Mitigation of reversible self-association and viscosity in a human IgG1 monoclonal antibody by rational, structure-guided Fv engineering

References

• Nelson AL, Dhimolea E, Reichert JM. Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov 2010; 9:767-74; PMID:20811384; http://dx.doi.org/10.1038/nrd3229
   PubMed Web of Science ®Google Scholar
• Wang W, Singh S, Zeng DL, King K, Nema S. Antibody structure, instability, and formulation. J Pharm Sci 2007; 96:1-26; PMID:16998873; http://dx.doi.org/10.1002/jps.20727
   PubMed Web of Science ®Google Scholar
• Liu J, Nguyen MD, Andya JD, Shire SJ. Reversible self-association increases the viscosity of a concentrated monoclonal antibody in aqueous solution. J Pharm Sci 2005; 94:1928-40; PMID:16052543; http://dx.doi.org/10.1002/jps.20347
   PubMed Web of Science ®Google Scholar
• Mason BD, Zhang L, Remmele RL, Jr, Zhang J. Opalescence of an IgG2 monoclonal antibody solution as it relates to liquid-liquid phase separation. J Pharm Sci 2011; 100:4587-96; PMID:21638285; http://dx.doi.org/10.1002/jps.22650
   PubMed Web of Science ®Google Scholar
• 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; PMID:20401522; http://dx.doi.org/10.1007/s11095-010-0125-7
   PubMed Web of Science ®Google Scholar
• 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; PMID:19705420; http://dx.doi.org/10.1002/jps.21898
   PubMed Web of Science ®Google Scholar
• Yadav S, Shire SJ, Kalonia DS. Factors affecting the viscosity in high concentration solutions of different monoclonal antibodies. J Pharm Sci 2010; 99:4812-29; PMID:20821382; http://dx.doi.org/10.1002/jps.22190
   PubMed Web of Science ®Google Scholar
• Laue T. Proximity energies: a framework for understanding concentrated solutions. J Mol Recognit 2012; 25:165-73; PMID:22407980; http://dx.doi.org/10.1002/jmr.2179
   PubMed Web of Science ®Google Scholar
• Kanai S, Liu J, Patapoff TW, Shire SJ. Reversible self-association of a concentrated monoclonal antibody solution mediated by Fab-Fab interaction that impacts solution viscosity. J Pharm Sci 2008; 97:4219-27; PMID:18240303; http://dx.doi.org/10.1002/jps.21322
   PubMed Web of Science ®Google Scholar
• Burckbuchler V, Mekhloufi G, Giteau AP, Grossiord JL, Huille S, Agnely F. Rheological and syringeability properties of highly concentrated human polyclonal immunoglobulin solutions. Eur J Pharm Biopharm 2010; 76:351-6; PMID:20719247; http://dx.doi.org/10.1016/j.ejpb.2010.08.002
   PubMed Web of Science ®Google Scholar
• Shire SJ, Shahrokh Z, Liu J. Challenges in the development of high protein concentration formulations. J Pharm Sci 2004; 93:1390-402; PMID:15124199; http://dx.doi.org/10.1002/jps.20079
   PubMed Web of Science ®Google Scholar
• Brems DN, Alter LA, Beckage MJ, Chance RE, DiMarchi RD, Green LK, Long HB, Pekar AH, Shields JE, Frank BH. Altering the association properties of insulin by amino acid replacement. Protein Eng 1992; 5:527-33; PMID:1438163; http://dx.doi.org/10.1093/protein/5.6.527
   PubMedGoogle Scholar
• Clodfelter DK, Pekar AH, Rebhun DM, Destrampe KA, Havel HA, Myers SR, Brader ML. Effects of non-covalent self-association on the subcutaneous absorption of a therapeutic peptide. Pharm Res 1998; 15:254-62; PMID:9523312; http://dx.doi.org/10.1023/A:1011918719017
   PubMed Web of Science ®Google Scholar
• Alford JR, Kendrick BS, Carpenter JF, Randolph TW. High concentration formulations of recombinant human interleukin-1 receptor antagonist: II. Aggregation kinetics. J Pharm Sci 2008; 97:3005-21; PMID:17924426; http://dx.doi.org/10.1002/jps.21205
   PubMed Web of Science ®Google Scholar
• 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; PMID:25875351; http://dx.doi.org/10.1080/19420862.2015.1029217
   PubMed Web of Science ®Google Scholar
• Barthelemy PA, Raab H, Appleton BA, Bond CJ, Wu P, Wiesmann C, Sidhu SS. Comprehensive analysis of the factors contributing to the stability and solubility of autonomous human VH domains. J Biol Chem 2008; 283:3639-54; PMID:18045863; http://dx.doi.org/10.1074/jbc.M708536200
   PubMed Web of Science ®Google Scholar
• Esfandiary R, Hayes DB, Parupudi A, Casas-Finet J, Bai S, Samra HS, Shah AU, Sathish HA. A systematic multitechnique approach for detection and characterization of reversible self-association during formulation development of therapeutic antibodies. J Pharm Sci 2013; 102:3089-99; PMID:23794522; http://dx.doi.org/10.1002/jps.23654
   PubMed Web of Science ®Google Scholar
• Esfandiary R, Parupudi A, Casas-Finet J, Gadre D, Sathish H. Mechanism of reversible self-association of a monoclonal antibody: role of electrostatic and hydrophobic interactions. J Pharm Sci 2015; 104:577-86; PMID:25407315; http://dx.doi.org/10.1002/jps.24237
   PubMed Web of Science ®Google Scholar
• Nishi H, Miyajima M, Wakiyama N, Kubota K, Hasegawa J, Uchiyama S, Fukui K. Fc domain mediated self-association of an IgG1 monoclonal antibody under a low ionic strength condition. J Biosci Bioeng 2011; 112:326-32; PMID:21783411; http://dx.doi.org/10.1016/j.jbiosc.2011.06.017
   PubMed Web of Science ®Google Scholar
• Wu SJ, 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 2010; 23:643-51; PMID:20543007; http://dx.doi.org/10.1093/protein/gzq037
   PubMed Web of Science ®Google Scholar
• 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; PMID:22352470; http://dx.doi.org/10.1021/mp200566k
   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; 28:1750-64; PMID:21626060; http://dx.doi.org/10.1007/s11095-011-0410-0
   PubMed Web of Science ®Google Scholar
• Nichols P, Li L, Kumar S, Buck PM, Singh SK, Goswami S, Balthazor B, Conley TR, Sek D, Allen MJ. Rational design of viscosity reducing mutants of a monoclonal antibody: hydrophobic vs. electrostatic inter-molecular interactions. MAbs 2015; 7:212-30; PMID:25559441; http://dx.doi.org/10.4161/19420862.2014.985504
   PubMed Web of Science ®Google Scholar
• Bethea D, Wu SJ, 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; 25:531-7; PMID:22915597; http://dx.doi.org/10.1093/protein/gzs047
   PubMed Web of Science ®Google Scholar
• Teplyakov A, Obmolova G, Wu SJ, Luo J, Kang J, O'Neil K, Gilliland GL. Epitope mapping of anti-interleukin-13 neutralizing antibody CNTO607. J Mol Biol 2009; 389:115-23; PMID:19361524; http://dx.doi.org/10.1016/j.jmb.2009.03.076
   PubMed Web of Science ®Google Scholar
• Chow CK, 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; PMID:26849155; http://dx.doi.org/10.1021/acs.molpharmaceut.5b00817
   PubMed Web of Science ®Google Scholar
• Tomar DS, Kumar S, Singh SK, Goswami S, Li L. Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development. MAbs 2016; 8:216-28; PMID:26736022; http://dx.doi.org/10.1080/19420862.2015.1128606
   PubMed Web of Science ®Google Scholar
• Chennamsetty N, Helk B, Voynov V, Kayser V, Trout BL. Aggregation-prone motifs in human immunoglobulin G. J Mol Biol 2009; 391:404-13; PMID:19527731; http://dx.doi.org/10.1016/j.jmb.2009.06.028
   PubMed Web of Science ®Google Scholar
• Obrezanova O, Arnell A, de la Cuesta RG, Berthelot ME, Gallagher TR, Zurdo J, Stallwood Y. Aggregation risk prediction for antibodies and its application to biotherapeutic development. MAbs 2015; 7:352-63; PMID:25760769; http://dx.doi.org/10.1080/19420862.2015.1007828
   PubMed Web of Science ®Google Scholar
• Sharma VK, Patapoff TW, Kabakoff B, Pai S, Hilario E, Zhang B, Li C, Borisov O, Kelley RF, Chorny I, et al. In silico selection of therapeutic antibodies for development: viscosity, clearance, and chemical stability. Proc Natl Acad Sci U S A 2014; 111:18601-6; PMID:25512516; http://dx.doi.org/10.1073/pnas.1421779112
   PubMed Web of Science ®Google Scholar
• Agrawal NJ, Helk B, Kumar S, Mody N, Sathish HA, Samra HS, Buck PM, Li L, Trout BL. Computational tool for the early screening of monoclonal antibodies for their viscosities. MAbs 2016; 8:43-8; PMID:26399600; http://dx.doi.org/10.1080/19420862.2015.1099773
   PubMed Web of Science ®Google Scholar
• Hasegawa H, Woods CE, Kinderman F, He F, Lim AC. Russell body phenotype is preferentially induced by IgG mAb clones with high intrinsic condensation propensity: relations between the biosynthetic events in the ER and solution behaviors in vitro. MAbs 2014; 6:1518-32; PMID:25484054; http://dx.doi.org/10.4161/mabs.36242
   PubMed Web of Science ®Google Scholar
• Jacobs SA, Wu SJ, Feng Y, Bethea D, O'Neil KT. Cross-interaction chromatography: a rapid method to identify highly soluble monoclonal antibody candidates. Pharm Res 2010; 27:65-71; PMID:19911257; http://dx.doi.org/10.1007/s11095-009-0007-z
   PubMed Web of Science ®Google Scholar
• Kohli N, Jain N, Geddie ML, Razlog M, Xu L, Lugovskoy AA. A novel screening method to assess developability of antibody-like molecules. MAbs 2015; 7:752-8; PMID:25961854; http://dx.doi.org/10.1080/19420862.2015.1048410
   PubMed Web of Science ®Google Scholar
• Sule SV, Dickinson CD, Lu J, Chow CK, Tessier PM. Rapid analysis of antibody self-association in complex mixtures using immunogold conjugates. Mol Pharm 2013; 10:1322-31; PMID:23383873; http://dx.doi.org/10.1021/mp300524x
   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; 6:483-92; PMID:24492294; http://dx.doi.org/10.4161/mabs.27431
   PubMed Web of Science ®Google Scholar
• Giudicelli V, Chaume D, Lefranc MP. IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res 2005; 33:D256-61; PMID:15608191; http://dx.doi.org/10.1093/nar/gki010
   PubMed Web of Science ®Google Scholar
• Gagnon P, Mayes T, Danielsson A. An adaptation of hydrophobic interaction chromatography for estimation of protein solubility optima. J Pharm Biomed Anal 1997; 16:587-92; PMID:9502154; http://dx.doi.org/10.1016/S0731-7085(97)00153-2
   PubMed Web of Science ®Google Scholar
• Haverick M, Mengisen S, Shameem M, Ambrogelly A. Separation of mAbs molecular variants by analytical hydrophobic interaction chromatography HPLC: overview and applications. MAbs 2014; 6:852-8; PMID:24751784; http://dx.doi.org/10.4161/mabs.28693
   PubMed Web of Science ®Google Scholar
• Jespers L, Schon O, James LC, Veprintsev D, Winter G. Crystal structure of HEL4, a soluble, refoldable human V(H) single domain with a germ-line scaffold. J Mol Biol 2004; 337:893-903; PMID:15033359; http://dx.doi.org/10.1016/j.jmb.2004.02.013
   PubMed Web of Science ®Google Scholar
• Dudgeon K, Rouet R, Kokmeijer I, Schofield P, Stolp J, Langley D, Stock D, Christ D. General strategy for the generation of human antibody variable domains with increased aggregation resistance. Proc Natl Acad Sci U S A 2012; 109:10879-84; PMID:22745168; http://dx.doi.org/10.1073/pnas.1202866109
   PubMed Web of Science ®Google Scholar
• Chothia C, Lesk AM. Canonical structures for the hypervariable regions of immunoglobulins. J Mol Biol 1987; 196:901-17; PMID:3681981; http://dx.doi.org/10.1016/0022-2836(87)90412-8
   PubMed Web of Science ®Google Scholar
• Henikoff S, Henikoff JG. Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A 1992; 89:10915-9; PMID:1438297; http://dx.doi.org/10.1073/pnas.89.22.10915
   PubMed Web of Science ®Google Scholar