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Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics

Title data

Brinson, Robert G. ; Marino, John P. ; Delaglio, Frank ; Arbogast, Luke W. ; Evans, Ryan M. ; Kearsley, Anthony ; Gingras, Geneviève ; Ghasriani, Houman ; Aubin, Yves ; Pierens, Gregory K. ; Jia, Xinying ; Mobli, Mehdi ; Grant, Hamish G. ; Keizer, David W. ; Schweimer, Kristian ; Ståhle, Jonas ; Widmalm, Göran ; Zartler, Edward R. ; Lawrence, Chad W. ; Reardon, Patrick N. ; Cort, John R. ; Xu, Ping ; Ni, Feng ; Yanaka, Saeko ; Kato, Koichi ; Parnham, Stuart R. ; Tsao, Desiree ; Blomgren, Andreas ; Rundlöf, Torgny ; Trieloff, Nils ; Schmieder, Peter ; Ross, Alfred ; Skidmore, Ken ; Chen, Kang ; Keire, David ; Freedberg, Darón I. ; Suter-Stahel, Thea ; Wider, Gerhard ; Ilc, Gregor ; Plavec, Janez ; Bradley, Scott A. ; Baldisseri, Donna M. ; Sforça, Mauricio Luis ; Zeri, Ana Carolina de Mattos ; Wei, Julie Yu ; Szabo, Christina M. ; Amezcua, Carlos A. ; Jordan, John B. ; Wikström, Mats:
Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics.
In: mAbs. Vol. 11 (2019) Issue 1 . - pp. 94-105.
ISSN 1942-0870
DOI: https://doi.org/10.1080/19420862.2018.1544454

Abstract in another language

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 changes and establishing comparability between biologic products. To address this measurement challenge, two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) methods were introduced that allow for the precise atomic-level comparison of the HOS between two proteins, including mAbs. Here, an inter-laboratory comparison involving 26 industrial, government and academic laboratories worldwide was performed as a benchmark using the NISTmAb, from the National Institute of Standards and Technology (NIST), to facilitate the translation of the 2D-NMR method into routine use for biopharmaceutical product development. Two-dimensional 1H,15N and 1H,13C NMR spectra were acquired with harmonized experimental protocols on the unlabeled Fab domain and a uniformly enriched-15N, 20%-13C-enriched system suitability sample derived from the NISTmAb. Chemometric analyses from over 400 spectral maps acquired on 39 different NMR spectrometers ranging from 500 MHz to 900 MHz demonstrate spectral fingerprints that are fit-for-purpose for the assessment of HOS. The 2D-NMR method is shown to provide the measurement reliability needed to move the technique from an emerging technology to a harmonized, routine measurement that can be generally applied with great confidence to high precision assessments of the HOS of mAb-based biotherapeutics.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biopolymers
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Biopolymers - Univ.-Prof. Dr. Paul Rösch
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biopolymers > Lehrstuhl Biopolymere - Apl. Prof. Dr. Birgitta Wöhrl
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 14 May 2019 07:09
Last Modified: 07 Jun 2019 07:27
URI: https://eref.uni-bayreuth.de/id/eprint/48917