In this practice-oriented two volume handbook, professionals from some of the largest biopharmaceutical companies and top academic researchers address the key concepts and challenges in the development of protein pharmaceuticals for medicinal chemists and drug developers of all trades.
Following an introduction tracing the rapid development of the protein therapeutics market over the last decade, all currently used therapeutic protein scaffolds are surveyed, from human and non-human antibodies to antibody mimetics, bispecific antibodies and antibody-drug conjugates. This ready reference then goes on to review other key aspects such as pharmacokinetics, safety and immunogenicity, manufacture, formulation and delivery. The handbook then takes a look at current key clinical applications for protein therapeutics, from respiratory and inflammation to oncology and immune-oncology, infectious diseases and rescue therapy. Finally, several exciting prospects for the future of protein therapeutics are highlighted and discussed.
About the Author
Tristan Vaughan is Vice President, Research and Development for antibody discovery and protein engineering at MedImmune. Based in Cambridge (UK), Dr. Vaughan leads the work of 110 scientists who are responsible for discovering and engineering around half of MedImmune's biologics portfolio, and who have delivered over 50 protein-based therapeutic candidates into the clinical phases of development. Dr. Vaughan joined MedImmune, previously Cambridge Antibody Technology, in 1993 and developed the platform technology which built the first human antibody libraries of 10 E10 members. He is also a key inventor of Humira and Benlysta. Dr. Vaughan has over 60 publications in peer-reviewed journals to his name.

Jane Osbourn is Vice President, Research and Development at MedImmune and Site Leader for MedImmune Cambridge (UK). An expert in antibody engineering, Dr. Osbourn joined MedImmune, formerly Cambridge Antibody Technology, in 1993, and is an originator of key peer-reviewed publications and patents. She made a significant contribution to the discovery and development of marketed drugs (Humira and Benlysta) and more than 40 clinical candidates. Dr. Osbourn has worked across a range of disease areas and currently leads a team of researchers developing biosuperior biologics medicines in oncology, cardiovascular disease and diabetes. In addition, she is Chair of the UK BioIndustry Association, a Director of Babraham Bioscience Technologies and a Director of Cambridge Enterprise.

Bahija Jallal is Executive Vice President of AstraZeneca and head of MedImmune, its global biologics research and development arm, based in Gaithersburg (USA). Prior to joining MedImmune, Dr. Jallal worked with Chiron Corporation where she served as vice president, drug assessment and development, and successfully established the company's translational medicine group. In 2013, Dr. Jallal earned the Grace Award from the Cancer Research Institute. She has authored over 70 peer-reviewed publications and has over 15 patents.

TABLE OF CONTENTS
Contents to Volume 1

Preface XVII

A Personal Foreword XXI

Acknowledgements XXIII

Part I Introduction to Protein Therapeutics: Past and Present 1

1 Early Recombinant Protein Therapeutics 3
Pierre De Meyts

2 Evolution of Antibody Therapeutics 25
Hervé Watier and Janice M. Reichert

Part II Antibodies: The Ultimate Scaffold for Protein Therapeutics 51

3 Human Antibody Structure and Function 53
Ponraj Prabakaran and Dimiter S. Dimitrov

4 Antibodies from Other Species 85
Melissa L. Vadnais, Michael F. Criscitiello, and Vaughn V. Smider

Part III Discovery and Engineering of Protein Therapeutics 113

5 Human Antibody Discovery Platforms 115
William R. Strohl

6 Beyond Antibodies: Engineered Protein Scaffolds for Therapeutic Development 161
Nishant K. Mehta and Jennifer R. Cochran

7 Protein Engineering: Methods and Applications 189
Claire Dobson

8 Bispecifics 229
Jijie Gu, Andrew McCluskey, and Tariq Ghayur

9 Antibody drug Conjugates (ADCs) 271
Dr Philip W. Howard

Contents to Volume 2

Preface XVII

A Personal Foreword XXI

Acknowledgements XXIII

Part IV Physiological and Manufacturing Considerations for Biologics 311

10 Pharmacokinetics of Therapeutic Proteins 313
Zheng Lu, Jennifer Sheng, and Wenhui Zhang

References 334

11 Safety Considerations for Biologics 341
Maggie Dempster, Lucinda R. Weir, and Rajni S. Fagg

12 Immunogenicity of Biologics 387
Matthew P. Baker, Timothy D. Jones, and Paul Chamberlain

13 Expression Systems for Recombinant Biopharmaceutical Production by Mammalian Cells in Culture 423
Adam J. Brown, Devika Kalsi, Alejandro Fernandez-Martell, Joe Cartwright, Nicholas O. W. Barber, Yash D. Patel, Richard Turner, Claire L. Bryant, Yusuf B. Johari, and David C. James

Abbreviations 450

References 452

14 Stability, Formulation, and Delivery of Biopharmaceuticals 469
Hanns-Christian Mahler and Andrea Allmendinger

Part V Clinical Applications 493

15 Protein Therapeutics in Autoimmune and Inflammatory Diseases 495
Anthony J. Coyle and Leigh S. Zawel

References 511

16 Antibody-Based Therapeutics in Oncology 521
Paul A. Moore, Ross La Motte-Mohs, Jonathan C. Li, and Gurunadh R. Chichili

17 Protein Therapeutics in Respiratory Medicine 587
Rahul Shrimanker and Ian D. Pavord

18 Antibodies for the Prevention, Treatment, and Preemption of Infectious Diseases 611
Steve Projan

19 Rescue Therapies 621
Stephan Glund

20 Biosimilars 645
Jun Wang

Part VI Future Horizons 661

21 Future Horizons and New Target Class Opportunities 663
Herren Wu, Carl Webster, Judy Paterson, Sandrine Guillard, Ron Jackson, and Ralph Minter

References 690

Index 701