LEADER 05165nam 2200625 450 001 9910822909903321 005 20200520144314.0 010 $a1-118-35469-9 010 $a1-118-35467-2 035 $a(CKB)2670000000529349 035 $a(EBL)1642416 035 $a(SSID)ssj0001131779 035 $a(PQKBManifestationID)11640337 035 $a(PQKBTitleCode)TC0001131779 035 $a(PQKBWorkID)11145210 035 $a(PQKB)10607560 035 $a(OCoLC)878139188 035 $a(MiAaPQ)EBC1642416 035 $a(Au-PeEL)EBL1642416 035 $a(CaPaEBR)ebr10845572 035 $a(CaONFJC)MIL578593 035 $a(OCoLC)858914524 035 $a(PPN)224806661 035 $a(EXLCZ)992670000000529349 100 $a20140318h20142014 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aBiophysical methods for biotherapeutics $ediscovery and development applications /$fedited by Tapan K. Das 210 1$aHoboken, New Jersey :$cJohn Wiley & Sons,$d2014. 210 4$dİ2014 215 $a1 online resource (381 p.) 300 $aDescription based upon print version of record. 311 $a0-470-93843-9 320 $aIncludes bibliographical references and index. 327 $aBiophysical Methods for Biotherapeutics; Contents; Preface; About the Editor; List of Contributors; Section 1 Early Discovery Stages and Biotherapeutic Candidate Selection; 1 Biophysical Methods Applied in Early Discovery of a Biotherapeutic: Case Study of an Egfr-Igf1r Bispecific Adnectin; 1.1 Introduction; 1.2 Target Identification; 1.3 Target Generation; 1.3.1 Multiple Constructs Strategy; 1.4 Hit Evaluation; 1.4.1 Qualitative and Rapid Self-Association Check; 1.4.2 Qualitative and Rapid Thermal Stability Check; 1.4.3 Confirmation of Binding; 1.5 Lead Selection; 1.5.1 Self-Association 327 $a1.5.2 Thermal Stability1.5.3 Binding Affinity, Kinetics, and Epitope; 1.6 Lead Optimization; 1.7 Lead Formatting; 1.7.1 Solubility; 1.7.2 Thermal Unfolding Behavior; 1.8 Final Development Candidate Selection; 1.9 Concluding Remarks; Acknowledgment; References; 2 X-ray Crystallography for Biotherapeutics; 2.1 Introduction to X-ray Crystallography; 2.1.1 Early X-Ray Crystallography for Biologics; 2.2 Modern X-ray Crystallography; 2.2.1 Construct Design and Protein Production; 2.2.2 Macromolecular Crystallization; 2.3 X-ray Data Collection; 2.3.1 Crystal Mounting; 2.3.2 Collecting a Data Set 327 $a2.3.3 Data Reduction2.4 Solving the Structure of the Crystal; 2.4.1 Molecular Replacement; 2.4.2 Heavy Atom Techniques; 2.4.3 Confirming the Validity of a Solution; 2.4.4 Building and Refining the Structure; 2.5 Understanding the Target Through Structure; 2.5.1 The Model; 2.5.2 The Protein Databank and Related Resources; 2.5.3 Information Provided by X-Ray Crystallography; 2.6 Applications of X-ray Crystallography to Biotherapeutics; 2.6.1 Antibody-Based Biotherapeutics; 2.6.2 Antibody Design; 2.6.3 Protein Receptor Interactions 327 $a2.7 Future Applications of Crystal Structures in Biotherapeutics2.7.1 Protein Engineering; 2.8 Conclusion; Acknowledgments; References; 3 Solubility and Early Assessment of Stability for Protein Therapeutics; 3.1 Introduction; 3.2 Measuring Protein Solubility; 3.2.1 Direct Measurement of Solubility: Concentration to Precipitation; 3.2.2 Indirect Assessment of Solubility: The Second Virial Coefficient (B22) and Self-Interaction Chromatography; 3.3 Assessment of Protein Stability; 3.3.1 Thermal Stability; 3.3.2 Aggregation; 3.3.3 Chemical Modifications; 3.4 Computational Predictions 327 $a3.4.1 Identifying Aggregation Promoting Regions3.4.2 Interaction Hot Spots; 3.5 Enhance the Solubility of Biotherapeutics; 3.5.1 Site-Directed Mutagenesis; 3.5.2 Pegylation; 3.5.3 Glycosylation; 3.5.4 Formulation Optimization; 3.6 Development of Rapid Methods to Identify Soluble and Stable Biotherapeutics; 3.7 Concluding Remarks; References; Section 2 First-in-Human and Up To Proof-of-Concept Clinical Trials; 4 Biophysical and Structural Characterization Needed Prior to Proof of Concept; 4.1 Introduction 327 $a4.2 Biophysical Methods for Elucidation of Protein Structure and Physiochemical Properties 330 $aWith a focus on practical applications of biophysical techniques, Biophysical Methods for Biotherapeutics helps formulation and analytical scientists in pharma and biotech better understand and use biophysical methods. Author Tapan K. Das links fundamental biophysics to the process of biopharmaceutical development using a chapter organization according to the steps of the drug development process. The text provides information to help organizations develop short- and long-term strategies for resource investment in biophysical research. 606 $aBiopharmaceutics$vMethods 615 0$aBiopharmaceutics 676 $a615.7 702 $aDas$b Tapan K. 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910822909903321 996 $aBiophysical methods for biotherapeutics$94106181 997 $aUNINA