Subcutaneous bioavailability of therapeutic antibodies as a function 
of FcRn binding affinity in mice

References

• Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007; 7:715 - 725
   PubMed Web of Science ®Google Scholar
• Montoyo HP, Vaccaro C, Hafner M, Ober RJ, Mueller W, Ward ES. Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice. Proc Natl Acad Sci USA 2009; 106:2788 - 2793; PMID: 19188594; http://dx.doi.org/10.1073/pnas.0810796106
   PubMed Web of Science ®Google Scholar
• Dall'Acqua WF, Woods RM, Ward ES, Palaszynski SR, Patel NK, Brewah YA, et al. Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences. J Immunol 2002; 169:5171 - 5180; PMID: 12391234
   PubMed Web of Science ®Google Scholar
• Gan Z, Ram S, Vaccaro C, Ober RJ, Ward ES. Analyses of the recycling receptor, FcRn, in live cells reveal novel pathways for lysosomal delivery. Traffic 2009; 10:600 - 614; PMID: 19192244; http://dx.doi.org/10.1111/j.1600-0854.2009.00887.x
   PubMed Web of Science ®Google Scholar
• Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2008; 84:548 - 558; PMID: 18784655; http://dx.doi.org/10.1038/clpt.2008.170
   PubMed Web of Science ®Google Scholar
• Deng R, Loyet KM, Lien S, Iyer S, DeForge LE, Theil FP, et al. Pharmacokinetics of humanized monoclonal anti-tumor necrosis factor-alpha antibody and its neonatal Fc receptor variants in mice and cynomolgus monkeys. Drug Metab Dispos 2010; 38:600 - 605; PMID: 20071453; http://dx.doi.org/10.1124/dmd.109.031310
   PubMed Web of Science ®Google Scholar
• Garg A, Balthasar JP. Physiologically-based pharmacokinetic (PBPK) model to predict IgG tissue kinetics in wild-type and FcRn-knockout mice. J Pharmacokinet Pharmacodyn 2007; 34:687 - 709; PMID: 17636457; http://dx.doi.org/10.1007/s10928-007-9065-1
   PubMed Web of Science ®Google Scholar
• Borvak J, Richardson J, Medesan C, Antohe F, Radu C, Simionescu M, et al. Functional expression of the MHC class I-related receptor, FcRn, in endothelial cells of mice. Int Immunol 1998; 10:1289 - 1298; PMID: 9786428; http://dx.doi.org/10.1093/intimm/10.9.1289
   PubMed Web of Science ®Google Scholar
• Zhu X, Meng G, Dickinson BL, Li X, Mizoguchi E, Miao L, et al. MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages and dendritic cells. J Immunol 2001; 166:3266 - 3276; PMID: 11207281
   PubMed Web of Science ®Google Scholar
• Zhou J, Johnson JE, Ghetie V, Ober RJ, Ward ES. Generation of mutated variants of the human form of the MHC class I-related receptor, FcRn, with increased affinity for mouse immunoglobulin G. J Mol Biol 2003; 332:901 - 913; PMID: 12972260; http://dx.doi.org/10.1016/S0022-2836(03)00952-5
   PubMed Web of Science ®Google Scholar
• Kim JK, Tsen MF, Ghetie V, Ward ES. Identifying amino acid residues that influence plasma clearance of murine IgG1 fragments by site-directed mutagenesis. Eur J Immunol 1994; 24:542 - 548; PMID: 8125126; http://dx.doi.org/10.1002/eji.1830240308
   PubMed Web of Science ®Google Scholar
• Yeung YA, Leabman MK, Marvin JS, Qiu J, Adams CW, Lien S, et al. Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates. J Immunol 2009; 182:7663 - 7671; PMID: 19494290; http://dx.doi.org/10.4049/jimmunol.0804182
   PubMed Web of Science ®Google Scholar
• Hansen RJ, Balthasar JP. Pharmacokinetic/pharmacodynamic modeling of the effects of intravenous immunoglobulin on the disposition of antiplatelet antibodies in a rat model of immune thrombocytopenia. J Pharm Sci 2003; 92:1206 - 1215; PMID: 12761810; http://dx.doi.org/10.1002/jps.10364
   PubMed Web of Science ®Google Scholar
• Deng R, Balthasar JP. Pharmacokinetic/pharmacodynamic modeling of IVIG effects in a murine model of immune thrombocytopenia. J Pharm Sci 2007; 96:1625 - 1637; PMID: 17238194; http://dx.doi.org/10.1002/jps.20828
   PubMed Web of Science ®Google Scholar
• Shields RL, Namenuk AK, Hong K, Meng YG, Rae J, Briggs J, et al. High resolution mapping of the binding site on human IgG1 for Fcgamma RI, Fcgamma RII, Fcgamma RIII and FcRn and design of IgG1 variants with improved binding to the Fcgamma R. J Biol Chem 2001; 276:6591 - 6604; PMID: 11096108; http://dx.doi.org/10.1074/jbc.M009483200
   PubMed Web of Science ®Google Scholar
• Petkova SB, Akilesh S, Sproule TJ, Christianson GJ, Al Khabbaz H, Brown AC, et al. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int Immunol 2006; 18:1759 - 1769; PMID: 17077181; http://dx.doi.org/10.1093/intimm/dxl110
   PubMed Web of Science ®Google Scholar
• Zuckier LS, Georgescu L, Chang CJ, Scharff MD, Morrison SL. The use of severe combined immunodeficiency mice to study the metabolism of human immunoglobulin G. Cancer 1994; 73:794 - 799; PMID: 8306262; http://dx.doi.org/10.1002/1097-0142(19940201)73:3+<794::AID-CNCR2820731308>3.0.CO;2-A
   PubMed Web of Science ®Google Scholar
• Zuckier LS, Chang CJ, Scharff MD, Morrison SL. Chimeric human-mouse IgG antibodies with shuffled constant region exons demonstrate that multiple domains contribute to in vivo half-life. Cancer Res 1998; 58:3905 - 3908; PMID: 9731501
   PubMed Web of Science ®Google Scholar
• Roopenian DC, Christianson GJ, Sproule TJ, Brown AC, Akilesh S, Jung N, et al. The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis and fate of IgG-Fc-coupled drugs. J Immunol 2003; 170:3528 - 3533; PMID: 12646614
   PubMed Web of Science ®Google Scholar
• Datta-Mannan A, Witcher DR, Tang Y, Watkins J, Wroblewski VJ. Monoclonal antibody clearance. Impact of modulating the interaction of IgG with the neonatal Fc receptor. J Biol Chem 2007; 282:1709 - 1717; PMID: 17135257; http://dx.doi.org/10.1074/jbc.M607161200
   PubMed Web of Science ®Google Scholar
• Datta-Mannan A, Witcher DR, Tang Y, Watkins J, Jiang W, Wroblewski VJ. Humanized IgG1 variants with differential binding properties to the neonatal Fc receptor: relationship to pharmacokinetics in mice and primates. Drug Metab Dispos 2007; 35:86 - 94; PMID: 17050651; http://dx.doi.org/10.1124/dmd.106.011734
   PubMed Web of Science ®Google Scholar
• Antohe F, Radulescu L, Gafencu A, Ghetie V, Simionescu M. Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells. Hum Immunol 2001; 62:93 - 105; PMID: 11182218; http://dx.doi.org/10.1016/S0198-8859(00)00244-5
   PubMed Web of Science ®Google Scholar
• Mahl JA, Vogel BE, Court M, Kolopp M, Roman D, Nogués V. The minipig in dermatotoxicology: methods and challenges. Exp Toxicol Pathol 2006; 57:341 - 345; PMID: 16713702; http://dx.doi.org/10.1016/j.etp.2006.03.004
   PubMed Web of Science ®Google Scholar
• Kagan L, Turner MR, Balu-Iyer SV, Mager DE. Subcutaneous Absorption of Monoclonal Antibodies: Role of Dose, Site of Injection and Injection Volume on Rituximab Pharmacokinetics in Rats. Pharm Res 2011; In press PMID: 21887597; http://dx.doi.org/10.1007/s11095-011-0578-3
   PubMed Web of Science ®Google Scholar
• Lu Y, Vernes JM, Chiang N, Ou Q, Ding J, Adams C, et al. Identification of IgG(1) variants with increased affinity to FcγRIIIa and unaltered affinity to FcγRI and FcRn: comparison of soluble receptor-based and cell-based binding assays. J Immunol Methods 2011; 365:132 - 141; PMID: 21185301; http://dx.doi.org/10.1016/j.jim.2010.12.014
   PubMed Web of Science ®Google Scholar
• Bosma MJ, Carroll AM. The SCID mouse mutant: definition, characterization and potential uses. Annu Rev Immunol 1991; 9:323 - 350; PMID: 1910681; http://dx.doi.org/10.1146/annurev.iy.09.040191.001543
   PubMed Web of Science ®Google Scholar
• Michel RB, Ochakovskaya R, Mattes MJ. Rapid blood clearance of injected mouse IgG2a in SCID mice. Cancer Immunol Immunother 2002; 51:547 - 556; PMID: 12384806; http://dx.doi.org/10.1007/s00262-002-0319-x
   PubMed Web of Science ®Google Scholar
• D'Argenio D, Schumitzky A, Wang X. ADAPT 5 User's Guide: Pharmacokinetic/Pharmacodynamic Systems Analysis Software. Biomedical Simulations Resource, Los Angeles 2009;
   Google Scholar