Beyond CHO cells: Cell-free protein synthesis for biotherapeutics

The production of recombinant proteins and antibodies using a cell-free synthesis step can now deliver industrially-relevant quantities of the target biologic. The technology is ideally suited to the rapid generation of antibody-drug conjugates (ADCs), bispecific antibodies, and other protein formats that do not require glycosylation for functionality. A proprietary technology allows for incorporation of a non-natural amino acid at the desired sequence location(s) that can subsequently be combined with site-specific conjugation chemistry to deliver highly precise drug to antibody ratio (DAR). This presentation will describe this alternative production technology in terms of the underlying technology, the technical challenges that have been overcome and the milestones achieved, and the benefits that can be delivered using this approach. In particular, a cell-free protein synthesis step enables extremely rapid (e.g, days) generation of candidate molecules once plasmid DNA is available. This allows for rapid screening of multiple candidate molecular sequences and formats without the need to utilize or generate any living cells (CHO, or otherwise) on the critical path to product expression. The applications of this technological approach will be highlighted and contrasted with the CHO workhorse of our industry