Technology Listings


Use of Thrombin Mutant to Reverse the Effect of Direct Thrombin Inhibitors

Application

The thrombin mutant provides a quick and powerful antidote to synthetic direct thrombin inhibitors.

Technical Summary

Direct thrombin inhibitors (DTIs) are a relatively new class of agents which specifically bind to and inactivate one or more of the active sites on the thrombin molecule. These drugs exhibit a number of advantages that make them uniquely attractive as potential therapeutic agents. Such advantages include the fact that Antithrombin III is not required as a cofactor, they can inhibit clot-bound thrombin, circulating inhibitors do not inhibit their function, and they do not appreciably bind to plasma proteins. With all of their advantages, however, problems remain for patients requiring the use of DTIs. Current antidote principles for DTI's (such as DFP thrombin, benzoyl thrombin, meizothrombin, etc.) have been too toxic or are not effective in fluid phase. Furthermore, DTIs have a propensity to cause hepatotoxicity and hemorrhage. The invention is a mutant thrombin that has a high affinity for thrombin inhibitors, but a low affinity for prothrombotic thrombin substrates such as fibrinogen. Consequently, the mutant thrombin can serve as an antidote for synthetic DTIs without many of the side effects associated with failed approaches.

Developmental Stage & Potential Market

The current estimate of patients treated with anticoagulants for atrial fibrillation (AF), deep vein thrombosis/pulmonary embolism (DVT/PE), acute ischemic stroke (IS), and unstable angina (UA) approaches 65 million. The market for anticoagulant agents in AF, DVT/PE, acute IS, and UA has been estimated at $5 billion.

Patent Information
App Type Country Serial No. Patent No. File Date Issued Date Expire Date
Nationalized PCT - Foreign Canada 2,680,736   3/15/2007    
Nationalized PCT - Foreign Japan 2009-500609   3/15/2007    
Nationalized PCT - Foreign India 3979/KOLNP/2008   3/15/2007    
Tech ID: 06009
Published: 2/24/2009
Category
Therapeutics

Contact
Rajsekhar Guddneppanavar
Licensing Associate
Emory University
RGUDDNE@emory.edu

Inventor(s)
Kenichi Tanaka
Enrico Di Cera
Stephen Hanson
Andras Gruber

Keywords
Cardiovascular