Method for the preparation of monomeric calicheamicin derivative/carrier conjugates

A method is provided for preparing monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation. These conjugates are prepared by incubating a calicheamicin derivative and a proteinaceous carrier in a solution comprising a phosphate buffered solution, a cosolvent comprising propylene glycol, an additive comprising at least one C6-C25 carboxylic acid, preferably having a pH in the range from about 7.0 to 8.5, and at a temperature ranging from about 25 DEG C. to about 37 DEG C. for a period of time ranging from about 2 hours to about 18 hours, and recovering monomeric calicheamicin derivative/carrier conjugates. Alternatively, the conjugates can be prepared by incubating the calicheamicin derivative and a proteinaceous carrier in a solution comprising a phosphate buffered solution and a cosolvent comprising t-butanol.