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Szabo M, Filep C, Nagy M, et al. N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product. J Pharm Biomed Anal. 2021;209:114483doi: 10.1016/j.jpba.2021.114483.
Szabo, M., Filep, C., Nagy, M., Sarkozy, D., Szigeti, M., Sperling, E., Csanky, E., & Guttman, A. (2021). N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product. Journal of pharmaceutical and biomedical analysis, 209114483. https://doi.org/10.1016/j.jpba.2021.114483
Szabo, Miklos, et al. "N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product." Journal of pharmaceutical and biomedical analysis vol. 209 (2021): 114483. doi: https://doi.org/10.1016/j.jpba.2021.114483
Szabo M, Filep C, Nagy M, Sarkozy D, Szigeti M, Sperling E, Csanky E, Guttman A. N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product. J Pharm Biomed Anal. 2021 Nov 25;209:114483. doi: 10.1016/j.jpba.2021.114483. Epub 2021 Nov 25. PMID: 34864596.
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J Pharm Biomed Anal. 2021 Nov 25;209:114483. doi: 10.1016/j.jpba.2021.114483. Epub 2021 Nov 25.

N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.

Journal of pharmaceutical and biomedical analysis

Miklos Szabo, Csenge Filep, Mate Nagy, Daniel Sarkozy, Marton Szigeti, Edit Sperling, Eszter Csanky, Andras Guttman

Affiliations

  1. Semmelweis Hospital, Miskolc, Hungary.
  2. Horváth Csaba Memorial Laboratory of Bioseparation Sciences, Research Center for Molecular Medicine, Faculty of Medicine, Doctoral School of Molecular Medicine, University of Debrecen, Hungary.
  3. Translational Glycomics Group, Research Institute for Biomolecular and Chemical Engineering, University of Pannonia, Hungary.
  4. Horváth Csaba Memorial Laboratory of Bioseparation Sciences, Research Center for Molecular Medicine, Faculty of Medicine, Doctoral School of Molecular Medicine, University of Debrecen, Hungary; Translational Glycomics Group, Research Institute for Biomolecular and Chemical Engineering, University of Pannonia, Hungary. Electronic address: [email protected].

PMID: 34864596 DOI: 10.1016/j.jpba.2021.114483

Abstract

Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use. The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients. Therefore, the glycosylation of biologics is an important critical quality attribute (CQA). The profile of asparagine linked carbohydrates is greatly dependent on the manufacturing process. Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product. For this reason, comprehensive N-glycosylation analysis is of high importance during production and release. Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control. To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level. This latter technique was also used for oligosaccharide sequencing for glycan structure validation. The results suggested no ADCC function - structure relationship due to the mostly core fucosylated biantennary glycans found. However, the presence of the high mannose structures probably affects the clearance rate of the drug.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Keywords: Capillary electrophoresis; Function; N-glycans; Structure; mAb

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this pa

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