REPORT SCOPE

INTRODUCTION

STUDY GOALS AND OBJECTIVES

This BCC Research report, Histone Methyltransferases: Global Markets for Research Tools, Diagnostics and Drug Discovery, provides an overview of the current overall state of the histone methyltransferases market, focusing specifically on tools and reagents, drug discovery trends and diagnostic potential. It describes existing platforms and technologies on the market, and a detailed analysis of the competitive environments, including new trends and segments for novel products and assay development. This study includes information about significant players, trends, and obstacles and other information affecting this market and its different sectors. Overall, this report will forecast current and future trends and developments in the histone methyltransferases segment and its potential market and partnerships for 2013 to 2018.

REASONS FOR DOING THIS STUDY

Epigenetics is defined as the study of heritable changes in gene expression caused by modifications other than changes in the DNA sequence. In eukaryotes, genomic DNA is packaged with histone proteins into the cell nucleus as chromatin. Examples of such modifications are DNA methylation and various histone modifications, both of which regulate gene expression without altering the underlying DNA sequence. Consequently, such modifications are not only important for proper development but can cause many pathological conditions including cancer.

Epigenetics is a very complex scientific discipline. It includes many molecular “players” essential for proper cell function. During the last decade, substantial efforts in epigenetics drug discovery were made. Today, the market for epigenetic therapeutics was evaluated by some analysts at over $600 million, based on sales of four products: Dacogen from Eisai, Vidaza and Istodax from Celgene, and Zolinza from Merck, which target two epigenetic pathways-DNA methyltransferases (DNMT) and histone deacteylases (HDAC).

Histone methyltransferases are another group of important epigenetic enzymes responsible for proper gene expression and silencing. For example, Ezh2 is one of the most well-studied histone methyltransferases. Over the past decade, it was deregulated in a variety of human cancers. Recently, the company Epizyme published a study in Nature Chemical Biology[1] where the Ezh2 inhibitor EPZ005687 was revealed. Moreover, other studies have shown that this large family of proteins can serve as an excellent predictive biomarker and target for diagnostics products development.

Overall, the discovery of novel potent inhibitors for the histone methyltransferases family gives hope for many stagnated pharmaceutical R&D programs. The discovery of novel drug candidates for proteins, such as Ezh2, opens enormous possibilities not only in oncology research but in stem cell biology, neurodegeneration and other diseases.

In summary, this report will focus on recent developments in the assay and reagents sector for methyltransferase studies, diagnostics products based on histone methylation research and drug candidates targeting histone methyltransferase activity. It will describe in detail market participants in research and products development, and overall collaborations between different pharma/biotech companies during last two to three years. This report will evaluate the current situation and forecast possible outcomes of histone methyltransferases assay/reagents development, diagnostics and therapeutics field for the next five years.

SCOPE AND FORMAT

This report is essentially a business tool that can help market players properly evaluate new commercial opportunities in the epigenetic-related space of the histone methyltransferases segment in the context of research tools, diagnostics and therapeutics submarkets. The geographic scope of this study is global. This market is generally complex and consists of a number of different segments, each of which is affected differently by scientific and technological developments. This report identifies the main positive and negative factors affecting each segment, and forecasts market growth, future trends and product development in every major segment of this market.

METHODOLOGY AND INFORMATION SOURCES

Both primary and secondary research methodologies were used in preparing this study. Initially, a comprehensive and exhaustive search of the literature on drug discovery and already marketed products was conducted. These secondary sources included drug discovery and science-related journals, textbooks, press releases, marketing literature, other product/promotional literature, annual reports, security analyst reports and other publications. A patent search and analysis were also conducted.

In a second phase, a series of semistructured interviews was conducted with company representatives, bench scientists, marketing representatives and other personnel at biotechnology and pharmaceutical companies. Other sources included academics, technology and consulting companies. Subsequent analysis of the documents and interviews notes was iterative.

INTENDED AUDIENCE

This report is intended for business development professionals, entrepreneurs and other investors who need to fully understand and properly evaluate each segment in the market for histone methyltransferases research and development. It provides insights into the market position of major companies, and shows new opportunities otherwise overlooked or less known to the business community.

ANALYST CREDENTIALS

Dr. Marianna Tcherpakov has more than eight years of experience as a bench scientist specializing in biochemistry, cell biology and industrial assay development. She has contributed to a number of scientific publications and holds several patents. She has expertise as an assay development scientist and is familiar with different research field trends and likely future developments.

REPORT HIGHLIGHTS

This report provides:
• An overview of the global market and commercial potential for histone methyltransferases (HMTs)
• Analyses of global market trends, with data for 2012, estimates for 2013, and projections of compound annual growth rates (CAGRs) through 2018
• Discussion of the history of epigenetics, descriptions of main epigenetic enzymes, targets for HMTs, the importance of HMTs in different cellular functions, and the role of HMTs in different diseases
• Market participants providing reagent and assay for HMT research, and estimates and evaluation in research tool development
• Patent analysis in HMT assay development
• Current pipelines and drug candidates in HMT drug discovery
• Comprehensive company profiles of major players.

Table Of Contents

TABLE OF CONTENTS

CHAPTER 1 INTRODUCTION 2

STUDY GOALS AND OBJECTIVES 2
REASONS FOR DOING THIS STUDY 2
SCOPE AND FORMAT 3
METHODOLOGY AND INFORMATION SOURCES 3
INTENDED AUDIENCE 3
ANALYST CREDENTIALS 3
RELATED BCC REPORTS 4
BCC ONLINE SERVICES 4
DISCLAIMER 4

CHAPTER 2 SUMMARY 6

SUMMARY TABLE GLOBAL MARKET FOR HISTONE METHYLTRANSFERASES
RESEARCH AND DEVELOPMENT, THROUGH 2018 ($ MILLIONS) 7
SUMMARY FIGURE GLOBAL MARKET FOR HISTONE METHYLTRANSFERASES
RESEARCH AND DEVELOPMENT, 2011-2018 ($ MILLIONS) 7

CHAPTER 3 INTRODUCTION TO HISTONE METHYLTRANSFERASES RESEARCH

AND PRODUCT DEVELOPMENT 10
OVERVIEW 10
DNA METHYLATION 12
DNA METHYLTRANSFERASES 13
DNA METHYLATION DETECTION TECHNIQUES 14
HISTONE MODIFICATIONS 15
TABLE 1 DIFFERENT CLASSES OF MODIFICATIONS IDENTIFIED ON
HISTONES 15
TABLE 2 MAIN CATEGORIES IN HISTONE-MODIFICATION ENZYMES 16
CHROMATIN METHYLATION REACTION 17
FIGURE 1 SCHEMATIC PRESENTATION OF METHYLATION REACTION 17
HISTONE METHYLTRANSFERASES: LYSINE METHYLATION 18
TABLE 3 EXAMPLES OF HISTONE LYSINE METHYLATION AND ITS
FUNCTIONAL OUTCOMES 19
Role of Lysine Methylation in Chromatin Transcription 20
HISTONE METHYLTRANSFERASES: ARGENINE METHYLATION 20
TABLE 4 EXAMPLES OF HISTONE ARGININE METHYLATION AND ITS
FUNCTIONAL OUTCOMES 22
Role of Arginine Methylation in Chromatin Transcription 22
PRDM FAMILY AND HISTONE METHYLTRANSFERASE ACTIVITY 23
TABLE 5 PRDM FAMILY MEMBERS, THEIR RELATED ENZYMATIC ACTIVITY
AND BINDING PARTNERS 24
TABLE 6 EXAMPLES OF EPIGENETIC ALTERATIONS IN DIFFERENT
PATHOLOGIES 25

CHAPTER 4 DEVELOPMENT OF RESEARCH TOOLS AND REAGENTS FOR

HISTONE METHYLTRANSFERASES STUDIES AND PRODUCT DEVELOPMENT 27
OVERVIEW 27
TABLE 7 PERCENTAGE OF COMMERCIAL KITS GENERALLY PURCHASED FOR
EPIGENETIC RESEARCH (%) 28
TABLE 8 SELECT SUPPLIERS OF EPIGENETIC PRODUCTS 29
REAGENTS AND ASSAYS REQUIRED FOR HISTONE
METHYLTRANSFERASES (HMT) STUDIES 30
TABLE 9 PRODUCT CATEGORIES FOR HMT RESEARCH, COMPANIES
MARKETING THE PRODUCTS AND AVERAGE PRICES 32
ANTIBODIES FOR HMT RESEARCH 32
TABLE 10 GLOBAL MARKET FOR ANTIBODIES BY INDUSTRY SEGMENT,
THROUGH 2016 ($ BILLIONS) 33
TABLE 11 DISTRIBUTION OF VARIOUS APPLICATIONS FOR ANTIBODIES AS A
RESEARCH TOOL (%) 33
TABLE 12 MAIN MARKET PARTICIPANTS IN RESEARCH ANTIBODY SEGMENT
AND THEIR RELATIVE MARKET SHARES (%) 34
TABLE 13 SOURCES OF ANTIBODIES SUPPLY FOR RESEARCH AND THEIR
PERCENTAGE ON THE MARKET 35
PRODUCTION OF PROTEIN AND ENZYMES FOR HMT RESEARCH 36
TABLE 14 PERCENTAGE USE OF SPECIFIC PROTEIN EXPRESSION
TECHNIQUES (%) 37
TABLE 15 GLOBAL MARKET FOR PROTEIN CHROMATOGRAPHY, THROUGH
2016 ($ MILLIONS) 38
TABLE 16 AVERAGE SPENDING PER SCIENTIST ON PURIFICATION AND
SEPARATION PRODUCTS (%) 39
TABLE 17 GLOBAL MARKET SHARES OF RECOMBINANT ENZYME MARKET
BY DIFFERENT TYPE OF ENZYME IN 2012 (%) 40
TABLE 18 GLOBAL RECOMBINANT ENZYME MARKET SHARES BY CUSTOMER
(%) 41
TABLE 19 LIST OF LYSINE HISTONE METHYLTRANSFERASES (KMT) AND
THEIR SUBSTRATES 41
TABLE 20 LIST OF LYSINE HISTONE DEMETHYLASES (KDM) AND THEIR
SUBSTRATES 43
TABLE 21 LIST OF ARGININE HISTONE METHYLTRANSFERASES AND THEIR
SUBSTRATES 44
MODULATORS AND INHIBITORS FOR HMT STUDIES 45
TABLE 22 LIST OF INHIBITORS USED IN HISTONE METHYLTRANSFERASE
RESEARCH AND PRODUCT DEVELOPMENT 46
SUBSTRATES USED IN HMTS ASSAYS 47
TABLE 23 SUBSTRATES FOR HMTS FOR IN VITRO STUDIES AND
PERCENTAGE OF THEIR USE (%) 47
IN VITRO ASSAY DEVELOPMENT MARKET FOR HMTS 48
TABLE 24 SELECT IN VITRO ASSAY AND COMMERCIAL KIT PROVIDERS 49
FIGURE 2 SCHEMATIC REPRESENTATION OF HMTS ASSAY DEVELOPMENT 49
TABLE 25 LIST OF DIFFERENT ASSAY SET-UPS FOR HMT ACTIVITY
MEASUREMENTS 51
Selected Market Participants in Assay Development for HMT
Activity 52
Perkin Elmer 52
G Bioscience 53
Epigentek 54
Cayman Chemical 54
BPS Bioscience 54
Reaction Biology 55
BellBrook Labs 55
Abcam 55
CisBio Bioassays 55
TABLE 26 SURVEY OF SCIENTISTS' OPINIONS ABOUT EPIGENETICS
SCREENING IN DRUG DISCOVERY (%) 57
TABLE 27 STUDIES AND ASSAY DEVELOPMENT IN SPECIFIC DISEASE AREAS
(%) 57
Active Motif 58
Biocius 59
BPS Bioscience 59
Cayman Chemical 60
EMD Millipore 60
Epigentek 61
Life Technologies 61
Perkin Elmer 61
Reaction Biology 62
TABLE 28 GLOBAL MARKET FOR RESEARCH TOOLS, REAGENTS AND ASSAYS
FOR HISTONE METHYLTRANSFERASE STUDIES, THROUGH 2018 ($
MILLIONS) 63
FIGURE 3 GLOBAL MARKET FOR RESEARCH TOOLS, REAGENTS AND ASSAYS
FOR HISTONE METHYLTRANSFERASE STUDIES, 2011-2018 ($ MILLIONS) 63

CHAPTER 5 HISTONE METHYLTRANSFERASES IN DRUG DISCOVERY AND

THERAPEUTICS DEVELOPMENT 65
OVERVIEW 65
TABLE 29 ALTERED HISTONE MODIFICATIONS IN DIFFERENT
PATHOLOGICAL CONDITIONS 65
TABLE 30 CURRENT APPROVED EPIGENETIC DRUGS ON THE MARKET 66
ZOLINZA 66
TABLE 31 SALES OF ZOLINZA, 2008-2010, ($ MILLIONS) 67
ISTODAX 67
TABLE 32 SALES OF ISTODAX, 2011 AND 2012 ($ MILLIONS) 68
VIDAZA 68
TABLE 33 SALES OF VIDAZA, 2010-2012 ($ MILLIONS) 69
DACOGEN 69
TABLE 34 SALES OF DACOGEN, 2009-2011 ($ MILLIONS) 70
TABLE 35 EXAMPLES OF EPIGENETIC DRUG DISCOVERY PROGRAMS 71
MARKET PARTICIPANTS IN THE HMT DRUG DISCOVERY SECTOR 73
CELLCENTRIC 73
CELLZOME (GSK) 76
CONSTELLATION PHARMACEUTICALS 77
DOMAINEX 78
EPITHERAPEUTICS APS 79
EPIZYME 80
TABLE 36 COMPANIES DEVELOPING THERAPEUTICS WITH HISTONE
METHYLTRANSFERASE AS A DRUG DISCOVERY TARGET 82
CURRENT DRUG CANDIDATES AND HMT INHIBITORS IN DEVELOPMENT 83
TABLE 37 RECENT DRUG DISCOVERY DEVELOPMENTS FOR HISTONE
METHYLTRANSFERASE INHIBITORS 84
G9A AND GLP INHIBITORS 85
DOT1L INHIBITORS 86
SMYD2 INHIBITORS 88
EZH2 INHIBITORS 89
SET7/9 INHIBITORS 91
INHIBITORS FOR PRMT4 93
ADDITIONAL HMTS AS DRUG DISCOVERY TARGETS 94
Nsd 2/WHSC1 94
MLL 94
Set8 95
Suv39H1 95
TABLE 38 POTENTIAL MARKETS FOR HMTS DRUG DISCOVERY ($ BILLIONS) 96
DEALS IN THE EPIGENETICS SECTOR AS INDICATORS FOR MARKET
DEVELOPMENT AND ACTIVITY 96
TABLE 39 DEALS IN EPIGENETICS MARKET IN THE LAST DECADE 96
TABLE 40 YEAR AND FUNDING AMOUNT FOR EPIGENETIC COMPANIES IN
HMT DRUG DISCOVERY 102
TABLE 41 GLOBAL DRUG DISCOVERY MARKET VALUE FOR HISTONE
METHYLTRANSFERASE RESEARCH, THROUGH 2018 ($ MILLIONS) 103
FIGURE 4 GLOBAL DRUG DISCOVERY MARKET VALUE FOR HISTONE
METHYLTRANSFERASE RESEARCH, 2011-2018 ($ MILLIONS) 103
ADDITIONAL DRUG DISCOVERY TARGETS RELATED TO HMT RESEARCH 103
TABLE 42 POTENTIAL EPIGENTICS TARGETS FOR DRUG DISCOVERY:
EPIGENETIC ENZYMES CLASSES IMPORTANT IN COVALENT MODIFICATION
OF DNA OR HISTONES 103
HISTONE DEMETHYLASES AS DRUG TARGETS AND THEIR IMPACT
ON HMT ACTIVITY 104
TABLE 43 RELATIONSHIP BETWEEN DEMETHYLASES,
METHYLTRASNFERASES AND THEIR RESPECTIVE HISTONE METHYLATION
SITES 108
CHROMATIN READERS AS DRUG TARGETS AND THEIR IMPACT ON
HMT ACTIVITY 108
TABLE 44 RELATIONSHIP BETWEEN HISTONE METHYLATION, METHYL
READERS AND THEIR FUNCTIONS 109

CHAPTER 6 HISTONE METHYLTRANSFERASES IN DIAGNOSTICS AND

BIOMARKER DEVELOPMENT 114
OVERVIEW 114
TABLE 45 NUMBER OF PUBMED PUBLICATIONS ON BIOMARKERS USING
DIFFERENT EPIGENETIC MECHANISMS, 2012 114
TABLE 46 DNA METHYLATION EVENTS AND THEIR RELATION TO
DIFFERENT PATHOLOGIES 115
TABLE 47 NUMBER OF PUBLICATIONS IN HISTONE METHYLATION AREA
BASED ON DIFFERENT SEARCH CRITERIA 118
TABLE 48 RELATIONSHIP BETWEEN HISTONE METHYLATION AND CANCER
PROGNOSIS 119
LUNG CANCER AND HISTONE MODIFICATIONS 120
PROSTATE CANCER AND HISTONE MODIFICATIONS 120
BREAST CANCER AND HISTONE MODIFICATIONS 121
LEUKEMIA AND HISTONE MODIFICATIONS 121
ESOPHAGEAL AND GASTRIC CANCERS AND HISTONE MODIFICATIONS 121
HISTONE MODIFICATIONS IN KIDNEY, LIVER AND PANCREATIC
CANCERS 122
TABLE 49 DIFFERENT HISTONE METHYLTRANSFERASES AND THEIR
ASSOCIATION TO CANCER DEVELOPMENT 124
TABLE 50 DEMETHYLASES AND THEIR ASSOCIATIONS WITH CANCER
DEVELOPMENT 127
TABLE 51 GLOBAL BIOMARKERS MARKET, THROUGH 2015 ($ BILLIONS) 129
MARKET PARTICIPANTS IN EPIGENETIC DIAGNOSTICS SPACE 129
TABLE 52 SELECT EPIGENTICS DIANGOSTICS COMPANIES 129
DIAGENODE 131
EPIGENOMICS AG 131
EPIONTIS 133
EXACT SCIENCES 134
MDXHEALTH (FORMERLY ONCOMETHYLOME SCIENCES) 134
ORION GENOMICS 135
OXFORD BIODYNAMICS 136
PROGNOSDX 137
RIBOMED BIOTECHNOLOGIES 138
SEQUENOM 139
VOLITIONRX 140
TABLE 53 EXAMPLES OF AVERAGE REVENUES IN EPIGENETIC DIAGNOSTICS
COMPANIES 141
TABLE 54 GLOBAL MARKET FOR HISTONE METHYLATION IN BIOMARKERS
AND DIAGNOSTICS PRODUCT DEVELOPMENT, THROUGH 2018 ($ MILLIONS) 143
FIGURE 5 GLOBAL MARKET FOR HISTONE METHYLATION IN BIOMARKERS
AND DIAGNOSTICS PRODUCT DEVELOPMENT, 2011-2018 ($ MILLIONS) 143
TABLE 55 DIAGNOSTICS MARKET VALUES IN ONCOLOGY SECTOR, 2013 ($
BILLIONS) 144

CHAPTER 7 IMPORTANCE OF PATENTS IN HISTONE METHYLTRANSFERASE

RESEARCH AND PRODUCT DEVELOPMENT 146
TABLE 56 WORLDWIDE PATENTS AND PATENT APPLICATION SEARCH IN
HISTONE METHYLTRANSFERASE RESEARCH USING SPECIFIC KEYWORDS
(NO. OF PATENTS) 146
TABLE 57 WORLDWIDE SEARCH FOR NUMBER OF PATENTS AND PATENT
APPLICATIONS IN HISTONE METHYLTRANSFERASE RESEARCH ACCORDING
TO ASSIGNEE 148

CHAPTER 8 MARKET SUMMARY 150

TABLE 58 NUMBER OF PUBLICATIONS USING HISTONE
METHYLTRANSFERASE AS SEARCH, 2000-2012 150
FIGURE 6 NUMBER OF PUBLICATIONS FROM 2000-2012 USING HISTONE
METHYLTRANSFERASE AS SEARCH 150
TABLE 59 DISTRIBUTION OF DRUG DEVELOPMENT PROGRAMS IN
EPIGENETIC SPACE (%) 151
TABLE 60 GLOBAL MARKET FOR HISTONE METHYLTRANSFERASES
RESEARCH AND DEVELOPMENT, THROUGH 2018 ($ MILLIONS) 152
FIGURE 7 GLOBAL MARKET FOR HISTONE METHYLTRANSFERASES
RESEARCH AND DEVELOPMENT, 2011-2018 ($ MILLIONS) 153
TABLE 61 EXAMPLES OF MARKET PARTICIPANTS IN HISTONE
METHYLTRANSFERASE SECTOR AND THEIR REPRESENTATIVE PRODUCTS 153

CHAPTER 9 PROFILES OF SELECT COMPANIES 156

CELLCENTRIC LTD. 156
CONSTELLATION PHARMACEUTICALS 157
DOMAINEX 158
EPITHERAPEUTICS APS 160
EPIZYME, INC. 161
EISAI CO., LTD. 162
GLAXOSMITHKLINE (GSK) 163

CHAPTER 10 LIST OF COMPANIES MENTIONED IN REPORT 167

ABCAM 167
ACTIVE MOTIF 167
ANASPEC 167
BELLBROOK LABS 167
BOEHRINGER INGELHEIM GMBH 167
CAYMAN CHEMICAL COMPANY 167
CELGENE CORPORATION 168
CELLCENTRIC LTD. 168
CELL SIGNALING TECHNOLOGY, INC. 168
CISBIO US 168
CONSTELLATION PHARMACEUTICALS 168
DIAGENODE INC. USA 168
DOMAINEX 169
EISAI CO., LTD. 169
EMD GROUP (EMD MILLIPORE) 169
ENZO LIFE SCIENCES, INC. 169
EPIGENOMICS AG 169
EPIGENTEK GROUP INC. 169
EPITHERAPEUTICS APS 170
EPIZYME, INC. 170
EXACT SCIENCES CORPORATION 170
G-BIOSCIENCES 170
GSK US 170
JOHNSON and JOHNSON 170
LIFE TECHNOLOGIES CORP. 171
MDXHEALTH, INC 171
MERCK CORPORATE HEADQUARTERS 171
METHYLGENE INC. 171
NEW ENGLAND BIOLABS 171
NOVARTIS INTERNATIONAL AG 171
ORION GENOMICS 172
PERKIN ELMER 172
PFIZER 172
PHARMACYCLICS, INC 172
PROGNOSDX HEALTH, INC. 172
RANA THERAPEUTICS INC. 172
REACTION BIOLOGY CORP. 173
RIBOMED BIOTECHNOLOGIES, INC. 173
SEQUENOM, INC. 173
SIGMA-ALDRICH 173
SIRTRIS 173
SYNDAX PHARMACEUTICALS, INC. 173
TAKEDA PHARMACEUTICALS U.S.A., INC. 174
THERMO FISHER SCIENTIFIC, INC. 174
VOLITIONRX 174
ZYMO RESEARCH CORPORATION 174



LIST OF TABLES

SUMMARY TABLE GLOBAL MARKET FOR HISTONE METHYLTRANSFERASES
RESEARCH AND DEVELOPMENT, THROUGH 2018 ($ MILLIONS) 7
TABLE 1 DIFFERENT CLASSES OF MODIFICATIONS IDENTIFIED ON HISTONES 15
TABLE 2 MAIN CATEGORIES IN HISTONE-MODIFICATION ENZYMES 16
TABLE 3 EXAMPLES OF HISTONE LYSINE METHYLATION AND ITS
FUNCTIONAL OUTCOMES 19
TABLE 4 EXAMPLES OF HISTONE ARGININE METHYLATION AND ITS
FUNCTIONAL OUTCOMES 22
TABLE 5 PRDM FAMILY MEMBERS, THEIR RELATED ENZYMATIC ACTIVITY
AND BINDING PARTNERS 24
TABLE 6 EXAMPLES OF EPIGENETIC ALTERATIONS IN DIFFERENT
PATHOLOGIES 25
TABLE 7 PERCENTAGE OF COMMERCIAL KITS GENERALLY PURCHASED FOR
EPIGENETIC RESEARCH (%) 28
TABLE 8 SELECT SUPPLIERS OF EPIGENETIC PRODUCTS 29
TABLE 9 PRODUCT CATEGORIES FOR HMT RESEARCH, COMPANIES
MARKETING THE PRODUCTS AND AVERAGE PRICES 32
TABLE 10 GLOBAL MARKET FOR ANTIBODIES BY INDUSTRY SEGMENT,
THROUGH 2016 ($ BILLIONS) 33
TABLE 11 DISTRIBUTION OF VARIOUS APPLICATIONS FOR ANTIBODIES AS A
RESEARCH TOOL (%) 33
TABLE 12 MAIN MARKET PARTICIPANTS IN RESEARCH ANTIBODY SEGMENT
AND THEIR RELATIVE MARKET SHARES (%) 34
TABLE 13 SOURCES OF ANTIBODIES SUPPLY FOR RESEARCH AND THEIR
PERCENTAGE ON THE MARKET 35
TABLE 14 PERCENTAGE USE OF SPECIFIC PROTEIN EXPRESSION
TECHNIQUES (%) 37
TABLE 15 GLOBAL MARKET FOR PROTEIN CHROMATOGRAPHY, THROUGH
2016 ($ MILLIONS) 38
TABLE 16 AVERAGE SPENDING PER SCIENTIST ON PURIFICATION AND
SEPARATION PRODUCTS (%) 39
TABLE 17 GLOBAL MARKET SHARES OF RECOMBINANT ENZYME MARKET BY
DIFFERENT TYPE OF ENZYME IN 2012 (%) 40
TABLE 18 GLOBAL RECOMBINANT ENZYME MARKET SHARES BY CUSTOMER
(%) 41
TABLE 19 LIST OF LYSINE HISTONE METHYLTRANSFERASES (KMT) AND
THEIR SUBSTRATES 41
TABLE 20 LIST OF LYSINE HISTONE DEMETHYLASES (KDM) AND THEIR
SUBSTRATES 43
TABLE 21 LIST OF ARGININE HISTONE METHYLTRANSFERASES AND THEIR
SUBSTRATES 44
TABLE 22 LIST OF INHIBITORS USED IN HISTONE METHYLTRANSFERASE
RESEARCH AND PRODUCT DEVELOPMENT 46
TABLE 23 SUBSTRATES FOR HMTS FOR IN VITRO STUDIES AND PERCENTAGE
OF THEIR USE (%) 47
TABLE 24 SELECT IN VITRO ASSAY AND COMMERCIAL KIT PROVIDERS 49
TABLE 25 LIST OF DIFFERENT ASSAY SET-UPS FOR HMT ACTIVITY
MEASUREMENTS 51
TABLE 26 SURVEY OF SCIENTISTS' OPINIONS ABOUT EPIGENETICS
SCREENING IN DRUG DISCOVERY (%) 57
TABLE 27 STUDIES AND ASSAY DEVELOPMENT IN SPECIFIC DISEASE AREAS
(%) 57
TABLE 28 GLOBAL MARKET FOR RESEARCH TOOLS, REAGENTS AND ASSAYS
FOR HISTONE METHYLTRANSFERASE STUDIES, THROUGH 2018 ($ MILLIONS) 63
TABLE 29 ALTERED HISTONE MODIFICATIONS IN DIFFERENT PATHOLOGICAL
CONDITIONS 65
TABLE 30 CURRENT APPROVED EPIGENETIC DRUGS ON THE MARKET 66
TABLE 31 SALES OF ZOLINZA, 2008-2010, ($ MILLIONS) 67
TABLE 32 SALES OF ISTODAX, 2011 AND 2012 ($ MILLIONS) 68
TABLE 33 SALES OF VIDAZA, 2010-2012 ($ MILLIONS) 69
TABLE 34 SALES OF DACOGEN, 2009-2011 ($ MILLIONS) 70
TABLE 35 EXAMPLES OF EPIGENETIC DRUG DISCOVERY PROGRAMS 71
TABLE 36 COMPANIES DEVELOPING THERAPEUTICS WITH HISTONE
METHYLTRANSFERASE AS A DRUG DISCOVERY TARGET 82
TABLE 37 RECENT DRUG DISCOVERY DEVELOPMENTS FOR HISTONE
METHYLTRANSFERASE INHIBITORS 84
TABLE 38 POTENTIAL MARKETS FOR HMTS DRUG DISCOVERY ($ BILLIONS) 96
TABLE 39 DEALS IN EPIGENETICS MARKET IN THE LAST DECADE 96
TABLE 40 YEAR AND FUNDING AMOUNT FOR EPIGENETIC COMPANIES IN
HMT DRUG DISCOVERY 102
TABLE 41 GLOBAL DRUG DISCOVERY MARKET VALUE FOR HISTONE
METHYLTRANSFERASE RESEARCH, THROUGH 2018 ($ MILLIONS) 103
TABLE 42 POTENTIAL EPIGENTICS TARGETS FOR DRUG DISCOVERY:
EPIGENETIC ENZYMES CLASSES IMPORTANT IN COVALENT MODIFICATION
OF DNA OR HISTONES 103
TABLE 43 RELATIONSHIP BETWEEN DEMETHYLASES,
METHYLTRASNFERASES AND THEIR RESPECTIVE HISTONE METHYLATION
SITES 108
TABLE 44 RELATIONSHIP BETWEEN HISTONE METHYLATION, METHYL
READERS AND THEIR FUNCTIONS 109
TABLE 45 NUMBER OF PUBMED PUBLICATIONS ON BIOMARKERS USING
DIFFERENT EPIGENETIC MECHANISMS, 2012 114
TABLE 46 DNA METHYLATION EVENTS AND THEIR RELATION TO DIFFERENT
PATHOLOGIES 115
TABLE 47 NUMBER OF PUBLICATIONS IN HISTONE METHYLATION AREA
BASED ON DIFFERENT SEARCH CRITERIA 118
TABLE 48 RELATIONSHIP BETWEEN HISTONE METHYLATION AND CANCER
PROGNOSIS 119
TABLE 49 DIFFERENT HISTONE METHYLTRANSFERASES AND THEIR
ASSOCIATION TO CANCER DEVELOPMENT 124
TABLE 50 DEMETHYLASES AND THEIR ASSOCIATIONS WITH CANCER
DEVELOPMENT 127
TABLE 51 GLOBAL BIOMARKERS MARKET, THROUGH 2015 ($ BILLIONS) 129
TABLE 52 SELECT EPIGENTICS DIANGOSTICS COMPANIES 129
TABLE 53 EXAMPLES OF AVERAGE REVENUES IN EPIGENETIC DIAGNOSTICS
COMPANIES 141
TABLE 54 GLOBAL MARKET FOR HISTONE METHYLATION IN BIOMARKERS
AND DIAGNOSTICS PRODUCT DEVELOPMENT, THROUGH 2018 ($ MILLIONS) 143
TABLE 55 DIAGNOSTICS MARKET VALUES IN ONCOLOGY SECTOR, 2013 ($
BILLIONS) 144
TABLE 56 WORLDWIDE PATENTS AND PATENT APPLICATION SEARCH IN
HISTONE METHYLTRANSFERASE RESEARCH USING SPECIFIC KEYWORDS
(NO. OF PATENTS) 146
TABLE 57 WORLDWIDE SEARCH FOR NUMBER OF PATENTS AND PATENT
APPLICATIONS IN HISTONE METHYLTRANSFERASE RESEARCH ACCORDING
TO ASSIGNEE 148
TABLE 58 NUMBER OF PUBLICATIONS USING HISTONE
METHYLTRANSFERASE AS SEARCH, 2000-2012 150
TABLE 59 DISTRIBUTION OF DRUG DEVELOPMENT PROGRAMS IN
EPIGENETIC SPACE (%) 151
TABLE 60 GLOBAL MARKET FOR HISTONE METHYLTRANSFERASES
RESEARCH AND DEVELOPMENT, THROUGH 2018 ($ MILLIONS) 152
TABLE 61 EXAMPLES OF MARKET PARTICIPANTS IN HISTONE
METHYLTRANSFERASE SECTOR AND THEIR REPRESENTATIVE PRODUCTS 153



LIST OF FIGURES

SUMMARY FIGURE GLOBAL MARKET FOR HISTONE METHYLTRANSFERASES
RESEARCH AND DEVELOPMENT, 2011-2018 ($ MILLIONS) 7
FIGURE 1 SCHEMATIC PRESENTATION OF METHYLATION REACTION 17
FIGURE 2 SCHEMATIC REPRESENTATION OF HMTS ASSAY DEVELOPMENT 49
FIGURE 3 GLOBAL MARKET FOR RESEARCH TOOLS, REAGENTS AND ASSAYS
FOR HISTONE METHYLTRANSFERASE STUDIES, 2011-2018 ($ MILLIONS) 63
FIGURE 4 GLOBAL DRUG DISCOVERY MARKET VALUE FOR HISTONE
METHYLTRANSFERASE RESEARCH, 2011-2018 ($ MILLIONS) 103
FIGURE 5 GLOBAL MARKET FOR HISTONE METHYLATION IN BIOMARKERS
AND DIAGNOSTICS PRODUCT DEVELOPMENT, 2011-2018 ($ MILLIONS) 143
FIGURE 6 NUMBER OF PUBLICATIONS FROM 2000-2012 USING HISTONE
METHYLTRANSFERASE AS SEARCH 150
FIGURE 7 GLOBAL MARKET FOR HISTONE METHYLTRANSFERASES
RESEARCH AND DEVELOPMENT, 2011-2018 ($ MILLIONS) 153

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Extra value: One year of free online updates included with this product There are today at least 1421 biological drugs known to affect more than 266 specific intracellular signaling pathways for the treatment ...


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