IP Library › Granted Patent US 12,698,342
Granted Patent B2
US 12,698,342 · App. 16/334,008 · Granted Aug 4, 2026

Therapy for drug-resistant cancer by administration of anti-HER2 antibody/drug conjugate

Inventors: Takahiro Jikoh (Tokyo, JP); Yusuke Ogitani (Tokyo, JP); Kazutaka Yoshihara (Tokyo, JP); Seiko Endo (Tokyo, JP); Yoshihiko Fujisaki (Tokyo, JP)
Assignee: DAIICHI SANKYO COMPANY, LIMITED
C07K16/32A61K31/4015A61K31/4741A61K47/68037A61P35/00
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Quick Facts
Patent No.
US 12,698,342
App. No.
16/334,008
Granted
Aug 4, 2026
Kind
B2
Abstract

As treatment effective for HER2-expressing cancer having resistance or refractoriness to an existing anti-HER2 drug, there are provided a therapeutic agent and a treatment method using an antibody-drug conjugate in which a linker and a drug represented by the formula: -(Succinimid-3-yl-N)—CH 2 CH 2 CH 2 CH 2 CH 2 —C(═O)-GGFG (SEQ ID NO: 5) —NH—CH 2 —O—CH 2 —C(═O)—(NH-DX) are conjugated to an anti-HER2 antibody.

Claims (47)

1 . A method for treating HER2-expressing cancer having resistance to an existing anti-HER2 drug, comprising administering a dose per administration of a range of 5.4 mg/kg to 6.4 mg/kg of an antibody-drug conjugate in which a linker and a drug represented by the following formula are conjugated to an anti-HER2 antibody to a human patient in need of the treatment of the HER2-expressing cancer having resistance to an existing anti-HER2 drug:

-(Succinimid-3-yl-N)—CH 2 CH 2 CH 2 CH 2 CH 2 —C(═O)-GGFG (SEQ ID NO: 5)-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 anti-HER2 antibody at position 3 thereof via a thioether bond and is connected to the methylene group in the linker structure containing this structure on the nitrogen atom at position 1,

(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

-GGFG- represents the tetrapeptide residue of -Gly-Gly-Phe-Gly- (SEQ ID NO: 5);

wherein the anti-HER2 antibody comprises (i) 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; or (ii) a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 1 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 2.

2 . The method according to claim 1 , wherein the existing anti-HER2 drug is at least one selected from the group consisting of trastuzumab emtansine, trastuzumab, pertuzumab, and lapatinib.

3 . The method according to claim 1 , wherein the existing anti-HER2 drug is trastuzumab emtansine.

4 . The method according to claim 1 , wherein the existing anti-HER2 drug is trastuzumab.

5 . The method according to claim 1 , wherein the human patient has a history of treatment with an existing anticancer drug.

6 . The method according to claim 5 , wherein the existing anticancer drug comprises trastuzumab emtansine.

7 . The method according to claim 5 , wherein the existing anticancer drug comprises trastuzumab.

8 . The method according to claim 5 , wherein the existing anticancer drug comprises irinotecan.

9 . The method according to claim 1 , wherein an average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate is in a range of 7 to 8.

10 . The method according to claim 1 , wherein an average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate is in a range of 7.5 to 8.

11 . The method according to claim 1 , wherein the anti-HER2 antibody comprises 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.

12 . The method according to claim 1 , wherein the anti-HER2 antibody comprises a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 1 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 2.

13 . The method according to claim 1 , wherein the antibody-drug conjugate is administered once every 3 weeks.

14 . The method according to claim 1 , wherein the cancer is at least one selected from the group consisting of breast cancer, gastric cancer, colorectal cancer, esophageal cancer, salivary gland cancer, pancreatic cancer, ovarian cancer, uterine cancer, lung cancer, and sarcoma.

15 . The method according to claim 1 , wherein the cancer is breast cancer.

16 . The method according to claim 1 , wherein the cancer is gastric cancer.

17 . The method according to claim 1 , wherein the cancer is colorectal cancer.

18 . The method according to claim 1 , wherein the cancer is salivary gland cancer.

19 . The method according to claim 1 , wherein the HER2-expressing cancer is HER2-overexpressing cancer.

20 . The method according to claim 1 , wherein the antibody-drug conjugate is administered together with a pharmaceutically acceptable formulation component.

21 . The method according to claim 1 , wherein the resistance is acquired by the cancer due to treatment with the existing anti-HER2 drug.

22 . The method according to claim 1 , wherein the dose per administration of the antibody-drug conjugate is 5.4 mg/kg.

23 . The method according to claim 1 , wherein the dose per administration of the antibody-drug conjugate is 6.4 mg/kg.

24 . The method according to claim 9 , wherein the anti-HER2 antibody comprises 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.

25 . The method according to claim 9 , wherein the anti-HER2 antibody comprises a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 1 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 2.

26 . The method according to claim 10 , wherein the anti-HER2 antibody comprises 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.

27 . The method according to claim 10 , wherein the anti-HER2 antibody comprises a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 1 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 2.

28 . A method for treating HER2-expressing cancer having resistance to an existing anti-HER2 drug, comprising administering a dose per administration of a range of 5.4 mg/kg to 6.4 mg/kg of an antibody-drug conjugate represented by the following Formula

to a human patient in need of the treatment of the HER2-expressing cancer having resistance to an existing anti-HER2 drug;

wherein in the Formula, a drug-linker is conjugated to the anti-HER2 antibody via a thioether bond, and

n represents an average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate;

wherein the average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate is 7 to 8;

wherein the anti-HER2 antibody comprises (i) 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; or (ii) a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 1 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 2;

wherein the antibody-drug conjugate is administered once every 3 weeks; and

wherein the cancer is at least one selected from the group consisting of breast cancer, gastric cancer, colorectal cancer, esophageal cancer, salivary gland cancer, pancreatic cancer, ovarian cancer, uterine cancer, lung cancer, and sarcoma.

29 . The method according to claim 1 , wherein an average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate is in a range of 7 to 8; and wherein the dose per administration of the antibody-drug conjugate is 5.4 mg/kg.

30 . The method according to claim 1 , wherein an average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate is in a range of 7 to 8; and wherein the dose per administration of the antibody-drug conjugate is 6.4 mg/kg.

31 . The method according to claim 1 , wherein an average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate is in a range of 7.5 to 8; and wherein the dose per administration of the antibody-drug conjugate is 5.4 mg/kg.

32 . The method according to claim 1 , wherein an average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate is in a range of 7.5 to 8; and wherein the dose per administration of the antibody-drug conjugate is 6.4 mg/kg.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 16, 2019
From: JIKOH, TAKAHIRO; OGITANI, YUSUKE; YOSHIHARA, KAZUTAKA; ENDO, SEIKO; FUJISAKI, YOSHIHIKO
To: DAIICHI SANKYO COMPANY, LIMITED
Reel/Frame 048617/0791 →
Priority Claims (3)
JP 2016-199341 · Oct 7, 2016 · national
JP 2017-097589 · May 16, 2017 · national
JP 2017-172814 · Sep 8, 2017 · national
Continuity (1)
Related Publication 20190330368A1 · Oct 31, 2019
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