Production of a stable recombinant human butyrylcholinesterase

Human butyrylcholinesterase (BChE) is an effective bioscavenger of organophosphates and has potential for acting as a pre-exposure prophylactic or post-exposure treatment for organophosphate (OP) nerve agents, such as sarin. Ideally, a single dose of BChE could be administered and protect the warfighter for days or even weeks while in combat. To be effective in a military setting, especially as a prophylactic, BChE must have a very long serum half-life and must be non-immunogenic. It is now well-established that the plasma half-life of recombinant BChE is strongly affected by the extent of its oligomerization, glycosylation, and sialylation. Clear Scientific (CS) will partner with General Biologics, Inc. (GB), to design, express, and purify recombinant human BChE that meets or exceeds the blood serum half-life of wild-type human BChE. The team will use a multi-faceted approach to confer the requisite properties of BChE (full sialylation and tetrameric form). By the end of Phase I, CS and GB will have determined the best mutant BChE candidates for sialylation optimization, pharmacokinetic (PK) studies in small animals, lead optimization, and scale-up to grams of product in Phase II.