Method for treating cancer comprising administration of anti-HER2 antibody-drug conjugate

Patent metadata

Field	Value
Publication number	US-11795236-B2
Application number	US-201816130615-A
Country	US
Kind code	B2
Filing date	Sep 13, 2018
Priority date	Jan 31, 2014
Publication date	Oct 24, 2023
Grant date	Oct 24, 2023

Abstract

As an antitumor drug which is excellent in terms of antitumor effect and safety and has an excellent therapeutic effect, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an anti-HER2 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 -(CH 2 )n 2 -C(═O)— wherein the anti-HER2 antibody is connected to the terminal L 1 , and the antitumor compound is connected to the carbonyl group of the —(CH 2 )n 2 -C(═O)— moiety with the nitrogen atom of the amino group at position 1 as the connecting position

First claim

The invention claimed is:

1. A method of treating HER2-low expressing cancer in an individual comprising administering to an individual with HER2-low expressing cancer a drug containing an antibody-drug conjugate or a salt thereof,
wherein the antibody-drug conjugate comprises a linker and an antitumor compound represented by the following formula and anti-HER2 antibody connected to the linker:
-(Succinimid-3-yl-N)—CH 2 CH 2 CH 2 CH 2 CH 2 —C(═O)-GGFG (SEQ ID NO: 3)-NH—CH 2 —O—CH 2 —C(═O)—(NH-DX)
wherein
-(Succinimid-3-yl-N)- has a structure represented by the following formula:

which is connected to the antibody at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1, and
(NH-DX) represents a group represented by the following formula:

wherein the nitrogen atom of the amino group at position 1 is the connecting position, and
wherein the HER2-low expressing cancer is lung cancer, urothelial cancer, colorectal cancer, prostate cancer, ovarian cancer, pancreatic cancer, breast cancer, bladder cancer, gastric cancer, gastrointestinal stromal tumor, uterine cervix cancer, esophageal cancer, squamous cell carcinoma, peritoneal cancer, liver cancer, hepatocellular cancer, colon cancer, rectal cancer, colorectal cancer, endometrial cancer, uterine cancer, salivary gland cancer, kidney cancer, vulval cancer, thyroid cancer, penis cancer, leukemia, malignant lymphoma, plasmacytoma, myeloma, or sarcoma.

2. The method of treating HER2-low expressing cancer according to claim 1 , wherein the anti-HER2 antibody comprises a heavy chain and a light chain selected from the group:
a heavy chain consisting of an amino acid sequence consisting of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain consisting of an amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO: 2, and
a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2.

3. The method of treating HER2-low expressing cancer according to claim 1 , wherein the anti-HER2 antibody comprises a heavy chain consisting of the amino acid sequence consisting of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO: 2.

4. The method of treating HER2-low expressing cancer according to claim 1 , wherein the anti-HER2 antibody comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2.

5. The method of treating HER2-low expressing cancer according to claim 1 , wherein the antibody-drug conjugate has an average number of units of the drug-linker structure conjugated per antibody in a range of from 2 to 8.

6. The method of treating HER2-low expressing cancer according to claim 1 , wherein the antibody-drug conjugate has an average number of units of the drug-linker structure conjugated per antibody in a range of from 3 to 8.

7. A method of treating HER2-low expressing cancer in an individual comprising administering to an individual with HER2-low expressing cancer a pharmaceutical composition containing an antibody-drug conjugate or a salt thereof as an active component and a pharmaceutically acceptable formulation component,
wherein the antibody-drug conjugate comprises a linker and an antitumor compound represented by the following formula and anti-HER2 antibody connected to the linker:
-(Succinimid-3-yl-N)—CH 2 CH 2 CH 2 CH 2 CH 2 —C(═O)-GGFG (SEQ ID NO: 3)-NH—CH 2 —O—CH 2 —C(═O)—(NH-DX)
wherein
-(Succinimid-3-yl-N)- has a structure represented by the following formula:

which is connected to the antibody at position 3 thereof and is connected to a methylene group in the linker structure containing this structure on the nitrogen atom at position 1, and
(NH-DX) represents a group represented by the following formula:

wherein the nitrogen atom of the amino group at position 1 is the connecting position, and
wherein the HER2-low expressing cancer is lung cancer, urothelial cancer, colorectal cancer, prostate cancer, ovarian cancer, pancreatic cancer, breast cancer, bladder cancer, gastric cancer, gastrointestinal stromal tumor, uterine cervix cancer, esophageal cancer, squamous cell carcinoma, peritoneal cancer, liver cancer, hepatocellular cancer, colon cancer, rectal cancer, colorectal cancer, endometrial cancer, uterine cancer, salivary gland cancer, kidney cancer, vulval cancer, thyroid cancer, penis cancer, leukemia, malignant lymphoma, plasmacytoma, myeloma, or sarcoma.

8. The method of treating HER2-low expressing cancer according to claim 7 , wherein the anti-HER2 antibody comprises a heavy chain and a light chain selected from the group:
a heavy chain consisting of an amino acid sequence consisting of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain consisting of an amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO: 2, and
a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2.

9. The method of treating HER2-low expressing cancer according to claim 7 , wherein the anti-HER2 antibody comprises a heavy chain consisting of the amino acid sequence consisting of amino acid residues 1 to 449 of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO: 2.

10. The method of treating HER2-low expressing cancer according to claim 7 , wherein the anti-HER2 antibody comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2.

11. The method of treating HER2-low expressing cancer according to claim 7 , wherein the antibody-drug conjugate has an average number of units of the drug-linker structure conjugated per antibody in a range of from 2 to 8.

12. The method of treating HER2-low expressing cancer according to claim 7 , wherein the antibody-drug conjugate has an average number of units of the drug-linker structure conjugated per antibody in a range of from 3 to 8.

Assignees

• Daiichi Sankyo Co Ltd

Inventors

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

Classifications

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K16/32 Primary

  against translation products of oncogenes · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6851

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