Pharmacokinetics of recombinant bifunctional fusion proteins

Expert Opinion on Drug Metabolism and Toxicology

Volumn 8, Issue 5, 2012, Pages 581-595

  Chen, Xiaoying ^a   Zaro, Jennica L ^a   Shen, Wei Chiang ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

disposition; fusion protein; pharmacokinetics; receptor binding; target mediated drug disposition

Indexed keywords

ABATACEPT; ALBIGLUTIDE; ALEFACEPT; ALPHA INTERFERON; ALTEPLASE; ASPARAGINASE; BELATACEPT; BETA INTERFERON; BLOOD CLOTTING FACTOR 8; BLOOD CLOTTING FACTOR 9; DENILEUKIN DIFTITOX; DENOSUMAB; DULAGLUTIDE; ERYTHROPOIETIN; ETANERCEPT; EYLEA; GLUCAGON LIKE PEPTIDE 1; GROWTH HORMONE; HYBRID PROTEIN; IMMUNOGLOBULIN; IMMUNOGLOBULIN FC FRAGMENT; INSULIN; INTERLEUKIN 11; INTERLEUKIN 2; INTERLEUKIN 2 L19; OMALIZUMAB; PE 38; PF 04603629; RECOMBINANT BIFUNCTIONAL FUSION PROTEIN; RILONACEPT; RITUXIMAB; ROMIPLOSTIM; TRANSFERRIN FUSION PROTEIN; TUCOTUZUMAB CELMOLEUKIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANKYLOSING SPONDYLITIS; BINDING AFFINITY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG DEGRADATION; DRUG DELIVERY SYSTEM; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG TISSUE LEVEL; DRUG UPTAKE; ENDOCYTOSIS; ENDOSOME; HALF LIFE TIME; HUMAN; IMMUNE DEFICIENCY; JUVENILE RHEUMATOID ARTHRITIS; KIDNEY; LIVER; MOLECULAR SIZE; NONHUMAN; PROTEIN DEGRADATION; PROTEIN DOMAIN; PSORIASIS VULGARIS; PSORIATIC ARTHRITIS; REVIEW; RHEUMATOID ARTHRITIS; STEADY STATE; THROMBOCYTOPENIA; TRANSCYTOSIS;

ANIMALS; DRUG DESIGN; HUMANS; MODELS, BIOLOGICAL; PROTEIN BINDING; RECOMBINANT FUSION PROTEINS;

EID: 84859978664     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2012.673585     Document Type: Review

References (101)

1. Meibohm B. Pharmacokinetics and Pharmacodynamics of Biotech Drugs: Principles and Case Studies in Drug Development. WILEY-VCH Verlag GmbH & Co. KGaA; Weinheim, FRG: 2006
2. Duttaroy A, Kanakaraj P, Osborn B, et al. Development of a long-acting insulin analog using albumin fusion technology. Diabetes 2005;54(1):251-8 (Pubitemid 40105120)
3. Osborn B, Olsen H, Nardelli B, et al. Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 2002;303(2):540-8 (Pubitemid 35231224)
4. Muller N, Schneider B, Pfizenmaier K, et al. Superior serum half life of albumin tagged TNF ligands. Biochem Biophys Res Commun 2010;396(4):793-9
5. Peters R, Low S, Kamphaus G, et al. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood 2010;115(10):2057-64
6. Schmidt SR. Fusion-proteins as biopharmaceuticals-applications and challenges. Curr Opin Drug Discov Devel 2009;12(2):284-95
7. Leader B, Baca Q, Golan D. Protein therapeutics: a summary and pharmacological classification. Nat Rev Drug Discov 2008;7(1):21-39
8. Martin ST, Tichy EM, Gabardi S. Belatacept: a novel biologic for maintenance immunosuppression after renal transplantation. Pharmacotherapy 2011;31(4):394-407
9. Teng LS, Jin KT, He KF, et al. Clinical applications of VEGF-trap (aflibercept) in cancer treatment. J Chin Med Assoc 2010;73(9):449-56
10. Aggarwal S. What's fueling the biotech engine-2007. Nat Biotechnol 2008;26(11):1227-33
11. Supersaxo A, Hein WR, Steffen H. Effect of molecular weight on the lymphatic absorption of water-soluble compounds following subcutaneous administration. Pharm Res 1990;7(2):167-9 (Pubitemid 20208069)
12. Brown LR. Commercial challenges of protein drug delivery. Expert Opin Drug Deliv 2005;2(1):29-42 (Pubitemid 40123881)
13. Widera A, Norouziyan F, Shen WC. Mechanisms of TfR-mediated transcytosis and sorting in epithelial cells and applications toward drug delivery. Adv Drug Deliv Rev 2003;55(11):1439-66 (Pubitemid 37464572)
14. Bai Y, Ann DK, Shen WC. Recombinant granulocyte colony-stimulating factortransferrin fusion protein as an oral myelopoietic agent. Proc Natl Acad Sci USA 2005;102(20):7292-6 (Pubitemid 40696372)
15. Amet N, Wang W, Shen WC. Human growth hormone-transferrin fusion protein for oral delivery in hypophysectomized rats. J Control Release 2010;141(2):177-82
16. Bitonti AJ, Dumont JA, Low SC, et al. Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway. Proc Natl Acad Sci USA 2004;101(26):9763-8 (Pubitemid 38869310)
17. Vallee S, Rakhe S, Reidy T, et al. Pulmonary administration of interferon Beta-1a-Fc fusion protein in non-human primates using an immunoglobulin transport pathway. J Interferon Cytokine Res 2011;32:1-7
18. Reilly RM, Sandhu J, Alvarez-Diez TM, et al. Problems of delivery of monoclonal antibodies. Pharmaceutical and pharmacokinetic solutions. Clin Pharmacokinet 1995;28(2):126-42
19. Forero A, Weiden PL, Vose JM, et al. Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non- Hodgkin lymphoma. Blood 2004;104(1):227-36 (Pubitemid 38879862)
20. Better M, Bernhard SL, Williams RE, et al. T cell-targeted immunofusion proteins from Escherichia coli. J Biol Chem 1995;270(25):14951-7
21. Syed S, Schuyler PD, Kulczycky M, et al. Potent antithrombin activity and delayed clearance from the circulation characterize recombinant hirudin genetically fused to albumin. Blood 1997;89(9):3243-52 (Pubitemid 27229809)
22. Hesketh P, Caguioa P, Koh H, et al. Clinical activity of a cytotoxic fusion protein in the treatment of cutaneous T-cell lymphoma. J Clin Oncol 1993;11(9):1682-90 (Pubitemid 23277319)
23. Kelley VE, Bacha P, Pankewycz O, et al. Interleukin 2-diphtheria toxin fusion protein can abolish cell-mediated immunity in vivo. Proc Natl Acad Sci USA 1988;85(11):3980-4
24. Ko YJ, Bubley GJ, Weber R, et al. Safety, pharmacokinetics, and biological pharmacodynamics of the immunocytokine EMD 273066 (huKSIL2): results of a phase I trial in patients with prostate cancer. J Immunother 2004;27(3):232-9 (Pubitemid 39118088)
25. Tang L, Persky AM, Hochhaus G, et al. Pharmacokinetic aspects of biotechnology products. J Pharm Sci 2004;93(9):2184-204 (Pubitemid 39129617)
26. Veng-Pedersen P, Gillespie W. Mean residence time in peripheral tissue: a linear disposition parameter useful for evaluating a drug's tissue distribution. J Pharmacokinet Biopharm 1984;12(5):535-43 (Pubitemid 15187618)
27. Straughn AB. Model-independent steady-state volume of distribution. J Pharm Sci 1982;71(5):597-8 (Pubitemid 12063747)
28. Perrier D, Mayersohn M. Noncompartmental determination of the steady-state volume of distribution for any mode of administration. J Pharm Sci 1982;71(3):372-3 (Pubitemid 12083746)
29. Richter WF, Grimm HP, Theil FP. Potential errors in the volume of distribution estimation of therapeutic proteins composed of differently cleared components. J Pharmacokinet Pharmacodyn 2011;38(5):581-93
30. Yates JW, Arundel PA. On the volume of distribution at steady state and its relationship with two-compartmental models. J Pharm Sci 2008;97(1):111-22
31. Carnemolla B, Borsi L, Balza E, et al. Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix. Blood 2002;99(5):1659-65 (Pubitemid 34533039)
32. Shin SU, Friden P, Moran M, et al. Transferrin-antibody fusion proteins are effective in brain targeting. Proc Natl Acad Sci USA 1995;92(7):2820-4
33. Zhou QH, Boado RJ, Lu JZ, et al. Monoclonal antibody-glial-derived neurotrophic factor fusion protein penetrates the blood-brain barrier in the mouse. Drug Metab Dispos 2010;38(4):566-72
34. Gautier JF, Fetita S, Sobngwi E, et al. Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes Metab 2005;31(3 Pt 1):233-42 (Pubitemid 40961520)
35. Pasta P, Vecchio G, Carrea G. Conformation and proteolysis of glucagon and insulin in surfactant and lipid solutions. Biochim Biophys Acta 1988;953(3):314-20 (Pubitemid 18099340)
36. Baggio LL, Huang Q, Brown TJ, et al. A recombinant human glucagon-like peptide (GLP)-1-albumin protein (albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes 2004;53(9):2492-500 (Pubitemid 39145610)
37. Barrington P, Chien JY, Tibaldi F, et al. LY2189265, a long-acting glucagon-like peptide-1 analogue, showed a dose-dependent effect on insulin secretion in healthy subjects. Diabetes Obes Metab 2011;13(5):434-8
38. Kim BJ, Zhou J, Martin B, et al. Transferrin fusion technology: a novel approach to prolonging biological half-life of insulinotropic peptides. J Pharmacol Exp Ther 2010;334(3):682-92
39. Schenk S, Schoenhals GJ, de Souza G, et al. A high confidence, manually validated human blood plasma protein reference set. BMC Med Genomics 2008;1:41
40. Anderson PM, Sorenson MA. Effects of route and formulation on clinical pharmacokinetics of interleukin-2. Clin Pharmacokinet 1994;27(1):19-31 (Pubitemid 24211094)
41. Takagi A, Masuda H, Takakura Y, et al. Disposition characteristics of recombinant human interleukin-11 after a bolus intravenous administration in mice. J Pharmacol Exp Ther 1995;275(2):537-43 (Pubitemid 26023602)
42. Johnson V, Maack T. Renal extraction, filtration, absorption, and catabolism of growth hormone. Am J Physiol 1977;233(3):F185-96
43. Rabkin R, Ryan MP, Duckworth WC. The renal metabolism of insulin. Diabetologia 1984;27(3):351-7 (Pubitemid 14044457)
44. Duttaroy A, Kanakaraj P, Osborn BL, et al. Development of a long-acting insulin analog using albumin fusion technology. Diabetes 2005;54(1):251-8 (Pubitemid 40105120)
45. Duckworth WC, Bennett RG, Hamel FG. Insulin degradation: progress and potential. Endocr Rev 1998;19(5):608-24 (Pubitemid 28467714)
46. Subramanian GM, Fiscella M, Lamouse-Smith A, et al. Albinterferon alpha-2b: a genetic fusion protein for the treatment of chronic hepatitis C. Nat Biotechnol 2007;25(12):1411-19 (Pubitemid 350233139)
47. Osborn BL, Sekut L, Corcoran M, et al. Albutropin: a growth hormone-albumin fusion with improved pharmacokinetics and pharmacodynamics in rats and monkeys. Eur J Pharmacol 2002;456(1-3):149-58 (Pubitemid 35351748)
48. Powell JS, Josephson NC, Quon D, et al. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia a patients. Blood 2012; [Epub ahead of print]
49. Dumont JA, Liu T, Low SC, et al. Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia a mice and dogs. Blood 2012; [Epub ahead of print]
50. Valentino LA. Recombinant FIXFc: a novel therapy for the royal disease? Expert Opin Biol Ther 2011;11(10):1361-8
51. Chen X, Lee HF, Zaro JL, et al. Effects of receptor binding on plasma half-life of bifunctional transferrin fusion proteins. Mol Pharm 2011;8(2):457-65
52. Authier F, Danielsen GM, Kouach M, et al. Identification of insulin domains important for binding to and degradation by endosomal acidic insulinase. Endocrinology 2001;142(1):276-89 (Pubitemid 32183689)
53. Smedsrod B, Einarsson M. Clearance of tissue plasminogen activator by mannose and galactose receptors in the liver. Thromb Haemost 1990;63(1):60-6 (Pubitemid 20057315)
54. Mager DE. Target-mediated drug disposition and dynamics. Biochem Pharmacol 2006;72(1):1-10 (Pubitemid 43795346)
55. Ducharme E, Weinberg JM. Etanercept. Expert Opin Biol Ther 2008;8(4):491-502 (Pubitemid 351570412)
56. Hoffman HM, Throne ML, Amar NJ, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum 2008;58(8):2443-52
57. Mager DE, JuskoWJ. General pharmacokinetic model for drugs exhibiting target-mediated drug disposition. J Pharmacokinet Pharmacodyn 2001;28(6):507-32 (Pubitemid 34289541)
58. Huang C. Receptor-Fc fusion therapeutics, traps, and MIMETIBODY technology. Curr Opin Biotechnol 2009;20(6):692-9
59. Schulte S. Half-life extension through albumin fusion technologies. Thromb Res 2009;124(Suppl 2):S6-8
60. Spiegelberg HL, Fishkin BG. The catabolism of human G immunoglobulins of different heavy chain subclasses. 3. The catabolism of heavy chain disease proteins and of Fc fragments of myeloma proteins. Clin Exp Immunol 1972;10(4):599-607
61. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007;7(9):715-25 (Pubitemid 47327396)
62. Israel EJ, Wilsker DF, Hayes KC, et al. Increased clearance of IgG in mice that lack beta 2-microglobulin: possible protective role of FcRn. Immunology 1996;89(4):573-8 (Pubitemid 26419660)
63. Anderson CL, Chaudhury C, Kim J, et al. Perspective- FcRn transports albumin: relevance to immunology and medicine. Trends Immunol 2006;27(7):343-8 (Pubitemid 43963476)
64. Chaudhury C, Mehnaz S, Robinson JM, et al. The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med 2003;197(3):315-22 (Pubitemid 36184238)
65. Dautry-Varsat A, Ciechanover A, Lodish H. pH and the recycling of transferrin during receptor-mediated endocytosis. Proc Natl Acad Sci USA 1983;80(8):2258-62 (Pubitemid 13097167)
66. Morgan E. Effect of pH and iron content of transferrin on its binding to reticulocyte receptors. Biochim Biophys Acta 1983;762(4):498-502 (Pubitemid 13077694)
67. De Lorenzo C, D'Alessio G. From immunotoxins to immunoRNases. Curr Pharm Biotechnol 2008;9(3):210-14 (Pubitemid 352024697)
68. Khawli LA, Hu P, Epstein AL. Cytokine, chemokine, and co-stimulatory fusion proteins for the immunotherapy of solid tumors. Handb Exp Pharmacol 2008(181):291-328
69. Pastan II, Kreitman RJ. Immunotoxins for targeted cancer therapy. Adv Drug Deliv Rev 1998;31(1-2):53-88 (Pubitemid 28191876)
70. Kreitman RJ, Pastan I. Accumulation of a recombinant immunotoxin in a tumor in vivo: fewer than 1000 molecules per cell are sufficient for complete responses. Cancer Res 1998;58(5):968-75 (Pubitemid 28182466)
71. Dumont JA, Low SC, Peters RT, et al. Monomeric Fc fusions: impact on pharmacokinetic and biological activity of protein therapeutics. BioDrugs 2006;20(3):151-60 (Pubitemid 43845335)
72. Wang YY, Lui PC, Li JY. Receptor-mediated therapeutic transport across the blood-brain barrier. Immunotherapy 2009;1(6):983-93
73. Jones AR, Shusta EV. Blood-brain barrier transport of therapeutics via receptor-mediation. Pharm Res 2007;24(9):1759-71 (Pubitemid 47206625)
74. Pardridge WM, Eisenberg J, Yang J. Human blood-brain barrier insulin receptor. J Neurochem 1985;44(6):1771-8 (Pubitemid 15000282)
75. Israel EJ, Taylor S, Wu Z, et al. Expression of the neonatal Fc receptor, FcRn, on human intestinal epithelial cells. Immunology 1997;92(1):69-74 (Pubitemid 27380883)
76. Hui EK, Boado RJ, Pardridge WM. Tumor necrosis factor receptor-IgG fusion protein for targeted drug delivery across the human blood-brain barrier. Mol Pharm 2009;6(5):1536-43
77. Boado RJ, Hui EK, Lu JZ, et al. Drug targeting of erythropoietin across the primate blood-brain barrier with an IgG molecular Trojan horse. J Pharmacol Exp Ther 2010;333(3):961-9
78. Arai R, Ueda H, Kitayama A, et al. Design of the linkers which effectively separate domains of a bifunctional fusion protein. Protein Eng 2001;14(8):529-32 (Pubitemid 32959476)
79. van Kerkhof P, Strous G. The ubiquitin-proteasome pathway regulates lysosomal degradation of the growth hormone receptor and its ligand. Biochem Soc Trans 2001;29(Pt 4):488-93 (Pubitemid 32783644)
80. Grant B, Donaldson J. Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol 2009;10(9):597-608
81. Levy G. Pharmacologic target-mediated drug disposition. Clin Pharmacol Ther 1994;56(3):248-52 (Pubitemid 24323915)
82. Mager DE, Krzyzanski W. Quasi-equilibrium pharmacokinetic model for drugs exhibiting target-mediated drug disposition. Pharm Res 2005;22(10):1589-96 (Pubitemid 41355898)
83. Yan X, Mager DE, Krzyzanski W. Selection between Michaelis-Menten and target-mediated drug disposition pharmacokinetic models. J Pharmacokinet Pharmacodyn 2010;37(1):25-47
84. Gibiansky L, Gibiansky E. Target-mediated drug disposition model for drugs that bind to more than one target. J Pharmacokinet Pharmacodyn 2010;37(4):323-46
85. Krippendorff BF, Kuester K, Kloft C, et al. Nonlinear pharmacokinetics of therapeutic proteins resulting from receptor mediated endocytosis. J Pharmacokinet Pharmacodyn 2009;36(3):239-60
86. Wolbink GJ, Aarden LA, Dijkmans BA. Dealing with immunogenicity of biologicals: assessment and clinical relevance. Curr Opin Rheumatol 2009;21(3):211-15
87. Barbosa MD. Immunogenicity of biotherapeutics in the context of developing biosimilars and biobetters. Drug Discov Today 2011;16(7-8):345-53
88. Putnam WS, Prabhu S, Zheng Y, et al. Pharmacokinetic, pharmacodynamic and immunogenicity comparability assessment strategies for monoclonal antibodies. Trends Biotechnol 2010;28(10):509-16
89. Strober BE, Menon K. Alefacept for the treatment of psoriasis and other dermatologic diseases. Dermatol Ther 2007;20(4):270-6 (Pubitemid 350030789)
90. Lundquist LM. Abatacept: a novel treatment for rheumatoid arthritis. Expert Opin Pharmacother 2007;8(14):2371-9 (Pubitemid 350001596)
91. Cines DB, Yasothan U, Kirkpatrick P. Romiplostim. Nat Rev Drug Discov 2008;7(11):887-8
92. Wang W, Ou Y, Shi Y. AlbuBNP, a recombinant B-type natriuretic peptide and human serum albumin fusion hormone, as a long-term therapy of congestive heart failure. Pharm Res 2004;21(11):2105-11 (Pubitemid 40941232)
93. Halpern W, Riccobene TA, Agostini H, et al. Albugranin, a recombinant human granulocyte colony stimulating factor (G-CSF) genetically fused to recombinant human albumin induces prolonged myelopoietic effects in mice and monkeys. Pharm Res 2002;19(11):1720-9 (Pubitemid 35305525)
94. Turturro F. Denileukin diftitox: a biotherapeutic paradigm shift in the treatment of lymphoid-derived disorders. Expert Rev Anticancer Ther 2007;7(1):11-17 (Pubitemid 46157644)
95. Wen X, Lyu MA, Zhang R, et al. Biodistribution, pharmacokinetics, and nuclear imaging studies of 111In-labeled rGel/BLyS fusion toxin in SCID mice bearing B cell lymphoma. Mol Imaging Biol 2011;13(4):721-9
96. Bang S, Nagata S, Onda M, et al. HA22 (R490A) is a recombinant immunotoxin with increased antitumor activity without an increase in animal toxicity. Clin Cancer Res 2005;11(4):1545-50 (Pubitemid 40315239)
97. Niculescu-Duvaz I. Technology evaluation: EMD-273063, EMD Lexigen. Curr Opin Mol Ther 2004;6(5):559-66 (Pubitemid 39386604)
98. Johnson EE, Lum HD, Rakhmilevich AL, et al. Intratumoral immunocytokine treatment results in enhanced antitumor effects. Cancer Immunol Immunother 2008;57(12):1891-902
99. Wagner K, Schulz P, Scholz A, et al. The targeted immunocytokine L19-IL2 efficiently inhibits the growth of orthotopic pancreatic cancer. Clin Cancer Res 2008;14(15):4951-60
100. Halin C, Gafner V, Villani ME, et al. Synergistic therapeutic effects of a tumor targeting antibody fragment, fused to interleukin 12 and to tumor necrosis factor alpha. Cancer Res 2003;63(12):3202-10 (Pubitemid 36735873)
101. Low SC, Nunes SL, Bitonti AJ, et al. Oral and pulmonary delivery of FSH-Fc fusion proteins via neonatal Fc receptor-mediated transcytosis. Hum Reprod 2005;20(7):1805-13 (Pubitemid 40932360)