Drug-like antibodies with high affinity, diversity and developability directly from next-generation antibody libraries

References

• Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1–3):3–16. doi:10.1016/S0169-409X(00)00129-0.
   PubMed Web of Science ®Google Scholar
• Wang W, Wang E, Balthasar J. Monoclonal Antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84(5):548–58. doi:10.1038/clpt.2008.170.
   PubMed Web of Science ®Google Scholar
• Jain T, Sun T, Durand S, Hall A, Houston NR, Nett JH, Sharkey B, Bobrowicz B, Caffry I, Yu Y, et al. Biophysical properties of the clinical-stage antibody landscape. Proc Natl Acad Sci. 2017;114(5):944–49. doi:10.1073/pnas.1616408114.
   PubMed Web of Science ®Google Scholar
• Bradbury ARM, Sidhu S, Dübel S, McCafferty J. Beyond natural antibodies: the power of in vitro display technologies. Nat Biotechnol. 2011;29(3):245–54. doi:10.1038/nbt.1791.
   PubMed Web of Science ®Google Scholar
• Naranjo L, Ferrara F, Blanchard N, Demangel C, D’Angelo S, Erasmus MF, Teixeira AA, Bradbury ARM. Recombinant antibodies against mycolactone. Toxins. 2019;11:346.
   Web of Science ®Google Scholar
• Spencer S, Bethea D, Raju TS, Giles-Komar J, Feng Y. Solubility evaluation of murine hybridoma antibodies. mAbs. 2012;4(3):319–25. doi:10.4161/mabs.19869.
   PubMed Web of Science ®Google Scholar
• Kumar S, Singh SK. Developability of biotherapeutics. Computational approaches. CRC Press; Boca Raton, Florida, USA: 2015.
   Google Scholar
• Gavel Y, Heijne G. Sequence differences between glycosylated and non-glycosylated Asn-X-Thr/Ser acceptor sites: implications for protein engineering. Protein Eng Des Sel. 1990;3(5):433–42. doi:10.1093/protein/3.5.433.
   Google Scholar
• Lowenthal MS, Davis KS, Formolo T, Kilpatrick LE, Phinney KW. Identification of novel N-glycosylation sites at noncanonical protein consensus motifs. J Proteome Res. 2016;15(7):2087–101. doi:10.1021/acs.jproteome.5b00733.
   PubMed Web of Science ®Google Scholar
• Sydow JF, Lipsmeier F, Larraillet V, Hilger M, Mautz B, Mølhøj M, Kuentzer J, Klostermann S, Schoch J, Voelger HR, et al. Structure-based prediction of asparagine and aspartate degradation sites in antibody variable regions. Plos One. 2014;9(6):e100736. doi:10.1371/journal.pone.0100736.
   PubMed Web of Science ®Google Scholar
• Kelly RL, Le D, Zhao J, Wittrup KD. Reduction of nonspecificity motifs in synthetic antibody libraries. J Mol Biol. 2018;430(1):119–30. doi:10.1016/j.jmb.2017.11.008.
   PubMed Web of Science ®Google Scholar
• Wu S-J, Luo J, O’Neil KT, Kang J, Lacy ER, Canziani G, Baker A, Huang M, Tang QM, Raju TS, et al. Structure-based engineering of a monoclonal antibody for improved solubility. Protein Eng Des Sel PEDS. 2010;23(8):643–51. doi:10.1093/protein/gzq037.
   PubMed Web of Science ®Google Scholar
• Bethea D, Wu S-J, Luo J, Hyun L, Lacy ER, Teplyakov A, Jacobs SA, O’Neil KT, Gilliland GL, Feng Y. Mechanisms of self-association of a human monoclonal antibody CNTO607. Protein Eng Des Sel. 2012;25(10):531–38. doi:10.1093/protein/gzs047.
   PubMed Web of Science ®Google Scholar
• Yadav S, Sreedhara A, Kanai S, Liu J, Lien S, Lowman H, Kalonia DS, Shire SJ. Establishing a link between amino acid sequences and self-associating and viscoelastic behavior of two closely related monoclonal antibodies. Pharm Res. 2011;28(7):1750–64. doi:10.1007/s11095-011-0410-0.
   PubMed Web of Science ®Google Scholar
• Alam ME, Geng SB, Bender C, Ludwig SD, Linden L, Hoet R, Tessier PM. Biophysical and sequence-based methods for identifying monovalent and bivalent antibodies with high colloidal stability. Mol Pharm. 2018;15(1):150–63. doi:10.1021/acs.molpharmaceut.7b00779.
   PubMed Web of Science ®Google Scholar
• Brych SR, Gokarn YR, Hultgen H, Stevenson RJ, Rajan R, Matsumura M. Characterization of antibody aggregation: role of buried, unpaired cysteines in particle formation. J Pharm Sci. 2010;99(2):764–81. doi:10.1002/jps.21868.
   PubMed Web of Science ®Google Scholar
• Marks JD, Hoogenboom HR, Bonnert TP, McCafferty J, Griffiths AD, Winter G. By-passing immunization. J Mol Biol. 1991;222(3):581–97. doi:10.1016/0022-2836(91)90498-U.
   PubMed Web of Science ®Google Scholar
• Barbas CF, Bain JD, Hoekstra DM, Lerner RA. Semisynthetic combinatorial antibody libraries: a chemical solution to the diversity problem. Proc Natl Acad Sci. 1992;89(10):4457–61. doi:10.1073/pnas.89.10.4457.
   PubMed Web of Science ®Google Scholar
• Little M, Welschof M, Braunagel M, Hermes I, Christ C, Keller A, Rohrbach P, Kürschner T, Schmidt S, Kleist C, et al. Generation of a large complex antibody library from multiple donors. J Immunol Methods. 1999;231(1–2):3–9. doi:10.1016/S0022-1759(99)00164-7.
   PubMed Web of Science ®Google Scholar
• Hanes J, Schaffitzel C, Knappik A, Plückthun A. Picomolar affinity antibodies from a fully synthetic naive library selected and evolved by ribosome display. Nat Biotechnol. 2000;18(12):1287–92. doi:10.1038/82407.
   PubMed Web of Science ®Google Scholar
• Griffiths’ AD, Williams SC, Hartley’ O, Tomlinson IM, Crosbyl WL, Jones’ PT, Low M, Allison TJ, Hoogenboom HR, Coxl JPL, et al. Isolation of high affinity human antibodies directly from large synthetic repertoires. EMBO J. 1994;13:3245–60. doi:10.1002/j.1460-2075.1994.tb06626.x.
   PubMed Web of Science ®Google Scholar
• Sblattero D, Bradbury A. Exploiting recombination in single bacteria to make large phage antibody libraries. Nat Biotechnol. 2000;18(1):75–80. doi:10.1038/71958.
   PubMed Web of Science ®Google Scholar
• Feldhaus MJ, Siegel RW, Opresko LK, Coleman JR, Feldhaus JMW, Yeung YA, Cochran JR, Heinzelman P, Colby D, Swers J, et al. Flow-cytometric isolation of human antibodies from a nonimmune saccharomyces cerevisiae surface display library. Nat Biotechnol. 2003;21(2):163–70. doi:10.1038/nbt785.
   PubMed Web of Science ®Google Scholar
• Sidhu SS, Li B, Chen Y, Fellouse FA, Eigenbrot C, Fuh G. Phage-displayed antibody libraries of synthetic heavy chain complementarity determining regions. J Mol Biol. 2004;338(2):299–310. doi:10.1016/j.jmb.2004.02.050.
   PubMed Web of Science ®Google Scholar
• Rothe C, Urlinger S, Löhning C, Prassler J, Stark Y, Jäger U, Hubner B, Bardroff M, Pradel I, Boss M, et al. The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of high-affinity antibodies. J Mol Biol. 2008;376(4):1182–200. doi:10.1016/j.jmb.2007.12.018.
   PubMed Web of Science ®Google Scholar
• Glanville J, Zhai W, Berka J, Telman D, Huerta G, Mehta GR, Ni I, Mei L, Sundar PD, Day GMR, et al. Precise determination of the diversity of a combinatorial antibody library gives insight into the human immunoglobulin repertoire. Proc Natl Acad Sci. 2009;106(48):20216–21. doi:10.1073/pnas.0909775106.
   PubMed Web of Science ®Google Scholar
• Ge X, Mazor Y, Hunicke-Smith SP, Ellington AD, Georgiou G. Rapid construction and characterization of synthetic antibody libraries without DNA amplification. Biotechnol Bioeng. 2010. doi:10.1002/bit.22712.
   PubMed Web of Science ®Google Scholar
• Prassler J, Thiel S, Pracht C, Polzer A, Peters S, Bauer M, Nörenberg S, Stark Y, Kölln J, Popp A, et al. HuCAL PLATINUM, a synthetic fab library optimized for sequence diversity and superior performance in mammalian expression systems. J Mol Biol. 2011;413(1):261–78. doi:10.1016/j.jmb.2011.08.012.
   PubMed Web of Science ®Google Scholar
• Villa A, Lovato V, Bujak E, Wulhfard S, Pasche N, Neri D. A novel synthetic naïve human antibody library allows the isolation of antibodies against a new epitope of oncofetal fibronectin. mAbs. 2011;3(3):264–72. doi:10.4161/mabs.3.3.15616.
   PubMed Web of Science ®Google Scholar
• Mahon CM, Lambert MA, Glanville J, Wade JM, Fennell BJ, Krebs MR, Armellino D, Yang S, Liu X, O’Sullivan CM, et al. Comprehensive interrogation of a minimalist synthetic CDR-H3 library and its ability to generate antibodies with therapeutic potential. J Mol Biol. 2013;425(10):1712–30. doi:10.1016/j.jmb.2013.02.015.
   PubMed Web of Science ®Google Scholar
• Schwimmer LJ, Huang B, Giang H, Cotter RL, Chemla-Vogel DS, Dy FV, Tam EM, Zhang F, Toy P, Bohmann DJ, et al. Discovery of diverse and functional antibodies from large human repertoire antibody libraries. J Immunol Methods. 2013;391(1–2):60–71. doi:10.1016/j.jim.2013.02.010.
   PubMed Web of Science ®Google Scholar
• Tiller T, Schuster I, Deppe D, Siegers K, Strohner R, Herrmann T, Berenguer M, Poujol D, Stehle J, Stark Y, et al. A fully synthetic human fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties. mAbs. 2013;5(3):445–70. doi:10.4161/mabs.24218.
   PubMed Web of Science ®Google Scholar
• Weber M, Bujak E, Putelli A, Villa A, Matasci M, Gualandi L, Hemmerle T, Wulhfard S, Neri D, Highly Functional A. Synthetic phage display library containing over 40 billion human antibody clones. Plos One. 2014;9:e100000. doi:10.1371/journal.pone.0100000.
   PubMed Web of Science ®Google Scholar
• Bai X, Kim J, Kang S, Kim W, Shim H, Novel A. Human scFv library with non-combinatorial synthetic CDR diversity. Plos One. 2015;10(10):e0141045. doi:10.1371/journal.pone.0141045.
   PubMed Web of Science ®Google Scholar
• Li K, Zettlitz KA, Lipianskaya J, Zhou Y, Marks JD, Mallick P, Reiter RE, Wu AM. A fully human scFv phage display library for rapid antibody fragment reformatting. Protein Eng Des Sel. 2015;28(10):307–16. doi:10.1093/protein/gzv024.
   PubMed Web of Science ®Google Scholar
• Pasello M, Zamboni S, Mallano A, Flego M, Picci P, Cianfriglia M, Scotlandi K. Design and construction of a new human naïve single-chain fragment variable antibody library, IORISS1. J Biotechnol. 2016;224:1–11. doi:10.1016/j.jbiotec.2016.02.034.
   PubMed Web of Science ®Google Scholar
• Maruthachalam BV, El-Sayed A, Liu J, Sutherland AR, Hill W, Alam MK, Pastushok L, Fonge H, Barreto K, Geyer CR. A single-framework synthetic antibody library containing a combination of canonical and variable complementarity-determining regions. ChemBioChem. 2017;18(22):2247–59. doi:10.1002/cbic.201700279.
   PubMed Web of Science ®Google Scholar
• Schofield DJ, Pope AR, Clementel V, Buckell J, Chapple SD, Clarke KF, Conquer JS, Crofts AM, Crowther SRE, Dyson MR, et al. Application of phage display to high throughput antibody generation and characterization. Genome Biol. 2007;8(11):R254. doi:10.1186/gb-2007-8-11-r254.
   PubMed Web of Science ®Google Scholar
• Hoet RM, Cohen EH, Kent RB, Rookey K, Schoonbroodt S, Hogan S, Rem L, Frans N, Daukandt M, Pieters H, et al. Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity. Nat Biotechnol. 2005;23(3):344–48. doi:10.1038/nbt1067.
   PubMed Web of Science ®Google Scholar
• Erasmus MF, D’Angelo S, Ferrara F, Naranjo L, Teixeira AA, Buonpane R, Stewart SM, Nastri HG, Bradbury ARM. A single donor is sufficient to produce a highly functional in vitro antibody library. Commun Biol. 2021;4(1):1–16. doi:10.1038/s42003-021-01881-0.
   PubMed Web of Science ®Google Scholar
• Collins AM, Wang Y, Roskin KM, Marquis CP, Jackson KJL. The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains. Philos Trans R Soc B Biol Sci. [Internet] 2015; 370(1676):20140236. Available from: [cited 2019 Sep 18]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528413/.
   PubMed Web of Science ®Google Scholar
• Ramsden DA, Wu GE. Mouse kappa light-chain recombination signal sequences mediate recombination more frequently than do those of lambda light chain. Proc Natl Acad Sci U S A. 1991;88:10721–25. doi:10.1073/pnas.88.23.10721.
   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):1743053. doi:10.1080/19420862.2020.1743053.
   PubMed Web of Science ®Google Scholar
• Yasuda S, Zhou Y, Wang Y, Yamamura M, Wang J-Y. A model integrating tonic and antigen-triggered BCR signals to predict the survival of primary B cells. Sci Rep. 2017;7(1):14888. doi:10.1038/s41598-017-13993-x.
   PubMedGoogle Scholar
• Boder ET, Wittrup KD. Yeast surface display for screening combinatorial polypeptide libraries. Nat Biotechnol. 1997;15(6):553–57. doi:10.1038/nbt0697-553.
   PubMed Web of Science ®Google Scholar
• Ferrara F, Kolnik M, D’Angelo S, Erasmus FM, Vorholt D, Bradbury ARM. Rapid purification of billions of circulating CD19+ B cells directly from leukophoresis samples. New Biotechnol. 2018;46:14–21.
   PubMed Web of Science ®Google Scholar
• Ferrara F, Naranjo LA, Kumar S, Gaiotto T, Mukundan H, Swanson B, Bradbury ARM. Using phage and yeast display to select hundreds of monoclonal antibodies: application to antigen 85, a tuberculosis biomarker. PLOS ONE. 2012;7:e49535. doi:10.1371/journal.pone.0049535.
   PubMed Web of Science ®Google Scholar
• Petri M, Wallace DJ, Spindler A, Chindalore V, Kalunian K, Mysler E, Neuwelt CM, Robbie G, White WI, Higgs BW, et al. Sifalimumab, a human anti–interferon-α monoclonal antibody, in systemic lupus erythematosus: a phase i randomized, controlled, dose-escalation study. Arthritis Rheum. 2013;65(4):1011–21. doi:10.1002/art.37824.
   PubMed Web of Science ®Google Scholar
• Guo X, Higgs BW, Bay-Jensen A-C, Wu Y, Karsdal MA, Kuziora M, Godwood A, Close D, Ryan PC, Roskos LK, et al. Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities in rheumatoid arthritis. Rheumatol Oxf Engl. 2018;57(1):175–84. doi:10.1093/rheumatology/kex383.
   PubMed Web of Science ®Google Scholar
• Hamilton JA. GM-CSF as a target in inflammatory/autoimmune disease: current evidence and future therapeutic potential. Expert Rev Clin Immunol. 2015;11(4):457–65. doi:10.1586/1744666X.2015.1024110.
   PubMed Web of Science ®Google Scholar
• Rincon M. Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012;33(11):571–77. doi:10.1016/j.it.2012.07.003.
   PubMed Web of Science ®Google Scholar
• Rossi J-F, Lu Z-Y, Jourdan M, Klein B. Interleukin-6 as a therapeutic target. Clin Cancer Res Off J Am Assoc Cancer Res. 2015;21(6):1248–57. doi:10.1158/1078-0432.CCR-14-2291.
   PubMed Web of Science ®Google Scholar
• Hagopian MM, Brekken RA. Stromal TGFβR2 signaling: a gateway to progression for pancreatic cancer. Mol Cell Oncol. 2015;2:e975606. doi:10.4161/23723556.2014.975606.
   PubMed Web of Science ®Google Scholar
• Abdiche YN. High-throughput antibody characterization. Genet Eng Biotechnol News. 2017;37(15):28–29. doi:10.1089/gen.37.15.13.
   Google Scholar
• Robinson A, Hines V, Wittrup K. Protein disulfide isomerase overexpression increases secretion of foreign proteins in saccharomyces cerevisiae. Bio/Technology. 1994;12(4):381–84. doi:10.1038/nbt0494-381.
   PubMed Web of Science ®Google Scholar
• Ferrara F, D’Angelo S, Gaiotto T, Naranjo L, Tian H, Gräslund S, Dobrovetsky E, Hraber P, Lund-Johansen F, Saragozza S, et al. Recombinant renewable polyclonal antibodies. mAbs. 2015;7(1):32–41. doi:10.4161/19420862.2015.989047.
   PubMed Web of Science ®Google Scholar
• He F, Woods CE, Becker GW, Narhi LO, Razinkov VI. High-throughput assessment of thermal and colloidal stability parameters for monoclonal antibody formulations. J Pharm Sci. 2011;100(12):5126–41. doi:10.1002/jps.22712.
   PubMed Web of Science ®Google Scholar
• Sule SV, Sukumar M, Weiss WF, Marcelino-Cruz AM, Sample T, Tessier PM. High-throughput analysis of concentration-dependent antibody self-association. Biophys J. 2011;101(7):1749–57. doi:10.1016/j.bpj.2011.08.036.
   PubMed Web of Science ®Google Scholar
• Liu Y, Caffry I, Wu J, Geng SB, Jain T, Sun T, Reid F, Cao Y, Estep P, Yu Y, et al. High-throughput screening for developability during early-stage antibody discovery using self-interaction nanoparticle spectroscopy. mAbs. 2014;6(2):483–92. doi:10.4161/mabs.27431.
   PubMed Web of Science ®Google Scholar
• Estep P, Caffry I, Yu Y, Sun T, Cao Y, Lynaugh H, Jain T, Vásquez M, Tessier PM, Xu Y. An alternative assay to hydrophobic interaction chromatography for high-throughput characterization of monoclonal antibodies. mAbs. 2015;7(3):553–61. doi:10.1080/19420862.2015.1016694.
   PubMed Web of Science ®Google Scholar
• Valadon P, Pérez-Tapia SM, Nelson RS, Guzmán-Bringas OU, Arrieta-Oliva HI, Gómez-Castellano KM, Pohl MA, Almagro JC. ALTHEA Gold LibrariesTM: antibody libraries for therapeutic antibody discovery. mAbs. 2019;11:516–31. doi:10.1080/19420862.2019.1571879.
   PubMed Web of Science ®Google Scholar
• Frenzel A, Schirrmann T, Hust M. Phage display-derived human antibodies in clinical development and therapy. mAbs. 2016;8(7):1177–94. doi:10.1080/19420862.2016.1212149.
   PubMed Web of Science ®Google Scholar
• Sheets MD, Amersdorfer P, Finnern R, Sargent P, Lindqvist E, Schier R, Hemingsen G, Wong C, Gerhart JC, Marks JD. Efficient construction of a large nonimmune phage antibody library: the production of high-affinity human single-chain antibodies to protein antigens. Proc Natl Acad Sci. 1998;95(11):6157–62. doi:10.1073/pnas.95.11.6157.
   PubMed Web of Science ®Google Scholar
• Söderlind E, Strandberg L, Jirholt P, Kobayashi N, Alexeiva V, Aberg AM, Nilsson A, Jansson B, Ohlin M, Wingren C, et al. Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries. Nat Biotechnol. 2000;18:852–56. doi:10.1038/78458.
   PubMed Web of Science ®Google Scholar
• Ponsel D, Neugebauer J, Ladetzki-Baehs K, Tissot K. High affinity, developability and functional size: the holy grail of combinatorial antibody library generation. Molecules. 2011;16(5):3675–700. doi:10.3390/molecules16053675.
   PubMed Web of Science ®Google Scholar
• Hötzel I, Theil F-P, Bernstein LJ, Prabhu S, Deng R, Quintana L, Lutman J, Sibia R, Chan P, Bumbaca D, et al. A strategy for risk mitigation of antibodies with fast clearance. mAbs. 2012;4(6):753–60. doi:10.4161/mabs.22189.
   PubMed Web of Science ®Google Scholar
• Sun A, Benet LZ. Late-stage failures of monoclonal antibody drugs: a retrospective case study analysis. Pharmacology. 2020;105(3–4):145–63. doi:10.1159/000505379.
   PubMed Web of Science ®Google Scholar
• Ellgaard L, Helenius A. Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol. 2003;4(3):181–91. doi:10.1038/nrm1052.
   PubMed Web of Science ®Google Scholar
• Shusta EV, Kieke MC, Parke E, Kranz DM, Wittrup KD. Yeast polypeptide fusion surface display levels predict thermal stability and soluble secretion efficiency. J Mol Biol. 1999;292(5):949–56. doi:10.1006/jmbi.1999.3130.
   PubMed Web of Science ®Google Scholar
• Julian MC, Li L, Garde S, Wilen R, Tessier PM. Efficient affinity maturation of antibody variable domains requires co-selection of compensatory mutations to maintain thermodynamic stability. Sci Rep. 2017;7(1):1–13. doi:10.1038/srep45259.
   PubMedGoogle Scholar
• Tiller KE, Li L, Kumar S, Julian MC, Garde S, Tessier PM. Arginine mutations in antibody complementarity-determining regions display context-dependent affinity/specificity trade-offs. J Biol Chem. 2017;292(40):16638–52. doi:10.1074/jbc.M117.783837.
   PubMed Web of Science ®Google Scholar
• Pepinsky RB, Silvian L, Berkowitz SA, Farrington G, Lugovskoy A, Walus L, Eldredge J, Capili A, Mi S, Graff C, et al. Improving the solubility of anti-LINGO-1 monoclonal antibody Li33 by isotype switching and targeted mutagenesis. Protein Sci Publ Protein Soc. 2010;19(5):954–66. doi:10.1002/pro.372.
   PubMed Web of Science ®Google Scholar
• Schmiedl A, Breitling F, Winter CH, Queitsch I, Dübel S. Effects of unpaired cysteines on yield, solubility and activity of different recombinant antibody constructs expressed in E. coli. J Immunol Methods. 2000;242(1–2):101–14. doi:10.1016/S0022-1759(00)00243-X.
   PubMed Web of Science ®Google Scholar
• Alam ME, Slaney TR, Wu L, Das TK, Kar S, Barnett GV, Leone A, Tessier PM. Unique impacts of methionine oxidation, tryptophan oxidation, and asparagine deamidation on antibody stability and aggregation. J Pharm Sci. 2020;109(1):656–69. doi:10.1016/j.xphs.2019.10.051.
   PubMed Web of Science ®Google Scholar
• Ellgaard L, Molinari M, Helenius A. Setting the standards: quality control in the secretory pathway. Science. 1999;286(5446):1882–88. doi:10.1126/science.286.5446.1882.
   PubMed Web of Science ®Google Scholar
• Kowalski JM, Parekh RN, Mao J, Wittrup KD. Protein folding stability can determine the efficiency of escape from endoplasmic reticulum quality control. J Biol Chem. 1998;273(31):19453–58. doi:10.1074/jbc.273.31.19453.
   PubMed Web of Science ®Google Scholar
• Kowalski JM, Parekh RN, Wittrup KD. Secretion Efficiency in Saccharomyces cerevisiae of bovine pancreatic trypsin inhibitor mutants lacking disulfide bonds is correlated with thermodynamic stability †. Biochemistry. 1998;37(5):1264–73. doi:10.1021/bi9722397.
   PubMed Web of Science ®Google Scholar
• Millward TA, Heitzmann M, Bill K, Längle U, Schumacher P, Forrer K. Effect of constant and variable domain glycosylation on pharmacokinetics of therapeutic antibodies in mice. Biologicals. 2008;36(1):41–47. doi:10.1016/j.biologicals.2007.05.003.
   PubMed Web of Science ®Google Scholar
• Bovenkamp FS, Hafkenscheid L, Rispens T, Rombouts Y. The emerging importance of IgG fab glycosylation in immunity. J Immunol. 2016;196(4):1435–41. doi:10.4049/jimmunol.1502136.
   PubMed Web of Science ®Google Scholar
• O’Neil BH, Allen R, Spigel DR, Stinchcombe TE, Moore DT, Berlin JD, Goldberg RM. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(24):3644–48. doi:10.1200/JCO.2007.11.7812.
   PubMed Web of Science ®Google Scholar
• Chung CH, Mirakhur B, Chan E, Le Q-T, Berlin J, Morse M, Murphy BA, Satinover SM, Hosen J, Mauro D, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-α-1,3-galactose. N Engl J Med. 2008;358(11):1109–17. doi:10.1056/NEJMoa074943.
   PubMed Web of Science ®Google Scholar
• Jefferis R. Posttranslational modifications and the immunogenicity of biotherapeutics. J Immunol Res. 2016;2016:1–15. doi:10.1155/2016/5358272.
   Web of Science ®Google Scholar
• Kuriakose A, Chirmule N, Nair P. Immunogenicity of biotherapeutics: causes and association with posttranslational modifications. J Immunol Res. 2016;2016:1–18. doi:10.1155/2016/1298473.
   Web of Science ®Google Scholar
• Kay J, Matteson EL, Dasgupta B, Nash P, Durez P, Hall S, Hsia EC, Han J, Wagner C, Xu Z, et al. Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum. 2008;58(4):964–75. doi:10.1002/art.23383.
   PubMed Web of Science ®Google Scholar
• Bender NK, Heilig CE, Dröll B, Wohlgemuth J, Armbruster F-P, Heilig B. Immunogenicity, efficacy and adverse events of adalimumab in RA patients. Rheumatol Int. 2006;27(3):269–74. doi:10.1007/s00296-006-0183-7.
   PubMed Web of Science ®Google Scholar
• Furie R, Stohl W, Ginzler EM, Becker M, Mishra N, Chatham WW, Merrill JT, Weinstein A, McCune WJ, Zhong J, et al. Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus. Arthritis Res Ther. 2008;10(5):R109. doi:10.1186/ar2506.
   PubMed Web of Science ®Google Scholar
• Getts DR, Getts MT, McCarthy DP, Chastain EM, Miller SD. Have we overestimated the benefit of human(ized) antibodies? mAbs. 2010;2(6):682–94. doi:10.4161/mabs.2.6.13601.
   PubMed Web of Science ®Google Scholar
• CAT-152 0102 Trabeculectomy Study Group. A phase III study of subconjunctival human anti–transforming growth factor β2 monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy. Ophthalmology. 2007;114(10):1822–1830.e2. doi:10.1016/j.ophtha.2007.03.050.
   PubMed Web of Science ®Google Scholar
• Masella AP, Bartram AK, Truszkowski JM, Brown DG, Neufeld JD. PANDAseq: paired-end assembler for illumina sequences. BMC Bioinformatics. 2012;13(1):31. doi:10.1186/1471-2105-13-31.
   PubMed Web of Science ®Google Scholar
• Ye J, Ma N, Madden TL, Ostell JM. IgBLAST: an immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res. 2013;41(W1):W34–40. doi:10.1093/nar/gkt382.
   PubMed Web of Science ®Google Scholar
• Lefranc MP. Unique database numbering system for immunogenetic analysis. Immunol Today. 1997;18(11):509. doi:10.1016/S0167-5699(97)01163-8.
   PubMedGoogle Scholar
• Lefranc M-P, Pommié C, Ruiz M, Giudicelli V, Foulquier E, Truong L, Thouvenin-Contet V, Lefranc G. IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev Comp Immunol. 2003;27(1):55–77. doi:10.1016/S0145-305X(02)00039-3.
   PubMed Web of Science ®Google Scholar
• Hernandez-Jimenez JA, Martinez-Ortega A, Salmeron-Garcia J, Cabeza JC, Prados, Ortiz R, Navas N. Study of aggregation in therapeutic monoclonal antibodies subjected to stress and long-term stability tests by analyzing size exclusion liquid chromatographic profiles. Int J Biol Macromol. 2018;118(Pt A):511–524. doi:10.1016/j.ijbiomac.2018.06.105. Epub 2018 Jun 23.
   Google Scholar