PEGylation of therapeutic proteins

Biotechnology Journal

Volumn 5, Issue 1, 2010, Pages 113-128

  Jevševar, Simona ^a   Kunstelj, Menči ^a   Porekar, Vladka Gaberc ^b  

^a Lek dd   (Slovenia)

^b NATIONAL INSTITUTE OF CHEMISTRY   (Slovenia)

Author keywords

Analysis; Immunogenicity; Pegylated therapeutics; PEGylation; Separation

Indexed keywords

BIOPHARMACEUTICALS; FOOD AND DRUG ADMINISTRATION; IMMUNOGENICITY; MOLECULAR SIZE; NANOBODIES; PEGYLATION; PHARMACOKINETIC PROPERTIES; PHYSICOCHEMICAL PROPERTY; POST-PRODUCTION; PROTEIN CONJUGATES; RAPID SCREENING; THERAPEUTIC PROTEIN;

LIGANDS; POLYETHYLENE GLYCOLS; PURIFICATION; SEPARATION;

PROTEINS;

ALPHA2B INTERFERON; ASPARAGINASE MACROGOL; BETA GLUCURONIDASE; CERTOLIZUMAB PEGOL; CONTINUOUS ERYTHROPOIESIS RECEPTOR ACTIVATOR; MACROGOL; MACUVERSE; PEGADEMASE; PEGAPTANIB; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; PEGVISOMANT; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; UNCLASSIFIED DRUG; URATE OXIDASE;

ARTICLE; CLINICAL TRIAL; DRUG ELIMINATION; DRUG FORMULATION; DRUG HALF LIFE; DRUG MANUFACTURE; DRUG SAFETY; DRUG SCREENING; HUMAN; HYPERURICEMIA; IMMUNOGENICITY; NONHUMAN; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; PROTEIN PURIFICATION; SEPARATION TECHNIQUE;

COATED MATERIALS, BIOCOMPATIBLE; DRUG CARRIERS; DRUG COMPOUNDING; POLYETHYLENE GLYCOLS; PROTEINS;

EID: 75649099024     PISSN: 18606768     EISSN: 18607314     Source Type: Journal    
DOI: 10.1002/biot.200900218     Document Type: Article

References (79)

1. Szymkowski, D. E., Creating the next generation of protein therapeutics through rational drug design. Curr. Opin. Drug Discov. Dev. 2005, 8, 590-600.
2. Abuchowski, A., Vanes, T., Palczuk, N. C., Davis, F. F., Alteration of immunological properties of bovine serum-albumin by covalent attachment of polyethylene-glycol. J. Biol. Chem. 1977, 252, 3578-3581.
3. Abuchowski, A., Mccoy, J. R., Palczuk, N. C., Vanes, T. et al., Effect of covalent attachment of polyethyleneglycol on immunogenicity and circulating life of bovine liver catalase. J. Biol. Chem. 1977, 252, 3582-3586.
4. Levy, Y., Hershfield, M. S., Fernandez-Mejia, C., Polmar, S. H. et al., Adenosine deaminase deficiency with late onset of recurrent infections: Response to treatment with polyethylene glycol-modified adenosine deaminase. J. Pediatr. 1988, 113, 312-317.
5. Ng, E.W., Shima, D.T., Calias, P., Cunningham, E.T., Jr. et al., Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat. Rev. Drug Discov. 2006, 5, 123-132.
6. Serruys, P.W., Heyndrickx, G. R., Patel, J., Cummins, P. A. et al., Effect of an anti-PDGF-beta-receptor-blocking antibody on restenosis in patients undergoing elective stent placement. Int. J. Cardiovasc. Intervent. 2003, 5, 214-222.
7. Baker, D. P., Lin, E.Y., Lin, K., Pellegrini, M. et al., N-terminally PEGylated human interferon-beta-1a with improved pharmacokinetic properties and in vivo efficacy in a melanoma angiogenesis model. Bioconjug. Chem. 2006, 17, 179-188.
8. Sherman, M. R., Saifer, M. G., Perez-Ruiz, F., PEG-uricase in the management of treatment-resistant gout and hyperuricemia. Adv. Drug Deliv. Rev. 2008, 60, 59-68.
9. Bailon, P., Won, C.Y., PEG-modified biopharmaceuticals. Expert. Opin. Drug Deliv. 2009, 6, 1-16.
10. Kang, J. S., DeLuca, P. P., Lee, K. C., Emerging PEGylated drugs. Expert Opin. Emerg. Drugs 2009, 14, 363-380.
11. Ryan, S. M., Mantovani, G., Wang, X., Haddleton, D. M. et al., Advances in PEGylation of important biotech molecules: Delivery aspects. Expert Opin. Drug Deliv. 2008, 5, 371-383.
12. Gebauer, M., Skerra, A., Engineered protein scaffolds as next-generation antibody therapeutics. Curr. Opin. Chem. Biol. 2009, 13, 245-255.
13. Nuttall, S. D., Walsh, R. B., Display scaffolds: Protein engineering for novel therapeutics. Curr. Opin. Pharmacol. 2008, 8, 609-615.
14. Skerra, A., Alternative non-antibody scaffolds for molecular recognition. Curr. Opin. Biotechnol. 2007, 18, 295-304.
15. Harmsen, M. M., De Haard, H. J., Properties, production, and applications of camelid single-domain antibody fragments. Appl. Microbiol. Biotechnol. 2007, 77, 13-22.
16. Wesolowski, J., Alzogaray, V., Reyelt, J., Unger, M. et al., Single domain antibodies: Promising experimental and therapeutic tools in infection and immunity. Med. Microbiol. Immunol. 2009, 198, 157-174.
17. Fishburn, C. S., The pharmacology of PEGylation: Balancing PD with PK to generate novel therapeutics. J. Pharm. Sci. 2008, 97, 4167-4183.
18. Hamidi, M., Rafiei, P., Azadi, A., Designing PEGylated therapeutic molecules: Advantages in ADMET properties. Expert Opin. Drug Discov. 2008. 1293, 3, 1293-1307.
19. Veronese, F. M., Caliceti, P., Schiavon, O., Branched and linear poly(ethylene glycol): Influence of the polymer structure on enzymological, pharmacokinetic, and immunological properties of protein conjugates. J. Bioact. Comp. Polym. 1997, 12, 196-207.
20. Kawai, F., Microbial degradation of polyethers. Appl. Microbiol. Biotechnol. 2002, 58, 30-38.
21. Mehvar, R., Modulation of the pharmacokinetics and pharmacodynamics of proteins by polyethylene glycol conjugation. J. Pharm. Pharm. Sci. 2000, 3, 125-136.
22. Beranova, M., Wasserbauer, R., Vancurova, D., Stifter, M. et al., Effect of cytochrome P-450 inhibition and stimulation on intensity of polyethylene degradation in microsomal fraction of mouse and rat livers. Biomaterials 1990, 11, 521-524.
23. Caliceti, P., Veronese, F. M., Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv. Drug Deliv. Rev. 2003, 55, 1261-1277.
24. Pasut, G., Veronese, F. M., Polymer-drug conjugation, recent achievements and general strategies . Prog.Polym. Sci. 2007, 32, 933-961.
25. Filpula, D., Zhao, H., Releasable PEGylation of proteins with customized linkers. Adv. Drug Deliv. Rev. 2008, 60, 29-49.
26. Basu, A., Yang, K., Wang, M., Liu, S. et al., Structure-function engineering of interferon-beta-1b for improving stability, solubility, potency, immunogenicity, and pharmacokinetic properties by site-selective mono-PEGylation. Bioconjug. Chem. 2006, 17, 618-630.
27. Bailon, P., Palleroni, A., Schaffer, C.A., Spence, C.L. 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, 195-202.
28. Sehon, A. H., Suppression of antibody responses by conjugates of antigens and monomethoxypoly(ethylene glycol). Adv. Drug Deliv. Rev. 1991, 6, 203-217.
29. Ganson, N. J., Kelly, S. J., Scarlett, E., Sundy, J. S. et al., Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase. Arthritis Res.Ther. 2006, 8, R12.
30. Judge, A., McClintock, K., Phelps, J. R., MacLachlan, I., Hypersensitivity and loss of disease site targeting caused by antibody responses to PEGylated liposomes. Mol. Ther. 2006, 13, 328-337.
31. Wang, X., Ishida, T., Kiwada, H., Anti-PEG IgM elicited by injection of liposomes is involved in the enhanced blood clearance of a subsequent dose of PEGylated liposomes. J. Control Release 2007, 119, 236-244.
32. Cheng, T. L., Chen, B. M., Chern, J.W., Wu, M. F. et al., Efficient clearance of poly(ethylene glycol)-modified immunoenzyme with anti-PEG monoclonal antibody for prodrug cancer therapy. Bioconjug. Chem. 2000, 11, 258-266.
33. Hamad, I., Hunter, A. C., Szebeni, J., Moghimi, S. M., Poly(ethylene glycol)s generate complement activation products in human serum through increased alternative pathway turnover and a MASP-2-dependent process. Mol. Immunol. 2008, 46, 225-232.
34. Bendele, A., Seely, J., Richey, C., Sennello, G. et al., Short communication: Renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol. Sci. 1998, 42, 152-157.
35. Caliceti, P., Schiavon, O., Veronese, F. M., Immunological properties of uricase conjugated to neutral soluble polymers. Bioconjug. Chem. 2001, 12, 515-522.
36. Richter, A.W., Akerblom, E., Antibodies against polyethylene glycol produced in animals by immunization with monomethoxy polyethylene glycol modified proteins. Int. Arch. Allergy Appl. Immunol. 1983, 70, 124-131.
37. Roberts, M. J., Bentley, M.D., Harris, J. M., Chemistry for peptide and protein PEGylation. Adv. Drug Deliv. Rev. 2002, 54, 459-476.
38. Harris, J. M., Chess, R. B., Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov. 2003, 2, 214-221.
39. Bukowski, R., Ernstoff, M. S., Gore, M. E., Nemunaitis, J. J. et al., Pegylated interferon alfa-2b treatment for patients with solid tumors: A phase I/II study. J. Clin. Oncol. 2002, 20, 3841-3849.
40. Gregoriadis, G., Jain, S., Papaioannou, I., Laing, P., Improving the therapeutic efficacy of peptides and proteins: A role for polysialic acids. Int. J. Pharm. 2005, 300, 125-130.
41. Abuchowski, A., Kazo, G. M., Verhoest, C. R. Jr., Van Es, T. et al., Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycol-asparaginase conjugates. Cancer Biochem. Biophys. 1984, 7, 175-186.
42. Zalipsky, S., Seltzer, R., Menon-Rudolph, S., Evaluation of a new reagent for covalent attachment of polyethylene glycol to proteins. Biotechnol. Appl. Biochem. 1992, 15, 100-114.
43. Zalipsky, S., Seltzer, R., Nho, K., Succinimidyl carbonates of polyethylene glycol, in: Dunn, R. L., Ottenbrite, R. M. (Ed.), Polymeric Drugs and Drug Delivery Systems, American Chemical Society, Wasington, DC 1991.
44. Kinstler, O., Molineux, G., Treuheit, M., Ladd, D. et al., Mono-N-terminal poly(ethylene glycol)-protein conjugates. Adv. Drug Deliv. Rev. 2002, 54, 477-485.
45. Molineux, G., The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta). Curr. Pharm. Des. 2004, 10, 1235-1244.
46. Veronese, F. M., Mero, A., Caboi, F., Sergi, M. et al., Site-specific pegylation of G-CSF by reversible denaturation. Bioconjug. Chem. 2007, 18, 1824-1830.
47. Doherty, D. H., Rosendahl, M. S., Smith, D. J., Hughes, J.M. et al., Site-specific PEGylation of engineered cysteine analogues of recombinant human granulocyte-macrophage colony-stimulating factor. Bioconjug. Chem. 2005, 16, 1291-1298.
48. Rosendahl, M. S., Doherty, D. H., Smith, D. J., Carlson, S. J. et al., A long-acting, highly potent interferon alpha-2 conjugate created using site-specific PEGylation. Bioconjug. Chem. 2005, 16, 200-207.
49. Humphreys, D. P., Heywood, S. P., Henry, A., Ait-Lhadj, L. et al., Alternative antibody Fab' fragment PEGylation strategies: Combination of strong reducing agents, disruption of the interchain disulphide bond and disulphide engineering. Protein Eng. Des. Sel. 2007, 20, 227-234.
50. Balan, S., Choi, J.W., Godwin, A., Teo, I. et al., Site-specific PEGylation of protein disulfide bonds using a three-carbon bridge. Bioconjug. Chem. 2007, 18, 61-76.
51. Shaunak, S., Godwin, A., Choi, J.W., Balan, S. et al., Site-specific PEGylation of native disulfide bonds in therapeutic proteins. Nat. Chem. Biol. 2006, 2, 312-313.
52. Deiters, A., Schultz, P. G., In vivo incorporation of an alkyne into proteins in Escherichia coli. Bioorg. Med. Chem. Lett. 2005, 15, 1521-1524.
53. Sato, H., Enzymatic procedure for site-specific pegylation of proteins. Adv. Drug Deliv. Rev. 2002, 54, 487-504.
54. Fontana, A., Spolaore, B., Mero, A., Veronese, F. M., Site-specific modification and PEGylation of pharmaceutical proteins mediated by transglutaminase. Adv. Drug Deliv. Rev. 2008, 60, 13-28.
55. DeFrees, S., Wang, Z. G., Xing, R., Scott, A. E. et al., GlycoPEGylation of recombinant therapeutic proteins produced in Escherichia coli. Glycobiology 2006, 16, 833-843.
56. Fee, C. J., Van Alstine, J. M., PEG-proteins: Reaction engineering and separation issues. Chem. Eng. Sci. 2006, 61, 924-939.
57. Kusterle, M., Jevsevar, S., Porekar, V. G., Size of pegylated protein conjugates studied by various methods. Acta Chim. Sloven. 2008, 55, 594-601.
58. Fee, C. J., Size comparison between proteins PEGylated with branched and linear Poly(Ethylene glycol) molecules. Biotechnol. Bioeng. 2007, 98, 725-731.
59. Seely, J. E., Richey, C.W., Use of ion-exchange chromatography and hydrophobic interaction chromatography in the preparation and recovery of polyethylene glycol-linked proteins. J. Chromatogr. A 2001, 908, 235-241.
60. Seely, J. E., Buckel, S. D., Green, P. D., Richey, C.W., Making site-specific PEGylation work. Biopharm Int. 2005, 18, 30-130.
61. Caserman, S., Kusterle, M., Kunstelj, M., Milunovic, T. et al., Correlations between in vitro potency of polyethylene glycol-protein conjugates and their chromatographic behavior. Anal. Biochem. 2009, 389, 27-31.
62. Chapman, A. P., Antoniw, P., Spitali, M., West, S. et al., Therapeutic antibody fragments with prolonged in vivo half-lives. Nat. Biotechnol. 1999, 17, 780-783.
63. Foser, S., Schacher, A., Weyer, K. A., Brugger, D. et al., Isolation, structural characterization, and antiviral activity of positional isomers of monopegylated interferon alpha-2a (PEGASYS). Protein Expr. Purif. 2003, 30, 78-87.
64. Yun, Q., Yang, R. E., Chen, T., Bi, J. et al., Reproducible preparation and effective separation of PEGylated recombinant human granulocyte colony-stimulating factor with novel ., PEG-pellet" PEGylation mode and ion-exchange chromatography. J. Biotechol. 2005. 118, 67-74.
65. Pabst, T. M., Buckley, J. J., Ramasubramanyan, N., Hunter, A. K., Comparison of strong anion-exchangers for the purification of a PEGylated protein. J. Chromatogr. A 2007, 1147, 172-182.
66. Edwards, C. K., III, Martin, S.W., Seely, J., Kinstler, O. et al., Design of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) for chronic inflammatory diseases. Adv. Drug Deliv. Rev. 2003, 55, 1315-1336.
67. Molek, J. R., Zydney, A. L., Ultrafiltration characteristics of pegylated proteins. Biotechnol. Bioeng. 2006, 95, 474-482.
68. Kou, D., Manius, G., Zhan, S., Chokshi, H. P., Size exclusion chromatography with Corona charged aerosol detector for the analysis of polyethylene glycol polymer. J. Chromatogr. A 2009, 1216, 5424-5428.
69. Montaudo, G., Samperi, F., Montaudo, M.S., Characterization of synthetic polymers by MALDI-MS. Prog.Polym. Sci. 2006, 31, 277-357.
70. Fee, C. J., Van Alstine, J. M., Prediction of the viscosity radius and the size exclusion chromatography behavior of PEGylated proteins. Bioconjug. Chem. 2004, 15, 1304-1313.
71. Gaberc-Porekar, V., Zore, I., Podobnik, B., Menart, V., Obstacles and pitfalls in the PEGylation of therapeutic proteins. Curr. Opin. Drug Discov. Dev. 2008, 11, 242-250.
72. Piedmonte, D. M., Treuheit, M.J., Formulation of Neulasta(R) (pegfilgrastim). Adv. Drug Deliv. Rev. 2008, 60, 50-58.
73. Kurfurst, M. M., Detection and molecular-weight determination of polyethylene glycol-modified hirudin by staining after sodium dodecyl-sulfate polyacrylamide-gel electrophoresis. Anal. Biochem. 1992, 200, 244-248.
74. Wang, Y. S., Youngster, S., Grace, M., Bausch, J. et al., Structural and biological characterization of pegylated recombinant interferon alpha-2b and its therapeutic implications. Adv. Drug Deliv. Rev. 2002, 54, 547-570.
75. Srebalus Barnes, C. A., Lim, A., Applications of mass spectrometry for the structural characterization of recombinant protein pharmaceuticals. Mass Spectrom. Rev. 2007, 26, 370-388.
76. Cindric, M., Cepo, T., Galic, N., Bukvic-Krajacic, M. et al., Structural characterization of PEGylated rHuG-CSF and location of PEG attachment sites. J. Pharm. Biomed. Anal. 2007, 44, 388-395.
77. Mero, A., Spolaore, B., Veronese, F. M., Fontana, A., Transglutaminase-mediated PEGylation of proteins: Direct identification of the sites of protein modification by mass spectrometry using a novel monodisperse PEG. Bioconjug. Chem. 2009, 20, 384-389.
78. Mahmood, I., Green, M. D., Pharmacokinetic and pharmacodynamic considerations in the development of therapeutic proteins. Clin. Pharmacokinet. 2005, 44, 331-347.
79. Roovers, R. C., van Dongen, G. A., van Bergen en Henegouwen, P. M., Nanobodies in therapeutic applications. Curr. Opin. Mol.Ther. 2007, 9, 327-335.