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A Comparison of the Oligosaccharide Structures of Antithrombin Derived from Plasma and Recombinant Using POTELLIGENT® Technology

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Abstract

Human antithrombin (AT) has two isoforms of which the predominant α-form is glycosylated on all four possible glycosylation sites and the lower abundant β-isoform lacks the oligosaccharide on Asn135. The main oligosaccharide structure of human AT consists of biantennary complex-type oligosaccharides lacking a core fucose. Generally, Chinese hamster ovary (CHO) cells produce recombinant human AT (rhAT) with core-fucosylated oligosaccharides. However, rhAT lacking core-fucose oligosaccharides can be produced by POTELLIGENT® technology, which uses FUT8 knockout CHO cells in production. The rhAT has more variable glycan structures, such as tetra-antennary complex type, highmannose type, and mannose 6-phosphate species as minor components compared to plasma-derived human AT (phAT). In addition, the site-specific glycan profile was different between two ATs. We evaluated the effect of these properties on efficacy and safety based on a comparison of rhAT made by that technology with phAT in terms of their respective oligosaccharide structures, site-specific oligosaccharide profiles, and the ratio of α- and β-forms. Although some structural differences were found between the rhAT and phAT, we concluded that these differences have no significant effect on the efficacy and safety of rhAT.

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Authors and Affiliations

  1. Bio Process Research and Development Laboratories, Production Division, Kyowa Kirin Co., Ltd., Takasaki, Gunma, 370?0013, Japan

    Yuki Yagi, Megumi Endo, Kumi Yanagisawa, Koichiro Nishimura & Katsuyoshi Yamazaki

  2. Takasaki Plant, Production Division, Kyowa Kirin Co., Ltd., Takasaki, Gunma, 370?0013, Japan

    Akira Okazaki

  3. Corporate Strategy & Planning Department, Kyowa Kirin Co., Ltd., Otemachi, Chiyoda, Tokyo, 100?0004, Japan

    Jun Fukuda

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  1. Yuki Yagi
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  2. Akira Okazaki
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  3. Megumi Endo
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  4. Kumi Yanagisawa
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  5. Jun Fukuda
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  6. Koichiro Nishimura
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  7. Katsuyoshi Yamazaki
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Correspondence to Yuki Yagi.

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Yagi, Y., Okazaki, A., Endo, M. et al. A Comparison of the Oligosaccharide Structures of Antithrombin Derived from Plasma and Recombinant Using POTELLIGENT® Technology. ANAL. SCI. 35, 1333–1340 (2019). https://doi.org/10.2116/analsci.19P181

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  • DOI: https://doi.org/10.2116/analsci.19P181

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