Epigenomics is a fast-growing biology field that is rapidly commercializing. Epigenomics research tools and products enable discovery of novel diagnostic biomarkers and drug targets. We previously examined the epigenetics market in 2007. Since that time, the FDA approved several epigenetic drugs for treating non-Hodgkin’s lymphomas and myelodysplastic syndromes. In the past 2 years, several epigenetic-based in-vitro diagnostics tests have been launched in the United States and Europe for early colon cancer detection. A significant number of additional drug candidates and diagnostics tests are in the clinical pipeline and ready to be commercialized during our forecast horizon.
 
We are interested in determining the particular diseases for which epigenomic-based diagnostics products will be used and the market and growth potential for these applications. We are also interested in understanding the scope of the future market potential for epigenetic drugs, including DNA methylase inhibitors and histone deacetylase inhibitors.
 
It is particularly timely to examine the epigenomics industry in 2010 given the changes in the industry and the increasing importance of gene regulation beyond DNA sequence.
 
We have compiled a study of important epigenomics technologies used in the four major applications of research tools, diagnostics, therapeutics, and cellular therapies. We define and describe the fundamental epigenomic technologies, the market driving forces, product types, main market applications, key companies, strategic alliances and acquisitions, future global market potential and product sales forecasts for the period 2009 through 2014.
 
We analyze in detail the clinical pipelines for both epigenetic-based diagnostics and therapeutics.
 
This study will be of particular interest to the molecular diagnostics industry, pharmaceutical manufacturers, biotechnology companies, and life science research tools companies. It will also be of interest to companies involved in drug and/or biomarker discovery programs; manufacturers of microarrays or next generation sequencing systems, high-grade antibodies, restriction enzymes or primers; bioinformatics developers, and cancer researchers and clinicians.
 
The study scope includes the major epigenomics technologies that are now, or likely to become, commercialized within the next 5 years. We examine the products flowing from these technologies, market segments into which these products are sold, and we forecast product sales for the period 2009 through 2014. We describe factors that are driving growth in these markets. Competitive dynamics and key trends in each of the market segments are discussed.
 
We examine the strategies of successful companies, strategic alliances, and the impact that large-scale epigenomic projects have on the industry. We profile the major companies in the industry.
 
The scope of our analysis includes DNA methylation and histone acetylation and methylation technologies; and the important market segments within research tools, diagnostics, therapies, and cellular therapeutics. We are particularly interested in cancer indications, which comprise the bulk of the diagnostics and therapies markets.

This Report:

• Provides a comprehensive overview of the global market for epigenomics
• Describes the major epigenomics technologies impacting the market today and emerging opportunities in biomarkers, diagnostics and therapeutics
• Contains global market forecasts for epigenomics, with trends and forecasts for growth through 2014
• Offers a focus on particular applications of epigenomics, including research tools, diagnostics, drugs and cloning/tissue engineering
• Discusses industry structure including, mergers and acquisitions, distribution of products, government regulation and industry trends
• Profiles the most competitive businesses in the industry.

TABLE OF CONTENTS

CHAPTER ONE: INTRODUCTION

    STUDY GOALS AND OBJECTIVES .. 1
    REASONS FOR DOING THE STUDY .. 1
    INTENDED AUDIENCE .. 2
    SCOPE OF REPORT .. 2
    METHODOLOGY .. 2
    INFORMATION SOURCES .. 3
   


CHAPTER TWO: SUMMARY

    SUMMARY .. 5
  SUMMARY TABLE GLOBAL VALUE OF EPIGENOMIC PRODUCTS,
    BY APPLICATION, THROUGH 2014 ($ MILLIONS) .. 6
  SUMMARY FIGURE GLOBAL VALUE OF EPIGENOMIC PRODUCTS,
    BY APPLICATION, 2008-2014 ($ MILLIONS) .. 6
       

CHAPTER THREE: OVERVIEW

     INTRODUCTION .. 8
     THE NEW PARADIGM OF EPIGENOMICS .. 8
  FIGURE 1 EPIGENOMICS: A NEW PARADIGM .. 9
     HOW EPIGENOMICS FITS WITHIN GENOMICS .. 10
  TABLE 1 GENOMICS PLATFORMS .. 10
      TECHNICAL SCOPE OF THIS REPORT .. 12
  TABLE 2 TECHNOLOGY SCOPE OF THIS REPORT .. 12
     MARKET POTENTIAL OF EPIGENOMICS .. 13
  TABLE 3 GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY
     APPLICATION, THROUGH 2014 ($ MILLIONS) .. 13
     EPIGENOMICS PRODUCTS .. 14
          RESEARCH TOOLS AND REAGENTS .. 14
          DIAGNOSTICS .. 15
          DRUGS .. 15
  FIGURE 2 ACTIVE CANCER EPIGENETIC DRUG CLINICAL TRIALS,
     BY PHASE AND INDICATION, JANUARY 2010 .. 16
     GROWTH DRIVING FORCES .. 17
          GROWTH IN LIFE SCIENCE FUNDING .. 17
          CREATION OF EPIGENOMIC MAPS .. 17
          AGING POPULATION IN DEVELOPED COUNTRIES .. 17
          NEED FOR BETTER CANCER THERAPIES .. 17
          GROWTH IN PERSONALIZED MEDICINE .. 18
     WHY EPIGENETIC TECHNOLOGY IS IMPORTANT.. 18
  FIGURE 3 EPIGENETIC PROCESSES CAN GENERATE ABNORMAL
      CELLS DURING CELL DEVELOPMENT .. 18
      LIFE CYCLE STATUS OF EPIGENOMICS TECHNOLOGIES.. 19
      HISTORICAL BACKGROUND .. 20
   TABLE 4 HISTORICAL OVERVIEW OF EPIGENOMICS .. 20
      THE EPIGENOMICS INDUSTRY.. 22
   TABLE 5 EPIGENOMICS INDUSTRY KEY COMPANIES.. 23
  

CHAPTER FOUR: EPIGENETIC TECHNOLOGIES

     INTRODUCTION .. 25
     EPIGENETIC ANALYSIS TECHNOLOGIES .. 25
  TABLE 6 EPIGENETIC ANALYSIS TECHNOLOGIES .. 26
           STATUS OF DNA AND HISTONE ANALYSIS
             TECHNOLOGIES .. 26
  TABLE 7 STATUS OF DNA METHYLATION AND HISTONE ANALYSIS TECHNOLOGIES .. 26
            DNA AND HISTONE ANALYSIS WORKFLOW .. 28
  FIGURE 4 UPSTREAM AND DOWNSTREAM STEPS IN EPIGENETIC
     ANALYSIS WORKFLOW .. 29
     DNA METHYLATION .. 29
           METHYLATED CYTOSINE--A FIFTH BASE .. 29
  FIGURE 5 EPIGENETIC CHANGES TO DNA AFFECT GENE
     EXPRESSION .. 30
           BIOLOGICAL ROLE OF DNA METHYLATION .. 30
  TABLE 8 BIOLOGICAL ROLES OF DNA METHYLATION .. 31
           DNA METHYLTRANSFERASE ENZYMES .. 32
           CPG ISLANDS .. 33
  TABLE 9 DESCRIPTION OF CPG ISLANDS .. 34
     HISTONE METHYLATION AND ACETYLATION .. 35
           HISTONES .. 35
           HISTONE MODIFICATIONS .. 36
  FIGURE 6 ACETYLATION OF HISTONE TAIL REGIONS .. 36
           HISTONE ACETYLATION AND METHYLATION ENZYMES .. 37
  FIGURE 7 HISTONE ACETYLATION AND METHYLATION ENZYMES .. 38
                Histone Acetyl Transferases (HAT) .. 38
                Histone Deacetylases (HDAC) .. 39
  TABLE 10 HDAC ENZYMES CLASSES .. 39
                Histone Methyltransferases and Demethylases .. 39
           INAPPROPRIATE METHYLATION AND ACETYLATION .. 40
  TABLE 11 MECHANISMS FOR INAPPROPRIATE METHYLATION
     AND ACETYLATION .. 40

CHAPTER FIVE: EPIGENOMIC ANALYSIS TECHNOLOGIES

     IMPORTANCE OF EPIGENOMIC RESEARCH TOOLS.. 41
     DNA METHYLATION RESEARCH TOOLS.. 42
  TABLE 12 DNA METHYLATION ANALYSIS ASSAYS .. 42
          DNA METHYLATION RESEARCH TOOLS (CONTINUED) .. 43
  TABLE 13 EMERGING DNA METHYLATION TECHNOLOGIES .. 44
  TABLE 14 ACROYNMS FOR DNA METHYLATION TECHNOLOGIES .. 45
     DNA METHYLATION ANALYSIS WORKFLOW .. 46
  FIGURE 8 METHYLATED DNA ANALYSIS WORKFLOW .. 47
          DNA METHYLATION ANALYSIS METHODS BY COVERAGE
             AND THROUGHPUT .. 47
  TABLE 15 DNA METHYLATION TECHNOLOGIES BY COVERAGE
     AND THROUGHPUT .. 48
          DNA METHYLATION ANALYSIS TYPES BY WORKFLOW .. 49
  TABLE 16 EXAMPLES OF DNA METHYLATION ASSAYS .. 49
     DNA METHYLATION ANALYSIS: UPSTREAM TECHNOLOGIES .. 50
  TABLE 17 METHYLATION RECOGNITION TECHNOLOGIES .. 50
          RESTRICTION ENZYME-BASED METHODS.. 51
  FIGURE 9 ANALYSIS OF DNA METHYLATION BY RESTRICTION
     ENZYMES .. 52
          BISULFITE-BASED METHODS .. 52
FIGURE 10 BISULFITE CONVERSION OF DNA .. 54
                 Analysis of Low Complexity DNA .. 55
          AFFINITY-BASED METHODS.. 56
          CHALLENGE OF HIGH BACKGROUND METHYLATED DNA.. 57
     GENOME WIDE DNA METHYLATION ANALYSIS .. 57
  TABLE 18 DNA METHYLATION ANALYSIS TECHNIQUES BY
     GENOME RESOLUTION .. 58
     HISTONE EPIGENETIC ANALYSIS TECHNOLOGIES .. 59
  TABLE 19 CHIP ASSAYS .. 60
          CHIP­CHIP AND CHIP-SEQ .. 61
  FIGURE 11 WORKFLOW SCHEMATIC FOR CHIP PLATFORMS.. 61
  TABLE 20 TECHNOLOGIES FOR MAPPING GENOMIC LOCATION OF
     CHROMATIN PROTEINS AND ENZYMES .. 62
     EMERGING DOWNSTREAM EPIGENETIC ANALYSIS
        PLATFORMS .. 63
          MICROARRAYS .. 63
  TABLE 21 MICROARRAY TYPES.. 63
  TABLE 22 COMPARISON OF DNA AND PROTEIN MICROARRAY
     TECHNOLOGIES .. 64
                 DNA Microarray Technologies .. 65
  FIGURE 12 MICROARRAY FEATURE DENSITY .. 66
  FIGURE 13 MICROARRAY RESOLUTION .. 66
  TABLE 23 MICROARRAY GENOME CONTENT .. 67
   TABLE 24 DNA MICROARRAY PLATFORM FEATURES .. 68
   TABLE 25 DNA MICROARRAY PLATFORM COMPARISON FOR
      MAJOR MANUFACTURERS .. 69
   Microarrays for Epigenetics Analysis .. 71
   FIGURE 14 MICROARRAYS ENHANCE MULTIPLEX CAPABILITIES
      OF EPIGENETICS ASSAYS.. 71
           NEXT GENERATION DNA SEQUENCING .. 73
   FIGURE 15 DNA SEQUENCING PLATFORMS .. 73
   FIGURE 16 NEXT GENERATION SEQUENCING TECHNOLOGIES
      WORKFLOW OVERVIEW .. 76
           SERIAL ANALYSIS OF GENE EXPRESSION .. 77
      ANTIBODIES .. 78
      ALTERNATIVES TO ANTIBODIES IN UPSTREAM ANALYSIS
         STEP .. 79
          

CHAPTER SIX: EPIGENETICS DIAGNOSTICS TECHNOLOGIES

     WHAT IS A BIOMARKER? .. 81
  TABLE 26 ROLE OF BIOMARKERS IN CLINICAL TRIAL DESIGN .. 81
     DNA METHYLATION AS A CANCER BIOMARKER .. 82
          DNA METHYLATION IN CANCER ETIOLOGY .. 82
  TABLE 27 BIOLOGICAL RATIONALE FOR DNA METHYLATION
    CANCER BIOMARKERS .. 83
  TABLE 28 CANCER-RELATED CELL PATHWAYS AND GENES
    AFFECTED BY HYPER-METHYLATION .. 84
               Cell Cycle Control .. 84
               Cell Invasion and Adhesion .. 84
               DNA Damage Repair .. 84
               Growth Factor Response .. 85
               Regulation of Apoptosis .. 85
               Hormonal Response .. 85
               Cytokine Signaling .. 85
  TABLE 29 CANCER-RELATED EPIGENETIC CHANGES .. 86
          COMPARISON OF MOLECULAR BIOMARKER PLATFORMS .. 87
  TABLE 30 COMPARISON OF KEY CANCER BIOMARKER
    TECHNOLOGY PLATFORMS.. 87
             ASSESSMENT OF DNA METHYLATION BIOMARKER
            COMPETITIVE POSITION .. 90
     EPIGENETIC BIOMARKER GENES .. 91
   TABLE 31 PUBLISHED DNA METHYLATION BIOMARKER GENES
     FOR CANCERS .. 92
   TABLE 32 DIFFERENTIALLY METHYLATED GENES IN
     NEUROLOGIC AND CARDIOVASCULAR DISORDERS .. 93
      BIOMARKER DISCOVERY PROCESS .. 93
      METHYLATION BIOMARKER DISCOVERY TECHNOLOGIES .. 94
   TABLE 33 DNA METHYLATION ANALYSIS TECHNOLOGIES IN
     BIOMARKER DISCOVERY .. 94
           GENOME-WIDE SCANNING FOR BIOMARKER DISCOVERY .. 95
      CASE STUDY: FROM RESEARCH TOOLS TO BIOMARKERS.. 96
      IN-VITRO DIAGNOSTIC DEVELOPMENT PROCESS .. 97
           PHASE 1: BIOMARKER DISCOVERY.. 97
           PHASE 2: BIOMARKER VALIDATION .. 97
           PHASE 3: FORMAL KIT DEVELOPMENT .. 98
           PHASE 4: CLINICAL VALIDATION .. 99
           PHASE 5: REGULATORY REVIEW AND APPROVAL .. 99
      FUTURE STATUS OF DNA METHYLATION BIOMARKERS .. 100
   TABLE 34 TECHNICAL HURDLES FOR DEVELOPMENT OF
     METHYLATION EPIGENETIC CANCER BIOMARKERS .. 100
    

CHAPTER SEVEN: EPIGENETIC CANCER DRUG TECHNOLOGIES

      INTRODUCTION .. 102
      EPIGENETICS IN TUMORIGENESIS .. 102
      EPIGENETIC GENES IN HUMAN CANCER .. 102
  TABLE 35 EPIGENETIC GENES ALTERED IN HUMAN CANCERS .. 103
      EPIGENETIC ENZYME DRUG TARGETS .. 105
  FIGURE 17 HISTONE DEACETYLASE REACTION .. 105
  TABLE 36 STATUS OF INHIBITORS OF EPIGENETIC ENZYMES
     TARGETING HISTONES .. 106
      HISTONE DEACETYLASE INHIBITORS .. 107
           BENEFITS OF HDAC INHIBITORS .. 108
           HDAC INHIBITOR DRUG CLASSES .. 109
  TABLE 37 HDAC INHIBITOR CLASSES AND RELATIVE POTENCY .. 109
                 Hydroxamates .. 110
  FIGURE 18 CHEMICAL STRUCTURE OF TRICHOSTATIN A, A
     HYDROXAMATE CLASS HDAC INHIBITOR .. 110
                 Aliphatic Acids .. 110
  FIGURE 19 PHENYLBUTYRIC ACID, AN ALIPHATIC ACID CLASS
     HDAC INHIBITOR .. 111
                 Cyclic Tetrapeptides .. 111
  FIGURE 20 APICIDIN A, A CYCLIC TETRAPEPTIDE CLASS HDAC
     INHIBITOR .. 111
               Benzamides .. 112
   FIGURE 21 ENTINOSTAT, A BENZAMIDE CLASS HDAC INHIBITOR .. 112
           HDAC INHIBITOR TECHNOLOGY TRENDS .. 113
   TABLE 38 HDAC INHIBITOR DRUG TECHNOLOGY TRENDS .. 113
                Enzyme Selectivity .. 113
   TABLE 39 HDAC INHIBITOR CLASS I AND II SELECTIVITY .. 115
                Potency .. 115
                Improvements in Drug-like Properties .. 116
           SELECTIVE HDAC COMPOUNDS CAN PROVIDE
             COMPETITIVE ADVANTAGE .. 116
   FIGURE 22 DISEASE HDAC ISOFORM GENE EXPRESSION PROFILE .. 117
           CHEMICAL DESIGN IS THE KEY TO HDAC INHIBITOR
             SELECTIVITY .. 118
   FIGURE 23 COMMON STRUCTURAL COMPONENT MOTIFS OF
      VORINOSTAT.. 118
HDAC INHIBITORS IN COMBINATION THERAPIES .. 120
   TABLE 40 DRUG CLASSES THAT CAN BE USED IN COMBINATION
      WITH HDAC INHIBITORS .. 121
      HDAC INHIBITORS AS THERAPIES OUTSIDE CANCER .. 122
           DERMATOLOGICAL DISORDERS .. 123
           PARASITIC DISEASES .. 123
           NEURODEGENERATIVE DISEASES .. 124
           DIABETES .. 125
           INFLAMMATORY DISEASES .. 125
           IMMUNE DISORDERS .. 125
      DNA METHYLTRANSFERASE INHIBITORS .. 126
   FIGURE 24 LEAD DNMT INHIBITOR COMPOUNDS .. 126
      TECHNICAL CHALLENGES FOR EPIGENETIC DRUG
         DEVELOPMENT .. 127
   TABLE 41 FUTURE CHALLENGES FOR EPIGENETIC DRUG
      DEVELOPMENT .. 127
 

CHAPTER EIGHT: EPIGENETICS CLONING AND CELLULAR  THERAPIES TECHNOLOGIES

     SOMATIC CELL NUCLEAR TRANSFER .. 129
  FIGURE 25 SOMATIC CELL NUCLEAR TRANSFER .. 129
  TABLE 42 TECHNOLOGY OPPORTUNITIES IN SOMATIC CELL
     NUCLEAR TRANSFER .. 130
     APPLICATIONS .. 130
          REPROGRAMMING FACTORS .. 131
  FIGURE 26 EPIGENETIC PROGRAMMING OF STEM CELLS.. 132
          QUALITY CONTROL ASSAYS IN CELLULAR THERAPIES .. 132
                           Tissue Engineering .. 133
                            Stem Cell Therapies .. 133
                            Non-stem Cell Therapies .. 134

CHAPTER NINE: LARGE SCALE REGIONAL EPIGENOMICS PROJECTS

     LARGE SCALE REGIONAL EPIGENOMICS PROJECTS .. 135
  TABLE 43 REGIONAL EPIGENOMICS INITIATIVES .. 136
          EUROPE .. 137
          UNITED STATES .. 138
          ASIA .. 139
             

CHAPTER TEN: CANCER DIAGNOSTICS APPLICATIONS

     ATTRACTIVE CANCER INDICATIONS FOR SCREENING MARKETS .. 141
  FIGURE 27 CANCER SCREENING OPPORTUNITY MATRIX FOR
     MOLECULAR DIAGNOSTICS .. 142
     EPIGENETICS AS A SCREENING PLATFORM.. 143
  FIGURE 28 NEW EPIGENETIC SCREENING PARADIGM .. 144
     DIAGNOSTIC SENSITIVITY AND SPECIFICITY .. 144
  FIGURE 29 SENSITIVITY AND SPECIFICITY .. 145
     STATUS OF DIAGNOSTICS TESTS FOR SELECTED CANCER
        INDICATIONS .. 146
          BLADDER CANCER.. 146
          CARCINOMA OF UNKNOWN PRIMARY (CUP) .. 147
  TABLE 44 COMMERCIAL MOLECULAR DIAGNOSTIC PLATFORMS
     FOR TISSUE OF ORIGIN TESTS .. 148
          CERVICAL CANCER.. 149
  TABLE 45 COMMERCIAL LANDSCAPE FOR HPV TESTS .. 150
         COLORECTAL CANCER .. 152
                     Colorectal Cancer Existing Screening Tests .. 152
  TABLE 46 CURRENT SCREENING AND DIAGNOSTICS TESTS FOR
     COLORECTAL CANCER .. 153
  TABLE 47 ACCURACY OF EXISTING COLORECTAL SCREENING
     TESTS .. 154
                     Molecular Colorectal Cancer Diagnostics Tests .. 155
  TABLE 48 COMMERCIAL LANDSCAPE FOR COLORECTAL
     MOLECULAR TESTS .. 155
 TABLE 49 COMPETITIVE SITUATION FOR CONVENTIONAL AND
     MOLECULAR COLON CANCER SCREENING TESTS .. 157
                     Colorectal Cancer Diagnostics Tests .. 158
          GASTRIC CANCER .. 158
          LUNG CANCER .. 159
           OVARIAN CANCER .. 161
   TABLE 50 OVARIAN CANCER SCREENING TESTS .. 161
   TABLE 51 OVARIAN CANCER DIAGNOSTIC TEST STATUS .. 162
           PANCREATIC CANCER .. 163
           PEDIATRIC CANCERS .. 163
           PROSTATE CANCER .. 164
      PERSONALIZED TREATMENT EPIGENETIC-BASED TESTS .. 166
      KEY CLINICAL REQUIREMENTS FOR AN EPIGENETIC-BASED
        DIAGNOSTICS TEST .. 166
   TABLE 52 REQUIREMENTS FOR AN EPIGENETICS BISULFITE
     DIAGNOSTIC ASSAY .. 167
      DNA METHYLATION DIAGNOSTICS PIPELINE .. 168
   TABLE 53 EPIGENETIC DIAGNOSTICS DEVELOPMENT PIPELINE .. 168
   TABLE 53 (CONTINUED).. 169
   

CHAPTER ELEVEN: THERAPEUTIC APPLICATIONS

     EPIGENETIC DRUG CLINICAL TRIALS .. 171
  TABLE 54 APPROVED EPIGENETIC DRUGS.. 171
  TABLE 55 NEXT GENERATION EPIGENETIC DRUGS .. 171
  FIGURE 30 ACTIVE CANCER EPIGENETIC DRUG CLINICAL
     TRIALS, BY DRUG CLASS AND CANCER TYPE, JANUARY 2010 .. 172
    FIGURE 31 ACTIVE CANCER EPIGENETIC DRUG CLINICAL
     TRIALS, BY PHASE AND INDICATION, JANUARY 2010 .. 174
  FIGURE 32 CURRENT EPIGENETIC CANCER DRUG CLINICAL
     TRIALS, BY DRUG AND TRIAL TYPE, JANUARY 2010 .. 175
  FIGURE 33 ACTIVE EPIGENETIC CANCER DRUG CLINICAL
     TRIALS, BY CLINICAL PHASE AND TRIAL TYPE, JANUARY 2010 .. 176
     EPIGENETIC DRUG NOMENCLATURE .. 177
  TABLE 56 EPIGENETIC DRUG NOMENCLATURE TABLE .. 177
  HDAC INHIBITOR CLINICAL TRIALS .. 178
  TABLE 57 HDAC INHIBITOR CLINICAL TRIALS SUMMARY .. 178
  TABLE 58 MBCD0103 INHIBITS SELECTED HDAC ENZYMES .. 181
       DNMT INHIBITORS CLINICAL TRIALS .. 183
  TABLE 59 DNMT INHIBITOR CLINICAL TRIALS SUMMARY .. 183
     EPIGENETIC DRUGS FOR NON-CANCER INDICATIONS.. 185
   TABLE 60 EPIGENETIC NON-CANCER DRUG LANDSCAPE .. 186

CHAPTER TWELVE: MARKET GROWTH DRIVING FORCES

     EPIGENETICS SCIENTIFIC PUBLICATIONS .. 188
  FIGURE 34 GROWTH IN SCIENTIFIC PUBLICATIONS RELATED TO
     EPIGENETICS (NUMBER OF PUBLICATIONS) .. 188
     GROWTH DRIVING FORCES .. 189
  TABLE 61 FORCES DRIVING EPIGENOMICS INDUSTRY GROWTH .. 189
          GROWTH IN FUNDING FOR LIFE-SCIENCE RESEARCH .. 189
  TABLE 62 STIMULUS FUNDING ALLOCATED TO UNITED STATES
     SCIENCE SPENDING .. 190
  FIGURE 35 ANNUAL NIH FUNDING BUDGET, 2000-2009 ($
     MILIONS).. 190
          CREATION OF EPIGENETIC MAPS .. 191
          RANGE OF OCCURRENCE OF EPIGENETIC CHANGES .. 192
          AGING POPULATIONS IN DEVELOPED COUNTRIES .. 192
          NEED FOR BETTER CANCER THERAPIES .. 193
          GROWTH IN PERSONALIZED MEDICINE .. 193
          UNDERSTANDING OF EPIGENETIC PROCESSES BEYOND CANCER .. 194

CHAPTER THIRTEEN: MARKET ANALYSIS

     MARKET SUMMARY.. 195
  TABLE 63 GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY
    APPLICATION, THROUGH 2014 ($ MILLIONS) .. 195
  TABLE 64 GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY
    GEOGRAPHY, THROUGH 2014 ($ MILLIONS) .. 197
     RESEARCH TOOLS MARKETS.. 197
          GLOBAL SALES BY PRODUCT .. 197
  TABLE 65 GLOBAL VALUE OF EPIGENOMIC ANALYSIS RESEARCH
    TOOLS, BY PRODUCT TYPE, THROUGH 2014 ($ MILLIONS) .. 198
               Kits .. 198
               Reagents .. 198
               Microarrays and Next Gen Sequencing .. 198
          EPIGENOMIC KIT SALES BY TECHNOLOGY .. 200
  TABLE 66 GLOBAL VALUE OF EPIGENOMICS RESEARCH TOOLS
    KITS, BY TECHNOLOGY, THROUGH 2014 ($ MILLION) .. 200
  TABLE 67 GLOBAL VALUE OF EPIGENOMIC ANALYSIS KITS, BY
    FORMAT, THROUGH 2014 ($ MILLIONS) .. 202
          DNA METHYLATION ANALYSIS KIT MARKET .. 202
   TABLE 68 GLOBAL VALUE OF DNA METHYLATION RESEARCH
     TOOLS KITS, BY ANALYSIS OBJECTIVE, THROUGH 2014 ($
     MILLIONS) .. 204
   TABLE 69 GLOBAL VALUE OF DNA METHYLATION RESEARCH
     TOOLS KITS, BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS) .. 205
   TABLE 70 GLOBAL VALUE OF DNA METHYLATION SINGLE LOCI
     RESEARCH TOOLS KITS, BY TECHNOLOGY, THROUGH 2014 ($
     MILLIONS) .. 206
   TABLE 71 GLOBAL VALUE OF DNA METHYLATION GENOME-WIDE
     RESEARCH TOOLS KITS BY TECHNOLOGY, THROUGH 2014 ($
     MILLIONS) .. 207
           HISTONE ANALYSIS KIT MARKET.. 208
   TABLE 72 GLOBAL VALUE OF HISTONE ANALYSIS KITS, BY
     TECHNOLOGY FORMAT, THROUGH 2014 ($ MILLIONS) .. 208
      EPIGENETICS MICROARRAY MARKETS .. 208
           MICROARRAYS AND NEXT GEN SEQUENCING AS
             DOWNSTREAM TOOLS .. 209
           MICROARRAY MARKET .. 209
   TABLE 73 GLOBAL VALUE OF EPIGENOMIC MICROARRAYS, BY
     APPLICATION, THROUGH 2014 ($ MILLIONS) .. 210
           RESEARCH TOOLS REAGENTS MARKET .. 211
   TABLE 74 GLOBAL VALUE OF RESEARCH TOOLS EPIGENOMIC
     REAGENTS, BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS) .. 211

CHAPTER FOURTEEN: EPIGENOMIC DIAGNOSTICS MARKET

     OVERVIEW OF CANCER DIAGNOSTICS MARKET .. 212
  TABLE 75 VALUE OF GLOBAL MOLECULAR DIAGNOSTICS
    PRODUCTS, BY APPLICATION, THROUGH 2014 ($ MILLIONS) .. 212
          CANCER MOLECULAR DIAGNOSTICS GROWTH DRIVERS .. 213
          EPIGENETICS-BASED DIAGNOSTICS MARKETS .. 213
  TABLE 76 PROJECTED CHANGE IN AGE 65-PLUS POPULATION BY
    REGION (%) .. 214
  TABLE 77 U..S.. CANCER INCIDENCE AND ESTIMATED TREATMENT
    DECISIONS, 2009 .. 216
  TABLE 78 GLOBAL VALUE OF EPIGENETIC DIAGNOSTIC ASSAYS,
    BY APPLICATION, THROUGH 2014 ($ MILLIONS) .. 217
  TABLE 79 GLOBAL VALUE OF EPIGENETIC DIAGNOSTIC ASSAYS,
    BY CANCER INDICATION, THROUGH 2014 ($ MILLIONS) .. 218
 

CHAPTER FIFTEEN: EPIGENETIC DRUGS MARKETS

    OVERVIEW .. 220
  CANCER DRUG MARKET GROWTH DRIVING FORCES .. 220
        CLINICAL PROOF OF PRINCIPLE OF EPIGENETIC DRUGS
          IS ESTABLISHED .. 222
        EPIGENETIC THERAPIES BEYOND CANCER .. 223
        EPIGENETIC DRUG MARKET SUMMARY .. 223
TABLE 80 GLOBAL VALUE OF EPIGENETIC DRUGS, BY CANCER
  INDICATION, THROUGH 2014 ($ MILLIONS) .. 224
             Hematological .. 224
             Solid Tumors .. 226
             EPIGENETIC DRUG MARKET BY DRUG CLASS.. 229
TABLE 81 GLOBAL VALUE OF EPIGENETIC DRUGS, BY DRUG
  CLASS, THROUGH 2014 ($ MILLIONS) .. 229
        HDAC INHIBITORS MARKETS .. 229
             Strategic Opportunities in HDAC Inhibitors .. 230
TABLE 82 SUMMARY OF HDAC INHIBITOR STRATEGIC
  OPPORTUNITIES FOR CANCER TREATMENT .. 230
             HDAC Inhibitor Drug Market Size by Indication .. 231
TABLE 83 GLOBAL VALUE OF HDAC INHIBITOR DRUGS, BY
  INDICATION, THROUGH 2014 ($ MILLIONS) .. 232
             HDAC Inhibitor Market Size by Technology .. 233
TABLE 84 GLOBAL VALUE OF HDAC INHIBITOR DRUGS, BY
  TECHNOLOGY, THROUGH 2014 ($ MILLIONS) .. 233
   DNMT INHIBITORS MARKET .. 234
TABLE 85 GLOBAL VALUE OF DNMT INHIBITOR DRUGS, BY
  INDICATION, THROUGH 2014 ($ MILLIONS) .. 235
TABLE 86 GLOBAL VALUE OF DNMT INHIBITOR DRUGS, BY
  TECHNOLOGY, THROUGH 2014 ($ MILLIONS) .. 236
   HEMATOLOGICAL CANCER EPIGENETIC DRUG MARKET .. 236
        OVERVIEW OF HEMATOLOGICAL CANCERS .. 236
TABLE 87 OVERVIEW OF MAJOR HEMATOLOGICAL
  MALIGNANCIES.. 237
TABLE 88 MDS DRUG COMPARISON .. 239
        HEMATOLOGICAL DRUG MARKET BY INDICATION .. 240
TABLE 89 HEMATOLOGICAL CANCER EPIGENETIC DRUGS, BY
  INDICATION, THROUGH 2014 ($ MILLIONS) .. 240
             HDAC Hematological Drug Market.. 241
TABLE 90 HDAC HEMATOLOGICAL CANCER EPIGENETIC DRUGS,
  BY INDICATION, THROUGH 2014 ($ MILLIONS) 
  TABLE 91 COMPARISON OF THE PTCL DRUGS, FOLYTYN AND ISTODAX.. 243
                  DNMT Hematological Drug Market .. 243
   TABLE 92 DNMT HEMATOLOGICAL CANCER EPIGENETIC DRUGS,
     BY INDICATION, THROUGH 2014 ($ MILLIONS) .. 244

CHAPTER SIXTEEN: CELL THERAPY ASSAYS MARKETS

  TABLE 93 EPIGENETIC CELL THERAPIES MARKETS, BY
    APPLICATION, THROUGH 2014 ($ MILLIONS) .. 245

CHAPTER SEVENTEEN: GEOGRAPHICAL MARKETS

  TABLE 94 EPIGENOMIC RESEARCH TOOLS MARKETS, BY
    GEOGRAPHY, THROUGH 2014 ($ MILLIONS) .. 247
  TABLE 95 EPIGENOMIC DIAGNOSTICS MARKETS, BY GEOGRAPHY,
    THROUGH 2014 ($ MILLIONS).. 248
  TABLE 96 NUMBER OF HOSPITALS AND CLINICS, BY
    GEOGRAPHICAL REGION .. 248
  TABLE 97 EPIGENOMIC PHARMACEUTICALS MARKETS, BY
    GEOGRAPHY, THROUGH 2014 ($ MILLIONS) .. 249
  TABLE 98 EPIGENOMIC CELL THERAPIES MARKETS, BY
    GEOGRAPHY, THROUGH 2014 ($ MILLIONS) .. 250

CHAPTER EIGHTEEN: COMPETITOR AND INDUSTRY DYNAMICS

      RESEARCH TOOLS .. 251
  TABLE 99 SCOPE OF EPIGENOMIC RESEARCH TOOLS SUPPLIERS.. 252
  FIGURE 36 CHIP-GRADE ANTIBODY SUPPLIER MARKET SHARES,
     2009 (%) .. 253
      DIAGNOSTICS .. 254
            SKILL SET FOR BIOTECHNOLOGY DIAGNOSTICS
                COMPANIES .. 254
            SHIFTING PARADIGM IN DIAGNOSTICS .. 255
            IN-VITRO DIAGNOSTICS COMPETITORS.. 256
  TABLE 100 IN-VITRO DIAGNOSTICS COMPETITORS .. 256
   TABLE 101 STRATEGIC ALLIANCE STATUS FOR BIOTECHNOLOGY
     EPIGENETICS DIAGNOSTICS FIRMS .. 258
  TABLE 102 COMPETITIVE LANDSCAPE FOR MOLECULAR
     DIAGNOSTICS TECHNOLOGIES .. 259
      EPIGENETIC DRUGS INDUSTRY .. 259
  TABLE 103 RELATIVE STRATEGIC POSITION FOR EPIGENOMIC
     DRUG COMPANIES .. 260
  FIGURE 37 EPIGENOMIC DRUG COMPANY MARKET SHARES, 2009.. 261
      EPIGENOMIC INDUSTRY STRATEGIC ALLIANCES .. 262
  TABLE 104 EPIGENOMICS STATEGIC ALLIANCES: 2007-2010 .. 263
      EPIGENOMICS INDUSTRY ACQUISITIONS .. 267
   TABLE 105 EPIGENOMICS INDUSTRY ACQUISITIONS, 2007­2010 .. 268

CHAPTER NINETEEN: PATENTS

      EPIGENOMICS PATENT ACTIVITY .. 270
  FIGURE 38 NUMBER OF EPIGENOMICS PATENTS, BY YEAR, 2000- 2009 .. 270
  FIGURE 39 NUMBER OF EPIGENOMICS PATENTS, BY
     GEOGRAPHY, 2000­2009 .. 271
RESEARCH TOOLS AND DIAGNOSTICS PATENT ACTIVITY.. 272
  TABLE 106 EPIGENOMICS AG RESEARCH TOOLS PATENT
     COVERAGE .. 272
  FIGURE 40 BIOTECHNOLOGY DIAGNOSTICS PATENTS, BY
     COMPANY (%) .. 274
  TABLE 107 PATENT STATUS FOR BIOTECHNOLOGY DIAGNOSTICS
     COMPANIES .. 275
      PHARMACEUTICALS PATENTS ACTIVITY .. 276
  TABLE 108 HDAC INHIBITOR PATENT CLAIMS, 2004­2006 .. 276
  FIGURE 41 NUMBER OF EPIGENOMICS DRUG PATENTS, BY
     TECHNOLOGY CLASS AND GEOGRAPHY.. 278
  FIGURE 42 NUMBER OF HDAC INHIBITOR PATENTS, BY COMPANY AND GEOGRAPHY .. 280
  FIGURE 43 NUMBER OF DNMT INHIBITOR PATENTS, BY
     COMPANY AND GEOGRAPHY .. 281
      PATENT CASE STUDIES.. 282

CHAPTER TWENTY: COMPANY PROFILES

     ABBOTT LABORATORIES.. 283
     ABCAM PLC.. .. 284
     ACCESS PHARMACEUTICALS .. 285
     ACETYLON PHARMACEUTICALS.. 286
     ACTIVE MOTIF .. 286
     AFFYMETRIX, INC.. .. 287
  TABLE 109 AFFYMETRIX STRATEGIC ALLIANCES .. 289
  AGILENT TECHNOLOGIES, INC.. .. 291
   ARNO THERAPEUTICS, INC.. .. 292
   ARUP LABORATORIES, INC.. 293
   ASTELLAS PHARMA, INC.. .. 293
   BAYER AG .. 294
   BIOFIELD CORP.. .. 295
   BIOSERVE BIOTECHNOLOGIES, LTD.. .. 295
   BIOVISION .. 295
   CELGENE CORPORATION .. 296
   CELLARTIS AB .. 298
   CELLCENTRIC LTD.. .. 298
   CELLERON THERAPEUTICS LTD.. .. 299
   CELLZOME AG .. 300
   CHIPSCREEN BIOSCIENCES LTD.. .. 301
   CHROMA THERAPEUTICS LTD.. .. 302
   CLAVIS PHARMA ASA .. 302
TABLE 110 CLAVIS PHARMA DRUG PIPELINE .. 303
   CONSTELLATION PHARMACEUTICALS .. 304
   CRYSTAL GENOMICS, INC.. .. 304
   CURIS .. 305
   EISAI CO.. LTD.. .. 305
   EPIGENOMICS AG .. 306
   EPIGENTEK .. 308
   EPITHERAPEUTICS .. 309
   ELIXIR PHARMACEUTICALS, INC.. .. 309
   ENVIVO PHARMACEUTICALS .. 310
   EOS SPA.. 311
   EPIONTIS GMBH .. 311
   EPIZYME, INC.. .. 312
   ES CELL INTERNATIONAL PTE LTD .. 313
   EXONHIT THERAPEUTICS SA .. 313
   F.. HOFFMANN-LA ROCHE, LTD.. 314
   GENEXTRA S..P..A .. 315
   GENPATHWAY, INC.. .. 316
   GLAXOSMITHKLINE .. 316
   HUYA BIOSCIENCE INTERNATIONAL .. 318
   ILLUMINA, INC.. .. 319
TABLE 111 ILLUMINA SEQUENCING TECHNOLOGY SPACE .. 321
   IMAGENES GMBH .. 322
   INTERNATIONAL DRUG DISCOVERY INSTITUTE .. 323
  ITALFARMACO SPA.. 323
   JOHNSON & JOHNSON .. 324
   KARUS THERAPEUTICS LTD.. .. 325
   LABORATORY CORPORATION OF AMERICA HOLDINGS .. 326
   LES LABORATOIRES SERVIER .. 327
   LIFE TECHNOLOGIES INC.. .. 328
   MERCK KGAA .. 330
   MERCK & CO.. INC.. .. 331
   METHYLGENE .. 332
TABLE 112 METHYLGENE HDAC INHIBITOR PRODUCT PIPELINE .. 333
   MILLIPORE .. 334
   NATUREWISE BIOTECH & MEDICALS CORP.. .. 335
   NOVARTIS .. 336
   ONCOLYS BIOPHARMA INC.. .. 337
   ONCOMETHYLOME SCIENCES S..A.. .. 338
TABLE 113 ONCOMETHYLOME DNA METHYLATION DIAGNOSTICS
  PIPELINE .. 339
   ORCHID CHEMICALS & PHARMACEUTICALS LIMITED .. 341
   ORION GENOMICS .. 342
TABLE 114 ORION STRATEGIC ALLIANCES .. 343
TABLE 115 ORION EPIGENETIC DIAGNOSTICS PIPELINE .. 344
   ORTHO BIOTECH.. 345
   PACIFIC BIOSCIENCES .. 345
   PHARMACYCLICS.. 346
   PROGEN PHARMACEUTICALS LTD.. .. 347
   PROGNOSDX HEALTH, INC.. .. 349
   QUEST DIAGNOSTICS .. 349
   ROCHE LIFE SCIENCES .. 350
   QIAGEN GMBH.. 353
   RAINDANCE TECHNOLOGIES .. 354
   REACTION BIOLOGY CORP.. .. 354
   REPLIGEN CORPORATION .. 355
   RUBICON GENOMICS .. 355
   S*BIO PTE LTD .. 357
TABLE 116 S*BIO HDAC INHIBITOR DRUG PIPELINE .. 358
   SCHERING PLOUGH CORPORATION .. 358
   SCOTTISH BIOMEDICAL LTD.. .. 359
   SEQUENOM, INC.. .. 360
   SEQWRIGHT .. 362
   SUPERGEN, INC.. .. 362
   SYNDAX PHARMACEUTICALS, INC.. .. 363
TABLE 117 ENTINOSTAT CLINICAL TRIALS SUMMARY STATUS .. 363
   SYSMEX CORPORATION .. 364
   TAIHO PHARMACEUTICALS .. 365
   TAKEDA PHARMACEUTICAL COMPANY LIMITED .. 365
   TARGECEPT, INC.. .. 366
   THEREPI INC.. 366
   TOPOTARGET A/S .. 366
TABLE 118 TOPOTARGET'S HDAC INHIBITOR PATENT PORTFOLIO .. 369
   VALIBIO SA .. 370
   VALIRX .. 371
   VERIDEX LLC .. 371
   ZYMO RESEARCH .. 372