Production of stable bispecific IgG1 by controlled Fab-arm exchange: Scalability from bench to large-scale manufacturing by application of standard approaches

摘要: The manufacturing of bispecific antibodies can be challenging for a variety reasons. For example, protein expression problems, stability issues, or the use non-standard approaches result in poor yield facility fit. In this paper, we demonstrate standard antibody platforms large-scale IgG1 by controlled Fab-arm exchange. Two parental that each contain single matched point mutation CH3 region were separately expressed Chinese hamster ovary cells and manufactured at 1000 L scale using platform fed-batch purification process was designed production. generated mixing two molecules under reducing conditions, resulting efficient exchange >95% kg scale. reductant removed via diafiltration, spontaneous reoxidation interchain disulfide bonds. Aside from nature molecule, extensive characterization demonstrated structural integrity maintained, including function stability. These results suitability format commercial-scale techniques.