Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges

ISBN-13: 9780470646274 / Angielski / Twarda / 2013 / 672 str.

Stefan R Schmidt

Opis

The state of the art in biopharmaceutical FUSION PROTEIN DESIGN Fusion proteins belong to the most lucrative biotech drugs--with Enbrel(R) being one of the best-selling biologics worldwide. Enbrel(R) represents a milestone of modern therapies just as Humulin(R), the first therapeutic recombinant protein for human use, approved by the FDA in 1982 and Orthoclone(R) 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.

Recenzje

Overall, this book is a bona fide companion for newcomers, as well as for experts in the pharmaceutical industry, in biotechnology or universities with affiliations to industry and medicine.   (mAbs, 15 April 2015)

Spis treści

PREFACE xxiii

CONTRIBUTORS xxv

PART I INTRODUCTION 1

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

1.1 History, 3

1.2 Definitions and Categories, 4

1.3 Patenting, 5

1.4 Design and Engineering, 6

1.5 Manufacturing, 10

1.6 Regulatory Challenges, 15

1.7 Competition and Market, 16

1.8 Conclusion and Future Perspective, 17

References, 18

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

2.1 Introduction, 25

2.2 Market Sales Dynamics of the FP Market, 25

2.3 Individual Drug Sales Analysis, 27

2.4 Pipeline Database Analysis, 32

Disclaimer, 36

Acknowledgment, 36

References, 36

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

3.1 Classification of FPs, 39

3.2 Factors for Commercial Success, 49

References, 54

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

4.1 Introduction, 57

4.2 Overview of General Properties of Linkers Derived From Naturally Occurring Multidomain Proteins, 58

4.3 Empirical Linkers in Recombinant Fusion Proteins, 59

4.4 Functionality of Linkers in Fusion Proteins, 66

4.5 Conclusions and Future Perspective, 70

References, 71

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

5.1 Introduction, 75

5.2 Basis of Therapeutic Protein Immunogenicity, 75

5.3 Tools for Immunogenicity Screening, 77

5.4 Approaches for Risk Assessment and Minimization, 81

5.5 Case Study and Clinical Experience, 83

5.6 Preclinical and Clinical Immunogenicity Assessment Strategy, 85

5.7 Conclusions, 87

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

6.1 Introduction, 93

6.2 Half–Life Extension Through Size and Recycling, 94

6.3 Half–Life Extension Through Increase of Hydrodynamic Radius, 100

6.4 Aggregate Forming Peptide Fusions, 102

6.5 Other Concepts, 103

6.6 Conclusions and Future Perspective, 103

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

7.1 Introduction, 107

7.2 FcRn and Monomeric Fc–Fusion Proteins, 108

7.3 Typical Applications, 109

7.4 Alternative Applications, 114

7.5 Expression and Purification of Monomeric Fc–Fusion Proteins, 116

7.6 Conclusions and Future Perspectives, 118

References, 118

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

8.1 Introduction, 123

8.2 Peptide Drugs, 124

8.3 Technologies Used for Reducing In Vivo Clearance of Therapeutic Peptides, 126

8.4 Fc–Fusion Proteins in Drug Development, 127

8.5 Peptide–Fc–Fusion Therapeutics, 131

8.6 Considerations and Challenges for Engineering Peptide–Fc–Fusion Therapeutics, 133

8.7 Conclusions, 138

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

9.1 Introduction, 143

9.2 Etanercept as a Prototypical Receptor–Fc–Based Cytokine Blocker, 144

9.3 Heteromeric Traps for Ligands Utilizing Multicomponent Receptor Systems with Shared Subunits, 144

9.4 Development and Clinical Application of an Interleukin 1 Trap: Rilonacept, 151

9.5 Development and Clinical Application of a VEGF Trap, 151

9.6 To Trap Or Not To Trap? Advantages and Disadvantages of Receptor–Fc Fusions and Traps Versus Antibodies, 152

9.7 Conclusion, 155

Acknowledgment, 155

References, 155

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

10.1 Concept, 163

10.2 Technological Aspects, 164

10.3 Typical Applications and Indications, 164

10.4 Successes and Failures in Preclinical and Clinical Research, 172

10.5 Challenges, 173

10.6 Future Perspectives, 174

10.7 Conclusion, 174

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

11.1 Introduction, 179

11.2 Clinically Validated Half–Life Extension Technologies An Overview, 180

11.3 Interferon–a Fused to Human Serum Albumin or AlbudAb A Direct Comparison of HSA and AlbudAb Fusion Technologies, 182

11.4 Nanobodies in the Development of Alternative Half–Life Extension Technologies Based on Single Immunoglobulin Variable Domains, 186

11.5 Novel Half–Life Extension Technologies Alternative Approaches to Single Immunoglobulin Variable Domains, 187

11.6 Conclusions, 188

References, 189

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

12.1 Disease Overview, 191

12.2 Fusion Protein SHG2210 Design, 192

12.3 Characterization of SHG2210, 193

12.4 Applications and Indications, 196

12.5 Future Perspectives, 197

12.6 Conclusion, 198

References, 198

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

13.1 Introduction, 201

13.2 The Role of O–Linked Oligosaccharide Chains in Glycoprotein Function, 202

13.3 Designing Long–Acting Agonists of Glycoprotein Hormones, 203

13.4 Conclusions, 207

References, 207

14 ELP–Fusion Technology for Biopharmaceuticals 211
Doreen M. Floss, Udo Conrad, Stefan Rose–John, and J urgen Scheller

14.1 Introduction, 211

14.2 ELP–based Protein Purification, 212

14.3 ELPylated Proteins in Medicine and Nanobiotechnology, 215

14.4 Molecular Pharming: a New Application for ELPylation, 217

14.5 Challenges and Future Perspectives, 221

14.6 Conclusion, 222

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

15.1 Introduction, 227

15.2 The GHLR–Fusions, 228

15.3 Expression and Purification, 229

15.4 Analysis of the LR–Fusions, 229

15.5 LR–Fusions: The Next Generation in Hormone Treatment, 234

15.6 Conclusion, 234

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

16.1 Introduction, 237

16.2 Description of Concept, 238

16.3 Limitations of the Latent Cytokine Technology, 240

16.4 Generation of Latent Cytokines, 242

16.5 Applications and Potential Clinical Indications, 244

16.6 Alternatives/Variants of Approach, 246

16.7 Challenges (Production and Development), 247

16.8 Conclusions and Future Perspectives, 248

Acknowledgments, 249

References, 249

IIB TOXIN: CYTOTOXIC FUSION PROTEINS 253

17 Fusion Proteins with Toxic Activity 253
Stefan R. Schmidt

17.1 Introduction, 253

17.2 Toxins, 254

17.3 Immunocytokines, 258

17.4 Human Enzymes, 259

17.5 Apoptosis Induction, 261

17.6 Fc–Based Toxicity, 263

17.7 Peptide–Based Toxicity, 264

17.8 Conclusions and Future Perspectives, 265

References, 265

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

18.1 Introduction, 271

18.2 Toxins Used in Immunotoxin Preparation, 272

18.3 Immunotoxin Design and Synthesis, 274

18.4 Clinical Update of Immunotoxin Trials, 278

18.5 Challenges and Perspective of Classic Immunotoxins, 284

18.6 Conclusions, 286

References, 286

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

19.1 Introduction, 295

19.2 Immunotherapeutic Strategy for Cancer: Fusion Proteins, 296

19.3 Immunotherapeutic Applications of Antibody–Targeted and Untargeted Fc Fusion Proteins, 297

19.4 Combination Fusion Proteins Therapy, 305

19.5 Mechanism of Action: Immunoregulatory T–Cell (Treg) Depletion and Fusion Protein Combination Therapy, 306

19.6 Future Directions, 309

19.7 Conclusion, 309

Acknowledgments, 310

References, 310

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

20.1 Introduction, 315

20.2 Targeted Toxins General Considerations, 316

20.3 Delivery Mode and Pharmacokinetics of Targeted Toxins in the Brain, 316

20.4 Preclinical and Clinical Studies with Targeted Toxins, 318

20.5 Conclusions and Future Developments of Targeted Toxins, 324

Disclosure, 325

References, 325

21 Immunokinases 329
Stefan Barth, Stefan Gattenl ohner, and Mehmet Kemal Tur

21.1 Introduction, 329

21.2 Protein Kinases, Apoptosis, and Cancer, 330

21.3 Therapeutic Strategies to Restore Missing Kinase Expression, 331

21.4 Analysis of Immunokinase Efficacy, 333

21.5 Outlook, 334

References, 334

22 ImmunoRNase Fusions 337
Wojciech Ardelt

22.1 Introduction, 337

22.2 Development of ImmunoRNase Fusion Proteins as Biopharmaceuticals, 339

22.3 Aspects of ImmunoRNase Design and Production, 344

22.4 Alternatives, 346

22.5 Conclusions and Future Perspectives, 347

References, 347

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

23.1 Introduction, 355

23.2 The Components, 355

23.3 ADEPT Systems with Carboxypeptidase G2 (CPG2), 357

23.4 Fusion Proteins, 359

23.5 Immunogenicity, 360

23.6 Conclusions and Future Outlook, 361

Acknowledgments, 361

References, 361

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

24.1 Introduction: Tumor–Targeted Superantigens AUnique Concept of Cancer Treatment, 365

24.2 Structure and Production of Tumor–Targeted Superantigens, 366

24.3 Tumor–Targeted Superantigens are Powerful Targeted Immune Activators and Useful for all Types of Malignancies, 367

24.4 Increasing the Therapeutic Window and Exposure by the Creation of a Novel TTS Fusion Protein with Minimal MHC Class II Affinity; Naptumomab Estafenatox, 370

24.5 Clinical Experience with TTS Therapeutic Fusion Proteins, 371

24.6 Combining TTS with Cytostatic and Immunomodulating Anticancer Drugs, 377

24.7 Conclusions, 379

References, 379

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

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

25.1 Introduction, 383

25.2 Targeting Organs, 383

25.3 Intracellular Delivery, 388

25.4 Oral Delivery, 391

25.5 Conclusions and Future Perspectives, 392

References, 393

26 Cell–Penetrating Peptide Fusion Proteins 397
Andres Mu∼noz–Alarcon, Henrik Helmfors, Kristin Karlsson, and U lo Langel

26.1 Introduction, 397

26.2 Typical Applications and Indications, 397

26.3 Technological Aspects, 399

26.4 Successes and Failures in Preclinical and Clinical Research, 402

26.5 Alternatives/Variants of This Approach, 405

26.6 Conclusions and Future Perspectives, 405

Acknowledgments, 406

References, 406

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

27.1 Why Target Heparan–Sulfate Proteoglycans with Fusion Proteins?, 413

27.2 Heparan Sulfate Structure and Biosynthesis Create Diversity and a Template for Targeting Specificity, 415

27.3 Tissue–Specific Expression of HSPGs and the Enzymes That Modify Them, 416

27.4 Heparin–Binding Proteins and Growth Factors, 416

27.5 Viruses Target Cells Through Heparin Binding, 417

27.6 Dissecting Heparin–Binding Protein Domains for Tissue–Specific Targeting, 418

27.7 Fusion Proteins Incorporating HBDs, 418

27.8 The Neuregulin 1 Growth Factor Has a Unique and Highly Specific HBD, 419

27.9 Using Neuregulin s HBD to Generate a Targeted Neuregulin Antagonist, 419

27.10 Tissue Targeting and Therapeutic Efficacy of a Heparin–Targeted NRG1 Antagonist Fusion Protein, 420

27.11 Conclusions and Future Perspectives, 423

References, 424

28 Bone–Targeted Alkaline Phosphatase 429
Jose Luis Millan

28.1 Detailed Description of the Concept, 429

28.2 Technical Aspects, 430

28.3 Applications and Indications, 432

28.4 Preclinical and Clinical Research, 433

28.5 Alternatives/Variants of This Approach, 434

28.6 Challenges in Production and Development, 436

28.7 Conclusions and Future Perspectives, 436

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

29.1 Detailed Description of the Concept, 441

29.2 Technological Aspects, 447

29.3 Typical Applications and Indications, 447

29.4 Alternatives and Variants of This Approach, 448

29.5 Conclusions and Future Perspectives, 448

References, 448

PART III BEYOND THE TRIPLE T–PARADIGM 453

IIIA NOVEL CONCEPTS, NOVEL SCAFFOLDS 455

30 Signal Converter Proteins 455
Mark L. Tykocinski

30.1 Introduction, 455

30.2 Historical Roots of Signal Conversion: Artificial Veto Cell Engineering and Protein Painting, 455

30.3 Trans Signal Converter Proteins, 458

30.4 Expanding Trans Signal Conversion Options: Redirecting Signals, 459

30.5 From Trans to Cis Signal Conversion: Driving Auto–Signaling, 460

30.6 Mechanistic Dividends of Chimerization, 461

30.7 Targeting Multiple Diseases with Individual Signal Converters, 462

30.8 Structural Constraints in SCP Design, 463

30.9 Coding SCP Functional Repertoires, 463

30.10 Expanding the Catalog of Inhibitory SCP, 464

30.11 Immune Activating SCP, 466

30.12 Experimental Tools for Screening SCP Candidates, 467

30.13 SCP Frontiers: Mining the Surface Protein Interactome, Rewiring Cellular Networks, 467

References, 468

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

31.1 Soluble T–cell Antigen Receptor (STAR) Fusion Technology and Utilities, 475

31.2 Expression and Purification of Recombinant Star Fusion Proteins, 477

31.3 Clinical and Research Product Applications, 478

31.4 Preclinical Testing Using Star Fusion Proteins, 481

31.5 Clinical Development of ALT–801, 487

31.6 Alternatives/Variants of This Approach, 488

31.7 Challenges, 489

31.8 Conclusions and Future Perspectives, 490

Acknowledgments, 490

References, 490

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

32.1 Introduction: The T Cell Receptor (TCR) as a Targeting Molecule, 495

32.2 Engineered High–Affinity Monoclonal TCRs (mTCR), 497

32.3 mTCR–Based Fusion Proteins for Therapeutic Applications, 500

32.4 Immune–Mobilizing Monoclonal TCRs Against Cancer (ImmTAC), 500

32.5 Conclusions and Future Perspectives, 503

Acknowledgments, 504

References, 504

33 Amediplase 507
Stefano Evangelista and Stefano Manzini

33.1 Introduction, 507

33.2 Source, Physico–Chemical Properties and Formulation, 508

33.3 Preclinical Studies, 510

33.4 Human Studies, 512

33.5 Historical Comparison with Other Thrombolytics, 517

33.6 Conclusions and Future Perspectives, 517

Acknowledgment, 517

References, 517

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

34.1 Introduction, 519

34.2 Novel Scaffolds Alternatives to Antibodies, 519

34.3 New Therapeutic Concepts with Nonantibody Binding Proteins, 523

34.4 Scaffold–Fusion Proteins Beyond Antibody Possibilities, 525

Acknowledgments, 526

References, 526

IIIB MULTIFUNCTIONAL ANTIBODIES 529

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

35.1 A Brief History of Bispecific Antibodies, 529

35.2 Asymmetric IgG–Like Bispecific Antibodies, 530

35.3 Symmetric IgG–Like Bispecific Antibodies, 531

35.4 IgG–Like Bispecific Antibodies with Fused Antibody Fragments, 533

35.5 Bispecific Constructs Based on the Fcg Fragment, 534

35.6 Bispecific Constructs Based on Fab Fragments, 535

35.7 Bispecific Constructs Based on Diabodies or Single–Chain Antibodies, 536

35.8 Bifunctional Fusions of Antibodies or Fragments with Other Proteins, 538

35.9 Bispecific Antibodies for Various Functions: How to Select the Right Format?, 539

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

36.1 Introduction, 545

36.2 DART1 Proteins, 546

36.3 Application of DART1 to Cross–Link Inhibitory and Activating Receptors, 546

36.4 Application of Bispecific Antibodies in Oncology, 547

36.5 U–DART Concept for Screening DART1 Candidate Targets and mAbs, 549

36.6 U–DART Concept for Applications in Autoimmune and Inflammatory Disease, 549

36.7 Conclusions and Future Perspectives, 554

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

37.1 Introduction, 557

37.2 Technical Aspects, 558

37.3 Potential Therapeutic Applications, 562

37.4 Future Perspectives, 566

37.5 Conclusions, 567

Acknowledgments, 567

References, 567

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

38.1 The CovX–Body Concept, 571

38.2 Technological Aspects, 571

38.3 Applications of the CovX–Body Technology, 578

References, 581

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

39.1 Introduction, 583

39.2 Immunoglobulin Fc as a Scaffold, 583

39.3 Design of Libraries Based on the Human IgG1 CH3 Domain, 584

39.4 TNF–a–Binding Fcab: Selection and Characterization of Fcab TNF353–2, 585

39.5 Conclusions and Future Perspectives, 588

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

40.1 Introduction, 591

40.2 DDD/AD Modules Based on PKA and AKAP, 592

40.3 Advantages and Disadvantages of the DNL Method, 592

40.4 Fab–Based Modules, 593

40.5 IgG–AD2–Modules, 594

40.6 Hexavalent Antibodies, 595

40.7 More Antibody–Based–Modules and Multivalent Antibodies, 596

40.8 Nonantibody–Based DNL Modules, 597

40.9 IFN–a2b–DDD2 Module and Immunocytokines, 597

40.10 Variations on the DNLTheme, 598

40.11 Conclusions and Future Perspective, 599

References, 599

INDEX 603

O autorze

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.

Blurb

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 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.