Antibody-conjugates with improved therapeutic index for targeting CD30 tumours and method for improving therapeutic index of antibody-conjugates

A method for treating CD30-positive cancer, comprising administering to a subject in need thereof an antibody-conjugate, comprising an antibody AB connected to a target molecule D via a linker L, wherein the antibody-conjugate is obtainable by:

• contacting a glycoprotein comprising 1-4 core N-acetylglucosamine moieties with a compound of the formula S(F1)x-P in the presence of a catalyst, wherein S(F1)x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q1, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F1)x moiety to the core-GlcNAc moiety, to obtain a modified antibody according to Formula (24):
• wherein S(F1)x and x are as defined above;
• AB represents an antibody;
• GlcNAc is N-acetylglucosamine;
• Fuc is fucose;
• b is 0 or 1;
• and y is 1, 2, 3 or 4;
• and
• (ii) reacting the modified antibody with a linker-conjugate comprising a functional group Q1 capable of reacting with functional group F1 and a target molecule D connected to Q1 via a linker L2 to obtain the antibody-conjugate wherein linker L comprises
• S—Z3-L2 and wherein Z3 is a connecting group resulting from the reaction between Q1 and F1,
• wherein antibody AB is capable of targeting CD30-expressing tumours and the antibody-conjugate has structure: