Modern Biopharmaceuticals: Recent Success Stories -- Contents -- 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 -- 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" -- 1.3.1 Molecular Genetics and Enzymatic Kinetics -- 1.3.2 Penicillin and Other Lifesaving Antibiotics -- 1.3.3 The Triumphal Procession of Vitamin C -- 1.4 A Small Molecule from Bacteria - A Huge Importance for Mankind -- 1.4.1 Plasmids: Transformation by Gene Transfer -- 1.4.2 DNA: The Molecule of Life -- 1.4.3 Immortalized Cells: The Source of Monoclonal Antibodies -- 1.4.4 Insulin: The First Biotech Blockbuster -- 1.4.5 Polymerase Chain Reaction: How to Infinitely Amplify DNA -- 1.5 Biopharmaceuticals - The Mainstay of Modern Biotechnology -- 1.5.1 Modern Biopharmaceuticals in Europe -- 1.6 Transformation of the Pharma Industry Through Biotechnology -- 1.6.1 The Market as Motivation for Transformation -- 1.6.2 Innovations and Where They do Come From -- 1.6.3 Mergers and Acquisitions in the Biopharmaceutical Industry and the Impact on Innovation -- 1.6.4 A Focus on the Opportunities of European Biotech Industry -- 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 -- 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 -- References -- 3 Pluripotent Stem Cell-Derived Cardiomyocytes for Industrial and Clinical Applications -- 3.1 Introduction -- 3.2 Pluripotent Stem Cells -- 3.2.1 Embryonic Stem Cells -- 3.2.2 Parthenogenetic Stem Cells -- 3.2.3 Germline Pluripotent Stem Cells -- 3.2.4 Induced 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 -- 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 -- 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.

5.6.1 Chemistries for Amplification and Detection -- 5.6.2 Choosing Between Two-Step and One-Step RT-PCR -- 5.6.3 Multiplexing Increases Accuracy and Throughput of Real-Time RT-PCR -- 5.6.4 Common Problems in Optimizing Multiplex, Real-Time RT-PCR -- 5.6.5 Novel Chemistries for Standardization of Multiplex, 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 -- 6 Massive Mutagenesis®: The Path to Smarter Genetic Libraries -- 6.1 Introduction -- 6.1.1 Directed Evolution and Biopharmaceuticals -- 6.1.2 Directed Evolution: The Process -- 6.1.3 Aiming for Bigger and Smarter Libraries -- 6.2 Massive Mutagenesis -- 6.2.1 Principle -- 6.2.2 Properties -- 6.2.3 Chip-Eluted Oligonucleotide Libraries for Mutagenesis -- 6.2.4 Comparison with Existing Mutagenesis Procedures -- 6.3 Sample Applications of Massive Mutagenesis -- 6.3.1 Fine-Tuning of the Specificity of an Antibody to be Used in Diagnostics -- 6.3.2 Biocatalysis of APIs -- 6.3.3 Improvement of an Antibody Neutralizing the Anthrax Toxin -- 6.3.4 Thermostable Vaccines -- 6.4 Conclusion and Perspectives -- References -- 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 -- 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 -- References -- 9 Precision Genome Surgery with Meganucleases: A Promising Biopharmaceutical for Gene Therapy -- 9.1 Introduction -- 9.2 Meganucleases -- 9.2.1 Zinc Finger Nucleases -- 9.2.2 Homing Endonucleases -- 9.2.3 Restriction Endonuclease-TFO Fusions -- 9.3 Prospects of Gene Therapy Using Meganucleases -- 9.4 Summary and Outlook -- References -- 10 Innovative Diagnostics Enhances and Advances the Impact of In Vivo Small-Animal Imaging in Drug Discovery and Pharmaceutical Development -- 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 -- 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 -- 11.7.1 Optoacoustic Signal Generation and Propagation.

11.7.2 Image Reconstruction -- 11.7.3 Multispectral Imaging -- 11.8 Quantification -- 11.9 Conclusion and Perspective for MSOT in Biopharmaceutical Development -- References -- 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 -- References -- Part IV: The Rise of Monoclonal Antibodies - The Premium Class of Biopharmaceuticals -- 13 Implementation of Advanced Technologies in Commercial Monoclonal Antibody Production -- 13.1 Part I: Commercial Antibody Process Development -- 13.1.1 Introduction -- 13.1.1.1 Essential Considerations for a Commercial Process Development -- 13.1.1.2 Major Challenges for Upstream and Downstream Processes -- 13.1.1.3 Dosage and Bulk Product Purity -- 13.1.1.4 High-Titer Cell Culture Processes and its Impact to Downstream Processes -- 13.1.1.5 Viral Clearance Strategy -- 13.1.2 Upstream Process -- 13.1.2.1 Cell Line Development -- 13.1.2.2 Media and Feeding Strategy Development -- 13.1.2.3 Bioreactor Process and Control -- 13.1.2.4 Impact of Cell Culture Process on Product Quality Attributes -- 13.1.3 Downstream Process -- 13.1.3.1 Harvest and Capture Process -- 13.1.3.2 Polishing Chromatography -- 13.1.3.3 Viral Filtration -- 13.1.3.4 Aseptic Filtration -- 13.2 Part II: Implementation of Membrane Technology in Antibody Large-Scale Purification -- 13.2.1 Introduction -- 13.2.1.1 Pros and Cons of Using Q Membrane Chromatography as a Purification Unit -- 13.2.1.2 Historical Studies of Q Membrane Chromatography in Antibody Production.

13.2.1.3 Operation Units for Membrane Chromatography.