Anti-HER2 antibody-drug conjugate
View Patent ↗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.
1. An antibody-drug conjugate, wherein a linker and an antitumor compound represented by the following formula and anti-HER2 antibody are connected:
-(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.
2. The antibody-drug conjugate according to claim 1 , wherein an average number of units of the selected one drug-linker structure conjugated per antibody is in a range of from 2 to 8.
3. The antibody-drug conjugate according to claim 1 , wherein an average number of units of the selected one drug-linker structure conjugated per antibody is in a range of from 3 to 8.
4. A drug containing the antibody-drug conjugate according to claim 1 or a salt thereof.
5. 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.
6. The antibody-drug conjugate 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.
7. The antibody-drug conjugate according to claim 6 , 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.
8. The antibody-drug conjugate according to claim 6 , 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.