LARGE SCALE PRODUCTION PROCESS FOR CAPPED AND UN-CAPPED ANTIBODY CYSTEINES AND THEIR USE IN THERAPEUTIC PROTEIN CONJUGATION

Optimizing production of selectively capped, and uncapped, cysteines on antibodies by manipulation of cell growth conditions including the deliberate depletion of cysteine and/or cystine in the cell culture process by way of media components, batch duration, or cell density to achieve efficient production of proteins including antibody-drug-conjugates (ADCs).; conjugating a TNB-capped cysteine-containing protein by reacting it with a reducing agent capable of detaching the TNB-capping moieties from the protein without significantly reducing antibody inter-chain sulfur bonds, and conjugating reduced sulfur bonds on the protein to a payload through a reactive linking moiety.