Development and manufacturing of a biobetter therapeutic: A case study

A Protein C (APC) is a naturally occurring human protease that has both anticoagulant and cytoprotective activities, with the latter being appropriate for treatment of ischemic stroke. ZZ Biotech has created a variant, 3K3A-APC, which reduces the anticoagulant activity while retaining its cytoprotective activity, thereby avoiding the dose-limiting side effect of unwanted bleeding. We describe the development of recombinant CHO-cell production and purification of 3K3A-APC, from small cultures to 2000-liter production. By working collaboratively, scientists from both companies were able to overcome this molecule’s challenges of complex post-translational modifications, enzyme isomers, and autodigestion. The result was a successful regulatory filing leading to a Phase 1 clinical trial, which recently completed. Michiel E. Ultee et al., J Bioanal Biomed 2013, 5:4 http://dx.doi.org/10.4172/1948-593X.S1.010