Modern Biopharmaceuticals E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1385

Veröffentlichungsjahr: 2013

Beschreibung

This collection of high-profile contributions provides a unique insight into the development of novel, successful biopharmaceuticals.

Outstanding authors, including Nobel laureate Robert Huber as well as prominent company researchers and CEOs, present valuable insider knowledge, limiting their scope to those procedures and developments with proven potential for the biotechnology industry. They cover all relevant aspects, from the establishment of biotechnology parks, the development of successful compounds and the implementation of efficient manufacturing processes, right up to the establishment of advanced delivery routes.

Leseprobe

Contents

Cover

Related Titles

Title Page

Copyright

Dedication

Foreword by Andreas Busch

Foreword by Günter Stock

Preface

Quotes

List of Contributors

Part I: Modern Biopharmaceuticals: Research is the Best Medicine – Sanitas Summum Bonus

Chapter 1: Twenty Thousand Years of Biotech – From “Traditional” to “Modern Biotechnology”

1.1 Biotechnology – The Science Creating Life

1.2 The Inauguration of Biotechnology

1.3 From “Traditional” to “Modern Biotechnology”

1.4 A Small Molecule from Bacteria – A Huge Importance for Mankind

1.5 Biopharmaceuticals – The Mainstay of Modern Biotechnology

1.6 Transformation of the Pharma Industry Through Biotechnology

1.7 Biopharmaceutical Production – Uncorking Bottlenecks or Wasting Surplus Capacity?

1.8 Conclusion and Outlook

References

Part II: Modern Biopharmaceutical Development Using Stem Cells, Tissues, and Whole Animals

Chapter 2: Induced Pluripotency as Substitute of Somatic Cell Nuclear Transfer? – The Impact of Induced Pluripotent Stem Cells on Drug Discovery and Regenerative Biopharmaceuticals

2.1 Introduction

2.2 Derivation and Growth of hESC

2.3 Signaling Pathways and Transcription Factors

2.4 Differentiation and Applications of hESC

2.5 Patient-Specific Nuclear Transfer Stem Cells

2.6 Patient-Specific Pluripotent Cells Through Direct Reprogramming of Adult Somatic Cells

2.7 Concluding Remarks and Outlook

Acknowledgment

References

Chapter 3: Pluripotent Stem Cell-Derived Cardiomyocytes for Industrial and Clinical Applications

3.1 Introduction

3.2 Pluripotent Stem Cells

3.3 High-Yield Differentiation of Pluripotent Stem Cells into Cardiomyocytes

3.4 Purification of Pluripotent Stem Cell-Derived Cardiomyocytes

3.5 Cardiomyocytes at an Industrial Scale

3.6 Utilization of Tissue Engineering Technologies to Advance Cellular Maturity

3.7 Concluding Remarks

References

Chapter 4: Industrialization of Functional Mouse Genomics Technologies for Biopharmaceutical Drug Discovery and Development

4.1 Introduction

4.2 The Mouse Genetics Story

4.3 Establishing Inducible Gene Targeting Tools

4.4 RNAi – Talking About a Revolution?

4.5 Further Shortening the Generation Timeline for RNAi Mouse Models

4.6 Adapting the Mouse Genetics Toolbox for New Applications

References

Part III: Innovative Development Tools for Modern Biopharmaceuticals

Chapter 5: Standardized Solutions for Quantitative and Real-Time RT-PCR to Accelerate Biopharmaceutical Development

5.1 Introduction

5.2 Potential of Real-Time RT-PCR in Biopharmaceutical Development

5.3 Accurate Gene Expression Analysis Depends on Standardized Preanalytical Steps

5.4 Accuracy of Real-Time RT-PCR Depends on Efficient cDNA Synthesis

5.5 Integration of Preanalytical Steps Streamlines Gene Expression Analysis

5.6 Overview of Methods for Real-Time RT-PCR

5.7 Developments in Real-Time PCR Instrumentation

5.8 The Need for Better Standardization of Quantification Methods

5.9 Conclusion and Outlook

References

Chapter 6: Massive Mutagenesis®: The Path to Smarter Genetic Libraries

6.1 Introduction

6.2 Massive Mutagenesis

6.3 Sample Applications of Massive Mutagenesis

6.4 Conclusion and Perspectives

6.5 Acknowledgments

References

Chapter 7: Cut & Go – FastDigest® with All Restriction Enzymes @ Same Temperature and Buffer: A New Paradigm in DNA Digestion to Speed-Up Biopharmaceutical Development

7.1 Introduction

7.2 Background

7.3 Prerequisites

7.4 Properties of FastDigest Enzymes

7.5 Conclusion and Outlook

References

Chapter 8: StarGate®: A High-Capacity Expression Cloning System to Speed-Up Biopharmaceutical Development

8.1 Introduction

8.2 Background

8.3 Workflow Overview

8.4 Universal Donor Vector Generation

8.5 StarGate Reactions for Gene Transfer and Clone Selection

8.6 The StarGate Acceptor Vector Portfolio

8.7 StarGate Mutagenesis System

8.8 StarGate Fusion Cloning System

8.9 Perspective

Acknowledgment

References

Chapter 9: Precision Genome Surgery with Meganucleases: A Promising Biopharmaceutical for Gene Therapy

9.1 Introduction

9.2 Meganucleases

9.3 Prospects of Gene Therapy Using Meganucleases

9.4 Summary and Outlook

References

Chapter 10: Innovative Diagnostics Enhances and Advances the Impact of In Vivo Small-Animal Imaging in Drug Discovery and Pharmaceutical Development1

10.1 “Molecular Imaging Set to Change the Decade!”

10.2 Progress in Imaging Technologies: Resolution Down to Microns, Histology Versus Tomography

10.3 Why Using Contrast and Imaging Agents

10.4 VISCOVER: See More Get More!

10.5 VISCOVER: A Landmark in Small-Animal In Vivo Imaging

10.6 VISCOVER Efficacy! From Physics to Efficacy: Advanced Nanotechnology Accomplishing Cutting-Edge Imaging

10.7 VISCOVER Pharmacology! From Structure to Pharmacology: VISCOVER's Versatility Illustrated by the Gadospin Product Family

10.8 The MRI Portfolio as an Example: Contrast Agents that will Transform Your Preclinical MRI Facility

10.9 VISCOVER Customized Agents: Imaging Agents Tailored for Your Research

10.10 VISCOVER In Vivo Imaging Examples: Track Tumor Progression in Real-Time in SmallAnimals

10.11 Summary and Outlook

References

Chapter 11: Revolutionizing Biopharmaceutical Development with Quantitative Multispectral Optoacoustic Tomography (MSOT)

11.1 Introduction

11.2 Molecular Imaging with MSOT

11.3 Overview of Performance Characteristics

11.4 Reporter Molecules

11.5 Sensitivity of Biomarker Detection

11.6 Anatomical and Functional Optoacoustic Imaging

11.7 Technical and Mathematical Principles of MSOT

11.8 Quantification

11.9 Conclusion and Perspective for MSOT in Biopharmaceutical Development

References

Chapter 12: Pharma Research Biobanking: Need, Socioethical Considerations, and Best Practice

12.1 Introduction

12.2 Research and Humane Animal Welfare

12.3 Rationale for Biobanking of Human Samples

12.4 Scientific Publications on Biobanks

12.5 Legal Framework of Biobanks for Research Purposes in Germany

12.6 Willingness to Donate Material

12.7 Practical Experiences in Building up a Biobank

12.8 Outlook and Summary

Acknowledgments

References

Part IV: The Rise of Monoclonal Antibodies – The Premium Class of Biopharmaceuticals

Chapter 13: Implementation of Advanced Technologies in Commercial Monoclonal Antibody Production

13.1 Part I: Commercial Antibody Process Development

13.2 Part II: Implementation of Membrane Technology in Antibody Large-Scale Purification

Acknowledgment

References

Chapter 14: A Real Success Story: Plantibodies for Human Therapeutic Use

14.1 Introduction

14.2 SWOT Analysis Reveals a Ripe Market for Plant Expression Systems

14.3 Current Status of Plant-Made Biopharmaceuticals

14.4 The CB Hep1 Case Story

14.5 Conclusion and Outlook

References

Part V: Smart Solutions for Global Challanges – Vaccine-Based Biopharmaceuticals

Chapter 15: A Modern Biopharmaceutical to Treat AIDS – Challenges in Designing HIV Env Immunogens for Developing a Vaccine

15.1 Introduction

15.2 Protective Efficacy of Neutralizing Monoclonal Antibodies in Passive Transfer

15.3 Challenges in Inducing Antibodies of Appropiate Specificity with Broadly Neutralizing Activity

15.4 Strategies to Design Immunogens that may Induce Neutralizing Antibodies of Protective Specificities by Vaccination

Acknowledgments

References

Chapter 16: Accelerated Biopharmaceutical Development: Vero Cell Technology and Pandemic Influenza Vaccine Production

16.1 Influenza

16.2 Influenza Vaccines

16.3 Vero-Derived Influenza Virus Vaccines

16.4 Vero-Derived H5N1 Candidate Pandemic Influenza Virus Vaccines

16.5 Development of a Vero-Derived A/H1N1v Pandemic Vaccine

16.6 Summary and Outlook

References

Part VI: Modern Biopharmaceuticals – The Holy Grail for Health and Wealth

Chapter 17: BioBenchmarking: The Global Perspective to Ensure Future Success of Biopharmaceutical Development

17.1 Diagnostic Benchmarking – The Best of Two Worlds

17.2 Biotechnology Companies Contend with Unique Circumstances, Yet Share Many of the Problems of Broad Industry. Benchmarking can be a Tool to Focus on the Real Key Issues

17.3 How Biotechs are Responding to the Changing Environment

17.4 A Wide Range of Performance Levels Exists Within the Biopharmaceutical Industry

17.5 Performance Level of Successful Biotech Companies

17.6 Learnings and Outlook for the Biopharmaceutical Business

References

Chapter 18: Basic Concepts for the Development of a Biosimilar Product: Experience with Omnitrope®, the First Ever Approved Similar Biopharmaceutical Product

18.1 Introduction

18.2 Pharmaceutical-Technical Development of Biosimilar Products

18.3 Nonclinical Development of Biosimilars

18.4 Clinical Development of Biosimilars

18.5 Risk Management and Post-approval Studies of Biosimilar Products

18.6 Regulatory Situation for Biosimilar Approval in Various Regions

18.7 Conclusion and Future Aspects

Acknowledgments

References

Chapter 19: Recombinant Factor VIII (Kogenate®) for the Treatment of Hemophilia A: The First and Only World-Wide Licensed Recombinant Protein Produced in High-Throughput Perfusion Culture

19.1 Introduction

19.2 Description of the Human Factor VIII Molecule

19.3 Overview of the Process Development Tasks

19.4 Cell Line and Culture Medium Development

19.5 High-Throughput Perfusion Fermentation with Cell Retention

19.6 Purification and Formulation

19.7 Manufacturing Plant Design and Operation

19.8 Conclusions

References

Part VII: From Innovative Tools to Improved Therapies – The Success of Second-Generation Biopharmaceuticals

Chapter 20: Posttranslational Modifications to Improve Biopharmaceuticals

20.1 Introduction

20.2 γ-Carboxylation and β-Hydroxylation

20.3 Amidation and Sulfation

20.4 Glycosylation

20.5 Engineering the Glycocomponent in Order to Optimize Alternative Production Systems

20.6 Conclusion

References

Chapter 21: The Development of Biomaterials for Delivery of Nucleic Acid Therapeutics

21.1 Introduction

21.2 Major Barriers in Delivery of Nucleic Acid Therapeutics

21.3 Techniques for Nucleic Acid Delivery

21.4 DNA Delivery

21.5 siRNA Delivery

21.6 Targeted Nucleic Acids Delivery for In Vivo Applications

21.7 Conclusions and Outlook

References

Part VIII: Biopharmaceutical Manufacturing and Downstream Processing – How to Uncork Bottlenecks

Chapter 22: Bright Future Outlook and Huge Challenges to Overcome: An Attempt to Write the Short Story of the Biopharma Industry with Current Status, Selected Issues, and Potential Solutions in Discovery, R&D, and Manufacturing

22.1 Introduction – Healthcare Crisis: Biopharma Successes Paired with Tough Challenges

22.2 Research and Development

22.3 Manufacturing

22.4 Summary

References

Chapter 23: Large-Scale Manufacturing of Biopharmaceuticals – Speed Up the Road to Market by Scale Up: the 6 × 15 000 l BI Bioreactors

23.1 Introduction – The Early Days of Industrial Biopharmaceutical Production

23.2 The Rise of Mammalian Cell Culture

23.3 Monoclonal Antibodies are the Biggest Market Drivers

23.4 The Biopharmaceutical Success Story Created the Need for Investments in Capacity

23.5 Combining Capacities and Products for Success

23.6 Facts and Figures – Conclusion and Perspective

References

Chapter 24: Reliable, Large-Scale Cleavage of Tags from Affinity-Purified Biopharmaceuticals

24.1 Introduction

24.2 Results

24.3 Discussion

References

Chapter 25: In Situ On-Line Monitoring of Fermentation Processes: A Cool Tool for Biopharmaceutical Production

25.1 Introduction

25.2 Single Parameter Sensor

25.3 Applications

25.4 Multiparameter Sensors

25.5 2D Fluorecence is a New Method for Bioprocess Monitoring

25.6 Discussion

References

Chapter 26: Queen Honeybee and Me: Forever Young? Conserved Pathways for Longevity

26.1 Summary: Sanitas Summum Bonus

26.2 Introduction

26.3 Orthogonal Pathways for Longevity in Mammals

26.4 The Value of Different Model Systems

26.5 Tools to Dissect Conserved Orthogonal Longevity Mechanisms

26.6 Common Antiaging Mechanisms and Longevity Pathways

26.7 Insights on Pure Human Mechanisms of Longevity Come from Centenarians

26.8 The Most Promising Approach to Increase Longevity: Sirtuins, SREBP, and Resveratrol

26.9 CR/DR (Without Malnutrition) is Key to Gain Health and Longevity

26.10 The Real Prototype for Longevity, Vitality, and Fertility: Queen Honeybee

26.11 Can we Learn from Queen Honeybee's Longevity? Yes, we can

26.12 Ad Meliorem – Conclusion and Perspective for Longevity in Humans

References

Index

Related Titles

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to my wife Zeynep and my family

Foreword by Andreas Busch

History and Future of Modern Biopharmaceuticals

It is my real pleasure to write a short welcoming note for the new book “Modern Biopharmaceuticals – Recent Success Stories.”

In the fashion of the first four volumes “Modern Biopharmaceuticals – Design, Development and Optimization,” when an introduction on the historical development of biopharmaceuticals was given by Nobel Laureate Robert Huber [1], this new edition starts with an historical outline of the evolution from “traditional biotechnology” 20 000 years ago to “modern biotechnology” as of today, presented by the editor [2]. Altogether, the book provides an overview of the most exciting innovations in biopharmaceutical development for the most pressing therapeutic areas with a high medical need. Each chapter highlights emerging research from some of the world's most respected scientists and managers who divulge their knowledge on how to transform the respective biotechnological treatment paradigms into cures for specific therapeutic areas. “Modern Biopharmaceuticals” also explores the current environment in healthcare and the pharmaceutical industry and examines drivers and challenges for the use of innovative biotechnologies for biopharmaceutical development.

Overall Biopharma Business

A snapshot of current biotechnology in Europe is given by some sector-specific diagnostic benchmarks from London-based Tefen Management Consulting [3] – similar to the first edition, which described the status of biopharmaceuticals in 2005 [4], and the impact of an ever-changing environment for pharmaceutical development, at that time from the perspective of McKinsey [5].

Process Optimization

In the first edition, the Bayer experience with different biopharmaceutical production systems was presented [6] and the industrial scale production of insulin by Novo Nordisk [7]. In this book, companies such as GE Healthcare Biosciences share their experience to cope with the increasing pressure by improving strategies and workflows [8], and Sartorius describe how they improve biopharmaceutical production by developing new and innovative process technologies [9].

Acceleration of Biopharmaceutical Development

This is followed by other “technological” improvements to design and produce modern biopharmaceuticals, for example, to increase cloning efficiency: previously the Gateway® system from Invitrogen was described [10], this time innovative technologies such as FastDigest® from Fermentas [11], and the IBA StarGate® expression cloning system [12]. Another approach to accelerate biopharmaceutical development is directed evolution to design smarter genetic libraries for effective biopharmaceuticals. Two examples were nicely described in the previous book by Nobel Laureate Manfred Eigen and colleagues from DirEvo (now a part of Bayer corporation) [13], and also by colleagues from Roche [14], now followed by another innovative technology with the same goal, applying a brute force method approach, Massive Mutagenesis® [15]. In addition, a new method of quantitative real-time PCR is presented to accelerate biopharmaceutical development [16].

Innovative Production of Biopharmaceuticals

Once the genetic blueprint of the modern biopharmaceutical is optimized and cloned into a high-level expression vector, the protein needs to be produced in an attractive host at a large and commercial scale. Besides the “common commercial” expression platforms, some highly innovative plant-based technologies were previously presented, for example, the moss bioreactor from greenovation [17], or the transient tobacco expression system magnICON™ from Icon Genetics [18]. Both systems are capable of designer glycosylation, (post-translational modification, PTM) and meanwhile, Icon Genetics was part of the Bayer Corporation to manufacture non-Hodgkin's lymphoma vaccines for phase I clinical trials. In this book, another striking example of plant-derived biopharmaceutical antibodies is presented: the world's first approved “plantibody” for human therapeutic use: all Cuban citizens born after 1980 received the hepatitis B vaccine, Heberbiovac. Over 12 million doses have been administered since 1992 in Cuba, and as a consequence, the Hepatitis B cases have fallen from more than 2000 per year (before vaccination began in 1992) to less than 50 a year now. This fantastic case study on vaccination against hepatitis B in Cuba shows how to efficiently apply biotechnology to foster economic growth and public health at the same time, also in developing countries [19].

Adjoining to transgenic plants, transgenic animals can also be used to cost-efficiently produce biopharmaceuticals. This was nicely shown with ATryn®, a human antithrombin III (AT) which is produced in transgenic goats, followed by easy downstream processing, that is, extraction from the goat's milk by cross-flow filtration which is used in the dairy industry since decades [20]. In the meantime, ATryn was approved in 2006 by the European Medicines Agency (EMA) for use in preventing clotting conditions during surgical procedures in patients with hereditary AT deficiency.