C-Met targeting compound-bioactive material conjugate and use thereof

Patent metadata

Field	Value
Publication number	US-9889206-B2
Application number	US-201414485062-A
Country	US
Kind code	B2
Filing date	Sep 12, 2014
Priority date	Sep 12, 2013
Publication date	Feb 13, 2018
Grant date	Feb 13, 2018

Abstract

Disclosed is a conjugate in which a c-Met targeting compound and a bioactive material are chemically conjugated with each other, and methods of use thereof.

First claim

What is claimed is:

1. A method of treating a cancer, comprising administering an antibody-drug conjugate comprising an anti-c-Met antibody and a cytotoxic agent, in which the anti-c-Met antibody and the cytotoxic agent are conjugated with each other, to a subject in need of cancer treatment,
wherein the anti-c-Met antibody binds to an epitope comprising a sequence of 5 to 19 consecutive amino acids of SEQ ID NO: 71 including the amino acid sequence EEPSQ (SEQ ID NO: 73) and comprises:
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, 22, 23, or 24;
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, 25, or 26;
a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, 27, 28, or 85;
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, 29, 30, 31, 32, 33, or 106;
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, 34, 35, or 36; and
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 13, 14, 15, 16, or 37.

2. The method of claim 1 , wherein the anti-c-Met antibody binds to an epitope of SEQ ID NO: 71, SEQ ID NO: 72, or SEQ ID NO: 73.

3. The method of claim 1 , wherein the anti-c-Met antibody 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, 14, 15, or 16.

4. The method of claim 1 , wherein the cytotoxic agent is at least one selected from the group consisting of maytansine, auristatin based drug, calicheamycin based drug, pyrrolobenzodiazepine based drug, duocarmycin, docetaxel, doxorubicin, carboplatin, cisplatin, cyclophosphamide, ifosfamide, nidran, nitrogen mustard, mechlorethamine HCl, bleomycin, mitomycin C, cytarabine, fluorouracil, gemcitabine, trimetrexate, methotrexate, etoposide, vinblastine, vinorelbine, alimta, altretamine, procarbazine, paclitaxel, taxotere, topotecan, irinotecan, and a radio-isotope.

5. A method for delivering a cytotoxic agent into a cell, comprising administering an antibody-drug conjugate comprising an anti-c-Met antibody and a cytotoxic agent, in which the anti-c-Met antibody and the cytotoxic agent are conjugated with each other, to a subject in need of intracellular delivery of the cytotoxic agent,
wherein the anti-c-Met antibody binds to an epitope comprising a sequence of 5 to 19 consecutive amino acids of SEQ ID NO: 71 including the amino acid sequence EEPSQ (SEQ ID NO: 73) and comprises:
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, 22, 23, or 24;
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, 25, or 26;
a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, 27, 28, or 85;
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, 29, 30, 31, 32, 33, or 106;
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, 34, 35, or 36; and
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 13, 14, 15, 16, or 37.

6. The method of claim 5 , wherein the anti-c-Met antibody binds to an epitope of SEQ ID NO: 71, SEQ ID NO: 72, or SEQ ID NO: 73.

7. The method of claim 5 , wherein the anti-c-Met antibody 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, 14, 15, or 16.

8. The method of claim 5 , wherein the cytotoxic agent is at least one selected from the group consisting of maytansine, auristatin based drug, calicheamycin based drug, pyrrolobenzodiazepine based drug, duocarmycin, docetaxel, doxorubicin, carboplatin, cisplatin, cyclophosphamide, ifosfamide, nidran, nitrogen mustard, mechlorethamine HCl, bleomycin, mitomycin C, cytarabine, fluorouracil, gemcitabine, trimetrexate, methotrexate, etoposide, vinblastine, vinorelbine, alimta, altretamine, procarbazine, paclitaxel, taxotere, topotecan, irinotecan, and a radio-isotope.

Assignees

• Samsung Electronics Co Ltd

Inventors

• Chae Su Young
• Kim Sunghyun
• Ko Eun
• Jeong Yun Ju
• Choi Jae Hyun

Classifications

• A61K47/6859 Primary

  the tumour determinant being from liver or pancreas cancer cell · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title

• A61K47/50 Primary

  the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates · CPC title