Wacker Biotech, a subsidiary of the Wacker Group, has recently completed a feasibility study with MedImmune, the global biologics research and development arm of AstraZeneca, for an antibody fragment using Wacker’s improved proprietary secretion technology, ESETEC 2.0. MedImmune commissioned this work in an effort to identify a cost-effective methodology for antibody fragment production for future therapies. The yields achieved with this enhanced version of the E. coli-based secretion system exceeded those of the original ESETEC technology by a factor of four.
Wacker has profoundly refined its ESETEC system, which is based on Escherichia coli bacteria, for the manufacture of pharmaceutical proteins. Targeted genetic modifications and process optimisation measures led to the development of new, extremely productive cell lines and fermentation procedures. As a result, complex molecules such as antibody fragments (Fab) can now be produced in yields of several grams per litre and can be secreted into the culture medium in active form.
Within only six weeks after obtaining the genes, Wacker was able to successfully produce MedImmune’s Fab antibody fragment and has achieved significant yields with its established ESETEC technology. The new ESETEC 2.0 version managed to surpass even these results: it delivered four times higher yields of correctly folded, fully functional antibody fragments in the culture medium when compared to the established ESETEC system. MedImmune has confirmed that the secreted fab was correctly assembled and bound to its target in vitro.
The company states that these results not only show that, for the production of antibody fragments that are difficult to manufacture, ESETEC technology is superior to established technologies. The findings also show that the new ESETEC 2.0 version offers advances in productivity that exceed industry optimised processes for mammalian cell cultures (CHO cells). Alongside the high yields that could be demonstrated for a variety of Fab antibody fragments, the production speed offers considerable advantages. With the new system, it only takes a few weeks to establish an efficient and industrial-scaled fermentation process for the manufacture of a Fab antibody.