Antibody-conjugates for targeting of tumours expressing ptk7

A process for preparing an antibody-conjugate, comprising:

• (i) contacting an antibody comprising y core N-acetylglucosamine (GlcNAc) moieties with a compound of the formula S(F)x—P in the presence of a catalyst to obtain a modified antibody according to Formula (26):
• wherein:
• AB is an anti-PTK7 antibody;
• wherein,
• y is 1, 2, 3 or 4;
• S(F)x—P is
• UDP is uridine diphosphate;
• Fuc is fucose;
• and
• w is 0 or 1,
• wherein the catalyst is capable of transferring S(F)x—P to the core -GlcNAc moiety;
• (ii) reacting the modified antibody with a compound according to structure (2):
• to obtain the antibody-conjugate, wherein:
• Q-L-D is

A method for targeting PTK7-expressing cells, comprising contacting an antibody-conjugate with cells, and wherein the antibody conjugate is according to general structure (1):

• wherein:
• AB is an anti-PTK7 antibody;
• L is a linker that links Z to D;
• Z is a connecting group;
• L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L′ is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—;
• D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof;
• b is 0 or 1;
• x is 1 or 2;
• and
• y is 1, 2, 3 or 4.

A method of treating cancer in a patient comprising administering to the patient in need thereof an antibody-conjugate, wherein the antibody conjugate is according to general structure (1):

• wherein:
• AB is an anti-PTK7 antibody;
• L is a linker that links Z to D;
• Z is a connecting group;
• L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L′ is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—;
• D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof;
• b is 0 or 1;
• x is 1 or 2;
• and
• y is 1, 2, 3 or 4.