Ebook: Development of Antibody-Based Therapeutics: Translational Considerations

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.

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Development of Antibody-Based Therapeutics: Translational Considerations examines important considerations necessary for the design of effective translational strategies during the development of antibody-based therapeutics. Translational strategies for development of antibody-based therapeutics require an understanding of the relationship between the ‘unit dose’ and ‘unit effect’ with respect to both beneficial and deleterious biological effects from early stages of development. The flow of information across various stages of development should provide opportunities to facilitate selection of more effective novel and next-generation drug candidates. Successful strategies for the development of monoclonal antibodies require integration of knowledge with regards to target antigen properties in health and disease, as well as antibody design criteria including affinity, isotype selection, pharmacokinetics/pharmacodynamics (PK/PD) properties, antibody cross-reactivity across species, and safety. Selection and evaluation of appropriate biomarkers in early preclinical development in “relevant” animal models should allow identification of potential risks and liabilities of an antibody drug candidate to humans and establishment of safe First-In-Human (FIH) dosing strategies. This volume provides a comprehensive review of the topics critical for establishing successful translational strategies for the development of antibody-based therapeutics.

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Development of Antibody-Based Therapeutics: Translational Considerations examines important considerations necessary for the design of effective translational strategies during the development of antibody-based therapeutics. Translational strategies for development of antibody-based therapeutics require an understanding of the relationship between the ‘unit dose’ and ‘unit effect’ with respect to both beneficial and deleterious biological effects from early stages of development. The flow of information across various stages of development should provide opportunities to facilitate selection of more effective novel and next-generation drug candidates. Successful strategies for the development of monoclonal antibodies require integration of knowledge with regards to target antigen properties in health and disease, as well as antibody design criteria including affinity, isotype selection, pharmacokinetics/pharmacodynamics (PK/PD) properties, antibody cross-reactivity across species, and safety. Selection and evaluation of appropriate biomarkers in early preclinical development in “relevant” animal models should allow identification of potential risks and liabilities of an antibody drug candidate to humans and establishment of safe First-In-Human (FIH) dosing strategies. This volume provides a comprehensive review of the topics critical for establishing successful translational strategies for the development of antibody-based therapeutics.
Content:
Front Matter....Pages i-xiv
Translational Strategies for Development of Antibody-Based Therapeutics: An Overview....Pages 1-7
Discovery Process for Antibody-Based Therapeutics....Pages 9-32
Technologies for the Generation of Human Antibodies....Pages 33-63
Application of Antibody Engineering in the Development of Next Generation Antibody-Based Therapeutics....Pages 65-93
Biophysical Considerations for Development of Antibody-Based Therapeutics....Pages 95-139
Considerations in Establishing Affinity Design Goals for Development of Antibody-Based Therapeutics....Pages 141-151
Bioanalytical Considerations for Development of Antibody-Based Therapeutics: Pharmacokinetics and Immunogenicity....Pages 153-181
Preclinical Considerations for Development of Antibody-Based Therapeutics in Oncology....Pages 183-240
Factors Impacting the Tumor Localization and Distribution of Antibody-Based Therapeutics in Oncology....Pages 241-253
Preclinical Safety Considerations for the Development of Antibody-Based Therapeutics....Pages 255-284
Application of Pharmacokinetic/Pharmacodynamic Modeling in the Development of Antibody-Based Therapeutics....Pages 285-302
Application of Population Pharmacokinetic-Pharmacodynamic Approaches in the Design of Translational Strategies for Development of Antibody-Based Therapeutics....Pages 303-330
Translational Biomarkers: Essential Tools in Development of Antibody-Based Therapeutics....Pages 331-340
Translational Research in Alzheimer’s Disease for Development of Antibody-Based Therapeutics....Pages 341-354
Considerations in Manufacturing Process Development for Antibody-Based Therapeutics....Pages 355-373
Strategies for Development of Next Generation Antibody-Based Therapeutics....Pages 375-390
Immune Complex Therapies for Treatment of Immune Thrombocytopenia....Pages 391-404
Application of Bioinformatics Principles for Target Evaluation....Pages 405-417
Concluding Remarks....Pages 419-421
Back Matter....Pages 423-425

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Development of Antibody-Based Therapeutics: Translational Considerations examines important considerations necessary for the design of effective translational strategies during the development of antibody-based therapeutics. Translational strategies for development of antibody-based therapeutics require an understanding of the relationship between the ‘unit dose’ and ‘unit effect’ with respect to both beneficial and deleterious biological effects from early stages of development. The flow of information across various stages of development should provide opportunities to facilitate selection of more effective novel and next-generation drug candidates. Successful strategies for the development of monoclonal antibodies require integration of knowledge with regards to target antigen properties in health and disease, as well as antibody design criteria including affinity, isotype selection, pharmacokinetics/pharmacodynamics (PK/PD) properties, antibody cross-reactivity across species, and safety. Selection and evaluation of appropriate biomarkers in early preclinical development in “relevant” animal models should allow identification of potential risks and liabilities of an antibody drug candidate to humans and establishment of safe First-In-Human (FIH) dosing strategies. This volume provides a comprehensive review of the topics critical for establishing successful translational strategies for the development of antibody-based therapeutics.
Content:
Front Matter....Pages i-xiv
Translational Strategies for Development of Antibody-Based Therapeutics: An Overview....Pages 1-7
Discovery Process for Antibody-Based Therapeutics....Pages 9-32
Technologies for the Generation of Human Antibodies....Pages 33-63
Application of Antibody Engineering in the Development of Next Generation Antibody-Based Therapeutics....Pages 65-93
Biophysical Considerations for Development of Antibody-Based Therapeutics....Pages 95-139
Considerations in Establishing Affinity Design Goals for Development of Antibody-Based Therapeutics....Pages 141-151
Bioanalytical Considerations for Development of Antibody-Based Therapeutics: Pharmacokinetics and Immunogenicity....Pages 153-181
Preclinical Considerations for Development of Antibody-Based Therapeutics in Oncology....Pages 183-240
Factors Impacting the Tumor Localization and Distribution of Antibody-Based Therapeutics in Oncology....Pages 241-253
Preclinical Safety Considerations for the Development of Antibody-Based Therapeutics....Pages 255-284
Application of Pharmacokinetic/Pharmacodynamic Modeling in the Development of Antibody-Based Therapeutics....Pages 285-302
Application of Population Pharmacokinetic-Pharmacodynamic Approaches in the Design of Translational Strategies for Development of Antibody-Based Therapeutics....Pages 303-330
Translational Biomarkers: Essential Tools in Development of Antibody-Based Therapeutics....Pages 331-340
Translational Research in Alzheimer’s Disease for Development of Antibody-Based Therapeutics....Pages 341-354
Considerations in Manufacturing Process Development for Antibody-Based Therapeutics....Pages 355-373
Strategies for Development of Next Generation Antibody-Based Therapeutics....Pages 375-390
Immune Complex Therapies for Treatment of Immune Thrombocytopenia....Pages 391-404
Application of Bioinformatics Principles for Target Evaluation....Pages 405-417
Concluding Remarks....Pages 419-421
Back Matter....Pages 423-425
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