Key Physicochemical Characteristics Influencing ADME Properties of Therapeutic Proteins

  • Xing JingEmail author
  • Yan Hou
  • William Hallett
  • Chandrahas G. Sahajwalla
  • Ping Ji
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1148)


Therapeutic proteins are a rapidly growing class of drugs in clinical settings. The pharmacokinetics (PK) of therapeutic proteins relies on their absorption, distribution, metabolism, and excretion (ADME) properties. Moreover, the ADME properties of therapeutic proteins are impacted by their physicochemical characteristics. Comprehensive evaluation of these characteristics and their impact on ADME properties are critical to successful drug development. This chapter summarizes all relevant physicochemical characteristics and their effect on ADME properties of therapeutic proteins.


Protein therapeutics Physicochemical characteristics Pharmacokinetics (PK) ADME 



Anti-drug antibody


Antibody drug conjugate


Absorption, distribution, metabolism, excretion


Asialoglycoprotein receptor


Circular dichroism


Capillary isoelectric focusing


Dynamic light scattering


Differential scanning calorimetry


Differential scanning fluorimetry


Extracellular matrix


Fragment antigen-binding domain


Fragment crystallizable domain


Neonatal Fc receptor


Fc gamma receptors


U.S. Food and Drug Administration


Förster resonance energy transfer




Immunoglobulin G


Isothermal titration calorimetry


Monoclonal antibody


Mannose receptor


Microscale thermophoresis


Molecular weight


Polyethylene glycol


Isoelectric point






Surface plasmon resonance




Time to peak concentration


Target mediated drug disposition


Tumor necrosis factor


Volume of distribution



The authors sincerely thank the critical review of the chapter from Dr. Sarah Schrieber and Dr. Vitaliy Klimov from Office of Clinical Pharmacology, FDA.


  1. Beck A, Reichert JM (2011) Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies. MAbs 3:415–416PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bernhards RC, Jing X, Vogelaar NJ, Robinson H, Schubot FD (2009) Structural evidence suggests that antiactivator ExsD from Pseudomonas aeruginosa is a DNA binding protein. Protein Sci 18(3):503–513PubMedPubMedCentralCrossRefGoogle Scholar
  3. Boswell CA, Tesar DB, Mukhyala K, Theil FP, Fielder PJ, Khawli LA (2010) Effects of charge on antibody tissue distribution and pharmacokinetics. Bioconjug Chem 21(12):2153–2163CrossRefPubMedGoogle Scholar
  4. Brange J, Volund A (1999) Insulin analogs with improved pharmacokinetic profiles. Adv Drug Deliv Rev 35:307–335PubMedCrossRefGoogle Scholar
  5. Brange J, Ribel U, Hansen JF, Dodson G, Hansen MT, Havelund S, Melberg SG, Norris F, Norris K, Snel L, Sorensen AR, Voigt HO (1988) Monomeric insulins obtained by protein engineering and their medical implications. Nature 333:679–682PubMedCrossRefGoogle Scholar
  6. Brange J, Owens DR, Kang S, Volund A (1990) Monomeric insulins and their experimental and clinical implications. Diabetes Care 13:923–954PubMedCrossRefGoogle Scholar
  7. Bumbaca D, Boswell CA, Fielder PJ, Khawli LA (2012) Physiochemical and biochemical factors influencing the pharmacokinetics of antibody therapeutics. AAPS J 14:554–558PubMedPubMedCentralCrossRefGoogle Scholar
  8. Caliceti P, Veronese FM (2003) Pharmacokinetic and biodistribution properties of poly (ethylene glycol)-protein conjugates. Adv Drug Deliv Rev 55:1261–1277PubMedCrossRefGoogle Scholar
  9. Cavagna L, Taylor WJ (2014) The emerging role of biotechnological drugs in the treatment of gout. Biomed Res Int 2014:264859. Scholar
  10. Coffey GP, Stefanich E, Palmieri S, Eckert R, Padilla-Eagar J, Fielder PJ, Pippig S (2004) In vitro internalization, intracellular transport, and clearance of an anti-CD11a antibody (Raptiva) by human T-cells. J Pharmacol Exp Ther 310(3):896–904PubMedCrossRefGoogle Scholar
  11. Dall’Acqua WF, Woods RM, Ward ES, Palaszynski SR, Patel NK, Brewah YA, Wu H, Kiener PA, Langermann S (2002) Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences. J Immunol 169(9):5171–5180PubMedCrossRefGoogle Scholar
  12. Dall’Acqua WF, Kiener PA, Wu H (2006) Properties of human IgG1s engineered for enhanced binding to the neonatal fc receptor (FcRn). J Biol Chem 281(33):23514–23524PubMedCrossRefGoogle Scholar
  13. Datta-Mannan A, Witcher DR, Lu J, Wroblewski VJ (2012) Influence of improved FcRn binding on the subcutaneous bioavailability of monoclonal antibodies in cynomolgus monkeys. MAbs 4(2):267–273PubMedPubMedCentralCrossRefGoogle Scholar
  14. Davies KA, Erlendsson K, Beynon HL, Peters AM, Steinsson K, Valdimarsson H, Walport MJ (1993) Splenic uptake of immune complexes in man is complement-dependent. J Immunol 151(7):3866–3873PubMedGoogle Scholar
  15. Deng R, Meng YG, Hoyte K, Lutman J, Lu Y, Iyer S, DeForge LE, Theil FP, Fielder PJ, Prabhu S (2012) Subcutaneous bioavailability of therapeutic antibodies as a function of FcRn binding affinity in mice. MAbs 4:101–109PubMedPubMedCentralCrossRefGoogle Scholar
  16. Dorai H, Ganguly S (2014) Mammalian cell-produced therapeutic proteins: heterogeneity derived from protein degradation. Curr Opin Biotechnol 30:198–204PubMedCrossRefGoogle Scholar
  17. Dostalek M, Gardner I, Gurbaxani BM, Rose RH, Chetty M (2013) Pharmacokinetics, pharmacodynamics and physiologically-based pharmacokinetic modelling of monoclonal antibodies. Clin Pharmacokinet 52(2):83–124CrossRefPubMedGoogle Scholar
  18. Egrie JC, Browne JK (2002) Development and characterization of darbepoetin alfa. Oncology (Williston Park) 16:13–22Google Scholar
  19. Fabini E, Danielson UH (2017) Monitoring drug-serum protein interactions for early ADME prediction through Surface Plasmon Resonance technology. J Pharm Biomed Anal 144:188–194PubMedCrossRefGoogle Scholar
  20. FDA Approved Drug Products Database of Labeling (2018) U.S. Food and Drug Administration. Accessed 01 Mar 2018
  21. Ghetie V, Ward ES (2000) Multiple roles for the major histocompatibility complex class I-related receptor FcRn. Annu Rev Immunol 18:739–766PubMedCrossRefPubMedCentralGoogle Scholar
  22. Ghetie V, Popov S, Borvak J, Radu C, Matesoi D, Medesan C, Ober RJ, Ward ES (1997) Increasing the serum persistence of an IgG fragment by random mutagenesis. Nat Biotechnol 15(7):637–640PubMedCrossRefPubMedCentralGoogle Scholar
  23. Graff CP, Wittrup KD (2003) Theoretical analysis of antibody targeting of tumor spheroids: importance of dosage for penetration, and affinity for retention. Cancer Res 63(6):1288–1296PubMedPubMedCentralGoogle Scholar
  24. Hamidi M, Azadi A, Rafiei P (2006) Pharmacokinetic consequences of pegylation. Drug Deliv 13(6):399–409PubMedCrossRefPubMedCentralGoogle Scholar
  25. Hanlon AD, Larkin MI, Reddick RM (2010) Free-solution, label-free protein-protein interactions characterized by dynamic light scattering. Biophys J 98(2):297–304PubMedPubMedCentralCrossRefGoogle Scholar
  26. Higel F, Seidl A, Sörgel F, Friess W (2016) N-glycosylation heterogeneity and the influence on structure, function and pharmacokinetics of monoclonal antibodies and Fc fusion proteins. Eur J Pharm Biopharm 100:94–100PubMedCrossRefGoogle Scholar
  27. Hilgenfeld R, Seipke G, Berchtold H, Owens DR (2014) The evolution of insulin glargine and its continuing contribution to diabetes care. Drugs 74(8):911–927PubMedPubMedCentralCrossRefGoogle Scholar
  28. Igawa T, Tsunoda H, Tachibana T, Maeda A, Mimoto F, Moriyama C, Nanami M, Sekimori Y, Nabuchi Y, Aso Y, Hattori K (2010) Reduced elimination of IgG antibodies by engineering the variable region. Protein Eng Des Sel 23(5):385–392PubMedCrossRefPubMedCentralGoogle Scholar
  29. Jevsevar S, Kunstelj M, Porekar VG (2010) PEGylation of therapeutic proteins. Biotechnol J 5(1):113–128PubMedCrossRefPubMedCentralGoogle Scholar
  30. Jing X, Jaw J, Robinson HH, Schubot FD (2010) Crystal structure and oligomeric state of the RetS signaling kinase sensory domain. Proteins 78(7):1631–1640PubMedPubMedCentralGoogle Scholar
  31. Johnson CM (2013) Differential scanning calorimetry as a tool for protein folding and stability. Arch Biochem Biophys 531(1–2):100–109PubMedCrossRefGoogle Scholar
  32. Kagan L (2014) Pharmacokinetic modeling of the subcutaneous absorption of therapeutic proteins. Drug Metab Dispos 42(11):1890–1905PubMedCrossRefGoogle Scholar
  33. Kanda Y, Yamada T, Mori K, Okazaki A, Inoue M, Kitajima-Miyama K, Kuni-Kamochi R, Nakano R, Yano K, Kakita S, Shitara K, Satoh M (2007) Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose, hybrid, and complex types. Glycobiology 17(1):104–118PubMedCrossRefGoogle Scholar
  34. Kanodia JS, Gadkar K, Bumbaca D, Zhang Y, Tong RK, Luk W, Hoyte K, Lu Y, Wildsmith KR, Couch JA, Watts RJ, Dennis MS, Ernst JA, Scearce-Levie K, Atwal JK, Ramanujan S, Joseph S (2016) Prospective design of anti-transferrin receptor bispecific antibodies for optimal delivery into the human brain. CPT Pharmacometrics Syst Pharmacol 5(5):283–291PubMedPubMedCentralCrossRefGoogle Scholar
  35. Keizer RJ, Huitema AD, Schellens JH, Beijnen JH (2010) Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet 49(8):493–507PubMedCrossRefGoogle Scholar
  36. Kelly SM, Price NC (2000) The use of circular dichroism in the investigation of protein structure and function. Curr Protein Pept Sci 1(4):349–384CrossRefGoogle Scholar
  37. Khawli LA, Goswami S, Hutchinson R, Kwong ZW, Yang J, Wang X, Yao Z, Sreedhara A, Cano T, Tesar D, Nijem I, Allison DE, Wong PY, Kao YH, Quan C, Joshi A, Harris RJ, Motchnik P (2010) Charge variants in IgG1: isolation, characterization, in vitro binding properties and pharmacokinetics in rats. MAbs 2:613–624PubMedPubMedCentralCrossRefGoogle Scholar
  38. Kinnunen HM, Mrsny RJ (2014) Improving the outcomes of biopharmaceutical delivery via the SC route by understanding the chemical, physical and physiological properties of the SC injection site. J Control Release 182:22–32PubMedCrossRefGoogle Scholar
  39. Kuo TT, Baker K, Yoshida M, Qiao SW, Aveson VG, Lencer WI (2010) Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol 30(6):777–789PubMedPubMedCentralCrossRefGoogle Scholar
  40. Lambert JM (2005) Drug-conjugated monoclonal antibodies for the treatment of cancer. Curr Opin Pharmacol 5:543–549PubMedCrossRefGoogle Scholar
  41. Lammerts van Bueren JJ, Bleeker WK, Bøgh HO, Houtkamp M, Schuurman J, van de Winkel JG, Parren PW (2006) Effect of target dynamics on pharmacokinetics of a novel therapeutic antibody against the epidermal growth factor receptor: implications for the mechanisms of action. Cancer Res 66(15):7630–7638PubMedCrossRefGoogle Scholar
  42. Lencer WI, Blumberg RS (2005) A passionate kiss, then run-exocytosis and recycling of IgG by FcRn. Trends Cell Biol 15(1):5–9PubMedCrossRefGoogle Scholar
  43. Levêque D, Wisniewski S, Jehl F (2005) Pharmacokinetics of therapeutic monoclonal antibodies used in oncology. Anticancer Res 25(3c):2327–2344PubMedGoogle Scholar
  44. Li B, Tesar D, Boswell CA, Cahaya HS, Wong A, Zhang J, Meng YG, Eigenbrot C, Pantua H, Diao J, Kapadia SB, Deng R, Kelley RF (2014) Framework selection can influence pharmacokinetics of a humanized therapeutic antibody through differences in molecule charge. MAbs 6(5):1255–1264PubMedPubMedCentralCrossRefGoogle Scholar
  45. List T, Neri D (2012) Biodistribution studies with tumor-targeting bispecific antibodies reveal selective accumulation at the tumor site. MAbs 4(6):775–783PubMedPubMedCentralCrossRefGoogle Scholar
  46. Liu L (2015) Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins. J Pharm Sci 104(6):1866–1884PubMedCrossRefGoogle Scholar
  47. Liu L (2018) Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins. Protein Cell 9(1):15–32PubMedCrossRefGoogle Scholar
  48. Liu L, Stadheim A, Hamuro L, Pittman T, Wang W, Zha D, Hochman J, Prueksaritanont T (2011) Pharmacokinetics of IgG1 monoclonal antibodies produced in humanized Pichia pastoris with specific glycoforms: a comparative study with CHO produced materials. Biologicals 39:205–210PubMedCrossRefGoogle Scholar
  49. Lobo ED, Hansen RJ, Balthasar JP (2004) Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci 93(11):2645–2668PubMedCrossRefGoogle Scholar
  50. Lorber B, Fischer F, Bailly M, Roy H, Kern D (2012) Protein analysis by dynamic light scattering: methods and techniques for students. Biochem Mol Biol Educ 40(6):372–382PubMedCrossRefPubMedCentralGoogle Scholar
  51. Macielag MJ (2012) Chemical properties of antimicrobials and their uniqueness. In: Dougherty T, Pucci M (eds) Antibiotic discovery and development. Springer, Boston, pp 793–820CrossRefGoogle Scholar
  52. Mager DE (2006) Target-mediated drug disposition and dynamics. Biochem Pharmacol 72(1):1–10PubMedCrossRefPubMedCentralGoogle Scholar
  53. Martin WL, West AP Jr, Gan L, Bjorkman PJ (2001) Crystal structure at 2.8Å of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell 7(4):867–877PubMedCrossRefPubMedCentralGoogle Scholar
  54. Martins JP, Kennedy PJ, Santos HA, Barrias C, Sarmento B (2016) A comprehensive review of the neonatal Fc receptor and its application in drug delivery. Pharmacol Ther 161:22–39PubMedCrossRefGoogle Scholar
  55. McLennan DN, Porter CJ, Charman SA (2005) Subcutaneous drug delivery and the role of the lymphatics. Drug Discov Today Technol 2:89–96PubMedCrossRefGoogle Scholar
  56. Mellman I, Plutner H (1984) Internalization and degradation of macrophage Fc receptors bound to polyvalent immune complexes. J Cell Biol 98:1170–1177PubMedCrossRefGoogle Scholar
  57. Owens DR (2012) Optimizing treatment strategies with insulin glargine in type 2 diabetes. Expert Rev Endocrinol Metab 7(4):377–393PubMedCrossRefGoogle Scholar
  58. Palmieri LC, Favero-Retto MP, Lourenco D, Lima LM (2013) A T3R3 hexamer of the human insulin variant B28Asp. Physicochem Chem 173–174:1–7Google Scholar
  59. Pechtner V, Karanikas CA, García-Pérez LE, Glaesner W (2017) A new approach to drug therapy: Fc-fusion technology. Prim Health Care 7:1Google Scholar
  60. Pergande MR, Cologna SM (2017) Isoelectric point separations of peptides and proteins. Proteomes 5(1)PubMedCentralCrossRefGoogle Scholar
  61. Pierce MM, Raman CS, Nall BT (1999) Isothermal titration calorimetry of protein-protein interactions. Methods 19(2):213–221PubMedCrossRefPubMedCentralGoogle Scholar
  62. Porter CJ, Charman SA (2000) Lymphatic transport of proteins after subcutaneous administration. J Pharm Sci 89:297–310PubMedCrossRefPubMedCentralGoogle Scholar
  63. Press OW, Hansen JA, Farr A (1988) Endocytosis and degradation of murine anti-human CD3 monoclonal antibodies by normal and malignant T-lymphocytes. Cancer Res 48(8):2249–2257PubMedPubMedCentralGoogle Scholar
  64. Qiu Y, Lv W, Xu M, Xu Y (2016) Single chain antibody fragments with pH dependent binding to FcRn enabled prolonged circulation of therapeutic peptide in vivo. J Control Release 229:37–47PubMedCrossRefPubMedCentralGoogle Scholar
  65. Ratanji KD, Derrick JP, Dearman RJ, Kimber I (2014) Immunogenicity of therapeutic proteins: influence of aggregation. J Immunotoxicol 11(2):99–109PubMedCrossRefPubMedCentralGoogle Scholar
  66. Rehlaender BN, Cho MJ (1998) Antibodies as carrier proteins. Pharm Res 15(11):1652–1656PubMedCrossRefPubMedCentralGoogle Scholar
  67. Richette P, Frazier A, Bardin T (2014) Pharmacokinetics considerations for gout treatments. Expert Opin Drug Metab Toxicol 10(7):949–957PubMedCrossRefPubMedCentralGoogle Scholar
  68. Richter WF, Bhansali SG, Morris ME (2012) Mechanistic determinants of biotherapeutics absorption following SC administration. AAPSJ 14(3):559–570PubMedCrossRefPubMedCentralGoogle Scholar
  69. Righetti PG (2004) Determination of the isoelectric point of proteins by capillary isoelectric focusing. J Chromatogr A 1037(1–2):491–499PubMedCrossRefPubMedCentralGoogle Scholar
  70. Schwartz AL (1991) Trafficking of asialoglycoproteins and the asialoglycoprotein receptor. Target Diagn Ther 4:3–39Google Scholar
  71. Senter PD (2009) Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 13:235–244PubMedCrossRefGoogle Scholar
  72. Shi S (2014) Biologics: an update and challenge of their pharmacokinetics. Curr Drug Metab 15(3):271–290PubMedCrossRefGoogle Scholar
  73. Sockolosky JT, Szoka FC (2015) The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy. Adv Drug Deliv Rev 91:109–124PubMedPubMedCentralCrossRefGoogle Scholar
  74. Song K, Yoon IS, Kim NA, Kim DH, Lee J, Lee HJ, Lee S, Choi S, Choi MK, Kim HH, Jeong SH, Son WS, Kim DD, Shin YK (2014) Glycoengineering of interferon-β 1a improves its physicochemical and pharmacokinetic properties. PLoS One 9(5):e96967PubMedPubMedCentralCrossRefGoogle Scholar
  75. Stefanich EG, Ren S, Danilenko DM, Lim A, Song A, Iyer S, Fielder PJ (2008) Evidence for an asialoglycoprotein receptor on nonparenchymal cells for O-linked glycoproteins. J Pharmacol Exp Ther 327:308–315PubMedCrossRefGoogle Scholar
  76. Strohl WR (2015) Fusion proteins for half-life extension of biologics as a strategy to make biobetters. BioDrugs 29(4):215–239PubMedPubMedCentralCrossRefGoogle Scholar
  77. Strohmeier GR, Brunkhorst BA, Seetoo KF, Meshulam T, Bernardo J, Simons ER (1995) Role of the FCγR subclasses FcγRII and FcγRIII in the activation of human neutrophils by low and high valency immune complexes. J Leukoc Biol 58(4):415–422PubMedCrossRefGoogle Scholar
  78. Supersaxo A, Hein WR, Steffen H (1990) Effect of molecular weight on the lymphatic absorption of water-soluble compounds following subcutaneous administration. Pharm Res 7(2):167–169PubMedCrossRefGoogle Scholar
  79. Tabrizi M, Bornstein GG, Suria H (2010) Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease. AAPS J 12(1):33–43PubMedCrossRefGoogle Scholar
  80. Thurber GM, Schmidt MM, Wittrup KD (2008) Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Adv Drug Deliv Rev 60(12):1421–1434PubMedPubMedCentralCrossRefGoogle Scholar
  81. Tibbitts J, Canter D, Graff R, Smith A, Khawli LA (2016) Key factors influencing ADME properties of therapeutic proteins: a need for ADME characterization in drug discovery and development. MAbs 8(2):229–245PubMedCrossRefGoogle Scholar
  82. Vaccaro C, Zhou J, Ober RJ, Ward ES (2005) Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. Nat Biotechnol 23(10):1283–1288CrossRefGoogle Scholar
  83. Veronese FM, Pasut G (2005) PEGylation, successful approach to drug delivery. Drug Discov Today 10(21):1451–1458PubMedCrossRefGoogle Scholar
  84. Vidarsson G, Dekkers G, Rispens T (2014) IgG subclasses and allotypes: from structure to effector functions. Front Immunol 5:520PubMedPubMedCentralCrossRefGoogle Scholar
  85. Volund A, Brange J, Drejer K, Jensen I, Markussen J, Ribel U, Sorensen AR, Schlichtkrull J (1991) In vitro and in vivo potency of insulin analogues designed for clinical use. Diabet Med 8(9):839–847PubMedCrossRefGoogle Scholar
  86. Vugmeyster Y, Xu X, Theil FP, Khawli LA, Leach MW (2012) Pharmacokinetics and toxicology of therapeutic proteins: advances and challenges. World J Biol Chem 3(4):73–92PubMedPubMedCentralCrossRefGoogle Scholar
  87. Wang W, Wang EQ, Balthasar J (2008) Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 84(5):548–558PubMedCrossRefGoogle Scholar
  88. Wang W, Erbe AK, Hank JA, Morris ZS, Sondel PM (2015) NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. Front Immunol 6:368PubMedPubMedCentralGoogle Scholar
  89. Weinstein JN, van Osdol W (1992) The macroscopic and microscopic pharmacology of monoclonal antibodies. Int J Immunopharmacol 14(3):457–463PubMedCrossRefGoogle Scholar
  90. Winkelhake JL, Nicolson GL (1976) Aglycosylantibody. Effects of exoglycosidase treatments on autochthonous antibody survival time in the circulation. J Biol Chem 251:1074–1080PubMedPubMedCentralGoogle Scholar
  91. Wright A, Morrison SL (1994) Effect of altered CH2-associated carbohydrate structure on the functional properties and in vivo fate of chimeric mouse-human immunoglobulin G1. J Exp Med 180:1087–1096PubMedCrossRefPubMedCentralGoogle Scholar
  92. Wright A, Sato Y, Okada T, Chang K, Endo T, Morrison S (2000) In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure. Glycobiology 10:1347–1355PubMedCrossRefPubMedCentralGoogle Scholar
  93. Wu AM, Senter PD (2005) Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 23:1137–1146PubMedCrossRefPubMedCentralGoogle Scholar
  94. Yang BB, Kido A (2011) Pharmacokinetics and pharmacodynamics of pegfilgrastim. Clin Pharmacokinet 50(5):295–306PubMedCrossRefPubMedCentralGoogle Scholar
  95. Yu M, Brown D, Reed C, Chung S, Lutman J, Stefanich E, Wong A, Stephan JP, Bayer R (2012) Production, characterization, and pharmacokinetic properties of antibodies with N-linked mannose-5 glycans. MAbs 4:475–487PubMedPubMedCentralCrossRefGoogle Scholar
  96. Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, Lazar GA, Roopenian DC, Desjarlais JR (2010) Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 28(2):157–159PubMedPubMedCentralCrossRefGoogle Scholar
  97. Zhao L, Shang EY, Sahajwalla CG (2012) Application of pharmacokinetics-pharmacodynamics/clinical response modeling and simulation for biologics drug development. J Pharm Sci 101(12):4367–4382PubMedCrossRefPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Xing Jing
    • 1
    Email author
  • Yan Hou
    • 1
  • William Hallett
    • 1
  • Chandrahas G. Sahajwalla
    • 1
  • Ping Ji
    • 1
  1. 1.U.S. Food and Drug Administration, Office of Clinical Pharmacology, DV IISilver SpringUSA

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