Synaffix B.v.

Synahix B.v.

Jorin Hoogenboom

Floris Louis Van Delft

Jorge Merijn Mathieu Verkade

Maria Antonia Wijdeven

Sander Sebastiaan Van Berkel

Petrus Josephus Jacobus Maria Van De Sande

Maria Antonia Van Berkel

The present invention concerns antibody-conjugate having general structure (2):AB-[(L)-{Z—(L)—(L)—(L)—(L)-D}]   (2)wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

Antibody-conjugates for targeting of tumours expressing Trop-2

The current invention concerns methods for the synthesis of 6-azido-6-deoxy-2-N-acetyl-monosaccharide-nucleoside diphosphate, in particular 6-azido-6-deoxy-2-N-acetyl-D-galactosamine-nucleoside diphosphate or 6-azido-6-deoxy-2-N-acetyl-D-glucosamine-nucleoside diphosphate. The synthesis method according to the invention is characterized by being highly efficient and high yielding. Also part of the present invention are key intermediates of this process.

Synthesis of 6-azido-6-deoxy-2-n-acetyl-hexosamine-nucleoside diphosphate

The invention relates to compounds of general structure (1): Q-(L)-(L)-(L)-(L)-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L, L, Land Lare each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21): wherein R&#x2550;C-alkyl, the wavy line indicates the connection to the remainder of the cytotoxin, and wherein D is conjugated to (L)by replacing the amine H atom, and to conjugates obtainable by reacting the compound according to the invention with a protein comprising a click probe F capable of reacting with click probe Q in a click reaction. The invention further relates to a bioconjugate according to general structure (2): Pr-[(L)-Z-(L)-(L)-(L)-(L)-D](2), wherein Z is a connecting group that is formed in a click reaction, Lis a linker that links Z to Pr and Pr is a (glyco)protein.

Enediyne conjugates

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Wageningen, Netherlands

Jorin Hoogenboom