RU-2025137433-A - ANTIBODY-DRUG CONJUGATE AND ITS APPLICATION

Inventors

• ГАО, Сяо
• Яо, Бин
• ПАНЬ, Фуцзюнь
• ХУЭЙ, Сиву
• ЧЖАО, Люй
• ФАНЬ, Лисюэ
• ДАНЬ, Мо
• У, Юйфэнь
• СУНЬ, Сёнфэй
• ВАН, Минсяо

Assignees

• СиЭсПиСи МЕГАЛИТ БИОФАРМАСЬЮТИКАЛ КО., ЛТД.

Dates

Publication Date

20260504

Application Date

20240628

Priority Date

20230629

Claims (20)

1. 1. An antibody-drug conjugate having a structure represented by formula (I) and a tautomer, mesomer, racemate, enantiomer, diastereoisomer, pharmaceutically acceptable salt, hydrate, solvate, or isotopically labeled compound thereof:
2. where A is selected from an antibody (e.g., a monoclonal antibody) or an antigen-binding fragment thereof;
3. L is a linker fragment, one end of which is connected to A and the other end is connected to the bioactive molecule D;
4. D is a bioactive molecule;
5. d corresponds to the molar ratio of the bioactive molecule to A (also called DAR, i.e. drug-antibody ratio) and is an integer or decimal fractional number selected from 1-12 (e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12);
6. If d is a decimal fractional number, it refers to the average number of linker-bioactive molecule (L-D) systems conjugated to one A.
7. 2. An antibody-drug conjugate having a structure represented by formula (I) and its tautomer, mesomer, racemate, enantiomer, diastereoisomer, pharmaceutically acceptable salt, hydrate, solvate, or isotopically labeled compound according to claim 1, characterized in that:
8. A is selected from an antibody or an antigen-binding fragment thereof targeting HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), EGFR, DLL3, TROP2, B7H3, B7H4, TF (tissue factor), c-Met, CD20, CD22, CD30, CD33, CD44, CD47, CD56, CD70, CD73, CD79B, CD105, CEA, A33, Cripto, EphA2, G250, MUC1, Lewis Y, EDB-FN, VEGFR, VEGF, PD-1, PD-L1, MET, RET, GPNMB, integrin, PSMA, tenascin-C, SLC44A4, claudin 18.2 or mesothelin.
9. 3. An antibody-drug conjugate having a structure represented by formula (I) and its tautomer, mesomer, racemate, enantiomer, diastereoisomer, pharmaceutically acceptable salt, hydrate, solvate or isotopically labeled compound according to any one of claims 1, 2, characterized in that:
10. A is an antibody or antigen-binding fragment thereof that targets B7H3; the antibody or antigen-binding fragment thereof comprises a heavy chain and/or a light chain, wherein the heavy chain comprises 3 complementarity determining regions (CDRs), wherein the amino acid sequence of the heavy chain complementarity determining region 1 (HCDR1) is presented in SEQ ID NO: 1, the amino acid sequence of the heavy chain complementarity determining region 2 (HCDR2) is presented in SEQ ID NO: 2, and the amino acid sequence of the heavy chain complementarity determining region 3 (HCDR3) is presented in SEQ ID NO: 3; the light chain comprises 3 light chain complementarity determining regions (CDRs), wherein the amino acid sequence of light chain complementarity determining region 1 (LCDR1) is shown in SEQ ID NO: 4, the amino acid sequence of light chain complementarity determining region 2 (LCDR2) is shown in SEQ ID NO: 5, and the amino acid sequence of light chain complementarity determining region 3 (LCDR3) is shown in SEQ ID NO: 6, the CDRs are defined according to the Kabat numbering scheme.
11. 4. An antibody-drug conjugate having a structure represented by formula (I) and its tautomer, mesomer, racemate, enantiomer, diastereoisomer, pharmaceutically acceptable salt, hydrate, solvate, or isotopically labeled compound according to any one of claims 1 to 3, characterized in that:
12. A is an antibody or antigen-binding fragment thereof targeting B7H3; the antibody to B7H3 or antigen-binding fragment thereof comprises a heavy chain and/or a light chain, wherein the sequence of the heavy chain variable region (HV) is presented in SEQ ID NO: 7, and the sequence of the light chain variable region (LV) is presented in SEQ ID NO: 8.
13. 5. An antibody-drug conjugate having a structure represented by formula (I) and its tautomer, mesomer, racemate, enantiomer, diastereoisomer, pharmaceutically acceptable salt, hydrate, solvate, or isotopically labeled compound according to any one of claims 1 to 4, characterized in that:
14. A is an antibody directed to B7H3, wherein the antibody to B7H3 further comprises a heavy chain constant region sequence or a variant thereof and/or a light chain constant region sequence or a variant thereof.
15. 6. An antibody-drug conjugate having a structure represented by formula (I) and its tautomer, mesomer, racemate, enantiomer, diastereoisomer, pharmaceutically acceptable salt, hydrate, solvate, or isotopically labeled compound according to any one of claims 1 to 5, characterized in that:
16. A is an antigen-binding fragment targeting B7H3, wherein the antigen-binding fragment is selected from Fab, Fab', Fab'-SH, Fv, scFv, and F(ab') 2 .
17. 7. An antibody-drug conjugate having a structure represented by formula (I) and a tautomer, mesomer, racemate, enantiomer, diastereoisomer, pharmaceutically acceptable salt, hydrate, solvate, or isotopically labeled compound thereof according to any one of claims 1 to 6, characterized in that:
18. A is an antibody or antigen-binding fragment thereof that targets B7H3, wherein the antibody to B7H3 or antigen-binding fragment thereof is a humanized or fully human antibody or antigen-binding fragment thereof.
19. 8. An antibody-drug conjugate having a structure represented by formula (I) and a tautomer, mesomer, racemate, enantiomer, diastereoisomer, pharmaceutically acceptable salt, hydrate, solvate, or isotopically labeled compound thereof according to any one of claims 1 to 7, characterized in that:
20. A is an antibody or antigen-binding fragment thereof that targets B7H3; the antibody to B7H3 comprises a heavy chain and/or a light chain, wherein the amino acid sequence of the heavy chain is presented in SEQ ID NO: 9 or SEQ ID NO: 10, and the amino acid sequence of the light chain is presented in SEQ ID NO: 11.