The Future of Systems Biology: Emerging Technologies and their Impact on Drug Discovery, Development and Diagnostics
Scripp Business Insights, September 2005
'The Future of Systems Biology: Emerging Technologies and their Impact on Drug Discovery, Development and Diagnostics' is a new report which analyzes how systems biology can be used to cut R&D time and costs through improved target identification and lead quality, better elucidation of ADME/Tox profiles, as well as optimizing clinical trial efficiency. This report provides a detailed insight into this complex new process and how it can be used to drive research and development in a variety of biologically-based industries. The competitive landscape of systems biology assessed in this report is supported by case studies of leading companies, enabling you to learn from their experiences and avoid the potential pitfalls. The future of pharmaceuticals lies in combination therapies and more personalized therapeutics. This report will help you to maximize the cost and time saving benefits offered by biological systems in these areas to secure your frontline position in the marketplace.
Key Features:
- Detailed case studies of the pharmaceutical companies using systems biology to improve the drug discovery and development process.
- In-depth profiles on all major companies operating in systems biology, including patent information
- Detailed interviews with three thought leaders in systems biology
- Comprehensive listing of all major international initiatives in systems biology as well as key non-profit research centres
Key Findings
- Reductionist biology, which has been the traditional source of drug discovery, will not supply the solutions to complex diseases such as cancer and diabetes.
- Systems biology can provide the most benefit in improving lead optimization as well as providing better strategies for clinical trials.
- Systems biology offers the opportunity to study targets in an integrated network rather than in isolation.
- Roche uses in silico technologies in approximately 50% of its projects, mostly drugs in Phase II and Phase III clinical trials.
Executive Summary
Introduction to systems biology
Key aspects and components of systems biology
Applications of systems biology
Emerging technologies and developments
Case studies and success stories
Interviews with thought leaders in systems biology
Chapter 1 Introduction to systems biology
Summary
Introduction
Introduction to systems biology
Research applications of systems biology
The evolution of systems biology
Mathematical modeling
Physiology and cell biology
And now…
Change from reductionist biology
New technologies
Chapter 2 Key aspects and components of systems biology
Summary
Introduction
Approaches to systems biology
Bottom-up approach
Top-down approach
The reality in systems biology: a combination of bottom-up and top-down
Key aspects of systems biology
System structures
System dynamics
The control method
The design method
Four basic steps in systems biology
Key technology components of systems biology
The "omics"
Genomics
Transcriptomics
Proteomics
The emerging "omic" – metabolomics
Data storage and mining
Bioinformatics
Network biology
Pathway analysis
Modeling and biosimulations
Chapter 3 Applications of systems biology
Summary
Introduction
Drivers of systems biology
Increase in R&D costs
Examples of how systems biology can lower costs:
Fall in R&D productivity
Drug failures in clinical trials
Systems biology in pharmaceutical discovery and development
Identification of drug targets
Examples of success:
Improving the quality of lead compounds
Improved ADMET prediction
Fewer costly failures due to toxicity
Examples of success:
Optimization of clinical trials
Example of success:
Identification of biomarkers
Biomarkers for drug discovery and validation
Examples of success:
Biomarkers for toxicity
Biomarkers and segmentation of patient populations
Examples of success:
Biomarkers and the FDA's Critical Path Initiative
Development of combination drug therapies
Additional indications for pharmaceuticals already on the market
Improved lead prioritization and optimization
Better clinical trials strategies
Regulatory/industry initiatives
The FDA's Critical Path Initiative
Examples of success:
National Institutes of Health (NIH) roadmap
Diagnostic applications for systems biology
Cancer
Diagnosis of cancer
Delineation of cancer by sub-groups for therapeutic decisions
Monitoring of efficacy of treatment
Examples of success:
Diabetes
Example of success:
Systems biology in bioprocess engineering
Examples of success:
Additional applications for systems biology
Agricultural improvement
Examples of success:
Cosmetics
Example of success:
Biodefense
Example of success:
Bioremediation
Examples of success:
Conclusions
Chapter 4 Emerging technologies and developments
Summary
Introduction
RNAi
siRNA – small interfering RNAs
miRNA – microRNAs
New proteomic technologies
Antibody arrays
Morphoproteomics
Time-of-flight Mass Spectrometry (MS)
Ion Trap MS
Maldi-TOF
Q-TOF MS
Liquid Chromatography (LC) Q-TOF MS-MS spectrometer
Emerging software developments
Systems Biology Markup Language (SBML)
Systems Biology Workbench (SBW)
CellDesigner
Cytoscape
Pathway Tools Software from SRI
PathwayStudio Central
SRS Pathway Editor from Lion Bioscience AG
Databases of interest
PANTHER database of proteins
KEGG: Kyoto Encyclopedia of Genes and Genomes
SPAD: Signaling Pathway Database
BIND: Biomolecular Interaction Network Database
HPRD: Human Protein Reference Database
GO: Gene Ontology
DIP: Database of Interacting Proteins
BioBase: Biological Databases / Biologische Datenbanken GmbH
PDB: Protein Data Bank
AfCS: Alliance for Cellular Signaling
BioModels Database
Initiatives in systems biology
International initiatives
E-Cell Project, Keio University, Japan
Kitano Symbiotic Systems Project
International Physiome Project
Standard Metabolic Reporting Structures (SMRS)
Virtual Cell Project – National Resource for Cell Analysis and Modeling
BioSPICE
Microbes Online
European initiatives
SystemsX
European Interaction Proteome
US initiatives
Biocomputation Program, DARPA
Genomes to Life Initiative, DOE
Metabolic Engineering Working Group, Multiple Agencies
National Centers for Systems Biology (NCSB), National Institute for General Medical Sciences (NIGMS), NIH
Key academic centers
MIT's Computational and Systems Biology Institute
Harvard University's Department of Systems Biology
The Center for Quantitative Biology, Princeton
Systems Biology Group at the University of Stuttgart, Germany
Intelligent Bioinformatics Systems Division (IBSD), German Cancer Research Center, Heidelberg, Germany
What is holding system biology back?
Lack of knowledge
Genomic
Proteomic
Biomolecular Networks
Need for better analytical tools
Lack of computing power
The conservative culture in Big Pharma
Failed promises in the past
Chapter 5 Case studies and success stories
Summary
Case studies
Johnson & Johnson Pharmaceutical Research and Development, (J&JPRD)
Integrative drug discovery using systems biology
Examples of success:
F. Hoffman-La Roche
Some software tools Roche uses
Examples of success:
Pfizer
Examples of success:
Lilly Systems Biology (Singapore)
GlaxoSmithKline's Scientific Computing and Mathematical Modeling
(SCMM) group
Additional success stories
In silico target screen for ALS treatment (Harvard University)
Creation of virtual asthma patients (Entelos/Aventis)
Diabetes biomarkers
Chapter 6 Interviews with thought leaders in systems biology
Summary
Introduction
1. What do you feel are systems biology greatest strengths?
Adriano Henney
Iya Khalil
Karin Jorga
2. What do you feel is holding back systems biology from being used more widely? (other than a lack of trained personnel)
AH
IK
KJ
3. Where do you feel systems biology has, and will have, the greatest impact in drug discovery and development – now, and in ten years?
AH
IK
KJ
Dr. Iya Khalil and Dr. Karin Jorga on success stories
Q. Are there any success stories, or examples of successful use of systems biology that you can share?
IK
KJ
Dr. Adriano Henney discusses how AstraZeneca moved into the field of systems biology
Q. How did AstraZeneca become involved in systems biology?
AH
Chapter 7 Key companies in systems biology
Introduction
Non-profit organizations
Institute for Systems Biology
Overview
Systems biology sector
Main therapeutic focus
Technology
Collaborations
Patents
Pathway analysis
Cellzome AG
Overview
Systems biology sector
Main therapeutic focus
Technology
Collaborations
Patents
GeneGo
Overview
Systems biology sector
Main therapeutic focus
Technology
Products
Collaborations
Licensing agreements
Patents
Hybrigenics SA
Hybrigenics USA
Overview
Systems biology sector
Main therapeutic focus
Technology
Products / Services
Collaborations
Patents
Ingenuity
Overview
Systems biology sector
Technology
Products
Services
Licensing agreements
Collaborations
Patents
Biosimulation and in silico modeling
Gene Network Sciences
Overview
Systems biology sector
Main therapeutic focus
Technology
Products
Collaborations
Licensing agreements
Patents
Genomatica
Overview
Systems biology sector
Main therapeutic focus
Technology
Products
Collaborations
Licensing agreements
Patents
Kenna Technologies
Overview
Systems biology sector
Primary therapeutic focus
Technology
Products
Collaborations
Patents
Physiomics Plc
Overview
Systems biology sector
Main therapeutic focus
Technology
Products
Collaborations
Patents
Data management companies
Genedata
Overview
Systems biology sector
Main therapeutic focus
Technology
Products
Collaborations
Licensing agreements
Patents
Genstruct
Overview
Systems biology sector
Main therapeutic focus
Technology
Collaborations
Licensing agreements
Patents
BG Medicine
Overview
Systems biology sector
Primary therapeutic focus
Technology
Collaborations
Patents
Chapter 8 Appendix
References
Journals
General References
Overviews
Pharmaceutical Discovery
Target Validation
Lead Optimization
In Silico Modeling
Bioinformatics
Systems biology for bioprocess engineering
Biomarkers
Pathways
Some Websites of Interest:
Overviews:
U.S. Government
Index
List of Figures
Figure 2.1: Basic steps in systems biology
Figure 3.2: Applications of systems biology
Figure 3.3: New chemical entities (NCEs) approved by year, 1999-2004
Figure 3.4: Drug discovery costs, 2003
Figure 3.5: Causes of drug failures, 2001
List of Tables
Table 3.1: Time and cost for compound discovery and development
Table 3.2: Time and cost for preclinical and clinical testing of lead compounds
Table 7.3: Key ISB patents and patent applications
Table 7.4: Key Cellzome AG patents
Table 7.5: Key GeneGo patent applications
Table 7.6: Key Hybrigenics patents and patent applications
Table 7.7: Key Ingenuity Medicine patents and patent applications
Table 7.8: Key GNS patent applications
Table 7.9: Key Genomatica patents
Table 7.10: Key Kenna Technologies patent
Table 7.11: Key Physiomics patent
Table 7.12: Key Genstruct patent applications
Table 7.13: Key BG Medicine patents and applications
- Johnson & Johnson Pharmaceutical Research and Development
- F. Hoffman-La Roche
- Pfizer
- Lilly Systems Biology
- GlaxoSmithKline
- Cellzome AG
- GeneGo
- Hybrigenics SA
- Ingenuity
- Gene Network Sciences
- Genomatica
- Kenna Technologies
- Physiomics Plc
- Genedata
- Genstruct
- BG Medicine
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