Development Of Antibody Based Therapeutics

Translational strategies for development of antibody-based therapeutics should allow understanding of the relationship between the ‘unit dose’ and ‘unit effect’ with respect to both beneficial and deleterious effects from early stages of development. The flow of information from later to earlier stages of development should provide opportunities to facilitate selection of more effective novel and next-generation drug candidates. Selection and evaluation of relevant biomarkers in early preclinical development in "relevant" animal models should allow for identifying potential risks to humans and establishing safe First-In-Human (FIH) dosing strategies. Hence, integration of knowledge with respect to target antigen properties such as antigen distribution, expression profile, kinetic properties, target pharmacology, antigen isoforms and pharmacological redundancy in health and disease, as well as antibody design criteria, such as antibody isotype, affinity, PK/PD and safety is a critical necessity for the design of effective translational strategies. Additionally, these factors will further offer critical differentiating characteristics for next-generation antibodies, and novel technologies prove instrumental in generation of biosuperior antibody candidates for market entry. This book will examine many important considerations necessary for the design of effective translational strategies during the development of antibody-based therapeutics.

With a key focus on recent developments and advances in the field, this book provides in-depth coverage of topics fundamental to the development of targeted therapeutics. The expansion of targeted modalities in rapidly evolving therapeutic areas, such as immune-oncology, and developments with respect to combination therapies, novel technologies, and the therapeutic application of antibody-drug conjugates, are presented. Additionally, the book builds upon topics discussed in the first edition (2012) where recent innovations warrant elaboration. This, the second edition of Development of Antibody-Based Therapeutics: Translational Considerations, represents a comprehensive evaluation of progress in the field, which sits alongside the first edition to inform, in detail, professional and academic researchers, as well as graduate students.

Approaches to the Purification, Analysis and Characterization of Antibody-Based Therapeutics provides the interested and informed reader with an overview of current approaches, strategies and considerations relating to the purification, analytics and characterization of therapeutic antibodies and related molecules. While there are obviously other books published in and around this subject area, they seem to be either older (c.a. year 2000 publication date) or are more limited in scope. The book will include an extensive bibliography of the published literature in the respective areas covered. It is not, however, intended to be a how-to methods book. Covers the vital new area of R&D on therapeutic antibodies Written by leading scientists and researchers Up-to-date coverage and includes a detailed bibliography

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

Still the most comprehensive reference source on the development, production and therapeutic application of antibodies, this second edition is thoroughly updated and now has 30% more content. Volume 1 covers selection and engineering strategies for new antibodies, while the second volume presents novel therapeutic concepts and antibodies in clinical study, as well as their potential. Volumes 3 and 4 feature detailed and specific information about each antibody approved for therapeutic purposes, including clinical data. This unique handbook concludes with a compendium of marketed monoclonal antibodies and an extensive index. Beyond providing current knowledge, the authors discuss emerging technologies, future developments, and intellectual property issues, such that this handbook meets the needs of academic researchers, decision makers in industry and healthcare professionals in the clinic.

This practical manual, written by well-known experts, reviews current indications for the use of IgG concentrates and some other modern immunomodulators and provides fundamental information on present-day immunomodulation in patients (and mice). The book opens by tracing the transition from IgG substitution to IgG immunomodulation and providing expert updates on immunomodulatory indications in autoimmune and inflammatory disorders, including hematologic, neurologic, dermatologic, and other diseases. Basic aspects of IgG concentrates, including methods of production, safety, currently available products, and mechanisms of action, are then discussed. An entire chapter is devoted to the different aspects of immunomodulatory IgG treatment in the bleeding disorder immune thrombocytopenia (ITP). Finally, the transition from polyclonal to monoclonal antibody (mAb) treatment is addressed in detail, covering mAb development, methods, mechanisms of action, adverse effects, and more. Particular attention is paid to the example of anti-CD20 (B-cell) antibody.

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.