Utility of physiologically based pharmacokinetic modeling to predict inter-antibody variability in monoclonal antibody pharmacokinetics in mice

References

• Mullard A. FDA approves 100th monoclonal antibody product. Nat Rev Drug Discov. 2021;20(7):491–15. doi:10.1038/d41573-021-00079-7.
   PubMed Web of Science ®Google Scholar
• Thomas VA, Balthasar JP. Understanding inter-individual variability in monoclonal antibody disposition. Antibodies (Basel). 2019;8(4):56. doi:10.3390/antib8040056.
   PubMedGoogle Scholar
• Xu Y, Roach W, Sun T, Jain T, Prinz B, Yu T-Y, Torrey J, Thomas J, Bobrowicz P, Vásquez M, et al. Addressing polyspecificity of antibodies selected from an in vitro yeast presentation system: a FACS-based, high-throughput selection and analytical tool. Protein Eng Des Sel. 2013;26(10):663–70. doi:10.1093/protein/gzt047.
   PubMed Web of Science ®Google Scholar
• Russell WMS, Burch RL. The principles of humane experimental technique. Methuen; 1959. https://norecopa.no/textbase/the-principles-of-humane-experimental-technique
   Google Scholar
• Han JJ. FDA modernization act 2.0 allows for alternatives to animal testing. Artif Organs. 2023;47(3):449–50. doi:10.1111/aor.14503.
   PubMed 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(5):385–92. doi:10.1093/protein/gzq009.
   PubMed Web of Science ®Google Scholar
• Li B, Tesar D, Boswell CA, Cahaya HS, Wong A, Zhang J, Meng YG, Eigenbrot C, Pantua H, Diao J, et al. Framework selection can influence pharmacokinetics of a humanized therapeutic antibody through differences in molecule charge. MAbs. 2014;6(5):1255–64. doi:10.4161/mabs.29809.
   PubMed Web of Science ®Google Scholar
• Boswell CA, Tesar DB, Mukhyala K, Theil F-P, Fielder PJ, Khawli LA. Effects of charge on antibody tissue distribution and pharmacokinetics. Bioconjug Chem. 2010;21(12):2153–63. doi:10.1021/bc100261d.
   PubMed Web of Science ®Google Scholar
• Bumbaca Yadav D, Sharma VK, Boswell CA, Hotzel I, Tesar D, Shang Y, Ying Y, Fischer SK, Grogan JL, Chiang EY, et al. Evaluating the use of antibody variable region (Fv) charge as a risk assessment tool for predicting typical cynomolgus Monkey pharmacokinetics. J Biol Chem. 2015;290(50):29732–41. doi:10.1074/jbc.M115.692434.
   PubMed Web of Science ®Google Scholar
• Schoch A, Kettenberger H, Mundigl O, Winter G, Engert J, Heinrich J, Emrich T. Charge-mediated influence of the antibody variable domain on FcRn-dependent pharmacokinetics. Proc Natl Acad Sci U S A. 2015;112(19):5997–6002. doi:10.1073/pnas.1408766112.
   PubMed Web of Science ®Google Scholar
• Datta-Mannan A, Thangaraju A, Leung D, Tang Y, Witcher DR, Lu J, Wroblewski VJ. Balancing charge in the complementarity-determining regions of humanized mAbs without affecting pI reduces non-specific binding and improves the pharmacokinetics. MAbs. 2015;7(3):483–93. doi:10.1080/19420862.2015.1016696.
   PubMed Web of Science ®Google Scholar
• Datta-Mannan A, Lu J, Witcher DR, Leung D, Tang Y, Wroblewski VJ. The interplay of non-specific binding, target-mediated clearance and FcRn interactions on the pharmacokinetics of humanized antibodies. MAbs. 2015;7(6):1084–93. doi:10.1080/19420862.2015.1075109.
   PubMed Web of Science ®Google Scholar
• Jain T, Sun TW, 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 U S A. 2017;114(5):944–49. doi:10.1073/pnas.1616408114.
   PubMed Web of Science ®Google Scholar
• Hötzel I, Theil FP, 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
• 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(52):18601–06. doi:10.1073/pnas.1421779112.
   PubMed Web of Science ®Google Scholar
• García CD, Hadley DJ, Wilson WW, Henry CS. Measuring protein interactions by microchip self-interaction chromatography. Biotechnol Prog. 2003;19(3):1006–10. doi:10.1021/bp025788z.
   PubMed Web of Science ®Google Scholar
• Tessier PM, Sandler SI, Lenhoff AM. Direct measurement of protein osmotic second virial cross coefficients by cross-interaction chromatography. Protein Sci. 2004;13(5):1379–90. doi:10.1110/ps.03419204.
   PubMed Web of Science ®Google Scholar
• Ahamed T, Ottens M, van Dedem GW, van der Wielen LA. Design of self-interaction chromatography as an analytical tool for predicting protein phase behavior. J Chromatogr A. 2005;1089(1–2):111–24. doi:10.1016/j.chroma.2005.06.065.
   PubMed Web of Science ®Google Scholar
• Johnson DH, Parupudi A, Wilson WW, DeLucas LJ. High-throughput self-interaction chromatography: applications in protein formulation prediction. Pharm Res. 2008;26(2):296. doi:10.1007/s11095-008-9737-6.
   PubMed Web of Science ®Google Scholar
• Le Brun V, Friess W, Bassarab S, Mühlau S, Garidel P. A critical evaluation of self-interaction chromatography as a predictive tool for the assessment of protein–protein interactions in protein formulation development: a case study of a therapeutic monoclonal antibody. Eur J Pharm Biopharm. 2010;75(1):16–25. doi:10.1016/j.ejpb.2010.01.009.
   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
• Bengali AN, Tessier PM. Biospecific protein immobilization for rapid analysis of weak protein interactions using self-interaction nanoparticle spectroscopy. Biotechnol Bioeng. 2009;104(2):240–50. doi:10.1002/bit.22392.
   PubMed Web of Science ®Google Scholar
• Jacobs SA, Wu S-J, Feng Y, Bethea D, O’Neil KT. Cross-interaction chromatography: a rapid method to identify highly soluble monoclonal antibody candidates. Pharm Res. 2010;27(1):65. doi:10.1007/s11095-009-0007-z.
   PubMed Web of Science ®Google Scholar
• Schlothauer T, Rueger P, Stracke JO, Hertenberger H, Fingas F, Kling L, Emrich T, Drabner G, Seeber S, Auer J, et al. Analytical FcRn affinity chromatography for functional characterization of monoclonal antibodies. MAbs. 2013;5(4):576–86. doi:10.4161/mabs.24981.
   PubMed Web of Science ®Google Scholar
• Cymer F, Schlothauer T, Knaupp A, Beck H. Evaluation of an FcRn affinity chromatographic method for IgG1-type antibodies and evaluation of IgG variants. Bioanalysis. 2017;9(17):1305–17. doi:10.4155/bio-2017-0109.
   PubMed Web of Science ®Google Scholar
• Wu Q, Lee HY, Wong PY, Jiang G, Gazzano-Santoro H. Development and applications of AlphaScreen-based FcRn binding assay to characterize monoclonal antibodies. J Immunol Methods. 2015;420:31–37. doi:10.1016/j.jim.2015.03.012.
   PubMed Web of Science ®Google Scholar
• Kraft TE, Richter WF, Emrich T, Knaupp A, Schuster M, Wolfert A, Kettenberger H. Heparin chromatography as an in vitro predictor for antibody clearance rate through pinocytosis. MAbs. 2020;12(1):1683432. doi:10.1080/19420862.2019.1683432.
   PubMed Web of Science ®Google Scholar
• Conner KP, Devanaboyina SC, Thomas VA, Rock DA. The biodistribution of therapeutic proteins: mechanism, implications for pharmacokinetics, and methods of evaluation. Pharmacology & Therapeutics. 2020;212:107574. doi:10.1016/j.pharmthera.2020.107574.
   PubMed Web of Science ®Google Scholar
• Liu L, Jacobsen FW, Everds N, Zhuang Y, Yu YB, Li N, Clark D, Nguyen MP, Fort M, Narayanan P, et al. Biological characterization of a Stable Effector Functionless (SEFL) monoclonal antibody scaffold in vitro. J Biol Chem. 2017;292(5):1876–83. doi:10.1074/jbc.M116.748707.
   PubMed Web of Science ®Google Scholar
• Kelly RL, Sun T, Jain T, Caffry I, Yu Y, Cao Y, Lynaugh H, Brown M, Vasquez M, Wittrup KD, et al. High throughput cross-interaction measures for human IgG1 antibodies correlate with clearance rates in mice. MAbs. 2015;7(4):770–77. doi:10.1080/19420862.2015.1043503.
   PubMed Web of Science ®Google Scholar
• Jones HM, Zhang Z, Jasper P, Luo H, Avery LB, King LE, Neubert H, Barton HA, Betts AM, Webster R. A physiologically-based pharmacokinetic model for the prediction of monoclonal antibody pharmacokinetics from in vitro data. CPT Pharmacometrics Syst Pharmacol. 2019;8(10):738–47. doi:10.1002/psp4.12461.
   PubMedGoogle Scholar
• Betts A, Keunecke A, van Steeg TJ, van der Graaf PH, Avery LB, Jones H, Berkhout J, van Steeg TJ, van der Graaf PH. Linear pharmacokinetic parameters for monoclonal antibodies are similar within a species and across different pharmacological targets: a comparison between human, cynomolgus monkey and hFcrn Tg32 transgenic mouse using a population-modeling approach. MAbs. 2018;10(5):751–64. doi:10.1080/19420862.2018.1462429.
   PubMed Web of Science ®Google Scholar
• Avery LB, Wade J, Wang M, Tam A, King A, Piche-Nicholas N, Kavosi MS, Penn S, Cirelli D, Kurz JC, et al. Establishing in vitro in vivo correlations to screen monoclonal antibodies for physicochemical properties related to favorable human pharmacokinetics. MAbs. 2018;10(2):244–55. doi:10.1080/19420862.2017.1417718.
   PubMed Web of Science ®Google Scholar
• Dostalek M, Prueksaritanont T, Kelley RF. Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates. MAbs. 2017;9(5):756–66. doi:10.1080/19420862.2017.1323160.
   PubMed Web of Science ®Google Scholar
• Kelly RL, Yu Y, Sun T, Caffry I, Lynaugh H, Brown M, Jain T, Xu Y, Wittrup KD. Target-independent variable region mediated effects on antibody clearance can be FcRn independent. MAbs. 2016;8(7):1269–75. doi:10.1080/19420862.2016.1208330.
   PubMed Web of Science ®Google Scholar
• Shah DK, Betts AM. Towards a platform PBPK model to characterize the plasma and tissue disposition of monoclonal antibodies in preclinical species and human. J Pharmacokinet Pharmacodyn. 2012;39(1):67–86. doi:10.1007/s10928-011-9232-2.
   PubMed Web of Science ®Google Scholar
• Yao Y-D, Sun T-M, Huang S-Y, Dou S, Lin L, Chen J-N, Ruan J-B, Mao C-Q, Yu F-Y, Zeng M-S, et al. Targeted delivery of PLK1-siRNA by ScFv suppresses Her2+ breast cancer growth and metastasis. Sci Transl Med. 2012;4(130):130ra148. doi:10.1126/scitranslmed.3003601.
   Web of Science ®Google Scholar
• Bumbaca D, Wong A, Drake E, Reyes AE 2nd, Lin BC, Stephan JP, Desnoyers L, Shen BQ, Dennis MS. Highly specific off-target binding identified and eliminated during the humanization of an antibody against FGF receptor 4. MAbs. 2011;3(4):376–86. doi:10.4161/mabs.3.4.15786.
   PubMed Web of Science ®Google Scholar
• Liu S, Verma A, Kettenberger H, Richter WF, Shah DK. Effect of variable domain charge on in vitro and in vivo disposition of monoclonal antibodies. MAbs. 2021;13(1):1993769. doi:10.1080/19420862.2021.1993769.
   PubMed Web of Science ®Google Scholar
• Grinshpun B, Thorsteinson N, Pereira JN, Rippmann F, Nannemann D, Sood VD, Fomekong Nanfack Y. Identifying biophysical assays and in silico properties that enrich for slow clearance in clinical-stage therapeutic antibodies. MAbs. 2021;13(1):1932230. doi:10.1080/19420862.2021.1932230.
   PubMed Web of Science ®Google Scholar
• Souders CA, Nelson SC, Wang Y, Crowley AR, Klempner MS, Thomas W Jr. A novel in vitro assay to predict neonatal Fc receptor-mediated human IgG half-life. MAbs. 2015;7(5):912–21. doi:10.1080/19420862.2015.1054585.
   PubMed Web of Science ®Google Scholar
• Chung S, Nguyen V, Lin YL, Lafrance-Vanasse J, Scales SJ, Lin K, Deng R, Williams K, Sperinde G, Li JJ, et al. An in vitro FcRn- dependent transcytosis assay as a screening tool for predictive assessment of nonspecific clearance of antibody therapeutics in humans. MAbs. 2019;11(5):942–55. doi:10.1080/19420862.2019.1605270.
   PubMed Web of Science ®Google Scholar
• Goulet DR, Watson MJ, Tam SH, Zwolak A, Chiu ML, Atkins WM, Nath A. Toward a combinatorial approach for the prediction of IgG half-life and clearance. Drug Metab Dispos. 2018;46(12):1900–07. doi:10.1124/dmd.118.081893.
   PubMed Web of Science ®Google Scholar
• Hu S, D’Argenio DZ. Predicting monoclonal antibody pharmacokinetics following subcutaneous administration via whole-body physiologically-based modeling. J Pharmacokinet Pharmacodyn. 2020;47(5):385–409. doi:10.1007/s10928-020-09691-3.
   PubMed Web of Science ®Google Scholar
• Hu S, Datta-Mannan A, D’Argenio DZ. Physiologically based modeling to predict monoclonal antibody pharmacokinetics in humans from in vitro physiochemical properties. MAbs. 2022;14(1):2056944. doi:10.1080/19420862.2022.2056944.
   PubMed Web of Science ®Google Scholar
• Avery LB, Wang M, Kavosi MS, Joyce A, Kurz JC, Fan YY, Dowty ME, Zhang M, Zhang Y, Cheng A, et al. Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies. MAbs. 2016;8(6):1064–78. doi:10.1080/19420862.2016.1193660.
   PubMed Web of Science ®Google Scholar
• Raybould MIJ, Marks C, Krawczyk K, Taddese B, Nowak J, Lewis AP, Bujotzek A, Shi J, Deane CM. Five computational developability guidelines for therapeutic antibody profiling. Proc Natl Acad Sci U S A. 2019;116(10):4025–30. doi:10.1073/pnas.1810576116.
   PubMed Web of Science ®Google Scholar
• Wang W, Lu P, Fang Y, Hamuro L, Pittman T, Carr B, Hochman J, Prueksaritanont T. Monoclonal antibodies with identical Fc sequences can bind to FcRn differentially with pharmacokinetic consequences. Drug Metab Dispos. 2011;39(9):1469–77. doi:10.1124/dmd.111.039453.
   PubMed Web of Science ®Google Scholar
• Datta-Mannan A, Brown R, Key S, Cain P, Feng Y. Pharmacokinetic developability and disposition profiles of bispecific antibodies: a case study with two molecules. Antibodies (Basel). 2021;11(1):11. doi:10.3390/antib11010002.
   Google Scholar
• Starr CG, Tessier PM. Selecting and engineering monoclonal antibodies with drug-like specificity. Curr Opin Biotechnol. 2019;60:119–27. doi:10.1016/j.copbio.2019.01.008.
   PubMed Web of Science ®Google Scholar
• Mock M, Jacobitz AW, Langmead CJ, Sudom A, Yoo D, Humphreys SC, Alday M, Alekseychyk L, Angell N, Bi V, et al. Development of in silico models to predict viscosity and mouse clearance using a comprehensive analytical data set collected on 83 scaffold-consistent monoclonal antibodies. MAbs. 2023;15:2256745. doi:10.1080/19420862.2023.2256745.
   PubMed Web of Science ®Google Scholar
• Datta-Mannan A, Croy JE, Schirtzinger L, Torgerson S, Breyer M, Wroblewski VJ. Aberrant bispecific antibody pharmacokinetics linked to liver sinusoidal endothelium clearance mechanism in cynomolgus monkeys. MAbs. 2016;8(5):969–82. doi:10.1080/19420862.2016.1178435.
   PubMed Web of Science ®Google Scholar
• Zhou J, Mateos F, Ober RJ, Ward ES. Conferring the binding properties of the mouse MHC class I-related receptor, FcRn, onto the human ortholog by sequential rounds of site-directed mutagenesis. J Mol Biol. 2005;345(5):1071–81. doi:10.1016/j.jmb.2004.11.014.
   PubMed Web of Science ®Google Scholar
• Denney W, Duvvuri S, Buckeridge C. Simple, automatic noncompartmental analysis: the PKNCA R package. J Pharmacokinet Pharmacodyn. 2015;42:S65–S65.
   Web of Science ®Google Scholar
• Wei T, Simko V. R package “corrplot”: visualization of a correlation matrix (version 0.84). Vienna; 2017.
   Google Scholar