Fusion Protein Technologies for Biopharmaceuticals


Book Description

The state of the art in biopharmaceutical FUSION PROTEIN DESIGN Fusion proteins belong to the most lucrative biotech drugs—with Enbrel® being one of the best-selling biologics worldwide. Enbrel® represents a milestone of modern therapies just as Humulin®, the first therapeutic recombinant protein for human use, approved by the FDA in 1982 and Orthoclone® the first monoclonal antibody reaching the market in 1986. These first generation molecules were soon followed by a plethora of recombinant copies of natural human proteins, and in 1998, the first de novo designed fusion protein was launched. Fusion Protein Technologies for Biopharmaceuticals examines the state of the art in developing fusion proteins for biopharmaceuticals, shedding light on the immense potential inherent in fusion protein design and functionality. A wide pantheon of international scientists and researchers deliver a comprehensive and complete overview of therapeutic fusion proteins, combining the success stories of marketed drugs with the dynamic preclinical and clinical research into novel drugs designed for as yet unmet medical needs. The book covers the major types of fusion proteins—receptor-traps, immunotoxins, Fc-fusions and peptibodies—while also detailing the approaches for developing, delivering, and improving the stability of fusion proteins. The main body of the book contains three large sections that address issues key to this specialty: strategies for extending the plasma half life, the design of toxic proteins, and utilizing fusion proteins for ultra specific targeting. The book concludes with novel concepts in this field, including examples of highly relevant multifunctional antibodies. Detailing the innovative science, commercial realities, and brilliant potential of fusion protein therapeutics, Fusion Protein Technologies for Biopharmaceuticals is a must for pharmaceutical scientists, biochemists, medicinal chemists, molecular biologists, pharmacologists, and genetic engineers interested in determining the shape of innovation in the world of biopharmaceuticals.




Therapeutic Antibody Engineering


Book Description

The field of antibody engineering has become a vital and integral part of making new, improved next generation therapeutic monoclonal antibodies, of which there are currently more than 300 in clinical trials across several therapeutic areas. Therapeutic antibody engineering examines all aspects of engineering monoclonal antibodies and analyses the effect that various genetic engineering approaches will have on future candidates. Chapters in the first part of the book provide an introduction to monoclonal antibodies, their discovery and development and the fundamental technologies used in their production. Following chapters cover a number of specific issues relating to different aspects of antibody engineering, including variable chain engineering, targets and mechanisms of action, classes of antibody and the use of antibody fragments, among many other topics. The last part of the book examines development issues, the interaction of human IgGs with non-human systems, and cell line development, before a conclusion looking at future issues affecting the field of therapeutic antibody engineering. - Goes beyond the standard engineering issues covered by most books and delves into structure-function relationships - Integration of knowledge across all areas of antibody engineering, development, and marketing - Discusses how current and future genetic engineering of cell lines will pave the way for much higher productivity




Treatment of Leukemia and Lymphoma


Book Description

New Treatments of Leukemia and Lymphoma describes the most important advances in the therapy of hematopoietic cancers that have been derived from recent discoveries in cancer cell biology, kinase biochemistry, and immunology. Detailed descriptions of the large number of new and effective agents that have recently become available for the treatment of leukemias and lymphomas as well as an understanding of their mechanisms of action and their integration into current therapy are provided. A number of experimental drug reagents currently in clinical investigation are also discussed. The therapies include conventional anti-metabolites, monoclonal antibodies directed to cell surface receptors, antibodies tagged with toxins and radiopharmaceuticals, inhibitors of specific kinases, stem cell transplants, and engineered T-cells designed to selectively target hematopoietic cancers. The contents of the book will allow practitioners and investigators alike to understand what is current and state of the art as well as what to look for in the future.* Provides an up-to-date, state of the art discussion of a rapidly changing field * Great breadth covering conventional chemotherapeutic agents, biologic agents such as antibodies, novel small molecule inhibitors and genetically engineered cells * Written by international experts in each of the fields




Protein Engineering and Design


Book Description

Experimental protein engineering and computational protein design are broad but complementary strategies for developing proteins with altered or novel structural properties and biological functions. By describing cutting-edge advances in both of these fields, Protein Engineering and Design aims to cultivate a synergistic approach to protein science




Bispecific Antibodies


Book Description

The concept of using bispecific antibodies for cancer therapy by retargeting immune effector cells was developed several years ago. Initial clinical studies were rather disappointing mainly due to low efficacy, severe side effects and the immunogenicity of the bispecific antibodies. The progress in antibody engineering finally led to the generation of new classes of bispecific antibodies lacking these obstacles. In addition, new applications were established, such as pre-targeting strategies in radioimmunotherapy and dual targeting approaches in order to improve binding, selectivity and efficacy. In this book, the different ways of generating bispecific antibodies are described, with emphasis on recombinant formats. The various applications of bispecific antibodies, e.g. in cellular cancer immunotherapy, radioimmunotherapy and pretargeting strategies are covered, and emerging applications such as dual targeting strategies, which involve the simultaneous inhibition of two targets, are addressed.




Monoclonal Antibody Production


Book Description

The American Anti-Vivisection Society (AAVS) petitioned the National Institutes of Health (NIH) on April 23, 1997, to prohibit the use of animals in the production of mAb. On September 18, 1997, NIH declined to prohibit the use of mice in mAb production, stating that "the ascites method of mAb production is scientifically appropriate for some research projects and cannot be replaced." On March 26, 1998, AAVS submitted a second petition, stating that "NIH failed to provide valid scientific reasons for not supporting a proposed ban." The office of the NIH director asked the National Research Council to conduct a study of methods of producing mAb. In response to that request, the Research Council appointed the Committee on Methods of Producing Monoclonal Antibodies, to act on behalf of the Institute for Laboratory Animal Research of the Commission on Life Sciences, to conduct the study. The 11 expert members of the committee had extensive experience in biomedical research, laboratory animal medicine, animal welfare, pain research, and patient advocacy (Appendix B). The committee was asked to determine whether there was a scientific necessity for the mouse ascites method; if so, whether the method caused pain or distress; and, if so, what could be done to minimize the pain or distress. The committee was also asked to comment on available in vitro methods; to suggest what acceptable scientific rationale, if any, there was for using the mouse ascites method; and to identify regulatory requirements for the continued use of the mouse ascites method. The committee held an open data-gathering meeting during which its members summarized data bearing on those questions. A 1-day workshop (Appendix A) was attended by 34 participants, 14 of whom made formal presentations. A second meeting was held to finalize the report. The present report was written on the basis of information in the literature and information presented at the meeting and the workshop.




Molecular Imaging


Book Description

The field of molecular imaging of living subjects have evolved considerably and have seen spectacular advances in chemistry, engineering and biomedical applications. This textbook was designed to fill the need for an authoritative source for this multi-disciplinary field. We have been fortunate to recruit over 80 leading authors contributing 75 individual chapters. Given the multidisciplinary nature of the field, the book is broken into six different sections: "Molecular Imaging technologies", "Chemistry", "Molecular Imaging in Cell and Molecular Biology", "Applications of Molecular Imaging", "Molecular Imaging in Drug Evaluation" with the final section comprised of chapters on computation, bioinformatics and modeling. The organization of this large amount of information is logical and strives to avoid redundancies among chapters. It encourages the use of figures to illustrate concepts and to provide numerous molecular imaging examples.







Transforming Glycoscience


Book Description

A new focus on glycoscience, a field that explores the structures and functions of sugars, promises great advances in areas as diverse as medicine, energy generation, and materials science, this report finds. Glycans-also known as carbohydrates, saccharides, or simply as sugars-play central roles in many biological processes and have properties useful in an array of applications. However, glycans have received little attention from the research community due to a lack of tools to probe their often complex structures and properties. Transforming Glycoscience: A Roadmap for the Future presents a roadmap for transforming glycoscience from a field dominated by specialists to a widely studied and integrated discipline, which could lead to a more complete understanding of glycans and help solve key challenges in diverse fields.




Antibody Engineering Volume 1


Book Description

Antibodies are indispensable tools for research, diagnosis, and therapy. Recombinant approaches allow the modification and improvement of nearly all antibody properties, such as affinity, valency, specificity, stability, serum half-life, effector functions, and immunogenicity. "Antibody Engineering" provides a comprehensive toolbox covering the well-established basics but also many exciting new techniques. The protocols reflect the latest "hands on" knowledge of key laboratories in this still fast-moving field. Newcomers will benefit from the proven step-by-step protocols, which include helpful practical advice; experienced antibody engineers will appreciate the new ideas and approaches. The book is an invaluable resource for all those engaged in antibody research and development.