Camptothecin-binding moiety conjugates

摘要

The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.

主权项

1. A conjugate of a camptothecin drug and a targeting moiety (TM) of the formula: TM-[L]-CPT, where TM is a cancer targeting monoclonal antibody; CPT is selected from the consisting of camptothecin, 10-hydroxy camptothecin, SN-38, topotecan, lurtotecan, 9-aminocamptothecin, and 9-nitrocamptothecin; and L is a linker system of the type X-Y-Z wherein X is an antibody coupling moiety comprising a defined polyethylene glycol (PEG) wherein the defined PEG contains a defined number of monomeric units that is between 1 and 12 monomeric units, Y is a lysosomally cleavable polypeptide, and Z is 4-aminobenzyloxy moiety, which is connected to the CPT drug, wherein Z is connected to a 20-hydroxy group of CPT by a carbonate or carbamate bond and X is connected to TM by a bond between a thiol group and a thiol-reactive moiety selected from the group consisting of maleimide, vinylsulfone, bromoacetamide, and iodoacetamide.