Comparative Assessment of the Structural Features of Originator Recombinant Human Follitropin Alfa Versus Recombinant Human Follitropin Alfa Biosimilar Preparations Approved in Non-European Regions.

Although the full primary structures of the alfa and beta subunits of reference r-hFSH-alfa and its biosimilars are identical, cell context-dependent differences in the expressing cell lines and manufacturing process can lead to variations in glycosylation profiles. In the present study, we compared the structural features of reference r-hFSH-alfa with those of five biosimilar preparations approved in different global regions outside Europe (Primapur®, Jin Sai Heng®, Follitrope®, Folisurge®, and Corneumon®) with respect to glycosylation, macro- and microheterogeneity, and other post-translational modifications and higher order structure. The mean proportion of N-glycosylation-site occupancy was highest in reference r-hFSH-alfa, decreasing sequentially in Primapur, Jin Sai Heng, Corneumon, Follisurge and Follitrope, respectively. The level of antennarity showed slightly higher complexity in Corneumon, Primapur and Follitrope versus reference r-hFSH-alfa, whereas Jin Sai Heng and Folisurge were aligned with reference r-hFSH-alfa across all N-glycosylation sites. Sialylation level was higher in Corneumon and Follitrope, but small differences were detected in other biosimilar preparations compared with reference r-hFSH-alfa. Jin Sai Heng showed higher levels of N-glyconeuramic acid than the other preparations. Minor differences in oxidation levels were seen among the different products. Therefore, in summary, we identified var ious differences in N-glycosylation occupancy, antennarity, sialylation and oxidation between reference r-hFSH-alfa and the biosimilar preparations analyzed.

Biological Functions of Interferon ß-1a Are Enhanced By Deamidation.

Human type I Interferons (IFN-ß, IFN-ɛ, IFN-κ, IFN-ω, and 12 subtypes of IFN-α) are a family of pleiotropic cytokines with antiviral, antiproliferative, and immunomodulatory activities. They signal through the same cell surface receptors, IFNAR1 and IFNAR2, yet evoking markedly differential potency. One differentiating factor of IFN-ß from other type I interferons is the presence of a consensus sequence (NG) for deamidation. Comparing almost completely deamidated IFN-ß-1a with untreated IFN-ß-1a, this present study reports the increased activities in 3 in-vitro bioassays testing the antiviral, antiproliferative, and immunomodulatory properties, respectively, of the molecule. Deamidated IFN-ß-1a has the potential to improve current therapies in multiple sclerosis, and its ability to potentiate the MHC-Class I expression suggests a clinical benefit in diseases where the downmodulation of the MHC-class I expression plays a role (eg, in immuno-oncology combination therapies or antiviral agents). The present study on IFN-ß deamidation adds a new prospective on deamidation as part of a posttranslational modification code that allows the modulation of the biological properties of proteins. Moreover, it underlines the unique IFN-ß-1a properties that differentiate this molecule from other members of the type I interferon family.