Oligosaccharide linker, linker-payload comprising the same and glycan chain-remodeled antibody-drug conjugate, preparation methods and uses thereof

An antibody-drug conjugate based on the site-specific conjugation at the N-glycosylation site in Fc region of an antibody, having the structure of a formula selected from the group consisting of formulas (II-1), (II-2), (II-3), (II-4) and (II-5):

• wherein
• R is hydrogen or α-L-fucosyl;
• q is 1 or 2;
• Ab is an antibody or antigen-binding fragment thereof which contains the Fc region of the antibody, wherein the antibody is an anti-CD19 antibody, an anti-CD20 antibody, an anti-CD22 antibody, an anti-CD25 antibody, an anti-CD30/TNFRSF8 antibody, an anti-CD33 antibody, an anti-CD37 antibody, an anti-CD44v6 antibody, an anti-CD56 antibody, an anti-CD70 antibody, an anti-CD71 antibody, an anti-CD74 antibody, an anti-CD79b antibody, an anti-CD117/KITk antibody, an anti-CD123 antibody, an anti-CD138 antibody, an anti-CD142 antibody, an anti-CD174 antibody, an anti-CD227/MUC1 antibody, an anti-CD352 antibody, an anti-CLDN18.2 antibody, an anti-DLL3 antibody, an anti-ErbB2/HER2 antibody, an anti-CN33 antibody, an anti-GPNMB antibody, an anti-ENPP3 antibody, an anti-Nectin-4 antibody, an anti-EGFRvIII antibody, an anti-SLC44A4/AGS-5 antibody, an anti-CEACAM5 antibody, an anti-PSMA antibody, an anti-TIM1 antibody, an anti-LY6E antibody, an anti-LIV1 antibody, an anti-Nectin4 antibody, an anti-SLITRK6 antibody, an anti-HGFR/cMet antibody, an anti-SLAMF7/CS1 antibody, an anti-EGFR antibody, an anti-BCMA antibody, an anti-AXL antibody, an anti-NaPi2B antibody, an anti-GCC antibody, an anti-STEAP1 antibody, an anti-MUC16 antibody, an anti-mesothelin antibody, an anti-ETBR antibody, an anti-EphA2 antibody, an anti-5T4 antibody, an anti-FOLR1 antibody, an anti-LAMP1 antibody, an anti-Cadherin 6 antibody, an anti-FGFR2 antibody, an anti-FGFR3 antibody, an anti-CA6 antibody, an anti-CanAg antibody, an anti-integrin-aV antibody, an anti-TDGF1 antibody, an anti-ephrin A4 antibody, an anti-TROP2 antibody, an anti-PTK7 antibody, an anti-NOTCH3 antibody, an anti-C4.4A antibody, an anti-FLT3 antibody;
• P is a payload selected from the group consisting of:
• L is a linker end, L is attached to P by an amide bond or ester bond or ether bond, and L is directly attached to carbonyl in the oligosaccharide moiety via —NH— in the L to form an amide bond, wherein when L is an unbranched linker end, L is attached to one P, and t is 1, while when L is a branched linker end, each branch can be attached to one P, and t is an integer greater than 1, wherein (i) when Lis an unbranched linker end, L is L2-L1-B or (ii) when L is a branched linker end, -L-(P)t is
• wherein
• B is selected from:
• —NH—CH2—U—, or —NH—CH2—U—(CH2)g—(CO)—, where g is 1, 2, 3, 4, 5 or 6;
• U is absent or O;
• L1 is absent or selected from -Gly-Gly-Phe-Gly-, -Phe-Lys-, -Val-Cit-, -Val-Lys-, -Gly-Phe-Leu-Gly-, -Ala-Leu-Ala-Leu-, -Ala-Ala-Ala- and a combination thereof;
• L2 is NH—C2-20 alkylene, wherein one or more —CH2— structures in the alkylene are optionally replaced by the following groups:
• —O— and —(CO)—, or L2 is an amino acid sequence comprising from 1 to 100 amino acids;
• Ld2 and each Ld1 are independently selected from
• wherein each i and j are independently selected from integers from 1 to 20, and R11 is C1-10 alkyl;
• M is LKa-L2-L1-B-P;
• each LKa is
• where * represents a moiety attached to L2;
• Q is NH2;
• d is 1, 2, or 3.