КЕЛЛОГ Бренда А. (US),СИНГХ Раджиева (US),ЧАРИ Рави В. Дж. (US)
申请号：
RU2011153288/10
公开号：
RU2011153288A
申请日:
2010.06.02
申请国别(地区):
RU
年份:
2013
代理人:
摘要：
1. A method of preparing a purified conjugate in solution, wherein the conjugate comprises an effector or reporter molecule coupled to a cell-binding agent, comprising the steps of: (a) linking the effector or reporter molecule to a bifunctional linker reagent for covalently linking the linker to an effector or reporter molecule and preparation of a crude first mixture thus containing effector or reporter molecules linked to a linker, (b) conjugation of a cell-binding agent with effector a ctor or reporter molecule linked to the linker by reacting the crude first mixture with a cell-binding agent to prepare the second mixture and (c) exposing the second mixture to tangential flow filtration, dialysis, gel filtration, adsorption chromatography, selective precipitation, or a combination thereof obtaining purified conjugate. 2. The method according to claim 1, characterized in that step (b) is performed in a solution with a pH from about 4 to about 9.3. The method according to claim 1, characterized in that the second mixture in step (b) is mostly free of unwanted crosslinked hydrolyzed particles resulting from intramolecular or intermolecular reactions. The method according to claim 1, characterized in that the effector molecule is a cytotoxic agent. The method according to claim 4, characterized in that the cytotoxic agent is a maytansinoid, taxane, CC1065 or their analogue. The method according to claim 4, characterized in that the cytotoxic agent is a maytansinoid. The method according to claim 6, characterized in that the maytansinoid includes a thiol group. The method according to claim 6, characterized in that1. Способ приготовления очищенного конъюгата в растворе, при этом конъюгат включает эффекторную или репортерную молекулу, соединенную со связывающимся с клетками агентом, включающий этапы: (а) связывания эффекторной или репортерной молекулы с бифункциональным линкерным реагентом для ковалентного присоединения линкера к эффекторной или репортерной молекуле и
