DNA Sequencing Equipment and Services Markets, 2nd Edition

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DNA Sequencing Equipment and Services Markets, 2nd Edition

August 1, 2009

Since the last edition of Kalorama Information's DNA Sequencing Equipment and
Services report, the market has been changing in unpredictable ways as second-
generation sequencers are being incrementally introduced and upgraded. On the
surface, the situation has become somewhat linear and predictable, but as Kalorama
Information biotech analyst Justin Saeks explains, it is actually a unique and relatively
volatile situation that is not seen often with life science tools markets. Third-generation
systems have the potential to completely change the market, or to simply join the pack.

Revenue growth has been unusually high, and all of the trends seem to indicate that
growth will continue in the near term. It is likely that completely new technologies will be
introduced at least every year or two, while second-generation sequencer
improvements also continue. In Kalorama Information biotech analyst Justin Saek's 2nd
edition of DNA Sequencing Equipment and Services Markets, these changes are
detailed and put in context, along with the following:

• DNA Sequencer Revenues by Industry and by Leading Systems
• Forecast of Sequencer Revenues to 2014
• Review of Important Sequencers and Comparison of Features and Drawbacks.
• Profiles of Major Companies in the Marketplace
• Affymetrix and Illumina Settlement and other Significant Litigation in the
Industry
• Major Industry Deals since 2008, Review of Deals 05-07, and Analyst
Commentary
• Over 70 Figures and Tables making market information accessible
• Review of Major Deals and Litigation affecting the marketplace.
• Review of Technologies Under Development
• Discussion of Funding Sources and Recent Grant Awardees
• Strategic Recommendations for Companies Operating in the DNA Sequencing
Market

Kalorama Information's DNA Sequencing Equipment and Service Markets represents
research culled from a variety of secondary sources. But the true insights originated

from interviews with market experts; these interviews were used to confirm numbers
and test forecast assumptions.

Companies profiled in the report include:

• 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)

Table of Contents

CHAPTER ONE: EXECUTIVE SUMMARY

• Introduction, Background, & Definition
• Introduction
o A Period of Rapid Developments
o Further Longer-Term Challenges
o Rapid Growth Overall, But Intense Competition
o Moving Into New Applications and Segments
o Customers’ Research Models Evolving
o Second-Generation Systems Getting Established
• Background
o Scope and Methodology
o Applications and Definitions
o Types of Samples
o DNA Sequencing Strategies
o 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
o Continued Acceleration in Sequence Output
o Phylogenetic Breakout of Genome Sequencing Projects
o Technologies Used in Genome Projects
o Types of Genome Projects in GOLD Database
o Technologies Used in Genome Projects by Type of Project
o Technologies Used in Genome Projects by Country
o Countries Leading Genome Projects
o Technologies Used in Genome Projects by Institution
o Technologies Used in Genome Projects by Funding Organization
o Technologies Used in Genome Projects by Domain
o Phenotypes of Genomes Being Sequenced
o Diseases / Conditions Associated With Genomes Being Sequenced
o Phylogenetic Breakout of Eukaryotic Genome Projects
• Funding Trends, Genome Centers, Consortia
o Introduction
o Major Sequencing Centers
o Major Funding Sources
o Annual Funding of Genome Projects by Organization
o Funding Relevance of Bacterial Sequencing Projects
o Funding Relevance of Non-Bacterial Genome Project
o NHGRI Annual Funding, Budget, Periodic Strategic Planning
o NHGRI Funds Large-Scale Sequencing Center
o NHGRI White Paper #4: The Future of Genome Sequencing
o The Cancer Genome Atlas Project
o Cancer Sequencing Projec
o FUGE - Functional Genomics in Norway
o National Plant Genome Initiative
o NSF / USDA Microbial Genome Sequencing Programs
o Other Initiatives and Consortia

CHAPTER THREE: DNA SEQUENCER PRODUCTS

• 454 Life Sciences (Branford, CT) / Roche
o Genome Sequencer FLX
• Applied Biosystems (Foster City, CA)
o ABI Prism 310 Genetic Analyzer
o ABI Prism 3100-Avant Genetic Analyzer
o Applied Biosystems 3100 Genetic Analyzer
o Applied Biosystems 3130xl Genetic Analyzer
o Applied Biosystems 3730 DNA Analyzer
o Applied Biosystems 3730xl DNA Analyzer
o SOLiD 3

• Beckman Coulter
o CEQ 8000; CEQ 8800
o GenomeLab GeXP Genetic Analysis System
• Dover Systems (Danaher Motion)
o Polonator G.007
o GE Healthcare
o MegaBACE 500
o MegaBACE 750
o MegaBACE 1000
o MegaBACE 1500
o MegaBACE 4000
o Helicos Genetic Analysis System
o Illumina Genome Analyzer II
o 4300
• Pacific Biosciences
o 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
o 454 Life Sciences GS FLX - Strengths / Advantages
o 454 Life Sciences GS FLX - Weaknesses / Disadvantages
o Applied Biosystems SOLiD - Strength / Advantages
o Applied Biosystems SOLiD - Weaknesses / Disadvantages
o Illumina Genome Analyzer - Strength / Advantages
o 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

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
o “Sequencing by Recognition”
• Harvard College
o “Electronic Sequencing in Nanopores”
• Oak Ridge National Laboratory / UT Battelle
o “DNA Transport and Sequencing Through a Quadrupole Gate”
• Princeton University
o “Nanogap Detector (Arrays) Inside Nanofluidic Channel for Fast Real-
Time DNA Sequencing”
• University of Arkansas, Fayetteville
o “Exploration of Solid-State Nanopore Reading Labeled Linear DNA
Sequence”
• University of California, San Diego

o “Genome Sequencing by Natural DNA Synthesis on Amplified DNA
Clones”
• University of Pennsylvania, Philadelphia
o “DNA Sequencing Using Nanopore-Nanoelectrode Devices for Sensing
and Manipulation”
• University of Pittsburgh
o “DNA Sequencing at a Stretch”
• Columbia University
o “DNA Sequencing with Reversible dNTP and Cleavable Fluorescent
ddNTP Terminators”
• Foundation for Applied Molecular Evolution, Inc.
o “Near Term Development of Reagents and Enzymes for Genome
Sequencing”
• Illumina
o “Development of a 10Gb Pyrosequencer”
• NHGRI Seeks to Advance Next Generation of Sequencing Technologies, August
2007
• Arizona State University, Tempe
o “Sequencing by Recognition”
• Brown University
o “Hybridization-assisted Nanopore DNA Sequencing”
• Duke University
o “Continuous Sequencing-by-Synthesis Based on a Digital Microfluidic
Platform”
• NABsys, Inc.
o “Hybridization-assisted Nanopore Sequencing”
• North Carolina State University, Raleigh
o “Sequencing DNA by Transverse Electrical Measurements in
Nanochannels”
• UMDNJ-New Jersey Medical School
o “Ribosome-based Single Molecule Method to Acquire Sequence Data
from Genomes”
• University of British Columbia, Vancouver
o “Nanopore Array Force Spectroscopy Chip for Rapid Clinical Genotyping”
• University of California, Irvine
o “High Throughput Low Cost DNA Sequencing Using Probe Tip Arrays”

Columbia University

o “3'-O-Modified Nucleotide Reversible Terminators for Pyrosequencing”

“An Integrated System for DNA Sequencing by Synthesis”

• University of New Mexico School of Medicine, Albuquerque
o “Polony Sequencing the Human Genome”
• University of Wisconsin, Madison

o “Sequence Acquisition from Mapped Single DNA Molecules”
• “NHGRI Aims to Make DNA Sequencing Faster, More Cost Effective”, October
2006
• Arizona State University
o “Fabrication of Universal DNA Nanoarrays for Sequencing by
Hybridization”
• Boston University
o “High-Throughput DNA Sequencing Using Design Polymers and
Nanopore Arrays”
• Case Western Reserve University
o “Large-Scale Nanopore Arrays for DNA Sequencing”
• General Electric Global Research
o “Closed Complex Single Molecule Sequencing”
o “High Accuracy Single Molecule DNA Sequencing by Synthesis”
• Lehigh University
o “Force Spectroscopy Platform for Label Free Genome Sequencing”
o “Genome Sequencing by Ligation Using Nano-Arrays of Single DNA
Molecules”
• University of North Carolina, Chapel Hill
o “Nanoscale Fluidic Technologies for Rapidly Sequencing Single DNA
Molecules”
• University of Washington, Seattle
o “Engineering MspA for Nanopore Sequencing”
• Baylor College of Medicine, HGSC
o “Ultrafast SBS Method for Large-Scale Human Resequencing”
• Intelligent Bio-Systems
o “High-Throughput DNA Sequencing by Synthesis Platform”
• NHGRI Expands Effort to Revolutionize Sequencing Technologies, August 2005
• Agencourt Personal Genomics [Applied Biosystems / Life Technologies]
o “Bead-Based Polony Sequencing (Supplemental)”
• Network Biosystems
o “$100,000 Genome Using Integrated Microfluidic CE”
• The State University of New York, Stony Brook (SUNY)
o “Ultra High Throughput DNA Sequencing System Based on 2D Monolith
Multi-Capillary Arrays and Nanoliter Reaction Volume”
• Columbia University
o “Modulating Nucleotide Size in DNA for Detection by Nanopore”
• Duke University
o “Droplet-Based Digital Microfluidic Genome Sequencing”
• Harvard University
o “Electronic Sequencing in Nanopores”
• Pacific Biosciences (formerly Nanofluidics)
o “Real-Time Multiplex Single-Molecule DNA Sequencing”
• New York University

o “Haplotype Sequencing Via Single Molecule Hybridization”
• Oxford University and The Scripps Research Institute
o “Single-Molecule DNA Sequencing with Engineered Nanopores”
o “Massively Parallel Cloning and Sequencing of DNA”
• University of Illinois at Urbana-Champaign
o “Sequencing a DNA Molecule Using a Synthetic Nanopore”
• VisiGen Biotechnologies
o “Real-Time DNA Sequencing”
• NHGRI Funds Next Generation of Sequencing Technologies, October 2004

CHAPTER TEN: CHALLENGES AND STRATEGIC RECOMMENDATIONS

• Market Challenges
o Challenge #1
o Challenge #2
o Challenge #3
o Challenge #3
o Challenge #4
o Challenge #5
o Challenge $6
o Challenge #7
• Strategic Recommendations
o Recommendation #1
o Recommendation #2
o Recommendation #3
o Recommendation #4
o Recommendation #5
o 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
• 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 9-6: NHGRI $1000 Genome Grant Awardees, October 2006
• Table 9-7: NHGRI $100,000 Genome Grant Awardees, October 2006

• Table 9-10: NHGRI $100,000 Genome Grant Awardees, October 2004
• Table 9-11: NHGRI $1000 Genome Grant Awardees, October 2004

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DNA Sequencing Equipment and Services Markets, 2nd Edition

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DNA Sequencing Equipment and Services Markets, 2nd Edition