RENT TEXTBOOKS

The state of the art in biopharmaceutical FUSION PROTEIN DESIGN

Fusion proteins belong to the most lucrative biotech drugs?with Enbrel® being one of the best-selling biologics worldwide. Enbrel® represents a milestone of modern therapies just as Humulin®, the first therapeutic recombinant protein for human use, approved by the FDA in 1982 and Orthoclone® the first monoclonal antibody reaching the market in 1986. These fi... MORErst generation molecules were soon followed by a plethora of recombinant copies of natural human proteins, and in 1998, the first de novo designed fusion protein was launched.

Fusion Protein Technologies for Biopharmaceuticals examines the state of the art in developing fusion proteins for biopharmaceuticals, shedding light on the immense potential inherent in fusion protein design and functionality. A wide pantheon of international scientists and researchers deliver a comprehensive and complete overview of therapeutic fusion proteins, combining the success stories of marketed drugs with the dynamic preclinical and clinical research into novel drugs designed for as yet unmet medical needs.

The book covers the major types of fusion proteins?receptor-traps, immunotoxins, Fc-fusions and peptibodies?while also detailing the approaches for developing, delivering, and improving the stability of fusion proteins. The main body of the book contains three large sections that address issues key to this specialty: strategies for extending the plasma half life, the design of toxic proteins, and utilizing fusion proteins for ultra specific targeting. The book concludes with novel concepts in this field, including examples of highly relevant multifunctional antibodies.

Detailing the innovative science, commercial realities, and brilliant potential of fusion protein therapeutics, Fusion Protein Technologies for Biopharmaceuticals is a must for pharmaceutical scientists, biochemists, medicinal chemists, molecular biologists, pharmacologists, and genetic engineers interested in determining the shape of innovation in the world of biopharmaceuticals.

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 Therape... MOREutic 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, Gráinne 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 Jürgen 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 Gattenlöhner 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, Göran 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
Andrés Muñoz-Alarcón, Henrik Helmfors, Kristin Karlsson and Ülo Langel

27. Cell-Specific Targeting of Fusion Proteins through Heparin-Binding
Jiajing Wang, Zhenzhong Ma, Jeffrey A. Loeb

28. Bone-Targeted Alkaline Phosphatase
José Luis Millán

29. Targeting Interferon Alpha to the Liver: Apolipoprotein A-I as a Scaffold for Protein Delivery
Jessica Fioravanti, Jesús 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 Björn 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 Woisetschläger, Florian Rüker, 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

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.