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Development of a highly efficient technology for purification of recombinant tissue plasminogen activator

DOI: https://doi.org/10.29296/25419218-2019-04-06
Issue: 
4
Year: 
2019

D.V. Chashchinova, N.A. Shamonov, R.A. Vassarais, D.A. Kudlai AO «GENERIUM», 10, Testovskaya, Moscow 123112, Russian Federation

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.

Keywords: 
chromatography
affinity sorbent
tissue plasminogen activator
alteplase

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