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

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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
References: 
  1. Collaborators G. B. D. C. o. D. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (London, England). 2017. T. 390; 10100: 1151–210. https://doi.org/10.1016/S0140-6736(17)32152-9
  2. Mokdad A. H., Forouzanfar M. H., Daoud F., Mokdad A. A., El Bcheraoui C.et al. Global burden of diseases, injuries, and risk factors for young people's health during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013, Lancet. 2016. T. 387; 10036: 2383–401. https://doi.org/10.1016/S0140-6736(16)00648-6
  3. Chapman S. N., Mehndiratta P., Johansen M. C., McMurry T. L., Johnston K. C., Southerland A. M. Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke, Vasc Health Risk Manag. 2014. T. 10: 75–87. https://doi.org/10.2147/VHRM.S39213
  4. Kowey P. R., Fisher L., Giardina E., et al. The tpa controversy and the drug approval process: The view of the cardiovascular and renal drugs advisory committee, JAMA. 1988. T. 260; 15: 2250–2. PMID: 3139900
  5. Powers Wj Fau, Rabinstein A. A., Rabinstein Aa Fau, Ackerson T., Ackerson T Fau,et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association; 1524–4628 (Electronic). https://doi.org/10.1161/STROKEAHA.118.020176
  6. Ibanez B Fau, James S., James S Fau, Agewall S., Agewall S Fau et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC); 1522–9645 (Electronic). https://doi.org/10.5603/KP.2018.0041
  7. Prikaz Ministerstva zdravoohranenija Rossijskoj Federatsii ot 22 janvarja 2016 g. №36n «Ob utverzhdenii trebovanij k komplektatsii lekarstvennymi preparatami i meditsinskimi izdelijami ukladok i naborov dlja okazanija skoroj meditsinskoj pomoschi, trebovanija k komplektatsii lekarstvennymi preparatami i meditsinskimi izdelijami ukladok i naborov dlja okazanija skoroj meditsinskoj pomoschi» [Elektronnyj istochnik] / https://www.garant.ru/products/ipo/prime/doc/71240210/ (data obraschenija 01.07.2016).[Order of the Ministry of Health of the Russian Federation dated January 22, 2016 No. 36n «On approval of requirements for completing drugs and medical products for styling and emergency medical kits, requirements for completing medical equipment and medical products for styling and emergency medical kits» (in Russian)]
  8. Rasporjazhenie Pravitel'stva Rossijskoj Federatsii ot 10 dekabrja 2018 g. № 2738-r «Perechen' zhiznenno neobhodimyh i vazhnejshih lekarstvennyh preparatov dlja meditsinskogo primenenija na 2019 god [Elektronnyj istochnik] https://spbmiac.ru/wp-content/uploads/2018/12/perechen' zhiznenno neobhodimyh i vazhnejshih lekarstvennyh preparatov na 2019-g.pdf. (data obraschenija 01.01.2019).[Order of the Ministry of Health of the Russian Federation dated January 22, 2016 №36n «On approval of requirements for completing drugs and medical products for styling and emergency medical kits, requirements for completing medical equipment and medical products for styling and emergency medical kits» (in Russian)]
  9. Ny T., Elgh F., Lund B. The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains, Proc Natl Acad Sci U S A. 1984. T. 81; 17: 5355-DOI: 10.1073/pnas.81.17.5355
  10. Collen D. On the regulation and control of fibrinolysis. Edward Kowalski Memorial Lecture, Thromb Haemost. 1980. T. 43; 2: 77–89. https://doi.org/10.1073/pnas.81.17.5355
  11. Kuznik B.I. Gemorragicheskie i tromboticheskie zabolevanija i sindromy u detej i podrostkov: Patogenez, klinika, diagnostika, terapija i profilaktika. B.I. Kuznik, V.G. Sturov N.Ju. Levshin, O.G. Maksimova, D.A. Kudlaj. – 2-e izd., pererab. i dop. – Novosibirsk: Nauka, 2018;– 524 s.[Kuznik B. I. Hemorrhagic and thrombotic diseases and syndromes in children and adolescents: Pathogenesis, clinic, diagnostics, treatment and prevention. B. I. Kuznik, V. G. Sturov N. Yu. Levshin, O. G. Maksimova, D. A. Kudlay. – 2nd ed., pererab. I DOP. Novosibirsk: Nauka, 2018; 524 (in Russian)].
  12. Rijken D. C., Wijngaards G., Zaal-de Jong M., Welbergen J. Purification and partial characterization of plasminogen activator from human uterine tissue, Biochim Biophys Acta. 1979. T. 580; 1: 140–53. https://doi/org/10.1016/0005-2795(79)90205-8
  13. Dodd I., Jalalpour S., Southwick W., Newsome P., Browne M. J., Robinson J. H. Large scale, rapid purification of recombinant tissue-type plasminogen activator, FEBS Lett. 1986. T. 209; 1: 13–7. PMID: 3100325
  14. Ivanov R., Sekareva G., Kravtsova O., Kudlaj D., Luk'janov S., Tihonova I., Demin A., Maksumova L., Nikitina I., Obuhov A., Zajtsev D., Stepanov A., Nosyreva M., Samsonov M. Pravila provedenija issledovanij bioanalogovyh lekarstvennyh sredstv (bioanalogov), Farmakokinetika i farmakodinamika. 2014; 1: 21–36.[Ivanov R., Sekareva G., Kravtsova O., Kudlay D., Lukyanov S., Tikhonova I., Demin A., Maksumova L., Nikitina I., Obukhov A., Zaitsev D., Stepanov A., nosyreva, M., Samsonov, M. Rules of studies of biosimilar medicinal products (biosimilars), Farmakokinetika i farmakodinamika. 2014; 1: 21–36 (in Russian)].
  15. Mamaev A.N., Kudlaj D.A. Vizualizatsija dannyh v prezentatsijah, otchetah i issledovanijah. M.: Prakticheskaja meditsina, 2011: 39. [Mamaev A. N., Kudlay D. A. data Visualization in presentations, reports and studies. M.: Practical medicine, 2011. 39 p (in Russian)].
  16. Council of Europe. European Pharmacopoeia 7.0. In: Monograph A. Strasbourg, Council of Europe – 2009 – Alteplase: 1352–5.