Investigating protein–excipient interactions of a multivalent V_HH therapeutic protein using NMR spectroscopy

References

• Manning MC, Matsuura JE, Kendrick BS, Meyer JD, Dormish JJ, Vrkljan M, Ruth JR, Carpenter JF, Sheftert E. Approaches for increasing the solution stability of proteins. Biotechnol Bioeng. 1995;48:506–10. PMID:18623515. doi:10.1002/bit.260480513.
   PubMed Web of Science ®Google Scholar
• Bannas P, Hambach J, Koch-Nolte F. Nanobodies and nanobody-based human heavy chain antibodies as antitumor therapeutics. Front Immunol. 2017;8:1603. PMID:29213270. doi:10.3389/fimmu.2017.01603.
   PubMed Web of Science ®Google Scholar
• Kheddo P, Cliff MJ, Uddin S, van der Walle Cf, Golovanov AP, van der Walle CF. Characterizing monoclonal antibody formulations in arginine glutamate solutions using 1 H NMR spectroscopy. mAbs. 2016;8:1245–58. PMID:2016:1481312. doi:10.1080/19420862.2016.1214786.
   PubMed Web of Science ®Google Scholar
• Arakawa T, Tsumoto K. The effects of arginine on refolding of aggregated proteins: not facilitate refolding, but suppress aggregation. Biochem Biophys Res Commun. 2003;304:148–52. PMID:12705899. doi:10.1016/s0006-291x(03)00578-3.
   PubMed Web of Science ®Google Scholar
• Borwankar AUD, J B, Twu A, Hung JJ, Dinin AK, Wilson BK, Yue J, Maynard JA, Truskett TM, Johnston KP. Viscosity reduction of a concentrated monoclonal antibody with arginine HCl and arginine glutamate. Ind Eng Chem Res. 2016;55:10. doi:10.1021/acs.iecr.6b02042.
   Web of Science ®Google Scholar
• Hoffmann C, Blume A, Miller I, Garidel P. Insights into protein-polysorbate interactions analysed by means of isothermal titration and differential scanning calorimetry. Eur Biophys J. 2009;38:557–68. PMID:19189101. doi:10.1007/s00249-009-0404-6.
   PubMed Web of Science ®Google Scholar
• Wang W, Wang YJ, Wang DQ. Dual effects of Tween 80 on protein stability. Int J Pharm. 2008;347:31–38. PMID:17692480. doi:10.1016/j.ijpharm.2007.06.042.
   PubMed Web of Science ®Google Scholar
• Arakawa T, Timasheff SN. Stabilization of protein structure by sugars. Biochemistry. 1982;21:6536–44. PMID:7150574. doi:10.1021/bi00268a033.
   PubMed Web of Science ®Google Scholar
• Hauptmann A, Podgorsek K, Kuzman D, Srcic S, Hoelzl G, Loerting T. Impact of buffer, protein concentration and sucrose addition on the aggregation and particle formation during freezing and thawing. Pharm Res. 2018;35:101. PMID:29556730. doi:10.1007/s11095-018-2378-5.
   PubMed Web of Science ®Google Scholar
• Mensink MA, Frijlink HW, van der Voort Maarschalk K, Hinrichs WL. How sugars protect proteins in the solid state and during drying (review): mechanisms of stabilization in relation to stress conditions. Eur J Pharm Biopharm. 2017;114:288–95. PMID:28189621. doi:10.1016/j.ejpb.2017.01.024.
   PubMed Web of Science ®Google Scholar
• Shimizu M, Nagashima HH,K, Suzuki T, SUZUKI T. Egg yolk antibody (Ig Y) stability in aqueous solution with high sugar concentrations. J Food Sci. 1994;59:10. doi:10.1111/j.1365-2621.1994.tb08122.x.
   Web of Science ®Google Scholar
• Jones LS, Randolph TW, Kohnert U, Papadimitriou A, Winter G, Hagmann ML, Manning MC, Carpenter JF. The effects of tween 20 and sucrose on the stability of anti-L-selectin during lyophilization and reconstitution. J Pharm Sci. 2001;90:1466–77. PMID:11745706. doi:10.1002/jps.1098.
   PubMed Web of Science ®Google Scholar
• Lee JC, Timasheff SN. The stabilization of proteins by sucrose. J Biol Chem. 1981;256:7193–201. PMID:7251592. doi:10.1016/S0021-9258(19)68947-7.
   PubMed Web of Science ®Google Scholar
• Kamerzell TJ, Esfandiary R, Joshi SB, Middaugh CR, Volkin DB. Protein-excipient interactions: mechanisms and biophysical characterization applied to protein formulation development. Adv Drug Deliv Rev. 2011;63:1118–59. PMID:21855584. doi:10.1016/j.addr.2011.07.006.
   PubMed Web of Science ®Google Scholar
• Arbogast LW, Brinson RG, Marino JP. Mapping monoclonal antibody structure by 2D 13C NMR at natural abundance. Anal Chem. 2015;87:3556–61. doi:10.1021/ac504804m. PMID:2015:354379.
   PubMed Web of Science ®Google Scholar
• Majumder S, Bhattacharya DS, Langford A, Ignatius AA. Utility of high resolution 2D NMR fingerprinting in assessing viscosity of therapeutic monoclonal antibodies. Pharm Res. 2022;39:529–39. PMID:35174433. doi:10.1007/s11095-022-03200-6.
   PubMed Web of Science ®Google Scholar
• Quinternet M, Starck J-P, Delsuc M-A, Kieffer B. Heteronuclear NMR provides an accurate assessment of therapeutic insulin’s quality. J Pharm Biomed Anal. 2013;78-79:252–54. PMID:2013:504829. doi:10.1016/j.jpba.2013.02.016.
   PubMed Web of Science ®Google Scholar
• Aubin Y, Hodgson DJ, Thach WB, Gingras G, Sauve S. Monitoring effects of excipients, formulation parameters and mutations on the high order structure of filgrastim by NMR. Pharm Res. 2015;32:3365–75. PMID:26043856. doi:10.1007/s11095-015-1713-3.
   PubMed Web of Science ®Google Scholar
• Bramham JE, Podmore A, Davies SA, Golovanov AP. Comprehensive assessment of protein and excipient stability in biopharmaceutical formulations using (1)H NMR spectroscopy. ACS Pharmacol Transl Sci. 2021;4:288–95. PMID:33659867. doi:10.1021/acsptsci.0c00188.
   PubMedGoogle Scholar
• Falk BT, Liang Y, McCoy MA. Diffusion profiling of therapeutic proteins by using solution NMR spectroscopy. ChemBioChem. 2019;20:896–99. PMID:30515922. doi:10.1002/cbic.201800631.
   PubMed Web of Science ®Google Scholar
• Singh SM, Bandi S, Jones DNM, Mallela KMG. Effect of polysorbate 20 and polysorbate 80 on the higher-order structure of a monoclonal antibody and Its Fab and Fc fragments probed using 2D nuclear magnetic resonance spectroscopy. J Pharm Sci. 2017;106:3486–98. PMID:28843351. doi:10.1016/j.xphs.2017.08.011.
   PubMed Web of Science ®Google Scholar
• Falk BT, Liang Y, Bailly M, Raoufi F, Kekec A, Pissarnitski D, Feng D, Yan L, Lin S, Fayadat-Dilman L, et al. NMR assessment of therapeutic peptides and proteins: correlations that reveal interactions and motions. ChemBioChem. 2020;21:315–19. PMID:31283075. doi:10.1002/cbic.201900296.
   PubMed Web of Science ®Google Scholar
• Poppe L, Jordan JB, Lawson K, Jerums M, Apostol I, Schnier PD. Profiling formulated monoclonal antibodies by 1H NMR spectroscopy. Anal Chem. 2013;85:9623–29. doi:10.1021/ac401867f. PMID:2013:1401415.
   PubMed Web of Science ®Google Scholar
• Poppe L, Knutson N, Cao S, Wikstrom M. In situ quantification of polysorbate in pharmaceutical samples of therapeutic proteins by hydrodynamic profiling by NMR spectroscopy. Anal Chem. 2019;91:7807–11. PMID:31117409. doi:10.1021/acs.analchem.9b01442.
   PubMed Web of Science ®Google Scholar
• Franks J, Glushka JN, Jones MT, Live DH, Zou Q, Prestegard JH. Spin diffusion editing for structural fingerprints of therapeutic antibodies. Anal Chem. 2016;88:1320–27. PMID:26653763. doi:10.1021/acs.analchem.5b03777.
   PubMed Web of Science ®Google Scholar
• Elliott KW, Delaglio F, Wikstrom M, Marino JP, Arbogast LW. Principal component analysis of 1D 1H diffusion edited NMR spectra of protein therapeutics. J Pharm Sci. 2021;110:3385–94. PMID:34166704. doi:10.1016/j.xphs.2021.06.027.
   PubMed Web of Science ®Google Scholar
• The PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC.
   Google Scholar
• Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, et al. Swiss-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 2018;46:W296–W303. PMID:29788355. doi:10.1093/nar/gky427.
   PubMed Web of Science ®Google Scholar
• Fleming PJ, Fleming KG. HullRad: fast calculations of folded and disordered protein and nucleic acid hydrodynamic properties. Biophys J. 2018;114:856–69. PMID:29490246. doi:10.1016/j.bpj.2018.01.002.
   PubMed Web of Science ®Google Scholar
• Arakawa T, Timasheff SN. Preferential interactions of proteins with salts in concentrated solutions. Biochemistry. 1982;21:6545–52. PMID:7150575. doi:10.1021/bi00268a034.
   PubMed Web of Science ®Google Scholar
• Sudrik CM, Cloutier T, Mody N, Sathish HA, Trout BL. Understanding the role of preferential exclusion of sugars and polyols from native state IgG1 monoclonal antibodies and its effect on aggregation and reversible self-association. Pharm Res. 2019;36:109. PMID:31127417. doi:10.1007/s11095-019-2642-3.
   PubMed Web of Science ®Google Scholar
• Taraban MB, DePaz RA, Lobo B, Yu YB. Water proton NMR: a tool for protein aggregation characterization. Anal Chem. 2017;89:5494–502. PMID:28440620. doi:10.1021/acs.analchem.7b00464.
   PubMed Web of Science ®Google Scholar
• Spiess C, Zhai Q, Carter PJ. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol Immunol. 2015;67:95–106. PMID:25637431. doi:10.1016/j.molimm.2015.01.003.
   PubMed Web of Science ®Google Scholar
• Von Kreudenstein TS, Escobar-Carbrera E, Lario PI, D’Angelo I, Brault K, Kelly J, Durocher Y, Baardsnes J, Woods RJ, Xie MH, et al. Improving biophysical properties of a bispecific antibody scaffold to aid developability: quality by molecular design. mAbs. 2013;5:646–54. PMID:23924797. doi:10.4161/mabs.25632.
   PubMed Web of Science ®Google Scholar
• Chanier T, Chames P. Nanobody engineering: toward next generation immunotherapies and immunoimaging of cancer. Antibodies (Basel). 2019;8 PMID:31544819. doi:10.3390/antib8010013.
   PubMedGoogle Scholar
• Kneller JM, Lu M, Bracken C. An effective method for the discrimination of motional anisotropy and chemical exchange. J Am Chem Soc. 2002;124:1852–53. PMID:2002:101697. doi:10.1021/ja017461k.
   PubMed Web of Science ®Google Scholar