Novel Expression Systems for Biomanufacturing
Therapeutics have evolved significantly over the past few decades, expanding from traditional small molecules to innovative modalities such as peptides, non-antibody based proteins, and advanced cell therapies. Accompanying this trend, enzymes are also increasingly being employed to perform complex chemical transformations with enhanced selectivity and specificity in the process to manufacture small molecule drug substances, all while promoting sustainability. All these advancements necessitate the development of scalable and robust process for the production of diverse biomolecules.
In the Process R&D Enabling Technologies group at Merck, we have recently established the Novel Expression Systems team to identify the most suitable hosts for the engineering and expression and of various biomolecules. We are exploring Bacillus subtilis and Komagataella phaffii (previously known as Pichia pastoris) as promising hosts that capitalize on the advantages of protein secretion. In this presentation, we will share preliminary findings demonstrating the successful production of a variety of target proteins in these hosts, including enzymes, peptides, and antibody derived molecules, with results achieved in bench-scale bioreactors. By closely collaborating with other internal partner groups, the ultimate goal is to enhance the understanding and efficiency throughout the DBTL (Design, Build, Test, Learn) cycle to achieve successful right-first-time scale-up and manufacturing.