Physicochemical Properties, Toxicity, and Specific Activity of a Follitropin Alpha Biosimilar

Воробьев, И И; Проскурина, О. В.; Khodak, Yu. A.; Государев, А. И.; Семихин, А. С.; Бырихина, Д. В.; Krasilshchikova, M. S.; Melnik, Bogdan S.; Serebryakova, Marina V.; Polzikov, M. A.

doi:10.1007/s11094-017-1525-3

Cited by 8 publications

(3 citation statements)

References 14 publications

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“…Core fucosylation of the glycans was found to be moderate and highly branched structures are more fucosylated than the biantennary ones. This distribution of N-glycans structures, composition, and charges (S8 and S9 Figs) is comparable to the previously published data for CHO-derived recombinant FSH [20,27,28].…”

Section: Resultssupporting

confidence: 90%

“…In vivo FSH biological activity was determined according to recommendations given in the European Pharmacopoeia, Ed.8.5 (Ch. 2285 and 2286) as described earlier [20], 21 rats per each group. This study was carried out in strict accordance with the GOST 33216–2014 “Guidelines for accommodation and care of animals.…”

Section: Methodsmentioning

confidence: 99%

“…In this paper, we present the development of CHO cell line, secreting mostly the heterodimeric FSH in large quantities and the process of FSH purification. The resulting FSH biosimilar was tested at the comparative preclinical study [20] and at the clinical level to prove its bioequivalence at pharmacokinetics study [21] and at pharmacodynamics study in women undergoing in vitro fertilization (NCT03088137).…”

Section: Introductionmentioning

confidence: 99%

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High-level expression of biologically active human follicle stimulating hormone in the Chinese hamster ovary cell line by a pair of tricistronic and monocistronic vectors

et al. 2019

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Recombinant human follicle stimulating hormone (FSH), produced in Chinese hamster ovary (CHO) cells, is widely used for treatment of fertility disorders and is subject to biosimilars development. Cell lines with high specific productivities may simplify the FSH production process. Here, we used our previously established expression system based on vector p1.1 to create new cell lines secreting heterodimeric FSH protein. To this end, we linked open reading frames of both FSH subunits by the wild-type internal ribosome entry site from the encephalomyocarditis virus (EMCV IRES). Intact and double-negative for the dihydrofolate reductase CHO cells were stably transfected by the FSH-coding plasmids. Stably transfected intact cells showed higher level of the FSH secretion and were utilized for subsequent methotrexate-driven transgene amplification, which doubled their productivity. The excess of the free α-subunit was corrected by transfecting the cells by the additional p1.1-based plasmid encoding the β-subunit of the FSH. Clonal cell lines obtained secreted mostly the heterodimeric FSH and possessed specific productivities up to 12.3±1.7 pg/cell/day. Candidate clonal cell line C-P1.3-FSH-G4 maintained a constant specific productivity for at least 2 months of culturing without the section pressure. The resulting FSH protein conformed to the international pharmaceutical quality criteria as evidenced by the receptor binding kinetics, distribution pattern of hormone isoforms and biological activity. In conclusion, our expression system offers a simple and cost-effective approach to production of FSH.

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Section: Resultssupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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