The business opportunity could be significant. Monoclonal antibodies represent a large market, producing over $100 billion a year of annual revenue, greater than any other biotechnology therapeutic. However, they’ve been developed for rare diseases and cancers which don’t have the incidence of COVID-19. This will require innovation in their manufacturing processes to accelerate production from the standard 9-12 months.
Traditionally, antibodies are manufactured in mammalian CHO cells. SwiftScale is proposing to manufacture antibodies out of bacterial E.coli cells, greatly reducing production times. The rationale for using mammalian cells has been that antibodies require glycosylation (the process of sugars attaching to a protein) in order to recognize the epitopes attached to the antigens they are intended to fight. This process typically occurs in the endoplasmic reticulum and golgi apparatus of a mammalian cell, and has thus far prevented wide scale manufacturing of antibodies from bacteria.
Glycosylation results from a post-translation modification in mammalian cell protein synthesis, and factors into the long lead time to manufacture mAbs. SwiftScale is proposing to create the glycosylation process outside the cell, and drastically reduce not just lead times, but the size of the manufacturing components. They claim a test tube could be used where a 50,000 liter bioreactor is used today.
The idea of developing antibodies out of bacteria is not new. In 2007, a University of Texas study analyzed the prospects for doing this. What’s changed is the market has grown nearly tenfold since then, and is poised to grow further with demand for COVID treatments.
In addition to glycosylation, bacterial mAbs will need to emulate the disulfide bonds created by mammalian cell engineered proteins, which is also essential for bonding with antigen epitopes. While the research at Cornell provides some insight into SwiftScale’s process, some of the actual techniques the company is using to overcome bacteria’s antibody production challenges remain proprietary. Nonetheless, the demand created by COVID vaccines could finally give this manufacturing technique the high volume application it’s been searching for.