BI HEX™ – Platform for Fast Track Generation of High Producer Cell Lines Leading to High-Titer Processes for Production of Therapeutic Proteins from Mammalian Cells

The majority of biopharmaceuticals is currently being expressed in mammalian cells, mostly Chinese hamster ovary (CHO) and mouse myeloma (NSO) cells. The two most prominent challenges for mammalian cell-based systems relate to (i) product titer in the cell culture fluid at the end of cultivation and (ii) development times from final drug candidate selection to an established process to produce clinical grade material. The newest generations of mammalian cell culture production processes evolve rapidly to overcome these limitations. Boehringer Ingelheim's current high expression (BI HEXTM) cell line generation concept combines many improvements including novel or modified genetic elements to improve transcription rate, high throughput screening concepts to obtain highly productive clones reliably, and host cell lines that grow to high densities in serum-free chemically defined media. Specific productivities above 50 pg per cell and day for monoclonal antibodies have been achieved in CHO cells and were successfully translated into product titers of up to 4 g/L in an 11-day process. Furthermore, a strategy is presented for supply of material for toxicological studies produced from CHO cells in as little as 15 months starting with cloning of product-encoding genetic sequences into BI HEX vectors. At the same time it ensures that the production cell generated during this program will have the high expression potential needed to avoid a change in production cell line at later stages in development.