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

被引：69

作者：

Brinson, Robert G. ^{[1
,2
]}

Marino, John P. ^{[1
,2
]}

Delaglio, Frank ^{[1
,2
]}

Arbogast, Luke W. ^{[1
,2
]}

Evans, Ryan M. ^{[3
]}

Kearsley, Anthony ^{[3
]}

Gingras, Genevieve ^{[4
]}

Ghasriani, Houman ^{[4
]}

Aubin, Yves ^{[4
]}

Pierens, Gregory K. ^{[5
]}

Jia, Xinying ^{[5
]}

Mobli, Mehdi ^{[5
]}

Grant, Hamish G. ^{[6
]}

Keizer, David W. ^{[6
]}

Schweimer, Kristian ^{[7
]}

Stahle, Jonas ^{[8
]}

Widmalm, Goran ^{[8
]}

Zartler, Edward R. ^{[9
]}

Lawrence, Chad W. ^{[10
]}

Reardon, Patrick N. ^{[10
,33
]}

Cort, John R. ^{[10
]}

Xu, Ping ^{[11
]}

Ni, Feng ^{[11
]}

Yanaka, Saeko ^{[12
,13
]}

Kato, Koichi ^{[12
,13
]}

Parnham, Stuart R. ^{[14
]}

Tsao, Desiree ^{[15
]}

Blomgren, Andreas ^{[16
]}

Rundlof, Torgny ^{[16
]}

Trieloff, Nils ^{[17
]}

Schmieder, Peter ^{[17
]}

Ross, Alfred ^{[18
]}

Skidmore, Ken ^{[19
]}

Chen, Kang ^{[20
]}

Keire, David ^{[20
]}

Freedberg, Daron I. ^{[21
]}

Suter-Stahel, Thea ^{[22
]}

Wider, Gerhard ^{[22
]}

Ilc, Gregor ^{[23
,24
]}

Plavec, Janez ^{[23
,24
]}

Bradley, Scott A. ^{[25
]}

Baldisseri, Donna M. ^{[26
]}

Sforca, Mauricio Luis ^{[27
]}

de Mattos Zeri, Ana Carolina ^{[28
]}

Wei, Julie Yu ^{[29
]}

Szabo, Christina M. ^{[30
]}

Amezcua, Carlos A. ^{[30
]}

Jordan, John B. ^{[31
]}

Wikstrom, Mats ^{[32
]}

机构：

[1] NIST, Inst Biosci & Biotechnol Res, Rockville, MD 20852 USA

[2] Univ Maryland, Rockville, MD USA

[3] NIST, Appl & Computat Math Div, Gaithersburg, MD 20899 USA

[4] Hlth Canada, Biol & Genet Therapies Directorate, Ctr Biol Evaluat, Ottawa, ON, Canada

[5] Univ Queensland, Ctr Adv Imaging, St Lucia, Qld, Australia

[6] Univ Melbourne, Bio21 Mol Sci & Biotechnol Inst, Melbourne, Vic, Australia

[7] Univ Bayreuth, Lehrstuhl Biopolymere, Bayreuth, Germany

[8] Stockholm Univ, Arrhenius Lab, Dept Organ Chem, Stockholm, Sweden

[9] Pfizer Essential Hlth, Analyt R&D, Lake Forest, IL USA

[10] Pacific Northwest Natl Lab, Earth & Biol Sci Directorate, Richland, DC USA

[11] Natl Res Council Canada, Human Hlth Therapeut Res Ctr, Dept Downstream Proc & Analyt, Montreal, PQ, Canada

[12] Natl Inst Nat Sci, Inst Mol Sci, Okazaki, Aichi, Japan

[13] Natl Inst Nat Sci, Exploratory Res Ctr Life & Living Syst, Okazaki, Aichi, Japan

[14] Univ South Carolina, Dept Biochem & Mol Biol, Charleston, SC USA

[15] Momenta Pharmaceut, Analyt Dev, Cambridge, MA USA

[16] Swedish Med Prod Agcy, Lab Unit, Uppsala, Sweden

[17] Leibniz Forsch Inst Mol Pharmakol FMP, NMR Supported Struct Biol, Berlin, Germany

[18] Roche Innovat Ctr Basel, Preclin CMC, Roche Pharmaceut Res & Early Dev, Basel, Switzerland

[19] Genentech Inc, Analyt Operat, San Francisco, CA USA

[20] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA

[21] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA

[22] Swiss Fed Inst Technol, Inst Mol Biol & Biophys, Dept Biol, Zurich, Switzerland

[23] EN FIST Ctr Excellence, NMR Ctr, Ljubljana, Slovenia

[24] Natl Inst Chem, NMR Ctr, Ljubljana, Slovenia

[25] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA

[26] Bruker BioSpin Corp, MRS Applicat Sci, Billerica, MA USA

[27] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Campinas, SP, Brazil

[28] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Synchrotron Light Lab LNLS, Campinas, SP, Brazil

[29] Biogen Inc, Prot Product Dev, 14 Cambridge Ctr, Cambridge, MA 02142 USA

[30] Baxter Healthcare, Baxter Pharmaceut R&D, Round Lake, IL USA

[31] Amgen Inc, Global Regulatory & R&D Policy, Thousand Oaks, CA 91320 USA

[32] Amgen Inc, Attribute Sci, Higher Order Struct, Thousand Oaks, CA 91320 USA

[33] Oregon State Univ, Corvallis, OR 97331 USA

来源：

MABS | 2019年 / 11卷 / 01期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

monoclonal antibody (mAb) therapeutics; NISTmAb; higher order structure; nuclear magnetic resonance spectroscopy (NMR); comparability; chemometrics; TECHNICAL DECISION-MAKING; PROTEIN NMR; RECONSTRUCTION; SENSITIVITY; FILGRASTIM; ABUNDANCE; SPECTRA; QUALITY;

D O I：

10.1080/19420862.2018.1544454

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 H-1,N-15 and H-1,C-13 NMR spectra were acquired with harmonized experimental protocols on the unlabeled Fab domain and a uniformly enriched-N-15, 20%-C-13-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.

引用

页码：94 / 105

页数：12

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