Therapeutic Proteins: Methods and Protocols by C. Mark Smales and David C. James


00407d97_medium.jpg Author C. Mark Smales and David C. James
Isbn 1627038485
File size 5.51MB
Year 2005
Pages 482
Language English
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Category biology



 

Therapeutic Proteins M E T H O D S I N M O L E C U L A R B I O L O G Y™ John M. Walker, SERIES EDITOR 328. New and Emerging Proteomic Techniques, edited by Dobrin Nedelkov and Randall W. Nelson, 2006 327. Epidermal Growth Factor: Methods and Protocols, edited by Tarun B. Patel and Paul J. Bertics, 2006 326. In Situ Hybridization Protocols, ThirdEdition, edited by Ian A. Darby and Tim D. Hewitson, 2006 325. Nuclear Reprogramming: Methods and Protocols, edited by Steve Pells, 2006 324. Hormone Assays in Biological Fluids, edited by Michael J. Wheeler and J. S. Morley Hutchinson, 2006 323. Arabidopsis Protocols, Second Edition, edited by Julio Salinas and Jose J. Sanchez-Serrano, 2006 322. Xenopus Protocols: Cell Biology and Signal Transduction , edited by X. Johné Liu, 2006 321. Microfluidic Techniques: Reviews and Protocols, edited by Shelley D. Minteer, 2006 320. Cytochrome P450 Protocols, Second Edition, edited by Ian R. Phillips and Elizabeth A. Shephard, 2006 319. Cell Imaging Techniques, Methods and Protocols, edited by Douglas J. Taatjes and Brooke T. Mossman, 2006 318. Plant Cell Culture Protocols, Second Edition, edited by Victor M. Loyola-Vargas and Felipe Vázquez-Flota, 2005 317. Differential Display Methods and Protocols, Second Edition, edited by Peng Liang, Jonathan Meade, and Arthur B. Pardee, 2005 316. Bioinformatics and Drug Discovery, edited by Richard S. Larson, 2005 315. Mast Cells: Methods and Protocols, edited by Guha Krishnaswamy and David S. Chi, 2005 314. DNA Repair Protocols: Mammalian Systems, Second Edition, edited by Daryl S. Henderson, 2005 313. Yeast Protocols: Second Edition, edited by Wei Xiao, 2005 312. Calcium Signaling Protocols: Second Edition, edited by David G. Lambert, 2005 311. Pharmacogenomics: Methods and Protocols, edited by Federico Innocenti, 2005 310. Chemical Genomics: Reviews and Protocols, edited by Edward D. Zanders, 2005 309. RNA Silencing: Methods and Protocols, edited by Gordon Carmichael, 2005 308. Therapeutic Proteins: Methods and Protocols, edited by C. Mark Smales and David C. James, 2005 307. Phosphodiesterase Methods and Protocols, edited by Claire Lugnier, 2005 306. Receptor Binding Techniques: Second Edition, edited by Anthony P. Davenport, 2005 305. Protein–Ligand Interactions: Methods and Applications, edited by G. Ulrich Nienhaus, 2005 304. Human Retrovirus Protocols: Virology and Molecular Biology, edited by Tuofu Zhu, 2005 303. NanoBiotechnology Protocols, edited by Sandra J. Rosenthal and David W. Wright, 2005 302. Handbook of ELISPOT: Methods and Protocols, edited by Alexander E. Kalyuzhny, 2005 301. Ubiquitin–Proteasome Protocols, edited by Cam Patterson and Douglas M. Cyr, 2005 300. Protein Nanotechnology: Protocols, Instrumentation, and Applications, edited by Tuan Vo-Dinh, 2005 299. Amyloid Proteins: Methods and Protocols, edited by Einar M. Sigurdsson, 2005 298. Peptide Synthesis and Application, edited by John Howl, 2005 297. Forensic DNA Typing Protocols, edited by Angel Carracedo, 2005 296. Cell Cycle Control: Mechanisms and Protocols, edited by Tim Humphrey and Gavin Brooks, 2005 295. Immunochemical Protocols, Third Edition, edited by Robert Burns, 2005 294. Cell Migration: Developmental Methods and Protocols, edited by Jun-Lin Guan, 2005 293. Laser Capture Microdissection: Methods and Protocols, edited by Graeme I. Murray and Stephanie Curran, 2005 292. DNA Viruses: Methods and Protocols, edited by Paul M. Lieberman, 2005 291. Molecular Toxicology Protocols, edited by Phouthone Keohavong and Stephen G. Grant, 2005 290. Basic Cell Culture Protocols, Third Edition, edited by Cheryl D. Helgason and Cindy L. Miller, 2005 289. Epidermal Cells, Methods and Applications, edited by Kursad Turksen, 2005 288. Oligonucleotide Synthesis, Methods and Applications, edited by Piet Herdewijn, 2005 287. Epigenetics Protocols, edited by Trygve O. Tollefsbol, 2004 286. Transgenic Plants: Methods and Protocols, edited by Leandro Peña, 2005 285. Cell Cycle Control and Dysregulation Protocols: Cyclins, Cyclin-Dependent Kinases, and Other Factors, edited by Antonio Giordano and Gaetano Romano, 2004 284. Signal Transduction Protocols, Second Edition, edited by Robert C. Dickson and Michael D. Mendenhall, 2004 283. Bioconjugation Protocols, edited by Christof M. Niemeyer, 2004 282. Apoptosis Methods and Protocols, edited by Hugh J. M. Brady, 2004 M E T H O D S I N M O L E C U L A R B I O L O G Y™ Therapeutic Proteins Methods and Protocols Edited by C. Mark Smales Protein Science Group, Department of Biosciences, University of Kent, Canterbury, Kent, UK and David C. James School of Engineering, University of Queensland, St. Lucia, Queensland, Australia © 2005 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 www.humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. Methods in Molecular BiologyTM is a trademark of The Humana Press Inc. All papers, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher. This publication is printed on acid-free paper. ∞ ANSI Z39.48-1984 (American Standards Institute) Permanence of Paper for Printed Library Materials. Cover illustration: Figure 2 from Chapter 21, “Solid-State Protein Formulation: Methodologies, Stability, and Excipient Effects,” by Yuh-Fun Maa and Scott P. Sellers. Cover design by Patricia F. Cleary. For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel.: 973-256-1699; Fax: 973-256-8341; E-mail: [email protected]; or visit our Website: www.humanapress.com Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $30.00 per copy is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Reporting Service is: [1-58829-390-4/05 $30.00 ]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 Library of Congress Cataloging in Publication Data Therapeutic proteins : methods and protocols / edited by C. Mark Smales and David C. James. p. ; cm. — (Methods in molecular biology ; 308) Includes bibliographical references and index. ISBN 1-58829-390-4 (alk. paper) eISBN 1-59259-922-2 1. Protein drugs—Laboratory manuals. I. Smales, C. Mark. II. James, David C. (David Cameron), 1963- . III. Series: Methods in molecular biology (Clifton, N.J.) ; v. 308. [DNLM: 1. Proteins—therapeutic use. 2. Proteins—chemical synthesis. 3. Proteins— isolation & purification. QU 55 T3976 2005] RS431.P75T475 2005 615'.3—dc22 2004021242 Preface With the recent completion of the sequencing of the human genome, it is widely anticipated that the number of potential new protein drugs and targets will escalate at an even greater rate than that observed in recent years. However, identification of a potential target is only part of the process in developing these new next generation protein-based “drugs” that are increasingly being used to treat human disease. Once a potential protein drug has been identified, the next rate-limiting step on the road to development is the production of sufficient authentic material for testing, characterization, clinical trials, and so on. If a protein drug does actually make it through this lengthy and costly process, methodology that allows the production of the protein on a scale large enough to meet demand must be implemented. Furthermore, large-scale production must not compromise the authenticity of the final product. It is also necessary to have robust methods for the purification, characterization, viral inactivation and continued testing of the authenticity of the final protein product and to be able to formulate it in a manner that retains both its biological activity and lends itself to easy administration. Therapeutic Proteins: Methods and Protocols covers all aspects of protein drug production downstream of the discovery stage. This volume contains contributions from leaders in the field of therapeutic protein expression, purification, characterization, formulation, and viral inactivation. The contributors are all based at highly esteemed industrial and academic institutions from around the world and contact details are provided if researchers wish to obtain further information from the authors. This book contains complete protocols set out in a simple step-by-step manner. It opens with an introductory chapter that discusses where therapeutic protein expression and downstream processing currently stand in terms of production, and contains thoughts on the direction of future developments from experts in the field. All other chapters contain a useful introduction describing the theory and background to the method, which is then followed by a list of all equipment and materials required to complete the protocol. The Methods section describes every step of the protocol and is cross-referenced to a Notes section that describes possible difficulties or problems that may arise, alternative methods and invaluable hints. Therapeutic Proteins: Methods and Protocols includes protocols for the production of therapeutic proteins using a variety of sources, including bacterial and yeast expression systems and insect and mammalian cells. Methods for the purification of the resulting protein product are also described, as are purification protocols for the more traditional methods of preparing therapeutic proteins such as those sourced from plasma. Protocols for the characterization of therapeutic proteins throughout the pro- v vi Preface duction process are described, along with viral inactivation and protein formulation methods and strategies. The book contains both general methods and information and specific case studies highlighting particular expression systems, proteins of interest or characterization procedures that may be equally applicable to other systems or recombinant proteins. A large number of people have helped to put this book together so that it ultimately provides an invaluable resource to all those working in the field of therapeutic protein production. I would especially like to thank all the contributors whom have all made many excellent suggestions, and indeed, improvements, to this book. I must also thank John Walker, the series editor, for asking me to edit this book, and for his help and advice in preparing the final product. Thanks also to those at Humana Press who have helped put this together. Finally I would like to thank my co-editor David James for all his help and advice and my family for their support. C. Mark Smales Contents Preface .............................................................................................................. v Contributors ..................................................................................................... xi 1 Biopharmaceutical Proteins: Opportunities and Challenges John R. Birch and Yemi Onakunle ........................................................ 1 2 Expression of Antibody Fragments by Periplasmic Secretion in Escherichia coli Andrew G. Popplewell, Mukesh Sehdev, Mariangela Spitali, and A. Neil C. Weir ........................................................................ 17 3 Secretory Production of Therapeutic Proteins in Escherichia coli Sang Yup Lee, Jong Hyun Choi, and Sang Jun Lee ............................. 31 4 Expression of Recombinant LTB Protein in Marine Vibrio VSP60 Wang Yili and Si Lusheng ................................................................... 43 5 Heterologous Gene Expression in Yeast Lee J. Byrne, Kenneth J. O’Callaghan, and Mick F. Tuite ................... 51 6 Pharmaceutical Proteins from Methylotrophic Yeasts Eric C. de Bruin, Erwin H. Duitman, Arjo L. de Boer, Marten Veenhuis, Ineke G. A. Bos, and C. Erik Hack .................... 65 7 Expression of Human Papillomavirus Type 16 L1 in Baculovirus Expression Systems: A Case Study Zheng Jin, Si Lusheng, and Wang Yili ................................................. 77 8 Large-Scale Transient Expression of Therapeutic Proteins in Mammalian Cells Sabine Geisse, Martin Jordan, and Florian M. Wurm ........................ 87 9 Site-Specific Integration for High-Level Protein Production in Mammalian Cells Bhaskar Thyagarajan and Michele P. Calos ........................................ 99 10 Production of Recombinant Therapeutic Proteins by Mammalian Cells in Suspension Culture Lily Chu, Ilse Blumentals, and Gargi Maheshwari ........................... 107 11 Transgene Control Engineering in Mammalian Cells Beat P. Kramer and Martin Fussenegger ........................................... 123 12 Fusion to Albumin as a Means to Slow the Clearance of Small Therapeutic Proteins Using the Pichia pastoris Expression System: A Case Study William P. Sheffield, Teresa R. McCurdy, and Varsha Bhakta ......... 145 vii viii Contents 13 High Throughput Recovery of Therapeutic Proteins from the Inclusion Bodies of Escherichia coli: An Overview Amulya K. Panda ............................................................................... 14 Isolation, Solubilization, Refolding, and Chromatographic Purification of Recombinant Human Growth Hormone from Inclusion Bodies of Escherichia coli cells: A Case Study Surinder M. Singh, A. N. S. Eshwari, Lalit C. Garg, and Amulya K. Panda .................................................................... 15 Large-Scale Preparation of Factor VIIa from Human Plasma: A Case Study Teruhisa Nakashima and Kazuhiko Tomokiyo .................................. 16 Purification of Clinical-Grade Monoclonal Antibodies by Chromatographic Methods Alberto L. Horenstein, Ilaria Durelli, and Fabio Malavasi ............... 17 Virus Elimination and Validation Nicola Boschetti and Anna Johnston ................................................ 18 Virus Removal by Nanofiltration Marina Korneyeva and Scott Rosenthal ............................................ 19 Determining Residual Host Cell Antigen Levels in Purified Recombinant Proteins by Slot Blot and Scanning Laser Densitometry Aaron P. Miles, Daming Zhu, and Allan Saul ................................... 20 Principles of Biopharmaceutical Protein Formulation: An Overview Scott P. Sellers and Yuh-Fun Maa ..................................................... 21 Solid-State Protein Formulation: Methodologies, Stability, and Excipient Effects Yuh-Fun Maa and Scott P. Sellers ..................................................... 22 Stabilization of Therapeutic Proteins by Chemical and Physical Methods Ken-ichi Izutsu .................................................................................. 23 Extraction and Characterization of Vaccine Antigens from Water-In-Oil Adjuvant Formulations Aaron P. Miles and Allan Saul .......................................................... 24 Probing Reversible Self-Association of Therapeutic Proteins by Sedimentation Velocity in the Analytical Ultracentrifuge Bernardo Perez-Ramirez and John J. Steckert .................................. 25 Biological Characterization of Pegylated Interferons: A Case Study Lei Xie, Constance Cullen, Sheri Bradshaw, Marc DeLorenzo, and Michael J. Grace .................................................................... 155 163 177 191 209 221 233 243 265 287 293 301 319 Contents ix 26 Characterization of Interferon α2B Pegylated Via Carboxyalkylation: A Case Study David C. Wylie, Marcio Voloch, Seoju Lee, Yan-Hui Liu, Collette Cutler, Brittany Larkin, and Susan Cannon-Carlson ...... 337 27 Quantifying Recombinant Proteins and Their Degradation Products Using SDS-PAGE and Scanning Laser Densitometry Aaron P. Miles and Allan Saul .......................................................... 349 28 Extraction and Denaturing Gel Electrophoretic Methodology for the Analysis of Yeast Proteins Kenneth J. O’Callaghan, Lee J. Byrne, and Mick F. Tuite ................. 357 29 Characterization of Therapeutic Proteins by Membrane and In-Gel Tryptic Digestion C. Mark Smales, Rosalyn J. Marchant, and Michèle F. Underhill .... 375 30 Oligosaccharide Release and MALDI-TOF MS Analysis of N-Linked Carbohydrate Structures from Glycoproteins Rodney G. Keck, John B. Briggs, and Andrew J. S. Jones ................. 381 31 Capillary Electrophoresis of Carbohydrates Derivatized with Fluorophoric Compounds Stacey Ma, Wendy Lau, Rodney G. Keck, John B. Briggs, Andrew J. S. Jones, Kathy Moorhouse, and Wassim Nashabeh.................................................................. 397 32 High-Throughput LC/MS Methodology for α(1→3)Gal Determination of Recombinant Monoclonal Antibodies: A Case Study Lihua Huang and Charles E. Mitchell ............................................... 411 33 Carbohydrate Structural Characterization of Fas Ligand Inhibitory Protein Lihua Huang, Charles E. Mitchell, Lei Yu, P. Clayton Gough, and Alice Riggin ............................................................................ 421 34 Top-Down Characterization of Protein Pharmaceuticals by Liquid Chromatography/Mass Spectrometry: Application to Recombinant Factor IX Comparability—A Case Study Jason C. Rouse, Joseph E. McClellan, Himakshi K. Patel, Michael A. Jankowski, and Thomas J. Porter ............................... 435 35 Sample Preparation Procedures for High-Resolution Nuclear Magnetic Resonance Studies of Aqueous and Stabilized Solutions of Therapeutic Peptides Mark J. Howard ................................................................................ 461 Index ............................................................................................................ 471 Contributors VARSHA BHAKTA • Canadian Blood Services, Research and Development Department, Hamilton, Ontario, Canada JOHN R. BIRCH • Lonza Biologics plc, Slough, UK ILSE BLUMENTALS • Merck & Co., Inc., Rahway, NJ INEKE G. A. BOS • Department of Immunopathology, Sanquin Research at CLB, Amsterdam, The Netherlands NICOLA BOSCHETTI • R & D Virology, ZLB Behring AG, Bern, Switzerland SHERI BRADSHAW • Schering Plough Research Institute, Union, NJ JOHN B. BRIGGS • Department of Analytical Chemistry, Genentech Inc., South San Francisco, CA LEE J. BYRNE • Department of Biosciences, University of Kent, Canterbury, Kent, UK MICHELE P. CALOS • Department of Genetics, Stanford University School of Medicine, Stanford, CA SUSAN CANNON-CARLSON • Schering-Plough Research Institute, Union, NJ JONG HYUN CHOI • Department of Chemical and Biomolecular Engineering, Metabolic and Biomolecular Engineering National Research Laboratory, Bioinformatics Research Center, BioProcess Engineering Research Center, and Center for Ultramicrochemical Process Systems, Korea Advanced Institute of Science and Technology, Daejeon, South Korea LILY CHU • Merck & Co., Inc., Rahway, NJ CONSTANCE CULLEN • Schering Plough Research Institute, Union, NJ COLLETTE CUTLER • Schering-Plough Research Institute, Union, NJ ARJO L. DE BOER • Eukaryotic Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Haren, The Netherlands ERIC C. DE BRUIN • Department of Immunopathology, Sanquin Research at CLB, Amsterdam, The Netherlands MARC DELORENZO • Schering Plough Research Institute, Union, NJ ERWIN DUITMAN • Eukaryotic Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Haren, The Netherlands ILARIA DURELLI • Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Turin, Italy and Research Center for Experimental Medicine (CeRMS), San Giovanni Battista Hospital, Turin, Italy A. N. S. ESHWARI • Product Development Cell, National Institute of Immunology, New Delhi, India MARTIN FUSSENEGGER • Institute for Chemical and BioEngineering, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland LALIT C. GARG • Gene Regulation Laboratory, National Institute of Immunology, New Delhi, India xi xii Contributors SABINE GEISSE • Novartis Pharma Research CT/BMP, Basel, Switzerland P. CLAYTON GOUGH • Bioproduct Research and Development, Lilly Research Laboratories, Eli Lilly and Company, , Indianapolis, IN MICHAEL J. GRACE • Schering Plough Research Institute, Union, NJ C. ERIK HACK • Departments of Immunopathology and Clinical Chemistry, Sanquin Research at CLB, VU Medical Centre, Amsterdam, The Netherlands ALBERTO L. HORENSTEIN • Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Turin, Italy and Research Center for Experimental Medicine (CeRMS), San Giovanni Battista Hospital, Turin, Italy MARK J. HOWARD • Department of Biosciences, University of Kent, Canterbury, Kent, UK LIHUA HUANG • Bioproduct Research and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN KEN-ICHI IZUTSU • National Institute of Health Sciences, Tokyo, Japan DAVID C. JAMES • School of Engineering, University of Queensland, St. Lucia, Queensland, Australia MICHAEL A. JANKOWSKI • Department of Characterization and Analytical Development, Wyeth BioPharma, Andover, MA ZHENG JIN • Institute for Cancer Research, College of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Peoples Republic of China ANNA JOHNSTON • CSIRO Health Science, Parkville, Melbourne, Australia ANDREW J. S. JONES • Department of Analytical Chemistry, Genentech Inc., South San Francisco, CA MARTIN JORDAN • Laboratory of Cellular Biotechnology, SV-IGBB-LBTC, EPFL, Lausanne, Switzerland RODNEY G. KECK • Department of Analytical Chemistry, Genentech Inc., South San Francisco, CA MARINA KORNEYEVA • Bayer Corporation Biological Products, Clayton, NC BEAT P. KRAMER • Institute for Chemical and BioEngineering, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland BRITTANY LARKIN • Schering-Plough Research Institute, Union, NJ WENDY LAU • Department of Analytical Chemistry, Genentech Inc., South San Francisco, CA SANG JUN LEE • Department of Chemical and Biomolecular Engineering and Center for Ultramicrochemical Process Systems, Metabolic and Biomolecular Engineering National Research Laboratory, Korea Advanced Institute of Science and Technology, Daejeon, South Korea SANG YUP LEE • Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering, Department of Biosystems, Bioinformatics Research Center, BioProcess Engineering Research Center and Center for Ultramicrochemical Process Systems, Korea Advanced Institute of Science and Technology, Daejeon, South Korea Contributors xiii SEOJU LEE • Neose Technologies Inc., Horsham, PA YAN-HUI LIU • Schering-Plough Research Institute, Union, NJ SI LUSHENG • Institute for Cancer Research, College of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Peoples Republic of China STACEY MA • Department of Analytical Chemistry, Genentech Inc., South San Francisco, CA YUH-FUN MAA • ALZA Corporation, Mountain View, CA GARGI MAHESHWARI • Merck & Co., Inc., Rahway, NJ FABIO MALAVASI • Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Turin, Italy and Research Center for Experimental Medicine (CeRMS), San Giovanni Battista Hospital, Turin, Italy ROSALYN J. MARCHANT • Department of Biosciences, University of Kent, Canterbury, Kent, UK JOSEPH E. MCCLELLAN • Department of Characterization and Analytical Development, Wyeth BioPharma, Andover MA TERESA R. MCCURDY • Research and Development Department, Canadian Blood Services, Hamilton, Ontario, Canada AARON P. MILES • Biochemical Assay Development and Quality Control, Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, Rockville, MD CHARLES E. MITCHELL • Bioproduct Research and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN KATHY MOORHOUSE • Department of Quality Control Clinical Development, Genentech Inc., South San Francisco, CA TERUHISA NAKASHIMA • Blood Products Research Department, The Chemo-SeroTherapeutic Research Institute, Kumamoto, Japan WASSIM NASHABEH • Department of Quality Control Clinical Development, Genentech Inc., South San Francisco, CA KENNETH J. O’CALLAGHAN • Department of Biosciences, University of Kent, Canterbury, Kent, UK YEMI ONAKUNLE • Lonza Biologics plc, Slough, UK AMULYA K. PANDA • Product Development Cell, National Institute of Immunology, New Delhi, India HIMAKSHI K. PATEL • Department of Characterization and Analytical Development, Wyeth BioPharma, Andover MA BERNARDO PEREZ-RAMIREZ • Scientific Director, BioFormulations Development, Genzyme, Framingham, MA ANDREW G. POPPLEWELL • Celltech R&D, Slough, UK THOMAS J. PORTER • Department of Characterization and Analytical Development, Wyeth BioPharma, Andover MA ALICE RIGGIN • Bioproduct Research and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN xiv Contributors SCOTT ROSENTHAL • Bayer Corporation Biological Products, Clayton, NC JASON C. ROUSE • Department of Characterization and Analytical Development, Wyeth BioPharma, Andover MA ALLAN SAUL • Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, Rockville MD MUKESH SEHDEV • Celltech R&D, Slough, UK SCOTT P. SELLERS • ALZA Corporation, Mountain View, CA WILLIAM P. SHEFFIELD • Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada SURINDER M. SINGH • Product Development Cell, National Institute of Immunology, New Delhi, India C. MARK SMALES • Protein Science Group, Department of Biosciences, University of Kent, Canterbury, Kent, UK MARIANGELA SPITALI • Celltech R&D, Slough, UK JOHN J. STECKERT • Characterization & Analytical Development, Wyeth BioPharma, Andover, MA BHASKAR THYAGARAJAN • Poetic Genetics, LLC, Burlingame, CA KAZUHIKO TOMOKIYO • Blood Products Research Department, The Chemo-SeroTherapeutic Research Institute, Kumamoto, Japan MICK F. TUITE • Department of Biosciences, University of Kent, Canterbury, Kent, UK MICHÈLE F. UNDERHILL • Department of Biosciences, University of Kent, Canterbury, Kent, UK MARTEN VEENHUIS • Eukaryotic Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Haren, The Netherlands MARCIO VOLOCH • Transkaryotic Therapies Inc., Cambridge, MA A. NEIL C. WEIR • Celltech R&D, Slough, UK FLORIAN M. WURM • Laboratory of Cellular Biotechnology, SV-IGBB-LBTC, EPFL, Lausanne, Switzerland DAVID C. WYLIE • Biotechnology Development, Schering-Plough Research Institute, Union, NJ LEI XIE • Schering Plough Research Institute, Union, NJ WANG YILI • Institute for Cancer Research, College of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Peoples Republic of China LEI YU • Bioproduct Research and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN DAMING ZHU • Biochemical Assay Development and Quality Control, Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, Rockville, MD Biopharmaceutical Proteins 1 1 Biopharmaceutical Proteins Opportunities and Challenges John R. Birch and Yemi Onakunle 1. Introduction Over the last 20 yr, there has been extraordinary growth in the biopharmaceutical industry based on the development of recombinant DNA and hybridoma technologies in the 1970s. Prior to this, the dependence on extraction from natural sources severely limited the range and quantity of proteins available for clinical use. Recombinant DNA technology made it possible to mass produce a wide range of natural and modified proteins for the first time. In addition, hybridoma technology introduced a new class of protein reagents—the monoclonal antibodies (MAbs)—that provided an alternative approach to treat many diseases. The earliest recombinant products were replacements for existing protein products, which were extracted from natural sources, such as blood and pituitaries. Insulin was the first recombinant protein to be approved in 1982, followed by growth hormone and blood-clotting Factor VIII. In some cases, the switch to recombinant products was also motivated by safety concerns related to the natural source. In the 1980s, concern existed that growth hormone derived from human pituitaries might transmit the prion agent responsible for Creutzfeld–Jacob disease; this protein is now produced in Escherichia coli. Recombinant technology has also allowed the production of viral vaccines, e.g., hepatitis B, without the need to use the potentially hazardous virus in the manufacturing process. In the second generation of products, there is a progression of new approaches to treat various diseases using recombinant proteins and MAbs. A significant proportion of applications are in the cancer field; other important areas include immune disorders and infectious diseases. The number of approved products has grown steadily. By mid-2003, 148 biopharmaceuticals were approved in the United States and Europe compared with 84 in 2000 (1,2; Table 1). Similarly, the number of products being evaluated has rapidly increased with estimates of many hundreds more in development From: Methods in Molecular Biology, vol. 308: Therapeutic Proteins: Methods and Protocols Edited by: C. M. Smales and D. C. James © Humana Press Inc., Totowa, NJ 1 2 Table 1 Approved Biopharmaceutical Proteins Hormones Product Protein Humulin® Human insulin Methionyl-human growth hormone (hGH) Humatrope® (somatropin) hGH Human insulin Novolin® hGH Nutropin® (somatropin) Norditropin® (somatropin) hGH Bio-Tropin® (somatropin) hGH Protropin® (somatrem) hGH Human insulin analog hGH Follicle-stimulating hormone Follicle-stimulating hormone Glucagon Glucagon Human insulin analog Human insulin analog Human chorionic gonadotropin Human B-type Natriuretic peptide Parathyroid hormone Forteo® (teriparatide) Somavert® (pegvisomant) Growth hormone analog (receptor antagonist) Company USA Production technology Cell line/ microbial species Diabetes hGH deficiency Eli Lilly Genentech 1982 1985 Microbial Microbial E. coli E. coli hGH deficiency Diabetes hGH deficiency hGH deficiency hGH deficiency 1987 1991 1993 1995 1995 Microbial Microbial Microbial Microbial Microbial E. coli S. cerevisiae E. coli E. coli E. coli hGH deficiency Diabetes AIDS-associated wasting Infertility Infertility Hypoglycemia Hypoglycemia Diabetes Diabetes Infertility Eli Lilly Novo Nordisk Genentech Novo Nordisk Bio-Technology General Pfizer/Pharmacia Eli Lilly Serono Organon Serono Novo Nordisk Eli Lilly Aventis Novo Nordisk Serono 1995 1996 1996 1997 1997 1998 1998 2000 2000 2000 Microbial Microbial Mammalian Mammalian Mammalian Microbial Microbial Microbial Microbial Mammalian E. coli E. coli Mouse C127 CHO CHO S. cerevisiae E. coli E. coli S. cerevisiae CHO Heart failure Scios 2001 Microbial E. coli Osteoporosis Acromegaly Eli Lilly Pfizer/Pharmacia 2002 2003 Microbial Microbial E. coli E. coli Birch and Onakunle Genotropin® (somatropin) Humalog® (insulin lispro) Serostim® (somatropin) Follistim® (follitropin-β) Gonal-F® (follitropin α) GlucaGen® (glucagon) Glucagon Lantus® (insulin glargine) NovoLog® (insulin aspart) Ovidrel® (choriogonadotropin α) Natrecor® (nesiritide) Therapeutic area Approval date for first indication Intron Roferon A® Epogen® (epoetin-α) Procrit® (epoetin-α) Actimmune® Interferon α-2b Interferon α-2a EPO EPO Interferon γ-1b G-CSF Neupogen® (filgrastim) Leukine® (sargramostim) Granulocyte/macrophage colony-stimulating factor Proleukin® (aldesleukin) Interleukin-2 (IL-2) Interferon β-1b Betaseron® Interferon β-1a Avonex® Consensus interferon Infergen® (interferon alfacon-1) Regranex® (becaplermin) Platelet-derived growth factor IL 11 Neumega® (oprelvekin) Ontak® (denileukin diftitox) IL-2/diphtheria toxin fusion protein Peg-Intron® Pegylated interferon α-2b (peginterferon alfa-2b) Aranesp® (darbepoietin-α) EPO analog Osteogenic protein 1 Bone morphogenic protein-7 IL-1 receptor antagonist Kineret® (anakinra) (IL-1 Ra) Neulasta® (pegfilgrastim) Pegylated (G-CSF) Interferon β-1a Rebif® Bone morphogenic protein-2 InFuse® (dibotermin α) Pegasys® (peginterferon alfa-2a) Pegylated interferon α-2a Biopharmaceutical Proteins Cytokines/receptor antagonists/growth factors A® Cancer, hepatitis Cancer, hepatitis Anaemia Anaemia Chronic granulomatous disease, osteopetrosis Neutropenia Cancer/bone marrow transplantation Renal carcinoma Multiple sclerosis Multiple sclerosis Hepatitis C Schering-Plough Hoffmann-La Roche Amgen Ortho Biotech/J&J InterMune 1986 1986 1989 1990 1990 Microbial Microbial Mammalian Mammalian Microbial E. coli E. coli CHO CHO E. coli Amgen Berlex 1991 1991 Microbial Microbial E. coli S. cerevisiae Chiron Berlex Inc./Chiron Biogen Idec InterMune 1992 1993 1996 1997 Microbial Microbial Mammalian Microbial E. coli E. coli CHO E. coli Diabetic ulcers Chemotherapy-induced thrombocytopenia T-cell lymphoma Ortho-McNeil/J&J Genetics Institute/ Wyeth-Ayerst Ligand/Seragen 1997 1997 Microbial Microbial S. cerevisiae E. coli 1999 Microbial E. coli Hepatitis C Schering-Plough 2001 Microbial E. coli Anemia Bone repair Rheumatoid arthritis Amgen Stryker Biotech Amgen 2001 2001 2001 Mammalian Mammalian Microbial CHO CHO E. coli Neutropenia Multiple sclerosis Bone repair Amgen Serono Medtronic Sofamor Danek Hoffmann-La Roche 2002 2002 2002 Microbial Mammalian Mammalian E. coli CHO CHO 2002 Microbial E. coli Hepatitis C (continued) 3 4 Table 1 (continued) Enzymes Product Activase® (alteplase) Pulmozyme® (dornase α) Cerezyme® (imiglucerase) Retavase® (reteplase) TNKase® (tenecteplase) Elitek® (rasburicase) Aldurazyme® (laronidase) Protein Human tPA Deoxyribonuclease β-Glucocerebrosidase Modified human tPA Modified human tPA Urate oxidase α-L-Iduronidase Fabrazyme® Agalsidase β Human α-galactosidase Therapeutic area Company USA Approval date for first indication Thrombolysis Cystic fibrosis Gauchers disease Thrombolysis Thrombolysis Uric acid management Mucopolysaccharidosis I (MPS1) Fabry disease Genentech Genentech Genzyme Centocor/J&J Genentech Sanofi-Synthelabo Genzyme/BioMarin 1987 1993 1994 1996 2000 2002 2003 Mammalian Mammalian Mammalian Microbial Mammalian Microbial Mammalian CHO CHO CHO E. coli CHO S. cerevisiae CHO Genzyme 2003 Mammalian CHO Baxter Healthcare Bayer Genetics Institute/ Wyeth Pharmaceuticals Novo Nordisk Genetics Institute/ Wyeth Pharmaceuticals Eli Lilly Baxter Healthcare 1992 1993 1997 Mammalian Mammalian Mammalian CHO BHK CHO 1999 2000 Mammalian Mammalian BHK CHO 2001 2003 Mammalian Mammalian CHO Production technology Cell line/ microbial species Blood factors Recombinate® Hemophilia Hemophilia Hemophilia Factor VIIa NovoSeven® ReFacto® (moroctocog-α) Factor VIII Hemophilia Hemophilia Xigris® (drotrecogin α) Advate Sepsis Hemophilia Human-activated Protein C Factor VIII Birch and Onakunle Factor VIII Factor VIII Factor IX Kogenate® BeneFIX® Target Antibody type Therapeutic area Company USA Cell line MAbs/fusion proteins Orthoclone OKT® 3 (Muromonab) ReoPro® (abciximab) CD3 Murine Transplant rejection Platelet GPIIb/IIIa receptor Chimeric Cardiovascular disease Rituxan® CD20 (rituximab) Zenapax® (daclizumab) Simulect® (basiliximab) Synagis® (palivizumab) IL-2 receptor IL-2 receptor Respiratory syncytial virus Remicade® (infliximab) Tumor necrosis factor Herceptin® (trastuzumab) Enbrel® (etanercept) HER2 receptor Tumor necrosis factor receptor/Ig G1 Fc Fusion protein Mylotarg® CD33 used as conjugate (gemtuzumab with calicheamicin ozogamicin) cytotoxin ® Campath (alemtuzumab) CD52 Zevalin® Ortho Biotech/J&J 1986 Eli Lilly/Centocor/ J&J Chimeric Non-Hodgkin’s lymphoma Genentech/ Biogen Idec Humanized Transplant rejection Hoffman La Roche Chimeric Transplant rejection Novartis Humanized Respiratory syncytial Medimmune virus infection Chimeric Crohns Disease/ Centocor/J&J rheumatoid arthritis Humanized Breast cancer Genentech Fusion protein Rheumatoid arthritis Amgen/ Wyeth Pharmaceuticals Humanized Acute myeloid leukemia Wyeth Pharmaceuticals 1994 Hybridoma (not recombinant) Sp2/0 1997 CHO 1997 1998 1998 NS0 NS0 NS0 1998 Sp2/0 1998 1998 CHO CHO 2000 NS0 2001 CHO 2002 CHO Humanized Chronic lymphocytic Berlex/Ilex Oncology leukemia Non-Hodgkin’s lymphoma Biogen Idec CD20 used as conjugate (ibritumomab tiuxetan) with Yttrium 90 Humira® (adalimumab) Tumor necrosis factor-α Amevive (alefacept) Leukocyte function-associated antigen-3/IgG fusion protein Xolair® (omalizumab) IgE Human Rheumatoid arthritis Fusion protein Psoriasis Abbot Laboratories Biogen Idec 2002 2003 CHO CHO Humanized Asthma CHO CD20 used as conjugate with iodine I 131 CD11a Epidermal growth factor receptor Murine Non-Hodgkin lymphoma Genentech/Novartis/ Tanox GSK/Corixa 2003 Bexxar® Humanized Chimeric Psoriasis Colorectal cancer 2003 2004 CHO Mouse myeloma Vascular endothelial growth factor Humanized Colorectal cancer Genentech/Xoma ImClone/ Bristol-Myers Squibb Genentech 2004 CHO (tositumomab) Raptiva® (efalizumab) Erbitux® (cetuximab) Avastin® (bevacizumab) Biopharmaceutical Proteins Product Approved date for first indication Murine 2003 5

Author C. Mark Smales and David C. James Isbn 1627038485 File size 5.51MB Year 2005 Pages 482 Language English File format PDF Category Biology Book Description: FacebookTwitterGoogle+TumblrDiggMySpaceShare With the recent completion of the sequencing of the human genome, it is widely anticipated that the number of potential new protein drugs and targets will escalate at an even greater rate than that observed in recent years. However, identification of a potential target is only part of the process in developing these new next generation protein-based “drugs” that are increasingly being used to treat human disease. Once a potential protein drug has been identified, the next rate-limiting step on the road to development is the production of sufficient authentic material for testing, charact- ization, clinical trials, and so on. If a protein drug does actually make it through this lengthy and costly process, methodology that allows the production of the protein on a scale large enough to meet demand must be implemented. Furthermore, large-scale production must not compromise the authenticity of the final product. It is also nec- sary to have robust methods for the purification, characterization, viral inactivation and continued testing of the authenticity of the final protein product and to be able to formulate it in a manner that retains both its biological activity and lends itself to easy administration. Therapeutic Proteins: Methods and Protocols covers all aspects of protein drug production downstream of the discovery stage. This volume contains contributions from leaders in the field of therapeutic protein expression, purification, characterization, f- mulation, and viral inactivation.     Download (5.51MB) Protein Purification: Principles, High Resolution Methods, And Applications By Jan-christer Janson Protein Chromatography: Methods and Protocols, 2nd ed. Rhinoviruses: Methods and Protocols Influenza Virus: Methods and Protocols Multiplex Biomarker Techniques: Methods and Applications Load more posts

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