DEVELOPMENT OF A HIGHLY EFFICIENT TECHNOLOGY FOR PURIFICATION OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR


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Abstract

Introduction. Alteplase (recombinant tissue plasminogen activator (rtPA)) is the main thrombolytic agent recommended for the therapy of ischemic stroke and myocardial infarction. Alteplase is obtained by a recombinant DNA technique in CHO cell culture. Revelyse® manufactured by AO «GENERIUM» is the first registered Actilyse (alteplase, Boehringer Ingelheim) biosimilar. The existing technologies to obtain alteplase are involved and have a low yield. Objective: to develop a highly efficient procedure for purification of alteplase. Material and methods. Alteplase-containing culture fluid (CF) (AO «GENERIUM»), Actilyse® (alteplase, Boehringer Ingelheim), the affinity sorbent CaptureSelect tPA (ThermoScientific). Results. A commercial alteplase purification procedure based on the affinity sorbent CaptureSelect tPA (Thermo Scientific) was developed and scaled. Conclusion. The developed alteplase purification procedure allows one to obtain a drug that is biosimilar to Actilyze® and meets the requirements of the Pharmacopoeia.

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About the authors

Daria V. Chashchinova

AO «GENERIUM»

Email: chacschinova@ibcgenerium.ru
researcher of the Scale-Up and Technology Transfer Department 10, Testovskaya, Moscow 123112, Russian Federation

Nikolay A. Shamonov

AO «GENERIUM»

Email: shamonov@ibcgenerium.ru
acting chief of the Scale-Up and Technology Transfer Department, Candidate of Biology Science 10, Testovskaya, Moscow 123112, Russian Federation

Roman A. Vassarays

AO «GENERIUM»

Email: vassarays@ibcgenerium.ru
researcher of the Scale-Up and Technology Transfer Department 10, Testovskaya, Moscow 123112, Russian Federation

Dmitry A. Kudlay

AO «GENERIUM»

Email: dakudlay@generium.ru
general director, Doctor of Medicine, Professor. 10, Testovskaya, Moscow 123112, Russian Federation

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