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Analysis Of New Trends In Tantalum-Niobium Industrial Technology

1, the state of special metal materials tantalum and niobium Engineering Research Center to start construction of a comprehensive August 8, 2005, the state of special metal materials tantalum and niobium Engineering Research Center for the opening ceremony! In Ningxia Orient Nonferrous Metals Group, was held. Ningxia Autonomous Region to Vice Chairman Zhang Wu, Science and Technology Department Director Liu Huan, Shizuishan City Acting Mayor Tian, as well as Ningxia Orient Nonferrous Metals Group Chairman He Jilin, inaugurated the center, marking the special state of Tantalum and Niobium Metal Material Engineering Technology Research Center building has already started.

National TantalumNiobium Special Metal Materials Engineering Research Center by the National Science and Technology approved the formation of the Chinese materials, tantalum and niobium metals beryllium areas and industrial areas in Ningxia Autonomous Region No. 1 National Engineering Research Center. Engineering Center of Ningxia Oriental Nonferrous Metal Group Company will be relying on marketoriented, focusing on breakthroughs in metal smelting and processing of special key technologies, continuous research, development and engineering achievements, to build platform for industry innovation to drive industrywide scientific and technological progress and new product development, to raise China’s specialty metals industry technology.

Ningxia Orient Nonferrous Metal Group Company is a research, production and technology development as one of national largescale enterprise group metals, in tantalum, niobium, beryllium and its alloys and specialty metals is strong in areas such as research and development capacity in the domestic same industry in the leading position in technology. Ningxia Orient TantalumNiobium Nonferrous Metals Group, the country will be special metal Material Engineering Technology Research Center set up as a turning point. The formation of the Engineering Center and the Group’s restructuring, resource optimization, combining full use of group 40 years and accumulated rich experience and preliminary scientific research and development of science and technology innovation platform built as far as integration of advantageous resources center construction works carried out in all members of the unit technical, research and development institutions and other resources, equipment, facilities and conditions for integration, and improve various facilities, to establish a rational engineering research environment for research and development and scientific research to provide a good environment and a strong guarantee, and strive to improve the overall technological innovation capability, so that the project the center into a tantalum, niobium, beryllium specialty metal smelting and processing technologies, and supporting the development of innovative equipment, the main results promote the use of an incubator of new technologies into the market and promoting China’s special metal materials technological progress and industrial upgrading .

2, Ningxia Orient Tantalum colored targeting the international market to open up new areas of application of niobium beryllium Commissioned by the State Science and Technology, Ningxia Autonomous Region Science and Technology Department recently held an expert on the northwest Ningxia Oriental Nonferrous Metal Group Companyowned Rare Metal Materials Research Institute “with niobium superconducting cavity plate production technology development” project was carried out onsite inspection. The project is a total investment of 3.5 billion U.S. dollars level for the hundreds of millions of electron volts of the world’s largest superconducting linear accelerator project will require superconducting niobium plate manufacturing process technology research and development be implemented. Superconducting linear accelerator project is a multicountry crossborder cooperation projects, built in Hamburg, Germany, total length of 33 km, engineering, need to consume about 500 tons of niobium sheet. The project is completed, it will greatly facilitate the physics, chemistry, materials science, environmental and earth sciences, structural biology and many other fields of scientific and technological progress to solve the nuclear waste disposal problem.

Experts believe that with the niobium superconducting cavity plate production technology research and development success, has opened up new applications of our areas of niobium material to fill gaps in the study of China so that China’s new materials, manufacturing techniques quickly with international practice. Through participation in international cooperation projects, so that the formation of tantalum powder in Ningxia, tantalum wire, tantalum and tantalum strip products, and superconducting materials such as tantalum a wide range of hightech products system, and full access to international markets, stabilize the country tantalum and niobium in the world top three position.

Through “with niobium superconducting cavity plate production technology development,” implementation of the project, the Northwest Rare Metal Materials Research Institute formed a stable performance superconducting niobium plate manufacturing process technology, impurity control, control of residual resistivity, grain size control, control of yield strength and hardness of control to achieve innovative results. In the manufacturing technology, product performance reached the international advanced level, to become the material basis for linear accelerator.

As a set of scientific research, production and technology development as one of the nation’s largest tantalum, niobium production base and the only scientific research and production base of berylliumNingxia Orient Nonferrous Metal Group Co., Ltd., based on independent innovation, to achieve the innovation and development.

In recent years, after a continuous selfdevelopment and technology research to develop a number of tracking international development, technology leadership to meet the needs of domestic and international market of new products to achieve a tantalum powder and tantalum wire of high grade and technological upgrading. Tantalum powder of its flagship product, the market has reached 70,000 hematocrit application level, hematocrit level of research to reach 15,000 or more into the international leading ranks. They developed new products, the semiconductor target with tantalum and niobium, nickel hydroxide, magnesium alloy and processing of special materials and so on, has become the promotion of economic growth in Ningxia, a new bright spot. The company has 14 national patents, 3 international patents. Last year, the Ministry of Science and formally approved Ningxia Orient Nonferrous Metal Group Co., Ltd. as “special statelevel TantalumNiobium Metal Material Engineering Technology Research Center” group also established a “demonstration base of Ningxia Hui Autonomous Region of international scientific cooperation.”

In recent years, they study, and research, focusing on innovation and team building for enterprise development to provide a strong technical support. They coorganized with the Nankai University, “lithium niobate crystal and device research and development of the Commonwealth” and the Beijing University of Science and Technology jointly launched a “Nanopowders Prepared by Homogeneous Reduction Research”, and Tsinghua University jointly launched a “Welding of Beryllium Research Laboratory , “has made substantial progress. While taking advantage of postdoctoral stations, the National Engineering Center, enterprise technology center platform with strong technical innovation to attract talented people to carry out joint research in the “stress of Beryllium study” and “beryllium deuteride and beryllium hydride preparation of technical studies,” etc. breakthroughs.

In addition, they light alloy with the Russian Academy of partnerships, the introduction of magnesium alloy melting and casting technology and some key equipment, through digestion and absorption of annual production capacity of 10,000 tons of magnesium alloy and processing of material production line. The “superconducting niobium cavity with the sheet production technology development” project was carried out with the German Electron Synchrotron Institute of the good cooperation the success of acceptance of this technology to enhance the technological level of China’s metal niobium and production capacity for our metal niobium and their processed material to enter the international market and lay a solid foundation of technology and market.

3, tantalum niobium new trend in the development of new materials, Rare Metal Materials technology is the new century, the field of materials science and engineering disciplines, one of the most attention is the hightech development of key materials, tantalum, niobium and new materials which play an important role. Modern hightech such as information technology, new energy technology, space technology, biotechnology, the development of superconducting technology, especially with the rare metal material is closely related to new materials, tantalum and niobium. Tantalum and niobium in hightech field of new materials, more and broader space for development, above all, tantalum and niobium capacitors to the highvolume areas of expansion; Second, the carbide cutting tool towards superhard, microfine sharp direction, the application market is expected to will remain steady climbing; again is a tantalum and niobium used in the aerospace industry, tantalum, niobiumbased alloys and other specialty alloys will continue to develop steadily.

In recent years, specialNb steel demand continues to grow, in addition to the developed countries, the Third World countries also have needs. Special superconducting materials will be used extensively for magnetic materials, and hightech computing technologies, and are being further expanded, tantalum, niobium materials, new applications will continue to be developed. Based on the world’s hightech industrial development process, the next 510 years, TantalumNiobium Industry will continue to maintain over 12% increase in sustainable development. TantalumNiobium development of new materials has broad development space and market prospects. The current application of new materials, tantalum and niobiumrelated hightech industries including electronics, precision ceramic and precision glass industry; electroacousticoptic devices; carbide, aerospace and electronic energy industry; biomedical engineering; superconductor industry; special steel and other industries.

4, Jiangxi trends: Jiangxi Tungsten Industry Group rare rare earth metals, deputy chief engineer Meng Fancheng introduced new materials, tantalum and niobium in hightech field, more and broader space for development, above all, tantalum and niobium capacitors to the highvolume areas of expansion; Second, the carbide cutting tool towards the superhard, microfine sharp direction, applications market is expected to remain steady climbing; again is a tantalum and niobium, as well as in the aerospace industry can not be replaced tantalum and niobiumbased alloys and other specialty alloys will continue to develop steadily. In recent years, specialNb steel demand continues to grow, in addition to the developed countries, the Third World countries also have needs.

Based on the world’s hightech industrial development process, the next 5 to 10 years TantalumNiobium Industry will continue to maintain over 12% increase in sustainable development. TantalumNiobium development of new materials has broad development space and market prospects. The current application of new materials, tantalum and niobiumrelated hightech industries including electronics, precision ceramic and precision glass industry; electroacousticoptic devices; carbide, aerospace and electronic energy industry; biomedical engineering; superconductor industry; special steel and other industries.

Jiangxi, development direction of new materials, Tantalum and Niobium As China’s most important resources in the province of tantalum and niobium and development of provinces, Jiangxi Province, will use its accumulated technology, and resources to accelerate development of new materials, tantalum and niobium the pace of development, using the available resources to promote tantalum and niobium of the industrialization of new materials, pace.

Jiangxi is rich in rare metal mineral resources, such as tantalum and niobium is an important resource for the supply of highmelting metals, the Jiangxi Province, tantalum and niobium deposits highest in the country, including rare and rare earth metals, Jiangxi Tungsten Industry Group, the share accounted for some of tantalum and niobium metal reserves 34% of the country’s total reserves could be mining accounted for 69% of the country. After years of development, Jiangxi Province, a longterm in order to concentrate and primary products as the main characteristics of the industry to be improved, in the depth of tantalum and niobium and other rare metals processing and development of new materials to be developed rapidly, making Jiangxi field of new materials in the formation of tantalum and niobium a certain technological advantages and strong research and development capabilities.

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Innovations In Epigenetics: Advances In Technologies, Diagnostics & Therapeutics-Aarkstore Enterprise

Three main mechanisms – DNA methylation, histone modifications and changes in non-coding RNA – have been elucidated in epigenetics. Each in its own way may provide the industry with a greater understanding into the underlying mechanism of diseases, act as a potential source for biomarkers of disease and provide new targets for therapeutic intervention.

Besides everyday DNA analytical tools, epigenetic researchers have needed to adopt more complex technologies such as chromatin immunoprecipitation (ChIP) and DNA methylation methodologies as well as develop analytical tools to decipher the vast amount of epigenetic information. Advances in these technologies should enable epigenetic research to reduce cost and increase sample throughput making it more commercially attractive in the industry to discover biomarkers and validate novel epigenetic targets for diagnostic and pharmacological development.

Epigenetic medicine has arrived. The market is worth over 0 million derived from the sale of three anticancer products which target two epigenetic pathways – DNA methyltransferase (DNMT) and histone deacteylase (HDAC) – and around thirty epigenetic drugs are under development from more than a dozen biotechnology companies. These drugs focus mainly on the treatment of cancer, neurodegenerative and infectious diseases although research is underway to explore the role for epigenetics in cardiovascular, metabolic, ocular and other diseases. Whilst this market is still in its infancy KOLs believe it is on the cusp of a revolution, one which could change how patients are diagnosed and treated in the future.

Key features of this report

• Identify leading companies at the forefront of epigenetic research who will drive the market to develop a new generation of epigenetic therapies and diagnostics.

• Provide case studies of these leading companies developing epigenetic therapies to treat cancer, neurodegenerative and infectious diseases.

• Analyze the key trends and issues confronting the development of epigenetic therapies.

• Review the alliances, mergers, acquisitions and business strategies adopted by biotechs and big pharma to capitalize on the latest epigenetic developments.

Scope of this report

• Identify the companies leading the field in epigenetic research across a range of therapeutic areas

• Review their business strategies and the development of their epigenetic programs

• Learn more about the latest developments in epigenetic research and how non-coding RNAs may open up another Pandora’s box for epigenetic research.

• Identify innovative pharmaceutical companies and discover the strategies they are adopting to tap into the epigenetic potential both as biomarkers of disease and targets for therapeutic intervention

 

Key Market Issues

• Declining industry productivity: It is a well documented fact that productivity in the pharma industry has declined during the past 15 years. The identification of new biomarkers of disease could aide the R&D process and support the preclinical and clinical development of small molecule therapeutics.

• Innovative new drug classes: The identification of underlying mechanisms of diseases could identify new target
for small molecule therapeutic intervention that may be used alone or in combination with traditional therapies to
extend their usage.

 

Key findings from this report

• New epigenetic therapies have entered the market. The first medicines were approved in 2006 for the treatment of cancer and a host of new small molecule therapies are now under development which are more selective and target different classes of chromatin modifying enzymes enabling a more targeted approach to treatment.

• The ability of innovative companies to generate intellectual property is a key driver for the sector as the market become more competitive in this new area of science. The unraveling of the human epigenome will be the first step in identifying new epigenetic markers which may have potential as biomarkers an area of considerable interest for the pharmaceutical industry at the present time.

Key questions answered

• Which companies are the market leaders in the epigenetics industry, identified through therapeutic areas (cancer, infectious diseases, neurodegenerative diseases, metabolic, cardiovascular, ophthalmic, other diseases) and recent alliances with the pharmaceutical companies?

• What are the key products of these companies and how do they exemplify the future direction of the epigenetic therapies?

• How is the pharmaceutical industry approaching the need for new targeted epigenetic therapies and what strategies are they taking?
 
 
  Table of Contents : 
Table of Contents
Innovations in Epigenetics
Executive summary 10
Introduction 10
Application in R&D & technological advances 10
Exploring new therapeutic targets 11
Epigenetic market, leading companies & pharmaceutical strategies 12
The future of epigenetics 13
Chapter 1 Introduction 16
What is epigenetics? 17
Epigenetics and phenotypes 19
Epigenetics a new biological paradigm 19
Epigenetics, genetics, genomics & pharmacogenomics 20
Molecular mechanisms associated with epigenetics 22
DNA methylation 22
Histone modifications 23
Nucleosome remodelling 23
Non-coding RNA 24
X chromosome inactivation 24
Gene imprinting 24
RNA interference 24
Epigenetic basis of disease 25
Epigenetic syndromes 25
Angelmann syndrome 25
Beckwith-Wiedemann syndrome 26
Prader-Willi syndrome 26
Why is epigenetics of interest to the pharmaceutical industry? 27
Biomarker discovery & diagnostics 28
Novel small molecule epigenetic therapeutics 28
Novel antisense therapeutics 28
Stem cells & regenerative medicines 29
Conclusions 29
Chapter 2 Application in R&D & technological advances 32
The application of epigenetics in drug R&D 33
DNA methylation biomarkers 34
Histone modification biomarkers 35
Technological advances in epigenetics 35
Chromatin immunoprecipitation 36
DNA methylation technologies 38
Non-coding RNA technologies 43
Bioinformatic modeling 43
Conclusions 44
Chapter 3 Exploring new therapeutic targets 48
Potential new therapeutic targets 49
Epigenetics in cancer 50
DNA methyltransferase & DNMT inhibitors 52
Case study: Vidaza (Celgene Corporation) & Dacogen (Eisai /J&J) 53
Case study: Zebularine a research tool 56
Histone acetylase (HAT) and histone deacetylase (HDAC) 59
Case study: Zolinza (Merck & Co.) 61
Case study: MGCD0103 (MethylGene/Taiho Pharmaceutical) 62
Case study: PCI-24781 (Pharmacyclics/Servier) 63
Histone demethylases and histone methyltranserases 65
Case study: PG11144 & PG11047 (Progen Pharmaceuticals) 66
Potential epigenetic based diagnostics 67
Diagnostic DNA methylation cancer biomarkers 67
Case study: Epi proColon (Epigenomics AG) 69
The next generation of epigenetic cancer biomarkers 71
Epigenetics in neurological disorders 72
Case study: EVP-0334 (EnVivo Pharmaceuticals) 73
Epigenetics in infectious diseases 75
Case study: MGCD290 (MethylGene) 75
Case study: siRNA targeting HIV-1 (Kevin Morris, Scripps, La Jolla) 76
Epigenetics in metabolic disorders 78
Epigenetics in cardiovascular disease 81
Epigenetics in ocular disorders 83
Case study: Kinase inhibitors (Otsuka Pharmaceutical/MethylGene) 84
Case study: Kinase inhibitors/S-adenosyl methionine (SAM) (Epizyme). 85
Conclusions 86
Chapter 4 Epigenetic market, leading companies & pharmaceutical strategies 90
Epigenetic market 91
Epigenetic therapeutic revenues: Now and the future 92
Leading epigenetic companies 93
4SC AG, Planegg-Martinsried, Germany 94
Celgene Corporation, Summit, New Jersey 95
Curis Inc, Cambridge, MA 96
Chroma Therapeutics Ltd, Oxon, UK 98
Constellation Pharmaceuticals, Cambridge, MA 99
EnVivo Pharmaceuticals, Watertown, MA 100
EpiTherapeutics Aps, Copenhagen, Denmark 101
Epizyme, Cambridge, MA 101
Gloucester Pharmaceuticals, Cambridge, MA 103
MethylGene, Inc. Montreal, Québec 104
Pharmacyclics, Sunnyvale, CA 106
Progen Pharmaceuticals, Brisbane, Australia 107
Repligen Corporation, Waltham, MA 108
SuperGen, Dublin, CA 109
Syndax Pharmaceuticals, Waltham, MA 112
TopoTarget, Copenhagen, Denmark 113
Summary of epigenetic-based companies 114
Recent alliances, mergers & acquisitions in epigenetics 115
Pharmaceutical strategies in epigenetics 118
GlaxoSmithKline, Middlesex, UK 118
Novartis, Basel, Switzerland 119
Merck & Co., Whitehouse, NJ 121
Eisai Corporation of North America, NJ 122
Takeda, Osaka, Japan 123
Overall conclusions 123
Chapter 5 The future of epigenetics 126
The future of epigenetics 127
Epigenetic consortia; unraveling the human epigenome 128
NIH’s Roadmap Epigenomics Program initiative 128
European Epigenome Network of Excellence 130
Human Epigenome Consortium 130
KOLs in epigenetics 131
John Mattick, Institute for Molecular Bioscience, University of Queensland,
Australia 132
Overview 132
Technology 133
Applications 133
Future 134
Kevin Morris, Scripps Institue, La Jolla, CA 134
Overview 134
Technology 135
Applications 135
Future 136
Monika Lachner, Max-Planck Institute of Immunobiology, Department of
Epigenetics, Freiburg, Germany 136
Overview 136
Technology 136
Applications 137
Future 137
Johnathan Whetstine, Department of Medicine, Massachusetts General
Hospital Cancer Center 137
Overview 138
Technology 138
Applications 138
Future 139
Peter Fraser, Head, Senior Fellow of the Medical Research Council, UK, The
Babraham Institute, Cambridge 139
Overview 139
Technology 140
Applications 140
Future 141
Summary of KOLs commentary 141
Challenges 142
Fundamental research 142
Technological demands 142
Financial constraints 143
Intellectual property 144
Opportunities 144
Biomarker discovery & diagnostics 144
Therapeutic intervention 145
Regenerative medicines 145
Conclusions 146
Chapter 6 Appendices 150
Glossary 150
Acknowledgements 156
Index 157
Index 157
Bibliography 159
Endnotes 165

List of Figures
Figure 1.1: Timeline of epigenetics study 18
Figure 1.2: Schematic of chromatin structure 22
Figure 1.3: Schematic of epigenetic mechanisms associated with health and disease 23
Figure 1.4: Epigenetic applications by the pharma industry 27
Figure 2.5: Epigenetics in the drug discovery & development process 34
Figure 2.6: Schematic of key technologies used in epigenetics 36
Figure 2.7: Schematic of ChIP technology 37
Figure 2.8: Epigenomics AG methylation specific PCR (MSP) methods 42
Figure 3.9: DNA methylation targets for epigenetic cancer therapies 51
Figure 3.10: Mechanism of action of HAT and HDAC 61
Figure 3.11: Epi proColon high throughput colorectal epigenetic test 70
Figure 3.12: Competitive pricing of Epi proColon 71
Figure 3.13: EnVivo’s HDAC project screening cascade 74
Figure 3.14: Agouti mice and epigenetic manipulation 79
Figure 3.15: Epizyme’s rational design of small molecule HMT inhibitors 85
Figure 4.16: Epigenetic therapies: product class and developmental phase 91
Figure 4.17: Epigenetic therapies: therapy target and developmental phase 92
Figure 4.18: CUDU-101 structure & design: combining multiple pharmacophores 97

List of Tables
Table 2.1: DNA methylation PCR methods 40
Table 2.2: Techniques to analyze DNA methylation 41
Table 3.3: Examples of DNMT inhibitors: potential anticancer agents targeting epigenetic pathways 54
Table 3.4: Examples of DNMT inhibitor research tools 55
Table 3.5: HDAC inhibitors: potential anticancer agents targeting epigenetic pathways 57
Table 3.6: Examples of HDAC inhibitor research tools 59
Table 3.7: Histone modification and their effect on gene expression 60
Table 3.8: Safety profiles of PCI-24781 rivals 64
Table 3.9: DNA methylation sites associated with cancers 67
Table 3.10: Validated and hypothetic miRNA targets for diabetes & obesity 81
Table 4.11: Epigenetic therapeutic revenues ($ m), 2009-2020 93
Table 4.12: Preliminary clinical data for Pharmacyclics PCI-24781 106
Table 4.13: Recent alliances, acquisitions and mergers in the epigenetic arena 117
Table 5.14: NIH Epigenetic Roadmap – funded epigenetic projects 129

 

Table of Contents
Innovations in Epigenetics
Executive summary 10
Introduction 10
Application in R&D & technological advances 10
Exploring new therapeutic targets 11
Epigenetic market, leading companies & pharmaceutical strategies 12
The future of epigenetics 13
Chapter 1 Introduction 16
What is epigenetics? 17
Epigenetics and phenotypes 19
Epigenetics a new biological paradigm 19
Epigenetics, genetics, genomics & pharmacogenomics 20
Molecular mechanisms associated with epigenetics 22
DNA methylation 22
Histone modifications 23
Nucleosome remodelling 23
Non-coding RNA 24
X chromosome inactivation 24
Gene imprinting 24
RNA interference 24
Epigenetic basis of disease 25
Epigenetic syndromes 25
Angelmann syndrome 25
Beckwith-Wiedemann syndrome 26
Prader-Willi syndrome 26
Why is epigenetics of interest to the pharmaceutical industry? 27
Biomarker discovery & diagnostics 28
Novel small molecule epigenetic therapeutics 28
Novel antisense therapeutics 28
Stem cells & regenerative medicines 29
Conclusions 29
Chapter 2 Application in R&D & technological advances 32
The application of epigenetics in drug R&D 33
DNA methylation biomarkers 34
Histone modification biomarkers 35
Technological advances in epigenetics 35
Chromatin immunoprecipitation 36
DNA methylation technologies 38
Non-coding RNA technologies 43
Bioinformatic modeling 43
Conclusions 44
Chapter 3 Exploring new therapeutic targets 48
Potential new therapeutic targets 49
Epigenetics in cancer 50
DNA methyltransferase & DNMT inhibitors 52
Case study: Vidaza (Celgene Corporation) & Dacogen (Eisai /J&J) 53
Case study: Zebularine a research tool 56
Histone acetylase (HAT) and histone deacetylase (HDAC) 59
Case study: Zolinza (Merck & Co.) 61
Case study: MGCD0103 (MethylGene/Taiho Pharmaceutical) 62
Case study: PCI-24781 (Pharmacyclics/Servier) 63
Histone demethylases and histone methyltranserases 65
Case study: PG11144 & PG11047 (Progen Pharmaceuticals) 66
Potential epigenetic based diagnostics 67
Diagnostic DNA methylation cancer biomarkers 67
Case study: Epi proColon (Epigenomics AG) 69
The next generation of epigenetic cancer biomarkers 71
Epigenetics in neurological disorders 72
Case study: EVP-0334 (EnVivo Pharmaceuticals) 73
Epigenetics in infectious diseases 75
Case study: MGCD290 (MethylGene) 75
Case study: siRNA targeting HIV-1 (Kevin Morris, Scripps, La Jolla) 76
Epigenetics in metabolic disorders 78
Epigenetics in cardiovascular disease 81
Epigenetics in ocular disorders 83
Case study: Kinase inhibitors (Otsuka Pharmaceutical/MethylGene) 84
Case study: Kinase inhibitors/S-adenosyl methionine (SAM) (Epizyme). 85
Conclusions 86
Chapter 4 Epigenetic market, leading companies & pharmaceutical strategies 90
Epigenetic market 91
Epigenetic therapeutic revenues: Now and the future 92
Leading epigenetic companies 93
4SC AG, Planegg-Martinsried, Germany 94
Celgene Corporation, Summit, New Jersey 95
Curis Inc, Cambridge, MA 96
Chroma Therapeutics Ltd, Oxon, UK 98
Constellation Pharmaceuticals, Cambridge, MA 99
EnVivo Pharmaceuticals, Watertown, MA 100
EpiTherapeutics Aps, Copenhagen, Denmark 101
Epizyme, Cambridge, MA 101
Gloucester Pharmaceuticals, Cambridge, MA 103
MethylGene, Inc. Montreal, Québec 104
Pharmacyclics, Sunnyvale, CA 106
Progen Pharmaceuticals, Brisbane, Australia 107
Repligen Corporation, Waltham, MA 108
SuperGen, Dublin, CA 109
Syndax Pharmaceuticals, Waltham, MA 112
TopoTarget, Copenhagen, Denmark 113
Summary of epigenetic-based companies 114
Recent alliances, mergers & acquisitions in epigenetics 115
Pharmaceutical strategies in epigenetics 118
GlaxoSmithKline, Middlesex, UK 118
Novartis, Basel, Switzerland 119
Merck & Co., Whitehouse, NJ 121
Eisai Corporation of North America, NJ 122
Takeda, Osaka, Japan 123
Overall conclusions 123
Chapter 5 The future of epigenetics 126
The future of epigenetics 127
Epigenetic consortia; unraveling the human epigenome 128
NIH’s Roadmap Epigenomics Program initiative 128
European Epigenome Network of Excellence 130
Human Epigenome Consortium 130
KOLs in epigenetics 131
John Mattick, Institute for Molecular Bioscience, University of Queensland,
Australia 132
Overview 132
Technology 133
Applications 133
Future 134
Kevin Morris, Scripps Institue, La Jolla, CA 134
Overview 134
Technology 135
Applications 135
Future 136
Monika Lachner, Max-Planck Institute of Immunobiology, Department of
Epigenetics, Freiburg, Germany 136
Overview 136
Technology 136
Applications 137
Future 137
Johnathan Whetstine, Department of Medicine, Massachusetts General
Hospital Cancer Center 137
Overview 138
Technology 138
Applications 138
Future 139
Peter Fraser, Head, Senior Fellow of the Medical Research Council, UK, The
Babraham Institute, Cambridge 139
Overview 139
Technology 140
Applications 140
Future 141
Summary of KOLs commentary 141
Challenges 142
Fundamental research 142
Technological demands 142
Financial constraints 143
Intellectual property 144
Opportunities 144
Biomarker discovery & diagnostics 144
Therapeutic intervention 145
Regenerative medicines 145
Conclusions 146
Chapter 6 Appendices 150
Glossary 150
Acknowledgements 156
Index 157
Index 157
Bibliography 159
Endnotes 165

List of Figures
Figure 1.1: Timeline of epigenetics study 18
Figure 1.2: Schematic of chromatin structure 22
Figure 1.3: Schematic of epigenetic mechanisms associated with health and disease 23
Figure 1.4: Epigenetic applications by the pharma industry 27
Figure 2.5: Epigenetics in the drug discovery & development process 34
Figure 2.6: Schematic of key technologies used in epigenetics 36
Figure 2.7: Schematic of ChIP technology 37
Figure 2.8: Epigenomics AG methylation specific PCR (MSP) methods 42
Figure 3.9: DNA methylation targets for epigenetic cancer therapies 51
Figure 3.10: Mechanism of action of HAT and HDAC 61
Figure 3.11: Epi proColon high throughput colorectal epigenetic test 70
Figure 3.12: Competitive pricing of Epi proColon 71
Figure 3.13: EnVivo’s HDAC project screening cascade 74
Figure 3.14: Agouti mice and epigenetic manipulation 79
Figure 3.15: Epizyme’s rational design of small molecule HMT inhibitors 85
Figure 4.16: Epigenetic therapies: product class and developmental phase 91
Figure 4.17: Epigenetic therapies: therapy target and developmental phase 92
Figure 4.18: CUDU-101 structure & design: combining multiple pharmacophores 97

List of Tables
Table 2.1: DNA methylation PCR methods 40
Table 2.2: Techniques to analyze DNA methylation 41
Table 3.3: Examples of DNMT inhibitors: potential anticancer agents targeting epigenetic pathways 54
Table 3.4: Examples of DNMT inhibitor research tools 55
Table 3.5: HDAC inhibitors: potential anticancer agents targeting epigenetic pathways 57
Table 3.6: Examples of HDAC inhibitor research tools 59
Table 3.7: Histone modification and their effect on gene expression 60
Table 3.8: Safety profiles of PCI-24781 rivals 64
Table 3.9: DNA methylation sites associated with cancers 67
Table 3.10: Validated and hypothetic miRNA targets for diabetes & obesity 81
Table 4.11: Epigenetic therapeutic revenues ($ m), 2009-2020 93
Table 4.12: Preliminary clinical data for Pharmacyclics PCI-24781 106
Table 4.13: Recent alliances, acquisitions and mergers in the epigenetic arena 117
Table 5.14: NIH Epigenetic Roadmap – funded epigenetic projects 12
 
 

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Disruptive Technology In The Enterprise: Future Trends, Impact And Vulnerabilities To Substitution-Aarkstore Enterprise

The motor car, mobile phones, personal computers, and so on, are all examples of disruptive technologies. There are numerous examples throughout modern business history of disruptive technologies appearing, apparently from nowhere, to threaten and ultimately displace existing technologies and the industries and vendors that grew up around them – such as the mainframe industry, communications and storage.

But disruption is rarely a consequence of technology innovation alone, rather a reflection of how existing organizations and markets deal with it. While disruptive innovation can be seen as a threat, it is also an opportunity, and indeed a necessity in the rapidly evolving world of IT and business technology.
Modern history suggests that accurate prediction of disruptive technologies is challenging, however a look at past examples can reveal important characteristics and similarities between disruptive technologies. This report aims to provide insight into the patterns and characteristics of potentially disruptive technologies and innovation trends, and provide ways of assessing vulnerability to disruption. As a result, organizations can use this insight to understood how best to avoid the threat of disruption.

Key features of this report

-A survey of CIOs in a variety of vertical industries and geographies provides insight into how innovation is managed, and where there is current vulnerability to disruption.
-A proprietary assessment model for gaining insight into how successful a potentially disruptive technology could be.
-Offers an assessment model for understanding and avoiding vulnerability to disruptive technologies.
-CIO survey reveals where there is most demand for improvements in technology performance and efficiency.
-Analysis of 4 new technologies showing which technologies could be potentially disruptive.

Scope of this report

a) Gain insight into where there are current vulnerabilities to technological disruption.
b) Understand how to identify and characterise potentially disruptive technologies.
c) Find out where CIOs believe there is the greatest need for technological improvement.
d) Gain access to a disruption assessment model, which provides a method for assessing vulnerability to disruption.
e) Understand which industries and organisations are potentially vulnerable to technological disruption.

Key findings from this report
Disruptions not only displace technologies, they also fundamentally shift the balance of power in entire industries and, often, spell the end for established market leading vendors.
There is nothing disruptive per se about any new technology; rather disruption comes from the manner in which the industry leaders and players manage it.
The drivers and inhibitors of disruption can be broadly divided into two factors: customer need (driver), such as greater performance, lower cost, scalability, portability etc. and; barriers to entry (inhibitor), which can include unproven ROI, lack of knowledge, cost of switchover, and so on.
Cloud computing is very likely to become a ubiquitous computing model once the challenges are dealt with, and once the issue of trust is overcome.
Virtualization’s promise of significantly reduced energy consumption costs and hardware estate costs, combined with the IT and business agility benefits it offers, and relative ease and cost of integration and deployment means that it is very likely to see massive uptake, and become an ubiquitous technology within 10 years.

Key questions answered

a) What characteristics are common to disruptive technologies?
b) How can organizations assess their vulnerability to disruption?
c) Will open source communication devices threaten the incumbent market leaders for mobile application development?
d) What impact will the adoption of cloud computing as an ubiquitous IT delivery system have on existing market leaders?
e) Will NAND Flash memory replace DRAM and disk in the data center?
 
 
  Table of Contents : 
Table of Contents
Disruptive Technology in the Enterprise
Executive summary 10
Strategies for assessing disruptive technology 10
NAND Flash storage 11
Infrastructure virtualization 12
Cloud computing 13
Open source communications devices 14
Chapter 1 Introduction and scope of the report 16
Introduction 16
Who is this report for? 17
Research methodology 17
Definitions 17
Disruptive technology 17
NAND Flash storage 17
Infrastructure virtualization 18
Cloud computing 18
Open source communications devices 18
Chapter 2 Strategies for assessing disruptive technology 20
Summary 20
Introduction 21
What is a disruptive technology? 21
Examples of disruptive technologies 22
Defining disruptive patterns 23
The Innovator’s Dilemma 23
The evolution of a disruptive technology 26
Characteristics of a disruptive technology 27
Drivers and inhibitors of disruption 31
Economic, regulatory and social factors 33
Intrinsic and extrinsic factors 33
Innovation and business value 35
Types of innovation 35
Business value through disruption 36
Strategies for predicting disruption 40
Impact versus adoption 40
Peripheral, non-disruptive innovation 41
Immature disruptive innovation 41
Maturing disruptive technology 42
Core, non-disruptive innovation 42
Disruption assessment model 43
1. Impact 43
2. Adoption 44
Assessing the current potential for disruption 45
Conclusions 54
Chapter 3 NAND Flash storage 56
Summary 56
Introduction 57
Why is it potentially disruptive? 58
Market context 59
Market opportunity 61
Portable devices 61
Data center 62
Drivers and inhibitors 64
Drivers 64
Inhibitors 65
Vendor landscape 67
Impact versus adoption assessment 71
Impact 71
Adoption 73
Impact versus adoption assessment chart 75
Conclusions 76
Chapter 4 Infrastructure virtualization 80
Summary 80
Introduction 81
Why virtualization is potentially disruptive 82
Market context 83
Market opportunity 85
Market drivers 87
Carbon footprint 87
Overcapacity and IT consolidation 87
IT agility 89
IT management and staff costs 89
Business continuity and agility 90
Inhibitors 91
Operational and business barriers 91
Automation and management challenges 92
Lack of interoperability 92
Challenges in maximizing benefits 93
Vendor landscape 94
Open source versus proprietary 95
VMware 97
Microsoft 98
XenSource 98
Citrix 99
Impact versus adoption assessment 100
Impact 100
Adoption 104
Impact versus adoption assessment chart 107
Conclusions 108
Chapter 5 Cloud computing 112
Summary 112
Introduction 113
Why is it potentially disruptive? 113
Market context 115
Market opportunity 117
Market drivers 119
Services-based approach to IT 119
‘Elasticity’ 121
Variable costs and usage-based models 121
Driving down costs in enterprise IT 121
New IT economies 122
Inhibitors 123
Lack of trust 123
Service adoption and management challenges 124
Matching optimal delivery models 124
Formulating the business case 124
Procurement processes 125
Migration challenges 125
Vendor landscape 126
Hardware vendors 126
Portable devices 127
Cloud infrastructure services providers 128
Cloud platforms 130
SaaS-backed platforms 130
Stack platforms 131
Stand-alone platforms 132
SaaS applications developers 132
Impact versus adoption assessment 134
Impact 134
Adoption 137
Impact versus adoption assessment chart 139
Conclusions 140
Chapter 6 Open source communications devices 142
Summary 142
Introduction 143
Why is it potentially disruptive? 144
Market context 145
Market opportunity 148
Market drivers 151
Market inhibitors 152
Vendor landscape 153
Impact versus adoption assessment 158
Impact 158
Adoption 160
Impact versus adoption assessment chart 162
Conclusions 163
Chapter 7 Index 165

List of Figures
Figure 2.1: The evolution of a disruptive technology 27
Figure 2.2: Interaction of intrinsic and extrinsic factors for disruption 34
Figure 2.3: Disruptive technology and business value 37
Figure 2.4: Business value applied to current innovations 39
Figure 2.5: Impact versus adoption – the progression of disruptive innovation 40
Figure 2.6: Areas of business value important to organizations – CIO respondent average ratings 46
Figure 2.7: The impact of innovations on enterprises in the next three years – CIO respondent average ratings 47
Figure 2.8: Business areas where there is most room for improvement? (% CIO respondents) 48
Figure 2.9: Technologies that have most transformed organizations in the last two years – CIO respondent average ratings 50
Figure 2.10: How organizations monitor upcoming technologies – CIO respondent average ratings 51
Figure 2.11: Does your organization have a future technology roadmap in place? (% CIO respondents) 52
Figure 2.12: How organizations test upcoming / innovative technologies before purchase – % CIO respondents 53
Figure 3.13: NAND Flash impact score summary 71
Figure 3.14: NAND Flash adoption score summary 73
Figure 3.15: Impact versus adoption final assessment chart – NAND flash storage 75
Figure 4.16: Data center overcapacity 88
Figure 4.17: The most pressing needs for improvement in the IT department – % CIO respondents 100
Figure 4.18: Infrastructure virtualization impact score summary 101
Figure 4.19: Infrastructure virtualization adoption score summary 104
Figure 4.20: Impact versus adoption final assessment chart – infrastructure virtualization 107
Figure 5.21: Cloud computing overlaps with other technology terms and trends 115
Figure 5.22: Cloud computing as an IT consumption model 116
Figure 5.23: Cloud computing – the competitive landscape 118
Figure 5.24: The gap between IT capacity and IT demand 120
Figure 5.25: Cloud computing impact score summary 134
Figure 5.26: Cloud computing adoption score summary 137
Figure 5.27: Impact versus adoption final assessment chart – cloud computing 139
Figure 6.28: Global smartphone annual shipments (000s), 2008-2014 150
Figure 6.29: Open source communications devices impact score summary 158
Figure 6.30: Open source communications adoption score summary 160
Figure 6.31: Impact versus adoption final assessment chart – open source communication devices 162

List of Tables
Table 2.1: Examples of disruptive technologies 22
Table 2.2: Characteristics of an early-stage disruptive technology 28
Table 2.3: Example of drivers and inhibitors of disruption 32
Table 2.4: Intrinsic and extrinsic factors for disruptive technologies 34
Table 2.5: Different types of innovation 35
Table 2.6: Criteria for measuring disruptiveness of innovations 41
Table 2.7: Business Insights survey results – where is there most room for improvement in business areas? (% CIO respondents) 49
Table 4.8: Cost savings possible through server consolidation 84
Table 6.9: Global smartphone annual shipments by OS (000s), 2008-2014 150
 
 

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