Fusion Protein Technologies for Biopharmaceuticals – Applications and Challenges

STEFAN R. SCHMIDT, PhD , is Vice President for Downstream Processing at Rentschler Biotechnology. Previously, he served as CSO at ERA Biotech and Associate Director for Protein Science at AstraZeneca. Dr. Schmidt has chaired many international conferences and written several original articles, reviews, and book chapters.

Preface Contributors Part I INTRODUCTION 1. Fusion Proteins: Applications and Challenges Stefan R. Schmidt 2. Analysing and Forecasting the Fusion Protein Market and Pipeline Mark Belsey and Giles Somer 3. Structural Aspects of Fusion Proteins Determining the Level of Commercial Success Mark Belsey and Giles Somer 4. Fusion Protein Linkers: Effects on Production, Bioactivity, and Pharmacokinetics Xiaoying Chen, Jennica Zaro, and Wei-Chiang Shen 5. Immunogenicity of Therapeutic Fusion Proteins: Contributory Factors and Clinical Experience Vibha Jawa, Leslie Cousens, Anne S. De Groot Part II THE TRIPLE T PARADIGM: TIME, TOXIN, TARGETING II a) TIME: FUSION PROTEIN STRATEGIES FOR HALF LIFE EXTENSION 6. Fusion Proteins for Half Life Extension Stefan R. Schmidt 7. Monomeric Fc Fusion Proteins Baisong Mei, Susan C. Low, Snejana Krassova, Robert T. Peters, Glenn F. Pierce and Jennifer A. Dumont 8. Peptide-Fc Fusion Therapeutics: Applications and Challenges Chichi Huang and Ronald V. Swanson 9. Receptor-Fc and Ligand Traps as High Affinity Biological Blockers: Development and Clinical Applications Aris N. Economides and Neil Stahl 10. Recombinant Albumin Fusion Proteins Thomas Weimer, Hubert J. Metzner and Stefan Schulte 11. Albumin Binding Fusion Proteins in the Development of Novel Long-Acting Therapeutics Adam Walker, Grainne Dunlevy and Peter Topley 12. Transferrin Fusion Protein Therapies: Acetylcholine Receptor-Transferrin Fusion Protein as a Model Dennis Keefe, Michael Heartlein and Serene Josiah 13. Half Life Extension Through O-Glycosylation Fuad Fares 14. ELP Fusion Technology for Biopharmaceuticals Doreen M. Floss, Udo Conrad, Stefan Rose-John and Jurgen Scheller 15. Ligand-Receptor Fusion Dimers Sarbendra L. Pradhananga, Ian R. Wilkinson, Eric Ferrandis, Peter J. Artymiuk, Jon R. Sayers and Richard J. Ross 16. Development of Latent Cytokine Fusion Proteins Lisa Mullen, Gill Adams, Rewas Fatah, David Gould, Anne Rigby, Michelle Sclanders, Apostolos Koutsokeras, Gayatri Mittal, Sandrine Vessillier and Yuti Chernajovsky II b) TOXIN: CYTOTOXIC FUSION PROTEINS 17. Fusion Proteins with Toxic Activity Stefan R. Schmidt 18. Classic Immunotoxins with Plant or Microbial Toxins Jung Hee Woo and Arthur Frankel 19. Targeted and Untargeted Fusion Proteins: Current Approaches to Cancer Immunotherapy Leslie A. Khawli, Peisheng Hu, and Alan L. Epstein 20. Development of Experimental Targeted Toxin Therapies for Malignant Glioma Nikolai G. Rainov and Volkmar Heidecke 21. Immunokinases Stefan Barth, Stefan Gattenlohner and Mehmet Kemal Tur 22. ImmunoRNase Fusions Wojciech Ardelt 23. Antibody Directed Enzyme Prodrug Therapy (ADEPT) Surinder K. Sharma 24. Tumor Targeted Superantigens Gunnar Hedlund, Goran Forsberg, Thore Nederman, Anette Sundstedt, Leif Dahlberg, Mikael Tiensuu and Mats Nilsson II c) TARGETING: FUSION PROTEINS ADDRESSING SPECIFIC CELLS, ORGANS AND TISSUES 25. Fusion Proteins with a Targeting Function Stefan R. Schmidt 26. Cell-Penetrating Peptide Fusion Proteins Andres Munoz-Alarcon, Henrik Helmfors, Kristin Karlsson and Ulo Langel 27. Cell-Specific Targeting of Fusion Proteins through Heparin-Binding Jiajing Wang, Zhenzhong Ma, Jeffrey A. Loeb 28. Bone-Targeted Alkaline Phosphatase Jose Luis Millan 29. Targeting Interferon Alpha to the Liver: Apolipoprotein A-I as a Scaffold for Protein Delivery Jessica Fioravanti, Jesus Prieto, Pedro Berraondo PART III: BEYOND THE TRIPLE T-PARADIGM III a) NOVEL CONCEPTS, NOVEL SCAFFOLDS 30. Signal Converter Proteins Mark L. Tykocinski 31. Soluble T-cell Antigen Receptors Peter R. Rhode 32. High Affinity monoclonal T-cell receptor (mTCR) fusions Nikolai M. Lissin, Namir J. Hassan and Bent K. Jakobsen 33. Amediplase Stefano Evangelista and Stefano Manzini 34. Breaking New Therapeutic Grounds: Fusion Proteins of DARPins and Other Non-Antibody Binding Proteins H. Kaspar Binz III b) MULTIFUNCTIONAL ANTIBODIES 35. Resurgence of Bispecific Antibodies Patrick A. Baeuerle and Tobias Raum 36. Novel Applications of Bispecific DART Proteins Syd Johnson, Bhaswati Barat, Paul Moore and Ezio Bonvini 37. Strand Exchange Engineered Domain (SEED): A Novel Platform Designed to Generate Mono and Multispecific Protein Therapeutics Alec W. Gross, Jessica P. Dawson, Marco Muda, Christie Kelton, Sean D. McKenna, and Bjorn Hock 38. CovX-Bodies Abhijit Bhat, Olivier Laurent, Rodney Lappe 39. Modular Antibody Engineering: Antigen Binding Immunoglobulin Fc CH3 Domains as Building Blocks for Bi-Specific Antibodies (mAb2) Maximilian Woisetschlager, Florian Ruker, Geert C Mudde, Gordana Wozniak-Knopp, Anton Bauer and Gottfried Himmler 40. Designer Fusion Modules for Building Multifunctional, Multivalent Antibodies and Immunoconjugates: The Dock-and-Lock Method Edmund A. Rossi David M. Goldenberg and Chien-Hsing Chang Index