Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation

A mammalian cell culture medium for the production of antibodies or antibody derivatives having reduced core fucosylation, comprising an effective amount of a fucose analog, wherein the fucose analog is selected from the group consisting of one of the following formulae (III) or (IV):

• or a biologically acceptable salt or solvate thereof, wherein each of formula (III) or (IV) can be the alpha or beta anomer or the corresponding aldose form;
• each of R1-R4 is independently selected from the group consisting of fluoro, chloro, —OH, —OC(O)H, —OC(O)C1-C10 alkyl, —OC(O)C2-C10 alkenyl, —OC(O)C2-C10 alkynyl, —OC(O)aryl, —OC(O)heterocycle, —OC(O)C1-C10 alkylene(aryl), —OC(O)C2-C10 alkenylene(aryl), —OC(O)C2-C10 alkynyl(aryl), —OC(O)C1-C10 alkylene heterocycle, —OC(O)C2-C10 alkenylene(heterocycle), —OC(O)C2-C10 alkynyl heterocycle, —OCH2OC(O) alkyl, —OCH2OC(O)O alkyl, —OCH2OC(O) aryl, —OCH2OC(O)O aryl,
• —OC(O)CH2O(CH2CH2O)nCH3, —OC(O)CH2CH2O(CH2CH2O)nCH3, —O-tri-C1-C3 alkylsilyl and —OC1-C10 alkyl, wherein each n is an integer independently selected from 0-5;
• and
• each of R2a and R3a is independently selected from the group consisting of H, F and Cl;
• R5 is selected from the group consisting
• of —CH3, —CHF2, —CH═C═CH2, —C≡CH, —C≡CCH3, —CH2C≡CH, —C(O)OCH3, —CH(OAc)CH3, —CN, —CH2CN, —CH2X (wherein X is Br, Cl or I), and methoxiran;
• wherein when R5 is other than —CH═C═CH2 or —CHF2, at least one of R1, R2, R3, R2a and R3a is fluoro or chloro.