Fusion Protein Technologies for Biopharmaceuticals

Applications and Challenges

Schmidt, Stefan R. (Herausgeber)

1. Auflage April 2013
672 Seiten, Hardcover
Wiley & Sons Ltd

ISBN: 978-0-470-64627-4

John Wiley & Sons

Kurzbeschreibung

This book presents the state-of-the-art for development of fusion proteins, demonstrates current concepts, describes multiple applications, and discusses typical challenges linked to these molecules. It overviews the multitude of possibilities to design novel protein drugs while balancing between proven concepts and new ideas that have not reached the clinic yet. The book is structured into three larger parts. First general issues and concepts are discussed before in the second part examples on the three categories (time, toxicity, and targeting) are presented. Finally, novel concepts and the rising class of multispecifc antibodies are described. Together, the chapters combine the success stories of marketed drugs with the dynamic preclinical and clinical research into novel drugs addressing unmet medical needs.

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PREFACE xxiii

CONTRIBUTORS xxv

PART I INTRODUCTION 1

1 Fusion Proteins: Applications and Challenges 3
Stefan R. Schmidt

References, 18

2 Analyzing and Forecasting the Fusion Protein Market and Pipeline 25
Mark Belsey and Giles Somers

Disclaimer, 36

Acknowledgment, 36

References, 36

3 Structural Aspects of Fusion Proteins Determining the Level of Commercial Success 39
Giles Somers

References, 54

4 Fusion Protein Linkers: Effects on Production, Bioactivity, and Pharmacokinetics 57
Xiaoying Chen, Jennica Zaro, and Wei-Chiang Shen

References, 71

5 Immunogenicity of Therapeutic Fusion Proteins: Contributory Factors and Clinical Experience 75
Vibha Jawa, Leslie Cousens, and Anne S. De Groot

Acknowledgment, 87

References, 87

PART II THE TRIPLE T PARADIGM: TIME, TOXIN, TARGETING 91

IIA TIME: FUSION PROTEIN STRATEGIES FOR HALF-LIFE EXTENSION 93

6 Fusion Proteins for Half-Life Extension 93
Stefan R. Schmidt

References, 104

7 Monomeric Fc-Fusion Proteins 107
Baisong Mei, Susan C. Low, Snejana Krassova, Robert T. Peters, Glenn F. Pierce, and Jennifer A. Dumont

References, 118

8 Peptide-Fc Fusion Therapeutics: Applications and Challenges 123
Chichi Huang and Ronald V. Swanson

Acknowledgment, 138

References, 138

9 Receptor-Fc and Ligand Traps as High-Affinity Biological Blockers: Development and Clinical Applications 143
Aris N. Economides and Neil Stahl

Acknowledgment, 155

References, 155

10 Recombinant Albumin Fusion Proteins 163
Thomas Weimer, Hubert J. Metzner, and Stefan Schulte

Acknowledgment, 174

References, 174

11 Albumin-Binding Fusion Proteins in the Development of Novel Long-Acting Therapeutics 179
Adam Walker, Grainne Dunlevy, and Peter Topley

References, 189

12 Transferrin Fusion Protein Therapies: Acetylcholine Receptor-Transferrin Fusion Protein as a Model 191
Dennis Keefe, Michael Heartlein, and Serene Josiah

References, 198

13 Half-Life Extension Through O-Glycosylation 201
Fuad Fares

References, 207

14 ELP-Fusion Technology for Biopharmaceuticals 211
Doreen M. Floss, Udo Conrad, Stefan Rose-John, and JEURurgen Scheller

References, 222

15 Ligand-Receptor Fusion Dimers 227
Sarbendra L. Pradhananga, Ian R. Wilkinson, Eric Ferrandis, Peter J. Artymiuk, Jon R. Sayers, and Richard J. Ross

References, 234

16 Development of Latent Cytokine Fusion Proteins 237
Lisa Mullen, Gill Adams, Rewas Fatah, David Gould, Anne Rigby, Michelle Sclanders, Apostolos Koutsokeras, Gayatri Mittal, Sandrine Vessillier, and Yuti Chernajovsky

Acknowledgments, 249

References, 249

IIB TOXIN: CYTOTOXIC FUSION PROTEINS 253

17 Fusion Proteins with Toxic Activity 253
Stefan R. Schmidt

References, 265

18 Classic Immunotoxins with Plant or Microbial Toxins 271
Jung Hee Woo and Arthur Frankel

References, 286

19 Targeted and Untargeted Fusion Proteins: Current Approaches to Cancer Immunotherapy 295
Leslie A. Khawli, Peisheng Hu, and Alan L. Epstein

Acknowledgments, 310

References, 310

20 Development of Experimental Targeted Toxin Therapies for Malignant Glioma 315
Nikolai G. Rainov and Volkmar Heidecke

Disclosure, 325

References, 325

21 Immunokinases 329
Stefan Barth, Stefan GattenlEURohner, and Mehmet Kemal Tur

References, 334

22 ImmunoRNase Fusions 337
Wojciech Ardelt

References, 347

23 Antibody-Directed Enzyme Prodrug Therapy (ADEPT) 355
Surinder K. Sharma

Acknowledgments, 361

References, 361

24 Tumor-Targeted Superantigens 365
Gunnar Hedlund, GEURoran Forsberg, Thore Nederman, Anette Sundstedt, Leif Dahlberg, Mikael Tiensuu, and Mats Nilsson

References, 379

IIC TARGETING: FUSION PROTEINS ADDRESSING SPECIFIC CELLS, ORGANS, AND TISSUES 383

25 Fusion Proteins with a Targeting Function 383
Stefan R. Schmidt

References, 393

26 Cell-Penetrating Peptide Fusion Proteins 397
Andres Mu~noz-Alarcon, Henrik Helmfors, Kristin Karlsson, and EURU lo Langel

Acknowledgments, 406

References, 406

27 Cell-Specific Targeting of Fusion Proteins through Heparin Binding 413
Jiajing Wang, Zhenzhong Ma, and Jeffrey A. Loeb

References, 424

28 Bone-Targeted Alkaline Phosphatase 429
Jose Luis Millan

Acknowledgments, 437

References, 437

29 Targeting Interferon-a to the Liver: Apolipoprotein A-I as a Scaffold for Protein Delivery 441
Jessica Fioravanti, Jesus Prieto, and Pedro Berraondo

References, 448

PART III BEYOND THE TRIPLE T-PARADIGM 453

IIIA NOVEL CONCEPTS, NOVEL SCAFFOLDS 455

30 Signal Converter Proteins 455
Mark L. Tykocinski

References, 468

31 Soluble T-Cell Antigen Receptors 475
Peter R. Rhode

Acknowledgments, 490

References, 490

32 High-Affinity Monoclonal T-Cell Receptor (mTCR) Fusions 495
Nikolai M. Lissin, Namir J. Hassan, and Bent K. Jakobsen

Acknowledgments, 504

References, 504

33 Amediplase 507
Stefano Evangelista and Stefano Manzini

Acknowledgment, 517

References, 517

34 Breaking New Therapeutic Grounds: Fusion Proteins of Darpins and Other Nonantibody Binding Proteins 519
Hans Kaspar Binz

Acknowledgments, 526

References, 526

IIIB MULTIFUNCTIONAL ANTIBODIES 529

35 Resurgence of Bispecific Antibodies 529
Patrick A. Baeuerle and Tobias Raum

References, 541

36 Novel Applications of Bispecific DART1 Proteins 545
Syd Johnson, Bhaswati Barat, Hua W. Li, Ralph F. Alderson, Paul A. Moore, and Ezio Bonvini

References, 554

37 Strand Exchange Engineered Domain (Seed): A Novel Platform Designed to Generate Mono and Multispecific Protein Therapeutics 557
Alec W. Gross, Jessica P. Dawson, Marco Muda, Christie Kelton, Sean D. McKenna, and Bjo¨rn Hock

Acknowledgments, 567

References, 567

38 CovX-Bodies 571
Abhijit Bhat, Olivier Laurent, and Rodney Lappe

References, 581

39 Modular Antibody Engineering: Antigen Binding Immunoglobulin Fc CH3 Domains as Building Blocks for Bispecific Antibodies (mAb2) 583
Maximilian WoisetschlEURager, Florian REURuker, Geert C. Mudde, Gordana Wozniak-Knopp, Anton Bauer, and Gottfried Himmler

Acknowledgments, 588

References, 589

40 Designer Fusion Modules for Building Multifunctional, Multivalent Antibodies, and Immunoconjugates: The Dock-and-Lock Method 591
Edmund A. Rossi, David M. Goldenberg, and Chien-Hsing Chang

References, 599

INDEX 603

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.