抗体治疗：产品开发、市场趋势及策略课题

Abstract

D&MD's Antibody Therapeutics market analysis report provides an update of the current market environment including clinical study status, progresses made in the area of collaborations and partnerships, patent situation, and finally the market status. These developments are primarily in the antibody market place and in clinical development areas as opposed to in the antibody discovery field as was observed in the early part of this decade.

Table of Contents

Chapter 1: Executive Summary

• Key Points 2004-2006

Chapter 2: Introduction, Scope, and Objectives

• Early Status and Current Products
• Driving Forces
• Customers
• Competition
• Scope and Objective

Chapter 3: Hybridoma Technology and Antibody Gene Manipulation

• Introduction
• Historical Roots
  • A Long Record of Advance
  • Founders of Immunology
• Classical Antibody Development
  • Polyclonal Antibodies: Still Standing
  • Polyclonal Antibodies Detect a Multiplicity of Epitopes
• Hybridoma Technology
  • Origins
  • Monoclonal Antibody Production
  • Uses of MAbs
  • Disadvantages of MAb Technology
• Genetic Immunization
• Molecular Biology Applied To Antibody Characterization
  • Production of Antibody Libraries
  • Display Technologies
  • Rationally Designed Antibodies
  • Varieties of Engineered Antibodies
  • Bispecific Antibodies
  • Designing Antibodies with Human-like Qualities
    • Chimeric Antibodies
    • Humanized Antibodies
    • Human Antibodies: Transgenic Mouse System
• References

Chapter 4: Status of Therapeutic Antibody Products

• Introduction
  • Difficulty in Cancer Treatment
  • Antibody Engineering: Light at the End of the Tunnel?
• Therapeutic Anticancer Antibodies
  • Panorex® (edrecolomab)
  • Rituxan® (rituximab)
  • Herceptin® (traztuzumab)
  • Mylotarg® (gentuzumab)
  • Campath® (alemtuzumab)
  • Zevalin™ (ibritumomab)
  • Erbitux™ (cetuximab)
  • Avastin™ (bevicizumab)
• Immunoconjugated Anticancer Recombinant Antibodies
  • Challenges in Developing Immunoconjugated Recombinant Antibodies
  • Exploiting Apoptosis-related Strategies
  • Use of Antibody Fragments in Immunoconjugate Technology
  • Optimizing the Effector Function of Recombinant Antibodies
  • Signal Regulation Strategy for Improved Recombinant Antibodies
  • Bifunctional Linkers and Low Molecular Weight Toxins in Recombinant
  • Antibody Design
  • Alternative Approaches to Immunoconjugates
• Cardiovascular Disorders
• Infectious Diseases
• Inflammatory Diseases
  • Raptiva™ (efalizumab)
  • Remicade® (infliximab)
  • Humira™ (adalimumab)
  • Xolair™ (omalizumab)
• Transplantation
  • Orthoclone OKT3® (muromomab-CD3)
  • Simulect® (basiliximab)
  • Zenapax® (daclizumab)
• References

Chapter 5: Clinical Studies

• Approved Antibody Therapeutics
• Therapeutic Antibodies in Development
• Failed Antibody Therapeutics
• Catastrophic Clinical Trial
  • Failed, Cancelled, and Disapproved Clinical Studies
• Status of A Few Selected Ongoing Clinical Studies
  • Phase I Studies
  • Phase II Studies
  • Phase III Studies
  • Products Approved in 2002- 2004

Chapter 6: Large Scale Manufacturing

• Overview
• Companies Involved
• Risks of Innovation in Biomanufacturing
• Bioprocessing Technologies
• Production Systems
  • Escherichia Coli
    • Q-cell Technology
    • TAT System
  • Mammalian Cell Culture
    • Cell Lines
    • Bioreactor Technology
    • Cell Culture Media
  • Yeast
  • Insect Cells
  • Transgenic Plants: Plantabodies
  • Transgenic Animals
  • Robotic Peptide Synthesis
• Antibody Glycosylation Issues
• New Purification Tools
• Monitoring Technologies
• Is There a Shortage in Manufacturing Capability?
  • Factors Affecting Biomolecule Production
• Insulin: A Case History of Recombinant Protein Production
• The Future
• References

Chapter 7: Business Development and Partnering

• Collaboration and Partnering
• Mergers and Acquisitions

Chapter 8: Patents and Intellectual Property Issues

• Introduction
• Intellectual Property Issues
  • Antibody Function Modulation Technologies
  • Litigation between CAT and Abbott
• Antibody Humanization
• Human Antibody Technology
• Antibody Production
  • Boss Patent, New Cabilly and MedImmune lawsuit
  • Xoma Patents
• Litigations and Co-licensing
  • CAT vs. Morphosys
  • CAT vs. Crucell
  • Cross-licensing between CAT and Xoma
  • Cross-licensing between CAT and Dyax
  • Cross-licensing between Xoma and Morphosys
  • Cross-licensing between Xoma and Dyax
• Court Rulings about Importing Data
• More Litigations
  • Xoma vs. Biosite
  • Applied Molecular Evolution vs. Morphosys
  • Corixa and GlaxoSmithKline vs. IDEC
  • Genentech vs. Chiron
  • Genentech, Novartis, and Tanox Settle Disputes involving Xolair and TNX-901
• The Single-Chain Antibody Technology
• Recent IP Issuance and Related Activities
  • Dyax's Patent Revoked
  • MorphoSys Obtains Approval for HuCALR Patent
  • MorphoSys Obtains Additional U.S. Patents on Antibody Technologies
  • Peregrine Receives US and European Patent
  • Genentech and Protein Design Labs Settle Patent License Dispute
  • A US Patent Issued on Polyclonal Antibody Libraries
• Abstracts of the Selected Patents Mentioned in the Text
  • Patent Number: US 4,816,397
  • Patent Number: US 4,816,567
  • Patent Number: US 5,175,384
  • Patent Number: US 5,223,409
  • Patent Number: US 5,225,539
  • Patent Number: US 5,403,484
  • Patent Number: US 5,427,908
  • Patent Number: US 5,434,340*
  • Patent Number: US 5,530,101
  • Patent Number: US 5,565,332
  • Patent Number: US 5,571,698
  • Patent Number: US 5,580,717
  • Patent Number: US 5,585,089
  • Patent Number: US 5,569,825
  • Patent Number: US 5,591,669
  • Patent Number: US 5,693,761
  • Patent Number: US 5,693,762
  • Patent Number: US 5,723,323
  • Patent Number: US 5,763,192
  • Patent Number: US 5,814,476
  • Patent Number: US 5,817,483
  • Patent Number: US 5,824,514
  • Patent Number: US 5,837,500
  • Patent Number: US 5,849,500
  • Patent Number: US 5,859,205
  • Patent Number: US 5,885,793
  • Patent Number: US 5,939,598
  • Patent Number: US 5,969,108
  • Patent Number: US 5,976,862
  • Patent Number: US 6,054,561
  • Patent Number: US 6,150,584
  • Patent Number: US 6,162,963
  • Patent Number: US 6,180,370
  • Patent Number: US 6,204,023
  • Patent Number: US 6,248,516
  • Patent Number: US 6,335,163
  • Patent Number: EP 368684

Chapter 9: Market Status

• Revenues from the Early Products
  • Reopro®
  • Rituxan®
  • Herceptin®
  • Remicade®
  • Synagis®
• Revenues from the Recently Approved Products
  • Avastin™
  • Erbitux™
  • Xolair™
  • Raptiva™
• New Product Approvals
  • Lucentis™
  • Tysabri®

Chapter 10: Company Profiles

Table of Exhibits

• Exhibit 2.1 Selection of Phage Antibodies from an Antibody Library
• Exhibit 2.2 Mechanisms of Actions In Vivo of Therapeutic Antibodies
• Exhibit 2.3 List of Companies Involved in the Discovery and Development of Antibody Therapeutics
• Exhibit 2.4 List of Therapeutic Monoclonal Antibodies Approved for Additional Indications, September 2006
• Exhibit 2.5 Primary Technology Portfolio of a Selected Group of Antibody Companies
• Exhibit 3.1 Major Events in the History of Immunology Compiled from Various Sources
• Exhibit 3.2 Basic Structure of an IgG Molecule
• Exhibit 3.3 A Space-filling Model of an IgG Molecule
• Exhibit 3.4 The GENOVAC Technology for the Production of Polyclonal (Steps 1- 4) and Monoclonal Antibodies (Steps 1- 7)
• Exhibit 3.5 Choices when Constructing a Binding-site Library
• Exhibit 3.6 Scheme Showing the Principle of Selection and Improvement of Binding Sites
• Exhibit 3.7 Schematic Diagram of Ribosomal Display
• Exhibit 3.8 Comparison of Structural Features of Human Antibody, Camelid Antibody, and Nanobodies
• Exhibit 3.9 Schematic Diagram Showing Structural Features of Single Chain Antibody (scFv) and Fab Fragment
• Exhibit 3.10 Various Forms of Bispecific Antibodies
• Exhibit 3.11 Various Types of Antibodies
• Exhibit 3.12 Schematic Diagram of the Generation of Human Antibody Mouse
• Exhibit 4.1 Various Mechanisms of Antibody Actions
• Exhibit 4.2 Approved Monoclonal Antibodies for the Treatment of Various Cancers
• Exhibit 4.3 Schematic Diagram Showing the Mechanism of ADCC
• Exhibit 4.4 Schematic Diagram Showing the Structural Feature of Epidermal Growth Factor Receptor and the Binding to its Ligand (egf)
• Exhibit 4.5 EGFR Expression in Various Tumors
• Exhibit 4.6 Approved Antibody Therapeutic for the treatment of Cardiovascular Disorders
• Exhibit 4.7 Summary of Antibody Studies in the Prevention and Treatment of Infectious Diseases
• Exhibit 4.8 Approved Antibody for the Treatment of Infectious Disease
• Exhibit 4.9 Approved MAbs for the Treatment of Inflammatory Diseases
• Exhibit 4.10 Inflammation in the Rheumatoid Joint
• Exhibit 4.11 Mode of Action of Xolair™
• Exhibit 4.12 Market for Drugs to Treat Asthma in US $ Million
• Exhibit 4.13 Approved MAb for the Treatment of Transplantation
• Exhibit 5.1 List of Approved Therapeutic Monoclonal Antibodies for Major Markets, September 2006
• Exhibit 5.2 List of Therapeutic Monoclonal Antibodies Approved for Additional Indications, September 2006
• Exhibit 5.3 Therapeutic Categories of Approved MAbs
• Exhibit 5.4 Types of MAbs Approved Between 1986 and 2006
• Exhibit 5.5 Types of MAbs Currently in Development
• Exhibit 5.6 List of Monoclonal Antibody Therapeutics in Development (assembled by alphabetized company names)
• Exhibit 5.7 List of Monoclonal Antibody Therapeutics in Development (assembled by therapeutic indication in alphabetical order)
• Exhibit 5.8 Therapeutic Categories of Clinical Trials
• Exhibit 5.9 Therapeutic Antibodies at Various Development Stages
• Exhibit 5.10 List of Late-Stage Clinical Trial Failures
• Exhibit 6.1 Distribution of Cell Culture Reactor Capability by Reactor Volume, Projected for 2006
• Exhibit 6.2 Selected North American Contract Manufacturer, Primarily of Biotherapeutics
• Exhibit 6.3 Selected Contract Manufacturers Outside of North America
• Exhibit 6.4 Selected Manufacturers Offering Excess Capacity Contracts
• Exhibit 6.5 Native and Engineered Disulfide Bond formation Pathways in the E. coli Periplasm
• Exhibit 6.6 A comparison of Widely Used Cell Lines for the Manufacturing of Biotherapeutics
• Exhibit 6.7 Processing of Asn-linked Oligosaccharides to a Representative Biantennary Complex Glycoprotein Structure
• Exhibit 7.1 Selected Companies with Antibody Discovery Platforms Which Formed Alliances in the Discovery and Development of Antibody Therapeutics
• Exhibit 7.2 Selected Companies with Antibody Engineering and Expression Platforms Which Formed Alliances
• Exhibit 7.3 Valuation of Collaborations
• Exhibit 7.4 Selected M&As In 2005 And Early 2006
• Exhibit 7.5 Detailed List of Alliances Involving a Selected Number of Antibody Drug Discovery and Development Companies
• Exhibit 8.1 Issued Patents of Xencor
• Exhibit 8.2 Patent Applications of Xencor
• Exhibit 8.3 Additional Patent Applications Related to Enhanced Antibody Function
• Exhibit 8.4 Issued Patents of Kyowa Hakko and BioWa
• Exhibit 8.5 Patent Applications of Kyowa Hakko and BioWa
• Exhibit 8.6 Flow-chart Showing Various Technologies Important for MAb Discovery, Modulation and Production and the Primary IP Holders of the Technologies
• Exhibit 8.7 Key Antibody Phage Display patents of Cambridge Antibody Technology
• Exhibit 8.8 Single-chain Antibody IP Portfolio of Micromet/Enzon
• Exhibit 8.9 A Selected List of Relevant US Patents
• Exhibit 9.1 Yearly Fundraising by the Biotechnology Industry
• Exhibit 9.2 Status of Market Capitalization of a Selected Group of Antibody Companies
• Exhibit 9.3 Major Monoclonal Antibody Sales, 2003- 2005
• Exhibit 9.4 Yearly Revenues Earned and Forecasted for Antibody Therapeutics
• Exhibit 9.5 Annual Sale of Rituxan® in $ million, 2001 - 2005
• Exhibit 9.6 Annual Sale of Herceptin® in $ million, 2000 - 2003
• Exhibit 9.7 Revenues Generated by RemicadeR, 2000 - 2005
• Exhibit 9.8 Revenues Generated by SynagisR, 2000 - 2005
• Exhibit 9.9 Quarterly Sales of Synagis® from 2001 to 2005
• Exhibit 9.10 Comparative Sales of Humira™ and Avastin™, 2003 to 2005
• Exhibit 9.11 Current and Projected Sales of Avastin™