臨床におけるプロテオミクス：プロテインバイオマーカー発見アプローチの再検討

Abstract

Protein biomarkers are appealing to drug developers because they can be used early in the drug research pipeline, which allows early elimination of ineffective or toxic compounds. Although the promise of these biomarkers is clear, the path to successful implementation of protein biomarkers is not. Perhaps the discovery-based approach is not the best way to tap the potential of protein biomarkers.

• Despite scientifi c advancements, protein biomarker discovery is slowing. What are the challenges facing companies and researchers that are hindering the discovery process?
• Researchers are rethinking the discovery-based approach. What other options and innovations are available? What companies are leading the way?
• The future of protein biomarkers is extremely promising for a multitude of businesses. What benefi ts are available for technology vendors, Big Pharma companies, researchers, and regulatory agencies? Can collaboration between any or all of these stakeholders ensure the success of protein biomarkers?

• Proteomics technologies: 2D PAGE, mass spectrometry, antibody microarrays, microfl uidics, label-free technologies.
• Alternatives to discovery-based approach: hypothesis-based approach, engineering better biomarkers, systems biology.
• Major players in protein biomarker discovery: Bayer, Eli Lilly, Novartis, Pfi zer, Roche.
• Outlook: The path toward successful protein biomarker discovery may include multiplexing strategies, collaborations among researchers and developers, and support from regulatory bodies.

Companies Mentioned in This Spectrum Report

• Applied Biosystems
• Axis Shield
• Bayer Pharmaceuticals
• Beyond Genomics
• Biacore
• Bioforce Nanoscience
• Bio-Rad
• Biosite
• Bruker Daltonics
• Cantion
• Clontech
• CODA Genomics
• Eisai
• Eli Lilly
• Fujirebio
• Gene News
• Genedata
• GeneProt
• Geneva Proteomics
• Genomic Solutions
• Genoptics
• GenTel Biosciences
• Integrated Genomics
• Invitrogen
• Johnson & Johnson
• Lumera
• Matritech
• Microfl uidics
• Millennium Pharmaceuticals
• Pfi zer
• Phadia US
• Power3 Medical Products
• Predictive Diagnostics
• Proteome Systems
• Quadraspec
• RBM
• Roche
• Rosetta Inpharmatics
• Sareum
• Shimadzu
• Target Discovery

Table of Contents

• Executive Summary
  • Strategic Considerations
  • Stakeholder Implications
• The State of the Art
• Key Proteomics Technologies
  • Two-Dimensional Polyacrylamide Gel Electrophoresis
  • Mass Spectrometry
  • Antibody Microarrays
  • Microfl uidics
  • Label-Free Technologies
• The Pipeline Problem: Why Is Discovery Slowing?
  • Challenges of Discovering Protein Biomarkers
  • The Imperfect Process of Discovering Protein Biomarkers
  • From Biomarker Discovery to Diagnostic Development
• Expanding Discovery-Based Research
  • Hypothesis-Based Approach
  • Engineering Better Biomarkers
  • Systems Biology
• Major Players in Protein Biomarker Discovery
  • Bayer Pharmaceuticals
  • Eli Lilly
  • Novartis
  • Pfi zer
  • Roche
• Sidebar: Eli Lilly' s Biomarker Development Strategy for Sepsis- A Case Study
• Outlook for Protein Biomarkers
  • Rethinking Discovery-Based Research
    • Looking Beyond Pattern-Only Discovery
    • Multiplexing Leads the Way
  • Supportive Regulatory Environment: The FDA Process
  • Building Strong Collaborations

• 1. Select Commercially Available Protein-Based Diagnostics
• 2. Proteomics Business Models
• 3. Key Proteomics Technology Vendors and Service Providers
• 4. Emerging Players in Protein Biomarker Discovery
• 5. FDA Critical Path Opportunities for Biomarkers
• 6. Considerations for Choosing a Diagnostic Development Partner

• 1. The 1,175 Identifi ed Proteins of the Human Plasma Proteome
• 2. Number of Novel Protein Analytes in FDA-Approved Diagnostic Tests, 1994-2002
• 3. Sensitivities and Specifi cities of Select FDA-Approved Protein Biomarkers
• 4. Alternate Approach: Suggested Technology Workfl ow for Developing Protein Biomarkers
• 5. Drug-Device Codevelopment Process: Key Steps During Development