Patent ID: 9353127
Filing Date: 2016-05-31
CPC Classification: A61K,A61P,C07D,C07K

Claim Text:
1. A method for preparing a conjugate comprising a cell-binding agent (CBA) conjugated to a cytotoxic compound with a linking group, the method comprising reacting a modified cytotoxic compound with a modified CBA at a pH of about 4 to about 9, wherein: a) the modified CBA comprises a residue of a bifunctional crosslinking agent bonded to the CBA, and the residue comprises the linking group and a thiol-reactive group; and b) the modified cytotoxic compound is produced by reacting an imine-containing compound represented by the following formula: or a pharmaceutically acceptable salt thereof, with an imine reactive reagent, wherein: X′ is selected from —H, an amine-protecting group, an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, a polyethylene glycol unit —(CH Y′ is selected from —H, an oxo group, an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, an optionally substituted 6- to 18-membered aryl, an optionally substituted 5- to 18-membered heteroaryl ring containing one or more heteroatoms independently selected from nitrogen, oxygen, and sulfur, an optionally substituted 3 to 18-membered heterocyclic ring having 1 to 6 heteroatoms; R R R, for each occurrence, is independently selected from the group consisting of —H, an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having from 1 to 10 carbon atoms, a polyethylene glycol unit —(CH R′ and R″ are each independently selected from —H, —OH, —R, —NHR, —NR n is an integer from 1 to 24; W is selected from C═O, C═S, CH R Z and Z′ are independently selected from —(CH n′ and na′ are the same or different, and are selected from 0, 1, 2 and 3; R R A and A′ are the same or different, and are independently selected from —O—, oxo (—C(═O)—), —CRR′O—, —CRR′—, —S—, —CRR′S—, —N(R R D and D′ are the same or different, and are independently absent or selected from the group consisting of an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having 1 to 10 carbon atoms, an amino acid, a peptide bearing 2 to 6 amino acids, and a polyethylene glycol unit (—OCH L is absent, or when present, comprises a thiol group, or is a polyethylene glycol unit (—OCH the imine reactive reagent is selected from the group consisting of sulfites (H