2. The method of claim 1 , wherein the small-molecule EGFR inhibitor and the anti-c-Met antibody or antigen-binding fragment thereof are administered simultaneously or sequentially in any order.

3. The method of claim 1 , wherein the small-molecule EGFR inhibitor comprises at least one selected from the group consisting of erlotinib and gefitinib.

4. The method of claim 1 , wherein the anti-c-Met antibody comprises:
a heavy chain comprising the amino acid sequence from the 18 th to 462 nd positions of SEQ ID NO: 62, the amino acid sequence from the 18 th to 461 st positions of SEQ ID NO: 64, or the amino acid sequence from the 18 th to 460 th positions of SEQ ID NO: 66; and
a light chain comprising the amino acid sequence from the 21 st to 240 th positions of SEQ ID NO: 68, the amino acid sequence from the 21 st to 240 th positions of SEQ ID NO: 70, or the amino acid sequence of SEQ ID NO: 108.

5. The method of claim 1 , wherein the anti-c-Met antibody is a monoclonal antibody.

6. The method of claim 1 , wherein the anti-c-Met antibody is a mouse antibody, a mouse-human chimeric antibody, or a humanized antibody.

7. The method of claim 1 , wherein the antigen-binding fragment is selected from the group consisting of scFv, (scFv) 2 , Fab, Fab′, and F(ab′) 2 of the anti-c-Met antibody.

8. The method of claim 1 , wherein the anti-c-Met antibody is provided by a bispecific antibody comprising an anti-c-Met antibody or an antigen-binding fragment thereof and a VEGF-binding fragment.

9. The method of claim 8 , wherein the VEGF-binding fragment is an anti-VEGF antibody, an antigen-binding fragment of the anti-VEGF antibody, a VEGF receptor, or a VEGF-binding region of the VEGF receptor.

10. The method of claim 8 , wherein the VEGF-binding fragment is bevacizumab, an antigen-binding fragment of bevacizumab, human VEGF Receptor 1 (SEQ ID NO: 113), the second Ig-like domain 2 (VIG2) of SEQ ID NO: 114, or a polypeptide comprising 101 to 1338 consecutive amino acids within the amino acid sequence of SEQ ID NO: 113, wherein the 101 to 1338 consecutive amino acids comprises SEQ ID NO: 114.

11. The method according to claim 8 , wherein the bispecific antibody further comprises a linker comprising 1 to 100 amino acids between the anti-c-Met antibody or the antigen-binding fragment thereof and the VEGF-binding fragment.

12. The method according to claim 1 , wherein the c-Met-induced or EGFR-induced cancer is an EGFR antagonist resistant cancer.

13. A method for overcoming resistance to an EGFR antagonist, comprising administering a pharmaceutically effective amount of a small-molecule EGFR inhibitor together with an anti-c-Met antibody or antigen-binding fragment thereof to a subject in need thereof,
wherein the anti c-Met antibody or the antigen-binding fragment thereof comprises:
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1,
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2,
a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3,
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10,
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 13.

Assignees

• Samsung Electronics Co Ltd
• Samsung Life Welfare Found

Inventors

• Lee Saet Byoul
• Choi Jae Hyun
• Kim Kyung Ah
• Lee Ji Min
• Jeong Yun Ju
• Park Keunchil
• Kim Youngwook
• Lee Yumi

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K39/3955 Primary

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title