Patent Challenges Post-MMA Third Annual FDA Regulatory and Compliance Symposium

1. Patent Challenges Post-MMAThird Annual FDA Regulatory and Compliance Symposium Presented by Richard J. Berman, PartnerArent Fox LLP Washington, DC August 23, 2007

2. Topics To Be Discussed Hatch-Waxman Summary Pre-MMA Law On Generic Exclusivity MMA Changes to Exclusivity Hypotheticals & Conclusions

3. Hatch-Waxman Summary • Pioneer drug manufacturer seeking to market new drug files New Drug Application (NDA) with FDA. • NDA must include data on safety and efficacy of drug. • If NDA is approved and pioneer holds patents in approved drug, pioneer must also disclose those patents to FDA. • FDA lists patents of approved drugs in the Approved Drug Products With Therapeutic Equivalence Evaluations, a.k.a. the “Orange Book.”

4. Hatch-Waxman Summary (cont’d) • When filing ANDA, generic required to make one of four certifications as to status of any patents. (I) no such patent information has been submitted to FDA (no patents in Orange Book). (II) patents in Orange Book have expired. (III) patent(s) in Orange Book set to expire on a certain date, and generic will not market until patent expiration. (IV) patent(s) in Orange Book is/are invalid or will not be infringed by manufacture, use, or sale of generic drug.

5. Hatch-Waxman Summary (cont’d) • If Paragraph I or II certification is made, ANDA may be approved immediately by FDA, assuming product is “approvable.” • If Paragraph III certification is made, approvable ANDA may be approved as of expiration date of the patent(s). • If Paragraph IV certification is made, such certification is deemed act of patent infringement.

6. Hatch-Waxman Summary (cont’d) • Pioneer given right to notice of ANDA filing if P.IV certification made: generic must send notice within 20 days after FDA accepts ANDA for filing. • Pioneer given 45 days after notice was received to sue generic. • If suit is not filed within 45 days of notification, approvable ANDA will be approved. • If suit is filed within 45 days, automatic 30 month stay of approval for ANDA, unless resolution of litigation occurs before that time.

7. Hatch-Waxman Summary (cont’d) Why go “Paragraph IV”? • First ANDA applicant with a P. IV Certification granted 180 days of marketing exclusivity. • Generic can charge approximately 2/3 price of pioneer if first on market. • Large incentive to be first applicant.

8. Pre-MMA Law On Generic Exclusivity (at least the gist of it) • First generic applicant to file an ANDA containing a P. IV certification is awarded 180 days of marketing exclusivity. • During exclusivity period, FDA cannot approve a subsequent ANDA with a P. IV certification for the same drug product. • Exclusivity period calculated from either the date of the first commercial marketing of the generic drug product or the date of a court decision declaring the patent invalid or not infringed, whichever is sooner. • Shared Exclusivity (Agency interpretation) – patent-by-patent approach.

9. MMA – Forfeiture Concept Introduced • Shared exclusivity – product-by-product approach • Exclusivity begins only upon commercial marketing (no court decision trigger). • Exclusivity forfeited if the “first applicant” generic fails to market drug within 75 days after certain events, including: appellate court’s decision in the generic’s favor; settlement finding the patent invalid or not infringed; or patent withdrawal.

10. Which patents to challenge? • Typical case: compound patent, method of treatment patent, formulation patent • compound patent: most difficult to challenge (validity only) • method of treatment patent: next most difficult to challenge (typically validity) • formulation patent: easiest to challenge (non-infringement or validity) • Challenges to newer “blockbuster” drugs frequently occur on “NCE minus 1” date (4th year of FDA-granted New Chemical Entity exclusivity)

11. Which patents to challenge (cont’d) • Hypo #1: • one compound patent (May 2009) • two formulation patents (Jun. 2016 and Jan. 2018) • “NCE minus 1” date May 2007 • “7 ½ year” rule – stay until ~ Jan. 2010 • easy call – likely P.III the compound patent, P.IV formulation patents

12. Which patents to challenge (cont’d) • Hypo #2: • one compound patent (May 2011) • two formulation patents (Jun. 2016 and Jan. 2018) • “NCE minus 1” date May 2007 • “7 ½ year” rule – stay until ~ Jan. 2010 • tougher call – P.III or P.IV compound patent?

13. Which patents to challenge (cont’d) • Hypo #3: • one compound patent (May 2014) • two formulation patents (Jun. 2016 and Jan. 2018) • “NCE minus 1” date May 2007 • “7 ½ year” rule – stay until ~ Jan. 2010 • toughest call – “forced” to challenge compound patent due to almost certain forfeiture of exclusivity

14. Real-World Implications • Pioglitazone (ACTOS®) litigation • One compound patent (Jan. 2011) • Several composition patents (2016) • “NCE minus 1” date Jul. 2003 – four generics file P.IV on composition patents and win • Two generics (Alphapharm and Mylan) P.IV compound patent and lose in district court and on appeal • No generic exclusivity if forfeiture provision was in force • “Win” on composition patents is really a “loss”

15. Problems To Confront • At least one generic will file on “NCE minus 1” date. • Cannot be “in the game” with a P. III certification on late-expiring compound patent. • Because no “passed” exclusivity, one generic can ruin exclusivity for all others.

16. Thank you! Any questions, please contact: Richard J. Berman Arent Fox LLP direct dial: 202.857.6232 e-mail: berman.richard@arentfox.com