1. BUSINESS SENSITIVE Battelle’s Research and Technologies Presentation to KRIBB Dr. Joan F. Adams Dr. Joyce Durnford June 20, 2006

2. BUSINESS SENSITIVE Life Science & Biotechnology Battelle’s diverse biological research and development activities range from basic research to product development Battelle recognizes the rapidly growing role of biological technology in almost all areas of our business Battelle is expanding and integrating its already significant activities in life sciences

3. BUSINESS SENSITIVE Principal areas of emphasis in application of biological sciences are: –Energy and fuels (renewable energy, biofuels, hydrogen generation) –Environmental cleanup and maintenance –Healthcare and biosecurity, specifically -Infectious disease (particularly diagnostics) -Toxicology and biomarkers discovery -Biothreat detection and defense –Biomimetic materials and molecular machines (for use in above applications) Applications of Life Sciences at Battelle

4. BUSINESS SENSITIVE Principal areas of emphasis in scientific and technical capabilities –Microbiology & systems biology of microbes (environmental, infectious agents) –Proteomics (strong technology development) –Genome sequencing at Joint Genome Institute –Mouse genetics facility (e.g. genetics of immune function, infectious disease, biomarkers) –Nanotechnology: biomimetics and for biological applications (materials, sensors, devices) –Preclinical and clinical (animal testing, BCL-3 facility, clinical trials) –Medical device development and testing Science and Technology Capabilities

5. BUSINESS SENSITIVE Is carried out at : –National laboratories managed by Battelle: PNNL, Oak Ridge, Brookhaven, NREL, INL –Co-located and other Battelle-owned facilities (e.g. Battelle N.W. Toxicology Lab., BEST) –Battelle Columbus and West Jefferson laboratories Approximately $300MM in Life Science R & D in 2005 Battelle Life Sciences R & D

6. BUSINESS SENSITIVE Biotechnology R&D

7. BUSINESS SENSITIVE Battelle Biotechnology Battelle Columbus Battelle Eastern Science Technology Center

8. BUSINESS SENSITIVE Integrated Approach for Biotech Solutions Biotech Labs Staff Facility Resources Microbiology Biochemistry Immunology Molecular Biology Virology BSL-3 Testing Genomics, Gene Expression, Proteomics Detection, Threat Definition Bioengineering Host-Pathogen Interactions Assay Development/ Refinement Sample Collection, Transportation Client Battelle Project Manager Capability Areas Biotech Solutions Client Interface

9. BUSINESS SENSITIVE Molecular Biology The molecular (immunology focused) biology team provides expertise in current nucleic acid and recombinant DNA technologies for diagnostics, pathogen detection and identification, and for biomarker development and analysis. Services provided by this group include: PCR and Microarray reagent development (multi-platforms) Gene Expression / Analysis and support of developmental bioinformatics platforms for Battelle and key clients Recombinant DNA services –Vector Development –Cloning cDNA library construction and screening DNA sequencing

10. BUSINESS SENSITIVE Cell Culture / Virology Integrated with microbiology, molecular biology, immunology, cell biology, pathology, zoology, and aerobiology. This is not a stand alone group within Biotechnology. Services this group provides include: Viral propagation, in vitro inactivation studies, molecular detection assays, vaccine efficacy, animal challenge studies, and viral genetic engineering. Development of molecular and immunological assays Experience in working with broad range of viruses In vivo & In vitro pre-clinical or clinical studies Release and stability testing

11. BUSINESS SENSITIVE Immunology This group is utilized heavily (internally) by numerous groups for general immunological support for diverse government projects. Services provided by this group include: Immunoassay refinement/establishment and validation for: Detection of immunoreactive signatures in environmental samples Serological response to disease and vaccination (flow, cell assays, microarrays, RT-PCR etc…) Support for medical device development Antibody characterization and production -Affinity/specificity determination and epitope mapping -Polyclonal, monoclonal, and single chain production Tissue processing (extraction of samples/tissues to include RNA/DNA) and culture

12. BUSINESS SENSITIVE Microbiology This group is also heavily utilized by different groups and clients for general microbiological support. Efforts are largely focused on sample collection and analysis for government clients. Services provided by this group include: Conventional and innovative microbial techniques for - Biodefense, environmental, food, clinical, and industrial microbiology clients Sample extraction method evaluation, development, and improvement Culture and extract (sample) stabilization Detection method evaluation and improvement Novel decontamination method development and evaluation Antimicrobial screening and evaluation

13. BUSINESS SENSITIVE Biochemistry This group has shifted from a predominant Process Development focus towards a maturing Formulation support approach. Services provided by this group include: –Formulation -Development of formulations for pharmaceuticals and vaccines -Stabilization of detection PCR and Antibody reagents and controlled release of proteins -Development of small molecule formulations for agrochemical and environmental applications –Process Development -Recombinant protein expression -Development and scale up of Protein Purification Processes -GLP protein purification for regulated animal testing -Manufacturing optimization

14. BUSINESS SENSITIVE Understanding An Individual’s Health Problem: Ability to associate individuals with activities Solutions: Define markers of stress, medical condition etc. Define subpopulation characteristics Determine exposure indicators

15. BUSINESS SENSITIVE Point-of-Collection Solutions Problem: Sample degradation and initial concentrations prevent accurate detection Solutions: Extraction - Difficult matrices, interfering substances Processing - Sample collection, concentration Stabilization - Prevention of sample loss, degradation

16. BUSINESS SENSITIVE Areas for Advanced Discussion Immune Modulators Problem: Innate immunity and hormone therapy exposes a new area of biological threats Genetically Modified Threats Problem: Transfer of pathogenic elements to other organisms Bioengineered Agent Defeat Problem: Defeat agent production without signature

17. BUSINESS SENSITIVE Biological Safety Level 3 (BSL-3) Facility –Continuous operation since 1995 –Animal rooms -9 BSL-3; 2 BSL-2 -Rodent, rabbit, swine, primate holding –Laboratories; 12 BSL-3, 8 BSL-2 -Aerosol Exposure Laboratory -Microbiology, virology –30 x 96 ft. barn for large animals Medical Research and Evaluation Facility – 38,000 ft 2 BSL3 Space Biofacility Large Animal Facility

18. BUSINESS SENSITIVE Pharmaceuticals and Medical Products

19. BUSINESS SENSITIVE Pharmaceuticals Focused on safety pharmacology and metabonomics applications in –Cardiovascular –Respiratory –Central nervous system –Gastro-intestinal system –Renal Strong toxicology capabilities Strong analytical services and regulatory compliance

20. BUSINESS SENSITIVE Clinical Toxicology Capabilities Oral – capsule and gavage Dosed Feed and Dosed Water Dermal - percutaneous toxicity, sensitization and skin painting Inhalation - nose-only, head only and whole-body exposure Intratracheal Instillation - unanesthetized guinea pig Intravenous - bolus injection and short-term or long-term continuous infusion Other Parenteral Routes - intraperitoneal, subcutaneous, intradermal, intramuscular and intraventricular Species - rodent, canine, non-human primate, rabbit and swine Regulatory Compliance Pre-Clinical Toxicology

21. BUSINESS SENSITIVE Medical Device Solutions - Customers Focus: Medical Device Industry Company Type: Mature, Stable, and Start-up Device Type: IVD, Clinical Laboratory Instruments, Drug Delivery Devices, others Device Class: FDA Class II and Class III or equivalent Over the last 15 years we have performed over 350 programs for 200 medical device companies

22. BUSINESS SENSITIVE Medical Device Examples

23. BUSINESS SENSITIVE EFET Product Platform EFET Platform Fiber CreationAerosol Creation Pre-Manufactured Fiber Mat In situ Fiber Creation Aerosol productAerosol process Charged aerosols Discharged aerosols

24. BUSINESS SENSITIVE Encapsulated Active Ingredients

25. BUSINESS SENSITIVE Leveraging EFET Technology BattellePharma Example of fiber generation

26. BUSINESS SENSITIVE Cell-Based Manufacturing Issues Current cell therapy processes are labor intensive and expensive. Conventional approaches established for the production and delivery of drugs are not usually adaptable to the needs of cell therapies. The largely manual methods originally created by the researchers who designed cell-based therapies are not scalable to commercial levels “Cell Processing” versus “Manufacturing”

27. BUSINESS SENSITIVE What will be required? A systems approach to problems solving that includes the right mix of advanced engineering and biomedical talent and capabilities. A deep understanding of technology productization & commercialization in multiple areas of medical products (i.e., drugs, biologics, and devices). Experience with regulatory requirements & trends. Innovative manufacturing for commercial success. What’s important must change – from “what’s possible” to “a reduction to practice of what you have.” That’s what ultimately counts!

28. BUSINESS SENSITIVE Cell-Based Therapies – Lessons Learned Each cell-based therapy is unique. One cannot use a one-size-fits-all approach to manufacturing. The process is the product. Production methodology will change from pre- clinical to clinical to commercial delivery. Don’t attempt to optimize stand-alone manufacturing elements using laboratory experimentation. In the context of manufacturing, cell process development is not all biology and device design controls are not all engineering.