January 29, 2018 Presentation about design, structure, and manufacturability of fusion proteins at PepTalk 2018
At this year's Peptalk Dr. Stefan R. Schmidt, Chief Scientific Officer at Rentschler Biopharma, presented strategies how to successfully manufacture complex fusion proteins.
Designed protein molecules with no counterpart in living organisms are susceptible to low expression, miss-assembly and mis-folding, disulfide scrambling, aggregation, and a sensitivity to protein degradation. Consequently, smart fusion protein design and efficient bioprocesses influence the manufacturability of fusion proteins.
The presentation outlined several case studies highlighting implemented strategies to obtain proteins with desired molecule properties. Examples included improved protein half-life by glycosylation, reduction of unwanted protein species by enforcing oligomerization via AA mutations, and implementation of new cultivation strategies to influence molecule properties.
Furthermore, complex fusion proteins suffer from a high level of product-related impurities. Consequently, careful fine tuning of DSP steps, including resin choice, wash conditions, and peak cutting parameters to eliminate incomplete molecules, is essential.
Altogether, the successful manufacturing of designed, next-generation therapeutic proteins incorporates a combination of theoretical and experimental methods.
Rentschler Biopharma SE
Dr. Alexander Starnecker
Manager Company Development