Combination therapy using c-Met inhibitor and IGF-1R inhibitor for c-Met inhibitor resistant cancers

Patent metadata

Field	Value
Publication number	US-10064939-B2
Application number	US-201514949041-A
Country	US
Kind code	B2
Filing date	Nov 23, 2015
Priority date	Nov 21, 2014
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

Abstract

A method of preventing and/or treating a cancer, the method including co-administering a dual inhibitor of c-Met (hereinafter, ‘c-Met inhibitor’) and an IGF-1R inhibitor to a subject in need thereof and a use of IGF-1R as a marker for resistance to a c-Met inhibitor.

First claim

What is claimed is:

1. A method of treating a cancer in a subject, or overcoming resistance to a c-Met inhibitor in a subject, the method comprising co-administering a pharmaceutically effective amount of a c-Met inhibitor and an insulin-like growth factor 1 receptor (IGF-1R) inhibitor to the subject, wherein the cancer is not responsive to treatment with the c-Met inhibitor in the absence of an IGF-1R inhibitor.

2. The method of claim 1 , wherein
the c-Met inhibitor and an IGF-1R inhibitor are co-administered in a single, mixed formulation, or
each of the c-Met inhibitor and an IGF-1R inhibitor are administered in separate compositions, simultaneously or sequentially in any order.

3. The method of claim 1 , wherein the c-Met inhibitor comprises at least one selected from the group consisting of an anti-c-Met antibody or an antigen-binding fragment thereof, an aptamer, siRNA, shRNA, microRNA, a small-molecule c-Met inhibitor or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein the c-Met inhibitor is an anti-c-Met antibody or an antigen-binding fragment thereof that comprises:
a heavy chain variable region comprising a CDR-H1 comprising SEQ ID NO: 1, a CDR-H2 comprising SEQ ID NO: 2, and a CDR-H3 comprising SEQ ID NO: 3; and
a light chain variable region comprising a CDR-L1 comprising SEQ ID NO: 10, a CDR-L2 comprising SEQ ID NO: 11, and a CDR-L3 comprising SEQ ID NO: 12, 13, 14, 15, or 16;
or
a heavy chain variable region comprising a CDR-H1 comprising SEQ ID NO: 1, a CDR-H2 comprising SEQ ID NO: 2, and a CDR-H3 comprising SEQ ID NO: 3, and
a light chain variable region comprising a CDR-L1 comprising SEQ ID NO: 106, a CDR-L2 comprising SEQ ID NO: 11, and a CDR-L3 comprising SEQ ID NO: 13.

5. The method of claim 4 , wherein the anti-c-Met antibody or an antigen-binding fragment thereof comprises:
a heavy chain variable region comprising SEQ ID NO: 17; and
a light chain variable region comprising SEQ ID NO: 113, 18, 19, 20, 21, or 107.

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

7. The method of claim 1 , wherein the c-Met inhibitor comprises at least one selected from the group consisting of crizotinib, cabozantinib, foretinib, PHA-665752, SU11274, SGX-523, PF-04217903, EMD 1214063, golvatinib, INCB28060, MK-2461, tivantinib, NVP-BVU972, AMG458, BMS 794833, BMS 777607, MGCD-265, AMG-208, BMS-754807, JNJ-38877605, and pharmaceutically acceptable salts thereof.

8. The method of claim 1 , wherein the IGF-1R inhibitor comprises at least one selected from the group consisting of an antibody, an aptamer, siRNA, shRNA, microRNA, a small-molecule IGF-1R inhibitor, and a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the IGF-1R inhibitor comprises at least one selected from the group consisting of linsitinib, NVP-AEW541, GSK1904529A, NVP-ADW742, BMS-536924, figitumumab, cixutumumab, dalotuzumab, R1507, XL-228, INSM-18, BMS-754807, AG-1024, GSK1838705A, PQ 401, and pharmaceutically acceptable salts thereof.

10. The method of claim 1 , wherein the cancer is resistant to treatment with a c-Met inhibitor in the absence of an IGF-1R inhibitor.

11. The method of claim 10 , wherein the cancer is resistant to treatment with an anti-c-Met antibody or antigen-binding fragment thereof in the absence of an IGF-1R inhibitor.

12. The method of claim 11 , wherein the cancer is gastric cancer or lung cancer.

13. A pharmaceutical composition comprising a c-Met inhibitor and an IGF-1R inhibitor,
wherein the c-Met inhibitor is an anti-c-Met antibody or an antigen-binding fragment thereof comprises:
a heavy chain variable region comprising a CDR-H1 comprising SEQ ID NO: 1, a CDR-H2 comprising SEQ ID NO: 2, and a CDR-H3 comprising SEQ ID NO: 3; and
a light chain variable region comprising a CDR-L1 comprising SEQ ID NO: 10, a CDR-L2 comprising SEQ ID NO: 11, and a CDR-L3 comprising SEQ ID NO: 12, 13, 14, 15, or 16; or
a heavy chain variable region comprising a CDR-H1 comprising SEQ ID NO: 1, a CDR-H2 comprising SEQ ID NO: 2, and a CDR-H3 comprising SEQ ID NO: 3, and
a light chain variable region comprising a CDR-L1 comprising SEQ ID NO: 106, a CDR-L2 comprising SEQ ID NO: 11, and a CDR-L3 comprising SEQ ID NO: 13.

Assignees

• Samsung Electronics Co Ltd
• Yonsei Univ Univ Industry Foundation Uif

Inventors

• Shim Seon Hui
• Lee Ji Min
• Jung Soo Yeon
• Kwon Woo Sun
• Kim Kyung Ah
• Kim Jeong Min
• Rha Sun Young
• Lee Won Suk

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/74

  involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors} · CPC title

• C07K2317/92

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

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title