Engineering Bivalency And Bispecificity In Protein Therapeutics And Protein Scaffold Development
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Engineering Bivalency And Bispecificity In Protein Therapeutics And Protein Scaffold Development
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Author : Cassie J. Liu
language : en
Publisher:
Release Date : 2016
Engineering Bivalency And Bispecificity In Protein Therapeutics And Protein Scaffold Development written by Cassie J. Liu and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
Multivalent and multifunctional proteins are abundant in nature. The avidity effect, a core principle of multivalent molecules, allows these proteins to tune biological functions and responses across a large dynamic range with varying specificity. Many protein therapeutics also take advantage of this evolvable tunability, the canonical example being the antibody. This thesis consists of two separate sections. Section One: I focus on the avidity effect of multivalent proteins and its therapeutic uses. As an illustrative case, our lab had previously created a protein variant that monomerically binds the c-MET tyrosine kinase. By dimerizing this variant, we find that we greatly increase its efficacy through increased apparent affinity to cell surface c-MET. Section Two: I focus on multispecific proteins and their uses in medical applications. Most current therapeutic protein scaffolds are single protein domains with monomeric binding and function. Combining these scaffolds to create multispecific functionality presents manufacturing challenges. Here the vascular endothelial growth factor (VEGF) protein is used as a stable, naturally bivalent scaffold for engineering bispecific proteins.
Fusion Protein Technologies For Biopharmaceuticals
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Author : Stefan R. Schmidt
language : en
Publisher: John Wiley & Sons
Release Date : 2013-01-28
Fusion Protein Technologies For Biopharmaceuticals written by Stefan R. Schmidt and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-01-28 with Medical categories.
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.
Bispecific Antibodies
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Author : Roland E. Kontermann
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-07-21
Bispecific Antibodies written by Roland E. Kontermann and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-07-21 with Medical categories.
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.
Protein Therapeutics
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Author : Tristan Vaughan
language : en
Publisher: John Wiley & Sons
Release Date : 2017-07-28
Protein Therapeutics written by Tristan Vaughan and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-07-28 with Medical categories.
In this practice-oriented two volume handbook, professionals from some of the largest biopharmaceutical companies and top academic researchers address the key concepts and challenges in the development of protein pharmaceuticals for medicinal chemists and drug developers of all trades. Following an introduction tracing the rapid development of the protein therapeutics market over the last decade, all currently used therapeutic protein scaffolds are surveyed, from human and non-human antibodies to antibody mimetics, bispecific antibodies and antibody-drug conjugates. This ready reference then goes on to review other key aspects such as pharmacokinetics, safety and immunogenicity, manufacture, formulation and delivery. The handbook then takes a look at current key clinical applications for protein therapeutics, from respiratory and inflammation to oncology and immune-oncology, infectious diseases and rescue therapy. Finally, several exciting prospects for the future of protein therapeutics are highlighted and discussed.
Antibody Fc Engineering Towards Better Therapeutics
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Author : Tianlei Ying
language : en
Publisher: Frontiers Media SA
Release Date : 2018-12-21
Antibody Fc Engineering Towards Better Therapeutics written by Tianlei Ying and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-12-21 with categories.
Protein Therapeutics 2 Volume Set
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Author : Tristan Vaughan
language : en
Publisher: John Wiley & Sons
Release Date : 2017-12-04
Protein Therapeutics 2 Volume Set written by Tristan Vaughan and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-12-04 with Medical categories.
In this practice-oriented two volume handbook, professionals from some of the largest biopharmaceutical companies and top academic researchers address the key concepts and challenges in the development of protein pharmaceuticals for medicinal chemists and drug developers of all trades. Following an introduction tracing the rapid development of the protein therapeutics market over the last decade, all currently used therapeutic protein scaffolds are surveyed, from human and non-human antibodies to antibody mimetics, bispecific antibodies and antibody-drug conjugates. This ready reference then goes on to review other key aspects such as pharmacokinetics, safety and immunogenicity, manufacture, formulation and delivery. The handbook then takes a look at current key clinical applications for protein therapeutics, from respiratory and inflammation to oncology and immune-oncology, infectious diseases and rescue therapy. Finally, several exciting prospects for the future of protein therapeutics are highlighted and discussed.
Therapeutic Antibody Engineering
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Author : William R Strohl
language : en
Publisher: Elsevier
Release Date : 2012-10-16
Therapeutic Antibody Engineering written by William R Strohl and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-10-16 with Medical categories.
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
Antibody Fusion Proteins
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Author : Steven M. Chamow
language : en
Publisher: Wiley-Liss
Release Date : 1999-04-13
Antibody Fusion Proteins written by Steven M. Chamow and has been published by Wiley-Liss this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999-04-13 with Science categories.
Thoroughly detailed and illustrated, this book examines the construction, properties, applications, and problems associated with specific types of fusion molecules used in clinical and research medicine. The editors present an overview of the field, followed by nine chapters divided into two general sections based on the two primary parts of the antibody molecule: Fab fusion proteins and Fc fusion proteins. In addition, numerous renowned scientists in the field have contributed outlines demonstrating man-made molecules that will be required not only to overcome the limitations of monoclonal antibodies, but also to extend the principle of selective targeting. Divided into specific, accessible sections, Antibody Fusion Proteins includes: * Chapters describing Fc fusion proteins, as well as several classes of antigen-binding proteins * Complete details on the design and molecular construction of genetically engineered fusion molecules * Useful information on molecular purification, large-scale production, practical applications, and their therapeutic potential * The latest data on forming fusion proteins with toxins, cytokines, or enzymes that can activate a prodrug
Animal Cell Biotechnology
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Author : Hansjörg Hauser
language : en
Publisher: Walter de Gruyter GmbH & Co KG
Release Date : 2014-11-10
Animal Cell Biotechnology written by Hansjörg Hauser and has been published by Walter de Gruyter GmbH & Co KG this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-11-10 with Science categories.
This book introduces fundamental principles and practical application of techniques used in the scalable production of biopharmaceuticals with animal cell cultures. A broad spectrum of subjects relevant to biologics production and manufacturing are reviewed, including the generation of robust cell lines, a survey of functional genomics for a better understanding of cell lines and processes, as well as advances in regulatory compliant upstream and downstream development. The book is an essential reference for all those interested in translational animal cell-based pharmaceutical biotechnology.
Innovations For Next Generation Antibody Drug Conjugates
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Author : Marc Damelin
language : en
Publisher: Springer
Release Date : 2018-05-29
Innovations For Next Generation Antibody Drug Conjugates written by Marc Damelin and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-05-29 with Medical categories.
Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field’s history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.