ALLEY, STEPHEN C.,JEFFREY, SCOTT C.,SUSSMAN, DJANGO,BENJAMIN, DENNIS R.,TOKI, BRIAN,BURKE, PATRICK J.
申请号：
ES09739983
公开号：
ES2458541T3
申请日:
2009.05.01
申请国别(地区):
ES
年份:
2014
代理人:
摘要：
Method for the preparation of an antibody or modified antibody derivative that exhibits reduced core fucosylation, comprising: culturing a host cell in a culture medium comprising an effective amount of a fucose analogue under suitable growth conditions, wherein the Host cell expresses the antibody or antibody derivative with an Fc domain having at least one complex of a chain of sugars linked by N-glucoside linked to the Fc domain through an N-acetylglucosamine of the reducing end of the sugar chain, and isolate the antibody or antibody derivatives from cells, wherein the fucose analog is selected from the group consisting of one of the following formulas (III) or (IV): ** Formula ** or a biologically acceptable salt or solvate of the same, wherein each formula (III) or (IV) may be the alpha or beta anomer or the corresponding aldose form； each R1-R4 is independently selected from the group consisting of fluorine, chlorine, -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) alkylene (aryl) C1-C10, -OC (O) alkylene (aryl) C2-C10, -OC (O ) C2-C10 alkynyl (aryl), -OC (O) C1-C10 heterocycle, -OC (O) C2C10 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) CH2O (CH2CH2O) nCH3, -O-tri-C1-C3 alkylsilyl and -O alkyl C1-C10, where each n is an integer independently selected from 0-5； and each 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 (where X is Br, Cl or I), and methoxyran； where, when R5 is different from -CH>； = C>； = CH2 or -CHF2, at least one of R1, R2, R3, R2a and R3a is fluorine or chlorine； and where the antibody or antibody derivative exhibits reduced core fucosyla
