Written by Expert: Wilfried, Director Science & Innovation.
Biopharmaceuticals are expensive due to the many years of research and development associated with the discovery, development, clinical testing, and market launch of these medicines. As an example; the Food and Drug Administration (FDA) approved a monoclonal antibody called ipilimumab (Yervoy; Bristol-Myers Squibb, New York, NY) for the treatment of metastatic melanoma. The benefit in survival above standard treatment is 3.7 months. The cost of ipilimumab is $120,000 for 4 doses. As staggering as that is, this biopharmaceutical drug is not alone in its lofty price.
If product yields could be significantly increased on our biotechnology platforms, this would allow drastic reductions in market price. An increase in production yield means manufacturing scale can be reduced, hence the cost of goods will be lower. Therefore, biopharmaceutical product yield is THE most important factor. With a rapidly increasing number of highly promising medicines manufactured through biotechnology in the pipeline, the race to develop better expression technology is on.
At Batavia Biosciences, my colleagues and I developed STEP® technology to dramatically increase production yields on mammalian cells, including the Chinese Hamster Ovary cell line (CHO cells). We employ this plasmid-based expression technology as part of a fully integrated technology platform for cell line and bioprocess development, combining it with high cell density manufacturing, and innovations in purification. I am proud that in every project we can demonstrate significant cost reductions in the manufacturing of recombinant proteins and antibodies.
STEP® technology
STEP® technology allows for the rapid (< 12 weeks) generation of stable CHO cell lines able to produce at least 10-fold higher protein yield compared to relevant benchmarks, while maintaining product quality. CHO cells are the workhorse of the biopharmaceutical industry, because they are versatile and easy to handle. But most importantly, they have been studied over several decades and at the heart of many successful product launches.
Our STEP® technology consists of a plasmid containing two unique features; (I) a molecular design that allows for very stringent cell selection and (II) novel potent expression enhancer elements. Highly stringent cell selection is ensured by cloning the gene sequence of the protein of interest, downstream of a CMV promotor, but upstream of a functionally impaired Zeocin antibiotic resistance marker. Since both coding sequences are genetically linked, one mRNA is transcribed that results in the parallel translation of two proteins. Since a cell will only survive stringent antibiotic selection when exceptionally high amounts of the impaired Zeocin protein is present, that cell per definition expresses proportionally high amounts of the protein of interest, saving us much time in clone selection.
The STEP® technology encompasses three variants of stringency by different functionally impaired Zeocin resistance markers, enabling our scientists to control the expression rate of the protein of interest. This way we can find the most optimal expression rate for all types of proteins, ensuring the highest possible expression rate. Glycan analysis of the produced proteins confirmed biological activity to be identical for the three stringency variants. Sialylation and glycosylation patterns were stable and matched with relevant benchmarks.
Regulatory scrutiny
The STEP® plasmids are completely synthesized to adhere to the regulatory guidelines. In combination with Batavia Biosciences’ pharmaceutical-grade CHO cell line, our STEP® technology provides a proven platform to manufacture stable, high expressing, CHO cell lines.
As a company dedicated to help bringing biopharmaceuticals to the market at higher speed, with reduced costs, and with a higher success rate, Batavia Biosciences has vast experience in developing mammalian cell lines. With our team of experienced researchers, using the newest technologies and techniques, we are well equipped to take on any challenge associated with cell line development.
