Development of Antibody-Based Therapeutics: Translational Considerations

426 Pages·2012·5.97 MB·English

by  Mohammad Tabrizi

Development of Antibody-Based Therapeutics
Mohammad A. Tabrizi
•
Gadi G. Bornstein Scott L. Klakamp
•
Editors
Development
of Antibody-Based
Therapeutics
Translational Considerations
123
Editors
Mohammad A.Tabrizi Scott L.Klakamp
MerckResearch Laboratory TakedaCalifornia, Inc.
Merck&CO Inc. South San Francisco, CA
PaloAlto, CA USA
USA
Gadi G.Bornstein
Pfizer CTI—New York
New York, NY
USA
ISBN 978-1-4419-5953-9 ISBN 978-1-4419-5955-3 (eBook)
DOI 10.1007/978-1-4419-5955-3
SpringerNewYorkHeidelbergDordrechtLondon
LibraryofCongressControlNumber:2012936109
(cid:2)SpringerScience+BusinessMediaNewYork2012
Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,
recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor
informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar
methodology now known or hereafter developed. Exempted from this legal reservation are brief
excerpts in connection with reviews or scholarly analysis or material supplied specifically for the
purposeofbeingenteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthe
work. Duplication of this publication or parts thereof is permitted only under the provisions of
theCopyrightLawofthePublisher’slocation,initscurrentversion,andpermissionforusemustalways
beobtainedfromSpringer.PermissionsforusemaybeobtainedthroughRightsLinkattheCopyright
ClearanceCenter.ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt
fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse.
While the advice and information in this book are believed to be true and accurate at the date of
publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor
anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with
respecttothematerialcontainedherein.
Printedonacid-freepaper
SpringerispartofSpringerScience+BusinessMedia(www.springer.com)
This book is dedicated to all patients who
are in need of improved therapies and who
inspire us to develop better drugs
Preface
Monoclonalantibodieshavebecomeakeytherapeuticmodalityforabroadrange
of diseases. The therapeutic potential of monoclonal antibodies is derived from
their exquisite specificity and high affinity binding to their antigen target. The
therapeutic utility of monoclonal antibodies was quickly realized after the
development of hybridoma technology by Kohler and Milstein in 1975.
The first generation of therapeutic antibodies was of murine origin. These
antibodies were of limited therapeutic value because patients who received these
agents developedanimmuneresponse tothe mouseprotein,referredtoashuman
anti-mouse antibody (HAMA) response. HAMA responses negatively impacted
the efficacy of antibodies of murine origin; this limitation fostered the develop-
ment of new antibody technologies to reduce the immunogenicity of murine
antibodies by making them more human-like. These technologies, employing
recombinant DNA methods, led to the development of chimeric antibodies;
chimeric antbodies maintain the murine variable region linked to human constant
regions and retain approximately 35% of murine protein sequences. Additional
improvements in recombinant DNA technology led to the development of
humanized antibodies, which retain about 5–10% of murine protein sequences.
With further advances in antibody technology, two major platforms are now
employed to generate fully human monoclonal antibodies. One platform relies on
display technologies, namely phage, ribosomes, or yeast that display human
antibody variable regions. The second major platform relies on transgenic mice
that have been genetically engineered to produce human antibodies.
Adirectconsequenceoftheabove-describedtechnologicaladvanceshasbeena
significant investment on the part of the biotechnology and pharmaceutical
industrytodevelopantibodiesandanexponentialgrowthinthetherapeuticmarket
for these agents. Moreover, several therapeutic monoclonal antibodies have
attained blockbuster status with sales exceeding the billion-dollar mark and
beyond.
Despite the exponential growth in the therapeutic market of monoclonal anti-
bodies, it is also important to note that there still remains a considerable unmet
medical need in the three main areas of study for investigational human
vii
viii Preface
monoclonal antibodies: cancer, immunological, and infectious diseases. It is
expected that therapeutic monoclonal antibodies will provide valuable new
treatment options for these diseases.
The main objective of this volume is to provide a comprehensive overview of
the translational considerations for developing antibody-based therapeutics from
discoverytotheclinic.Theinitiatingeventthatultimatelyledtothepublicationof
this endeavor originated from a perennial annual short course at the Protein
Engineering Summit (PEGS) that we introduced in2008 and still teach currently.
Fromourexperienceswiththiscourse,werealizedthatmanyscientists,bothinthe
academic and biotechnology/pharmaceutical community, do not possess in-depth
knowledge of all aspects of antibody drug discovery and development; we
therefore concluded a more formal and thorough discussion was warranted.
The topics covered have been carefully selected. Each chapter focuses on a
specific aspect of translational strategies during the development of antibody-
basedtherapeutics.Althoughsometopicsmaynotappeartobedirectlyconcerned
withtranslationalconsiderationsoraretechnicalinnature,addressingtheancillary
aspects of antibody drug discovery and development should provide the reader
with a broader understanding of the strategies involved in the drug development
process of these agents. We envision that someone who has little if any current
knowledge about therapeutic antibodies will be able to read this book and glean
substantial insights from leading scientists across a broad range of expertise.
Weareindebtedtoourmanycolleaguesfortheircontributionstothisendeavor.
Contents
1 Translational Strategies for Development
of Antibody-Based Therapeutics: An Overview . . . . . . . . . . . . . . 1
Mohammad Tabrizi, Gadi Gazit Bornstein and Scott L. Klakamp
2 Discovery Process for Antibody-Based Therapeutics . . . . . . . . . . 9
Heather H. Shih
3 Technologies for the Generation of Human Antibodies . . . . . . . . 33
Ramesh R. Bhatt, John S. Haurum and C. Geoffrey Davis
4 Application of Antibody Engineering in the Development
of Next Generation Antibody-Based Therapeutics . . . . . . . . . . . . 65
Randall J. Brezski and Juan Carlos Almagro
5 Biophysical Considerations for Development
of Antibody-Based Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . 95
Andrew W. Drake and Giuseppe A. Papalia
6 Considerations in Establishing Affinity Design Goals
for Development of Antibody-Based Therapeutics . . . . . . . . . . . . 141
Mohammad Tabrizi
7 Bioanalytical Considerations for Development
of Antibody-Based Therapeutics: Pharmacokinetics
and Immunogenicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Cherryl B. Funelas and Scott L. Klakamp
ix
x Contents
8 Preclinical Considerations for Development
of Antibody-Based Therapeutics in Oncology. . . . . . . . . . . . . . . . 183
Gregory Landes and Kathleen Elias
9 Factors Impacting the Tumor Localization and Distribution
of Antibody-Based Therapeutics in Oncology. . . . . . . . . . . . . . . . 241
David C. Blakey
10 Preclinical Safety Considerations for the Development
of Antibody-Based Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . 255
Lolke de Haan
11 Application of Pharmacokinetic/Pharmacodynamic Modeling
in the Development of Antibody-Based Therapeutics. . . . . . . . . . 285
Donald E. Mager
12 Application of Population Pharmacokinetic-Pharmacodynamic
Approaches in the Design of Translational Strategies
for Development of Antibody-Based Therapeutics . . . . . . . . . . . . 303
Feng Jin
13 Translational Biomarkers: Essential Tools in Development
of Antibody-Based Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . 331
Mohammad A. Tabrizi and Cherryl B. Funelas
14 Translational Research in Alzheimer’s Disease for Development
of Antibody-Based Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . 341
Eric C. Yuen, Enchi Liu and Gene G. Kinney
15 Considerations in Manufacturing Process Development
for Antibody-Based Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . 355
Paula C. Miller and Peiling Xu
16 Strategies for Development of Next Generation
Antibody-Based Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
Mohammad Tabrizi and Gadi Gazit Bornstein
17 Immune Complex Therapies for Treatment
of Immune Thrombocytopenia . . . . . . . . . . . . . . . . . . . . . . . . . . 391
Rong Deng and Joseph P. Balthasar
Contents xi
18 Application of Bioinformatics Principles
for Target Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405
Anthony Carvalloza, Mohammad Fallahi and Sahba Tabrizifard
19 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
Mohammad Tabrizi, Gadi Gazit Bornstein and Scott L. Klakamp
Editors Biography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
Contributors
Juan Carlos Almagro Structural Biology, Biologics Research, Centocor R&D
Inc., Radnor, PA, USA
Joseph P. Balthasar Department of Pharmaceutical Sciences, University at
Buffalo, The State University of New York, Buffalo, NY, USA
Ramesh R. Bhatt Sea Lane Biotechnologies, Mountain View, CA, USA
David C. Blakey Oncology Discovery, AstraZeneca, Macclesfield, Cheshire, UK
GadiGazitBornsteinCentersforTherapeuticInnovation(CTI),PfizerInc.,New
York, NY, USA
Randall J. Brezski Antibody Engineering, Biologics Research, Centocor R&D,
Radnor, PA, USA
AnthonyCarvallozaScrippsFlorida,TheScrippsResearchInstitute,Jupiter,FL,
USA
C. Geoffrey Davis Angelica Therapeutics Inc., Auburn, CA, USA
Rong Deng Genentech, Inc., South San Francisco, CA, USA
Andrew W. Drake Biological Sciences, Takeda California, Inc., South San
Francisco, CA, USA
Kathleen Elias Experimental Medicine, Takeda California, South San Francisco,
CA, USA
MohammadFallahi ScrippsFlorida,TheScrippsResearchInstitute,Jupiter,FL,
USA
Cherryl Funelas Analytical Sciences & DMPK, Takeda California, Inc., South
San Francisco, CA, USA
Lolke de Haan MedImmune, Cambridge, UK
xiii