AstraZeneca Wins One Battle, But Loses Another (And Perhaps the War) on SYMBICORT Patent Term Extension

By Kurt R. Karst –   

The U.S. Patent and Trademark Office (“PTO”) has finally issued a final decision in the long-running dispute over eligibility for a Patent Term Extension (“PTE”) for U.S. Patent No. 5,674,860 (“the ‘860 patent”) covering AstraZeneca LP’s SYMBICORT (budesonide and formoterol fumarate dihydrate) Inhalation Aerosol (Docket No. FDA-2007-E-0440), which FDA approved under NDA No. 021929 on July 21, 2006 at “04:36:00 PM,” according to the FDA approval letter. The PTO’s verdict: a denial of PTE.

By way of background, under the PTE statute at 35 U.S.C. § 156, the term of a patent claiming a drug is extended from the original expiration date of the patent if: (1) the term of the patent has not expired; (2) the patent has not been previously extended; (3) the PTE application is submitted to the PTO by the owner of record within 60 days of NDA approval; (4) the product, use, or method of manufacturing claimed has been subject to a “regulatory review period” before it is commercially marketed; and (5) the NDA is the first permitted commercial use of the drug product.

As we reported way back in July 2008 (see here), there were two impediments to obtaining a PTE for the ‘860 patent: (1) timely submission of the PTE application to the PTO after approval of the SYMBICORT marketing application (the PTE application was submitted on day 61) (35 U.S.C. § 156(d)(1)); and (2) FDA’s previous approval of NDAs for drug products containing either budesonide or formoterol fumarate dihydrate (35 U.S.C. § 156(a)(5)(A)).  As such, the PTO issued a decision on June 13, 2008 denying a PTE, but allowing AstraZeneca the opportunity to submit a request for reconsideration. 

AstraZeneca took up the PTO on its offer and submitted a request for reconsideration on December 16, 2008.  [Coincidentally, December 16, 2008 is the same day the PTO denied a PTE for a patent covering AstraZeneca’s PRILOSEC OTC (omeprazole magnesium) Delayed-Release Tablets . . . . on the same two grounds that the PTO cited for denying a PTE for the ‘860 patent on SYMBICORT (see our previous post here).  AstraZeneca also submitted a request for reconsideration with respect to that decision, which has not yet been ruled on.]  AstraZeneca argues in its reconsideration request, among other things, that SYMBICORT is a combination of two active ingredients that have an “unexpected synergistic effect such that the resultant pharmacologic effects are greater than the sum of their constituents,” and thus FDA’s approval of SYMBICORT is the first permitted commercial use of the drug product.  As we previously reported, the PTO has regularly rejected “synergistic combination” arguments.  And in 2012, the U.S. District Court for the Eastern District of Virginia rejected the argument in Avanir Pharm. v. Kappas, Case No. 12-00069 (E.D. Va. March 21, 2012) (see our previous post here).

On June 24, 2011, AstraZeneca filed an additional response to the June 13, 2008 PTO decision.  AstraZeneca’s response came after the the U.S. District Court for the Eastern District of Virginia ruled in The Medicines Company v. Kappos, 731 F. Supp. 2d 470 (E.D. Va. 2010), that the 60-day period for timely submitting a PTE application should be calculated under a next business day construction of the statute such that an NDA approval decision after 4:30 PM starts the 60-day clock on the next business day.  This decision was codified in section 37 of the Leahy-Smith America Invents Act, titled “Calculation of 60-Day Period for Application of Patent Term Extension” (see our previous post here), which added the following to 35 U.S.C. § 156(d):

For purposes of determining the date on which a product receives permission under the second sentence of this paragraph, if such permission is transmitted after 4:30 P.M., Eastern Time, on a business day, or is transmitted on a day that is not a business day, the product shall be deemed to receive such permission on the next business day.  For purposes of the preceding sentence, the term "business day" means any Monday, Tuesday, Wednesday, Thursday, or Friday, excluding any legal holiday under section 6103 of title 5.

Armed with the decision in the The Medicines Company and the change to the statute, AstraZeneca argued that its PTE application for the ‘860 patent was timely, because FDA approved NDA No. 021929 at 4:36:00 PM on Friday, July 21, 2006, thereby making Monday, July 24, 2006 day 1 of the 60-day period (the PTE application was submitted to the PTO on September 19, 2006).

The PTO, in its January 2014 decision, while agreeing that AstraZeneca’s PTE application for the ‘860 patent was indeed timely in light of the decision in the The Medicines Company and the change Congress made to the PTE statute, nevertheless denied AstraZeneca’s reconsideration request on the basis that the approval of SYMBICORT does not constitute the first permitted commercial marketing of either budesonide or formoterol fumarate dihydrate.  In doing so, the PTO once again rejected the “synergistic combination” theory – both as a matter of statutory interpretation and when considering precedent, including In re Alcon, 13 USPQ2d 1115 (Comm’s Pat. & Trademarks 1989), Glaxo Operations UK Ltd. v. Quigg, 894 F.2d 392 (Fed. Cir. 1990), Arnold P’ship v. Dudas, 262 F.3d 1338 (Fed. Cir. 2004), and Avanir Pharm.:

When Congress provided a definition of “product” for purposes of determining which kinds of products, when subject to a regulatory review period and claimed in a patent, would give rise to patent term extension, the definition indicated that a new drug had either an active ingredient as a single entity or multiple active ingredients which are in combination with one another.  See § 156(f)(2)(A).  The language of section 156(f) recites that the term “product,” means “a drug product,” which in turm, means “the active ingredient of a new drug … as a single entity or in combination with another active ingredient.”  Applying the statutory language here, a drug product, SYMBICORT®, means the active ingredient (budesonide) of a “new drug” in combination with another active ingredient (formoterol fumarate).  There is no escaping the plain language that the statute contemplates an active ingredient as a single entity in a new drug or an active ingredient in combination with another active ingredient in a new drug.  To conclude that a single active ingredient can be a combination of two or more active ingredients would render superfluous the statutory language “or in combination with another active ingredient.[”]

Whether the PTO’s decision will now truly put to rest the “synergistic combination” PTE theory remains to be seen.