Antibody drug discovery / Clive R. Wood, editor.

pharmacy bookfair2016

Includes bibliographical references and index.

Contributors -- Foreword John McCafferty -- Preface Clive R.Wood -- Chapter 1 Humanization of Antibodies Olivier Léger and José W. Saldanha -- 1.1 Introduction -- 1.1.1 First step: chimerization -- 1.2 CDR Grafting: Standard Technology -- 1.2.1 Choice of CDR region to graft -- 1.2.2 Choice of human framework acceptor regions -- 1.2.2.1 Fixed frameworks -- 1.2.2.2 Best fit -- 1.2.2.3 Consensus -- 1.2.2.4 Germline -- 1.2.3 Backmutations -- 1.3 Affinity versus Stability -- 1.4 Alternative Approaches -- 1.4.1 Veneering or resurfacing -- 1.4.2 Grafting of abbreviated CDRs containing specificity-determining residues 1.4.3 Superhumanization1.4.4 Human string content optimization -- 1.4.5 Framework shuffling and human framework adaptation -- 1.4.6 Combinatorial library approaches -- 1.4.6.1 Guided selection -- 1.4.6.2 Framework libraries -- 1.4.7 HumaneeringTM technology -- 1.5 Concluding Remarks -- References -- Chapter 2 Selection and Screening of Antibody Phage Display Libraries David R. Buckler, Darren Schofield, Daniel J. Sexton, David Lowe and Tristan J. Vaughan -- 2.1 Introduction -- 2.2 Antibody Gene Rearrangement and Variable Region Sequence Diversity 2.2.1 Antibody architecture and germline gene segment recombination2.2.2 Variable region sequence diversity and structure guiding library design -- 2.2.3 Amplification of variable region sequence repertoires -- 2.2.4 Antibody sequence databases -- 2.3 Antibody Display Libraries in Ff Bacteriophage -- 2.3.1 Phage biology and early use as a display system -- 2.3.2 Variation of display format and control of display level -- 2.3.2.1 Coat protein display position -- 2.3.2.2 Display format, scFv vs. Fab -- 2.3.2.3 Signal peptide and vector design -- 2.3.2.4 Control of functional display level and valency 2.3.2.5 Maximizing library size2.3.2.6 Assessment of diversity -- 2.3.3 Representative large non-immune libraries -- 2.4 Library Selection -- 2.4.1 Antigen immobilization -- 2.4.2 Overview of phage display selection -- 2.4.3 Advantages and successes of phage display -- 2.4.3.1 Species cross-reactivity -- 2.4.3.2 Homolog binders -- 2.4.3.3 Rare epitopes -- 2.4.3.4 Exquisite specificity -- 2.4.3.5 Cell surface antigens -- 2.4.3.6 Toxins -- 2.4.3.7 High-throughput generation of reagents for proteomics -- 2.4.4 Advances in selection technology -- 2.5 Library Screening -- 2.5.1 Primary screening methods 2.5.2 Secondary screening methods2.5.3 High-throughput antibody purification -- 2.6 Future Applications of Antibody Phage Display -- 2.6.1 Antibody phage display in the proteomics arena -- 2.6.2 Quality protein reagents -- 2.6.3 Affinity maturation of antibody outputs -- 2.6.4 Antibody format and production -- 2.7 Conclusions -- References -- Chapter 3 Affinity Maturation Approaches for Antibody Lead Optimization David Lowe, Trevor Wilkinson and Tristan J. Vaughan -- 3.1 Introduction -- 3.2 Measuring the Affinity of Antibody-Antigen Complexes -- 3.2.1 Improving antibody affinity and potency