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1. Invitrogen/GIBCO workshops David Zhao Soverin Karmiol Sergei Aleshkov Waterside Conference Date: May 3rd, 2006 Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it. Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it.

2. 2 Agenda Agenda Company Overview – GIBCO/Invitrogen (David Zhao) Medium Optimization: Different Strategies (Soverin Karmiol) BIPTM (Bulk IGF-1 Products)– An animal origin free recombinant IGF-1 for Bioproduction (David Zhao and Sergei Aleshkov)

3. Company overview Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it. Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it.

4. 4 The Cell Culture Universe We consider ourselves covering whole cell culture universe rather than a media supplier The cell culture universe includes cell as factories. Cell as tools for cell function studies and cell as products such as cell therapy. The great degree of overlaps in these areas allow us to leverage our capacity and technologies very well.We consider ourselves covering whole cell culture universe rather than a media supplier The cell culture universe includes cell as factories. Cell as tools for cell function studies and cell as products such as cell therapy. The great degree of overlaps in these areas allow us to leverage our capacity and technologies very well.

5. 5 Acquiring Key Competencies Over years of M and A, integration and harmonization, Invitrogen become a leader in biotech industry. Our cell culture business has become stronger than ever because the new capacities and technologies under big Invitrogen umbrella. Over years of M and A, integration and harmonization, Invitrogen become a leader in biotech industry. Our cell culture business has become stronger than ever because the new capacities and technologies under big Invitrogen umbrella.

6. 6 The Innovation Hub Partnering Invitrogen will allow you to discover myriad way to improve your business. Partnering Invitrogen will allow you to discover myriad way to improve your business.

7. 7 Why Invitrogen/GIBCO? Partnering with Cell Culture Experts Cell culture supplier Long history and extensive experience on media and cells Focused on cell culture materials and processes Broad platforms for Bioproduction Different tools developed – Such as novel scale-down models BioPharmaceutical Companies Product focus (Recombinant proteins, IgG and vaccine) Selected platform based on business need Large scale production Process development

8. Medium Optimization: Different Strategies Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it. Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it.

9. 9 Basal Medium Optimization Last 35 years has demonstrated that different cell types require different concentrations of the same basal medium components for survival, proliferation and various phenotypic expressions.

10. 10 Optimization Goal Determine cell requirements for components Provide the cell with the appropriate building blocks so that they are available at the right time and in the right amount. Supply the cell with sufficient and appropriate fuel so that energy is not limiting: reduce metabolic load Balance nutrient composition- minimize competition

11. 11 Essentiality Absolute- no response in the absence of the nutrient; at zero concentration, zero performance; unable to synthesis compound. Conditional- response possible but not maximal; at zero concentration, response is present but not maximal; able to synthesis compound but not to meet requirement

12. 12 Theoretical Basal Optimization Titrations

13. 13 Theoretical Basal Optimization Titrations

14. 14 Basal metabolic needs - Ionic balances, basal protein turn-over (cell house-keeping activities) Work related needs - Synthesis of a pharmaceutical peptide, expression of differentiation marker, vaccine production

15. 15 Competition Amino acids largest homologous nutrient group- 20. There are approximately 8 amino acid transporters- condition for competition. The process of optimization resolves this competition.

16. 16 Adaptation Cells of interest cultured in a medium lacking desirable traits Medium containing more desirable traits. Hope: there is a significant correspondence between phenotypic repertoire of cells and new medium. This is a high risk activity because the requirements of the cells are not addressed. A better approach is to systematically take the medium and reorganize the medium component concentrations to meet the requirements of the cells of interest for a particular function.

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18. 18 Spent Medium Analysis This analysis is valuable as a first approximation of media component needs No obvious way to optimize a medium from these results. In medium optimization the underlying question is what are the requirements. In this case what are the requirements of these high density cells in a depleted medium containing waste products for maximal protein production

19. 19 Disadvantages The basal composition is empirically determined by a series of bioassays the endpoint of which is the desired outcome (proliferation, expression of specific marker, protein synthesis). Optimization entails the manipulation of at least 75 basal components.

20. 20 Optimization Disadvantages Labor intensive: All basal components made as pre-stocks DOE required to manage the complexity and interactions

21. 21 Instrumentation For the manipulation to be efficiently executed, high-throughput-type instrumentation is necessary. Instrumentation: liquid handler (performing the various titrations), incubator (environmental control), plate reader (quantitation) and instrumentation to control processes such as micro-bioreactor.

22. 22 RAMP/SimCellTM Workflow

23. 23 SimCellTM Automated System

24. 24 BioProcessors SimCellTM MicroBioreactor Array

25. 25 Light shading represents >20% difference Dark shading represents <20% difference MBAs and Bioreactor are most similar. Odyssey Comparison: Proteins from 2-D PAGE

26. 26 Basal Medium Optimization (Summary) Advantages: Determine appropriate basal concentrations Reduce basal component competition Maximize energy utilization Determine inhibitory components Remove undefined components

27. 27 Summary Cells in culture require a unique set of conditions to function properly. Coordination of these conditions is necessary for optimal performance The execution of an optimization procedure is important in achieving the coordination.

28. BIPTM (Bulk IGF-1 Products)– An animal origin free recombinant IGF-1 for Bioproduction David Zhao Sergei Aleshkov Waterside Conference Date: may 3rd, 2006 Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it. Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it.

29. Development of BIPTM Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it. Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it.

30. 30 Different types of media Our definitions for CD, PF and AOF are different from many other vendors. Our CD media don’t have protein and must be AOF.Our definitions for CD, PF and AOF are different from many other vendors. Our CD media don’t have protein and must be AOF.

31. 31 Human recombinant IGF-1

32. 32 E. Coli Expression Folding Different procedures used with different specific activities High specific activity achieved for BIPTM AOF – Animal Origin Free to Secondary Level Scale up Two different vendors for manufacturing Easy to use Scalable from grams to kgs Regulatory friendly (AOF and traceability) Stringent QC MCF-7 cells used HPLC SDS-PAGE gel Endotoxin Animal Origin Human /Animal Origin Components Invitrogen Policy – Multi-pronged approach Replace -Source non-animal components where possible -Develop chemically defined product Segregate - Facility solutions Mitigate - Source to minimize risk Species/geography - Cleaning Validated viral clearance -Treatment Radiation/other technologies Animal Origin Human /Animal Origin Components Invitrogen Policy – Multi-pronged approach Replace -Source non-animal components where possible -Develop chemically defined product Segregate - Facility solutions Mitigate - Source to minimize risk Species/geography - Cleaning Validated viral clearance -Treatment Radiation/other technologies

33. 33 Introduction

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35. 35 Approach to Animal Origin Components Replace Source non-animal components where possible Develop chemically defined product Segregate Facility solutions Mitigate Source to minimize risk Species/geography Cleaning Validated viral clearance Treatment Radiation/other technologies Animal Origin Human /Animal Origin Components Invitrogen Policy – Multi-pronged approach Replace -Source non-animal components where possible -Develop chemically defined product Segregate - Facility solutions Mitigate - Source to minimize risk Species/geography - Cleaning Validated viral clearance -Treatment Radiation/other technologies Animal Origin Human /Animal Origin Components Invitrogen Policy – Multi-pronged approach Replace -Source non-animal components where possible -Develop chemically defined product Segregate - Facility solutions Mitigate - Source to minimize risk Species/geography - Cleaning Validated viral clearance -Treatment Radiation/other technologies

36. BIPTM Specifications Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it. Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it.

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39. 39 Documentations Today, the state of our industry is strong, and getter stronger. Let me share some data with you to underline this point. First, important to many of you in this room, our financial situation is greatly improved. Biotech financing is steadily improving, with more than $14B raised so far this year, compared to $12B in the first 9 months of 2003, and $9 B in all of 2001 There is no doubt that Imclone and others have caused investors to put a premium on lower risk, later stage developments, but companies at various stages are still attracting capital. We also see much greater stability – in terms of cash on hand – with nearly 70% of companies in the industry holding more than two years’ cash. Today, the state of our industry is strong, and getter stronger. Let me share some data with you to underline this point. First, important to many of you in this room, our financial situation is greatly improved. Biotech financing is steadily improving, with more than $14B raised so far this year, compared to $12B in the first 9 months of 2003, and $9 B in all of 2001 There is no doubt that Imclone and others have caused investors to put a premium on lower risk, later stage developments, but companies at various stages are still attracting capital. We also see much greater stability – in terms of cash on hand – with nearly 70% of companies in the industry holding more than two years’ cash.

40. BIPTM - Biological properties and applications Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it. Good afternoon. It is my pleasure to be here, at the first BIO Emerging Company Investor Forum. I have had the pleasure of working with many of the investors in this room, and it is great to see so many customers in the audience as well. I’d like to thank BIO Executive Director Carl Feldbaum, chairman Richard Pops and Business Development leader Morrie Ruffin, along with the whole BIO team, for putting this event together and inviting me to be a part of it.

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54. 54 Acknowledgement GIBCO/Invitrogen Ferenc Boldog David Judd Lynn Pajak Mary Lynn Tilkins Curt Mancuso David Dugan Brain Burgin Deborah Behlmaier Sackamone Phommachanh Jim Mysliwiec Bob Kenerson Bob Burriers

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