PROTEIN FRAGMENTATION CONTROL STRATEGY BY RE-OXIDATION IN DOWNSTREAM CHROMATOGRAPHY

摘要

Methods for the production of high purity recombinant protein such as monoclonal antibodies (mAb) using disulfide bond re-oxidation are provided. In particular, the present disclosure provides methods for converting partial molecules (e.g., antibody fragments) to full molecules (e.g., full antibodies) comprising admixing a starting solution comprising the partial molecules with a redox buffer comprising a redox pair which comprises at least one thiol reducing agent (e.g., cysteine) and at least one thiol oxidizing agent (e.g., cystine), wherein the redox buffer re-oxidizes the partial molecules to full molecules. The disclosed methods can be used, e.g., to prevent or mitigate the formation of partial molecules during protein purification, or to reprocess or rescue a solution comprising partial molecules (e.g., a partially degraded pharmaceutical formulation).