The Future of Personalized Medicine
The impact of proteomics on drug discovery and clinical trial design
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| Personalized Medicine: The impact of proteomics on drug discovery and clinical trial design’ is a management report that analyses how proteomics will streamline drug development and lead to the more cost-effective development of niche personalized products of the future. Proteomics promises lower R&D costs and the opportunities of new revenue streams through the identification of new drug targets in the treatment of diseases such as cancer and Alzheimer's. Use this report to identify the most important technologies, their applications in drug discovery and clinical trial design and the leading companies driving development of this exciting new area. The pharmaceutical industry has so far been slow to take up proteomic technology and strategic alliances and acquisitions will be central to the pharmaceutical industry's uptake of proteomics. This report identifies the key technologies that will enable pharmaceutical companies to develop new niche products, improve drug attrition rates, increase the speed of clinical development and target new drug markets. |
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By Global Business Insights / Publication Date: 1st October 2004
Contents:
Table of Contents
The Future of Personalized Medicine: The Impact of
Proteomics on Drug Discovery and Clinical Trial Design.
Executive summary 10
Introduction to proteomics 10
Proteomic technologies 11
Proteomic applications in drug discovery 12
Proteomic applications in clinical trial design and personalized medicine 13
Pharma and proteomic company alliances 13
Chapter 1
Introduction to proteomics 16
Summary 16
Introduction 17
The human genome versus the proteome 19
Identification of human genome 19
Applications to proteomics 20
The relationship between the proteome and the genome 22
The genome 22
Proteins 23
From genes to proteins 26
Proteomics 28
Conclusions 29
Chapter 2
Proteomic technologies 32
Summary 32
Laboratory methods used in proteomics 33
Separation techniques 33
Identification techniques 33
Interactions techniques 33
Separation techniques 37
2-dimensional polyacrylamide gel electrophoresis (2-D PAGE) 37
Liquid chromatography (LC) 37
Protein arrays 38
Identification techniques 39
Mass spectrometry 39
Protein-protein interaction techniques 41
Automation 42
Pre-fractionation 42
Separation 43
Identification 44
Complete proteomics solutions 45
The future of automation in proteomics 45
Conclusions 47
Bioinformatics and databases 48
Data analysis 49
Databases 49
Laboratory information management systems (LIMS) 51
Conclusions 52
Overall conclusions 52
Chapter 3
Proteomic applications in drug discovery 56
Summary 56
Introduction 57
Optimizing the R&D process 59
Early selection of efficacious and non-toxic drug targets 64
Toxicoproteomics 66
Pharmacoproteomics 67
Conclusions 68
Accelerating the discovery of new targets for therapeutic candidates 69
Therapeutic proteins 69
Protein targets 73
Mining the proteome is an alternative approach for drug discovery 73
Conclusions 74
Chapter 4
Proteomic applications in clinicaltrial design and personalized medicine 76
Summary 76
Development of new biomarkers 77
Biomarkers as clinical endpoints 79
Responders and non-responders 79
Patients with adverse reactions 81
Patients in different stages of a disease, or other subsets of patients 81
Monitor clinical responses in new and comparator drugs - allowing potential
strategic alliances 83
Patients with disease resistance 84
Niche markets 85
Conclusions 85
Application of biomarkers by therapy area 86
Oncoproteomics 87
Application in the diagnosis of ovarian cancer 87
Application in the diagnosis of prostate cancer 88
Application in the diagnosis of breast cancer 88
Application in the diagnosis of esophageal cancer 89
Neuroproteomics 89
Application in the diagnosis of Alzheimer’s diseases 89
Application in the diagnosis of amyotrophic lateral sclerosis (ALS) 90
Cardioproteomics 90
Cardiovascular markers 90
Respiratory markers 91
Application in organ transplantation 91
Post-marketing applications of biomarkers 92
Conclusions 93
Conclusions 94
Conclusions 94
Chapter 5
Pharmaceutical and proteomic company alliances 98
Summary 98
Introduction 99
Recent collaborations and alliances of pharma and proteomic based
companies 101
Abbott 101
Altana 101
AstraZeneca 101
Aventis 102
Bayer 102
Bristol-Myers Squibb 103
Boehringer Ingelheim 104
Daiichi 105
Eli Lilly 105
Fujisawa 106
GlaxoSmithKline 106
Johnson & Johnson 106
Lundbeck 106
Merck & Co. 107
Merck KGaA 107
Novartis 107
Pfizer 108
Proteome Sciences 109
Procter & Gamble 109
Roche 109
Schering AG 110
Sumitomo Chemical 110
Takeda 112
UCB 113
Wyeth 113
Conclusions 113
Chapter 6
Appendix 116
2-dimensional polyacrylamide gel electrophoresis (2-D PAGE) 116
Summary 118
Liquid chromatography (LC) 119
Gel filtration chromatography 120
Ion exchange chromatography 120
Affinity chromatography 120
Partitioning chromatography 121
LC summary 121
High performance liquid chromatography 121
Protein arrays 122
Expression arrays 123
Functional arrays 125
Reverse arrays 125
Protein array summary 126
Mass spectrometry (MS) 127
Electro-spray ionization 129
Laser desorption/ionization 131
MALDI 131
SELDI 132
Protein-protein interactions 134
Fluorescence resonance energy transfer 136
Bioinformatics databases 137
Summary 137
Sequence databases and alignment tools 138
Domain and 3-dimensional structure databases 139
Databases of biochemical pathways 141
‘Techniques’ databases 142
The human proteome organization 143
Index 1447
References 146
Website references 153
List of Figures
Figure 1.1: Nearly 500 proteins identified through proteomics have known functions in disease20
Figure 1.2: The basic structure of the (unwound) DNA helix 22
Figure 1.3: The general structure of an amino acid and peptide bond 24
Figure 1.4: The active site of the bacterial serine protease subtilisin 25
Figure 1.5: The process of protein synthesis 26
Figure 2.6: Techniques used in proteomics 35
Figure 2.7: The role and scope of bioinformatics in proteomics research 48
Figure 3.8: Only 30% of drugs produce revenues that exceed the average R&D cost 59
Figure 3.9: Industry average attrition curves, 2004 60
Figure 3.10: US pharmaceutical industry R&D expenditure and NCEs approvals, 1995-2003 61
Figure 3.11: Strategies for analysis of toxicoproteomic data 66
Figure 3.12: The impact of protein probes on drug discovery 72
Figure 4.13: Three stages of diagnostic development 78
Figure 4.14: The predicted individual response to any one drug 80
Figure 6.15: Example of a 2-D PAGE gel 117
Figure 6.16: Representation of liquid chromatography 119
Figure 6.17: Typical high performance liquid chromatography set-up 122
Figure 6.18: Representation of a ‘sandwich’ – type expression array 124
Figure 6.19: A typical ESI instrument set up 130
Figure 6.20: Simplified diagram of MALDI apparatus 132
Figure 6.21: Representation of the yeast two hybrid system 135
Figure 6.22: Schematic representation of FRET for investigating protein-protein interactions 136
Figure 6.23: Representation of FRET for investigating protein-protein interactions 141
Figure 6.24: Example of a pathway diagram from KEGG 142
List of Tables:
Table 1.1: The single- and three-letter amino acid codes 23
Table 1.2: The codons and the amino acids that they specify 27
Table 2.3: Summary of key proteomics technologies 36
Table 2.4: A selection of protein array manufacturers* 39
Table 2.5: Automation of proteomic platforms 46
Table 2.6: Summary of proteomics databases* 50
Table 3.7: Constant dollar reduction in total cost per new drug, 2002 61
Table 3.8: R&D spend on drug development, 2002 64
Table 3.9: New biologics 69
Table 3.10: Recombinant proteins 70
Table 3.11: Protein drug targets 71
Table 3.12: New proteomic targets 73
Table 4.13: Proteomic biomarkers 78
Table 4.14: Correlation of survival with HER-2 over-expression 82
Table 5.15: Colloborations implementing proteomics technologies 100