Comprehensive characterization of higher order structure changes in methionine oxidized monoclonal antibodies via NMR chemometric analysis and biophysical approaches

References

• Lu RM, Hwang YC, Liu IJ, Lee CC, Tsai HZ, Li HJ, Wu HC Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci. 2020;27(1):1–16. doi: 10.1186/s12929-019-0592-z. PMID: 31894001.
   PubMed Web of Science ®Google Scholar
• Waldmann TA Immunotherapy: past, present and future. Nat Med. 2003;9(3):269–277. doi: 10.1038/nm0303-269. PMID: 12612576.
   PubMed Web of Science ®Google Scholar
• Reichert JM, Rosensweig CJ, Faden LB, Dewitz MC Monoclonal antibody successes in the clinic. Nat Biotechnol. 2005;23(9):1073–1078. doi: 10.1038/nbt0905-1073. PMID: 16151394.
   PubMed Web of Science ®Google Scholar
• Wang Z, Wang G, Lu H, Li H, Tang M, Tong A Development of therapeutic antibodies for the treatment of diseases. Mol Biomed. 2022;3(1):35. doi: 10.1186/s43556-022-00100-4. PMID: 36418786.
   PubMedGoogle Scholar
• Cohen RD, Pielak GJ. A cell is more than the sum of its (dilute) parts: a brief history of quinary structure. Protein Sci. 2017;26:403–413. doi:10.1002/pro.3092. PMID: WOS:000394992700003.
   PubMed Web of Science ®Google Scholar
• Berkowitz SA, Engen JR, Mazzeo JR, Jones GB. Analytical tools for characterizing biopharmaceuticals and the implications for biosimilars. Nat Rev Drug Discov. 2012;11(7):527–540. doi: 10.1038/nrd3746. PMID: WOS:000305969300022.
   PubMed Web of Science ®Google Scholar
• Woodcock J, Griffin J, Behrman R, Cherney B, Crescenzi T, Fraser B, Hixon D, Joneckis C, Kozlowski S, Rosenberg A, et al. Opinion - the FDA’s assessment of follow-on protein products: a historical perspective. Nat Rev Drug Discov. 2007;6(6):437–442. doi:10.1038/nrd2307. PMID: WOS:000246992000012.
   PubMed Web of Science ®Google Scholar
• Eon-Duval A, Broly H, Gleixner R. Quality attributes of recombinant therapeutic proteins: an assessment of impact on safety and efficacy as part of a quality by design development approach. Biotechnol Progr. 2012;28(3):608–622. doi: 10.1002/btpr.1548. PMID: WOS:000304989800002.
   PubMed Web of Science ®Google Scholar
• Bailly M, Mieczkowski C, Juan V, Metwally E, Tomazela D, Baker J, Uchida M, Kofman E, Raoufi F, Motlagh S, et al. Predicting antibody developability profiles through early stage discovery screening. MAbs. 2020;12(1):12. doi:10.1080/19420862.2020.1743053. PMID: WOS:000523273600001.
   Web of Science ®Google Scholar
• Beck A, Liu H. Macro- and micro-heterogeneity of natural and recombinant IgG antibodies. Antibodies (Basel). 2019;8(1):18. doi: 10.3390/antib8010018. PMID: 31544824.
   PubMedGoogle Scholar
• Houde D, Peng Y, Berkowitz SA, Engen JR. Post-translational modifications differentially affect IgG1 conformation and receptor binding. Molecular & Cellular Proteomics: MCP. 2010;9:1716–1728. doi:10.1074/mcp.M900540-MCP200. PMID: 20103567.
   PubMed Web of Science ®Google Scholar
• Walsh G. Post-translational modifications of protein biopharmaceuticals. Drug Discov Today. 2010;15(17–18):773–780. doi: 10.1016/j.drudis.2010.06.009. PMID: 20599624.
   PubMed Web of Science ®Google Scholar
• Gao X, JYA J, Veeravalli K, Wang YJ, Zhang T, Mcgreevy W, Zheng K, Kelley RF, Laird MW, Liu J, et al. Effect of Individual Fc methionine oxidation on FcRn binding: Met252 oxidation impairs FcRn binding more profoundly than Met428 oxidation. J Pharm Sci-Us. 2015;104(2):368–377. doi:10.1002/jps.24136. PMID: WOS:000349089500009.
   PubMed Web of Science ®Google Scholar
• Hermeling S, Crommelin DJ, Schellekens H, Jiskoot W. Structure-immunogenicity relationships of therapeutic proteins. Pharm Res. 2004;21(6):897–903. doi: 10.1023/b:pham.0000029275.41323.a6. PMID: 15212151.
   PubMed Web of Science ®Google Scholar
• Luo Q, Joubert MK, Stevenson R, Ketchem RR, Narhi LO, Wypych J. Chemical modifications in therapeutic protein aggregates generated under different stress conditions. J Biol Chem. 2011;286:25134–25144. doi:10.1074/jbc.M110.160440. PMID: 21518762.
   PubMed Web of Science ®Google Scholar
• Joubert MK, Luo Q, Nashed-Samuel Y, Wypych J, Narhi LO. Classification and characterization of therapeutic antibody aggregates. J Biol Chem. 2011;286:25118–25133. doi:10.1074/jbc.M110.160457. PMID: 21454532.
   PubMed Web of Science ®Google Scholar
• Wang W, Vlasak J, Li Y, Pristatsky P, Fang Y, Pittman T, Roman J, Wang Y, Prueksaritanont T, Ionescu R. Impact of methionine oxidation in human IgG1 Fc on serum half-life of monoclonal antibodies. Mol Immunol. 2011;48:860–866. doi:10.1016/j.molimm.2010.12.009. PMID: 21256596.
   PubMed Web of Science ®Google Scholar
• Solomon TL, Delaglio F, Giddens JP, Marino JP, Yu YB, Taraban MB, Brinson RG. Correlated analytical and functional evaluation of higher order structure perturbations from oxidation of NISTmAb. MAbs. 2023;15(1):2160227. doi: 10.1080/19420862.2022.2160227. PMID: 36683157.
   PubMed Web of Science ®Google Scholar
• Bandi S, Singh SM, Shah DD, Upadhyay V, Mallela KMG. 2D NMR analysis of the effect of asparagine deamidation versus methionine oxidation on the structure, stability, aggregation, and function of a therapeutic protein. Mol Pharmaceut. 2019;16(11):4621–4635. doi: 10.1021/acs.molpharmaceut.9b00719. PMID: WOS:000494894300018.
   PubMed Web of Science ®Google Scholar
• Shah DD, Singh SM, Mallela KMG. Effect of chemical oxidation on the higher order structure, stability, aggregation, and biological function of interferon alpha-2a: role of local structural changes detected by 2D NMR. Pharm Res. 2018;35(12):232. doi: 10.1007/s11095-018-2518-y. PMID: 30324266.
   PubMed Web of Science ®Google Scholar
• Torosantucci R, Schoneich C, Jiskoot W. Oxidation of therapeutic proteins and peptides: structural and biological consequences. Pharm Res. 2014;31(3):541–553. doi: 10.1007/s11095-013-1199-9. PMID: 24065593.
   PubMed Web of Science ®Google Scholar
• Cerofolini L, Ravera E, Fischer C, Trovato A, Sacco F, Palinsky W, Angiuoni G, Fragai M, Baroni F. Integration of NMR spectroscopy in an analytical workflow to evaluate the effects of oxidative stress on Abituzumab: beyond the fingerprint of mAbs. Anal Chem. 2023;95(24):9199–9206. doi: 10.1021/acs.analchem.3c00317. PMID: 37278511.
   PubMed Web of Science ®Google Scholar
• Mo J, Yan Q, So CK, Soden T, Lewis MJ, Hu P. Understanding the impact of methionine oxidation on the biological functions of IgG1 antibodies using hydrogen/Deuterium exchange mass spectrometry. Anal Chem. 2016;88(19):9495–9502. doi: 10.1021/acs.analchem.6b01958. PMID: 27575380.
   PubMed Web of Science ®Google Scholar
• WFt W, Gabrielson JP, Al-Azzam W, Chen G, Davis DL, Das TK, Hayes DB, Houde D, Singh SK. Technical decision making with higher order structure data: perspectives on higher order structure characterization from the biopharmaceutical industry. J Pharm Sci. 2016;105(12):3465–3470. doi: 10.1016/j.xphs.2016.09.003. PMID: 27743675.
   PubMed Web of Science ®Google Scholar
• 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(1):95–102. doi: 10.1016/j.drudis.2013.07.019. PMID: 23928097.
   PubMed Web of Science ®Google Scholar
• Masson GR, Burke JE, Ahn NG, Anand GS, Borchers C, Brier S, Bou-Assaf GM, Engen JR, Englander SW, Faber J, et al. Recommendations for performing, interpreting and reporting hydrogen deuterium exchange mass spectrometry (HDX-MS) experiments. Nat Methods. 2019;16(7):595–602. doi:10.1038/s41592-019-0459-y. PMID: 31249422.
   PubMed Web of Science ®Google Scholar
• Johnson DT, Di Stefano LH, Jones LM. Fast photochemical oxidation of proteins (FPOP): a powerful mass spectrometry–based structural proteomics tool. J Biol Chem. 2019;294(32):11969–11979. doi: 10.1074/jbc.REV119.006218. PMID: 31262727.
   PubMed Web of Science ®Google Scholar
• Lin Y, Moyle AB, Beaumont VA, Liu LL, Polleck S, Liu H, Shi H, Rouse JC, Kim HY, Zhang Y, et al. Characterization of higher order structural changes of a thermally stressed monoclonal antibody via mass spectrometry footprinting and other biophysical approaches. Anal Chem. 2023;95(46):16840–16849. doi:10.1021/acs.analchem.3c02422. PMID: 37933954.
   PubMedGoogle Scholar
• Rosato A, Tejero R, Montelione GT. Quality assessment of protein NMR structures. Curr Opin Struct Biol. 2013;23:715–724. doi:10.1016/j.sbi.2013.08.005. PMID: 24060334.
   PubMed Web of Science ®Google Scholar
• Huang C, Kalodimos CG. Structures of large protein complexes determined by nuclear magnetic resonance spectroscopy. Annu Rev Biophys. 2017;46(1):317–336. doi: 10.1146/annurev-biophys-070816-033701. PMID: 28375736.
   PubMedGoogle Scholar
• Wecksler AT, Lundin V, Williams AJ, Veeravalli K, Reilly DE, Grieco SH. Bioprocess development and characterization of a C-Labeled hybrid bispecific antibody produced in. Antibodies. 2023;12(1):16. doi: 10.3390/antib12010016. PMID: WOS:000953958300001.
   Web of Science ®Google Scholar
• Tokunaga Y, Takeuchi K, Okude J, Ori K, Torizawa T, Shimada I. Structural fingerprints of an intact monoclonal antibody acquired under formulated storage conditions via 15 N direct detection nuclear magnetic resonance. J Med Chem. 2020;63(10):5360–5366. doi: 10.1021/acs.jmedchem.0c00231. PMID: WOS:000585210700021.
   PubMed Web of Science ®Google Scholar
• Hodgson DJ, Ghasriani H, Aubin Y. Assessment of the higher order structure of Humira(R), Remicade(R), Avastin(R), Rituxan(R), Herceptin(R), and Enbrel(R) by 2D-NMR fingerprinting. J Pharm Biomed Anal. 2019;163:144–152. doi:10.1016/j.jpba.2018.09.056. PMID: 30296716.
   PubMed Web of Science ®Google Scholar
• Brinson RG, Marino JP, Delaglio F, Arbogast LW, Evans RM, Kearsley A, Gingras G, Ghasriani H, Aubin Y, Pierens GK, et al. Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics. MAbs. 2019;11(1):94–105. doi:10.1080/19420862.2018.1544454. PMID: 30570405.
   PubMed Web of Science ®Google Scholar
• Chen K, Long DS, Lute SC, Levy MJ, Brorson KA, Keire DA. Simple NMR methods for evaluating higher order structures of monoclonal antibody therapeutics with quinary structure. J Pharm Biomed Anal. 2016;128:398–407. doi:10.1016/j.jpba.2016.06.007. PMID: 27344629.
   PubMed Web of Science ®Google Scholar
• Wang DY, Park J, Patil SM, Smith CJ, Leazer JL, Keire DA, Chen K. An NMR-Based similarity metric for higher order structure quality assessment among US marketed insulin therapeutics. J Pharm Sci-Us. 2020;109(4):1519–1528. doi: 10.1016/j.xphs.2020.01.002. PMID: WOS:000522855200012.
   PubMed Web of Science ®Google Scholar
• Poppe L, Jordan JB, Lawson K, Jerums M, Apostol I, Schnier PD. Profiling Formulated Monoclonal Antibodies by 1 H NMR Spectroscopy. Anal Chem. 2013;85(20):9623–9629. doi: 10.1021/ac401867f. PMID: 24006877.
   PubMed Web of Science ®Google Scholar
• Arbogast LW, Brinson RG, Formolo T, Hoopes JT, Marino JP. 2D H-1(N), N-15 correlated NMR methods at natural abundance for obtaining structural maps and statistical comparability of monoclonal antibodies. Pharm Res-Dordr. 2016;33(2):462–475. doi: 10.1007/s11095-015-1802-3. PMID: WOS:000368073300017.
   PubMed Web of Science ®Google Scholar
• Arbogast LW, Delaglio F, Schiel JE, Marino JP. Multivariate analysis of two-Dimensional 1 H, 13 C methyl NMR spectra of monoclonal antibody therapeutics to facilitate assessment of higher order structure. Anal Chem. 2017;89(21):11839–11845. doi: 10.1021/acs.analchem.7b03571. PMID: 28937210.
   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(7):3556–3561. doi: 10.1021/ac504804m. PMID: 25728213.
   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;110:3385–3394. doi:10.1016/j.xphs.2021.06.027. PMID: 34166704.
   PubMed Web of Science ®Google Scholar
• Amezcua CA, Szabo CM. Assessment of higher order structure comparability in therapeutic proteins using nuclear magnetic resonance spectroscopy. J Pharm Sci. 2013;102:1724–1733. doi:10.1002/jps.23531. PMID: 23568791.
   PubMed Web of Science ®Google Scholar
• Poppe L, Jordan JB, Rogers G, Schnier PD. On the analytical superiority of 1D NMR for fingerprinting the higher order structure of protein therapeutics compared to multidimensional NMR methods. Anal Chem. 2015;87(11):5539–5545. doi: 10.1021/acs.analchem.5b00950. PMID: 25929316.
   PubMed Web of Science ®Google Scholar
• Elliott KW, Ghasriani H, Wikstrom M, Giddens JP, Aubin Y, Delaglio F, Marino JP, Arbogast LW. Comparative analysis of one-dimensional protein fingerprint by line shape Enhancement and two-dimensional 1 H, 13 C methyl NMR methods for characterization of the higher order structure of IgG1 monoclonal antibodies. Anal Chem. 2020;92(9):6366–6373. doi: 10.1021/acs.analchem.9b05385. PMID: 32267681.
   PubMed Web of Science ®Google Scholar
• Beaumont VA, Liu L, Shi H, Rouse JC, Kim HY. Application of NMR and chemometric analyses to better understand the quality attributes in pH and thermally degraded monoclonal antibodies. Pharm Res. 2023;40(10):2457–2467. doi: 10.1007/s11095-023-03600-2. PMID: 37798537.
   PubMedGoogle Scholar
• Sitasuwan P, Powers TW, Medwid T, Huang YT, Bare B, Lee LA. Enhancing the multi-attribute method through an automated and high-throughput sample preparation. MAbs. 2021;13(1). doi:10.1080/19420862.2021.1978131. PMID: WOS:000701311500001.
   PubMed Web of Science ®Google Scholar
• Puig-Castellvi F, Perez Y, Pina B, Tauler R, Alfonso I. Compression of multidimensional NMR spectra allows a faster and more accurate analysis of complex samples. Chem Commun (Camb). 2018;54(25):3090–3093. doi: 10.1039/c7cc09891j. PMID: 29411785.
   PubMed Web of Science ®Google Scholar
• Chumsae C, Gaza-Bulseco G, Sun J, Liu H. Comparison of methionine oxidation in thermal stability and chemically stressed samples of a fully human monoclonal antibody. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;850:285–294. doi:10.1016/j.jchromb.2006.11.050. PMID: 17182291.
   PubMed Web of Science ®Google Scholar
• Garber E, Demarest SJ. A broad range of Fab stabilities within a host of therapeutic IgGs. Biochem Bioph Res Co. 2007;355:751–757. doi:10.1016/j.bbrc.2007.02.042. PMID: WOS:000245001300025.
   PubMed Web of Science ®Google Scholar
• Hinterholzer A, Stanojlovic V, Regl C, Huber CG, Cabrele C, Schubert M. Identification and quantification of oxidation products in full-length biotherapeutic antibodies by NMR spectroscopy. Anal Chem. 2020;92(14):9666–9673. doi: 10.1021/acs.analchem.0c00965. PMID: 32530275.
   PubMed Web of Science ®Google Scholar
• Tokunaga Y, Takeuchi K. Role of NMR in high ordered structure characterization of monoclonal antibodies. Int J Mol Sci. 2020;22(1):46. doi: 10.3390/ijms22010046. PMID: 33375207.
   PubMed Web of Science ®Google Scholar
• Yagi H, Zhang Y, Yagi-Utsumi M, Yamaguchi T, Iida S, Yamaguchi Y, Backbone KK. (1)H, (13)C, and (15)N resonance assignments of the Fc fragment of human immunoglobulin G glycoprotein. Biomol NMR Assign. 2015;9(2):257–260. doi: 10.1007/s12104-014-9586-7. PMID: 25291979.
   PubMed Web of Science ®Google Scholar
• Burkitt W, Domann P, O’Connor G. Conformational changes in oxidatively stressed monoclonal antibodies studied by hydrogen exchange mass spectrometry. Protein Sci. 2010;19:826–835. doi:10.1002/pro.362. PMID: 20162626.
   PubMed Web of Science ®Google Scholar
• Rosenberg AS. Effects of protein aggregates: an immunologic perspective. AAPS J. 2006;8(3):E501–507. doi: 10.1208/aapsj080359. PMID: 17025268.
   PubMed Web of Science ®Google Scholar
• Lin JC, Glover ZK, Sreedhara A. Assessing the utility of circular dichroism and FTIR spectroscopy in monoclonal-antibody comparability studies. J Pharm Sci. 2015;104:4459–4466. doi:10.1002/jps.24683. PMID: 26505267.
   PubMed Web of Science ®Google Scholar
• Brinson RG, Elliott KW, Arbogast LW, Sheen DA, Giddens JP, Marino JP, Delaglio F. Principal component analysis for automated classification of 2D spectra and interferograms of protein therapeutics: influence of noise, reconstruction details, and data preparation. J Biomol NMR. 2020;74(10–11):643–656. doi: 10.1007/s10858-020-00332-y. PMID: WOS:000551391700001.
   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(1):288–295. doi: 10.1021/acsptsci.0c00188. PMID: 33659867.
   PubMedGoogle Scholar
• Casagrande F, Degardin K, Ross A. Protein NMR of biologicals: analytical support for development and marketed products. J Biomol NMR. 2020;74(10–11):657–671. doi: 10.1007/s10858-020-00318-w. PMID: 32350692.
   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(2):1320–1327. doi: 10.1021/acs.analchem.5b03777. PMID: 26653763.
   PubMed Web of Science ®Google Scholar
• Stracke J, Emrich T, Rueger P, Schlothauer T, Kling L, Knaupp A, Hertenberger H, Wolfert A, Spick C, Lau W, et al. A novel approach to investigate the effect of methionine oxidation on pharmacokinetic properties of therapeutic antibodies. MAbs. 2014;6(5):1229–1242. doi:10.4161/mabs.29601. PMID: 25517308.
   PubMed Web of Science ®Google Scholar
• Bertolotti-Ciarlet A, Wang W, Lownes R, Pristatsky P, Fang Y, McKelvey T, Li Y, Li Y, Drummond J, Prueksaritanont T, et al. Impact of methionine oxidation on the binding of human IgG1 to FcRn and Fcγ receptors. Mol Immunol. 2009;46(8–9):1878–1882. doi:10.1016/j.molimm.2009.02.002. PMID: 19269032.
   PubMed Web of Science ®Google Scholar
• Majumder S, Saati A, Philip S, Liu LL, Stephens E, Rouse JC, Ignatius AA. Utility of high resolution NMR methods to probe the impact of chemical modifications on higher order structure of monoclonal antibodies in relation to antigen binding. Pharm Res-Dordr. 2019;36(9). doi:10.1007/s11095-019-2652-1. PMID: WOS:000479149500001.
   PubMed Web of Science ®Google Scholar
• Liu H, Ponniah G, Zhang HM, Nowak C, Neill A, Gonzalez-Lopez N, Patel R, Cheng G, Kita AZ, Andrien B. In vitro and in vivo modifications of recombinant and human IgG antibodies. MAbs. 2014;6(5):1145–1154. doi: 10.4161/mabs.29883. PMID: 25517300.
   PubMed Web of Science ®Google Scholar