LARGE-SCALE PRODUCTION PROCESS FOR HARVESTED AND UNLARGED ANTIBODY CYSTEINS AND THEIR USE IN THE CONJUGATION OF THERAPEUTIC PROTEINS

摘要

the present invention relates to the optimization of the production of selectively capped and uncapped cysteines in antibodies through the manipulation of cell growth conditions including the deliberate depletion of cysteine and / or cystine in the cell culture process by means of components of the medium, duration batch, or cell density to achieve efficient protein production including antibody-drug conjugates (adcs); conjugation of a tnb-capped cysteine protein by reacting with a reducing agent capable of separating the tnb-capping components from the protein without significantly reducing the inter-antibody sulfur bonds, and conjugation of the reduced sulfur bonds in the protein with a payload through a reactive connection component.