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Hydrogen/deuterium exchange-mass spectrometry analysis of high concentration biotherapeutics: application to phase-separated antibody formulations

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 779-788 | Received 16 Nov 2018, Accepted 23 Feb 2019, Published online: 19 Mar 2019

References

  • Walsh G. Biopharmaceutical benchmarks 2014. Nat Biotechnol. 2014;32:992–1000. doi:10.1038/nbt.3040.
  • Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. MAbs. 2015;7:9–14. doi:10.4161/19420862.2015.989042.
  • Shire SJ, Shahrokh Z, Liu J. Challenges in the development of high protein concentration formulations. J Pharm Sci. 2004;93:1390–402. doi:10.1002/JPS.20079.
  • Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004;93:2645–68. doi:10.1002/JPS.20178.
  • Turner MR, Balu-Iyer SV. Challenges and opportunities for the subcutaneous delivery of therapeutic proteins. J Pharm Sci. 2018;107:1247–60. doi:10.1016/j.xphs.2018.01.007.
  • Yadav S, Laue TM, Kalonia DS, Singh SN, Shire SJ. The influence of charge distribution on self-association and viscosity behavior of monoclonal antibody solutions. Mol Pharm. 2012;9:791–802. doi:10.1021/mp200566k.
  • Yadav S, Liu J, Shire SJ, Kalonia DS. Specific interactions in high concentration antibody solutions resulting in high viscosity. J Pharm Sci. 2010;99:1152–68. doi:10.1002/JPS.21898.
  • Chi EY, Krishnan S, Randolph TW, Carpenter JF. Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation. Pharm Res. 2003;20:1325–36. doi:10.1023/A:1025771421906.
  • Ahamed T, Esteban BNA, Ottens M, Gwk VD, Lam VDW, Bisschops MAT, Lee A, Pham C, Thömmes J. Phase behavior of an intact monoclonal antibody. Biophys J. 2007;93:610–19. doi:10.1529/BIOPHYSJ.106.098293.
  • Mason BD, Zhang-van Enk J, Zhang L, Remmele RL, Zhang J. Liquid-liquid phase separation of a monoclonal antibody and nonmonotonic influence of hofmeister anions. Biophys J. 2010;99:3792–800. doi:10.1016/J.BPJ.2010.10.040.
  • Nishi H, Miyajima M, Nakagami H, Noda M, Uchiyama S, Fukui K. Phase separation of an IgG1 antibody solution under a low ionic strength condition. Pharm Res. 2010;27:1348–60. doi:10.1007/s11095-010-0125-7.
  • Lewus RA, Darcy PA, Lenhoff AM, Sandler SI. Interactions and phase behavior of a monoclonal antibody. Biotechnol Prog. 2011;27:280–89. doi:10.1002/btpr.536.
  • Chow C-K, Allan BW, Chai Q, Atwell S, Lu J. Therapeutic antibody engineering to improve viscosity and phase separation guided by crystal structure. Mol Pharm. 2016;13:915–23. doi:10.1021/acs.molpharmaceut.5b00817.
  • Reiche K, Hartl J, Blume A, Garidel P. Liquid-liquid phase separation of a monoclonal antibody at low ionic strength: influence of anion charge and concentration. Biophys Chem. 2017;220:7–19. doi:10.1016/J.BPC.2016.08.003.
  • Konermann L, Pan J, Liu Y-H. Hydrogen exchange mass spectrometry for studying protein structure and dynamics. Chem Soc Rev. 2011;40:1224–34. doi:10.1039/C0CS00113A.
  • Huang RY-C, Chen G. Higher order structure characterization of protein therapeutics by hydrogen/deuterium exchange mass spectrometry. Anal Bioanal Chem. 2014;406:6541–58. doi:10.1007/s00216-014-7924-3.
  • Masson GR, Jenkins ML, Burke JE. An overview of hydrogen deuterium exchange mass spectrometry (HDX-MS) in drug discovery. Expert Opin Drug Discov. 2017;12:981–94. doi:10.1080/17460441.2017.1363734.
  • Wei H, Mo J, Tao L, Russell RJ, Tymiak AA, Chen G, Iacob RE, Engen JR. Hydrogen/deuterium exchange mass spectrometry for probing higher order structure of protein therapeutics: methodology and applications. Drug Discov Today. 2014;19:95–102. doi:10.1016/j.drudis.2013.07.019.
  • Houde D, Engen JR. Conformational analysis of recombinant monoclonal antibodies with hydrogen/deuterium exchange mass spectrometry. Methods Mol Biol. 2013;269–89. [Internet]. doi:10.1007/978-1-62703-327-5_17.
  • Arora J, Hickey JM, Majumdar R, Esfandiary R, Bishop SM, Samra HS, Middaugh CR, Weis DD, Volkin DB. Hydrogen exchange mass spectrometry reveals protein interfaces and distant dynamic coupling effects during the reversible self-association of an IgG1 monoclonal antibody. MAbs. 2015;7:525–39. doi:10.1080/19420862.2015.1029217.
  • Houde D, Nazari ZE, Bou-Assaf GM, Weiskopf AS, Rand KD. Conformational analysis of proteins in highly concentrated solutions by dialysis-coupled hydrogen/deuterium exchange mass spectrometry. J Am Soc Mass Spectrom. 2016;27:669–76. doi:10.1007/s13361-015-1331-7.
  • Wang A, Robertson AD, Bolen DW. Effects of a naturally occurring compatible osmolyte on the internal dynamics of ribonuclease A. Biochemistry. 1995;34:15096–104. doi:10.1021/bi00046a016.
  • Lim WK, Rösgen J, Englander SW. Urea, but not guanidinium, destabilizes proteins by forming hydrogen bonds to the peptide group. Proc Natl Acad Sci. 2009;106:2595–600. doi:10.1073/pnas.0812588106.
  • Manikwar P, Majumdar R, Hickey JM, S V T, Samra HS, Sathish HA, Bishop SM, Middaugh CR, Weis DD, Volkin DB. Correlating excipient effects on conformational and storage stability of an IgG1 monoclonal antibody with local dynamics as measured by hydrogen/deuterium-exchange mass spectrometry. J Pharm Sci. 2013;102:2136–51. doi:10.1002/jps.23543.
  • Rey M, Sarpe V, Burns KM, Buse J, Baker CAH, van Dijk M, Wordeman L, Bonvin AMJJ, Schriemer DC. Mass spec studio for integrative structural biology. Structure. 2014;22:1538–48. doi:10.1016/J.STR.2014.08.013.
  • Bramucci E, Paiardini A, Bossa F, Pascarella S. PyMod: sequence similarity searches, multiple sequence-structure alignments, and homology modeling within PyMOL. BMC Bioinformatics. 2012;13:S2. doi:10.1186/1471-2105-13-S4-S2.
  • Janson G, Zhang C, Prado MG, Paiardini A. PyMod2.0: improvements in protein sequence-structure analysis and homology modeling within PyMOL. Bioinformatics. 2016;33:444–46. doi:10.1093/bioinformatics/btw638.