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Key Physicochemical Characteristics Influencing ADME Properties of Therapeutic Proteins

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Therapeutic Enzymes: Function and Clinical Implications

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1148))

Abstract

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.

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Abbreviations

ADA:

Anti-drug antibody

ADC:

Antibody drug conjugate

ADME:

Absorption, distribution, metabolism, excretion

ASGPR:

Asialoglycoprotein receptor

CD:

Circular dichroism

cIEF:

Capillary isoelectric focusing

DLS:

Dynamic light scattering

DSC:

Differential scanning calorimetry

DSF:

Differential scanning fluorimetry

ECM:

Extracellular matrix

Fab:

Fragment antigen-binding domain

Fc:

Fragment crystallizable domain

FcRn:

Neonatal Fc receptor

FcγR:

Fc gamma receptors

FDA:

U.S. Food and Drug Administration

FRET:

Förster resonance energy transfer

GlcNAc:

N-acetylglucosamine

IgG:

Immunoglobulin G

ITC:

Isothermal titration calorimetry

mAb:

Monoclonal antibody

ManR:

Mannose receptor

MST:

Microscale thermophoresis

MW:

Molecular weight

PEG:

Polyethylene glycol

pI:

Isoelectric point

PK:

Pharmacokinetics

SC:

Subcutaneous

SPR:

Surface plasmon resonance

T1/2:

Half-life

Tmax:

Time to peak concentration

TMDD:

Target mediated drug disposition

TNF:

Tumor necrosis factor

Vd:

Volume of distribution

References

  • Beck A, Reichert JM (2011) Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies. MAbs 3:415–416

    PubMed  PubMed Central  Google Scholar 

  • 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):503–513

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):2153–2163

    CAS  PubMed  Google Scholar 

  • Brange J, Volund A (1999) Insulin analogs with improved pharmacokinetic profiles. Adv Drug Deliv Rev 35:307–335

    CAS  PubMed  Google Scholar 

  • 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 333:679–682

    CAS  PubMed  Google Scholar 

  • Brange J, Owens DR, Kang S, Volund A (1990) Monomeric insulins and their experimental and clinical implications. Diabetes Care 13:923–954

    CAS  PubMed  Google Scholar 

  • Bumbaca D, Boswell CA, Fielder PJ, Khawli LA (2012) Physiochemical and biochemical factors influencing the pharmacokinetics of antibody therapeutics. AAPS J 14:554–558

    CAS  PubMed  PubMed Central  Google Scholar 

  • Caliceti P, Veronese FM (2003) Pharmacokinetic and biodistribution properties of poly (ethylene glycol)-protein conjugates. Adv Drug Deliv Rev 55:1261–1277

    CAS  PubMed  Google Scholar 

  • Cavagna L, Taylor WJ (2014) The emerging role of biotechnological drugs in the treatment of gout. Biomed Res Int 2014:264859. https://doi.org/10.1155/2014/264859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):896–904

    CAS  PubMed  Google Scholar 

  • 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):5171–5180

    PubMed  Google Scholar 

  • 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):23514–23524

    PubMed  Google Scholar 

  • 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):267–273

    PubMed  PubMed Central  Google Scholar 

  • 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):3866–3873

    CAS  PubMed  Google Scholar 

  • 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 4:101–109

    PubMed  PubMed Central  Google Scholar 

  • Dorai H, Ganguly S (2014) Mammalian cell-produced therapeutic proteins: heterogeneity derived from protein degradation. Curr Opin Biotechnol 30:198–204

    CAS  PubMed  Google Scholar 

  • 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):83–124

    CAS  PubMed  Google Scholar 

  • Egrie JC, Browne JK (2002) Development and characterization of darbepoetin alfa. Oncology (Williston Park) 16:13–22

    Google Scholar 

  • Fabini E, Danielson UH (2017) Monitoring drug-serum protein interactions for early ADME prediction through Surface Plasmon Resonance technology. J Pharm Biomed Anal 144:188–194

    CAS  PubMed  Google Scholar 

  • FDA Approved Drug Products Database of Labeling (2018) U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020563s176lbl.pdf. Accessed 01 Mar 2018

  • Ghetie V, Ward ES (2000) Multiple roles for the major histocompatibility complex class I-related receptor FcRn. Annu Rev Immunol 18:739–766

    CAS  PubMed  Google Scholar 

  • 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):637–640

    CAS  PubMed  Google Scholar 

  • 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):1288–1296

    CAS  PubMed  Google Scholar 

  • Hamidi M, Azadi A, Rafiei P (2006) Pharmacokinetic consequences of pegylation. Drug Deliv 13(6):399–409

    CAS  PubMed  Google Scholar 

  • Hanlon AD, Larkin MI, Reddick RM (2010) Free-solution, label-free protein-protein interactions characterized by dynamic light scattering. Biophys J 98(2):297–304

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 100:94–100

    CAS  PubMed  Google Scholar 

  • Hilgenfeld R, Seipke G, Berchtold H, Owens DR (2014) The evolution of insulin glargine and its continuing contribution to diabetes care. Drugs 74(8):911–927

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):385–392

    CAS  PubMed  Google Scholar 

  • Jevsevar S, Kunstelj M, Porekar VG (2010) PEGylation of therapeutic proteins. Biotechnol J 5(1):113–128

    CAS  PubMed  Google Scholar 

  • Jing X, Jaw J, Robinson HH, Schubot FD (2010) Crystal structure and oligomeric state of the RetS signaling kinase sensory domain. Proteins 78(7):1631–1640

    CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson CM (2013) Differential scanning calorimetry as a tool for protein folding and stability. Arch Biochem Biophys 531(1–2):100–109

    CAS  PubMed  Google Scholar 

  • Kagan L (2014) Pharmacokinetic modeling of the subcutaneous absorption of therapeutic proteins. Drug Metab Dispos 42(11):1890–1905

    PubMed  Google Scholar 

  • 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):104–118

    CAS  PubMed  Google Scholar 

  • 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):283–291

    CAS  PubMed  PubMed Central  Google Scholar 

  • Keizer RJ, Huitema AD, Schellens JH, Beijnen JH (2010) Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet 49(8):493–507

    CAS  PubMed  Google Scholar 

  • Kelly SM, Price NC (2000) The use of circular dichroism in the investigation of protein structure and function. Curr Protein Pept Sci 1(4):349–384

    CAS  PubMed  Google Scholar 

  • 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 2:613–624

    PubMed  PubMed Central  Google Scholar 

  • 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 182:22–32

    CAS  PubMed  Google Scholar 

  • 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):777–789

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lambert JM (2005) Drug-conjugated monoclonal antibodies for the treatment of cancer. Curr Opin Pharmacol 5:543–549

    CAS  PubMed  Google Scholar 

  • 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):7630–7638

    CAS  PubMed  Google Scholar 

  • Lencer WI, Blumberg RS (2005) A passionate kiss, then run-exocytosis and recycling of IgG by FcRn. Trends Cell Biol 15(1):5–9

    CAS  PubMed  Google Scholar 

  • Levêque D, Wisniewski S, Jehl F (2005) Pharmacokinetics of therapeutic monoclonal antibodies used in oncology. Anticancer Res 25(3c):2327–2344

    PubMed  Google Scholar 

  • 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):1255–1264

    PubMed  PubMed Central  Google Scholar 

  • List T, Neri D (2012) Biodistribution studies with tumor-targeting bispecific antibodies reveal selective accumulation at the tumor site. MAbs 4(6):775–783

    PubMed  PubMed Central  Google Scholar 

  • 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):1866–1884

    CAS  PubMed  Google Scholar 

  • Liu L (2018) Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins. Protein Cell 9(1):15–32

    CAS  PubMed  Google Scholar 

  • 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 39:205–210

    CAS  PubMed  Google Scholar 

  • Lobo ED, Hansen RJ, Balthasar JP (2004) Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci 93(11):2645–2668

    CAS  PubMed  Google Scholar 

  • 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):372–382

    CAS  PubMed  Google Scholar 

  • Macielag MJ (2012) Chemical properties of antimicrobials and their uniqueness. In: Dougherty T, Pucci M (eds) Antibiotic discovery and development. Springer, Boston, pp 793–820

    Google Scholar 

  • Mager DE (2006) Target-mediated drug disposition and dynamics. Biochem Pharmacol 72(1):1–10

    CAS  PubMed  Google Scholar 

  • Martin WL, West AP Jr, Gan L, Bjorkman PJ (2001) Crystal structure at 2.8Ã… of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell 7(4):867–877

    CAS  PubMed  Google Scholar 

  • 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 161:22–39

    CAS  PubMed  Google Scholar 

  • McLennan DN, Porter CJ, Charman SA (2005) Subcutaneous drug delivery and the role of the lymphatics. Drug Discov Today Technol 2:89–96

    CAS  PubMed  Google Scholar 

  • Mellman I, Plutner H (1984) Internalization and degradation of macrophage Fc receptors bound to polyvalent immune complexes. J Cell Biol 98:1170–1177

    CAS  PubMed  Google Scholar 

  • Owens DR (2012) Optimizing treatment strategies with insulin glargine in type 2 diabetes. Expert Rev Endocrinol Metab 7(4):377–393

    CAS  PubMed  Google Scholar 

  • Palmieri LC, Favero-Retto MP, Lourenco D, Lima LM (2013) A T3R3 hexamer of the human insulin variant B28Asp. Physicochem Chem 173–174:1–7

    Google Scholar 

  • Pechtner V, Karanikas CA, García-Pérez LE, Glaesner W (2017) A new approach to drug therapy: Fc-fusion technology. Prim Health Care 7:1

    Google Scholar 

  • Pergande MR, Cologna SM (2017) Isoelectric point separations of peptides and proteins. Proteomes 5(1)

    Google Scholar 

  • Pierce MM, Raman CS, Nall BT (1999) Isothermal titration calorimetry of protein-protein interactions. Methods 19(2):213–221

    CAS  PubMed  Google Scholar 

  • Porter CJ, Charman SA (2000) Lymphatic transport of proteins after subcutaneous administration. J Pharm Sci 89:297–310

    CAS  PubMed  Google Scholar 

  • 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):2249–2257

    CAS  PubMed  Google Scholar 

  • 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 229:37–47

    CAS  PubMed  Google Scholar 

  • Ratanji KD, Derrick JP, Dearman RJ, Kimber I (2014) Immunogenicity of therapeutic proteins: influence of aggregation. J Immunotoxicol 11(2):99–109

    CAS  PubMed  Google Scholar 

  • Rehlaender BN, Cho MJ (1998) Antibodies as carrier proteins. Pharm Res 15(11):1652–1656

    CAS  PubMed  Google Scholar 

  • Richette P, Frazier A, Bardin T (2014) Pharmacokinetics considerations for gout treatments. Expert Opin Drug Metab Toxicol 10(7):949–957

    CAS  PubMed  Google Scholar 

  • Richter WF, Bhansali SG, Morris ME (2012) Mechanistic determinants of biotherapeutics absorption following SC administration. AAPSJ 14(3):559–570

    CAS  PubMed  PubMed Central  Google Scholar 

  • Righetti PG (2004) Determination of the isoelectric point of proteins by capillary isoelectric focusing. J Chromatogr A 1037(1–2):491–499

    CAS  PubMed  Google Scholar 

  • Schwartz AL (1991) Trafficking of asialoglycoproteins and the asialoglycoprotein receptor. Target Diagn Ther 4:3–39

    CAS  Google Scholar 

  • Senter PD (2009) Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 13:235–244

    CAS  PubMed  Google Scholar 

  • Shi S (2014) Biologics: an update and challenge of their pharmacokinetics. Curr Drug Metab 15(3):271–290

    CAS  PubMed  Google Scholar 

  • Sockolosky JT, Szoka FC (2015) The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy. Adv Drug Deliv Rev 91:109–124

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):e96967

    PubMed  PubMed Central  Google Scholar 

  • 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 327:308–315

    CAS  PubMed  Google Scholar 

  • Strohl WR (2015) Fusion proteins for half-life extension of biologics as a strategy to make biobetters. BioDrugs 29(4):215–239

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):415–422

    CAS  PubMed  Google Scholar 

  • 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):167–169

    CAS  PubMed  Google Scholar 

  • Tabrizi M, Bornstein GG, Suria H (2010) Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease. AAPS J 12(1):33–43

    CAS  PubMed  Google Scholar 

  • Thurber GM, Schmidt MM, Wittrup KD (2008) Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Adv Drug Deliv Rev 60(12):1421–1434

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):229–245

    CAS  PubMed  Google Scholar 

  • 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):1283–1288

    CAS  PubMed  Google Scholar 

  • Veronese FM, Pasut G (2005) PEGylation, successful approach to drug delivery. Drug Discov Today 10(21):1451–1458

    CAS  PubMed  Google Scholar 

  • Vidarsson G, Dekkers G, Rispens T (2014) IgG subclasses and allotypes: from structure to effector functions. Front Immunol 5:520

    PubMed  PubMed Central  Google Scholar 

  • 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):839–847

    CAS  PubMed  Google Scholar 

  • 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):73–92

    PubMed  PubMed Central  Google Scholar 

  • Wang W, Wang EQ, Balthasar J (2008) Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 84(5):548–558

    CAS  PubMed  Google Scholar 

  • Wang W, Erbe AK, Hank JA, Morris ZS, Sondel PM (2015) NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. Front Immunol 6:368

    PubMed  PubMed Central  Google Scholar 

  • Weinstein JN, van Osdol W (1992) The macroscopic and microscopic pharmacology of monoclonal antibodies. Int J Immunopharmacol 14(3):457–463

    CAS  PubMed  Google Scholar 

  • Winkelhake JL, Nicolson GL (1976) Aglycosylantibody. Effects of exoglycosidase treatments on autochthonous antibody survival time in the circulation. J Biol Chem 251:1074–1080

    CAS  PubMed  Google Scholar 

  • 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 180:1087–1096

    CAS  PubMed  Google Scholar 

  • 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 10:1347–1355

    CAS  PubMed  Google Scholar 

  • Wu AM, Senter PD (2005) Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 23:1137–1146

    CAS  PubMed  Google Scholar 

  • Yang BB, Kido A (2011) Pharmacokinetics and pharmacodynamics of pegfilgrastim. Clin Pharmacokinet 50(5):295–306

    CAS  PubMed  Google Scholar 

  • 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 4:475–487

    PubMed  PubMed Central  Google Scholar 

  • 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):157–159

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):4367–4382

    CAS  PubMed  Google Scholar 

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Acknowledgments

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

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Authors and Affiliations

  1. U.S. Food and Drug Administration, Office of Clinical Pharmacology, DV II, Silver Spring, MD, USA

    Xing Jing, Yan Hou, William Hallett, Chandrahas G. Sahajwalla & Ping Ji

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  1. Xing Jing
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  2. Yan Hou
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Correspondence to Xing Jing .

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  1. Department of Biotechnology, Agricultural University of Athens, Athens, Greece

    Nikolaos Labrou

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Jing, X., Hou, Y., Hallett, W., Sahajwalla, C.G., Ji, P. (2019). Key Physicochemical Characteristics Influencing ADME Properties of Therapeutic Proteins. In: Labrou, N. (eds) Therapeutic Enzymes: Function and Clinical Implications. Advances in Experimental Medicine and Biology, vol 1148. Springer, Singapore. https://doi.org/10.1007/978-981-13-7709-9_6

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