Insights into the IgG heavy chain engineering patent landscape as applied to IgG4 antibody development

References

• Morell A, Skvaril F, Steinberg AG, Van Loghem E, Terry WD. Correlations between the concentrations of the four sub-classes of IgG and Gm Allotypes in normal human sera. J Immunol [Internet]. 1972;108:195–206. http://www.ncbi.nlm.nih.gov/pubmed/4622006.
   PubMed Web of Science ®Google Scholar
• Salfeld JG. Isotype selection in antibody engineering. Nat Biotechnol [Internet]. 2007 [cited 2016 Jan 18];25:1369–72. doi:10.1038/nbt1207-1369.
   PubMed Web of Science ®Google Scholar
• Ishizaka T, Ishizaka K, Salmon S, Fudenberg H. Biologic activities of aggregated gamma-globulin. 8. Aggregated immunoglobulins of different classes. J Immunol. 1967;99:82–91.
   PubMed Web of Science ®Google Scholar
• Brüggemann M, Williams GT, Bindon CI, Clark MR, Walker MR, Jefferis R, Waldmann H, Neuberger MS. Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med. 1987;166:1351–61. doi:10.1084/jem.166.5.1351.
   PubMed Web of Science ®Google Scholar
• Bindon CI, Hale G, Brüggemann M, Waldmann H. Human monoclonal IgG isotypes differ in complement activating function at the level of C4 as well as C1q. J Exp Med [Internet]. 1988;168:127–42. doi:10.1084/jem.168.1.127.
   PubMed Web of Science ®Google Scholar
• Riechmann L, Clark M, Waldmann H, Winter G. Reshaping human antibodies for therapy. Nature. 1988;332:323–27. doi:10.1038/332323a0.
   PubMed Web of Science ®Google Scholar
• Tao MH, Smith RI, Morrison SL. Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation. J Exp Med. 1993;178:661–67. doi:10.1084/jem.178.2.661.
   PubMed Web of Science ®Google Scholar
• Schumaker VN, Calcott MA, Spiegelberg HL, Mueller-Eberhard HJ. Ultracentrifuge studies of the binding of IgG of different subclasses to the Clq subunit of the first component of complement. Biochemistry. 1976;15:5175–81. doi:10.1021/bi00668a035.
   PubMed Web of Science ®Google Scholar
• Isaacs JD, Wing MG, Greenwood JD, Hazleman BL, Hale G, Waldmann H. A therapeutic human IgG4 monoclonal antibody that depletes target cells in humans. Clin Exp Immunol. 1996;106:427–33. doi:10.1046/j.1365-2249.1996.d01-876.x.
   PubMed Web of Science ®Google Scholar
• Greenwood J, Clark M, Waldmann H. Structural motifs involved in human IgG antibody effector functions. Eur J Immunol [Internet] 1993;23:1098–104.
   Google Scholar
• Ravetch JV, Kinet JP. Fc receptors. Annu Rev Immunol. 1991;9:457–92. doi:10.1146/annurev.iy.09.040191.002243.
   PubMed Web of Science ®Google Scholar
• Koene HR, Kleijer M, Algra J, Roos D, von Dem Borne AE, de Haas M. Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood. 1997;90:1109–14.
   PubMed Web of Science ®Google Scholar
• Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S, Daëron M. Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood. 2009;113:3716–25. doi:10.1182/blood-2008-03-146472.
   PubMed Web of Science ®Google Scholar
• Hussain K, Hargreaves CE, Roghanian A, Oldham RJ, Claude Chan HT, Mockridge CI, Chowdhury F, Frend??us B, Harper KS, Strefford JC, et al. Upregulation of F??RIIb on monocytes is necessary to promote the superagonist activity of TGN1412. Blood. 2015;125:102–10. doi:10.1182/blood-2014-07-591040.
   PubMed Web of Science ®Google Scholar
• Brusco A, Saviozzi S, Cinque F, DeMarchi M, Boccazzi C, De Lange G, Van Leeuwen AM, Carbonara AO. Molecular characterization of immunoglobulin G4 gene isoallotypes. Eur J Immunogenet [Internet]. 1998;25:349–55. doi:10.1046/j.1365-2370.1998.00113.x.
   PubMedGoogle Scholar
• Scapin G, Yang X, Prosise WW, McCoy M, Reichert P, Johnston JM, Kashi RS, Strickland C. Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab. Nat Struct Mol Biol [Internet]. 2015 [cited 2017 Mar 1];22:953–58. doi:10.1038/nsmb.3129.
   PubMed Web of Science ®Google Scholar
• Frangione B, Milstein C, Pink JRL. Immunoglobulins: structural Studies of Immunoglobulin G. Nature. 1969;221:145–48. doi:10.1038/221145a0.
   PubMed Web of Science ®Google Scholar
• Liu H, May K. Structural variations, chemical modifications and possible impacts to stability and biological function Disulfide bond structures of IgG molecules © 2012 Landes Bioscience. MAbs. 2012;4:17–23. doi:10.4161/mabs.4.1.18347.
   PubMed Web of Science ®Google Scholar
• Neergaard MS, Nielsen AD, Parshad H, Van De Weert M. Stability of monoclonal antibodies at high-concentration: head-to-head comparison of the IgG1 and IgG4 subclass. J Pharm Sci [Internet]. 2014;103:115–27. doi:10.1002/jps.23788.
   PubMed Web of Science ®Google Scholar
• Ejima D, Tsumoto K, Fukada H, Yumioka R, Nagase K, Arakawa T, Philo JS. Effects of acid exposure on the conformation, stability, and aggregation of monoclonal antibodies. Proteins [Internet]. 2007;66:954–62. doi:10.1002/prot.21243.
   PubMed Web of Science ®Google Scholar
• Angal S, King DJ, Bodmer MW, Turner A, Lawson AD, Roberts G, Pedley B, Adair JR. A single amino acid substitution abolishes the heterogeneity of chimeric mouse/human (IgG4) antibody. Mol Immunol. 1993;30:105–08. doi:10.1016/0161-5890(93)90432-B.
   PubMed Web of Science ®Google Scholar
• Labrijn AF, Buijsse AO, van Den Bremer ETJ, Verwilligen AYW, Bleeker WK, Thorpe SJ, Killestein J, Polman CH, Aalberse RC, Schuurman J, et al. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo. Nat Biotechnol. 2009;27:767–71. doi:10.1038/nbt.1553.
   PubMed Web of Science ®Google Scholar
• van der Neut Kolfschoten M, Schuurman J, Losen M, Bleeker WK, Martínez-Martínez P, Vermeulen E, Den Bleker TH, Wiegman L, Vink T, Aarden LA, et al. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science. 2007;317:1554–57. doi:10.1126/science.1144603.
   PubMed Web of Science ®Google Scholar
• Davies AM, Rispens T, Den Bleker TH, McDonnell JM, Gould HJ, Aalberse RC, Sutton BJ. Crystal structure of the human IgG4 CH3 dimer reveals the role of Arg409 in the mechanism of Fab-arm exchange. Mol Immunol. 2013;54:1–7. doi:10.1016/j.molimm.2012.12.019.
   PubMed Web of Science ®Google Scholar
• Sarmay G, Lund J, Rozsnyay Z, Gergely J, Jefferis R. Mapping and comparison of the interaction sites on the Fc region of IgG responsible for triggering antibody dependent cellular cytotoxicity (ADCC) through different types of human Fc gamma receptor. Mol Immunol. 1992;29:633–39. doi:10.1016/0161-5890(92)90200-H.
   PubMed Web of Science ®Google Scholar
• Tao MH, Morrison SL. Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. J Immunol. 1989;143:2595–601.
   PubMed Web of Science ®Google Scholar
• Walker MR, Lund J, Thompson KM, Jefferis R. Aglycosylation of human IgG1 and IgG3 monoclonal antibodies can eliminate recognition by human cells expressing Fc gamma RI and/or Fc gamma RII receptors. Biochem J. 1989;259:347–53. doi:10.1042/bj2590347.
   PubMed Web of Science ®Google Scholar
• Mueller JP, Giannoni MA, Hartman SL, Elliott EA, Squinto SP, Matis LA, Evans MJ. Humanized porcine VCAM-specific monoclonal antibodies with chimeric IgG2/G4 constant regions block human leukocyte binding to porcine endothelial cells. Mol Immunol. 1997;34:441–52. doi:10.1016/S0161-5890(97)00042-4.
   PubMed Web of Science ®Google Scholar
• Lau C, Gunnarsen KS, Høydahl LS, Andersen JT, Berntzen G, Pharo A, Lindstad JK, Ludviksen JK, Brekke O-L, Barratt-Due A, et al. Chimeric anti-CD14 IGG2/4 hybrid antibodies for therapeutic intervention in pig and human models of inflammation. J Immunol [Internet]. 2013;191:4769–77. doi:10.4049/jimmunol.1301653.
   PubMed Web of Science ®Google Scholar
• An Z, Forrest G, Moore R, Cukan M, Haytko P, Huang L, Vitelli S, Zhao JZ, Lu P, Hua J, et al. IgG2m4, an engineered antibody isotype with reduced Fc function. MAbs. 2009;1:572–79. doi:10.4161/mabs.1.6.10185.
   PubMed Web of Science ®Google Scholar
• Schlothauer T, Herter S, Koller CF, Grau-Richards S, Steinhart V, Spick C, Kubbies M, Klein C, Umaña P, Mössner E. Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions. Protein Eng Des Sel. 2016;29:457–66. doi:10.1093/protein/gzw039.
   PubMed Web of Science ®Google Scholar
• Petkova SB, Akilesh S, Sproule TJ, Christianson GJ, Al Khabbaz H, Brown AC, Presta LG, Meng YG, Roopenian DC. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. International Immunology [Internet]. 2006;18:1759–69. doi:10.1093/intimm/dxl110.
   PubMed Web of Science ®Google Scholar
• Deng R, Loyet KM, Lien S, Iyer S, Deforge LE, Theil F-P, Lowman HB, Fielder PJ, Prabhu S. Pharmacokinetics of humanized monoclonal anti-TNF{alpha} antibody and its FcRn variants in mice and cynomolgus monkeys. Drug Metab Dispos [Internet]. 2010;38:600–05. doi:10.1124/dmd.109.031310.
   PubMed Web of Science ®Google Scholar
• Dall’Acqua WF, Kiener PA, Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem [Internet]. 2006;281:23514–24. doi:10.1074/jbc.M604292200.
   PubMed Web of Science ®Google Scholar
• Robbie GJ, Criste R, Dall’Acqua WF, Jensen K, Patel NK, Losonsky GA, Griffin MP. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013;57:6147–53. doi:10.1128/AAC.01285-13.
   PubMed Web of Science ®Google Scholar
• Hinton PR, Johlfs MG, Xiong JM, Hanestad K, Ong KC, Bullock C, Keller S, Tang MT, Tso JY, Vásquez M, et al. Engineered human IgG antibodies with longer serum half-lives in primates. J Biol Chem [Internet]. 2004;279:6213–16. doi:10.1074/jbc.C300470200.
   PubMed Web of Science ®Google Scholar
• Datta-Mannan A, Witcher DR, Lu J, Wroblewski VJ. Influence of improved FcRn binding on the subcutaneous bioavailability of monoclonal antibodies in cynomolgus monkeys. MAbs [Internet]. 2012;4:267–73. doi:10.4161/mabs.4.2.19364.
   PubMed Web of Science ®Google Scholar
• Gaudinski MR, Coates EE, Houser KV, Chen GL, Yamshchikov G, Saunders JG, Holman LSA, Gordon I, Plummer S, Hendel CS, et al. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. PLoS Med. 2018;15:1–20. doi:10.1371/journal.pmed.1002593.
   Web of Science ®Google Scholar
• Monnet C, Jorieux S, Souyris N, Zaki O, Jacquet A, Fournier N, Crozet F, De Romeuf C, Bouayadi K, Urbain R, et al. Combined glyco- and protein-Fc engineering simultaneously enhance cytotoxicity and half-life of a therapeutic antibody. MAbs. 2014;6:422–36. doi:10.4161/mabs.27854.
   PubMed Web of Science ®Google Scholar
• Booth BJ, Ramakrishnan B, Narayan K, Wollacott AM, Babcock GJ, Shriver Z, Viswanathan K. Extending human IgG half-life using structure-guided design. MAbs [Internet]. 2018:1–13. doi:10.1080/19420862.2018.1490119.
   Web of Science ®Google Scholar
• Igawa T, Tsunoda H, Tachibana T, Maeda A, Mimoto F, Moriyama C, Nanami M, Sekimori Y, Nabuchi Y, Aso Y, et al. Reduced elimination of IgG antibodies by engineering the variable region. Protein Eng Des Sel. 2010;23:385–92. doi:10.1093/protein/gzq009.
   PubMed Web of Science ®Google Scholar
• Labrijn AF, Rispens T, Meesters J, Rose RJ, Den Bleker TH, Loverix S, van Den Bremer ETJ, Neijssen J, Vink T, Lasters I, et al. Species-specific determinants in the IgG CH3 domain enable fab-arm exchange by affecting the noncovalent CH3-CH3 interaction strength. J Immunol. 2011;187:3238–46. doi:10.4049/jimmunol.1100967.
   PubMed Web of Science ®Google Scholar
• Peters SJ, Smales CM, Henry AJ, Stephens PE, West S, Humphreys DP. Engineering an improved IgG4 molecule with reduced disulfide bond heterogeneity and increased fab domain thermal stability. J Biol Chem. 2012;287:24525–33. doi:10.1074/jbc.M112.369744.
   PubMed Web of Science ®Google Scholar
• Harris RJ. Processing of C-terminal lysine and arginine residues of proteins isolated from mammalian cell culture. J Chromatogr A. 1995;705:129–34. doi:10.1016/0021-9673(94)01255-D.
   PubMed Web of Science ®Google Scholar
• Tran B, Grosskopf V, Wang X, Yang J, Walker D, Yu C, McDonald P. Investigating interactions between phospholipase B-Like 2 and antibodies during Protein A chromatography. J Chromatogr A [Internet]. 2016;1438:31–38. doi:10.1016/j.chroma.2016.01.047.
   PubMed Web of Science ®Google Scholar
• Borrok MJ, Wu Y, Beyaz N, Yu XQ, Oganesyan V, Dall’Acqua WF, Tsui P. PH-dependent binding engineering reveals an FcRn affinity threshold that governs IgG recycling. J Biol Chem. 2015;290:4282–90. doi:10.1074/jbc.M114.603712.
   PubMed Web of Science ®Google Scholar