ФИШКИН Нейтан (US),МИЛЛЕР Майкл (GB),ЛИ Вей (US),СИНГХ Раджива (US)
申请号：
RU2013142179/04
公开号：
RU2013142179A
申请日:
2012.02.15
申请国别(地区):
RU
年份:
2015
代理人:
摘要：
1. A method of producing a conjugate comprising a cell binding agent (CBA) conjugated to a cytotoxic compound via a linking group, said method comprising reacting a modified cytotoxic compound with a modified CBA at a pH of from about 4 to 9, wherein: a) the modified CBA includes the residue of a bifunctional crosslinking agent associated with CBA, and the specified residue includes a linking group and a group capable of interacting with a thiol； and b) the modified cytotoxic compound includes a thiol group and a group represented by the formula: where Y is a leaving group and is a sulfite (HSO, HSO or a salt of HSO, SO or HSO formed by a cation), metabisulfite (HSO or a salt of SO formed by a cation), mono, di-, tri- and tetratiophosphate (POSH, POSH, POSH, PSH or a salt of POS, POS2, POS or PS formed by a cation), thiophosphate ester (RO) PS (OR), RS-, RSO, RSCO, RSO, thiosulfate ( HSO or SO salt formed by cation), dithionite (HSO or SO salt formed by cation), phosphorodithioate (P (= S) (OR) (S) (O H) or a salt formed by a cation), hydroxamic acid (RC (= O) NOH or a salt formed by a cation), formaldehyde sulfoxylate (HOCHSO or a HOCHSO salt formed by a cation, for example, HOCHSO Na), or a mixture thereof, where R is linear or branched alkyl having from 1 to 10 carbon atoms and is substituted with at least one substituent selected from —N (R), —CHOH, —SOH, and —OH； R is optionally optionally substituted with an alkyl substituent described herein； R is a linear or branched alkyl having from 1 to 6 carbon atoms； R is linear, branched or1. Способ получения конъюгата, включающего агент, связывающийся с клетками (СВА), конъюгированный с цитотоксическим соединением посредством связывающей группы, причем указанный способ включает взаимодействие модифицированного цитотоксического соединения с модифицированным СВА при рН приблизительно от 4 до 9, причем:а) модифицированный СВА включает остаток бифункционального сшивающего агента, связанный с СВА, а указанный остаток включ
