Molecular Diagnostics Markets

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 41
3.1.1.2 Products and Applications 42
3.1.1.3 Oncology 43
3.1.2 SNPs and Genes: Medical Utility (Clinical Applications) 43
3.1.2.1 Clinical Application Initiatives 45
3.1.2.2 A Sampling of Clinical Application Collaborations 46
3.1.2.3 Collaborative Relationships 48
3.2 Diagnostic Testing Using DNA 49
3.2.1 HIV 51
3.2.2 Hepatitis Serologic Markers and Nucleic Acid Testing 53
3.2.2.1 Hepatitis A Virus (HAV) 53
3.2.2.2 Hepatitis B Virus (HBV) 54
3.2.2.3 Hepatitis C Virus (HCV) 57
3.2.2.4 Hepatitis D Virus (HDV) 62
3.2.2.5 Hepatitis E Virus (HEV) 62
3.2.2.6 HBV/HCV Viral Load and Drug Resistance 62
3.2.3 Severe Acute Respiratory Syndrome (SARS) 64
3.2.3.1 New Approach to Diagnosing Avian Influenza 65
3.2.3.2 Microarray or DNA Chip-Based Tests 67
3.2.4 Cancer Detection Using PCR 68
3.2.4.1 Lung Cancer 68
3.2.4.2 Oral Cancer 69
3.2.4.3 Prostate Cancer 69
3.2.4.4 Chronic Myelogenous Leukemia 69
3.2.4.5 Malignant Gliomas 70
3.2.4.6 Colorectal Cancer 70
3.2.4.7 Breast Cancer 70
3.2.4.8 Bladder Cancer 70
3.2.5 Microbiology Testing 70
3.2.5.1 Chlamydia 71
3.2.5.2 Gonorrhea 71
3.2.5.3 Tuberculosis 71
3.2.5.4 Group B Streptococcus 74
3.2.5.5 Pathogenic Enteric Bacteria 76
3.2.5.6 Bordetella pertussis 77
3.2.5.7 Legionella Pneumophila 77
3.2.5.8 Peridontal Bacteria 77
3.2.5.9 Pneumocystis Carinii 77
3.2.5.10 Methicillin-resistant Staphylococcus Aureus 78
3.2.6 Blood Screening 78
3.3 SNPs in Clinical Diagnostics 83
3.3.1 Functional Genomics 87
3.3.2 Paternity Testing 87
3.4 Industrial Testing and Food Diagnostics 88
3.4.1 The Market 88
3.4.2 Detection of H. pylori by PCR 91
3.4.3 Detection of E. coli 0157 91
3.4.4 Detection of Enteric Viruses 91
3.5 Forensics Market 92
3.5.1 Isolation of DNA for PCR Profiling 93
3.5.2 Analysis by PCR-Based DNA Typing 94
3.5.3 Rapid Isolation of DNA for RFLP and PCR 94
3.5.4 DNA for PCR-STR Typing 94
3.6 Bioterrorism and Molecular Diagnostics 94
3.6.1 Introduction 94
3.6.1.1 Current Biological Threat Detection Systems 97
3.6.1.2 Use of DNA Microarrays and Biochips for Gene Expression Profiles in BWA 98
3.6.1.3 Advantages and Disadvantages of Host Gene Expression Profiling as a Biothreat Detection System 99
3.6.2 Biological Warfare Agents 100
3.6.2.1 Anthrax 100
3.6.2.2 Botulinum Toxin 101
3.6.2.3 Ricin 101
3.6.2.4 IVD Industry and Bioterrorism Preparedness 101
3.6.2.4.1 Brucellosis 101
3.6.2.4.2 Cholera 102
3.6.2.5 Rapid Lateral Flow Immunoassays 103
3.6.2.6 Biosensors 104
3.6.2.6.1 Antibody and Synthetic Receptor-Based Sensors 104
3.6.2.6.2 DNA Sensors 105
3.6.2.6.3 Reagentless Sensors 106
3.6.3 Anthrax in Clinical Samples 107
3.6.3.1 Overview of Anthrax and Its Infectivity 107
3.6.3.2 Rapid Tests 109
3.6.3.2.1 PCR Tests 109
3.7 Cystic Fibrosis Testing 110
3.8 HLA Sequencing-Based Typing Kits 112
3.9 Cytogenetic Testing 114
3.9.1 Hereditary Hemochromatosis 116
3.9.2 Apolipoprotein E (ApoE) Genotyping 116
3.9.3 Fragile X Syndrome 117
3.9.4 Methylenetetrahydrofolate Reductase (MTHFR) Carrier Testing 118
3.10 Developments in Biochips for Clinical Applications 119
3.10.1 Roche AmpliChip Microarray 119
3.10.2 Breast Cancer DNA Chips 119
3.10.3 eSensor DNA Detection System 120
3.11 Pharmacogenomics 121
3.11.1 Coumadin 122
3.12 Thrombic Disorders 124

4. Trends in Molecular Diagnostics 125
4.1 Pharmacogenomics 125
4.1.1 The Market 125
4.1.1.1 Oncology 125
4.1.1.2 Toxicogenomics 125
4.1.2 Market Influences and Forecast 126
4.2 DNA Microarrays 126
4.2.1 Techniques 131
4.2.2 The Market 131
4.2.3 Identification of Sequence SNPs 131
4.2.4 Determining Gene Expression Levels 132
4.2.4.1 Hybridization Tests 132
4.2.4.2 Oligonucleotide Probes 133
4.2.5 Molecular Diagnostics Entry into Point-of-Care Testing 133
4.3 Emerging Markets of DNA Arrays 133
4.3.1 Pharmacogenomics 135
4.3.2 Adoption of Amplified Screening Technology 135
4.3.3 Advances in Automated Testing 135
4.3.4 Increased Focus on Safety of Blood Supply 136
4.3.5 Development of Emerging Markets for NAT Technology 136
4.3.6 Cancer 136
4.3.7 Human Leukocyte Antigen Typing 136
4.3.8 Neonatal Screening 137
4.4 Drivers and Restraints 138
4.5 Market Forecast 139
4.6 Business Trends in the Industry 139
4.6.1 Molecular Diagnostics Industry Trends 139
4.6.1.1 Adoption of Amplified Screening Technology 139
4.6.1.2 Advances in Automated Testing 139
4.6.1.3 Responsiveness to Newly Emerging Threats 140
4.6.1.4 Increased Focus on Safety of Blood Supply 140
4.6.1.5 Growth in Viral Load Testing 140
4.6.1.6 Development of Emerging Markets for NAT Technology 140
4.6.1.7 Improvements in Detection Technologies 141
4.6.2 Pharmaceutical Industry Trends 141
4.6.3 Acquisitions, License Agreements and Partnerships 143
4.6.4 Ethical, Legal and Social Issues Related to the Use of Genetic Information 146
4.6.5 Regulatory Issues 146
4.6.6 Reimbursement Issues 147
4.6.6.1 Cystic Fibrosis 147
4.6.6.2 Viral Load Testing 147
4.6.6.3 NMP22 147
4.6.6.4 iFOB Reimbursement 147

5. Molecular Diagnostics Automated Instrumentation Approved for Market by the FDA 148
5.1 Gene Expression Profiling 149
5.2 Proteomic Multiplex Assays 149
5.3 Solution-Phase Multiplexing 149
5.4 RNA Interference (RNAi) 150
5.4.1 Role of RNAi in Drug Target Validation 151
5.4.2 Other Companies Involved in the RNAi Market 151
5.5 DNA Tags 152

6. Market Trends and Forecasts 153
6.1 Market Dynamics 153
6.1.1 Technological Perspective on Molecular Diagnostics 153
6.1.2 Molecular Diagnostics Market Opportunities 153
6.1.3 Market Forces 154
6.1.3.1 Adoption of Amplified Screening Technology 155
6.1.3.2 Advances in Automated Testing 155
6.1.3.3 Responsiveness to Newly Emerging Threats 155
6.1.3.4 Increased Focus on Safety of Blood Supply 156
6.1.3.5 Growth in Viral Load Testing 156
6.1.3.6 Development of Emerging Markets for NAT Technology 156
6.1.3.7 Improvements in Detection Technologies 157
6.2 Future Considerations for Molecular Diagnosis 157
6.3 Role of Genomics in Transforming Pharmaceutical R&D 158
6.4 Cancer Markers 158
6.5 Cytology Markers 159
6.6 RNA Detection 159
6.7 Diagnosis of Inherited Disease 159
6.8 Ethical Considerations 159
6.9 NAT and Personalized Medicine 161
6.10 Five Molecular Diagnostics Growth Areas 161
6.11 Specific Commercial Nucleic Acid Probes 161
6.12 Novel Amplification Techniques in the Market 162
6.13 Ramification Amplification Method (RAM) 163
6.14 Invader Assays/Third Wave Technologies 163
6.15 Molecular Beacons 165
6.16 HLA Sequencing-Based Typing Kits 166
6.17 Prenatal Diagnosis 166
6.18 Newborn Screening 167
6.19 NAT and Preventive Medicine: NAT-Based Assays 167
6.20 Prenatal and Pre-implantation Diagnosis 168
6.21 FISH-Based Tests on Fetal Cells 168
6.22 Companion Therapeutic/Diagnostic Approach 168
6.23 Sample Preparation Market 169

7. Corporate Directory 170
7.1 Abbott Laboratories 170
7.2 Affymetrix 174
7.3 Agendia 182
7.4 Agilent Technologies 182
7.5 Ambion 183
7.6 Applied Biosystems Group 183
7.7 Beckman Coulter 187
7.8 BioGenex 190
7.9 bioMérieux 190
7.10 Bio-Rad Laboratories 190
7.11 Biotage 191
7.12 Biotest 191
7.13 Caliper Life Sciences 192
7.14 Celera Group 194
7.15 Cellomics 195
7.16 Cepheid 195
7.17 Chiron (Novartis) 196
7.18 Ciphergen Biosystems 197
7.19 CuraGen 198
7.20 Cytocell Technologies 203
7.21 Dako A/S (formerly DakoCytomation A/S) 203
7.22 DiaDexus 204
7.23 Digene 206
7.24 Enzo Biochem 206
7.25 Epigenomics 206
7.26 Epoch Biosciences 207
7.27 EraGen Biosciences 207
7.28 Eurogentec 207
7.29 Exiqon 208
7.30 Gene Link 208
7.31 Gene Logic 208
7.32 GeneOhm Sciences 210
7.33 Genisphere 211
7.34 Gen-Probe 211
7.35 Genzyme 213
7.36 Hamilton Thorne Biosciences 214
7.37 ID Biomedical 214
7.38 Illumina 215
7.39 Incyte 218
7.40 Innogenetics 220
7.41 Interleukin Genetics 221
7.42 Invitrogen 222
7.43 Kreatech Biotechnology 224
7.44 LabCorp 224
7.45 LI-COR Biosciences 224
7.46 Matritech 225
7.47 Meridian Bioscience 227
7.48 Monogram Biosciences 228
7.49 Motorola 230
7.50 MWG Biotech 231
7.51 Myriad Genetics 231
7.52 Nanogen 233
7.53 Nanosys 235
7.54 NimbleGen Systems 236
7.55 Nuvelo 236
7.56 Nymox Pharmaceutical 237
7.57 Orchid BioSciences 238
7.58 Orchid Cellmark 238
7.59 Organon International 241
7.60 Ortho-Clinical Diagnostics 241
7.61 Ostex International 243
7.62 PerSeptive Biosystems 243
7.63 PharMingen 243
7.64 PPD 243
7.65 PPGx (DNA Sciences Laboratories) 244
7.66 Prodesse 244
7.67 Professional Genetics Laboratory 244
7.68 Promega 245
7.69 QIAGEN 245
7.70 Quantum Biotechnologies 248
7.71 Quidel 248
7.72 Response Biomedical 250
7.73 Roche Diagnostics 250
7.74 Siemens 253
7.75 Sequenom 254
7.76 SurModics 256
7.77 Tepnel Life Sciences 257
7.78 Thermo Fisher Scientific 257
7.79 Third Wave Technologies 258
7.80 Tm Bioscience 259
7.81 Visible Genetics 259
7.82 VisiGen Biotechnologies 260
7.83 Vysis 260
7.84 Alternative Sequencing Companies 260
7.84.1 Callida Genomics, Inc. 260
7.84.2 Mobious Genomics, Ltd. 260
7.84.3 Perlegen Sciences, Inc. 260
7.84.4 Solexa, Ltd. 261
7.84.5 U.S. Genomics, Inc. 261

8. Market Overview 262
8.1 Snapshot of Molecular Diagnostics Industry Structure 263
8.2 Global Molecular Diagnostics Testing Market 264
8.3 U.S. Molecular Diagnostics Testing Market 266
8.4 European Molecular Diagnostics Market 267
8.5 Japanese Molecular Diagnostics Testing Market 268
8.6 Overview of the European Molecular Diagnostics Country Markets 268
8.6.1 France 268
8.6.2 Germany 268
8.6.3 The United Kingdom 268
8.6.4 Italy 269
8.6.5 Spain 269

Appendix 1: Biowarfare Agents 270

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: Serologic and Clinical Course of Acute HBV Infection 55
Figure 3.4: Primary Causes of Chronic Liver Disease 57
Figure 3.5: Combination Therapy in Typical HCV Infection 58
Figure 3.6: Time Course of Markers in Typical HCV Infection 59
Figure 3.7: Bacillus anthracis 108
Figure 8.1: Molecular Diagnostics Market Segmentation 262
Figure 8.2: Molecular Diagnostics Market Segmentation by Technology 263
Figure 8.3: Breakout of the Molecular Diagnostics Marketplace 265
Figure 8.4: U.S. Molecular Diagnostics Market Segments 2007 266

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: Annual U.S. Market for DNA Probe Diagnostics, 1998 to 2012 35
Table 3.6: Annual Global Market for DNA Probe Diagnostics, 1998 to 2009 35
Table 3.7: Estimated Market Share of Major Competitors in U.S. DNA/PCR Kit Research Market 37
Table 3.8: Estimated Market Share of Major Competitors in U.S. DNA/PCR Kit Diagnostics Market 37
Table 3.9: Roche PCR Licenses 37
Table 3.10: DNA Probe Market Segments in the U.S. 38
Table 3.11: Companies Marketing Products Using DNA Probes 40
Table 3.12: Companies Marketing Multiple Products in Molecular Diagnostics Sector 40
Table 3.13: Global Sales of DNA Probe Kits, 1998 to 2005 41
Table 3.14: Companies Marketing DNA Detection Platforms 41
Table 3.15: Companies Marketing Genotyping Technologies 44
Table 3.16: Companies Marketing Clinical Genotyping Technologies 45
Table 3.17: Summary of Assays for HIV Viral Load Testing 51
Table 3.18: Global Market for HIV Diagnostic Testing, 2000 to 2012 53
Table 3.19: U.S. Market for HIV Diagnostic Testing, 2000 to 2012 53
Table 3.20: Serologic Diagnosis of HBV Infections* 55
Table 3.21: Unusual HBV Serologic Profiles Requiring Further Evaluation 56
Table 3.22: Recommendations for HBV Diagnostic Testing 56
Table 3.23: Lower Detection Limits of HBV DNA Assays 56
Table 3.24: Recommendations for HCV Diagnostic Testing 60
Table 3.25: Important HCV Statistics 60
Table 3.26: Global Market for HAV Diagnostic Testing, 2000 to 2008 62
Table 3.27: U.S. Market for HAV Diagnostic Testing, 2000 to 2008 63
Table 3.28: Global Market for HBV Diagnostic Testing, 2000 to 2008 63
Table 3.29: U.S. Market for HBV Diagnostic Testing, 2000 to 2008 63
Table 3.30: Global Market for HCV Diagnostic Testing, 2000 to 2008 63
Table 3.31: U.S. Market for HCV Diagnostic Testing, 2000 to 2008 64
Table 3.32: Global Market for SARS Diagnostics Testing, 2002 to 2008 65
Table 3.33: U.S. Market for SARS Diagnostics Testing, 2002 to 2008 65
Table 3.34: Global Market for Molecular Diagnostics Cancer Testing, 2000 to 2008 68
Table 3.35: Annual Volume of NAT Infectious Disease Testing, 2000 to 2008 72
Table 3.36: Global Market Dollar Volume of NAT STD Testing, 2000 to 2008 72
Table 3.37: U.S. Market Dollar Volume of NAT STD Testing, 2000 to 2009 72
Table 3.38: U.S. Market Share of NAT STD Testing 73
Table 3.39: Global Market for Chlamydia Diagnostic Testing, 2000 to 2009 73
Table 3.40: U.S. Market for Chlamydia Diagnostic Testing, 2000 to 2009 73
Table 3.41: Global Market for Gonorrhea Diagnostic Testing, 2000 to 2008 73
Table 3.42: Global Market for TB Diagnostic Testing, 2000 to 2008 74
Table 3.43: Global Market for DNA Group B Streptococcus Diagnostic Testing, 2000 to 2009 74
Table 3.44: U.S. Market for Group B Streptococcus Diagnostic Testing, 2000 to 2009 74
Table 3.45: Gen-Probe Clinical Diagnostic Products for the Detection of Non-Viral Micro-organisms 76
Table 3.46: Global Market for Blood-Screening Diagnostic Testing, 2000 to 2008 80
Table 3.47: U.S. Market for Blood-Screening Diagnostic Testing, 2000 to 2008 80
Table 3.48: Leading Players in SNP Genotyping 84
Table 3.49: Global Market for SNP Genotyping, 2000 to 2011 84
Table 3.50: DNA-Analysis Market Competitors 87
Table 3.51: Leading Companies in Medical Utility of SNPs 87
Table 3.52: Competitors in the Field of Identity Genomics Testing 88
Table 3.53: U.S. Market for Food-Screening Diagnostic Testing Using Molecular Diagnostics Techniques, 2000 to 2008 90
Table 3.54: Methods for Detection of Salmonella in Food Using Molecular Diagnostics Methods 91
Table 3.55: U.S. Market for Forensic Diagnostics Testing, 2000 to 2010 93
Table 3.56: U.S. Market for Biological Threat Detection Testing, 2000 to 2010 97
Table 3.57: Biotest Reagents 100
Table 3.58: Variation of CF Carrier Risks by Ethnic Group 111
Table 3.59: Reasons for CF Testing 111
Table 3.60: Variation of CF Detection Rates by Ethnic Background 111
Table 3.61: Global Market for CF Diagnostic Testing, 2000 to 2008 111
Table 3.62: U.S. Market for CF Diagnostic Testing, 2000 to 2008 111
Table 3.63: Commercial CF-Screening Products 112
Table 3.64: Emerging CF-Screening Products 112
Table 3.65: CF Screening Technology Summary 112
Table 3.66: U.S. Market for HLA Type Testing, 2000 to 2008 113
Table 3.67: Competitors in HLA Testing 114
Table 3.68: U.S. Market for NAT Genetic-Disease Testing, 2000 to 2008 115
Table 3.69: Non-U.S. Market for NAT Genetic-Disease Testing, 2000 to 2008 115
Table 3.70: U.S. Market for NAT Cytogenetic-Disease Testing, 2000 to 2008 115
Table 3.71: Non-U.S. Market for NAT Cytogenetic-Disease Testing, 2000 to 2008 115
Table 3.72: Carrier Rates of Common HFE Mutations in Caucasians 116
Table 3.73: Results and Diagnosis for Fragile X Syndrome 117
Table 3.74: Principal Competitors in Pharmacogenetics R&D for Personalized Medicine 121
Table 3.75: Principal Competitors in Pharmacogenetics Patient Testing 121
Table 4.1: DNA-Sequencing Market Players 128
Table 4.2: Global Market for DNA Chips, 2000 to 2007 128
Table 4.3: Top Ten Companies for Molecular Diagnostics Patents 146
Table 6.1: Companies Licensed to Sell Custom Molecular Beacon Probes 166
Table 6.2: U.S. Sample Preparation Market, 2005 to 2012 169
Table 7.1: Products Marketed by Abbott in the Diagnostics Market 173
Table 7.2: Summary of Selected Affymetrix Expression-Profiling Customers 177
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 221
Table 7.5: Nanogen Product Sales, 2000 to 2006 233
Table 7.6: Rarely-Expressed Genes as Therapeutic Product Candidates 237
Table 7.7: Roche Diagnostics Key Products 251
Table 7.8: Sales by Region 252
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 262