Anti-ErbB2 antibody-drug conjugate and composition thereof, preparation method therefor, and use thereof

1. A preparation method of an antibody-drug conjugate represented by Formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof, or a solvate of the foregoing,

wherein:

A is an anti-ErbB2 antibody, wherein the anti-ErbB2 antibody is Trastuzumab;

X is N;

Y is N or CR 1 , and R 1 is H or C 1 -C 10 alkyl;

L is

D is a cytotoxic agent group of Formula (D1) or a stereoisomer thereof,

wherein R 2 is —CH 2 N 3 , R 3 is selected from the group consisting of H and —OH, and R 4 is selected from the group consisting of H, —NH 2 , Cl, Br, I and —OS(O) 2 R 6 , wherein R 6 is H, C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl or C 6 -C 14 aryl, and the alkyl, cycloalkyl and aryl are each optionally substituted with one or more halogen substituents;

a is an integer selected from the group consisting of 2-10; and

all the cytotoxic agent groups are conjugated to the lysine residues of the same peptide segment of the light chain of the antibody;

the method comprising the steps of:

(1) preparing a compound of Formula (I-A):

(2) obtaining a compound of Formula (I-B) by reacting the compound of Formula (I-A) with pentafluorophenol using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide and/or dichloromethane

(3) obtaining a mixture of a variety of antibody-drug conjugates having different a values by conjugating the compound of Formula (I-B) from step (2) with the anti-ErbB2 antibody; and

(4) obtaining the antibody-drug conjugate represented by Formula (I) by purifying the mixture from step (3) with hydrophobic interaction chromatography (HIC) method, said method utilizing a stationary phase that comprises a phenyl resin;

wherein a mobile phase A of the HIC method comprises ammonia sulfate and disodium hydrogen phosphate; and a mobile phase B of the HIC method comprises disodium hydrogen phosphate and isopropanol.

2. The preparation method according to claim 1 , wherein Y is CR 1 .

3. The preparation method according to claim 1 , wherein R 1 is H.

4. The preparation method according to claim 1 , wherein a is 2, 3 or 4.

5. The preparation method according to claim 1 , wherein the antibody-drug conjugate is represented by Formula (I-1):

wherein A is Trastuzumab.

6. The preparation method according to claim 1 , wherein R 6 is H, C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl or C 6 -C 14 aryl, and the alkyl, cycloalkyl and aryl are each optionally substituted with 1, 2, 3, 4 or 5 halogen substituents.

7. The preparation method according to claim 1 , wherein the one or more halogen substituents are one or more F substituents.