METHOD FOR FURTHER UPSCALING THE LARGE-SCALE PRODUCTION OF THE ONCOLYTIC H-1 PROTOPARVOVIRUS (H-1PV) USING A CARRIER-BASED PRODUCTION PROCESS COMBINED WITH AN OPTIMIZED CELL CULTURE MEDIUM

• Main Authors: LEUCHS, Barbara, VOGEL, Martin, PHAN, Linh Minh Phuc, WOHLFARTH, Daniel, FREHTMAN, Veronika, BRUNECKER, Adrian
• Format: Patent
• Language: English
• Published: 28.03.2024
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; VINEGAR; WINE

The present invention provides a method for upstream optimization the large-scale parvovirus production, preferably the oncolytic protoparvovirus H-1 (H-1PV). It is based on microcarriers or macrocarriers and their respective use in suspension or fixed-bed, an optimized cell culture medium, and a medium exchange strategy. In summary, with the optimized cell culture medium and the new medium exchange strategy, the inventors established a reduction in seeded cell density and animal serum, leading to an animal serum-free harvest. The tested carriers are best suited for a high H-1PV yield, cell growth, and bead-to-bead transfer capability, wherein the inventors additionally scaled up the process from 24-well plates to Erlenmeyer, Spinner flask and iCellis nano. As a conclusion, the present invention provides a large-scale method for producing the oncolytic protoparvovirus H-1 with a high virus yield, while lowering production costs and avoiding undesired products of animal origin at the same time.