Dale L. Oxender and Leonard E. Post (ed.) Novel Therapeutics from Modern Biotechnology. From Laboratory to Human Testing

Springer-Verlag Berlin Heidelberg 1999. (Softcover reprint of the hardcover I st edition 1999). ISBN: 978-3-540-65927-3.
A cover story of Business Week Magazine in January 1984 stated "Biotech Comes of Age". In February 1986, Venture Magazine had a cover article entitled "The Biotech Revolution is Here". This article went on to say "New Genetic Technologies Will Transform Our Lives". These announcements were made many years after the first biotechnology companies, such as Genentech, Cetus, Amgen and Biogen, were formed- to commercialize the "New Biology".
At the time of writing this book, there are over 1300 biotech companies developing new technologies or identifying potential biotech drugs. Most of these companies were started in the height of the "high-technology hype", although companies are still forming as the technology advances.
A more recent survey showed only a relatively small number of Food and Drug Administration (FDA) approvals among over several hundred biotechnology products now in clinical trial. One could ask why it has taken so long to produce biotechnology products. Part of the reason is that each new class of biotech products brings with it a set of problems that need to be solved before.
they enter clinical trials. These problems are often unique to biotechnology products, such as peptides, proteins, monoclonal antibodies, nucleic acids and cellular therapies.
Although the "biotech" therapeutics represent unique scientific issues, there are now numerous examples that show that the principles of drug development apply to the newer systems as well as to development of novel small synthetic compounds. For example, there needs to be a well-controlled process for making the therapeutics, appropriate analytical methodologies to characterize the product, appropriate formulation to store and deliver the.
therapy to the patient, and a thorough. characterization of the safety issues surrounding the new entity.
Our goal in this volume is to address the particular problems associated with several classes of biotechnology products and, at the same time, demonstrate that the principles are the same as in development of small new chemical entities. We have invited several scientists at biotechnology or pharmaceutical companies to share with us some of the unique problems that they encountered in getting biotech products into clinical trials and how they solved them.
The first chapter addresses Fda regulatory expectations for biotech products. The next several chapters discuss general issues common to each class of biotech drug, such as proteins, peptides and nucleic acids. The balance of the chapters deals with specific biotech drugs that have successfully made it into clinical trials.
We would like to express our appreciation to the authors and the companies in which they work. The patience of the staff of Springer-Verlag is also appreciated. Special thanks goes to Joyce Peplinski for secretarial and organizational assistance.
D.L. Oxender, L.E. Post.
Chapter 1. Overview of Regulatory Expectations for Introducing Novel Therapies into Clinical Trials.
Chapter 2. Preparation of Clinical Trial Supplies of Biopharmaceuticals.
- Preclinical Studies.
- Clinical Supplies.
- Purification of rDNA-Derived Anti-RSV Mab.
- Product Quality Issues.
- Process Design and Validation.
- Process Economics and the Future of Chromatography.
- Conclusions.
Chapter 3. Proteins as Drugs: Analysis, Formulation and Delivery.
- The Analysis of Protein Pharmaceuticals.
- Formulation.
- Delivery.
Chapter 4. Strategies for Dealing With the Immunogenicity of Therapeutic Proteins.
- Case Histories of Protein Therapeutic Development.
- Strategies Under Development for Increasing the Therapeutic Value of Proteins and Peptides.
- Choosing the Proper Strategy for a Protein Therapeutic.
- The Future of Protein Therapeutics.
Chapter 5. Targeted Toxin Hybrid Proteins.
- Introduction (Protein Toxins That Inhibit Protein Synthesis; Structure and Function of Pseudomonas Exotoxin; Types of Toxins Made with Pe).
- Preclinical Development of Anti-Tac(Fv) Toxins;).
- Preclinical Development of Inerleukin 6 – Pe4e.
Chapter 6. Sb 209763: a humanized Monoclonal Antibody for the Prophylaxis and Treatment of Respiratory Syncytial Virus Infection.
- Early Challenges in the Development of Sb 209763.
- Preclinical Evaluation Prior to Testing in Humans.
- Challenges for the Early Clinical Development of Sb 209763.
Chapter 7. Preclinical Development of Antisense Therapeutics.
- Pharmacology of Antisense Oligodeoxynucleotides.
- Pharmacokinetics and Toxicity of Oligodeoxynucleotide Therapeutics.
- Chemistry, Manufacture and Control of Phosphorothioate Oligodeoxynucleotide Drugs.
- Formulation and Drug Delivery of Oligodeoxynucleotides.
Chapter 8. Formulation and Delivery of Nucleic Acids.
- Formulation of Dna.
- Delivery to Target Cells.
- Cell Entry.
- Endosomal Release.
- Nuclear Localization.
- Gene Expression.
Chapter 9. Safe, Efficient Production of Retroviral Vectors.
- Vectors.
- Production of Retroviral Vectors.
- Downstream Processing.
- Gmp production of Retroviral Veytors.
- In-Process Assays.
- Quality Control.
- Safety.
Chapter 10. Clinical Systems for the Production of Cells and Tissues for Human Therapy.
- Cell Therapy and Tissue Engineering.
- Critical Requirements for Ex Vivo Cell Production.
- Cell-Culture Devices and Procedures.
- Applications for On-Site Delivery of Therapeutic Cell Production.