2018
DOI: 10.1080/19420862.2018.1544454
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Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics

Abstract: The increased interest in using monoclonal antibodies (mAbs) as a platform for biopharmaceuticals has led to the need for new analytical techniques that can precisely assess physicochemical properties of these large and very complex drugs for the purpose of correctly identifying quality attributes (QA). One QA, higher order structure (HOS), is unique to biopharmaceuticals and essential for establishing consistency in biopharmaceutical manufacturing, detecting process-related variations from manufacturing chang… Show more

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Cited by 76 publications
(88 citation statements)
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“…18 Subsequent work on monoclonal antibody HOS comparison reported even lower thresholds for the same protein across many laboratories. 31 However, most published studies on NMR spectral comparison for peptide or protein HOS of different brands of drugs lack quantification or a numerical similarity score and proposed threshold. Such a numerical score if reproducible and robust could be useful for evaluating the equivalence of generic or biosimilar drugs to the RLD.…”
Section: Conclusion and Discussionmentioning
confidence: 99%
“…18 Subsequent work on monoclonal antibody HOS comparison reported even lower thresholds for the same protein across many laboratories. 31 However, most published studies on NMR spectral comparison for peptide or protein HOS of different brands of drugs lack quantification or a numerical similarity score and proposed threshold. Such a numerical score if reproducible and robust could be useful for evaluating the equivalence of generic or biosimilar drugs to the RLD.…”
Section: Conclusion and Discussionmentioning
confidence: 99%
“…Eine wichtige sich entwickelnde Anwendung von NMR in der pharmazeutischen Industrie ist die Qualitätskontrolle durch Messung von Methylspektren bei natürlicher Isotopenhäufigkeit von biologischen Therapeutika, wie monoklonalen Antikçrpern (150 kDa). [15][16][17]38] Die Mçglichkeit mit vollständig protonierten Systemen mit hohem Molekulargewicht zu Arbeiten und zur selben Zeit eine exzellente Artefaktunterdrückung zu bewerkstelligen macht das gs-XL-ALSOFAST-HMQC ideal für diese Anwendung. Wir haben die Leistung von verschiedenen Experimenten an einer Lçsung eines monoklonalen Antikçrpers (40 mg mL À1 ) bei 323 K getestet (Abbildung 5 D) und haben die Signal-Rausch-Verhältnisse für ausgewählte Signale dieser Fingerabdruck-Spektren ausgewertet.…”
Section: Analyse Der Struktur Hçherer Ordnung Bei Therapeutischen Antunclassified
“…mit einem einzigen Spektrum überprüft werden kann. [15][16][17][18] Auch hier kann die Messung auf einem Hochfeld-Spektrometer gut einen Tag in Anspruch nehmen.…”
Section: Introductionunclassified
“…Producing crystalline mAbs is challenging, owing to the complexity of mAb HOS and the degree of mAb conformational heterogeneity. However, several complementing technologies have evolved in recent years to ascertain structure and interactions, including circular dichroism (CD), infrared (IR) and raman spectroscopy, cryogenic-electron microscopy, and nuclear magnetic resonance (NMR) spectroscopy [148,150,151,152,153,154,155,156,157]. Of the technologies available for HOS elucidation, 2D-NMR and X-Ray crystallography (followed by MS) provide the highest sensitivity and local specificity.…”
Section: Computational Approaches For Aggregation Prediction and Rmentioning
confidence: 99%