Prologue.

Dedication.

Foreword.

Quotes.

Executive Summary.

List of Contributors.

Introduction.

Current Status of Biopharmaceuticals: Approved Products and Trends in Approvals (G. Walsh).

PART I: BIOPHARMACEUTICALS USED IN MOLECULAR MEDICINE.

From Genome to Clinic—Correlation Between Genes, Diseases and Biopharmaceuticals.

1. Beginning to Understand the End of the Chromosome (T. Cech).

2. The Role of Pharmacogenetic / Pharmacogenomics in Drug Development and Regulatory Review: Current Status (S. Huang & L. Lesko).

3. Large-scale Detection of Genetic Variation: The Key to Personalized Medicine (J. Geistlinger & P. Ahnert).

4. A System Biology Approach to Target Identification and Validation for Human Chronic Disease Drug Discovery (B. Rothberg, et al.).

5. The Development of Herceptin®: Paving the Way for Indivdualized Cancer Therapy (T. Gutjahr & C. Reinhardt).

siRNA—The Magic Bullet and Other Gene Therapeutical Approaches.

6. Adenovirus-based Gene Therapy: Therapeutic Angiogenesis with Adenovirus 5 Fibroblast Growth Factor-4 (Ad5FGF-4) in Patients with Chronic Myocardial Ischemia (M. McCaman, et al.).

7. MIDGE Vectors and dSLIM Immunomodulators: DNA-based Molecules for Gene Therapeutic Strategies (M. Scmidt, et al.).

8. Nonprotein-coding RNAs and their Potential as Biopharmaceuticals (M. Szymanski, et al.).

9. Double-stranded Decoy Oligonucleotides as New Biopharmaceuticals (A. Wagner & H. von der Leyen).

10. Rational siRNA Design for RNA Interference: Optimizations for Therapeutic Use and Current Applications (A. Khvorova, et al.).

Mobilis in Mobile—Human Embryonic Stem Cell and Other Sources for Cell Therapy.

11. The First Cloned Human Embryo: An Unlimited Source of Stem Cells for Therapeutic Cloning (W. Hwang, et al.).

12. Myocardial Regeneration Strategies Using Human Embryonic Stem Cells (I. Kehat, et al.).

13. Gene and Cell-based Therapies for Cardiovascular Disease (A. Mangi).

14. Spheramine®: A Cell Therapeutic Approach to Parkinson's Disease (E. Reissig, et al.).

15. Applying Human Cells to Organogenesis and Transplantation (B. Dekel & Y. Reisner).

VOLUME 2

PART II: BIOPHARMACEUTICALS AND THEIR MODE OF ACTION.

Quid pro Quo—Lysis vs. Coagulation in the Fine-tuned Balance of the Clotting Cascade.

1. Mechanisms of Serine Proteinase Activation: Insights for the Development of Biopharmaceuticals for Coagulation and Fibrinolysis (R. Friedrich).

2. Application of the Principle of Polyvalency to Protease Inhibition (L. Moroder).

3. A New Technology Standard for Safety and Efficacy in Factor VIII Replacement Therapy; Designing an Advanced Category rFVIII Concentrate (N. Riedel & F. Dorner).

Errare Humanum Est—What Causes Cancer and How to Selectively Fight Tumors.

4. Biopharmaceuticals Drugs From Natural Sources (D. Newman, et al.).

5. Biopharmaceutical as Targeting vehicles for In situ Radiotherapy of Malignancies (R. Reilly).

6. New Directions in Tumor Therapy—Amino Acid Deptetion with GlutaDON® as Treatment for Cancer (R. Kalhammer & N. Sethuraman).

Mundus Vult Decipi—High Mutation Rates of HIV and New Paradigms for Treatment.

7. AIDS Gene Therapy: A Vector Selectively Able to Destroy Latently HIV-1-infected Cells (F. Vázquez & R. Oya).

8. Combinatorial RNA-based Therapies for HIV-1 (K. Morris & J. Rossi).

PART III: IMPROVING THE DEVELOPMENT OF BIOPHARMACEUTICALS.

Citius, Altius, Fortius—Acceleration by High Throughput and Ultra-HT.

1. Design of Modern Biopharmaceuticals by Ultra-high-throughput Screening and Directed Evolution (M. Rarbach, et al.).

2. Learning from Viruses: High-throughput Cloning Using the Gateway® System to Transfer Genes without Restriction Enzymes (J. Chesnut).

In Vivo Veritas—Early Target Validation in Knock-out Mice and More.

3. Target Validation: An Important Early Step in the Development of Novel Biopharmaceuticals in the Post-genomic Era (C. Bagowski).

4. Genetically Modified Mice in Medical and Pharmaceutical Research (C. Brakebuch).

5. An NIH Model Organism for Biopharmaceutical and Biomedical Research: The Lower Eukayote Dictyostelium discoideum (T. Winckler, et al.).

Revolution by Evolution—Rational Design for Desire and Scientific Art of Optimization.

6. Releasing the Spring: Cofactor- and Substrate-assisted Activation of Factor IXa (H. Brandstette & K. Sichler).

7. Accelerating Diagnostic Product Development Process with Molecular Rational Design and Directed Evolution (H. Sobek, et al.).

VOLUME 3

PART IV: PRODUCTION OF BIOPHARMACEUTICALS.

The Industry's Workhorses—Mammalian Expression System.

1. Manufacture of Recombinant Biopharmaceutical Proteins by Cultivated Mammalian Cells in Bioreactors (F. Wurm).

2. Alternative Strategies and New Cell Lines for High-level Production of Biopharmaceuticals (T. Rose, et al.).

3. PER.C6^® Cells for the Manufacture of Biopharmaceutical Proteins (C. Yallop, et al.).

4.  Use of the Glutamine Synthetase (GS) Expression System for the Rapid Development of Highly Productive Mammalian Cell Processes (J. Birch, et al.).

Vivat, Crescat, Floreat—A Ripe and Blooming Market for Transgenic Animals and Plants.

5. Biopharmaceuticals Derived from Transgenic Plants and Animals (J. Baez).

6. Production of Recombinant Proteins in Plants (V. Klimyuk, et al.).

7. Humanized Glycosylation: Production of Biopharmaceuticals in a Moss Bioreactor (G. Gorr & S. Wagner).

8. ExpressTec: High-level Expression of Biopharmaceuticals in Cereal Grains (N. Huang & D. Yang).

9. Biopharmaceutical Production in Cultured Plant Cells (S. Schillberg, et al.).

10. Producing Biopharmaceuticals in the Desert: Building an Abiotic Stress Tolerance in Plants for Salt, Heat, and Drought (S. Gepstein, et al.).

11. The First Biopharmaceutical from Transgenic Animals: ATryn^® (Y. Echelard, et al.).

Alea Non lacta Est—Improving Established Expression Systems.

12. Producing Modern Biopharmaceuticals: The Bayer HealthCare Pharma Experience with a Range of Expression Systems (H. apeler).

13. Advanced Expression of Biopharmaceuticals in Yeast at Industrial Scale: The Insulin Success Story (A. Andersen & I. Diers).

14. Baculovirus-based Production of Biopharmaceuticals Using Insect Cell Culture Processes.

15. Robust and Cost-effective Cell-free Expression of Biopharmaceuticals: Escherichia Coli and Wheat Embryo (L. Miles).

When Success Raises its Ugly Head—Outsourcing to Uncork the Capacity Bottleneck.

16. Contract Manufacturing of Biopharmaceuticals Including Antibodies or Antibody Fragments (J. Hempel & P. Hess).

PART V: BIOPHARMACEUTICALS USED FOR DIAGNOSTICS AND IMAGING.

From Hunter to Craftsman—Engineering Antibodies with Nature's Universal Toolbox.

1. Thirty Years of Monoclonal Antibodies: A Long Way to Pharmaceutical and Success (U. Gottschalk & K. Mundt).

2. Modern Antibody Technology: The Impact on Drug Development (S. Moroney & A. Plückthun).

3. Molecular Charcterization of Autoantibody Responses in Autoimmune Diseases: Implications for Diagnosis and Understanding of Autoimmunity (C. Breiethaupt).

Find, Fight, and Follow—Target-specific troika from Mother Nature's Pharmacopoiea.

4. Molecular Imaging and Applications for Pharmaceutical R&D (J. Orsel & T. Schaeffter).

5. Design and Development of Probes for In vivo Molecular and  Functional Imaging of Cancer and Cancer Therapies by Positron Emission Tomography (PET) (E. Aboagye).

6. Ligand-based Targeting of Disease: From Antibodies to Small Organic (Synthetic) Ligands (M. Silacci & D. Neri).

7. Ultrasound Theranostics: Antibody-based Microbubble Conjugates as Targeted In vivo contrast Agents and Advanced Drug Delivery Systems (A. Briel, et al.).

Getting Insight—Sense the Urgency for Early Diagnostics.

8. Development of Multi-marker-based Diagnostic Assays with the ProteinChip^® System (A. Wiesner).

9. Early Detection of Lung Cancer: Metabolic Profiling of Humaqn Breath with Ion Mobility Spectrometers (J. Baumbach, et al.).

VOLUME 4

PART VI: ADVANCED APPLICATION ROUTES FOR BIOPHARMACEUTICALS.

Getting Inside—Quest for the Best and How to Improve Delivery.

1. Advanced Drug Delivery Systems for Biopharmaceuticals (G. Hildebrand & S. Harnisch).

Pathfinder—New Ways for Peptides, Proteins and Co.

2. Poly(ethylene) Glycol Conjugates of Biopharmaceuticals in Drug Delivery (M. Bentley, et al.).

3. Novel Vaccine Adjuvants Based on Cationic Peptide Delivery Systems (K. Lingnau, et al.).

4. The Evolving Role of Oralin^TM (Oral Spray Insulin) in the Treatment of Diabetes Using a Novel RapidMist^TM Diabetes Management System (P. Modi).).

5. Improvement of Intestinal Absorption of Peptide and Protide Biopharmaceuticals by Various Approaches (A. Yamamoto).

Via Mala—The Stoney Road of DNA Delivery: Back-pack, Feed-back, and Pay-Back.

6. DNA Vaccine Delivery from Poly(ortho ester) Miocrospheres (C. Wang, et al.).

7. Liposomal In vivo Gene Delivery (S. Kawakami, et al.).

8. Programmed Packaging: A New Drug Delivery System and Its Application to Gene Therapy (K. Kogure, et al.).

Getting Beyond—Rocket Science vs. Science Fiction.

9. Bionanotechnology and Its Role to Improve Biopharmaceuticals (O. Kayser).

PART VII: FROM TRANSCRIPTION TO PRESCRIPTION OF BIOPHARMACEUTICALS.

Dosis Facit Venenum—The Therapeutic Windows Between Systemic Toxicity and Lack of Efficacy.

1. Analytics in Quality Control and In vivo (M. Hildebrand).

2. Design, Development and Optimization: Crystal Structures of Microsomal Cytochromes P450 (D. Vinkovic, et al.).

3. Mettox^TM  : A Suite of Predictive In silico and In vitro Assays for Metabolic and Genotoxicological Profiling of Preclinical Drug Candidates (M. Murray).

Happy End: Claims to Fame and Approval.

4. Considerations for Developing Biopharmaceuticals: FDA Perspective (K. Brorson, et al.).

5. The Regulatory Environment for Biopharmaceuticals in the EU (A. Wenzel & C. Sonnega).

PART VIII: FROM BENCH TO BEDSIDE - THE AFTERMATHS.

Think Big and Dealmaking for Growth—Global Changes in the Health-care Sector.

1. Healthcare Trends and their Impact on the Biopharmaceutical Industry: Biopharmaceuticals Come of Age (A. Moscho, et al.).

News and Views—Quo Vadis, Biopharmaceuticals?

2. mondoBIOTECH: The Swiss biotech BOUTIQUE (D. Bevec & F. Cavalli).

3. G-CSF and Bioequivalence: The Emergence of Healthcare Economics (J. Harris).

Light at the End of the Tunnel or Back to the Roots?

4. Bioinformatics: From Peptides to Profiled Leads (P. Wrede & M. Filter).

5. Engineering and Overproduction of Polyketide Natural Products (M. Lovato Tse & C. Khosla).

Epilog.

More About the Editor.

Supplement CD-ROM.

Subject Index.