1. 1 THOMSON REUTERS INTEGRITY SM INFLUENZA A: A New Challenging Opportunity for Market Impact

2. THOMSON REUTERS INTEGRITY: SUMMARY This use case will focus on Influenza A and, specifically on Oseltamivir Phosphate (Tamiflu®), a currently available drug being used to treat this challenging disease. It will also demonstrate how to analyze current synthetic approaches to this compound, looking for new opportunities for chemical intermediate and reagent producers.

3. THOMSON REUTERS INTEGRITY: INFLUENZA Influenza is highly contagious acute viral infection of the respiratory tract causing the flu, a disease with symptoms that include fever, myalgia, headache, malaise, cough, sore throat, rhinitis and other common cold-like symptoms Influenza A (H1N1) and the 2009 Influenza Pandemic Swine influenza (swine flu) is a respiratory disease of pigs caused by type A influenza virus that regularly causes outbreaks of influenza in pigs. The incidence of swine flu in humans is normally quite low. In spring 2009, however, an outbreak occurred in Mexico and spread quickly to parts of the U.S., with other travel-related cases reported soon thereafter in various European and Asian countries. A new strain of the H1N1 virus is responsible for these cases. The 2009 influenza pandemic has spread internationally with unprecedented speed. The World Health Organization reports that as of November 22, 2009, more than 622,480 laboratory- confirmed cases of influenza A (H1N1) infection, including at least 7,826 deaths, have been officially registered in at least 207 countries worldwide. The influenza A (H1N1) virus is susceptible to treatment with the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza), but not to amantadine or rimantadine.

4. THOMSON REUTERS INTEGRITY: DISEASE BRIEFING: INFLUENZA Select the Disease Briefings Knowledge Area from the pull down menu on the Integrity home page

5. THOMSON REUTERS INTEGRITY: DISEASE BRIEFING: INFLUENZA Select the Influenza disease briefing from the left hand quick access menu or using the Disease Briefing search field where the browse Index can be used to find and select terms.

6. THOMSON REUTERS INTEGRITY: DISEASE BRIEFING: INFLUENZA In the Facts About Influenza, specific information can be found, for example, click Special Focus: Influenza A (H1N1) and 2009 Influenza Pandemic

7. THOMSON REUTERS INTEGRITY: DISEASE BRIEFING: INFLUENZA This provides information on the H1N1 virus, Interspecies Transmission, Gene Reassortment and other relevant information…

8. THOMSON REUTERS INTEGRITY: DISEASE BRIEFING: INFLUENZA … including current drug treatment and vaccines available. To find more information on the cited products, for example, Tamiflu®, go to the Drugs & Biologics Knowledge Area by selecting from the drop down menu at the top left hand side of the page.

9. THOMSON REUTERS INTEGRITY: PRODUCT RECORD Once in this Knowledge Area, select the Drug Name search field. Open the browse Index and type in a partial term in the lookup box. Click Lookup and then select the name and then OK to automatically copy it back into the search form. Click Start or hit return to launch the search

10. THOMSON REUTERS INTEGRITY: PRODUCT RECORD The Product Record is retrieved. The Full Record display provides general and chemical information about the product…

11. THOMSON REUTERS INTEGRITY: PRODUCT RECORD … a Product Summary, a Development Status Summary and links to Related Information in the other Knowledge Areas of Integrity.

12. THOMSON REUTERS INTEGRITY: PRODUCT RECORD Click the Sales button…

13. THOMSON REUTERS INTEGRITY: PRODUCT RECORD: Sales …to open a pop-up window with sales figures. Due to the Influenza pandemic, the sales for this product have grown substantially in 2009. This makes the compound interesting selection for the development of improved chemical syntheses or sales of intermediates.

14. THOMSON REUTERS INTEGRITY: PRODUCT RECORD: Related Information Click on the Related Information link to move to the Organic Synthesis Knowledge Area where synthetic schemes related to this product can be displayed.

15. THOMSON REUTERS INTEGRITY: ORGANIC SYNTHESIS SCHEMES The related schemes include a synthesis text, intermediates and reagents lists, sources (patents and references) and Related Information in other Knowledge Areas. From the synthesis schemes for Tamiflu®, view the intermediates by going to Options and selecting Intermediate List.

16. THOMSON REUTERS INTEGRITY: ORGANIC SYNTHESIS INTERMEDIATE LIST A full list of related intermediates is shown with their structure, molecular weight, molecular formula and Standard InChIKey. Select and click on any intermediate of interest to pull out access further information...

17. THOMSON REUTERS INTEGRITY: ORGANIC SYNTHESIS INTERMEDIATE FULL RECORD … including the chemical name, supplier information and Related information in other Knowledge Areas. Click Show All to view suppliers. Click the Drugs & Biologics Related Information button to view products currently synthesized using this intermediate.

18. THOMSON REUTERS INTEGRITY: ALL RELATED INFORMATION VIA QUICK SEARCH A list of records appears showing that this intermediate can be supplied not only for the synthesis of Tamiflu® but also in other 3 products, two of which are under active development in early phases.

19. THOMSON REUTERS INTEGRITY: SUPPORT/HELP For questions about Integrity’s contents or features, send a message via the Help Request / Suggestion Form in Integrity or contact integritysupport @prous.com