Antibody-drug conjugate

Patent metadata

Field	Value
Publication number	US-9808537-B2
Application number	US-201615180203-A
Country	US
Kind code	B2
Filing date	Jun 13, 2016
Priority date	Oct 11, 2012
Publication date	Nov 7, 2017
Grant date	Nov 7, 2017

Abstract

As an antitumor drug which is excellent in terms of antitumor effect and safety, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an antibody via a linker having a structure represented by the following formula: -L 1 -L 2 -L P -NH—(CH 2 )n 1 -L a -L b -L c - wherein the antibody is connected to the terminal of L 1 , and the antitumor compound is connected to the terminal of L c with the nitrogen atom of the amino group at position 1 as a connecting position.

First claim

The invention claimed is:

1. An antibody-drug conjugate, comprising a linker that is connected to an antibody, having the following formula:
-(Succinimid-3-yl-N)—CH 2 CH 2 CH 2 CH 2 CH 2 —C(═O)-GGFG-NH—CH 2 —O—CH 2 —C(═O)—

and an antitumor compound that is connected to the linker, wherein -(Succinimid-3-yl-N)— has a structure having the following formula:

which is connected to the antibody at position 3 thereof and is connected to a methylene group in the linker containing this structure on the nitrogen atom at position 1, and the antitumor compound is connected to the carbon atom of the carbonyl group within the —NH—CH 2 —O—CH 2 —C(═O)— moiety.

2. The antibody-drug conjugate according to claim 1 , wherein the linker and the antitumor compound are in the following structure:
-(Succinimid-3-yl-N)—CH 2 CH 2 CH 2 CH 2 CH 2 —C(═O)-GGFG-NH—CH 2 —O—CH 2 —C(═O)—(NH-DX)

wherein -(NH-DX) represents a group having the following formula:

wherein the nitrogen atom of the amino group at position 1 is the connecting position.

3. The antibody-drug conjugate according to claim 1 , wherein an average of 2 to 8 linker and antitumor compound structures are conjugated to the antibody.

4. The antibody-drug conjugate according to claim 1 , wherein an average of 3 to 8 linker and antitumor compound structures are conjugated to the antibody.

5. The antibody-drug conjugate according to claim 1 , wherein the antibody is an anti-B7-H3 antibody, an anti-CD30 antibody, an anti-CD33 antibody, or an anti-CD70 antibody.

6. The antibody-drug conjugate according to claim 1 , wherein the antibody is an anti-B7-H3 antibody.

7. A drug containing the antibody-drug conjugate according to claim 1 , or a salt thereof.

8. An antitumor drug and/or anticancer drug containing the antibody-drug conjugate according to claim 1 , or a salt thereof.

9. A method of treating cancer in an individual comprising administering to an individual with cancer the drug according to claim 8 , wherein the cancer is lung cancer, kidney cancer, urothelial cancer, colorectal cancer, prostate cancer, glioblastoma multiforme, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer, or esophageal cancer.

10. A pharmaceutical composition containing the antibody-drug conjugate according to claim 1 , or a salt thereof as an active component, and a pharmaceutically acceptable formulation component.

11. The antibody-drug conjugate according to claim 2 , wherein an average of 2 to 8 linker and antitumor compound structures are conjugated to the antibody.

12. The antibody-drug conjugate according to claim 2 , wherein an average of 3 to 8 linker and antitumor compound structures are conjugated to the antibody.

13. The antibody-drug conjugate according to claim 2 , wherein the antibody is an anti-B7-H3 antibody, an anti-CD30 antibody, an anti-CD33 antibody, or an anti-CD70 antibody.

14. The antibody-drug conjugate according to claim 2 , wherein the antibody is an anti-B7-H3 antibody.

15. A drug containing the antibody-drug conjugate according to claim 2 , or a salt thereof.

16. An antitumor drug and/or anticancer drug containing the antibody-drug conjugate according to claim 2 , or a salt thereof.

17. A method of treating cancer in an individual comprising administering to an individual with cancer the drug according to claim 16 , wherein the cancer is lung cancer, kidney cancer, urothelial cancer, colorectal cancer, prostate cancer, glioblastoma multiforne, ovarian cancer, pancreatic cancer, breast cancer, melanoma, liver cancer, bladder cancer, stomach cancer, or esophageal cancer.

18. A pharmaceutical composition containing the antibody-drug conjugate according to claim 2 , or a salt thereof as an active component, and a pharmaceutically acceptable formulation component.

Assignees

• Daiichi Sankyo Co Ltd

Inventors

• Masuda Takeshi
• Naito Hiroyuki
• Nakada Takashi
• Yoshida Masao
• Ashida Shinji
• Miyazaki Hideki
• Kasuya Yuji
• Morita Koji
• Abe Yuki
• Ogitani Yusuke

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• A61K47/6889 Primary

  Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment · CPC title

• C07D491/22

  in which the condensed system contains four or more hetero rings · CPC title