Anti-claudin antibody-drug conjugate and pharmaceutical use thereof

A ligand-drug conjugate of general formula (Pc-L-Y-D) or a pharmaceutically acceptable salt thereof:

• wherein:
• Y is selected from the group consisting of —O—(CRaRb)m—CR1R2—C(O)—, —O—CR1R2—(CRaRb)m, —O—CR1R2—, —NH—(CRaRb)m—CR1R2—C(O)— and —S—(CRaRb)m—CR1R2—C(O)—;
• Ra and Rb are identical or different and are each independently selected from the group consisting of hydrogen, deuterium, halogen, alkyl, haloalkyl, deuterated alkyl, alkoxy, hydroxy, amino, cyano, nitro, hydroxyalkyl, cycloalkyl and heterocyclyl;
• or, Ra and Rb, together with carbon atoms connected thereto, form cycloalkyl or heterocyclyl;
• R1 is selected from the group consisting of halogen, haloalkyl, deuterated alkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, heterocyclyl, aryl and heteroaryl;
• R2 is selected from the group consisting of hydrogen, halogen, haloalkyl, deuterated alkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, heterocyclyl, aryl and heteroaryl;
• or, R1 and R2, together with carbon atoms connected thereto, form cycloalkyl or heterocyclyl;
• or, Ra and R2, together with carbon atoms connected thereto, form cycloalkyl or heterocyclyl;
• m is an integer from 0 to 4;
• n is a decimal or an integer from 1 to 10;
• L is a linker unit;
• Pc is an anti-claudin18.2 antibody or an antigen-binding fragment thereof;
• preferably
• wherein the anti-claudin18.2 antibody or the antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein:
• i) the heavy chain variable region comprises an HCDR1, an HCDR2 and an HCDR3 having sequences identical to those of an HCDR1, an HCDR2 and an HCDR3 of a heavy chain variable region set forth in SEQ ID NO:
• 5, and the light chain variable region comprises an LCDR1, an LCDR2 and an LCDR3 having sequences identical to those of an LCDR1, an LCDR2 and an LCDR3 of a light chain variable region set forth in SEQ ID NO:
• 6;
• or
• ii) the heavy chain variable region comprises an HCDR1, an HCDR2 and an HCDR3 having sequences identical to those of an HCDR1, an HCDR2 and an HCDR3 of a heavy chain variable region set forth in SEQ ID NO:
• 3, and the light chain variable region comprises an LCDR1, an LCDR2 and an LCDR3 having sequences identical to those of an LCDR1, an LCDR2 and an LCDR3 of a light chain variable region set forth in SEQ ID NO:
• 4.