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Native mass spectrometry combined with enzymatic dissection unravels glycoform heterogeneity of biopharmaceuticals

Author

Listed:
  • Therese Wohlschlager

    (University of Salzburg
    University of Salzburg)

  • Kai Scheffler

    (University of Salzburg
    Thermo Fisher Scientific GmbH)

  • Ines C. Forstenlehner

    (University of Salzburg
    University of Salzburg
    Novartis, Sandoz GmbH)

  • Wolfgang Skala

    (University of Salzburg
    University of Salzburg)

  • Stefan Senn

    (University of Salzburg
    University of Salzburg)

  • Eugen Damoc

    (Thermo Fisher Scientific GmbH)

  • Johann Holzmann

    (University of Salzburg
    Novartis, Sandoz GmbH)

  • Christian G. Huber

    (University of Salzburg
    University of Salzburg)

Abstract

Robust manufacturing processes resulting in consistent glycosylation are critical for the efficacy and safety of biopharmaceuticals. Information on glycosylation can be obtained by conventional bottom–up methods but is often limited to the glycan or glycopeptide level. Here, we apply high-resolution native mass spectrometry (MS) for the characterization of the therapeutic fusion protein Etanercept to unravel glycoform heterogeneity in conditions of hitherto unmatched mass spectral complexity. Higher spatial resolution at lower charge states, an inherent characteristic of native MS, represents a key component for the successful revelation of glycan heterogeneity. Combined with enzymatic dissection using a set of proteases and glycosidases, assignment of specific glycoforms is achieved by transferring information from subunit to whole protein level. The application of native mass spectrometric analysis of intact Etanercept as a fingerprinting tool for the assessment of batch-to-batch variability is exemplified and may be extended to demonstrate comparability after changes in the biologic manufacturing process.

Suggested Citation

  • Therese Wohlschlager & Kai Scheffler & Ines C. Forstenlehner & Wolfgang Skala & Stefan Senn & Eugen Damoc & Johann Holzmann & Christian G. Huber, 2018. "Native mass spectrometry combined with enzymatic dissection unravels glycoform heterogeneity of biopharmaceuticals," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04061-7
    DOI: 10.1038/s41467-018-04061-7
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    Cited by:

    1. Luis F. Schachner & Christopher Mullen & Wilson Phung & Joshua D. Hinkle & Michelle Irwin Beardsley & Tracy Bentley & Peter Day & Christina Tsai & Siddharth Sukumaran & Tomasz Baginski & Danielle DiCa, 2024. "Exposing the molecular heterogeneity of glycosylated biotherapeutics," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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