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

Patent metadata

Field	Value
Publication number	US-10792371-B2
Application number	US-201815884963-A
Country	US
Kind code	B2
Filing date	Jan 31, 2018
Priority date	Sep 12, 2013
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

Provided is a conjugate including a c-Met targeting compound and a bioactive material and methods of use of the conjugate.

First claim

What is claimed is:

1. A 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,
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 (SEQID 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 antibody-drug conjugate 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.

3. The antibody-drug conjugate of claim 1 , wherein the cytotoxic agent comprises a functional group capable of forming a chemical bond with the anti-c-Met antibody.

4. The antibody-drug conjugate of claim 2 , wherein the cytotoxic agent comprises a functional group capable of forming a chemical bond with the anti-c-Met antibody.

5. The antibody-drug conjugate of claim 4 , wherein the functional group is capable of thiol coupling, amine coupling, or reductive amination, with the anti-c-Met antibody.

6. The antibody-drug conjugate of claim 5 , wherein the functional group is linked to the cytotoxic agent via a linker, wherein the linker is an amino acid, an amino acid derivative, a peptide comprising 1 to 10 amino acids, a C1-C12 alkyl group, a hydrophilic spacer comprising 1 to 12 ethylene glycol units (—CH2CH2-O—), or a combination thereof.

7. The antibody-drug conjugate 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.

8. The antibody-drug conjugate 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.

9. A method of preparing the antibody-drug conjugate of claim 1 , comprising conjugating an anti-c-Met antibody and a 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 (SEQID 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.

10. The method of claim 9 , wherein the anti-c-Met antibody binds to an epitope of SEQ ID NO: 71, SEQ ID NO: 72, or SEQ ID NO: 73.

11. The method of claim 9 , 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.

12. The method of claim 9 , 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.

13. A method for improving the efficacy of an anti-c-Met antibody, comprising conjugating the anti-c-Met antibody with a 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 (SEQID 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.

14. The method of claim 13 , wherein the anti-c-Met antibody binds to an epitope of SEQ ID NO: 71, SEQ ID NO: 72, or SEQ ID NO: 73.

15. The method of claim 13 , 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.

16. The method of claim 13 , 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

• A61K47/6803

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title

• A61K47/6859 Primary

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

• A61K39/395

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6851

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