This edited work presents studies that clarify several aspects of the development and application of therapeutic enzymes. Therapeutic enzymes exhibit fascinating features and opportunities, and represent a significant and promising subcategory of modern biopharmaceuticals for the treatment of several severe diseases. Research and drug developments efforts and the advancements in biotechnology over the past twenty years have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of both rare and common disorders. The introduction and regulatory approval of twenty different recombinant enzymes has enabled effective enzyme-replacement therapy.

This book covers mainly three areas of recombinant therapeutic enzymes and their clinical and pharmaceutical technology: (i) overview of the production process and biochemical characterization of therapeutic enzymes, (ii) focuses upon the engineering strategies and delivery methods of therapeutic enzymes,(iii) clinical applications of selected therapeutic enzymes, including aspects on their mechanisms of action and information on safety, immunogenicity issues and various adverse events of the enzymes used for therapy.

The topic of this book is particularly relevant to academics, researchers and students undertaking advanced undergraduate/postgraduate programs in the biopharmaceutical/biotechnology area who wish to gain a comprehensive understanding of enzyme-based therapeutic molecules.

Zusammenfassung
Therapeutic enzymes exhibit fascinating features and opportunities, and represent a significant and promising subcategory of modern biopharmaceuticals for the treatment of several severe diseases. Research and drug developments efforts and the advancements in biotechnology over the past twenty years have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of both rare and common disorders. The introduction and regulatory approval of twenty different recombinant enzymes has enabled effective enzyme-replacement therapy. This volume aims to overview these therapeutic enzymes, focusing in particular on more recently approved enzymes produced by recombinant DNA technology. This volume is composed of four sections. Section 1 provides an overview of the production process and biochemical characterization of therapeutic enzymes, while Section 2 focuses upon the engineering strategies and delivery methods of therapeutic enzymes. Section 3 highlights the clinical applications of approved therapeutic enzymes, including aspects on their structure, indications and mechanisms of action. Together with information on these mechanisms, safety and immunogenicity issues and various adverse events of the recombinant enzymes used for therapy are discussed. Section 4, provides discussion on the prospective and future developments of new therapeutic enzymes. This book is aimed at academics, researchers and students undertaking advanced undergraduate/postgraduate programs in the biopharmaceutical/biotechnology area who wish to gain a comprehensive understanding of enzyme-based therapeutic molecules.

Inhalt

Section 1: Production and characterization of therapeutic enzymes Chapter 1. Introduction to therapeutic enzymes Fuhrmann G, Leroux JC, Institute of Pharmaceutical Sciences Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Str. 10, HCI H 301, 8093, Zurich, Switzerland Chapter 2. Upstream processing technologies Ian Marison, Dublin City University, Glasnevin, Dublin 9, Ireland

Chapter 3. Downstream processing technologies N. Labrou, Department Biotechnology, University of Athens

Chapter 4. Enzyme Manufacturing Process and Quality Control Evaluations Ingrid Markovic, Ph.D., Laboratory of Biochemistry, Division of Therapeutic Proteins, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, FDA

Chapter 5. Regulatory guidance in the production of therapeutic enzymes John Geigert, PhD, RAC, BioPharmaceutical Quality Solutions

Chapter 6. Biophysical methods for the characterization of Enzyme Therapeutics Bertrand Raynal Patrick England, CNRS-UMR3528, Institut Pasteur, Department of Structural Biology and Chemistry

Chapter 7. Clinical Development of a therapeutic enzyme Baldo BA, 11 Bent Street, Lindfield, NSW, 2070, Australia

Section 2: Engineering and delivery of therapeutic enzymes

Chapter 8. Chemical modifications of therapeutic proteins Mark D. Distefano, Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA

Chapter 9. Formulation of therapeutic enzymes Sathy V. Balu-Iyer, Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Amherst, NY14260, USA

Chapter 10. Engineering of therapeutic enzymes for improving activity Georgiou, G, University of Texas, Austin

Chapter 11. Engineering of therapeutic enzymes for improving stability Tokuriki N, Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada

Chapter 12. Design and engineering of deimmunized therapeutic enzymes Griswold KE, Thayer School of Engineering, Dartmouth, Hanover, NH, United States

Chapter 13. Nanoparticles for delivery of therapeutic enzymes Champion JA, Department of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia Chapter 14. Targeted delivery of therapeutic enzymes Gianneschi NC, Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093, USA

Chapter 15. Oral and inhalable enzyme therapies Khosla C, Division of Biology, California Institute of Technology, Pasadena, California, USA Chapter 16. Regulatory issues Anurag S. Rathore, Ph.D., DBT Center of Excellence for Biopharmaceutical Technology, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi, 110016, India

Section 3: Structure, indications and mechanisms for enzymes approved for human therapy

Chapter 17. Enzyme replacement therapies Harmatz P, 1UCSF Benioff Children's Hospital Oakland, Oakland, California

Chapter 18. Pharmacodynamics and pharmacokinetics issues of enzyme replacement therapy Qi Y, BioMarin Pharmaceutical Inc., 105 Digital Dr, Novato, CA, 94949, USA

Chapter 19. Enzyme therapy for lysosomal storage disorders Hollak CE, Department of Internal Medicine, Division of Endocrinology and Metabolism, SPHINX, Amsterdam Lysosome Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

Chapter 20. Enzyme therapy for myocardial infarction Kunamneni A, Center for Global Health, Department of Internal Medicine, University of New Mexico and New Mexico VA Health Care System, Albuquerque - 87108, New Mexico, USA

Chapter 21. Enzyme therapy for chronic gout Shannon JA, Philadelphia College of Osteopathic Medicine, School of Pharmacy, Suwanee, GA, USA

Chapter 22. Enzyme therapy for tumor lysis syndrome Lopez-Olivo MA, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

Chapter 23. Enzyme therapy for collagen-based disorders Kaplan FT, Indiana Hand to Shoulder Center, 8501 Harcourt Rd, Indianapolis, IN 46260 USA

Chapter 24. Enzyme therapy for severe combined immunodeficiency disease Onodera M, Department of Human Genetics, National Research Institute for Child Health and Development, Japan

Chapter 25. Enzyme therapy for detoxification of methotrexate Wang A, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Chapter 26. Enzyme therapy vitreomacular adhesion Rodríguez-Hurtado FJ, Servicio de Oftalmología, Hospital Virgen de las Nieves, Granada, España

Chapter 27. L-Asparaginase as anticancer agent N. Labrou, Department Biotechnology, University of Athens

Chapter 28. Pancreatic enzyme replacement therapy Berry AJ, University of Virginia Health System, Charlottesville, Virginia Section 4:…