Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges

Description

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 first 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. Content: Chapter 1 Fusion Proteins: Applications and Challenges (pages 1–24): Stefan R. SchmidtChapter 2 Analyzing and Forecasting the Fusion Protein Market and Pipeline (pages 25–37): Mark Belsey and Giles SomersChapter 3 Structural Aspects of Fusion Proteins Determining the Level of Commercial Success (pages 39–56): Giles SomersChapter 4 Fusion Protein Linkers: Effects on Production, Bioactivity, and Pharmacokinetics (pages 57–73): Xiaoying Chen, Jennica Zaro and Wei?Chiang ShenChapter 5 Immunogenicity of Therapeutic Fusion Proteins: Contributory Factors and Clinical Experience (pages 75–90): Vibha Jawa, Leslie Cousens and Anne S. De GrootChapter 6 Fusion Proteins for Half?Life Extension (pages 91–106): Stefan R. SchmidtChapter 7 Monomeric Fc?Fusion Proteins (pages 107–121): Baisong Mei, Susan C. Low, Snejana Krassova, Robert T. Peters, Glenn F. Pierce and Jennifer A. DumontChapter 8 Peptide?Fc Fusion Therapeutics: Applications and Challenges (pages 123–142): Chichi Huang and Ronald V. SwansonChapter 9 Receptor?Fc and Ligand Traps as High?Affinity Biological Blockers: Development and Clinical Applications (pages 143–162): Aris N. Economides and Neil StahlChapter 10 Recombinant Albumin Fusion Proteins (pages 163–178): Thomas Weimer, Hubert J. Metzner and Stefan SchulteChapter 11 Albumin?Binding Fusion Proteins in the Development of Novel Long?Acting Therapeutics (pages 179–190): Adam Walker, Grainne Dunlevy and Peter TopleyChapter 12 Transferrin Fusion Protein Therapies: Acetylcholine Receptor?Transferrin Fusion Protein as a Model (pages 191–199): Dennis Keefe, Michael Heartlein and Serene JosiahChapter 13 Half?Life Extension through O?Glycosylation (pages 201–209): Fuad FaresChapter 14 ELP?Fusion Technology for Biopharmaceuticals (pages 211–226): Doreen M. Floss, Udo Conrad, Stefan Rose?John and Jurgen SchellerChapter 15 Ligand?Receptor Fusion Dimers (pages 227–235): Sarbendra L. Pradhananga, Ian R. Wilkinson, Eric Ferrandis, Peter J. Artymiuk, Jon R. Sayers and Richard J. RossChapter 16 Development of Latent Cytokine Fusion Proteins (pages 237–252): Lisa Mullen, Gill Adams, Rewas Fatah, David Gould, Anne Rigby, Michelle Sclanders, Apostolos Koutsokeras, Gayatri Mittal, Sandrine Vessillier and Yuti ChernajovskyChapter 17 Fusion Proteins with Toxic Activity (pages 253–269): Stefan R. SchmidtChapter 18 Classic Immunotoxins with Plant or Microbial Toxins (pages 271–293): Jung Hee Woo and Arthur FrankelChapter 19 Targeted and Untargeted Fusion Proteins: Current Approaches to Cancer Immunotherapy (pages 295–314): Leslie A. Khawli, Peisheng Hu and Alan L. EpsteinChapter 20 Development of Experimental Targeted Toxin Therapies for Malignant Glioma (pages 315–328): Nikolai G. Rainov and Volkmar HeideckeChapter 21 Immunokinases (pages 329–336): Stefan Barth, Stefan Gattenlohner and Mehmet Kemal TurChapter 22 ImmunoRNase Fusions (pages 337–353): Wojciech ArdeltChapter 23 Antibody?Directed Enzyme Prodrug Therapy (ADEPT) (pages 355–363): Surinder K. SharmaChapter 24 Tumor?Targeted Superantigens (pages 365–381): Gunnar Hedlund, Goran Forsberg, Thore Nederman, Anette Sundstedt, Leif Dahlberg, Mikael Tiensuu and Mats NilssonChapter 25 Fusion Proteins with a Targeting Function (pages 383–395): Stefan R. SchmidtChapter 26 Cell?Penetrating Peptide Fusion Proteins (pages 397–411): Andres Munoz?Alarcon, Henrik Helmfors, Kristin Karlsson and Ulo LangelChapter 27 Cell?Specific Targeting of Fusion Proteins through Heparin Binding (pages 413–427): Jiajing Wang, Zhenzhong Ma and Jeffrey A. LoebChapter 28 Bone?Targeted Alkaline Phosphatase (pages 429–439): Jose Luis MillanChapter 29 Targeting Interferon?? to the Liver: Apolipoprotein A?I as a Scaffold for Protein Delivery (pages 441–452): Jessica Fioravanti, Jesus Prieto and Pedro BerraondoChapter 30 Signal Converter Proteins (pages 453–473): Mark L. TykocinskiChapter 31 Soluble T?Cell Antigen Receptors (pages 475–493): Peter R. RhodeChapter 32 High?Affinity Monoclonal T?Cell Receptor (mTCR) Fusions (pages 495–505): Nikolai M. Lissin, Namir J. Hassan and Bent K. JakobsenChapter 33 Amediplase (pages 507–518): Stefano Evangelista and Stefano ManziniChapter 34 Breaking New Therapeutic Grounds: Fusion Proteins of Darpins and Other Nonantibody Binding Proteins (pages 519–527): Hans Kaspar BinzChapter 35 Resurgence of Bispecific Antibodies (pages 529–543): Patrick A. Baeuerle and Tobias RaumChapter 36 Novel Applications of Bispecific DART® Proteins (pages 545–555): Syd Johnson, Bhaswati Barat, Hua W. Li, Ralph F. Alderson, Paul A. Moore and Ezio BonviniChapter 37 Strand Exchange Engineered Domain (Seed): A Novel Platform Designed to Generate Mono and Multispecific Protein Therapeutics (pages 557–569): Alec W. Gross, Jessica P. Dawson, Marco Muda, Christie Kelton, Sean D. McKenna and Bjorn HockChapter 38 CovX?Bodies (pages 571–582): Abhijit Bhat, Olivier Laurent and Rodney LappeChapter 39 Modular Antibody Engineering: Antigen Binding Immunoglobulin Fc CH3 Domains as Building Blocks for Bispecific Antibodies (mAb2) (pages 583–589): Maximilian Woisetschlager, Florian Ruker, Geert C. Mudde, Gordana Wozniak?Knopp, Anton Bauer and Gottfried Himmler