1. © 2009 Pharmaceutical Law Group PC Market Exclusivity Paradigm Gregory J. Glover, MD, JD Pharmaceutical Law Group Gregory.Glover@pharmalawgrp.com www.pharmalawgrp.com

2. © 2009 Pharmaceutical Law Group PC 2 Market Exclusivity Paradigm Overview  These slides will provide a graphic presentation of the market protection paradigm using a hypothetical representative example.  Topics covered include: A.the relative timing of patent protection and regulatory approval; B.five-year and three-year new product exclusivity (often described as data exclusivity); C.Orphan Drug Exclusivity; D.Patent Term Restoration; E.Pediatric Exclusivity; and F.Hatch-Waxman Patent Litigation and the operation of the 30- month stay.

3. © 2009 Pharmaceutical Law Group PC 3 Market Exclusivity Paradigm  Our example is a product with one patent.  In this example, a provisional application was filed, the utility (regular) application was filed within a year, and the patent was issued within three years.  The patent term is 20 years from the date of filing.  Note that the IND became effective – a requirement for the start of clinical trials – after the patent issued and many years after the patent filing. This scenario is often the case because companies file patent applications before knowing that a product will be suitable for clinical trials.  In this example, the NDA is filed four years after the IND became effective, and the NDA is approved one year after the NDA filing.

4. © 2009 Pharmaceutical Law Group PC 4 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26

5. © 2009 Pharmaceutical Law Group PC 5 Market Exclusivity Paradigm  Our example is a product with one patent.  In this example, a provisional application was filed, the utility (regular) application was filed within a year, and the patent was issued within three years.  The patent term is 20 years from the date of filing.  Note that the IND became effective – a requirement for the start of clinical trials – after the patent issued and many years after the patent filing. This scenario is often the case because companies file patent applications before knowing that a product will be suitable for clinical trials.  In this example, the NDA is filed four years after the IND became effective, and the NDA is approved one year after the NDA filing.

6. © 2009 Pharmaceutical Law Group PC 6 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26

7. © 2009 Pharmaceutical Law Group PC 7 Market Exclusivity Paradigm  Our example is a product with one patent.  In this example, a provisional application was filed, the utility (regular) application was filed within a year, and the patent was issued within three years.  The patent term is 20 years from the date of filing.  Note that the IND became effective – a requirement for the start of clinical trials – after the patent issued and many years after the patent filing. This scenario is often the case because companies file patent applications before knowing that a product will be suitable for clinical trials.  In this example, the NDA is filed four years after the IND became effective, and the NDA is approved one year after the NDA filing.

8. © 2009 Pharmaceutical Law Group PC 8 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26

9. © 2009 Pharmaceutical Law Group PC 9 Market Exclusivity Paradigm  If our product is a “new chemical entity,” it will be eligible for 5 years of new product exclusivity.  For five years after NDA approval, FDA cannot accept for filing a generic application (ANDA or 505(b)(2)). However, FDA may accept for filing a generic application that contains a patent certification that the patent is invalid, not infringed, or not enforceable – a Paragraph IV certification.  5-year exclusivity is independent of any patent protection that might be available.

10. © 2009 Pharmaceutical Law Group PC 10 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26

11. © 2009 Pharmaceutical Law Group PC 11 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Data Exclusivity, NCE Patent Application Filed Patent Issued Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26

12. © 2009 Pharmaceutical Law Group PC 12 Market Exclusivity Paradigm  If our product is not a “new chemical entity,” it will be eligible for 3 years of new product exclusivity.  For three years, FDA may not approve a generic application for the same indication or condition of approval as the approved product.  3-year exclusivity is independent of any patent protection that might be available.  A product may be eligible for either 5-year or 3-year exclusivity – but not both.

13. © 2009 Pharmaceutical Law Group PC 13 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Data Exclusivity, NCE Patent Application Filed Patent Issued Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26

14. © 2009 Pharmaceutical Law Group PC 14 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Data Exclusivity, NCE Patent Application Filed Patent Issued Data Exclusivity, Non-NCE Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26

15. © 2009 Pharmaceutical Law Group PC 15 Market Exclusivity Paradigm  If our product also qualifies for Orphan Drug Exclusivity – generally, a product for treating fewer than 200,000 patients in the United States per year – then, our product is eligible for 7 years of market exclusivity following product approval.  During the 7-year period, FDA cannot approve the same drug for the same indication – even if the second applicant generates completely independent data.

16. © 2009 Pharmaceutical Law Group PC 16 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Data Exclusivity, NCE Patent Application Filed Patent Issued Data Exclusivity, Non-NCE Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26

17. © 2009 Pharmaceutical Law Group PC 17 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Data Exclusivity, NCE Patent Application Filed Patent Issued Data Exclusivity, Non-NCE Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Orphan Drug Market Exclusivity

18. © 2009 Pharmaceutical Law Group PC 18 Market Exclusivity Paradigm  Patent term restoration is designed to restore to the patent term some of the time that was lost in the process of satisfying the requirements for regulatory approval.  If our patent and our product meet the requirements for patent term restoration, the duration of the restored is calculated as one-half the period in clinical trials – from the IND effective date to the filing of the NDA -- plus the entire period of FDA review.  The restored period cannot exceed 5 years, and the patent life following product approval cannot exceed 14 years.  For our product, the restored term is 3 years -- 2 years (one-half of the 4-year clinical trials period), plus one year of regulatory review.

19. © 2009 Pharmaceutical Law Group PC 19 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Data Exclusivity, NCE Patent Application Filed Patent Issued Data Exclusivity, Non-NCE Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Orphan Drug Market Exclusivity

20. © 2009 Pharmaceutical Law Group PC 20 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Data Exclusivity, NCE Patent Application Filed Patent Issued Data Exclusivity, Non-NCE Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Orphan Drug Market Exclusivity Patent Term Restoration

21. © 2009 Pharmaceutical Law Group PC 21 Market Exclusivity Paradigm  If our product is eligible for Pediatric Exclusivity – because the drug sponsor completed studies in accordance with a Written Request from FDA – then, our product is eligible for an additional six-months of exclusivity added on to any other exclusivity that has not expired.  For example, 5-year exclusivity becomes 5 years and 6 months; 3-year exclusivity becomes 3-years and six-months; and 7-year Orphan Drug exclusivity becomes 7 years and 6 months.  With respect to patent protection, the generic applicant must certify that the expiration date of any patent is six months later than the actual expiration date. Accordingly, any generic applicant that is waiting for patent expiration before marketing its product will need to delay marketing for an additional six months.

22. © 2009 Pharmaceutical Law Group PC 22 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Data Exclusivity, NCE Patent Application Filed Patent Issued Data Exclusivity, Non-NCE Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Orphan Drug Market Exclusivity PTR

23. © 2009 Pharmaceutical Law Group PC 23 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Data Exclusivity, NCE Patent Application Filed Patent Issued Data Exclusivity, Non-NCE Provisional Application Filed Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Orphan Drug Market Exclusivity PTR Pediatric Drug Patent Certification

24. © 2009 Pharmaceutical Law Group PC 24 Original Patent Term - 20 years Pediatric Drug Patent Certification IND Effective NDA Approved Pediatric Drug Exclusivity, NCE Data Exclusivity, NCE Patent Application Filed Patent Issued Data Exclusivity, Non-NCE Provisional Application Filed PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Orphan Drug Market Exclusivity NDA Filed Market Exclusivity

25. © 2009 Pharmaceutical Law Group PC 25 Original Patent Term - 20 years Pediatric Drug Patent Certification IND Effective NDA Approved Pediatric Drug Exclusivity, NCE Data Exclusivity, NCE Patent Application Filed Patent Issued Pediatric Drug Exclusivity, Non-NCE Data Exclusivity, Non-NCE Provisional Application Filed PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Orphan Drug Market Exclusivity NDA Filed Market Exclusivity

26. © 2009 Pharmaceutical Law Group PC 26 Original Patent Term - 20 years Pediatric Drug Patent Certification IND Effective NDA Approved Pediatric Drug Exclusivity, NCE Data Exclusivity, NCE Patent Application Filed Patent Issued Pediatric Drug Exclusivity, Non-NCE Data Exclusivity, Non-NCE Provisional Application Filed PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Orphan Drug Market Exclusivity Pediatric Drug Exclusivity NDA Filed Market Exclusivity

27. © 2009 Pharmaceutical Law Group PC 27 Market Exclusivity Paradigm  The Effective Patent Life is the period of patent protection following product approval – after taking into consideration any applicable Patent Term Restoration and Pediatric Exclusivity. The Effective Patent Life is substantially shorter than the original 20-year patent term.

28. © 2009 Pharmaceutical Law Group PC 28 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Pediatric Exclusivity

29. © 2009 Pharmaceutical Law Group PC 29 Market Exclusivity Paradigm Original Patent Term - 20 years IND Effective NDA Filed NDA Approved Effective Patent Life Patent Application Filed Patent Issued Provisional Application Filed PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Pediatric Exclusivity

30. © 2009 Pharmaceutical Law Group PC 30 Market Exclusivity Paradigm  The product sponsor must file a patent listing for each patent that claims the product or a method of using the product. These patents are listed in the Orange Book.  A generic applicant must make one of four patent certifications: (i) no patent information was filed; (ii) the patent has expired; (iii) the patent will expire on a specific date, and the generic applicant does not intend to market its product before that date; and (iv) the patent is invalid, not infringed (by the generic product), or not enforceable.  If a generic applicant files an application containing a Paragraph IV certification that the patent is invalid, not infringed, or not enforceable, the generic applicant must provide notice to the patent owner and the sponsor of the original product.

31. © 2009 Pharmaceutical Law Group PC 31 Original Patent Term - 20 years Pediatric Exclusivity IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed Effective Patent Life PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Market Exclusivity Paradigm

32. © 2009 Pharmaceutical Law Group PC 32 Original Patent Term - 20 years Pediatric Exclusivity IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed ANDA filed, Notice Effective Patent Life PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Market Exclusivity Paradigm

33. © 2009 Pharmaceutical Law Group PC 33 Market Exclusivity Paradigm  The act of filing a generic application containing a Paragraph IV certification is deemed to be an act of patent infringement for the purpose of initiating patent litigation.  The patent owner has 45-days (from the notice of an application containing a Paragraph IV certification) to bring a patent infringement suit against the generic applicant.

34. © 2009 Pharmaceutical Law Group PC 34 Original Patent Term - 20 years Pediatric Exclusivity IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed ANDA filed, Notice Effective Patent Life PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Market Exclusivity Paradigm

35. © 2009 Pharmaceutical Law Group PC 35 Original Patent Term - 20 years Pediatric Exclusivity IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed ANDA filed, Notice Patent Infringement Suit Effective Patent Life PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Market Exclusivity Paradigm

36. © 2009 Pharmaceutical Law Group PC 36 Market Exclusivity Paradigm  If the patent owner initiates a patent infringement suit within 45 days, then FDA cannot approve the generic application for 30- months, unless – before that time – the patent is deemed to be invalid, not infringed, or not enforceable.  The 30-month stay nearly always expires before the end of the Effective Patent Life. In most circumstances, a product is eligible for only one 30-month Stay regardless of the number of patents listed in the Orange Book.

37. © 2009 Pharmaceutical Law Group PC 37 Original Patent Term - 20 years Pediatric Exclusivity IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed ANDA filed, Notice Patent Infringement Suit Effective Patent Life PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Market Exclusivity Paradigm

38. © 2009 Pharmaceutical Law Group PC 38 Original Patent Term - 20 years Pediatric Exclusivity IND Effective NDA Filed NDA Approved Patent Application Filed Patent Issued Provisional Application Filed ANDA filed, Notice Patent Infringement Suit 30-month Stay Effective Patent Life PTR Years 1 3 5 7 9 11 13 15 17 19 21 23 25 2 4 6 8 10 12 14 16 18 20 22 24 26 Market Exclusivity Paradigm

39. © 2009 Pharmaceutical Law Group PC 39 Market Exclusivity Paradigm  Summary – relative timing of patent protection and regulatory approval – five-year and three-year new product exclusivity – Orphan Drug Exclusivity – Patent Term Restoration – Pediatric Exclusivity – Hatch-Waxman Patent Litigation, including the 30-month stay

40. © 2009 Pharmaceutical Law Group PC 40 Gregory J. Glover, MD, JD Pharmaceutical Law Group PC 900 Seventh Street, NW Suite 650 Washington, DC 20001 202-589-1780 (telephone) 202-318-2198 (facsimile) Gregory.Glover@PharmaLawGrp.com Contact Information