1. CHAU BUI UC BERKELEY NOVEMBER 3, 2008 IEOR 190G Sanofi-Aventis vs. Apotex Plavix® Patent Case

2. Plavix® Patent Case Outline 1. Introduction 2. Plavix® Patent 3. Patent litigations 4. Court decision 5. Opinion 6. Questions

3. 1. Introduction Plavix®  a prescription medication for heart attacks, stroke, peripheral vascular disease  the second highest selling pharmaceutical  the largest market share  In 2005, $5.9 billion was sold Cloridrogel  Active ingredient for Plavix  The dextro-rotatory enatiomer of methyl alpha tetrahydro thiano pyradyl chlorophenyl acetate (MATTPCA)  The enantiomer is bisulfate salt  The patent of producing cloridrogel is held by Bristol in the US, and Sanofi-Aventis in the other countries Sanofi-Aventis  A multinational pharmaceutical company  The fourth largest pharmaceutical company  Research, develop, manufacture and market pharmaceutical products, including Plavix® Apotex  Founded in 1974  The largest producer of generic drugs in Canada  Produces over 300 generic pharmaceuticals  Market generic clopidogrel in 2006

4. 2. Plavix® Patent

5. 2. Plavix® Patent (cont’)

6. What are enantiomers? Enantiomers are molecules that have the same molecular formula and sequence of bonded atom, but different spatial arrangements. Enantiomers are capable of rotating plane-polarized light.  Dextro-rotatory enantiomers rotate polarized light to the right.  Levo-rotatory enantiomers rotate polarized light to the left  Racemate is mixture of equal amount of dextro and levo enanatiomers, exhibiting no optical activity.

7. 2. Plavix® Patent (cont’) Process of preparation of dextro-rotatory enantiomer from the racemate Racemate Solution salt Crystalline Salt acetoneRecrystallisation acetone Alkaline With Aqueous NaHCO3 Dextro-rotatory enatiomer Precipitate Hydrogen Sulfate Of Dextro-rotatory enantiomer

8. 3. Patent litigation Timeline  Racemate of was first identified prior  US patent was filed in 1983  Dextro-rotatory enantiomer of was carried forward  US patent was filed in 1988  In 2006, generic cloridogrel was marketed by Apotex  In 2006, Bristol-Myers Squibb filed a suit to Apotex for patent infrigement.

9. 3. Patent litigation (cont’) Apotex’s position  Anticipation  The bisulfate salt was invalid over the previous patent. The patent ‘596 disclosed the method of producing MATTPC where bisulfate salt was stated as preference. F.3d at 1376.  Obviousness  A person of ordinary skill in the art is able to separate dextro- rotatory MATTPC based on the patent ‘596. 470 F.3d at 1378.

10. 3. Patent litigation (cont’) Sanofi’s claims  Influence of levo-rotatory enantiomer  Influence of bisulfate of enantiomer  There are over 50 salts to choose from  Experiment is needed to determine the suitable salt  Influence of salt form  crystalline form  The difference in solubility of enantiomer

11. 4. Court decision In 2006, Federal Circuit affirmed Apotex’s generic clopidogrel bisulfate product infringes the ‘265 patent In 2007, generic cloridogrel was halted in retail pharmaceuticals in the U.S. In 2008, Sanofi wins protection for Plavix patent in Canada.

12. 5. Opinion “Intellectual property rights are essential for the research-based pharmaceutical and biotech industry to continue to develop innovative medicines to treat serious diseases.”

13. 6. Questions ?? ?

14. Bibliography US patent 4,847,265 US patent 4,529,596 http://www.fr.com/news/2007/July/Sanofivapotex.p df http://www.fr.com/news/2007/July/Sanofivapotex.p df http://patentdocs.typepad.com/patent_docs/2006/12 /sanofisynthelab.html http://patentdocs.typepad.com/patent_docs/2006/12 /sanofisynthelab.html http://www.google.com/patents?id=Vbk4AAAAEBAJ &dq=4,847,265 http://www.google.com/patents?id=Vbk4AAAAEBAJ &dq=4,847,265 http://www.google.com/patents?id=zeA7AAAAEBAJ http://www.pubs.acs.org/cen/news/84/i37/8437pla vix.html http://www.pubs.acs.org/cen/news/84/i37/8437pla vix.html