Patent ID: 6913748

Claim:
A method of making a conjugate comprising a cell binding agent and one or more small molecule drugs, wherein said conjugate is represented by formula (V): wherein CB represents the cell binding agent, A represents the small molecule drug linked by a disulfide moiety, R, R 1 , R 2 and R 3 are the same or different and are H, methyl, ethyl, or linear, branched or cyclic alkyl having 3 to 6 carbon atoms, n is 0 or an integer from 1 to 4, and m is an integer of 1 to 10 or more, said method comprising: (1) reacting the cell binding agent with a cross-linker of the formula (I): wherein X and Y are the same or different and are H, CONR 4 R 5 or NO 2 , provided that X and Y are not both H at the same time, R 4 and R 5 are the same or different and are each H, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl or tert-butyl, and Z is SO 3 − M + or H, wherein M + represents a metal ion or a tetra alkyl ammonium ion, to thereby give a compound of the formula (III): wherein p represents an integer of 1 to 10 or more, and (2) reacting the compound of the formula (III) with one or more small molecule drugs comprising a free thiol group.