Engineering as a means to improve the pharmacokinetics of injected therapeutic proteins

Proteins and Peptides: Pharmacokinetic, Pharmacodynamic, and Metabolic Outcomes

Volumn , Issue , 2009, Pages 129-162

  Dennis, Mark S ^a   Yeung, Yik A ^a   Lowman, Henry B ^a   Kelley, Robert F ^a  

^a GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84862591434     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (191)

1. Brown LR. Commercial challenges of protein drug delivery. Expert Opin Drug Deliv 2005; 2(1):29-42.
2. Renkin EM, Robinson RR. Glomerular filtration. N Engl J Med 1974; 290(14):785-789.
3. Felgenhauser K. Protein filtration and secretion at human body fluid barriers. Pflugers Arch 1980; 384:9-17.
4. Daugherty AL, Mrsny RJ. Formulation and delivery issues for monoclonal antibody therapeutics. Adv Drug Deliv Rev 2006; 58:686-706.
5. Frokjaer S, Otzen DE. Protein drug stability: a formulation challenge. Nat Rev Drug Discov 2005; 4:298-306.
6. Barbosa MDFS, Celis E. Immunogenicity of protein therapeutics and the interplay between tolerance and antibody responses. Drug Discov Today 2007; 12:674-681.
7. Labhasetwar V, Song C, Levy RJ. Nanoparticle drug delivery systems for restenosis. Adv Drug Deliv Rev 1997; 24(1):63-85.
8. Saukkonen T, Amin R, Williams RM, et al. Dose-dependent effects of recombinant human insulin-like growth factor (IGF)-I/IGF binding protein-3 complex on overnight growth hormone secretion and insulin sensitivity in type 1 diabetes. J Biol Chem 2004; 89(9):4634-4641.
9. Ferrara N, Hillan KJ, Gerber HP, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 2004; 3:391-400.
10. Ferrara N, Damico L, Shams N, et al. Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular agerelated macular degeneration. Retina 2006; 26:859-870.
11. Stein TP, Leskiw MJ, Wallace HW. Measurement of half-life human plasma fibrinogen. Am J Physiol 1978; 234(5):D504-D510.
12. Rogentine GN Jr., Rowe DS, Bradley J, et al. Metabolism of human immunoglobulin D (IgD). J Clin Invest 1966; 45(9):1467-1478.
13. Barth WF, Wochner RD, Waldmann TA, et al. Metabolism of human gamma macroglobulins. J Clin Invest 1964; 43:1036-1048.
14. Strober W, Wochner RD, Barlow MH, et al. Immunoglobulin metabolism in ataxia telangiectasia. J Clin Invest 1968; 47(8):1905-1915.
15. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007; 7(9):715-725.
16. Anderson CL, Chaudhury C, Kim J, et al. Perspective-FcRn transports albumin: relevance to immunology and medicine. Trends Immunol 2006; 27(7):343-348.
17. Brambell FW, Halliday R, Morris IG. Interference by human and bovine serum and serum protein fractions with the absorption of antibodies by suckling rats and mice. Proc R Soc Lond B Biol Sci 1958; 149(934):1-11.
18. Simister NE, Mostov KE. An Fc receptor structurally related to MHC class I antigens. Nature 1989; 337(6203):184-187.
19. Brambell FW, Hemmings WA, Morris IG. A theoretical model of gamma-globulin catabolism. Nature 1964; 203:1352-1354.
20. Ghetie V, Hubbard JG, Kim JK, et al. Abnormally short serum half-lives of IgG in beta 2-microglobulin-deficient mice. Eur J Immunol 1996; 26(3):690-696.
21. 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): 573-578.
22. Junghans RP, Anderson CL. The protection receptor for IgG catabolism is the beta2-microglobulin-containing neonatal intestinal transport receptor. Proc Natl Acad Sci U S A 1996; 93(11):5512-5516.
23. Wani MA, Haynes LD, Kim J, et al. Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta2-microglobulin gene. Proc Natl Acad Sci U S A 2006; 103(13):5084-5089.
24. Mayer B, Zolnai A, Frenyo LV, et al. Localization of the sheep FcRn in the mammary gland. Vet Immunol Immunopathol 2002; 87(3-4):327-330.
25. Leach JL, Sedmak DD, Osborne JM, et al. Isolation from human placenta of the IgG transporter, FcRn, and localization to the syncytiotrophoblast: implications for maternal-fetal antibody transport. J Immunol 1996; 157(8):3317-3322.
26. Kacskovics I, Kis Z, Mayer B, et al. FcRn mediates elongated serum half-life of human IgG in cattle. Int Immunol 2006; 18(4):525-536.
27. Burmeister WP, Gastinel LN, Simister NE, et al. Crystal structure at 2.2 A resolution of the MHC-related neonatal Fc receptor. Nature 1994; 372(6504):336-343.
28. West AP Jr., Bjorkman PJ. Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex-related Fc receptor. Biochemistry 2000; 39(32):9698-9708.
29. Martin WL, West AP Jr., Gan L, et al. Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell 2001; 7(4):867-877.
30. Chaudhury C, Mehnaz S, Robinson JM, et al. The major histocompatibility complexrelated Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med 2003; 197(3):315-322.
31. Chaudhury C, Brooks CL, Carter DC, et al. Albumin binding to FcRn: distinct from the FcRn-IgG interaction. Biochemistry 2006; 45(15):4983-4990.
32. Sanchez LM, Penny DM, Bjorkman PJ. Stoichiometry of the interaction between the major histocompatibility complex-related Fc receptor and its Fc ligand. Biochemistry 1999; 38(29):9471-9476.
33. Burmeister WP, Huber AH, Bjorkman PJ. Crystal structure of the complex of rat neonatal Fc receptor with Fc. Nature 1994; 372(6504):379-383.
34. The PyMOL Molecular Graphics System. DeLano Scientific, 2002. Available at: http://www.pymol.org.
35. Kim JK, Firan M, Radu CG, et al. Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn. Eur J Immunol 1999; 29(9):2819-2825.
36. Shields RL, Namenuk AK, Hong K, et al. High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem 2001; 276(9):6591-6604.
37. Zhou J, Johnson JE, Ghetie V, et al. 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(4):901-913.
38. Zhou J, Mateos F, Ober RJ, et al. 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):1071-1081.
39. Andersen JT, Dee Qian J, Sandlie I. The conserved histidine 166 residue of the human neonatal Fc receptor heavy chain is critical for the pH-dependent binding to albumin. Eur J Immunol 2006; 36(11):3044-3051.
40. Praetor A, HunzikerW. Beta(2)-Microglobulin is important for cell surface expression and pH-dependent IgG binding of human FcRn. J Cell Sci 2002; 115(pt 11):2389-2397.
41. Raghavan M, Bonagura VR, Morrison SL, et al. Analysis of the pH dependence of the neonatal Fc receptor/immunoglobulin G interaction using antibody and receptor variants. Biochemistry 1995; 34(45):14649-14657.
42. Ober RJ, Martinez C, Vaccaro C, et al. Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor, FcRn. J Immunol 2004; 172(4):2021-2029.
43. Prabhat P, Gan Z, Chao J, et al. Elucidation of intracellular recycling pathways leading to exocytosis of the Fc receptor, FcRn, by using multifocal plane microscopy. Proc Natl Acad Sci U S A 2007; 104(14):5889-5894.
44. Ober RJ, Martinez C, Lai X, et al. Exocytosis of IgG as mediated by the receptor, FcRn: an analysis at the single-molecule level. Proc Natl Acad Sci U S A 2004; 101(30):11076-11081.
45. Borvak J, Richardson J, Medesan C, et al. Functional expression of the MHC class I-related receptor, FcRn, in endothelial cells of mice. Int Immunol 1998; 10(9): 1289-1298.
46. Zhu X, Meng G, Dickinson BL, 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(5):3266-3276.
47. Dickinson BL, Badizadegan K, Wu Z, et al. Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J Clin Invest 1999; 104(7):903-911.
48. Schlachetzki F, Zhu C, Pardridge WM. Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier. J Neurochem 2002; 81(1):203-206.
49. Deane R, Sagare A, Hamm K, et al. IgG-assisted age-dependent clearance of Alzheimer’s amyloid beta peptide by the blood-brain barrier neonatal Fc receptor. J Neurosci 2005; 25(50):11495-11503.
50. Akilesh S, Huber TB, Wu H, et al. Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proc Natl Acad Sci U S A 2008; 105(3):967-972.
51. Antohe F, Radulescu L, Gafencu A, et al. Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells. Hum Immunol 2001; 62(2):93-105.
52. Simister NE. Placental transport ofimmunoglobulin G. Vaccine 2003; 21(24):3365-3369.
53. Spiekermann GM, Finn PW, Ward ES, et al. Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung. J Exp Med 2002; 196(3):303-310.
54. Maddon PJ, Dalgleish AG, McDougal JS, et al. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 1986; 47(3):333-348.
55. Clark SJ, Jefferies WA, Barclay AN, et al. Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin-related domains. Proc Natl Acad Sci U S A 1987; 84(6):1649-1653.
56. Chamow SM, Peers DH, Byrn RA, et al. Enzymatic cleavage of a CD4 immunoadhesin generates crystallizable, biologically active Fd-like fragments. Biochemistry 1990; 29(42):9885-9891.
57. Garrett TP, Wang J, Yan Y, et al. Refinement and analysis of the structure of the first two domains of human CD4. J Mol Biol 1993; 234(3):763-778.
58. Smith DH, Byrn RA, Marsters SA, et al. Blocking of HIV-1 infectivity by a soluble, secreted form of the CD4 antigen. Science 1987; 238(4834):1704-1707.
59. Traunecker A, Luke W, Karjalainen K. Soluble CD4 molecules neutralize human immunodeficiency virus type 1. Nature 1988; 331(6151):84-86.
60. Berger EA, Fuerst TR, Moss B. A soluble recombinant polypeptide comprising the amino-terminal half of the extracellular region of the CD4 molecule contains an active binding site for human immunodeficiency virus. Proc Natl Acad Sci U S A 1988; 85(7):2357-2361.
61. Capon DJ, Chamow SM, Mordenti J, et al. Designing CD4 immunoadhesins for AIDS therapy. Nature 1989; 337(6207):525-531.
62. Hodges TL, Kahn JO, Kaplan LD, et al. Phase 1 study of recombinant human CD4-immunoglobulin G therapy of patients with AIDS and AIDS-related complex. Antimicrob Agents Chemother 1991; 35(12):2580-2586.
63. Byrn RA, Mordenti J, Lucas C, et al. Biological properties of a CD4 immunoadhesin. Nature 1990; 344(6267):667-670.
64. Traunecker A, Schneider J, Kiefer H, et al. Highly efficient neutralization of HIV with recombinant CD4-immunoglobulin molecules. Nature 1989; 339(6219):68-70.
65. Kahn JO, Allan JD, Hodges TL, et al. The safety and pharmacokinetics of recombinant soluble CD4 (rCD4) in subjects with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase 1 study. Ann Intern Med 1990; 112(4):254-261.
66. Mordenti J, Chen SA, Moore JA, et al. Interspecies scaling of clearance and volume of distribution data for five therapeutic proteins. Pharm Res 1991; 8(11):1351-1359.
67. Joos B, Trkola A, Kuster H, et al. Long-term multiple-dose pharmacokinetics of human monoclonal antibodies (MAbs) against human immunodeficiency virus type 1 envelope gp120 (MAb 2G12) and gp41 (MAbs 4E10 and 2F5). Antimicrob Agents Chemother 2006; 50(5):1773-1779.
68. Jazayeri JA, Carroll GJ. Fc-based cytokines: prospects for engineering superior therapeutics. BioDrugs 2008; 22(1):11-26.
69. Deng B, Banu N, Malloy B, et al.An agonist murinemonoclonal antibody to the human c-Mpl receptor stimulates megakaryocytopoiesis. Blood 1998; 92(6):1981-1988.
70. Zhang L, Zhang X, Barrisford GW, et al. Lexatumumab (TRAIL-receptor 2 mAb) induces expression of DR5 and promotes apoptosis in primary and metastatic renal cell carcinoma in a mouse orthotopic model. Cancer Lett 2007; 251(1):146-157.
71. Mitoma H, Horiuchi T, Hatta N, et al. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology 2005; 128(2):376-392.
72. Kaymakcalan Z, Kalghatgi L, Xiong L. Differential TNF-neutralizing potencies of adalimumab, etanercept and infliximab. Clin Immunol 2006; 119(suppl 1):S77-S78.
73. Kaymakcalan Z, Sakorafas P, Bose S. Etanercept, infliximab and adalimumb bind to soluble and transmembrane TNF with similar affinities. Clin Immunol 2006; 119(S1): S75.
74. Scallon B, Cai A, Solowski N, et al. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther 2002; 301(2):418-426.
75. Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther 2004; 76(6): 628-638.
76. 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 U S A 2004; 101(26):9763-9768.
77. Korth-Bradley JM, Rubin AS, Hanna RK, et al. The pharmacokinetics of etanercept in healthy volunteers. Ann Pharmacother 2000; 34(2):161-164.
78. Jones AJ, Papac DI, Chin EH, et al. Selective clearance of glycoforms of a complex glycoprotein pharmaceutical caused by terminal N-acetylglucosamine is similar in humans and cynomolgus monkeys. Glycobiology 2007; 17(5):529-540.
79. Weisman MH, Moreland LW, Furst DE, et al. Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. Clin Ther 2003; 25(6):1700-1721.
80. den Broeder A, van de Putte L, Rau R, et al. A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis. J Rheumatol 2002 29(11):2288-2298.
81. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008; 117(2):244-279.
82. Anderson PJ. Tumor necrosis factor inhibitors: clinical implications of their different immunogenicity profiles. Semin Arthritis Rheum 2005; 34(5 suppl 1):19-22.
83. Li J, Yang C, Xia Y, et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 2001; 98(12):3241-3248.
84. Basser RL, O’Flaherty E, Green M, et al. Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor. Blood 2002; 99(7):2599-2602.
85. Morell AG, Gregoriadis G, Scheinberg IH, et al. The role of sialic acid in determining the survival of glycoproteins in the circulation. J Biol Chem 1971; 246(5):1461-1467.
86. Stockert RJ. The asialoglycoprotein receptor: relationships between structure, function, and expression. Physiol Rev 1995; 75(3):591-609.
87. Stahl PD. The mannose receptor and other macrophage lectins. Curr Opin Immunol 1992; 4(1):49-52.
88. Park EI, Mi Y, Unverzagt C, et al. The asialoglycoprotein receptor clears glycoconjugates terminating with sialic acid alpha 2,6GalNAc. Proc Natl Acad Sci U S A 2005; 102(47):17125-17129.
89. Lee SJ, Evers S, Roeder D, et al. Mannose receptor-mediated regulation of serum glycoprotein homeostasis. Science 2002; 295(5561):1898-1901.
90. Park EI, Manzella SM, Baenziger JU. Rapid clearance of sialylated glycoproteins by the asialoglycoprotein receptor. J Biol Chem 2003; 278(7):4597-4602.
91. Keck R, Nayak N, Lerner L, et al. Characterization of a complex glycoprotein whose variable metabolic clearance in humans is dependent on terminal Nacetylglucosamine content. Biologicals 2008; 36(1):49-60.
92. Olafsen T, Kenanova VE, Wu AM. Tunable pharmacokinetics: modifying the in vivo half-life of antibodies by directed mutagenesis of the Fc fragment. Nat Protoc 2006; 1(4):2048-2060.
93. Ghetie V, Popov S, Borvak J, et al. Increasing the serum persistence of an IgG fragment by random mutagenesis. Nat Biotechnol 1997; 15(7):637-640.
94. Dall’Acqua WF, Woods RM, Ward ES, et al. Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences. J Immunol 2002; 169(9): 5171-5180.
95. Petkova SB, Akilesh S, Sproule TJ, 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(12):1759-1769.
96. Hinton PR, Xiong JM, Johlfs MG, et al. An engineered human IgG1 antibody with longer serum half-life. J Immunol 2006; 176(1):346-356.
97. Datta-Mannan A, Witcher DR, Tang Y, et al. Monoclonal antibody clearance. Impact of modulating the interaction of IgG with the neonatal Fc receptor. J Biol Chem 2007; 282(3):1709-1717.
98. Datta-Mannan A, Witcher DR, Tang Y, et al. Humanized IgG1 variants with differential binding properties to the neonatal Fc receptor: relationship to pharmacokinetics in mice and primates. Drug Metab Dispos 2007; 35(1):86-94.
99. Vaccaro C, Bawdon R, Wanjie S, et al. Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Proc Natl Acad Sci U S A 2006; 103(49):18709-18714.
100. Dall’acqua WF, Kiener PA, Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem 2006; 281(33): 23514-23524.
101. Hinton PR, Johlfs MG, Xiong JM, et al. Engineered human IgG antibodies with longer serum half-lives in primates. J Biol Chem 2004; 279(8):6213-6216.
102. Peters T Jr. All About Albumin. San Diego: Academic Press, Inc, 1996:432.
103. Ghuman J, Zunszain PA, Petitpas I, et al. Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol 2005; 353:38-52.
104. Cormode EJ, Lyster DM, Israels S. Analbuminemia in a neonate. J Pediatr 1975; 86:862-867.
105. Schultze HE, Heremans JF. Molecular biology of human proteins: with special reference to plasma proteins. Vol 1. Nature and Metabolism of Extracellular Proteins. Amsterdam, London, New York: Elsevier, 1966.
106. Wong K, Cleland LG, Poznanski MJ. Enhanced anti-inflammatory effects and reduce immunogenicity of bovine liver superoxide dismutase by conjugation with homologous albumin. Agent Action 1980; 10:231-239.
107. Remy MH, Poznansky MJ. Immunogenicity and antigenicity of soluble cross-linked enzyme/albumin polymers: advantages for enzyme therapy. Lancet 1978; 2(8080): 68-70.
108. Poznansky MJ, Soluble enzyme-albumin conjugates: new possibilities for enzyme replacement therapy. Methods Enzymol 1988; 137:566-574.
109. Poznansky MJ, Halford J, Taylor D. Growth hormone-albumin conjugates, reduced renal toxicity and altered plasma clearance. FEBS Lett 1988; 239(1):18-22.
110. Stehle G, Sinn H, Wunder A, et al. Plasma protein (albumin) catabolism by the tumor itself-implicaions for tumor metabolism and genesis of cachexia. Crit Rev Oncol Hematol 1997; 26:77-100.
111. Fiume L, Bolondi L, Busi C, et al. Doxorubicin coupled to lactosaminated albumin inhibits the growth of hepatocellular carcinomas induced in rats by diethylnitrosamine J Hepatology 2005; 43:645-652.
112. Stehle G, Sinn H, Wunder A, et al. The loading rate determines tumor targeting properties of methotrexate-albumin conjugates in rats. Anticancer Drugs 1997; 8:677-685.
113. Smith BJ, Popplewell A, Athwal D, et al. Prolonged in vivo residence times of antibody fragments associated with albumin. Bioconjug Chem 2001; 12:750-756.
114. Leger R, Robitaille M, Quraishi O, et al. Synthesis and in vitro analysis of atrial natriuretic peptide-albumin conjugates. Bioorg Med Chem Lett 2003; 13:3571-3575.
115. Holmes DL, Thibaudeau K, L’Archeveque B, et al. Site specific 1:1 opioid:albumin conjugate with in vitro activity and long in vivo duration. Bioconjugate Chem 2000; 11(4):439-444.
116. Leger R, Benquet C, Huang X, et al. Kringle 5 peptide-albumin conjugates with antimigratory activity. Bioorg Med Chem Lett 2004; 14:841-845.
117. Shechter Y, Mironchik M, Rubinraut S, et al. Albumin-insulin conjugate releasing insulin slowly under physiological conditions: a new concept for long-acting insulin. Bioconjugate Chem 2005; 16:913-920.
118. Yeh P, Landais D, Lemaitre M, et al. Design of yeast-secreted albumin derivatives for human therapy: biological and antiviral properties of a serum albumin-CD4 genetic conjugate. Proc Natl Acad Sci U S A 1992; 89:1904-1908.
119. Syed S, Schuyler P, Kulczycky M, et al. Potent antithrombin activity and delayed clearance from the circulation characterize recombinant hirudin genetically fused to albumin. Blood 1997; 89(9):3243-3252.
120. Marques JA, George JK, Smith IJ, et al. A barbourin-albumin fusion protein that is slowly cleared in vivo retains the ability to inhibit platelet aggregation in vitro. Thromb Haemost 2001; 86:902-908.
121. 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):1720-1729.
122. Osborn BL, Olsen HS, Nardellli B, et al. Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. JPET 2002; 303:540-548.
123. 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 Pharm 2002; 456(1-3):149-158.
124. Sung C, Nardellli B, Lafleur DW, et al. An IFN-b-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates. J Interferon Cytokine Res 2003; 23:25-36.
125. Bouquet C, Frau E, Opolon P, et al. Systemic administration of a recombinant adenovirus encoding a HSA-angiostatin kringle 1-3 conjugate inhibits MDA-MB-231 tumor growth and metastasis in a transgenic model of spontaneous eye cancer. Mol Ther 2003; 7(2):174-184.
126. 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):2105-2111.
127. Melder RJ, Osborn BL, Riccobene T, et al. Pharmacokinetics and in vitro and in vivo anti-tumor response of an interleukin-2-human serum albumin fusion protein in mice. Cancer Immunol Immunother 2005; 54:535-547.
128. Duttaroy A, Kanakaraj P, Osborn B, et al. Development of a long-acting insulin analog using albumin fusion technology. Diabetes 2005; 54(1):251-258.
129. Huang Y-S, Chen Z, Chen Y-Q, et al. Preparation and characterization of a novel exendin-4 human serum albumin fusion protein expressed in Pichia pastoris. J Peptide Sci 2008; 14:588-595.
130. Muller D, Karle A, Meißburger B, et al. Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. J Biol Chem 2007; 282:12650-12660.
131. Sterling K. The turnover rate of serum albumin in man as measured by I-131-tagged albumin. J Clin Invest 1957; 30:1228-1237.
132. Reed RG, Peters T Jr. Turnover of serum albumin-palmitate complexes. Fed Proc 1984; 43:1858.
133. Stevens DK, Eyre RJ, Bull RJ. Adduction of hemoglobin and albumin in vivo by metabolites of trichloroethylene, trichloroacetate, and dichloroacetate in rats and mice. Fundam Appl Toxicol 1992; 19:336-342.
134. Hatton MWC, Richardson M, Winocour PD. On glucose transport and non-enzymic glycation of proteins in vivo. J Theor Biol 1993; 161:481-490.
135. Subramanian GM, Fiscella M, Lamousé-Smith A, et al. Albinterferon α-2b: a genetic fusion protein for the treatment of chronic hepatitis C. Nat Biotech 2007; 25(12): 1411-1419.
136. 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; 53:2492-2500.
137. Kratz F, Muller-Driver R, Hofmann I, et al. A novel macromolecular prodrug concept exploiting endogenous serum albumin as a drug carrier for cancer chemotherapy. J Med Chem 2000; 43:1253-1256.
138. Mansour AM, Drevs J, Esser N, et al. A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Cancer Res 2003; 63:4062-4066.
139. Kim JG, Baggio LL, Bridon DP, et al. Development and characterization of a glucagon-like peptide 1-albumin conjugate: the ability to activate the glucagon-like peptide 1 receptor in vivo. Diabetes 2003; 52(3):751-759.
140. Jette L, Leger R, Thibaudeau K, et al. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology 2005; 146(7):3052-3058.
141. Thibaudeau K, Leger R, Huang X, et al. Synthesis and evaluation of insulin-human serum albumin conjugates. Bioconjugate Chem 2005; 16:1000-1008.
142. Curry S, Mandelkow H, Brick P, et al. Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat Struct Biol 1998; 5(9):827-835.
143. Kurtzhals P, Havelund S, Jonassen I, et al. Albumin binding insulins acylated with fatty acids: characterization of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effect in vivo. Biochem J 1995; 312:725-731.
144. Markussen J, Havelund S, Kurtzhals P, et al. Soluble, fatty acid acylated insulins bind albumin and show protracted action in pigs. Diabetologia 1996; 39:281-288.
145. Danne T, Lupke K, Walte K, et al. Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes. Diabetes 2003; 26(11):3087-3092.
146. Koehler MFT, Zobel K, Beresini MH, et al. Albumin affinity tags increase peptide half-life in vivo. Bioorg Med Chem Lett 2002; 12(20):2883-2886.
147. Manoharan M, Inamati GB, Lesnik EA, et al. Improving antisense oligonucleotide binding to human serum albumin: dramatic effect of ibuprofen conjugation. Chembiochem 2002; 12:1257-1260.
148. Johansson MU, Frick I-M, Nilsson H, et al. Structure, specificity, and mode of interaction for bacterial albumin-binding modules. J Biol Chem 2002; 277(10): 8114-8120.
149. Nygren P-A, Uhlen M. In vivo stabilization of a human recombinant CD4 derivative by fusion to a serum-albumin-binding receptor. Vaccine 1991; 91:363-368.
150. Makrides SC, Nygren P-A, Andrews B, et al. Extended in vivo half-life of human soluble complement receptor type I fused to a serum albumin-binding receptor. J Pharmacol Exp Ther 1996; 277(1):534-542.
151. Stork R, Muller D, Kontermann RE. A novel tri-functional antibody fusion protein with improved pharmacokinetic properties generated by fusing a bispecific singlechain diabody with an albumin-binding domain from streptococcal protein G. Protein Eng Des Sel 2007; 20(11):569-576.
152. Tolmachev V, Orlova A, Pehrson R, et al. Radionuclide therapy of HER2-positive microxenografts using a 177Lu-labeled HER2-specific affibody molecule. Cancer Res 2007; 67(6):2773-2782.
153. Jonsson A, Dogan J, Herne N, et al. Engineering of a femtomolar affinity binding protein to human serum albumin. Protein Eng Des Sel 2008; 21(8):515-527.
154. Nguyen A, Reyes AE II, Zhang M, et al. The pharmacokinetics of an albumin binding Fab (AB.Fab) can be modulated as a function of affinity for albumin. Protein Eng Des Sel 2006; 19(7):291-297.
155. Lejon S, Frick I-M, Bjorck L, et al. Crystal structure and biological implications of a bacterial albumin binding module in complex with human serum albumin. J Biol Chem 2004; 279(41):42924-42928.
156. Sjolander A, Nygren P-A, Stahl S, et al. The serum albumin-binding region of streptococcal protein G: a bacterial fusion partner with carrier-related properties. J Immunol Methods 1997; 201:115-123.
157. Libona C, Corvaïaa N, Haeuwa J-F, et al. The serum albumin-binding region of streptococcal protein G (BB) potentiates the immunogenicity of the G130-230 RSV-A protein. Vaccine 1999; 17(5):406-414.
158. Goetsch L, Haeuw JF, Champion T, et al. Identification of B-and T-cell epitopes of BB, a carrier protein derived from the G protein of Streptococcus Strain G148. Clin Diagn Lab Immunol 2003; 10(1):125-132.
159. Dennis MS, Zhang M, Meng YG, et al. Albumin binding as a general stategy for improving the pharmacokinetics of proteins. J Biol Chem 2002; 277(38):35035-35043.
160. Hollinger P, Wing M, Pound JD, et al. Retargeting serum immunoglobulins with bispecific diabodies. Nat Biotech 1997; 15:632-636.
161. Holt LJ, Basran A, Jones K, et al. Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs. Protein Eng Des Sel 2008; 21(5):283-288.
162. Damascelli B, Cantu G, Mattavelli F, et al. Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007). Cancer 2001; 92(10):2592-2602.
163. Donohue JH, Rosenberg SA. The fate of interleukin-2 after in vivo administration. J Immunol 1983; 130(5):2203-2208.
164. Koumenis IL, Shahrokh Z, Leong S, et al. Modulating pharmacokinetics of an antiinterleukin-8 F(ab’)(2) by amine-specific PEGylation with preserved bioactivity. Int J Pharm 2000; 198(1):83-95.
165. Lee LS, Conover C, Shi C, et al. Prolonged circulating lives of single-chain Fv proteins conjugated with polyethylene glycol: a comparison of conjugation chemistries and compounds. Bioconjug Chem 1999; 10(6):973-981.
166. Knauf MJ, Bell DP, Hirtzer P, et al. Relationship of effective molecular size to systemic clearance in rats of recombinant interleukin-2 chemically modified with water-soluble polymers. J Biol Chem 1988; 263(29):15064-15070.
167. Bendele A, Seely J, Richey C, et al. Short communication: renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol Sci 1998; 42(2):152-157.
168. Caliceti P, Veronese FM, Jonak Z. Immunogenic and tolerogenic properties of monomethoxypoly(ethylene glycol) conjugated proteins. Farmaco 1999; 54(7):430-437.
169. Monfardini C, Schiavon O, Caliceti P, et al. A branched monomethoxypoly(ethylene glycol) for protein modification. Bioconjug Chem 1995; 6(1):62-69.
170. Kinstler OB, Brems DN, Lauren SL, et al. Characterization and stability of N-terminally PEGylated rhG-CSF. Pharm Res 1996; 13(7):996-1002.
171. Gaertner HF, Offord RE. Site-specific attachment of functionalized poly(ethylene glycol) to the amino terminus of proteins. Bioconjug Chem 1996; 7(1):38-44.
172. Goodson RJ, Katre NV. Site-directed pegylation of recombinant interleukin-2 at its glycosylation site. Biotechnology 1990; 8(4):343-346.
173. Richter AW, Akerblom E. Antibodies against polyethylene glycol produced in animals by immunization with monomethoxy polyethylene glycol modified proteins. Int Arch Allergy Appl Immunol 1983; 70(2):124-131.
174. Ettinger LJ, Kurtzberg J, Voute PA, et al. An open-label, multicenter study of polyethylene glycol-L-asparaginase for the treatment of acute lymphoblastic leukemia. Cancer 1995; 75(5):1176-1181.
175. Zeuzem S, Feinman SV, Rasenack J, et al. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 2000; 343(23):1666-1672.
176. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358(9286):958-965.
177. Bailon P, Palleroni A, Schaffer CA, et al. Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C. Bioconjug Chem 2001; 12(2):195-202.
178. Molineux G. Pegylation: engineering improved pharmaceuticals for enhanced therapy. Cancer Treat Rev 2002; 28(suppl A):13-16.
179. Holmes FA, O’Shaughnessy JA, Vukelja S, et al. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 2002; 20(3):727-731.
180. Chapman AP, Antoniw P, Spitali M, et al. Therapeutic antibody fragments with prolonged in vivo half-lives. Nat Biotechnol 1999; 17(8):780-783.
181. Junutula JR, Bhakta S, Raab H, et al. Rapid identification of reactive cysteine residues for site-specific labeling of antibody-Fabs. J Immunol Methods 2008; 332(1-2):41-52.
182. Filpula D, Zhao H. Releasable PEGylation of proteins with customized linkers. Adv Drug Deliv Rev 2008; 60(1):29-49.
183. Veronese FM, Schiavon O, Pasut G, et al. PEG-doxorubicin conjugates: influence of polymer structure on drug release, in vitro cytotoxicity, biodistribution, and antitumor activity. Bioconjug Chem 2005; 16(4):775-784.
184. Kemp SF, Fielder PJ, Attie KM, et al. Pharmacokinetic and pharmacodynamic characteristics of a long-acting growth hormone (GH) preparation (nutropin depot) in GH-deficient children. J Clin Endocrinol Metab 2004; 89(7):3234-3240.
185. Sinclair AM, Elliott S. Glycoengineering: the effect of glycosylation on the properties of therapeutic proteins. J Pharm Sci 2005; 94(8):1626-1635.
186. Gregoriadis G, Fernandes A, Mital M, et al. Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics. Cell Mol Life Sci 2000; 57(13-14):1964-1969.
187. Alley SC, Benjamin DR, Jeffrey SC, et al. Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjugate Chem 2008; 19:759-765.
188. Vaishnaw AK, TenHoor CN, Pharmacokinetics, biologic activity, and tolerability of alefacept by intravenous and intramuscular administration. J Pharmacokinet Pharmacodyn 2002; 29(5-6):415-426.
189. Dianello CA, Setting the cytokine trap for autoimmunity. Nat Med 2003; 9:20-22.
190. Balan V, Nelson DR, Sulkowski MS, et al. A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy. Antiviral Ther 2006; 11(1):35-45.
191. Yao Z, Dai W, Perry J, et al. Effect of albumin fusion on the biodistribution of interleukin-2. Cancer Immunol Immunother 2004; 53(5):404-410.