Table of Contents

TABLE OF CONTENTS

CHAPTER ONE: EXECUTIVE SUMMARY

• Introduction, Background, & Definition
• Introduction
  • A Period of Rapid Developments
  • Further Longer-Term Challenges
  • Rapid Growth Overall, But Intense Competition
  • Moving Into New Applications and Segments
  • Customers’ Research Models Evolving
  • Second-Generation Systems Getting Established
• Background
  • Scope and Methodology
  • Applications and Definitions
  • Types of Samples
  • DNA Sequencing Strategies
  • DNA Sequencing Chemistries and Techniques
• Sanger Sequencing
• Reversible Terminators
• Single Nucleotide Addition; Pyrosequencing

CHAPTER TWO: SEQUENCER MARKET TRENDS

• Industry and Technology Trends
• Continual Improvements Expand Next-Generation Market
• Spread of Targeted Enrichment, Sequence-Capture Products and Services
• Synergies Appearing Between Life Science Companies’ Products
• SNP and Other Experiments Moving to Sequencing for Higher Detail
• Market Fragmenting Into Multiple Applications, Products
• Miniaturization of Sanger and CE Technology
• Rise of Consumer Genomics, Genetic Testing
• Genome Sequencing Trends
  • Continued Acceleration in Sequence Output
  • Phylogenetic Breakout of Genome Sequencing Projects
  • Technologies Used in Genome Projects
  • Types of Genome Projects in GOLD Database
  • Technologies Used in Genome Projects by Type of Project
  • Technologies Used in Genome Projects by Country
  • Countries Leading Genome Projects
  • Technologies Used in Genome Projects by Institution
  • Technologies Used in Genome Projects by Funding Organization
  • Technologies Used in Genome Projects by Domain
  • Phenotypes of Genomes Being Sequenced
  • Diseases / Conditions Associated With Genomes Being Sequenced
  • Phylogenetic Breakout of Eukaryotic Genome Projects
• Funding Trends, Genome Centers, Consortia
  • Introduction
  • Major Sequencing Centers
  • Major Funding Sources
  • Annual Funding of Genome Projects by Organization
  • Funding Relevance of Bacterial Sequencing Projects
  • Funding Relevance of Non-Bacterial Genome Project
  • NHGRI Annual Funding, Budget, Periodic Strategic Planning
  • NHGRI Funds Large-Scale Sequencing Center
  • NHGRI White Paper #4: The Future of Genome Sequencing
  • The Cancer Genome Atlas Project
  • Cancer Sequencing Projec
  • FUGE – Functional Genomics in Norway
  • National Plant Genome Initiative
  • NSF / USDA Microbial Genome Sequencing Programs
  • Other Initiatives and Consortia

CHAPTER THREE: DNA SEQUENCER PRODUCTS

• 454 Life Sciences (Branford, CT) / Roche
  • Genome Sequencer FLX
• Applied Biosystems (Foster City, CA)
  • ABI Prism 310 Genetic Analyzer
  • ABI Prism 3100-Avant Genetic Analyzer
  • Applied Biosystems 3100 Genetic Analyzer
  • Applied Biosystems 3130 Genetic Analyzer
  • Applied Biosystems 3130xl Genetic Analyzer
  • Applied Biosystems 3500 Genetic Analyzer
  • Applied Biosystems 3730 DNA Analyzer
  • Applied Biosystems 3730xl DNA Analyzer
  • SOLiD 3
• Beckman Coulter
  • CEQ 8000; CEQ 8800
  • GenomeLab GeXP Genetic Analysis System
• Dover Systems (Danaher Motion)
  • Polonator G.007
  • GE Healthcare
  • MegaBACE 500
  • MegaBACE 750
  • MegaBACE 1000
  • MegaBACE 1500
  • MegaBACE 4000
• Helicos Biosciences
  • Helicos Genetic Analysis System
• Illumina / Solexa
  • Illumina Genome Analyzer II
• LI-COR Biosciences (Lincoln, NE)
  • 4300
• Pacific Biosciences
  • SMRT Technology

CHAPTER FOUR: DNA SEQUENCER MARKET FORECAST

• Revenues and Forecast
• Current Market (01-08)
• Forecasted Market: ABI as a Market Bellweather
• Growth Indicators

CHAPTER FIVE: COMPETITIVE ANALYSIS OF SEQUENCER MARKET

• Introduction
• Next- and Next-Next-Generation Creating Turbulence
• Capillary Electrophoresis Maintains Large Segment
• Second-, Third-Generation Battle Still Up in the Air
• DNA Sequencer Market Shares
• Features and Strengths of Second-Generation Sequencers
  • 454 Life Sciences GS FLX – Strengths / Advantages
  • 454 Life Sciences GS FLX – Weaknesses / Disadvantages
  • Applied Biosystems SOLiD – Strength / Advantages
  • Applied Biosystems SOLiD – Weaknesses / Disadvantages
  • Illumina Genome Analyzer – Strength / Advantages
  • Illumina Genome Analyzer – Weaknesses / Disadvantages

CHAPTER SIX: INTELLECTUAL PROPERTY AND LITIGATION

• Patent Interference Between Life Technologies and Pacific Biosciences
• Helicos Appeals European Patent Office Decision on Illumina Patent
• Illumina Files ‘841 Patent Infringement Suit Against Affymetrix
• Affymetrix and Illumina Settle Case Over ‘243, ‘432, ‘531, ‘365, and ‘716
• Applied Biosystems and Illumina Claims and Counter-claims Both Unsuccessful
• Fluidigm and Applied Biosystems Agree to End Case
• Beckman Coulter and Applied Biosystems Settle Outstanding Legal Disputes
• Cepheid and Idaho Technology Settle Dispute Over PCR Patents
• Enzo Biochem Disputes CalTech Sequencing Patents
• Huang v. CalTech
• Applied Biosystems and Amersham plc (GE Healthcare) Settle Sequencing Patent Litigation

CHAPTER SEVEN: DEALS

• Significant DNA Sequencing Equipment Deals

CHAPTER EIGHT: CORPORATE PROFILES

• 454 Life Sciences / Roche
• Applied Biosystems / Life Technologies
• Beckman Coulter (Fullerton, CA)
• GE Healthcare Life Sciences
• Helicos Biosciences
• Illumina / Solexa
• LI-COR Biosciences (Lincoln, NE)

CHAPTER NINE: TECHNOLOGIES UNDER DEVELOPMENT

• Introduction
• Human Microbiome Project Awards Funds for Technology Development, Data Analysis and Ethical Research
• NHGRI Seeks DNA Sequencing Technologies Fit for Routine Laboratory and Medical Use, August 2008
• Arizona State University, Tempe
  • “Sequencing by Recognition”
• Harvard College
  • “Electronic Sequencing in Nanopores”
• Oak Ridge National Laboratory / UT Battelle
  • “DNA Transport and Sequencing Through a Quadrupole Gate”
• Princeton University
  • “Nanogap Detector (Arrays) Inside Nanofluidic Channel for Fast Real-Time DNA Sequencing”
• University of Arkansas, Fayetteville
  • “Exploration of Solid-State Nanopore Reading Labeled Linear DNA Sequence”
• University of California, San Diego
  • “Genome Sequencing by Natural DNA Synthesis on Amplified DNA Clones”
• University of Pennsylvania, Philadelphia
  • “DNA Sequencing Using Nanopore-Nanoelectrode Devices for Sensing and Manipulation”
• University of Pittsburgh
  • “DNA Sequencing at a Stretch”
• Columbia University
  • “DNA Sequencing with Reversible dNTP and Cleavable Fluorescent ddNTP Terminators”
• Foundation for Applied Molecular Evolution, Inc.
  • “Near Term Development of Reagents and Enzymes for Genome Sequencing”
• Illumina
  • “Development of a 10Gb Pyrosequencer”
• NHGRI Seeks to Advance Next Generation of Sequencing Technologies, August 2007
• Arizona State University, Tempe
  • “Sequencing by Recognition”
• Brown University
  • “Hybridization-assisted Nanopore DNA Sequencing”
• Duke University
  • “Continuous Sequencing-by-Synthesis Based on a Digital Microfluidic Platform”
• NABsys, Inc.
  • “Hybridization-assisted Nanopore Sequencing”
• North Carolina State University, Raleigh
  • “Sequencing DNA by Transverse Electrical Measurements in Nanochannels”
• UMDNJ-New Jersey Medical School
  • “Ribosome-based Single Molecule Method to Acquire Sequence Data from Genomes”
• University of British Columbia, Vancouver
  • “Nanopore Array Force Spectroscopy Chip for Rapid Clinical Genotyping”
• University of California, Irvine
  • “High Throughput Low Cost DNA Sequencing Using Probe Tip Arrays”
• Columbia University
  • “3′-O-Modified Nucleotide Reversible Terminators for Pyrosequencing”
• “An Integrated System for DNA Sequencing by Synthesis”
• University of New Mexico School of Medicine, Albuquerque
  • “Polony Sequencing the Human Genome”
• University of Wisconsin, Madison
  • “Sequence Acquisition from Mapped Single DNA Molecules”
• “NHGRI Aims to Make DNA Sequencing Faster, More Cost Effective”, October 2006
• Arizona State University
  • “Fabrication of Universal DNA Nanoarrays for Sequencing by Hybridization”
• Boston University
  • “High-Throughput DNA Sequencing Using Design Polymers and Nanopore Arrays”
• Case Western Reserve University
  • “Large-Scale Nanopore Arrays for DNA Sequencing”
• General Electric Global Research
  • “Closed Complex Single Molecule Sequencing”
• Helicos Biosciences
  • “High Accuracy Single Molecule DNA Sequencing by Synthesis”
• Lehigh University
  • “Force Spectroscopy Platform for Label Free Genome Sequencing”
• University of California, San Diego
  • “Genome Sequencing by Ligation Using Nano-Arrays of Single DNA Molecules”
• University of North Carolina, Chapel Hill
  • “Nanoscale Fluidic Technologies for Rapidly Sequencing Single DNA Molecules”
• University of Washington, Seattle
  • “Engineering MspA for Nanopore Sequencing”
• Baylor College of Medicine, HGSC
  • “Ultrafast SBS Method for Large-Scale Human Resequencing”
• Intelligent Bio-Systems
  • “High-Throughput DNA Sequencing by Synthesis Platform”
• NHGRI Expands Effort to Revolutionize Sequencing Technologies, August 2005
• Agencourt Personal Genomics [Applied Biosystems / Life Technologies]
  • “Bead-Based Polony Sequencing (Supplemental)”
• Network Biosystems
  • “$100,000 Genome Using Integrated Microfluidic CE”
• The State University of New York, Stony Brook (SUNY)
  • “Ultra High Throughput DNA Sequencing System Based on 2D Monolith Multi-Capillary Arrays and Nanoliter Reaction Volume”
• Columbia University
  • “Modulating Nucleotide Size in DNA for Detection by Nanopore”
• Duke University
  • “Droplet-Based Digital Microfluidic Genome Sequencing”
• Harvard University
  • “Electronic Sequencing in Nanopores”
• Pacific Biosciences (formerly Nanofluidics)
  • “Real-Time Multiplex Single-Molecule DNA Sequencing”
• New York University
  • “Haplotype Sequencing Via Single Molecule Hybridization”
• Oxford University and The Scripps Research Institute
  • “Single-Molecule DNA Sequencing with Engineered Nanopores”
• University of California, San Diego
  • “Massively Parallel Cloning and Sequencing of DNA”
• University of Illinois at Urbana-Champaign
  • “Sequencing a DNA Molecule Using a Synthetic Nanopore”
• VisiGen Biotechnologies
  • “Real-Time DNA Sequencing”
• NHGRI Funds Next Generation of Sequencing Technologies, October 2004

CHAPTER TEN: CHALLENGES AND STRATEGIC RECOMMENDATIONS

• Market Challenges
  • Challenge #1
  • Challenge #2
  • Challenge #3
  • Challenge #3
  • Challenge #4
  • Challenge #5
  • Challenge $6
  • Challenge #7
• Strategic Recommendations
  • Recommendation #1
  • Recommendation #2
  • Recommendation #3
  • Recommendation #4
  • Recommendation #5
  • Recommendation #6

LIST OF EXHIBITS

CHAPTER TWO: SEQUENCER MARKET TRENDS

• Table 2-1: Completely Sequenced Genomes in GOLD, 1995-2008(Without Publication, With Publication)
• Figure 2-1: Completely Sequenced Genomes in GOLD, 1999-2008
• Table 2-2: Domains of Completed Genomes in GOLD by Year, 1995-2008 (Archaes’, Bacteria, Eukaryota’)
• Figure 2-2: Domains of Completely Sequenced Genomes in GOLD by Year, 1999-2008 (Archaes’, Bacteria, Eukaryota’)
• Table 2-3: Genome Projects in IMG by Domain, 2005-2008 (Cumulative)
• Figure 2-3: Genome Projects in IMG by Domain, 2005-2008 (Cumulative)
• Table 2-4: Phylogenetic Groups of Sequencing Projects in GOLD, 1998-2008 (Cumulative)
• Figure 2-4: Phylogenetic Groups of Sequencing Projects in GOLD, 1998-2008 (Cumulative)
• Table 2-5: Phylogenetic Distribution of Bacterial Genome Projects, Q1 2007
• Figure 2-5: Phylogenetic Distribution, Bacterial Genome Projects, Q1 2007
• Table 2-6: Phylogenetic Distribution of Bacterial Genome Projects, Q1 2009
• Figure 2-6: Phylogenetic Distribution, Bacterial Genome Projects, Q1 2009
• Table 2-7: Category / Phylogeny of Metagenomics Projects (Cumulative)
• Figure 2-7: Category/Phylogeny of Metagenomics Projects in GOLD, 2008-2009 Cumulative
• Table 2-8: Technology Used in Genome Projects, ’95-Q1’09
• Figure 2-8: Sequencer Technology Used in Genome Projects ’95-Q1’09
• Table 2-9: Types of Projects in GOLD, ‘95-Q1’09
• Figure 2-9: Types of Projects in GOLD, ‘95-Q1’09 (Cumulative)
• Table 2-10: Systems Used in Genome Projects by Type, ’95-Q1’09 (Sanger, Illumina)
• Table 2-11: Systems Used in Genome Projects by Type, ’95-Q1’09
• Table 2-12: Systems Used in Genome Projects by Type, ’95-Q1’09 Figure 2-10: Systems Used in Genome Projects by Type, ’95-Q1’09
• Table 2-13: Systems Used in Genome Projects by Country, ’95-Q1’09
• Table 2-14: Systems Used in Genome Projects by Country, ’95-Q1’09
• Figure 2-11: Systems Used in Genome Projects by Country, ’95-Q1’09
• Table 2-15: Countries Leading Projects, ’95-Q1’09
• Figure 2-12: Countries Leading Projects, ’95-Q1 ’09
• Table 2-16: Systems Used in Genome Projects by Institute, ’95-Q1’09
• Table 2-17: Systems Used in Genome Projects by Inst, ’95-Q1’09 Figure 2-13: Systems Used in Genome Projects by Inst, ’95-Q1’09
• Table 2-18: Systems Used in Genome Projects by Funding Org., ’95-Q1’09
• Table 2-19: Systems Used in Genome Projects by Funding Organization, ’95-Q1’09
• Figure 2-14: Systems Used in Genome Projects by Funding Organization, ’95-Q1’09
• Table 2-20: System Used in Genome Projects by Domain, ’95-Q1’09
• Table 2-21: System Used in Genome Projects by Domain, ’95-Q1’09
• Table 2-22: System Used in Genome Projects by Domain, ’95-Q1’09
• Figure 2-15: Systems Used in Genome Projects by Domain, ’95-Q1’09
• Figure 2-16: Systems Used in Genome Projects by Domain, ’95-Q1’09
• Table 2-23: Phenotypes of Projects in GOLD, ’95-Q1 ’09
• Figure 2-17: Phenotypes of Projects in GOLD, ’95-Q1 ’09
• Table 2-24: Diseases/Conditions Associated with Projects, ’95-Q1’09
• Figure 2-18: Diseases/Conditions Associated with Projects, ’95-Q1 ’09
• Table 2-25: Eukaryotic Genome Projects in GOLD, ’07-09
• Figure 2-19: Eukaryotic Genome Projects in GOLD, ’07-’09 (Cumulative)
• Table 2-26: Number of Genome Projects by Institute, ’95- Q1 ’09
• Figure 2-20 Number of Genome Projects by Institute, ’95- Q1 ’09 Cumulative
• Table 2-26 Funding Sources of Genome Projects, ’95-Q1 ’09
• Figure 2-21: Funding Sources of Genome Projects, ’95-Q1 ’09
• Table 2-26: Funding of Genome Projects by Organization, Q1’07-Q1’09
• Figure 2-21: Funding of Genome Projects, 2007-2009 ($M)
• Figure 2-22: Human Genome Project Funding, DOE & NIH ’90-’03
• Table 2-27: Relevance of Bacterial Sequencing Projects, ’95 – Q1 ’09, (Cumulative)
• Figure 2-23: Relevance of Bacterial Sequencing Projects, ’95- Q1 ’09 (Cumulative)
• Table 2-28: Relevance of Non-Bacterial Sequencing Project, ’95 – Q1 ’09, (Cumulative)
• Figure 2-24: Relevance of Non-Bacterial Sequencing Projects, ’95- Q1 ’09 (Cumulative)
• Table 2-29: NHGRI Budget by Year
• Figure 2-25: NHGRI Budget by Year incl. ARRA, 2006-2010
• Table 2-30: 2010 Estimated NHGRI Budget by Mechanism
• Figure 2-26: 2010 Estimated NHGRI Budget by Mechanism (percent)
• Table 2-31: NHGRI Budget by Activity, 2008-2010 (Medical Sequencing, Genomic Function, Technology Development, Computation Genomics, Large-scale Sequencing
• Table 2-32: NHGRI Extramural Budget, 2006-2010
• Figure 2-27: NHGRI Extramural Budget by Activity, 2008 Comparable
• Figure 2-28: NHGRI Extramural Budget by Activity, 2009 Estimated
• Figure 2-9: NHGRI Extramural Budget by Activity, 2010 Estimated
• Table 2-33: NHGRI Budget by Mechanism (No. And Amount), FY 2008, FY 2009 and FY2010
• Table 2-34: Large-Scale Sequencing Centers NHGRI Funding, 2004-2006
• Figure 2-10: NHGRI Funded Large-Scale Sequencing Centers ’04-’06
• Table 2-34: Large-Scale Sequencing Centers NHGRI Funding by Year, 2007-2008
• Figure 2-11: NHGRI Funded Large-Scale Sequencing Centers ’07-’08
• Figure 2-12: Broad Institute Organizational Structure
• Table 2-35: FUGE Funding Recipients
• Table 2-36: Plant Genome Comparative Sequencing Program (PGCSP) Awards, 2007-2008
• Table 2-37: Plant Genome Research Program GEPR, TRMS, and TRPGR Awards, 2007
• Table 2-38: Plant Genome Research Program GEPR, TRMS, and TRPGR Awards, 2008 (Institution, Title, Total Award, Duration)
• Table 2-39: NSF / USDA Microbial Genome Sequencing Program Awards, 2007-2009
• Table 2-40: Other Initiatives and Consortia Supporting Technology Development, 2009Table 2-41: Other Initiatives and Consortia Performing DNA Sequencing, 2009
• Table 2-41: Other Initiatives and Consortia Performing DNA Sequencing, 2009
• Table 2-41 (continued): Other Initiatives and Consortia Performing DNA Sequencing, 2009

CHAPTER THREE: PRODUCTS

• Table 3-1: Key Systems and Technologies Currently in the Market (Company, Product, Comments)

CHAPTER FOUR: MARKETS

• Table 4-1: Revenues, 2001-2008 DNA Sequencer Equipment
• Table 4-2: Growth Rate, 2001-2008 DNA Sequencer Equipment
• Figure 4-1: Revenues, DNA Sequencer Equipment Market, ’01-’08
• Figure 4-2: ABI Sequencing Revenues, Q3 2001 – Q3 2008
• Figure 4-3: ABI Sequencing Revenues, Q4 2004 – Q3 2008
• Figure 4-4: Cost of Sequencing a Genome
• Table 4-3: 2008-2014 DNA Sequencer Equipment Market Forecast
• Figure 4-5: DNA Sequencer Equipment Market Forecast, 2008-2014
• Table 4-4: Growth Rate, 2008-2014 DNA Sequencer Equipment
• Figure 4-6: Growth Rate, DNA Sequencers, 2008-2014

CHAPTER FIVE: COMPETITIVE ANALYSIS OF SEQUENCER MARKET

• Table 5-1: Revenues & Market Shares, DNA Sequencer Systems, 2006 & 2008
• Figure 5-1: Estimated DNA Sequencer Revenues by Company, 2006 & 2008
• Table 5-2: Comparison of Second-Generation Sequencers, 2007
• Table 5-3: Comparison of Second-Generation Sequencers, 2009

CHAPTER SIX: INTELLECTUAL PROPERTY AND LITIGATION

• Table 6-1: Select Early Sequencing-Related Patents Assigned or Licensed to Life Technologies / Applied Biosystems

CHAPTER SEVEN: DEALS

• Table 7-1: Significant Deals in the DNA Sequencing Equipment and Services Market

CHAPTER NINE: TECHNOLOGIES UNDER DEVELOPMENT

• Table 9-1: NIH Human Microbiome Project Technology Development Awards, 2008
• Table 9-2: NHGRI $1000 Genome Grant Awardees, August 2008
• Table 9-3: NHGRI $100,000 Genome Grant Awardees, August 2008
• Table 9-4: NHGRI $1000 Genome Grant Awardees, August 2007
• Table 9-5: NHGRI $100,000 Genome Grant Awardees, August 2007
• Table 9-6: NHGRI $1000 Genome Grant Awardees, October 2006
• Table 9-7: NHGRI $100,000 Genome Grant Awardees, October 2006
• Table 9-8: NHGRI $100,000 Genome Grant Awardees, August 2005
• Table 9-9: NHGRI $1000 Genome Grant Awardees, August 2005
• Table 9-10: NHGRI $100,000 Genome Grant Awardees, October 2004
• Table 9-11: NHGRI $1000 Genome Grant Awardees, October 2004