TABLE OF CONTENTS

1. Overview 9
1.1 Statement of Report 9
1.2 About This Report 9
1.3 Scope of the Report 9
1.4 Objectives 9
1.5 Methodology 10
1.6 Executive Summary 12

2. Introduction to Molecular Diagnostics and PCR Technology 15
2.1 Science Overview: Introduction to Genomics and Its Opportunity 15
2.2 Impact of the Human Genome Project on Molecular Diagnostics 17
2.3 Considerations for Molecular and Clinical Diagnosis 18
2.4 Molecular Diagnosis in the Post-Genomic Era 19
2.5 Advances in Molecular Diagnostics Technologies 20
2.6 Genetic Variability and Disease 22
2.7 Major Technology Platforms 22
2.7.1 Gene-based Amplification Technologies 23
2.7.2 Detection of Amplified Gene Products 23
2.7.3 Target-Based Gene Amplification 24
2.7.3.1 Polymerase Chain Reaction 24
2.7.3.2 Real-time PCR 25
2.7.3.3 Nucleic Acid Sequence-Based Amplification 26
2.7.4 Probe-Based Amplification 26
2.7.4.1 Ligase Chain Reaction 26
2.7.4.2 Strand Displacement Amplification 26
2.7.4.3 Qß-replicase Amplified Probe Assay 26
2.7.5 Signal-Based Amplification 27
2.7.5.1 Branched DNA (bDNA) 27
2.7.6 Other Gene Amplification Technologies 27
2.7.6.1 Immuno-PCR 27
2.7.6.2 Bio-Barcode Assay 27

3. Nucleic Acid Test Applications 29
3.1 Blood Testing and Infectious Diseases 30
3.1.1 Molecular Diagnostics Market 30
3.1.1.1 Methods for DNA Detection and Gene Sequencing 42
3.1.1.2 Products and Applications 43
3.1.1.3 Oncology 44
3.1.2 SNPs and Genes: Medical Utility (Clinical Applications) 44
3.1.2.1 Clinical Application Initiatives 46
3.1.2.2 A Sampling of Clinical Application Collaborations 47
3.1.2.3 Collaborative Relationships 49
3.2 Diagnostic Testing Using DNA 50
3.2.1 HIV 52
3.2.2 Hepatitis Serologic Markers and Nucleic Acid Testing 54
3.2.2.1 Hepatitis A Virus (HAV) 54
3.2.2.2 Hepatitis B Virus (HBV) 55
3.2.2.3 Hepatitis C Virus (HCV) 58
3.2.2.4 Hepatitis D Virus (HDV) 63
3.2.2.5 Hepatitis E Virus (HEV) 63
3.2.2.6 HBV/HCV Viral Load and Drug Resistance 63
3.2.3 Severe Acute Respiratory Syndrome (SARS) 65
3.2.3.1 New Approach to Diagnosing Avian Influenza 66
3.2.3.2 Microarray or DNA Chip-Based Tests 68
3.2.4 Cancer Detection Using PCR 69
3.2.4.1 Lung Cancer 69
3.2.4.2 Oral Cancer 70
3.2.4.3 Prostate Cancer 70
3.2.4.4 Chronic Myelogenous Leukemia 70
3.2.4.5 Malignant Gliomas 71
3.2.4.6 Colorectal Cancer 71
3.2.4.7 Breast Cancer 71
3.2.4.8 Bladder Cancer 71
3.2.5 Microbiology Testing 71
3.2.5.1 Chlamydia 72
3.2.5.2 Gonorrhea 72
3.2.5.3 Tuberculosis 72
3.2.5.4 Group B Streptococcus 75
3.2.5.5 Pathogenic Enteric Bacteria 77
3.2.5.6 Bordetella pertussis 78
3.2.5.7 Legionella Pneumophila 78
3.2.5.8 Peridontal Bacteria 78
3.2.5.9 Pneumocystis Carinii 78
3.2.5.10 Methicillin-resistant Staphylococcus Aureus 79
3.2.6 Blood Screening 79
3.3 SNPs in Clinical Diagnostics 84
3.3.1 Functional Genomics 88
3.3.2 Paternity Testing 88
3.4 Industrial Testing and Food Diagnostics 89
3.4.1 The Market 89
3.4.2 Detection of H. pylori by PCR 92
3.4.3 Detection of E. coli 0157 92
3.4.4 Detection of Enteric Viruses 92
3.5 Forensics Market 93
3.5.1 Isolation of DNA for PCR Profiling 94
3.5.2 Analysis by PCR-Based DNA Typing 95
3.5.3 Rapid Isolation of DNA for RFLP and PCR 95
3.5.4 DNA for PCR-STR Typing 95
3.6 Bioterrorism and Molecular Diagnostics 95
3.6.1 Introduction 95
3.6.1.1 Current Biological Threat Detection Systems 98
3.6.1.2 Use of DNA Microarrays and Biochips for Gene Expression Profiles in BWA
99
3.6.1.3 Advantages and Disadvantages of Host Gene Expression Profiling as a
Biothreat Detection System 100
3.6.2 Biological Warfare Agents 101
3.6.2.1 Anthrax 101
3.6.2.2 Botulinum Toxin 102
3.6.2.3 Ricin 102
3.6.2.4 IVD Industry and Bioterrorism Preparedness 102
3.6.2.4.1 Brucellosis 102
3.6.2.4.2 Cholera 103
3.6.2.5 Rapid Lateral Flow Immunoassays 104
3.6.2.6 Biosensors 105
3.6.2.6.1 Antibody and Synthetic Receptor-Based Sensors 105
3.6.2.6.2 DNA Sensors 106
3.6.2.6.3 Reagentless Sensors 107
3.6.3 Anthrax in Clinical Samples 108
3.6.3.1 Overview of Anthrax and Its Infectivity 108
3.6.3.2 Rapid Tests 110
3.6.3.2.1 PCR Tests 110
3.7 Cystic Fibrosis Testing 111
3.8 HLA Sequencing-Based Typing Kits 113
3.9 Cytogenetic Testing 115
3.9.1 Hereditary Hemochromatosis 117
3.9.2 Apolipoprotein E (ApoE) Genotyping 117
3.9.3 Fragile X Syndrome 118
3.9.4 Methylenetetrahydrofolate Reductase (MTHFR) Carrier Testing 119
3.10 Developments in Biochips for Clinical Applications 120
3.10.1 Roche AmpliChip Microarray 120
3.10.2 Breast Cancer DNA Chips 120
3.10.3 eSensor DNA Detection System 121
3.11 Pharmacogenomics 122
3.11.1 Coumadin 123
3.12 Thrombic Disorders 125

4. Trends in Molecular Diagnostics 126
4.1 Pharmacogenomics 126
4.1.1 The Market 126
4.1.1.1 Oncology 126
4.1.1.2 Toxicogenomics 126
4.1.2 Market Influences and Forecast 127
4.2 DNA Microarrays 127
4.2.1 Techniques 132
4.2.2 The Market 132
4.2.3 Identification of Sequence SNPs 132
4.2.4 Determining Gene Expression Levels 133
4.2.4.1 Hybridization Tests 133
4.2.4.2 Oligonucleotide Probes 134
4.2.5 Molecular Diagnostics Entry into Point-of-Care Testing 134
4.3 Emerging Markets of DNA Arrays 134
4.3.1 Pharmacogenomics 136
4.3.2 Adoption of Amplified Screening Technology 136
4.3.3 Advances in Automated Testing 136
4.3.4 Increased Focus on Safety of Blood Supply 137
4.3.5 Development of Emerging Markets for NAT Technology 137
4.3.6 Cancer 137
4.3.7 Human Leukocyte Antigen Typing 137
4.3.8 Neonatal Screening 138
4.4 Drivers and Restraints 139
4.5 Market Forecast 140
4.6 Business Trends in the Industry 140
4.6.1 Molecular Diagnostics Industry Trends 140
4.6.1.1 Adoption of Amplified Screening Technology 140
4.6.1.2 Advances in Automated Testing 140
4.6.1.3 Responsiveness to Newly Emerging Threats 141
4.6.1.4 Increased Focus on Safety of Blood Supply 141
4.6.1.5 Growth in Viral Load Testing 141
4.6.1.6 Development of Emerging Markets for NAT Technology 141
4.6.1.7 Improvements in Detection Technologies 142
4.6.2 Pharmaceutical Industry Trends 142
4.6.3 Acquisitions, License Agreements and Partnerships 144
4.6.4 Ethical, Legal and Social Issues Related to the Use of Genetic Information
147
4.6.5 Regulatory Issues 147
4.6.6 Reimbursement Issues 148
4.6.6.1 Cystic Fibrosis 148
4.6.6.2 Viral Load Testing 148
4.6.6.3 NMP22 148

5. Molecular Diagnostics Automated Instrumentation Approved for Market by the
FDA 149
5.1 Gene Expression Profiling 150
5.2 Proteomic Multiplex Assays 150
5.3 Solution-Phase Multiplexing 150
5.4 RNA Interference (RNAi) 151
5.4.1 Role of RNAi in Drug Target Validation 152
5.4.2 Other Companies Involved in the RNAi Market 152
5.5 DNA Tags 153

6. Market Trends and Forecasts 154
6.1 Market Dynamics 154
6.1.1 Technological Perspective on Molecular Diagnostics 154
6.1.2 Molecular Diagnostics Market Opportunities 154
6.1.3 Market Forces 155
6.1.3.1 Adoption of Amplified Screening Technology 156
6.1.3.2 Advances in Automated Testing 156
6.1.3.3 Responsiveness to Newly Emerging Threats 156
6.1.3.4 Increased Focus on Safety of Blood Supply 157
6.1.3.5 Growth in Viral Load Testing 157
6.1.3.6 Development of Emerging Markets for NAT Technology 157
6.1.3.7 Improvements in Detection Technologies 158
6.2 Future Considerations for Molecular Diagnosis 158
6.3 Role of Genomics in Transforming Pharmaceutical R&D 159
6.4 Cancer Markers 159
6.5 Cytology Markers 160
6.6 RNA Detection 160
6.7 Diagnosis of Inherited Disease 160
6.8 Ethical Considerations 160
6.9 NAT and Personalized Medicine 162
6.10 Five Molecular Diagnostics Growth Areas 162
6.11 Specific Commercial Nucleic Acid Probes 162
6.12 Novel Amplification Techniques in the Market 163
6.13 Ramification Amplification Method (RAM) 164
6.14 Invader Assays/Third Wave Technologies 164
6.15 Molecular Beacons 166
6.16 HLA Sequencing-Based Typing Kits 167
6.17 Prenatal Diagnosis 167
6.18 Newborn Screening 168
6.19 NAT and Preventive Medicine: NAT-Based Assays 168
6.20 Prenatal and Pre-implantation Diagnosis 169
6.21 FISH-Based Tests on Fetal Cells 169
6.22 Companion Therapeutic/Diagnostic Approach 169
6.23 Sample Preparation Market 170

7. Corporate Directory 171
7.1 Abbott Laboratories 171
7.2 Affymetrix 175
7.3 Agendia 183
7.4 Agilent Technologies 183
7.5 Ambion 184
7.6 Applied Biosystems Group 184
7.7 Beckman Coulter 188
7.8 BioGenex 191
7.9 bioMérieux 191
7.10 Bio-Rad Laboratories 191
7.11 Biotage 192
7.12 Biotest 192
7.13 Caliper Life Sciences 193
7.14 Celera Group 195
7.15 Cellomics 196
7.16 Cepheid 196
7.17 Chiron (Novartis) 197
7.18 Ciphergen Biosystems 198
7.19 CuraGen 199
7.20 Cytocell Technologies 204
7.21 Dako A/S (formerly DakoCytomation A/S) 204
7.22 DiaDexus 205
7.23 Digene 207
7.24 Enzo Biochem 207
7.25 Epigenomics 207
7.26 EraGen Biosciences 208
7.27 Eurogentec 208
7.28 Exiqon 208
7.29 Gene Link 209
7.30 Gene Logic 209
7.31 GeneOhm Sciences 211
7.32 Genisphere 211
7.33 Gen-Probe 212
7.34 Genzyme 214
7.35 Hamilton Thorne Biosciences 215
7.36 ID Biomedical 215
7.37 Illumina 216
7.38 Incyte 219
7.39 Innogenetics 221
7.40 Interleukin Genetics 222
7.41 Invitrogen 223
7.42 Kreatech Biotechnology 224
7.43 LabCorp 225
7.44 LI-COR Biosciences 225
7.45 Matritech 226
7.46 Meridian Bioscience 228
7.47 Monogram Biosciences 229
7.48 Motorola 231
7.49 MWG Biotech 231
7.50 Myriad Genetics 232
7.51 Nanogen 233
7.52 Nanosys 236
7.53 NimbleGen Systems 237
7.54 Nuvelo 237
7.55 Nymox Pharmaceutical 238
7.56 Orchid BioSciences 239
7.57 Orchid Cellmark 239
7.58 Organon International 242
7.59 Ortho-Clinical Diagnostics 242
7.60 Ostex International 244
7.61 PerSeptive Biosystems 244
7.62 PharMingen 244
7.63 PPD 244
7.64 PPGx (DNA Sciences Laboratories) 244
7.65 Prodesse 245
7.66 Professional Genetics Laboratory 245
7.67 Promega 246
7.68 QIAGEN 246
7.69 Quantum Biotechnologies 249
7.70 Response Biomedical 249
7.71 Roche Diagnostics 249
7.72 Siemens 253
7.73 Sequenom 253
7.74 SurModics 256
7.75 Tepnel Life Sciences 257
7.76 Third Wave Technologies 257
7.77 Tm Bioscience 258
7.78 Visible Genetics 259
7.79 VisiGen Biotechnologies 259
7.80 Vysis 259
7.81 Alternative Sequencing Companies 259
7.81.1 Callida Genomics, Inc. 259
7.81.2 Mobious Genomics, Ltd. 259
7.81.3 Perlegen Sciences, Inc. 259
7.81.4 Solexa, Ltd. 260
7.81.5 U.S. Genomics, Inc. 260

8. Market Overview 261
8.1 Snapshot of Molecular Diagnostics Industry Structure 262
8.2 Global Molecular Diagnostics Testing Market 263
8.3 U.S. Molecular Diagnostics Testing Market 265
8.4 European Molecular Diagnostics Market 266
8.5 Japanese Molecular Diagnostics Testing Market 267
8.6 Overview of the European Molecular Diagnostics Country Markets 267
8.6.1 France 267
8.6.2 Germany 267
8.6.3 The United Kingdom 267
8.6.4 Italy 268
8.6.5 Spain 268

Appendix 1: Biowarfare Agents 269


LIST OF FIGURES

Figure 2.1: Segment of Double-Stranded DNA Showing the Base-Pair Relationship 16
Figure 3.1: Applications of Molecular Diagnostics Technology Platforms 30
Figure 3.2: Overall Structure of Nucleic Acid Testing Market 32
Figure 3.3: Applications of Key Players and Market Share in Molecular
Diagnostics Testing Markets 35
Figure 3.4: Serologic and Clinical Course of Acute HBV Infection 56
Figure 3.5: Primary Causes of Chronic Liver Disease 58
Figure 3.6: Combination Therapy in Typical HCV Infection 59
Figure 3.7: Time Course of Markers in Typical HCV Infection 60
Figure 3.8: Bacillus anthracis 109
Figure 8.1: Molecular Diagnostics Market Segmentation 261
Figure 8.2: Molecular Diagnostics Market Segmentation by Technology 262
Figure 8.3: Breakout of the Molecular Diagnostics Marketplace 264
Figure 8.4: U.S. Molecular Diagnostics Market Segments 2007 265


LIST OF TABLES

Table 3.1: Global Market for Molecular Diagnostics Testing, 2000 to 2012 33
Table 3.2: U.S. Market for Molecular Diagnostics Testing, 2004 to 2012 33
Table 3.3: Global Market for Nucleic Acid Testing, 2000 to 2012 34
Table 3.4: Summary of Molecular Diagnostics Testing 34
Table 3.5: Share of Molecular Diagnostics Testing by Testing Type 35
Table 3.6: Key Players and Market Share in Molecular Diagnostics Testing Market
35
Table 3.7: Annual U.S. Market for DNA Probe Diagnostics, 1998 to 2012 36
Table 3.8: Annual Global Market for DNA Probe Diagnostics, 1998 to 2009 36
Table 3.9: Estimated Market Share of Major Competitors in U.S. DNA/PCR Kit
Research Market 38
Table 3.10: Estimated Market Share of Major Competitors in U.S. DNA/PCR Kit
Diagnostics Market 38
Table 3.11: Roche PCR Licenses 38
Table 3.12: DNA Probe Market Segments in the U.S. 39
Table 3.13: Companies Marketing Products Using DNA Probes 41
Table 3.14: Companies Marketing Multiple Products in Molecular Diagnostics
Sector 41
Table 3.15: Global Sales of DNA Probe Kits, 1998 to 2005 42
Table 3.16: Companies Marketing DNA Detection Platforms 42
Table 3.17: Companies Marketing Genotyping Technologies 45
Table 3.18: Companies Marketing Clinical Genotyping Technologies 46
Table 3.19: Summary of Assays for HIV Viral Load Testing 52
Table 3.20: Global Market for HIV Diagnostic Testing, 2000 to 2012 54
Table 3.21: U.S. Market for HIV Diagnostic Testing, 2000 to 2012 54
Table 3.22: Serologic Diagnosis of HBV Infections* 56
Table 3.23: Unusual HBV Serologic Profiles Requiring Further Evaluation 57
Table 3.24: Recommendations for HBV Diagnostic Testing 57
Table 3.25: Lower Detection Limits of HBV DNA Assays 57
Table 3.26: Recommendations for HCV Diagnostic Testing 61
Table 3.27: Important HCV Statistics 61
Table 3.28: Global Market for HAV Diagnostic Testing, 2000 to 2008 63
Table 3.29: U.S. Market for HAV Diagnostic Testing, 2000 to 2008 64
Table 3.30: Global Market for HBV Diagnostic Testing, 2000 to 2008 64
Table 3.31: U.S. Market for HBV Diagnostic Testing, 2000 to 2008 64
Table 3.32: Global Market for HCV Diagnostic Testing, 2000 to 2008 64
Table 3.33: U.S. Market for HCV Diagnostic Testing, 2000 to 2008 65
Table 3.34: Global Market for SARS Diagnostics Testing, 2002 to 2008 66
Table 3.35: U.S. Market for SARS Diagnostics Testing, 2002 to 2008 66
Table 3.36: Global Market for Molecular Diagnostics Cancer Testing, 2000 to 2008
69
Table 3.37: Annual Volume of NAT Infectious Disease Testing, 2000 to 2008 73
Table 3.39: Global Market Dollar Volume of NAT STD Testing, 2000 to 2008 73
Table 3.39: U.S. Market Dollar Volume of NAT STD Testing, 2000 to 2009 73
Table 3.40: U.S. Market Share of NAT STD Testing 74
Table 3.41: Global Market for Chlamydia Diagnostic Testing, 2000 to 2009 74
Table 3.42: U.S. Market for Chlamydia Diagnostic Testing, 2000 to 2009 74
Table 3.43: Global Market for Gonorrhea Diagnostic Testing, 2000 to 2008 74
Table 3.44: Global Market for TB Diagnostic Testing, 2000 to 2008 75
Table 3.45: Global Market for DNA Group B Streptococcus Diagnostic Testing, 2000
to 2009 75
Table 3.46: U.S. Market for Group B Streptococcus Diagnostic Testing, 2000 to
2009 75
Table 3.47: Gen-Probe Clinical Diagnostic Products for the Detection of
Non-Viral Micro-organisms 77
Table 3.48: Global Market for Blood-Screening Diagnostic Testing, 2000 to 2008
81
Table 3.49: U.S. Market for Blood-Screening Diagnostic Testing, 2000 to 2008 81
Table 3.50: Leading Players in SNP Genotyping 85
Table 3.51: Global Market for SNP Genotyping, 2000 to 2011 85
Table 3.52: DNA-Analysis Market Competitors 88
Table 3.53: Leading Companies in Medical Utility of SNPs 88
Table 3.54: Competitors in the Field of Identity Genomics Testing 89
Table 3.55: U.S. Market for Food-Screening Diagnostic Testing Using Molecular
Diagnostics Techniques, 2000 to 2008 91
Table 3.56: Methods for Detection of Salmonella in Food Using Molecular
Diagnostics Methods 92
Table 3.57: U.S. Market for Forensic Diagnostics Testing, 2000 to 2010 94
Table 3.58: U.S. Market for Biological Threat Detection Testing, 2000 to 2010 98
Table 3.59: Biotest Reagents 101
Table 3.60: Variation of CF Carrier Risks by Ethnic Group 112
Table 3.61: Reasons for CF Testing 112
Table 3.62: Variation of CF Detection Rates by Ethnic Background 112
Table 3.63: Global Market for CF Diagnostic Testing, 2000 to 2008 112
Table 3.64: U.S. Market for CF Diagnostic Testing, 2000 to 2008 112
Table 3.65: Commercial CF-Screening Products 113
Table 3.66: Emerging CF-Screening Products 113
Table 3.67: CF Screening Technology Summary 113
Table 3.68: U.S. Market for HLA Type Testing, 2000 to 2008 114
Table 3.69: Competitors in HLA Testing 115
Table 3.70: U.S. Market for NAT Genetic-Disease Testing, 2000 to 2008 116
Table 3.71: Non-U.S. Market for NAT Genetic-Disease Testing, 2000 to 2008 116
Table 3.72: U.S. Market for NAT Cytogenetic-Disease Testing, 2000 to 2008 116
Table 3.73: Non-U.S. Market for NAT Cytogenetic-Disease Testing, 2000 to 2008
116
Table 3.74: Carrier Rates of Common HFE Mutations in Caucasians 117
Table 3.75: Results and Diagnosis for Fragile X Syndrome 118
Table 3.76: Principal Competitors in Pharmacogenetics R&D for Personalized
Medicine 122
Table 3.77: Principal Competitors in Pharmacogenetics Patient Testing 122
Table 4.1: DNA-Sequencing Market Players 129
Table 4.2: Global Market for DNA Chips, 2000 to 2007 129
Table 4.3: Top Ten Companies for Molecular Diagnostics Patents 147
Table 6.1: Companies Licensed to Sell Custom Molecular Beacon Probes 167
Table 6.2: U.S. Sample Preparation Market, 2005 to 2012 170
Table 7.1: Products Marketed by Abbott in the Diagnostics Market 174
Table 7.2: Summary of Selected Affymetrix Expression-Profiling Customers 178
Table 7.3: PACE Product Sales as a Percentage of Total Company Revenue, 2000 to
2005 213
Table 7.4: Innogenetics HLA Products for Genetic Testing and Transplantation 222
Table 7.5: Nanogen Product Sales, 2000 to 2006 234
Table 7.6: Rarely-Expressed Genes as Therapeutic Product Candidates 238
Table 7.7: Roche Diagnostics Key Products 251
Table 7.8: Sales by Region 251
Table 7.9: Sales by Business Area 252
Table 7.10: Product Line Sales 2005 252
Table 7.11: Growth Drivers 252
Table 8.1: Number of Molecular Diagnostics Tests in the U.S., 2000 to 2008 261
Table 8.2: Global Molecular Diagnostics Testing Revenues, 2000 to 2012 264
Table 8.3: Global Distribution of Molecular Diagnostics Testing 264
Table 8.4: U.S. Molecular Diagnostics Testing Market, 2004 to 2012 266
Table 8.5: European Molecular Diagnostics Testing Market, 2005 to 2012 266
Table 8.6: Japanese Molecular Diagnostics Testing Market, 2005 to 2012 267

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