PTO Denies PTE for SYMBICORT Patent; Decision Puts to Rest the Notion of PTE Availability for Synergistic Combinations Containing Previously Approved Drugs

July 8, 2008

In June, the U.S. Patent and Trademark Office (“PTO”) determined that AstraZeneca’s U.S. Patent No. 5,674,860 (“the ‘860 patent”), which covers the drug product SYMBICORT (budesonide; formoterol fumarate dihydrate) Inhalation Aerosol, is ineligible for a Patent Term Extension (“PTE”).  The PTO’s decision is important in that it clarifies the Office’s position that a PTE is not available for a drug product containing two previously approved active ingredients that purportedly act synergistically to create a new product.

Under the PTE statute at 35 U.S.C. § 156, the term of a patent claiming a drug shall be 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 New Drug Application (“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.  In this case, the PTO denied AstraZeneca’s PTE request because the SYMBICORT NDA was not the first permitted commercial use of budesonide or formoterol fumarate dihydrate, and also because the PTE application was not submitted within the 60-day statutory period.  (Spoiler Alert: While this post deals solely with the first basis for the PTO’s denial, the second basis – i.e., not meeting the 60-day period criterion – is another issue simmering at the PTO that we will post on in the near future.)

FDA approved SYMBICORT on July 21, 2006 for the long-term maintenance treatment of asthma in patients 12 years of age and older.  SYMBICORT contains two previously approved active ingredients.  On September 19, 2006, AstraZeneca submitted a PTE application to the PTO.  AstraZeneca takes the position in its application that the ‘860 patent is eligible for a PTE because “the combination of budesonide and formoterol fumarate dihydrate as a new active ingredient required full scientific review by the FDA.”  AstraZeneca apparently relies on the PTO’s Manual of Patent Examining Procedure (“MPEP”), which states, in relevant part, that “an approved product having two active ingredients, which are not shown to have a synergistic effect or have pharmacological interaction, will not be considered to have a single active ingredient made of the two active ingredients.”  This statement seems to raise the possibility that two previously approved active ingredients could synergistically interact to yield a new product eligible for a PTE. 

The PTO first addressed (to our knowledge) the issue of PTEs for combination drug products containing previously approved active ingredients in a 1994 decision concerning EMLA (lidocaine; prilocaine) Topical Cream.  In that case, the PTO determined that, consistent with the legislative history of 35 U.S.C. § 156, a patent claiming a combination of two previously and separately approved active ingredients is not eligible for a PTE, “notwithstanding any enhanced effect of the combination.”  More recently, in 2004, the U.S. Court of Appeals for the Federal Circuit stated in Arnold Partnership v. Dudas that “this court doubts that synergistic effects are an appropriate distinction for [PTE] policies, particularly where the statutory language does not distinguish between synergistic and nonsynergistic combinations.”  Notwithstanding these decisions, patent owners have continued to raise the possibility of a PTE for a patent covering a combination drug product containing two previously approved active ingredients, presumably because of the ambiguity of the MPEP passage quoted above.

In June 2007, the PTO issued a preliminary analysis in which the Office determined that SYMBICORT “is nothing more than a combination of previously approved active ingredients” and therefore fails to meet the statutory PTE criterion that the NDA approval represents the first permitted commercial use of the drug product.  “Whether the product is a synergistic or nonsynergistic combination of active ingredients is of no consequence to a determination of compliance with [this statutory criterion],” states the PTO in reliance on the dicta in Arnold Partnership.  In a December 2007 letter to the PTO, FDA agreed that the ‘860 patent is ineligible for a PTE because the SYMBICORT NDA “does not represent the first permitted commercial marketing or use of either of the active ingredients in this ‘product.’”  FDA also states that the SYMBICORT NDA “was approved on July 21, 2006, which makes the submission of the [PTE] application on September 19, 2006, NOT timely . . . .” (i.e., the PTE application was submitted on the 61st day after the date of NDA approval).

On June 13, 2008, the PTO issued a final decision that the ‘860 patent is ineligible for a PTE.  The decision goes to great lengths to clarify the MPEP statement on synergistic effect:

The synersistic effect of the active ingredients formoterol fumarate dehydrate and budesonide has no relevance in determining “first permitted commercial marketing or use of the product” . . . .  Applicant’s reliance on MPEP § 2751 is misplaced.  The statement in the MPEP does not require that the USPTO treat an alleged synergistic combination drug product with two active ingredients as a single active ingredient made up of the two active ingredients for [PTE] purposes.  Rather, MPEP § 2751 merely explains that a product having two active ingredients, without synergy, will not be treated as a single active ingredient.  This does not imply that a showing of synergy in a product having two active ingredients, each of which was previously approved for commercial marketing or use, must be considered to be a single active ingredient for [PTE] purposes.

It is unclear whether AstraZeneca will submit a request for reconsideration of the PTO’s June 2008 decision.  The company has until later this summer to do so. 

By Kurt R. Karst    

Categories: Hatch-Waxman