Verfügbarkeit: Protein therapeutics

Protein therapeutics: Volume 2

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Bibliographische Detailangaben
Weitere Verfasser:	Vaughan, Tristan (HerausgeberIn), Osbourn, Jane (HerausgeberIn), Jallal, Bahija (HerausgeberIn)
Format:	Buch
Sprache:	English
Veröffentlicht:	Weinheim, Germany Wiley-VCH [2017]
Schriftenreihe:	Methods and principles in medicinal chemistry Volume 71b Methods and principles in medicinal chemistry volume 71
Online-Zugang:	Inhaltsverzeichnis
Beschreibung:	XXI, Seiten 311-717 Illustrationen, Diagramme

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245	1	0	\|a Protein therapeutics \|n Volume 2 \|c edited by Tristan Vaughan, Jane Osbourn, and Bahija Jallal
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Datensatz im Suchindex

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adam_text	CONTENTS TO VOLUME 1 PREFACE X V A PERSONAL FOREWORD XIX ACKNOWLEDGMENTS XXI PART I INTRODUCTION TO PROTEIN THERAPEUTICS: PAST AND PRESENT 1 1 EARLY RECOMBINANT PROTEIN THERAPEUTICS 3 PIERRE DE MEYTS 2 EVOLUTION OF ANTIBODY THERAPEUTICS 25 HERVE WOTIER AND JANICE M. REICHERT PART II ANTIBODIES: THE ULTIMATE SCAFFOLD FOR PROTEIN THERAPEUTICS 51 3 HUMAN ANTIBODY STRUCTURE AND FUNCTION 53 PONRAJ PRABAKARAN AND DIMITERS. DIMITROV 4 ANTIBODIES FROM OTHER SPECIES 85 MELISSA L VADNAIS, MICHAEL F. CRISCITIELLO, AND VAUGHN V. 5MIDER PART III DISCOVERY AND ENGINEERING OF PROTEIN THERAPEUTICS 113 5 HUMAN ANTIBODY DISCOVERY PLATFORMS 115 WILLIAM R. STROHL 6 BEYOND ANTIBODIES: ENGINEERED PROTEIN SCAFFOLDS FOR THERAPEUTIC DEVELOPMENT 161 NISHANT K. MEHTA AND JENNIFER R. COCHRAN 7 PROTEIN ENGINEERING: METHODS AND APPLICATIONS 189 CLAIRE DOBSON AND WILLIAM DALL ACQUA 8 BISPECIFICS 229 JIJIE GU, ANDREW MCCLUSKEY, AND TARIQ GHAYUR 9 ANTIBODY-DRUG CONJUGATES (ADCS) 271 PHILIP W. HOWARD CONTENTS TO VOLUME 2 PREFACE X V A PERSONAL FOREWORD XIX ACKNOWLEDGMENTS XXI PART IV PHYSIOLOGICAL AND MANUFACTURING CONSIDERATIONS FOR BIOLOGIES 311 10 PHARMACOKINETICS OF THERAPEUTIC PROTEINS 313 ZHENG LU, JENNIFER SHENG, AND WENHUI ZHANG 10.1 ABSORPTION 313 10.2 DISTRIBUTION 315 10.3 METABOLISM AND ELIMINATION 316 10.3.1 FCRN-MEDIATED SALVAGE AND THE NONSPECIFIC (LINEAR) CLEARANCE 317 10.3.2 TARGET-MEDIATED DRUG DISPOSITION 318 10.3.3 IMMUNOGENICITY-INDUCED CLEARANCE CHANGE 320 10.3.4 FRAGMENT OF MABS 322 10.3.5 VARIABILITY 323 10.3.6 RENAL CLEARANCE OF MABS 324 10.4 PHARMACOKINETIC MODELING OF THERAPEUTIC PROTEINS 325 REFERENCES 334 11 SAFETY CONSIDERATIONS FOR BIOLOGIES 341 MAGGIE DEMPSTER, LUCINDA R. WEIR, AND RAJNIS. FAGG 11.1 INTRODUCTION 341 11.2 SMALL MOLECULES VERSUS LARGE MOLECULES - A COMPARISON 342 11.3 TOXICITY RELATED TO EXAGGERATED PHARMACOLOGY - IMPORTANCE OF SPECIES SELECTION 344 11.4 TOXICITY UNRELATED TO EXAGGERATED PHARMACOLOGY 347 11.4.1 CYTOKINE STORM 347 11.4.2 UNEXPECTED TOXICITY 348 11.5 REGULATORY GUIDANCE 349 11.6 DEVELOPMENT CONSIDERATIONS DUE TO BIOLOGICAL CHARACTERISTICS 350 11.6.1 EARLY DISCOVERY - INFORMATION NEEDED TO SET THE STAGE AND EARLY STUDIES 350 11.6.1.1 NEW TARGETS/PATHWAYS 350 11.6.1.2 ALTERNATE HIT/LEAD DISCOVERY APPROACHES FOR EXISTING TARGETS 352 11.6.1.3 NEW LEAD OPTIMIZATION METHODS 354 11.6.1.4 FEASIBILITY/TRACTABILITY ASSESSMENT 360 11.7 FIRST IN HUMAN (FIH) TO REGISTRATION 366 11.7.1 CROSS-REACTIVITY STUDY 366 11.7.2 SAFETY PHARMACOLOGY 367 11.7.3 IN VIVO STUDIES 367 11.7.4 SELECTION OF DOSE LEVELS 369 11.7.5 PHARMACOKINETICS/PHARMACODYNAMICS 369 11.7.6 IMMUNOGENICITY 370 11.7.7 IMMUNOTOXICITY 371 11.7.8 REPRODUCTIVE TOXICITY 371 11.7.8.1 FERTILITY 372 11.7.8.2 EMBRYOFETAL DEVELOPMENT AND PRE- AND POSTNATAL DEVELOPMENT 372 11.7.9 GENOTOXICITY AND CARCINOGENICITY 374 11.8 SELECTION OF A SAFE STARTING DOSE FOR FIRST TIME IN HUMAN CLINICAL STUDY 374 11.9 SUMMARY 375 REFERENCES 376 12 IMMUNOGENICITY OF BIOLOGIES 387 MATTHEW R BAKER; TIMOTHY D. JONES, AND PAUL CHAMBERLAIN 12.1 INTRODUCTION 387 12.2 MECHANISTIC VIEW OF IMMUNOGENICITY: INNATE AND ADAPTIVE IMMUNITY 388 12.2.1 INNATE IMMUNITY 388 12.2.1.1 DENDRITIC CELLS 388 12.2.1.2 ENDOCYTOSIS OF PROTEINS BY DC 390 12.2.1.3 INNATE IMMUNE RECEPTORS 391 12.2.2 ADAPTIVE IMMUNITY 393 12.2.2.1 ANTIGEN PROCESSING 393 12.2.2.2 T-CELL RECOGNITION OF MHC - PEPTIDE COMPLEXES 397 12.2.2.3 IMMUNOGENICITY RISK MITIGATION BY PROTEIN ENGINEERING 398 12.2.2.4 IMMUNOGENICITY AND THE PROPERTIES OF ANTIGENS 399 12.2.2.5 IMMUNOLOGICAL TOLERANCE 400 12.3 IMMUNOGENICITY OF PROTEIN THERAPEUTICS IN AUTOLOGOUS CELL THERAPIES 402 12.4 REGULATORY CONTEXT 403 12.5 APPLICATION OF THE RISK-BASED APPROACH FOR UNDESIRABLE IMMUNOGENICITY 405 12.5.1 LINKAGE TO PRODUCT LIFE CYCLE 405 12.5.2 INITIAL RISK ASSESSMENT FOR LEAD CANDIDATE SELECTION 405 12.5.3 EARLY SCREENING TO IDENTIFY CRYPTIC B-CELL EPITOPES 406 12.5.4 CONTROL OF PRODUCT QUALITY 407 12.5.5 IND-ENABLING SAFETY STUDIES 408 12.5.6 FIRST-TIME-IN-HUMAN STUDIES 409 12.6 CLINICAL PROOF OF CONCEPT AND BEYOND 410 12.7 FUTURE PERSPECTIVES 411 REFERENCES 411 13 EXPRESSION SYSTEMS FOR RECOMBINANT BIOPHARMACEUTICAL PRODUCTION BY MAMMALIAN CELLS IN CULTURE 423 ADAM 1 BROWN, DEVIKA KALSI, ALEJANDRO FERNANDEZ-MARTELL, JOE CARTWRIGHT, NICHOLAS 0.1 N. BARBER, YASH D. PATEL, RICHARD TURNER, CLAIRE L BRYANT, YUSUF B. JOHARI, AND DAVID C. JAMES 13.1 INTRODUCTION 423 13.2 HOST CELL SYSTEMS 425 13.2.1 CHINESE HAMSTER OVARY (CHO) CELLS 425 13.2.2 ALTERNATIVE MAMMALIAN CELL HOSTS 428 13.2.3 NON-MAMMALIAN EXPRESSION SYSTEMS 428 13.3 MAMMALIAN CELL TRANSFECTION 430 13.3.1 METHODOLOGIES 430 13.3.2 BIOPROCESS APPLICATION 431 13.3.3 GENE TARGETING 432 13.4 CONTROLLING RECOMBINANT GENE EXPRESSION 433 13.4.1 INTRODUCTION 433 13.4.2 PROMOTERS 434 13.4.3 UNTRANSLATED REGIONS, EPIGENETIC REGULATORY ELEMENTS, AND PROTEIN-CODING SEQUENCES 435 13.4.3.1 UNTRANSLATED REGIONS 435 13.4.3.2 EPIGENETIC REGULATORY ELEMENTS 436 13.4.3.3 PROTEIN-CODING SEQUENCES 437 13.5 SELECTION AND AMPLIFICATION SYSTEMS 437 13.6 TRANSIENT PRODUCTION SYSTEMS 438 13.6.1 CHO CELL ENGINEERING FOR INCREASED TRANSIENT PRODUCTION 439 13.6.2 RECOMBINANT DNA DELIVERY MECHANISMS 439 13.6.3 PROCESS AND MEDIA OPTIMIZATION 440 13.7 PROTEIN PURIFICATION 440 13.7.1 CLARIFICATION 441 13.7.2 CHROMATOGRAPHY 441 13.7.2.1 AFFINITY CHROMATOGRAPHY 441 13.7.2.2 ION-EXCHANGE CHROMATOGRAPHY 442 13.7.2.3 HYDROPHOBIC INTERACTION CHROMATOGRAPHY 443 13.7.2.4 13.7.3 13.7.4 13.7.5 13.8 13.8.1 13.8.2 13.8.3 13.8.4 13.8.5 13.8.6 13.8.7 13.8.8 14 14.1 14.2 14.3 14.3.1 14.3.2 14.3.2.1 14.3.3 14.3.3.1 14.3.3.2 14.3.3.3 14.3.3.4 14.4 14.5 15 15.1 15.2 15.2.1 15.2.2 15.2.3 15.2.4 MIXED-MODE CHROMATOGRAPHY 443 MEMBRANES 443 ECONOMICS 444 FUTURE TRENDS AND CONCLUSIONS 445 CHO CELL ENGINEERING FOR ENHANCED BIOPROCESSING PROPERTIES 445 PROGRAMMED CELL DEATH 446 FOLDING AND ASSEMBLY MACHINERY 446 UNFOLDED PROTEIN RESPONSE 447 SECRETORY PATHWAY 447 GLYCOSYLATION PATHWAYS 447 GENE EDITING 449 DIRECTED EVOLUTION APPROACH 449 MIRNAS - A NOVEL CELL ENGINEERING APPROACH 450 ABBREVIATIONS 450 REFERENCES 452 STABILITY, FORMULATION, AND DELIVERY OF BIOPHARMACEUTICALS 469 HANNS-CHRISTIAN MAHLER AND ANDREA ALLMENDINGER INTRODUCTION 469 STABILITY 469 DRUG PRODUCT DEVELOPMENT 471 PRODUCT REQUIREMENTS 472 CONTAINER CLOSURE SYSTEM (CCS) 473 SOME CHALLENGES WITH CONTAINER CLOSURE SYSTEMS 473 DEVELOPMENT OF THE PROTEIN FORMULATION 475 DOSAGE FORM 475 FORMULATION COMPOSITION 476 STABILITY TESTING 480 ANALYTICAL METHOD PANEL 482 HANDLING AND ADMINISTRATION CONSIDERATIONS 484 SUMMARY AND CONCLUSION 487 REFERENCES 487 PART V CLINICAL APPLICATIONS 493 PROTEIN THERAPEUTICS IN AUTOIMMUNE AND INFLAMMATORY DISEASES 495 ANTHONY1 COYLE AND LEIGH 5. ZAWEL INTRODUCTION 495 RHEUMATOID ARTHRITIS 495 TNF-OC ANTAGONISTS 496 INHIBITION OF CO-STIMULATION 497 ANTI-IE-1 BASED THERAPIES 498 ANTI-IE-6 THERAPIES 498 15.2.5 B-CELL DEPLETION THERAPIES 499 15.3 PSORIASIS 500 15.4 TNF-OE ANTAGONIST THERAPY 500 15.5 ANTI-IL-12/IL-23 THERAPIES 501 15.6 ANTI-IL-17 THERAPIES 502 15.7 ATOPIE DERMATITIS 502 15.7.1 ANTI-IL-4/IL-13 THERAPIES 503 15.8 INFLAMMATORY BOWEL DISEASE (IBD) 503 15.8.1 PATHOPHYSIOLOGY OF IBD 504 15.8.2 ANTI-TNF-CC THERAPIES IN IBD 505 15.8.3 INTEGRIN INHIBITORS 506 15.8.4 IL-12/IL-23 THERAPIES 507 15.9 SYSTEMIC LUPUS ERYTHEMATOSUS 507 15.9.1 B-CELL-DIRECTED THERAPIES 508 15.9.1.1 RITUXIMAB 508 15.9.1.2 EPRATUZUMAB 508 15.9.1.3 BELIMUMAB 509 15.9.1.4 OTHER REGULATORS OF B CELLS SURVIVAL 509 15.9.2 TYPE I INTERFERONS AND SEE 510 15.10 CONCLUSIONS 511 REFERENCES 511 16 ANTIBODY-BASED THERAPEUTICS IN ONCOLOGY 521 PAUL A. MOORE, ROSS LA MOTTE-MOHS, JONATHAN C. LI, AND GURUNADH R. CHICHILI 16.1 INTRODUCTION 521 16.2 TARGETING CELL-SURFACE SIGNALING PATHWAYS IN SOLID TUMORS 522 16.2.1 ANTIBODY TARGETING OF RECEPTOR TYROSINE KINASES (RTKS) PATHWAYS 522 16.2.1.1 ERBB FAMILY 522 16.2.1.2 EGER 529 16.2.1.3 HER2 530 16.2.1.4 HER3 531 16.2.1.5 INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR (IGF-1R) 532 16.2.1.6 PDGFR - PDGFROC 532 16.2.1.7 KIT FAMILY - COLONY-STIMULATING FACTOR 1 RECEPTOR (CSF1R) AND KIT 533 16.2.1.8 VEGFR FAMILY - VEGFR1, VEGFR2, AND VEGFR3 533 16.2.1.9 VEGFR1 534 16.2.1.10 VEGFR2 534 16.2.1.11 VEGFR3 534 16.2.1.12 FGFR FAMILY - FGFR2, FGFR2B, AND FGFR3 535 16.2.1.13 HGFR FAMILY - PROTO-ONCOGENEC-MET (MET) AND RECEPTEUR DORIGINE NANTAIS (RON) 535 16.2.1.14 16.2.2 16.2.2.1 16.2.2.2 16.2.2.3 16.2.2.4 16.3 16.3.1 16.3.2 16.3.2.1 16.3.2.2 16.3.2.3 16.3.3 16.4 16.4.1 16.4.1.1 16.4.1.2 16.4.1.3 16.4.2 16.5 17 17.1 17.2 17.2.1 17.2.2 17.2.3 17.2.4 17.3 17.3.1 17.3.2 17.4 17.5 17.5.1 17.5.2 17.5.3 17.6 17.7 EPHR FAMILY 536 TARGETING OF ADDITIONAL SIGNALING PATHWAYS AND CELL-SURFACE ANTIGENS 537 NOTCH SIGNALING PATHWAY 537 WNT - FZD PATHWAY 538 DEATH RECEPTORS - TRAILR1 AND TRAILR2 538 ADDITIONAL CELL-SURFACE ANTIGENS 539 TARGETING OF IMMUNE MODULATORS 540 TUMOR IMMUNOLOGY 540 CHECK-POINT INHIBITORS 542 CYTOTOXIC T-LYMPHOCYTE ANTIGEN-4 (CTLA-4) 542 PROGRAMMED DEATH-1 (PD-1) AND PD-1 LIGAND 545 TARGETING OF ADDITIONAL PUTATIVE CHECK-POINT INHIBITOR PATHWAYS 548 CO-STIMULATORY PATHWAYS 552 BISPECIFIC ANTIBODIES 557 IMMUNE CELL RE-TARGETING 558 LYMPHOID EFFECTORS 558 HEMATOLOGICAL MALIGNANCIES 561 SOLID TUMORS 563 DUAL TARGETING OF TWO RECEPTOR PATHWAYS ON CANCER CELL USING BSABS 566 CONCLUSIONS AND FUTURE DIRECTIONS 568 REFERENCES 570 PROTEIN THERAPEUTICS IN RESPIRATORY MEDICINE 587 RAHUL SHRIMANKER AND IAN D. PAVORD INTRODUCTION 587 ASTHMA 588 PHENOTYPES OF ASTHMA 590 BIOMARKERS 591 THE THL PATHWAY 593 THE TH2 PATHWAY 594 TH2-TARGETED THERAPIES 595 IMMUNOGLOBULIN E 595 INTERLEUKIN 5 597 MEPOLIZUMAB 597 OTHER ANTI-IL-5-TARGETED TREATMENTS 600 INTERLEUKIN 4 602 INTERLEUKIN 13 604 INTERLEUKIN 9 606 OTHER RESPIRATORY USES OF MONOCLONAL ANTIBODIES 606 SUMMARY 607 REFERENCES 608 18 ANTIBODIES FOR THE PREVENTION, TREATMENT, AND PREEMPTION OF INFECTIOUS DISEASES 611 STEVE PROJAN 18.1 PROPHYLAXIS AND PRECISION MEDICINE 611 18.2 ANTIBACTERIAL IMMUNE THERAPY - A NINETEENTH CENTURY BREAKTHROUGH 612 18.2.1 WHY HAS IT TAKEN SO LONG FOR NOVEL IMMUNOTHERAPEUTICS? 612 18.2.2 MONOCLONAL ANTIBODIES FOR THE PREVENTION AND TREATMENT OF VIRAL INFECTIONS 613 18.2.3 S. AUREUS: NO LONGER THE HOSPITAL SCOURGE? 614 18.2.4 MONOCLONAL ANTIBODIES TO PREVENT, TREAT OR PREEMPT STAPHYLOCOCCAL INFECTIONS 614 18.2.5 R AERUGINOSA: THE BACTERIAL COCKROACH 615 18.2.6 IMMUNE EVASION: A BRIDGE TOO FAR? 616 18.2.7 MONOCLONAL ANTIBODIES FOR C. DIFFICILE INFECTION: A WINNING BET OR A CRAP SHOOT 616 18.2.8 ARE TWO ANTIBODIES ENOUGH; IS SIX TOO MANY? 617 18.2.9 PROPHYLAXIS OR TREATMENT? BEWARE OF FALSE DICHOTOMIES 617 18.3 OTHER POTENTIAL ANTI-INFECTIVE MABS 617 18.3.1 SAFETY: HUMAN ENOUGH FOR YOU? 617 18.3.2 ANOTHER PRECINCT IS HEARD FROM: IMMUNOMODULATORY AGENTS FOR THE TREATMENT OF CHRONIC INFECTIONS 618 18.3.3 ARE WE THERE YET? EASY-TO-USE, FAST-TURNAROUND, POINT-OF-CARE DIAGNOSTICS 618 18.3.4 ARE BIOLOGIC DRUGS GOING TO BE TOO EXPENSIVE TO TREAT INFECTIONS? 619 REFERENCES 619 19 RESCUE THERAPIES 621 STEPHAN GLUND AND MONIKA KROEZ 19.1 INTRODUCTION 621 19.1.1 CLINICAL DEVELOPMENT PECULIARITIES 621 19.2 ANTIDOTES/REVERSAL AGENTS 622 19.2.1 INTRODUCTION 622 19.2.2 ANTI-DIGOXIN FAB 622 19.2.2.1 BACKGROUND 622 19.2.2.2 MODE OF ACTION 623 19.2.2.3 STUDIES IN VOLUNTEERS 624 19.2.2.4 DOSE CONSIDERATIONS 624 19.2.2.5 COST CONSIDERATIONS 624 19.2.2.6 STUDIES IN PATIENTS 625 19.2.2.7 SAFETY 625 19.2.3 IDARUCIZUMAB AND ANDEXANET ALFA: REVERSAL AGENTS FOR ORAL ANTICOAGULANTS 625 19.2.3.1 BACKGROUND 625 19.2.3.2 IDARUCIZUMAB 626 19.2.3.3 ANDEXANET ALFA 628 19.2.4 GLUCARPIDASE 629 19.2.4.1 BACKGROUND 629 19.2.4.2 MODE OF ACTION 629 19.2.4.3 STUDIES IN VOLUNTEERS 630 19.2.4.4 STUDIES IN PATIENTS 630 19.2.4.5 SAFETY 630 19.2.4.6 IMMUNOGENICITY 631 19.2.5 SELECTED REVERSAL-AGENT APPROACHES IN CLINICAL TESTING 631 19.2.5.1 BUTYRYLCHOLINESTERASE (PROTEXIA; TV-1380) 631 19.2.5.2 ANTI-METHAMPHETAMINE ANTIBODIES 631 19.3 ANTIVENOMS AND ANTITOXINS 631 19.3.1 BACKGROUND AND HISTORY 632 19.3.2 EPIDEMIOLOGY OF ENVENOMING 633 19.3.2.1 EFFECTS OF IMMUNOGLOBULIN DESIGN ON ANTISERUM PHARMACOKINETICS 633 19.3.3 GENERATION OF ANTIVENOMS AND ANTITOXINS 634 19.3.4 SPECIFICITY 635 19.3.4.1 ANTI-ANTHRAX APPROACHES 635 19.3.5 SAFETY AND TOLERABILITY 637 19.4 CONCLUSION 638 REFERENCES 638 20 BIOSIMILARS 645 JUN WANG 20.1 INTRODUCTION 645 20.2 CONCEPT AND DEFINITION OF BIOSIMILARS 645 20.2.1 GENERIC SMALL MOLECULE DRUGS COMPARED WITH BIOSIMILARS 645 20.2.2 DEFINITION AND INTERPRETATION OF BIOSIMILARS 647 20.3 RATIONALE AND SIGNIFICANCE OF BIOSIMILARS 648 20.3.1 THE POTENTIAL FOR COST REDUCTION 648 20.3.2 THE SCALE OF THE OPPORTUNITY TO REDUCE COST 650 20.4 CURRENT APPROVALS AND TRENDS 651 20.4.1 BIOSIMILAR APPROVALS 651 20.4.2 REGULATORY PATHWAYS FOR BIOSIMILARS 653 20.4.2.1 QUALITY 654 20.4.2.2 NON-CLINICAL AND CLINICAL STUDIES 655 20.5 CHALLENGES AND FUTURE TRENDS 656 REFERENCES 658 PART VI FUTURE HORIZONS 661 21 FUTURE HORIZONS AND NEW TARGET CLASS OPPORTUNITIES 663 HERREN WU, CARL WEBSTER, JUDY PATERSON, SANDRINE GUILLARD, RON JACKSON, AND RALPH M INTER 21.1 INTRODUCTION 663 21.2 TARGETING THE CENTRAL NERVOUS SYSTEM 663 21.2.1 THE OPPORTUNITY 663 21.2.2 THE CHALLENGE 664 21.2.3 NATURES SOLUTION 665 21.2.4 TARGETING PATHWAYS INTO THE BRAIN 666 21.2.5 LESSONS FROM PRECLINICAL STUDIES 669 21.2.6 ADME IN THE BRAIN 670 21.2.7 PATH TO THE CLINIC 671 21.2.8 FUTURE PERSPECTIVES 671 21.3 INTRACELLULAR BIOLOGIES 672 21.3.1 THE OPPORTUNITY FOR INTRACELLULAR BIOLOGIES 672 21.3.2 THE CHALLENGES OF INTRACELLULAR DELIVERY 672 21.3.3 NATURES SOLUTION TO THE CHALLENGES OF INTRACELLULAR DELIVERY: AB TOXINS 674 21.3.4 RE-ENGINEERING AB TOXINS FOR NOVEL THERAPEUTIC FUNCTIONS 675 21.3.5 ALTERNATIVE DELIVERY STRATEGIES FOR INTRACELLULAR BIOLOGIES 677 21.3.6 INCREASING THE POTENCY OF INTRACELLULAR PAYLOADS 678 21.3.7 CONCLUSIONS AND OUTLOOK FOR INTRACELLULAR BIOLOGIES 679 21.4 BUILDING ON THE SUCCESS OF TRADITIONAL MONOCLONAL ANTIBODIES 679 21.4.1 RISE OF NON-TRADITIONAL ANTIBODIES 680 21.4.1.1 BISPECIFIC ANTIBODY AND MULTISPECIFIC BIOLOGIES 681 21.4.1.2 ANTIBODY-DRUG CONJUGATES 683 21.4.2 DAWN OF IN VIVO EXPRESSED BIOLOGIES 684 21.4.3 ORAL BIOLOGIES 688 21.4.4 CONCLUSIONS 690 REFERENCES 690 INDEX 701
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illustrated	Illustrated
indexdate	2024-07-10T07:50:29Z
institution	BVB
language	English
oai_aleph_id	oai:aleph.bib-bvb.de:BVB01-029752859
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owner	DE-29 DE-11 DE-19 DE-BY-UBM
owner_facet	DE-29 DE-11 DE-19 DE-BY-UBM
physical	XXI, Seiten 311-717 Illustrationen, Diagramme
publishDate	2017
publishDateSearch	2017
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publisher	Wiley-VCH
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series	Methods and principles in medicinal chemistry
series2	Methods and principles in medicinal chemistry
spelling	Protein therapeutics Volume 2 edited by Tristan Vaughan, Jane Osbourn, and Bahija Jallal Weinheim, Germany Wiley-VCH [2017] XXI, Seiten 311-717 Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Methods and principles in medicinal chemistry Volume 71b Methods and principles in medicinal chemistry volume 71 Vaughan, Tristan edt Osbourn, Jane edt Jallal, Bahija edt (DE-604)BV044349964 2 Methods and principles in medicinal chemistry Volume 71b (DE-604)BV035418617 71,2 Methods and principles in medicinal chemistry volume 71 (DE-604)BV035418617 71 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029752859&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis
spellingShingle	Protein therapeutics Methods and principles in medicinal chemistry
title	Protein therapeutics
title_auth	Protein therapeutics
title_exact_search	Protein therapeutics
title_full	Protein therapeutics Volume 2 edited by Tristan Vaughan, Jane Osbourn, and Bahija Jallal
title_fullStr	Protein therapeutics Volume 2 edited by Tristan Vaughan, Jane Osbourn, and Bahija Jallal
title_full_unstemmed	Protein therapeutics Volume 2 edited by Tristan Vaughan, Jane Osbourn, and Bahija Jallal
title_short	Protein therapeutics
title_sort	protein therapeutics
url	http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029752859&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
volume_link	(DE-604)BV044349964 (DE-604)BV035418617
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