Office of Technology Transfer – University of Michigan

Thermal Stabilization of Cocaine Esterase

Technology #4512

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Roger Sunahara
Managed By
Ed Pagani
Associate Director, Health Technologies 734-763-3558
Patent Protection
US Patent Pending
US Patent Pending


Cocaine is considered to be the most addictive of all substances of abuse. Estimates for 2006 suggest that over half of all illicit drug-based emergency department visits involved cocaine, with over 500,000 occurrences. The devastating medical and social cost of cocaine addiction and overdose make discovery of pharmacological agents to block the addictive effects of cocaine an important goal. Unfortunately, developing a classical antagonist to block the actions of a pleiotropic inhibitor like cocaine has proven difficult, as small molecules that compete with cocaine binding could potentially be abused as they can also have neurological effects. To circumvent this problem, agents that intercept cocaine in the bloodstream to alter its distribution or accelerate its clearance have been explored. In particular, cocaine esterase from bacteria (CocE) have proven effective against cocaine-induced lethality in vivo. However, its effectiveness is limited by its unstability, resulting in dramatic time-dependent inactivation.


Researchers at the University of Michigan have developed mutated CocE polypeptides for treating and preventing cocaine addiction. These mutations give rise to increased stability, with uses for neutralizing cocaine in vitro for drug screening applications or in vivo for therapeutic applications. As compared to wild type CocE with thermal instability that results in the short half-life at 37C, the mutant has a longer half life at body temperature. Such stable forms of CocE would potentially eliminate the problem of aggregation during large scale production, formulation, and storage of this very important protein therapeutic drug.

Applications and Advantages


  • Treatment and prevention of cocaine addiction.


  • Enhanced stability and longer half life expands use of CocE as a therapeutic and diagnostic tool.