Expression of a Fab Fragment in CHO and Pichia pastoris

Mammalian cell expression systems are currently essential for production of glycosylated biopharmaceuticals such as monoclonal antibodies or molecules requiring even more complex glycan structures. Various host cell and vector systems aimed at improving expression levels and quality have been established (1, 2). Development of biopharmaceutical product candidates from genes to clinical trials should be based on technology platforms that will require no major changes in the entire development chain, including manufacturing once a product candidate has successfully progressed through phase 1–2 clinical testing. The intrinsic cost structure thus is widely determined by the category of technology platform chosen very early in development. Development time is currently considered by modern management to be of utmost importance. Antibody fragments (Fabs) represent an interesting category of potential biopharmaceuticals (3, 4). About 20% of all Fabs have glycosylation sites that putatively might contribute to their biological in vivo performance (5). We investigated two different state-of-theart technology platforms — the CHO mammalian system and the Pichia pastoris yeast system — to produce Fab fragments with identical primary sequence and compared the results. We analyzed the time needed for development of different technology platforms and intrinsic parameters such as specific and volumetric productivity as well as quality criteria based on preclinical and in vitro properties.