Epigenomics: Emerging Opportunities in Biomarkers, Diagnostics and Therapeutics

Report Summary

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

REASONS FOR DOING THE STUDY

INTENDED AUDIENCE

SCOPE OF REPORT

METHODOLOGY

INFORMATION SOURCES

RELATED BCC REPORTS

BCC ONLINE SERVICES

DISCLAIMER

CHAPTER TWO: SUMMARY

 

SUMMARY

SUMMARY TABLE GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY APPLICATION, THROUGH 2014 ($ MILLIONS)

SUMMARY FIGURE GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY APPLICATION, 2008-2014 ($ MILLIONS)

CHAPTER THREE: OVERVIEW

INTRODUCTION

THE NEW PARADIGM OF EPIGENOMICS

FIGURE 1 EPIGENOMICS: A NEW PARADIGM

HOW EPIGENOMICS FITS WITHIN GENOMICS

TABLE 1 GENOMICS PLATFORMS

TECHNICAL SCOPE OF THIS REPORT

TABLE 2 TECHNOLOGY SCOPE OF THIS REPORT

MARKET POTENTIAL OF EPIGENOMICS

TABLE 3 GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY APPLICATION, THROUGH 2014 ($ MILLIONS)

EPIGENOMICS PRODUCTS

RESEARCH TOOLS AND REAGENTS

DIAGNOSTICS

DRUGS

FIGURE 2 ACTIVE CANCER EPIGENETIC DRUG CLINICAL TRIALS, BY PHASE AND INDICATION, JANUARY 2010

GROWTH DRIVING FORCES

GROWTH IN LIFE SCIENCE FUNDING

CREATION OF EPIGENOMIC MAPS

AGING POPULATION IN DEVELOPED COUNTRIES

NEED FOR BETTER CANCER THERAPIES

GROWTH IN PERSONALIZED MEDICINE

WHY EPIGENETIC TECHNOLOGY IS IMPORTANT

FIGURE 3 EPIGENETIC PROCESSES CAN GENERATE ABNORMAL CELLS DURING CELL DEVELOPMENT

LIFE CYCLE STATUS OF EPIGENOMICS TECHNOLOGIES

HISTORICAL BACKGROUND

TABLE 4 HISTORICAL OVERVIEW OF EPIGENOMICS

THE EPIGENOMICS INDUSTRY

TABLE 5 EPIGENOMICS INDUSTRY KEY COMPANIES

CHAPTER FOUR: EPIGENETIC TECHNOLOGIES

INTRODUCTION

EPIGENETIC ANALYSIS TECHNOLOGIES

TABLE 6 EPIGENETIC ANALYSIS TECHNOLOGIES

STATUS OF DNA AND HISTONE ANALYSIS TECHNOLOGIES

TABLE 7 STATUS OF DNA METHYLATION AND HISTONE ANALYSIS TECHNOLOGIES

DNA AND HISTONE ANALYSIS WORKFLOW

FIGURE 4 UPSTREAM AND DOWNSTREAM STEPS IN EPIGENETIC ANALYSIS WORKFLOW

DNA METHYLATION

METHYLATED CYTOSINE—A FIFTH BASE

FIGURE 5 EPIGENETIC CHANGES TO DNA AFFECT GENE EXPRESSION

BIOLOGICAL ROLE OF DNA METHYLATION

TABLE 8 BIOLOGICAL ROLES OF DNA METHYLATION

DNA METHYLTRANSFERASE ENZYMES

CPG ISLANDS

TABLE 9 DESCRIPTION OF CPG ISLANDS

HISTONE METHYLATION AND ACETYLATION

HISTONES

HISTONE MODIFICATIONS

FIGURE 6 ACETYLATION OF HISTONE TAIL REGIONS

HISTONE ACETYLATION AND METHYLATION ENZYMES

FIGURE 7 HISTONE ACETYLATION AND METHYLATION ENZYMES

Histone Acetyl Transferases (HAT)

Histone Deacetylases (HDAC)

TABLE 10 HDAC ENZYMES CLASSES

Histone Methyltransferases and Demethylases

INAPPROPRIATE METHYLATION AND ACETYLATION

TABLE 11 MECHANISMS FOR INAPPROPRIATE METHYLATION AND ACETYLATION

CHAPTER FIVE: EPIGENOMIC ANALYSIS TECHNOLOGIES

IMPORTANCE OF EPIGENOMIC RESEARCH TOOLS

DNA METHYLATION RESEARCH TOOLS

TABLE 12 DNA METHYLATION ANALYSIS ASSAYS

TABLE 13 EMERGING DNA METHYLATION TECHNOLOGIES

TABLE 14 ACROYNMS FOR DNA METHYLATION TECHNOLOGIES

DNA METHYLATION ANALYSIS WORKFLOW

FIGURE 8 METHYLATED DNA ANALYSIS WORKFLOW

DNA METHYLATION ANALYSIS METHODS BY COVERAGE AND THROUGHPUT

TABLE 15 DNA METHYLATION TECHNOLOGIES BY COVERAGE AND THROUGHPUT

DNA METHYLATION ANALYSIS TYPES BY WORKFLOW

TABLE 16 EXAMPLES OF DNA METHYLATION ASSAYS

DNA METHYLATION ANALYSIS: UPSTREAM TECHNOLOGIES

TABLE 17 METHYLATION RECOGNITION TECHNOLOGIES

RESTRICTION ENZYME-BASED METHODS

FIGURE 9 ANALYSIS OF DNA METHYLATION BY RESTRICTION ENZYMES

BISULFITE-BASED METHODS

Bisulfite-based Methods (Continued)

FIGURE 10 BISULFITE CONVERSION OF DNA

Analysis of Low Complexity DNA

AFFINITY-BASED METHODS

CHALLENGE OF HIGH BACKGROUND METHYLATED DNA

GENOME WIDE DNA METHYLATION ANALYSIS

TABLE 18 DNA METHYLATION ANALYSIS TECHNIQUES BY GENOME RESOLUTION

HISTONE EPIGENETIC ANALYSIS TECHNOLOGIES

TABLE 19 CHIP ASSAYS

CHIP-CHIP AND CHIP-SEQ

FIGURE 11 WORKFLOW SCHEMATIC FOR CHIP PLATFORMS

TABLE 20 TECHNOLOGIES FOR MAPPING GENOMIC LOCATION OF CHROMATIN PROTEINS AND ENZYMES

EMERGING DOWNSTREAM EPIGENETIC ANALYSIS PLATFORMS

MICROARRAYS

TABLE 21 MICROARRAY TYPES

TABLE 22 COMPARISON OF DNA AND PROTEIN MICROARRAY TECHNOLOGIES

DNA Microarray Technologies

FIGURE 12 MICROARRAY FEATURE DENSITY

FIGURE 13 MICROARRAY RESOLUTION

TABLE 23 MICROARRAY GENOME CONTENT

TABLE 24 DNA MICROARRAY PLATFORM FEATURES

TABLE 25 DNA MICROARRAY PLATFORM COMPARISON FOR MAJOR MANUFACTURERS

Microarrays for Epigenetics Analysis

FIGURE 14 MICROARRAYS ENHANCE MULTIPLEX CAPABILITIES OF EPIGENETICS ASSAYS

NEXT GENERATION DNA SEQUENCING

FIGURE 15 DNA SEQUENCING PLATFORMS

FIGURE 16 NEXT GENERATION SEQUENCING TECHNOLOGIES WORKFLOW OVERVIEW

SERIAL ANALYSIS OF GENE EXPRESSION

ANTIBODIES

ALTERNATIVES TO ANTIBODIES IN UPSTREAM ANALYSIS

STEP

CHAPTER SIX: EPIGENETICS DIAGNOSTICS TECHNOLOGIES

WHAT IS A BIOMARKER?

TABLE 26 ROLE OF BIOMARKERS IN CLINICAL TRIAL DESIGN

DNA METHYLATION AS A CANCER BIOMARKER

DNA METHYLATION IN CANCER ETIOLOGY

TABLE 27 BIOLOGICAL RATIONALE FOR DNA METHYLATION CANCER BIOMARKERS

TABLE 28 CANCER-RELATED CELL PATHWAYS AND GENES AFFECTED BY HYPER-METHYLATION

Cell Cycle Control

Cell Invasion and Adhesion

DNA Damage Repair

Growth Factor Response

Regulation of Apoptosis

Hormonal Response

Cytokine Signaling

TABLE 29 CANCER-RELATED EPIGENETIC CHANGES

COMPARISON OF MOLECULAR BIOMARKER PLATFORMS

TABLE 30 COMPARISON OF KEY CANCER BIOMARKER TECHNOLOGY PLATFORMS

ASSESSMENT OF DNA METHYLATION BIOMARKER COMPETITIVE POSITION

EPIGENETIC BIOMARKER GENES

TABLE 31 PUBLISHED DNA METHYLATION BIOMARKER GENES FOR CANCERS

TABLE 32 DIFFERENTIALLY METHYLATED GENES IN NEUROLOGIC AND CARDIOVASCULAR DISORDERS

BIOMARKER DISCOVERY PROCESS

METHYLATION BIOMARKER DISCOVERY TECHNOLOGIES

TABLE 33 DNA METHYLATION ANALYSIS TECHNOLOGIES IN BIOMARKER DISCOVERY

GENOME-WIDE SCANNING FOR BIOMARKER DISCOVERY

CASE STUDY: FROM RESEARCH TOOLS TO BIOMARKERS

IN-VITRO DIAGNOSTIC DEVELOPMENT PROCESS

PHASE 1: BIOMARKER DISCOVERY

PHASE 2: BIOMARKER VALIDATION

PHASE 3: FORMAL KIT DEVELOPMENT

PHASE 4: CLINICAL VALIDATION

PHASE 5: REGULATORY REVIEW AND APPROVAL

FUTURE STATUS OF DNA METHYLATION BIOMARKERS

TABLE 34 TECHNICAL HURDLES FOR DEVELOPMENT OF METHYLATION EPIGENETIC CANCER BIOMARKERS

CHAPTER SEVEN: EPIGENETIC CANCER DRUG TECHNOLOGIES

INTRODUCTION

EPIGENETICS IN TUMORIGENESIS

EPIGENETIC GENES IN HUMAN CANCER

TABLE 35 EPIGENETIC GENES ALTERED IN HUMAN CANCERS

EPIGENETIC ENZYME DRUG TARGETS

FIGURE 17 HISTONE DEACETYLASE REACTION

TABLE 36 STATUS OF INHIBITORS OF EPIGENETIC ENZYMES TARGETING HISTONES

HISTONE DEACETYLASE INHIBITORS

BENEFITS OF HDAC INHIBITORS

HDAC INHIBITOR DRUG CLASSES

TABLE 37 HDAC INHIBITOR CLASSES AND RELATIVE POTENCY

Hydroxamates

FIGURE 18 CHEMICAL STRUCTURE OF TRICHOSTATIN A, A HYDROXAMATE CLASS HDAC INHIBITOR

Aliphatic Acids

FIGURE 19 PHENYLBUTYRIC ACID, AN ALIPHATIC ACID CLASS HDAC INHIBITOR

Cyclic Tetrapeptides

FIGURE 20 APICIDIN A, A CYCLIC TETRAPEPTIDE CLASS HDAC INHIBITOR

Benzamides

FIGURE 21 ENTINOSTAT, A BENZAMIDE CLASS HDAC INHIBITOR

HDAC INHIBITOR TECHNOLOGY TRENDS

TABLE 38 HDAC INHIBITOR DRUG TECHNOLOGY TRENDS

Enzyme Selectivity

TABLE 39 HDAC INHIBITOR CLASS I AND II SELECTIVITY

Potency

Improvements in Drug-like Properties

SELECTIVE HDAC COMPOUNDS CAN PROVIDE COMPETITIVE ADVANTAGE

FIGURE 22 DISEASE HDAC ISOFORM GENE EXPRESSION PROFILE

CHEMICAL DESIGN IS THE KEY TO HDAC INHIBITOR SELECTIVITY

FIGURE 23 COMMON STRUCTURAL COMPONENT MOTIFS OF VORINOSTAT

HDAC INHIBITORS IN COMBINATION THERAPIES

TABLE 40 DRUG CLASSES THAT CAN BE USED IN COMBINATION WITH HDAC INHIBITORS

HDAC INHIBITORS AS THERAPIES OUTSIDE CANCER

DERMATOLOGICAL DISORDERS

PARASITIC DISEASES

NEURODEGENERATIVE DISEASES

DIABETES

INFLAMMATORY DISEASES

IMMUNE DISORDERS

DNA METHYLTRANSFERASE INHIBITORS

FIGURE 24 LEAD DNMT INHIBITOR COMPOUNDS

TECHNICAL CHALLENGES FOR EPIGENETIC DRUG DEVELOPMENT

TABLE 41 FUTURE CHALLENGES FOR EPIGENETIC DRUG

DEVELOPMENT

CHAPTER EIGHT: EPIGENETICS CLONING AND CELLULAR THERAPIES TECHNOLOGIES

SOMATIC CELL NUCLEAR TRANSFER

FIGURE 25 SOMATIC CELL NUCLEAR TRANSFER

TABLE 42 TECHNOLOGY OPPORTUNITIES IN SOMATIC CELL NUCLEAR TRANSFER

APPLICATIONS

REPROGRAMMING FACTORS

FIGURE 26 EPIGENETIC PROGRAMMING OF STEM CELLS

QUALITY CONTROL ASSAYS IN CELLULAR THERAPIES

Tissue Engineering

Stem Cell Therapies

Non-stem Cell Therapies

CHAPTER NINE: LARGE SCALE REGIONAL EPIGENOMICS PROJECTS

LARGE SCALE REGIONAL EPIGENOMICS PROJECTS

TABLE 43 REGIONAL EPIGENOMICS INITIATIVES

EUROPE

UNITED STATES

ASIA

CHAPTER TEN: CANCER DIAGNOSTICS APPLICATIONS

ATTRACTIVE CANCER INDICATIONS FOR SCREENING MARKETS

FIGURE 27 CANCER SCREENING OPPORTUNITY MATRIX FOR MOLECULAR DIAGNOSTICS

EPIGENETICS AS A SCREENING PLATFORM

FIGURE 28 NEW EPIGENETIC SCREENING PARADIGM

DIAGNOSTIC SENSITIVITY AND SPECIFICITY

FIGURE 29 SENSITIVITY AND SPECIFICITY

STATUS OF DIAGNOSTICS TESTS FOR SELECTED CANCER INDICATIONS

BLADDER CANCER

CARCINOMA OF UNKNOWN PRIMARY (CUP)

TABLE 44 COMMERCIAL MOLECULAR DIAGNOSTIC PLATFORMS FOR TISSUE OF ORIGIN TESTS

CERVICAL CANCER

TABLE 45 COMMERCIAL LANDSCAPE FOR HPV TESTS

COLORECTAL CANCER

Colorectal Cancer Existing Screening Tests

TABLE 46 CURRENT SCREENING AND DIAGNOSTICS TESTS FOR COLORECTAL CANCER

TABLE 47 ACCURACY OF EXISTING COLORECTAL SCREENING TESTS

Molecular Colorectal Cancer Diagnostics Tests

TABLE 48 COMMERCIAL LANDSCAPE FOR COLORECTAL MOLECULAR TESTS

TABLE 49 COMPETITIVE SITUATION FOR CONVENTIONAL AND MOLECULAR COLON CANCER SCREENING TESTS

Colorectal Cancer Diagnostics Tests

GASTRIC CANCER

LUNG CANCER

OVARIAN CANCER

TABLE 50 OVARIAN CANCER SCREENING TESTS

TABLE 51 OVARIAN CANCER DIAGNOSTIC TEST STATUS

PANCREATIC CANCER

PEDIATRIC CANCERS

PROSTATE CANCER

PERSONALIZED TREATMENT EPIGENETIC-BASED TESTS

KEY CLINICAL REQUIREMENTS FOR AN EPIGENETIC-BASED DIAGNOSTICS TEST

TABLE 52 REQUIREMENTS FOR AN EPIGENETICS BISULFITE DIAGNOSTIC ASSAY

DNA METHYLATION DIAGNOSTICS PIPELINE

TABLE 53 EPIGENETIC DIAGNOSTICS DEVELOPMENT PIPELINE

CHAPTER ELEVEN: THERAPEUTIC APPLICATIONS

EPIGENETIC DRUG CLINICAL TRIALS

TABLE 54 APPROVED EPIGENETIC DRUGS

TABLE 55 NEXT GENERATION EPIGENETIC DRUGS

FIGURE 30 ACTIVE CANCER EPIGENETIC DRUG CLINICAL TRIALS, BY DRUG CLASS AND CANCER TYPE, JANUARY 2010

FIGURE 31 ACTIVE CANCER EPIGENETIC DRUG CLINICAL TRIALS, BY PHASE AND INDICATION, JANUARY 2010

FIGURE 32 CURRENT EPIGENETIC CANCER DRUG CLINICAL TRIALS, BY DRUG AND TRIAL TYPE, JANUARY 2010

FIGURE 33 ACTIVE EPIGENETIC CANCER DRUG CLINICAL TRIALS, BY CLINICAL PHASE AND TRIAL TYPE, JANUARY 2010

EPIGENETIC DRUG NOMENCLATURE

TABLE 56 EPIGENETIC DRUG NOMENCLATURE TABLE

HDAC INHIBITOR CLINICAL TRIALS

TABLE 57 HDAC INHIBITOR CLINICAL TRIALS SUMMARY

TABLE 58 MBCD0103 INHIBITS SELECTED HDAC ENZYMES

DNMT INHIBITORS CLINICAL TRIALS

TABLE 59 DNMT INHIBITOR CLINICAL TRIALS SUMMARY

EPIGENETIC DRUGS FOR NON-CANCER INDICATIONS

TABLE 60 EPIGENETIC NON-CANCER DRUG LANDSCAPE

CHAPTER TWELVE: MARKET GROWTH DRIVING FORCES

EPIGENETICS SCIENTIFIC PUBLICATIONS

FIGURE 34 GROWTH IN SCIENTIFIC PUBLICATIONS RELATED TO EPIGENETICS (NUMBER OF PUBLICATIONS)

GROWTH DRIVING FORCES

TABLE 61 FORCES DRIVING EPIGENOMICS INDUSTRY GROWTH

GROWTH IN FUNDING FOR LIFE-SCIENCE RESEARCH

TABLE 62 STIMULUS FUNDING ALLOCATED TO UNITED STATES SCIENCE SPENDING

FIGURE 35 ANNUAL NIH FUNDING BUDGET, 2000-2009 ($ MILIONS)

CREATION OF EPIGENETIC MAPS

RANGE OF OCCURRENCE OF EPIGENETIC CHANGES

AGING POPULATIONS IN DEVELOPED COUNTRIES

NEED FOR BETTER CANCER THERAPIES

GROWTH IN PERSONALIZED MEDICINE

UNDERSTANDING OF EPIGENETIC PROCESSES BEYOND CANCER

CHAPTER THIRTEEN: MARKET ANALYSIS

MARKET SUMMARY

TABLE 63 GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY APPLICATION, THROUGH 2014 ($ MILLIONS)

TABLE 64 GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY GEOGRAPHY, THROUGH 2014 ($ MILLIONS)

RESEARCH TOOLS MARKETS

GLOBAL SALES BY PRODUCT

TABLE 65 GLOBAL VALUE OF EPIGENOMIC ANALYSIS RESEARCH TOOLS, BY PRODUCT TYPE, THROUGH 2014 ($ MILLIONS)

Kits

Reagents

Microarrays and Next Gen Sequencing

EPIGENOMIC KIT SALES BY TECHNOLOGY

TABLE 66 GLOBAL VALUE OF EPIGENOMICS RESEARCH TOOLS KITS, BY TECHNOLOGY, THROUGH 2014 ($ MILLION)

TABLE 67 GLOBAL VALUE OF EPIGENOMIC ANALYSIS KITS, BY FORMAT, THROUGH 2014 ($ MILLIONS)

DNA METHYLATION ANALYSIS KIT MARKET

TABLE 68 GLOBAL VALUE OF DNA METHYLATION RESEARCH TOOLS KITS, BY ANALYSIS OBJECTIVE, THROUGH 2014 ($ MILLIONS)

TABLE 69 GLOBAL VALUE OF DNA METHYLATION RESEARCH TOOLS KITS, BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

TABLE 70 GLOBAL VALUE OF DNA METHYLATION SINGLE LOCI RESEARCH TOOLS KITS, BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

TABLE 71 GLOBAL VALUE OF DNA METHYLATION GENOME-WIDE RESEARCH TOOLS KITS BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

HISTONE ANALYSIS KIT MARKET

TABLE 72 GLOBAL VALUE OF HISTONE ANALYSIS KITS, BY TECHNOLOGY FORMAT, THROUGH 2014 ($ MILLIONS)

EPIGENETICS MICROARRAY MARKETS

MICROARRAYS AND NEXT GEN SEQUENCING AS DOWNSTREAM TOOLS

MICROARRAY MARKET

TABLE 73 GLOBAL VALUE OF EPIGENOMIC MICROARRAYS, BY APPLICATION, THROUGH 2014 ($ MILLIONS)

RESEARCH TOOLS REAGENTS MARKET

TABLE 74 GLOBAL VALUE OF RESEARCH TOOLS EPIGENOMIC REAGENTS, BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

CHAPTER FOURTEEN: EPIGENOMIC DIAGNOSTICS MARKET

OVERVIEW OF CANCER DIAGNOSTICS MARKET

TABLE 75 VALUE OF GLOBAL MOLECULAR DIAGNOSTICS PRODUCTS, BY APPLICATION, THROUGH 2014 ($ MILLIONS)

CANCER MOLECULAR DIAGNOSTICS GROWTH DRIVERS

EPIGENETICS-BASED DIAGNOSTICS MARKETS

TABLE 76 PROJECTED CHANGE IN AGE 65-PLUS POPULATION BY REGION (%)

TABLE 77 U.S. CANCER INCIDENCE AND ESTIMATED TREATMENT DECISIONS, 2009

TABLE 78 GLOBAL VALUE OF EPIGENETIC DIAGNOSTIC ASSAYS, BY APPLICATION, THROUGH 2014 ($ MILLIONS)

TABLE 79 GLOBAL VALUE OF EPIGENETIC DIAGNOSTIC ASSAYS, BY CANCER INDICATION, THROUGH 2014 ($ MILLIONS)

CHAPTER FIFTEEN: EPIGENETIC DRUGS MARKETS

OVERVIEW

CANCER DRUG MARKET GROWTH DRIVING FORCES

CLINICAL PROOF OF PRINCIPLE OF EPIGENETIC DRUGS

IS ESTABLISHED

EPIGENETIC THERAPIES BEYOND CANCER

EPIGENETIC DRUG MARKET SUMMARY

TABLE 80 GLOBAL VALUE OF EPIGENETIC DRUGS, BY CANCER INDICATION, THROUGH 2014 ($ MILLIONS)

Hematological

Solid Tumors

EPIGENETIC DRUG MARKET BY DRUG CLASS

TABLE 81 GLOBAL VALUE OF EPIGENETIC DRUGS, BY DRUG CLASS, THROUGH 2014 ($ MILLIONS)

HDAC INHIBITORS MARKETS

Strategic Opportunities in HDAC Inhibitors

TABLE 82 SUMMARY OF HDAC INHIBITOR STRATEGIC OPPORTUNITIES FOR CANCER TREATMENT

HDAC Inhibitor Drug Market Size by Indication

TABLE 83 GLOBAL VALUE OF HDAC INHIBITOR DRUGS, BY INDICATION, THROUGH 2014 ($ MILLIONS)

HDAC Inhibitor Market Size by Technology

TABLE 84 GLOBAL VALUE OF HDAC INHIBITOR DRUGS, BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

DNMT INHIBITORS MARKET

TABLE 85 GLOBAL VALUE OF DNMT INHIBITOR DRUGS, BY INDICATION, THROUGH 2014 ($ MILLIONS)

TABLE 86 GLOBAL VALUE OF DNMT INHIBITOR DRUGS, BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

HEMATOLOGICAL CANCER EPIGENETIC DRUG MARKET

OVERVIEW OF HEMATOLOGICAL CANCERS

TABLE 87 OVERVIEW OF MAJOR HEMATOLOGICAL MALIGNANCIES

TABLE 88 MDS DRUG COMPARISON

HEMATOLOGICAL DRUG MARKET BY INDICATION

TABLE 89 HEMATOLOGICAL CANCER EPIGENETIC DRUGS, BY INDICATION, THROUGH 2014 ($ MILLIONS)

HDAC Hematological Drug Market

TABLE 90 HDAC HEMATOLOGICAL CANCER EPIGENETIC DRUGS, BY INDICATION, THROUGH 2014 ($ MILLIONS)

TABLE 91 COMPARISON OF THE PTCL DRUGS, FOLYTYN AND ISTODAX

DNMT Hematological Drug Market

TABLE 92 DNMT HEMATOLOGICAL CANCER EPIGENETIC DRUGS, BY INDICATION, THROUGH 2014 ($ MILLIONS)

CHAPTER SIXTEEN: CELL THERAPY ASSAYS MARKETS

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

CHAPTER SEVENTEEN: GEOGRAPHICAL MARKETS

TABLE 94 EPIGENOMIC RESEARCH TOOLS MARKETS, BY

GEOGRAPHY, THROUGH 2014 ($ MILLIONS)

TABLE 95 EPIGENOMIC DIAGNOSTICS MARKETS, BY GEOGRAPHY, THROUGH 2014 ($ MILLIONS)

TABLE 96 NUMBER OF HOSPITALS AND CLINICS, BY GEOGRAPHICAL REGION

TABLE 97 EPIGENOMIC PHARMACEUTICALS MARKETS, BY GEOGRAPHY, THROUGH 2014 ($ MILLIONS)

TABLE 98 EPIGENOMIC CELL THERAPIES MARKETS, BY GEOGRAPHY, THROUGH 2014 ($ MILLIONS)

CHAPTER EIGHTEEN: COMPETITOR AND INDUSTRY DYNAMICS

RESEARCH TOOLS

TABLE 99 SCOPE OF EPIGENOMIC RESEARCH TOOLS SUPPLIERS

FIGURE 36 CHIP-GRADE ANTIBODY SUPPLIER MARKET SHARES, 2009 (%)

DIAGNOSTICS

SKILL SET FOR BIOTECHNOLOGY DIAGNOSTICS COMPANIES

SHIFTING PARADIGM IN DIAGNOSTICS

IN-VITRO DIAGNOSTICS COMPETITORS

TABLE 100 IN-VITRO DIAGNOSTICS COMPETITORS

TABLE 101 STRATEGIC ALLIANCE STATUS FOR BIOTECHNOLOGY EPIGENETICS DIAGNOSTICS FIRMS

TABLE 102 COMPETITIVE LANDSCAPE FOR MOLECULAR DIAGNOSTICS TECHNOLOGIES

EPIGENETIC DRUGS INDUSTRY

TABLE 103 RELATIVE STRATEGIC POSITION FOR EPIGENOMIC DRUG COMPANIES

FIGURE 37 EPIGENOMIC DRUG COMPANY MARKET SHARES, 2009

EPIGENOMIC INDUSTRY STRATEGIC ALLIANCES

TABLE 104 EPIGENOMICS STATEGIC ALLIANCES: 2007-2010

EPIGENOMICS INDUSTRY ACQUISITIONS

TABLE 105 EPIGENOMICS INDUSTRY ACQUISITIONS, 2007-2010

CHAPTER NINETEEN: PATENTS

EPIGENOMICS PATENT ACTIVITY

FIGURE 38 NUMBER OF EPIGENOMICS PATENTS, BY YEAR, 2000-2009

FIGURE 39 NUMBER OF EPIGENOMICS PATENTS, BY GEOGRAPHY, 2000-2009

RESEARCH TOOLS AND DIAGNOSTICS PATENT ACTIVITY

TABLE 106 EPIGENOMICS AG RESEARCH TOOLS PATENT COVERAGE

FIGURE 40 BIOTECHNOLOGY DIAGNOSTICS PATENTS, BY COMPANY (%)

TABLE 107 PATENT STATUS FOR BIOTECHNOLOGY DIAGNOSTICS COMPANIES

PHARMACEUTICALS PATENTS ACTIVITY

TABLE 108 HDAC INHIBITOR PATENT CLAIMS, 2004-2006

FIGURE 41 NUMBER OF EPIGENOMICS DRUG PATENTS, BY TECHNOLOGY CLASS AND GEOGRAPHY

FIGURE 42 NUMBER OF HDAC INHIBITOR PATENTS, BY COMPANY AND GEOGRAPHY

FIGURE 43 NUMBER OF DNMT INHIBITOR PATENTS, BY COMPANY AND GEOGRAPHY

PATENT CASE STUDIES

CHAPTER TWENTY: COMPANY PROFILES

ABBOTT LABORATORIES

ABCAM PLC.

ACCESS PHARMACEUTICALS

ACETYLON PHARMACEUTICALS

ACTIVE MOTIF

AFFYMETRIX, INC.

TABLE 109 AFFYMETRIX STRATEGIC ALLIANCES

AGILENT TECHNOLOGIES, INC.

ARNO THERAPEUTICS, INC.

ARUP LABORATORIES, INC

ASTELLAS PHARMA, INC.

BAYER AG

BIOFIELD CORP.

BIOSERVE BIOTECHNOLOGIES, LTD.

BIOVISION

CELGENE CORPORATION

CELLARTIS AB

CELLCENTRIC LTD.

CELLERON THERAPEUTICS LTD.

CELLZOME AG

CHIPSCREEN BIOSCIENCES LTD.

CHROMA THERAPEUTICS LTD.

CLAVIS PHARMA ASA

TABLE 110 CLAVIS PHARMA DRUG PIPELINE

CONSTELLATION PHARMACEUTICALS

CRYSTAL GENOMICS, INC.

CURIS

EISAI CO. LTD.

EPIGENOMICS AG

EPIGENTEK

EPITHERAPEUTICS

ELIXIR PHARMACEUTICALS, INC.

ENVIVO PHARMACEUTICALS

EOS SPA

EPIONTIS GMBH

EPIZYME, INC.

ES CELL INTERNATIONAL PTE LTD

EXONHIT THERAPEUTICS SA

F. HOFFMANN-LA ROCHE, LTD.

GENEXTRA S.P.A

GENPATHWAY, INC.

GLAXOSMITHKLINE

HUYA BIOSCIENCE INTERNATIONAL

ILLUMINA, INC.

TABLE 111 ILLUMINA SEQUENCING TECHNOLOGY SPACE

IMAGENES GMBH

INTERNATIONAL DRUG DISCOVERY INSTITUTE

ITALFARMACO SPA

JOHNSON & JOHNSON

KARUS THERAPEUTICS LTD.

LABORATORY CORPORATION OF AMERICA HOLDINGS

LES LABORATOIRES SERVIER

LIFE TECHNOLOGIES INC.

MERCK KGAA

MERCK & CO. INC.

METHYLGENE

TABLE 112 METHYLGENE HDAC INHIBITOR PRODUCT PIPELINE

MILLIPORE

NATUREWISE BIOTECH & MEDICALS CORP.

NOVARTIS

ONCOLYS BIOPHARMA INC.

ONCOMETHYLOME SCIENCES S.A.

TABLE 113 ONCOMETHYLOME DNA METHYLATION DIAGNOSTICS PIPELINE

ORCHID CHEMICALS & PHARMACEUTICALS LIMITED

ORION GENOMICS

TABLE 114 ORION STRATEGIC ALLIANCES

TABLE 115 ORION EPIGENETIC DIAGNOSTICS PIPELINE

ORTHO BIOTECH

PACIFIC BIOSCIENCES

PHARMACYCLICS

PROGEN PHARMACEUTICALS LTD.

PROGNOSDX HEALTH, INC.

QUEST DIAGNOSTICS

ROCHE LIFE SCIENCES

QIAGEN GMBH

RAINDANCE TECHNOLOGIES

REACTION BIOLOGY CORP.

REPLIGEN CORPORATION

RUBICON GENOMICS

S*BIO PTE LTD

TABLE 116 S*BIO HDAC INHIBITOR DRUG PIPELINE

SCHERING PLOUGH CORPORATION

SCOTTISH BIOMEDICAL LTD.

SEQUENOM, INC.

SEQWRIGHT

SUPERGEN, INC.

SYNDAX PHARMACEUTICALS, INC.

TABLE 117 ENTINOSTAT CLINICAL TRIALS SUMMARY STATUS

SYSMEX CORPORATION

TAIHO PHARMACEUTICALS

TAKEDA PHARMACEUTICAL COMPANY LIMITED

TARGECEPT, INC.

THEREPI INC

TOPOTARGET A/S

TABLE 118 TOPOTARGET’S HDAC INHIBITOR PATENT PORTFOLIO

VALIBIO SA

VALIRX

VERIDEX LLC

ZYMO RESEARCH

LIST OF TABLES

SUMMARY TABLE GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY

APPLICATION, THROUGH 2014 ($ MILLIONS)

TABLE 1 GENOMICS PLATFORMS

TABLE 2 TECHNOLOGY SCOPE OF THIS REPORT

TABLE 3 GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY

APPLICATION, THROUGH 2014 ($ MILLIONS)

TABLE 4 HISTORICAL OVERVIEW OF EPIGENOMICS

TABLE 5 EPIGENOMICS INDUSTRY KEY COMPANIES

TABLE 6 EPIGENETIC ANALYSIS TECHNOLOGIES

TABLE 7 STATUS OF DNA METHYLATION AND HISTONE ANALYSIS

TECHNOLOGIES

TABLE 8 BIOLOGICAL ROLES OF DNA METHYLATION

TABLE 9 DESCRIPTION OF CPG ISLANDS

TABLE 10 HDAC ENZYMES CLASSES

TABLE 11 MECHANISMS FOR INAPPROPRIATE METHYLATION AND

ACETYLATION

TABLE 12 DNA METHYLATION ANALYSIS ASSAYS

TABLE 13 EMERGING DNA METHYLATION TECHNOLOGIES

TABLE 14 ACROYNMS FOR DNA METHYLATION TECHNOLOGIES

TABLE 15 DNA METHYLATION TECHNOLOGIES BY COVERAGE AND

THROUGHPUT

TABLE 16 EXAMPLES OF DNA METHYLATION ASSAYS

TABLE 17 METHYLATION RECOGNITION TECHNOLOGIES

TABLE 18 DNA METHYLATION ANALYSIS TECHNIQUES BY GENOME

RESOLUTION

TABLE 19 CHIP ASSAYS

TABLE 20 TECHNOLOGIES FOR MAPPING GENOMIC LOCATION OF

CHROMATIN PROTEINS AND ENZYMES

TABLE 21 MICROARRAY TYPES

TABLE 22 COMPARISON OF DNA AND PROTEIN MICROARRAY

TECHNOLOGIES

TABLE 23 MICROARRAY GENOME CONTENT

TABLE 24 DNA MICROARRAY PLATFORM FEATURES

TABLE 25 DNA MICROARRAY PLATFORM COMPARISON FOR MAJOR

MANUFACTURERS

TABLE 26 ROLE OF BIOMARKERS IN CLINICAL TRIAL DESIGN

TABLE 27 BIOLOGICAL RATIONALE FOR DNA METHYLATION

CANCER BIOMARKERS

TABLE 28 CANCER-RELATED CELL PATHWAYS AND GENES

AFFECTED BY HYPER-METHYLATION

TABLE 29 CANCER-RELATED EPIGENETIC CHANGES

TABLE 30 COMPARISON OF KEY CANCER BIOMARKER

TECHNOLOGY PLATFORMS

TABLE 31 PUBLISHED DNA METHYLATION BIOMARKER GENES FOR

CANCERS

TABLE 32 DIFFERENTIALLY METHYLATED GENES IN NEUROLOGIC

AND CARDIOVASCULAR DISORDERS

TABLE 33 DNA METHYLATION ANALYSIS TECHNOLOGIES IN

BIOMARKER DISCOVERY

TABLE 34 TECHNICAL HURDLES FOR DEVELOPMENT OF

METHYLATION EPIGENETIC CANCER BIOMARKERS

TABLE 35 EPIGENETIC GENES ALTERED IN HUMAN CANCERS

TABLE 36 STATUS OF INHIBITORS OF EPIGENETIC ENZYMES

TARGETING HISTONES

TABLE 37 HDAC INHIBITOR CLASSES AND RELATIVE POTENCY

TABLE 38 HDAC INHIBITOR DRUG TECHNOLOGY TRENDS

TABLE 39 HDAC INHIBITOR CLASS I AND II SELECTIVITY

TABLE 40 DRUG CLASSES THAT CAN BE USED IN COMBINATION

WITH HDAC INHIBITORS

TABLE 41 FUTURE CHALLENGES FOR EPIGENETIC DRUG

DEVELOPMENT

TABLE 42 TECHNOLOGY OPPORTUNITIES IN SOMATIC CELL

NUCLEAR TRANSFER

TABLE 43 REGIONAL EPIGENOMICS INITIATIVES

TABLE 44 COMMERCIAL MOLECULAR DIAGNOSTIC PLATFORMS

FOR TISSUE OF ORIGIN TESTS

TABLE 45 COMMERCIAL LANDSCAPE FOR HPV TESTS

TABLE 46 CURRENT SCREENING AND DIAGNOSTICS TESTS FOR

COLORECTAL CANCER

TABLE 47 ACCURACY OF EXISTING COLORECTAL SCREENING

TESTS

TABLE 48 COMMERCIAL LANDSCAPE FOR COLORECTAL

MOLECULAR TESTS

TABLE 49 COMPETITIVE SITUATION FOR CONVENTIONAL AND

MOLECULAR COLON CANCER SCREENING TESTS

TABLE 50 OVARIAN CANCER SCREENING TESTS

TABLE 51 OVARIAN CANCER DIAGNOSTIC TEST STATUS

TABLE 52 REQUIREMENTS FOR AN EPIGENETICS BISULFITE

DIAGNOSTIC ASSAY

TABLE 53 EPIGENETIC DIAGNOSTICS DEVELOPMENT PIPELINE

TABLE 54 APPROVED EPIGENETIC DRUGS

TABLE 55 NEXT GENERATION EPIGENETIC DRUGS

TABLE 56 EPIGENETIC DRUG NOMENCLATURE TABLE

TABLE 57 HDAC INHIBITOR CLINICAL TRIALS SUMMARY

TABLE 58 MBCD0103 INHIBITS SELECTED HDAC ENZYMES

TABLE 59 DNMT INHIBITOR CLINICAL TRIALS SUMMARY

TABLE 60 EPIGENETIC NON-CANCER DRUG LANDSCAPE

TABLE 61 FORCES DRIVING EPIGENOMICS INDUSTRY GROWTH

TABLE 62 STIMULUS FUNDING ALLOCATED TO UNITED STATES

SCIENCE SPENDING

TABLE 63 GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY

APPLICATION, THROUGH 2014 ($ MILLIONS)

TABLE 64 GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY

GEOGRAPHY, THROUGH 2014 ($ MILLIONS)

TABLE 65 GLOBAL VALUE OF EPIGENOMIC ANALYSIS RESEARCH

TOOLS, BY PRODUCT TYPE, THROUGH 2014 ($ MILLIONS)

TABLE 66 GLOBAL VALUE OF EPIGENOMICS RESEARCH TOOLS

KITS, BY TECHNOLOGY, THROUGH 2014 ($ MILLION)

TABLE 67 GLOBAL VALUE OF EPIGENOMIC ANALYSIS KITS, BY

FORMAT, THROUGH 2014 ($ MILLIONS)

TABLE 68 GLOBAL VALUE OF DNA METHYLATION RESEARCH

TOOLS KITS, BY ANALYSIS OBJECTIVE, THROUGH 2014 ($

MILLIONS)

TABLE 69 GLOBAL VALUE OF DNA METHYLATION RESEARCH

TOOLS KITS, BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

TABLE 70 GLOBAL VALUE OF DNA METHYLATION SINGLE LOCI

RESEARCH TOOLS KITS, BY TECHNOLOGY, THROUGH 2014 ($

MILLIONS)

TABLE 71 GLOBAL VALUE OF DNA METHYLATION GENOME-WIDE

RESEARCH TOOLS KITS BY TECHNOLOGY, THROUGH 2014 ($

MILLIONS)

TABLE 72 GLOBAL VALUE OF HISTONE ANALYSIS KITS, BY

TECHNOLOGY FORMAT, THROUGH 2014 ($ MILLIONS)

TABLE 73 GLOBAL VALUE OF EPIGENOMIC MICROARRAYS, BY

APPLICATION, THROUGH 2014 ($ MILLIONS)

TABLE 74 GLOBAL VALUE OF RESEARCH TOOLS EPIGENOMIC

REAGENTS, BY TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

TABLE 75 VALUE OF GLOBAL MOLECULAR DIAGNOSTICS

PRODUCTS, BY APPLICATION, THROUGH 2014 ($ MILLIONS)

TABLE 76 PROJECTED CHANGE IN AGE 65-PLUS POPULATION BY

REGION (%)

TABLE 77 U.S. CANCER INCIDENCE AND ESTIMATED TREATMENT

DECISIONS, 2009

TABLE 78 GLOBAL VALUE OF EPIGENETIC DIAGNOSTIC ASSAYS, BY

APPLICATION, THROUGH 2014 ($ MILLIONS)

TABLE 79 GLOBAL VALUE OF EPIGENETIC DIAGNOSTIC ASSAYS, BY

CANCER INDICATION, THROUGH 2014 ($ MILLIONS)

TABLE 80 GLOBAL VALUE OF EPIGENETIC DRUGS, BY CANCER

INDICATION, THROUGH 2014 ($ MILLIONS)

TABLE 81 GLOBAL VALUE OF EPIGENETIC DRUGS, BY DRUG CLASS,

THROUGH 2014 ($ MILLIONS)

TABLE 82 SUMMARY OF HDAC INHIBITOR STRATEGIC

OPPORTUNITIES FOR CANCER TREATMENT

TABLE 83 GLOBAL VALUE OF HDAC INHIBITOR DRUGS, BY

INDICATION, THROUGH 2014 ($ MILLIONS)

TABLE 84 GLOBAL VALUE OF HDAC INHIBITOR DRUGS, BY

TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

TABLE 85 GLOBAL VALUE OF DNMT INHIBITOR DRUGS, BY

INDICATION, THROUGH 2014 ($ MILLIONS)

TABLE 86 GLOBAL VALUE OF DNMT INHIBITOR DRUGS, BY

TECHNOLOGY, THROUGH 2014 ($ MILLIONS)

TABLE 87 OVERVIEW OF MAJOR HEMATOLOGICAL MALIGNANCIES

TABLE 88 MDS DRUG COMPARISON

TABLE 89 HEMATOLOGICAL CANCER EPIGENETIC DRUGS, BY

INDICATION, THROUGH 2014 ($ MILLIONS)

TABLE 90 HDAC HEMATOLOGICAL CANCER EPIGENETIC DRUGS, BY

INDICATION, THROUGH 2014 ($ MILLIONS)

TABLE 91 COMPARISON OF THE PTCL DRUGS, FOLYTYN AND

ISTODAX

TABLE 92 DNMT HEMATOLOGICAL CANCER EPIGENETIC DRUGS, BY

INDICATION, THROUGH 2014 ($ MILLIONS)

TABLE 93 EPIGENETIC CELL THERAPIES MARKETS, BY

APPLICATION, THROUGH 2014 ($ MILLIONS)

TABLE 94 EPIGENOMIC RESEARCH TOOLS MARKETS, BY

GEOGRAPHY, THROUGH 2014 ($ MILLIONS)

TABLE 95 EPIGENOMIC DIAGNOSTICS MARKETS, BY GEOGRAPHY,

THROUGH 2014 ($ MILLIONS)

TABLE 96 NUMBER OF HOSPITALS AND CLINICS, BY

GEOGRAPHICAL REGION

TABLE 97 EPIGENOMIC PHARMACEUTICALS MARKETS, BY

GEOGRAPHY, THROUGH 2014 ($ MILLIONS)

TABLE 98 EPIGENOMIC CELL THERAPIES MARKETS, BY

GEOGRAPHY, THROUGH 2014 ($ MILLIONS)

TABLE 99 SCOPE OF EPIGENOMIC RESEARCH TOOLS SUPPLIERS

TABLE 100 IN-VITRO DIAGNOSTICS COMPETITORS

TABLE 101 STRATEGIC ALLIANCE STATUS FOR BIOTECHNOLOGY

EPIGENETICS DIAGNOSTICS FIRMS

TABLE 102 COMPETITIVE LANDSCAPE FOR MOLECULAR

DIAGNOSTICS TECHNOLOGIES

TABLE 103 RELATIVE STRATEGIC POSITION FOR EPIGENOMIC

DRUG COMPANIES

TABLE 104 EPIGENOMICS STATEGIC ALLIANCES: 2007-2010

TABLE 105 EPIGENOMICS INDUSTRY ACQUISITIONS, 2007-2010

TABLE 106 EPIGENOMICS AG RESEARCH TOOLS PATENT COVERAGE

TABLE 107 PATENT STATUS FOR BIOTECHNOLOGY DIAGNOSTICS

COMPANIES

TABLE 108 HDAC INHIBITOR PATENT CLAIMS, 2004-2006

TABLE 109 AFFYMETRIX STRATEGIC ALLIANCES

TABLE 110 CLAVIS PHARMA DRUG PIPELINE

TABLE 111 ILLUMINA SEQUENCING TECHNOLOGY SPACE

TABLE 112 METHYLGENE HDAC INHIBITOR PRODUCT PIPELINE

TABLE 113 ONCOMETHYLOME DNA METHYLATION DIAGNOSTICS

PIPELINE

TABLE 114 ORION STRATEGIC ALLIANCES

TABLE 115 ORION EPIGENETIC DIAGNOSTICS PIPELINE

TABLE 116 S*BIO HDAC INHIBITOR DRUG PIPELINE

TABLE 117 ENTINOSTAT CLINICAL TRIALS SUMMARY STATUS

TABLE 118 TOPOTARGET’S HDAC INHIBITOR PATENT PORTFOLIO

LIST OF FIGURES

SUMMARY FIGURE GLOBAL VALUE OF EPIGENOMIC PRODUCTS, BY

APPLICATION, 2008-2014 ($ MILLIONS)

FIGURE 1 EPIGENOMICS: A NEW PARADIGM

FIGURE 2 ACTIVE CANCER EPIGENETIC DRUG CLINICAL TRIALS, BY

PHASE AND INDICATION, JANUARY 2010

FIGURE 3 EPIGENETIC PROCESSES CAN GENERATE ABNORMAL

CELLS DURING CELL DEVELOPMENT

FIGURE 4 UPSTREAM AND DOWNSTREAM STEPS IN EPIGENETIC

ANALYSIS WORKFLOW

FIGURE 5 EPIGENETIC CHANGES TO DNA AFFECT GENE

EXPRESSION

FIGURE 6 ACETYLATION OF HISTONE TAIL REGIONS

FIGURE 7 HISTONE ACETYLATION AND METHYLATION ENZYMES

FIGURE 8 METHYLATED DNA ANALYSIS WORKFLOW

FIGURE 9 ANALYSIS OF DNA METHYLATION BY RESTRICTION

ENZYMES

FIGURE 10 BISULFITE CONVERSION OF DNA

FIGURE 11 WORKFLOW SCHEMATIC FOR CHIP PLATFORMS

FIGURE 12 MICROARRAY FEATURE DENSITY

FIGURE 13 MICROARRAY RESOLUTION

FIGURE 14 MICROARRAYS ENHANCE MULTIPLEX CAPABILITIES OF

EPIGENETICS ASSAYS

FIGURE 15 DNA SEQUENCING PLATFORMS

FIGURE 16 NEXT GENERATION SEQUENCING TECHNOLOGIES

WORKFLOW OVERVIEW

FIGURE 17 HISTONE DEACETYLASE REACTION

FIGURE 18 CHEMICAL STRUCTURE OF TRICHOSTATIN A, A

HYDROXAMATE CLASS HDAC INHIBITOR

FIGURE 19 PHENYLBUTYRIC ACID, AN ALIPHATIC ACID CLASS

HDAC INHIBITOR

FIGURE 20 APICIDIN A, A CYCLIC TETRAPEPTIDE CLASS HDAC

INHIBITOR

FIGURE 21 ENTINOSTAT, A BENZAMIDE CLASS HDAC INHIBITOR

FIGURE 22 DISEASE HDAC ISOFORM GENE EXPRESSION PROFILE

FIGURE 23 COMMON STRUCTURAL COMPONENT MOTIFS OF

VORINOSTAT

FIGURE 24 LEAD DNMT INHIBITOR COMPOUNDS

FIGURE 25 SOMATIC CELL NUCLEAR TRANSFER

FIGURE 26 EPIGENETIC PROGRAMMING OF STEM CELLS

FIGURE 27 CANCER SCREENING OPPORTUNITY MATRIX FOR

MOLECULAR DIAGNOSTICS

FIGURE 28 NEW EPIGENETIC SCREENING PARADIGM

FIGURE 29 SENSITIVITY AND SPECIFICITY

FIGURE 30 ACTIVE CANCER EPIGENETIC DRUG CLINICAL TRIALS,

BY DRUG CLASS AND CANCER TYPE, JANUARY 2010

FIGURE 31 ACTIVE CANCER EPIGENETIC DRUG CLINICAL TRIALS,

BY PHASE AND INDICATION, JANUARY 2010

FIGURE 32 CURRENT EPIGENETIC CANCER DRUG CLINICAL

TRIALS, BY DRUG AND TRIAL TYPE, JANUARY 2010

FIGURE 33 ACTIVE EPIGENETIC CANCER DRUG CLINICAL TRIALS,

BY CLINICAL PHASE AND TRIAL TYPE, JANUARY 2010

FIGURE 34 GROWTH IN SCIENTIFIC PUBLICATIONS RELATED TO

EPIGENETICS (NUMBER OF PUBLICATIONS)

FIGURE 35 ANNUAL NIH FUNDING BUDGET, 2000-2009 ($ MILIONS)

FIGURE 36 CHIP-GRADE ANTIBODY SUPPLIER MARKET SHARES,

2009 (%)

FIGURE 37 EPIGENOMIC DRUG COMPANY MARKET SHARES, 2009

FIGURE 38 NUMBER OF EPIGENOMICS PATENTS, BY YEAR, 2000-

2009

FIGURE 39 NUMBER OF EPIGENOMICS PATENTS, BY GEOGRAPHY,

2000-2009

FIGURE 40 BIOTECHNOLOGY DIAGNOSTICS PATENTS, BY COMPANY

(%)

FIGURE 41 NUMBER OF EPIGENOMICS DRUG PATENTS, BY

TECHNOLOGY CLASS AND GEOGRAPHY

FIGURE 42 NUMBER OF HDAC INHIBITOR PATENTS, BY COMPANY

AND GEOGRAPHY

FIGURE 43 NUMBER OF DNMT INHIBITOR PATENTS, BY COMPANY

AND GEOGRAPHY