Adme and Translational Pharmacokinetics / Pharmacodynamics of Therapeutic Proteins

Applications in Drug Discovery and Development
1. Auflage 2015
ISBN: 978-1-118-89864-2
Verlag: Wiley

Buch, Englisch, 480 Seiten, Format (B × H): 220 mm x 287 mm, Gewicht: 1310 g

With an emphasis on the fundamental and practical aspects of ADME for therapeutic proteins, this book helps readers strategize, plan and implement translational research for biologic drugs.

• Details cutting-edge ADME (absorption, distribution, metabolism and excretion) and PKPD (pharmacokinetic / pharmacodynamics) modeling for biologic drugs
• Combines theoretical with practical aspects of ADME in biologic drug discovery and development and compares innovator biologics with biosimilar biologics and small molecules with biologics,  giving a lessons-learned perspective
• Includes case studies about leveraging ADME to improve biologics drug development for monoclonal antibodies, fusion proteins, pegylated proteins, ADCs, bispecifics, and vaccines
• Presents regulatory expectations and industry perspectives for developing biologic drugs in USA, EU, and Japan
• Provides mechanistic insight into biodistribution and target-driven pharmacokinetics in important sites of action such as tumors and the brain

Autoren/Hrsg.

Zhou, Honghui

Theil, Frank-Peter

Fachgebiete

• Naturwissenschaften Chemie Chemie Allgemein Pharmazeutische Chemie, Medizinische Chemie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakotherapie, Psychopharmakotherapie

Inhaltsverzeichnis

List of Contributors xvii

Foreword xix

1 ADME for Therapeutic Biologics: What Can We Leverage from Great Wealth of ADME Knowledge and Research for Small Molecules 1
Weirong Wang and Thomayant Prueksaritanont

1.1 Introduction 1

1.2 SM Drug Discovery and Development: Historical Perspective 1

1.2.1 Evolving Role of DMPK: Paradigm Shift 1

1.2.2 Key Enablers to Successful DMPK Support 2

1.2.3 Regulatory Considerations 3

1.3 LM Drug Discovery and Development 3

1.3.1 Role of DMPK: Current State 3

1.3.2 SM/LM DMPK Analogy 4

1.3.3 Leveraging SM Experience: Case Examples 6

1.4 Conclusions 8

References 8

2 Protein Engineering: Applications to Therapeutic Proteins and Antibodies 13
Andrew G. Popplewell

2.1 Introduction 13

2.2 Methods of Protein Engineering 13

2.2.1 General Techniques 13

2.2.2 Introducing Specific, Directed Sequence Changes 14

2.2.3 Fragment Fusion 14

2.2.4 Gene Synthesis 14

2.2.5 Molecular “Evolution” through Display and Selection 14

2.3 Applications of Protein Engineering to Non-Antibody Therapeutic Proteins 16

2.4 Applications of Protein Engineering to Therapeutic Antibodies 16

2.4.1 Reduction of Immunogenicity 17

2.4.2 Improving Stability and Biophysical Properties 17

2.4.3 Tailoring Mechanism of Action 19

2.4.4 Influencing Distribution and PK 19

2.4.5 Improving Ligand/Receptor Interaction 20

2.5 Future Perspectives 20

References 21

3 Therapeutic Antibodies—Protein Engineering to Influence ADME, PK, and Efficacy 25
Tatsuhiko Tachibana, Kenta Haraya, Yuki Iwayanagi and Tomoyuki Igawa

3.1 Introduction 25

3.2 Relationship between pI and Pharmacokinetics 26

3.2.1 pI and Clearance 26

3.2.2 pI and Distribution 26

3.2.3 pI and SC Absorption 27

3.2.4 pI and FcRn Function 27

3.3 Nonspecific/Specific Of

Über Autor(innen)

Honghui Zhou is a Senior Director and Janssen Fellow, at Janssen Research & Development, LLC and US head of Pharmacological and Translational Modeling. Board-certified by the American Board of Clinical Pharmacology and a Fellow of American Association of Pharmaceutical Scientists (AAPS) and American College of Clinical Pharmacology (ACCP), he has authored 200 peer-reviewed scientific papers, book chapters, and conference abstracts and co-edited the book Drug-Drug Interactions for Therapeutic Biologics (Wiley, 2013).

Frank-Peter Theil heads nonclinical development at UCB Biopharma. Dr. Theil has authored and co-authored 40 research publications, three book chapters and he has given numerous invited presentations at national and international scientific meetings. He is a member of the American Association of Pharmaceutical Scientists (AAPS) and American Society of Clinical Pharmacology and Therapeutics (ASCPT).