Polymer–Protein Conjugates: From Pegylation and Beyond helps researchers by offering a unique reference and guide into this fascinating area. Sections cover the challenges surrounding the homogeneity of conjugates, their purity and polymer toxicity on long-term use, and how to deal with the risk of immunogenicity. These discussions help researchers design new projects by taking into account the latest innovations for safe and site selective polymer conjugation to proteins. PEG has been the gold standard and likely will play this role for many years, but alternatives are coming into the market, some of which have already been launched.
After five decades of improvements, the ideas in this book are entering into a new era of innovation because of the advances in genetic engineering, biochemistry and a better understanding of the results from clinical use of PEG conjugates in humans.
1. Part 1. Introduction and general aspects of the technology - p. xxv 2. 1. Evolution of polymer conjugation to proteins - p. 3 3. 2. PEGylated proteins: A rational design for mitigating clearance mechanisms and altering biodistribution - p. 23 4. 3. Overcoming barriers for tumor-targeted drug delivery: the power of macromolecular anticancer drugs with the EPR effect and the modulation of vascular physiology - p. 41 5. Part 2. Toxicity and immunogenicity studies and clinical stage conjugate products - p. 58 6. 4. PEG–protein conjugates: nonclinical and clinical toxicity considerations - p. 61 7. 5. Immunological responses to PEGylated proteins: anti-PEG antibodies - p. 103 8. 6. Immunogenicity assessment of PEGylated proteins, Lonquex, a PEGylated G-CSF case study - p. 125 9. 7. PEG–protein conjugates; regulatory requirements for characterization - p. 141 10. 8. PEGylation of human coagulation factor VIII and other plasma proteins - p. 155 11. 9. Pegvorhyaluronidase alfa: a PEGylated recombinant human hyaluronidase PH20 for the treatment of cancers that accumulate hyaluronan - p. 175 12. 10. Challenges in the analytical characterization of PEGylated asparaginase - p. 205 13. Part 3. Novel site-selective methods of conjugation - p. 231 14. 11. Glycan-targeted PEGylation for selective modification of proteins - p. 235 15. 12. Sialyltransferase-mediated glycoPEGylation - p. 251 16. 13. Enzymatic approaches to new protein conjugates - p. 271 17. 14. Site-specific polymer–protein conjugates by Cys mutation - p. 297 18. 15. Site-specific PEGylation of interferon beta-1b: from bench to clinic - p. 317 19. 16. Protein modification by bis-alkylation - p. 351 20. Part 4. Alternative non-PEG polymers and architectures - p. 385 21. 17. In vivo properties of therapeutic bioconjugates composed of proteins and architecturally/functionally complex polymers - p. 389 22. 18. Poly(2-oxazoline)–protein conjugates - p. 407 23. 19. Polysaccharides for protein and peptide conjugation - p. 421 24. 20. Polysialylation of human coagulation factor VIII - p. 455 25. PEGylation and polymer conjugation - p. 471 26. Index - p. 473
Polymer–Protein Conjugates: From Pegylation and Beyond helps researchers by offering a unique reference and guide into this fascinating area. Sections cover the challenges surrounding the homogeneity of conjugates, their purity and polymer toxicity on long-term use, and how to deal with the risk of immunogenicity. These discussions help researchers design new projects by taking into account the latest innovations for safe and site selective polymer conjugation to proteins. PEG has been the gold standard and likely will play this role for many years, but alternatives are coming into the market, some of which have already been launched.
After five decades of improvements, the ideas in this book are entering into a new era of innovation because of the advances in genetic engineering, biochemistry and a better understanding of the results from clinical use of PEG conjugates in humans.
1. Part 1. Introduction and general aspects of the technology - p. xxv 2. 1. Evolution of polymer conjugation to proteins - p. 3 3. 2. PEGylated proteins: A rational design for mitigating clearance mechanisms and altering biodistribution - p. 23 4. 3. Overcoming barriers for tumor-targeted drug delivery: the power of macromolecular anticancer drugs with the EPR effect and the modulation of vascular physiology - p. 41 5. Part 2. Toxicity and immunogenicity studies and clinical stage conjugate products - p. 58 6. 4. PEG–protein conjugates: nonclinical and clinical toxicity considerations - p. 61 7. 5. Immunological responses to PEGylated proteins: anti-PEG antibodies - p. 103 8. 6. Immunogenicity assessment of PEGylated proteins, Lonquex, a PEGylated G-CSF case study - p. 125 9. 7. PEG–protein conjugates; regulatory requirements for characterization - p. 141 10. 8. PEGylation of human coagulation factor VIII and other plasma proteins - p. 155 11. 9. Pegvorhyaluronidase alfa: a PEGylated recombinant human hyaluronidase PH20 for the treatment of cancers that accumulate hyaluronan - p. 175 12. 10. Challenges in the analytical characterization of PEGylated asparaginase - p. 205 13. Part 3. Novel site-selective methods of conjugation - p. 231 14. 11. Glycan-targeted PEGylation for selective modification of proteins - p. 235 15. 12. Sialyltransferase-mediated glycoPEGylation - p. 251 16. 13. Enzymatic approaches to new protein conjugates - p. 271 17. 14. Site-specific polymer–protein conjugates by Cys mutation - p. 297 18. 15. Site-specific PEGylation of interferon beta-1b: from bench to clinic - p. 317 19. 16. Protein modification by bis-alkylation - p. 351 20. Part 4. Alternative non-PEG polymers and architectures - p. 385 21. 17. In vivo properties of therapeutic bioconjugates composed of proteins and architecturally/functionally complex polymers - p. 389 22. 18. Poly(2-oxazoline)–protein conjugates - p. 407 23. 19. Polysaccharides for protein and peptide conjugation - p. 421 24. 20. Polysialylation of human coagulation factor VIII - p. 455 25. PEGylation and polymer conjugation - p. 471 26. Index - p. 473
