Synaffix B.v.

Brian Maria Gerardus Janssen

Floris Louis Van Delft

Maria Antonia Wijdeven

Sander Sebastiaan Van Berkel

Jorge Merijn Mathieu Verkade

Petrus Josephus Jacobus Maria Van De Sande

Ryan Heesbeen

Inge Catharina Josephina Hurkmans

Remon Van Geel

Remon Gvan Eel

The present invention concerns novel and improved antibody-conjugates for targeting CD30. The inventors found that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1-4 core N-acetylglucosamine moieties with a compound of the formula S(F)-P in the presence of a catalyst, wherein S(F)is a sugar derivative comprising x functional groups Fcapable of reacting with a functional group Q, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F)moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Qcapable of reacting with functional group Fand a target molecule D connected to Qvia a linker Lto obtain the antibody-conjugate wherein linker L comprises S&#x2014;Z-Land wherein Zis a connecting group resulting from the reaction between Qand F. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting CD30-expressing cells.

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

The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found N that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1-4 core N-acetylglucosamine moieties with a compound of the formula S(F)-P in the presence of a catalyst, wherein S(F)is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F)moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Qcapable of reacting with functional group Fand a target molecule D connected to Qvia a linker Lto obtain the antibody-conjugate wherein linker L comprises S&#x2014;Z-Land wherein Zis a connecting group resulting from the reaction between Qand F. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.

Antibody-conjugates with improved therapeutic index for targeting HER2 tumours and method for improving therapeutic index of antibody-conjugates

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MJ Eindhoven, Netherlands

Brian Maria Gerardus Janssen