PTO Denies PTE for ADVAIR DISKUS Patent; Office Again Clarifies that PTEs are Not Available for “Synergistic Combinations” Containing Previously Approved Drugs

By Kurt R. Karst –      

The Patent and Trademark Office’s (“PTO’s”) recent denial of a Patent Term Extension (“PTE”) for U.S. Patent No. 5,270,305, which was reissued as U.S. Patent No. RE40,045 (“the ‘045 patent”), covering Glaxo’s ADVAIR DISKUS (fluticasone propionate; salmeterol xinafoate) should be the last word from the PTO on the availability of PTEs for so-called “synergistic combinations” of previously aproved drugs.  Glaxo’s PTE application was initially submitted to the PTO in October 2000 and was last amended in August 2008 after the issuance of the reissue patent. 

As we previously reported, the PTO’s June 2008 decision, in which the Office denied a PTE for a patent covering SYMBICORT (budesonide; formoterol fumarate dihydrate) Inhalation Aerosol, clarified the PTO’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.  Until then, companies – including Glaxo – relied on a statement in § 2751 of the PTO’s Manual of Patent Examining Procedure (“MPEP”) that seemed to raise the possibility that two previously approved active ingredients could synergistically interact to yield a new product eligible for a PTE.  MPEP § 2751 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.”  

Companies relied on this statement notwithstanding a 1994 PTE decision concerning EMLA (lidocaine; prilocaine) Topical Cream, in which the PTO determined that, consistent with the legislative history of the PTE statute at 35 U.S.C. § 156, a patent claiming a combination of two previously and separately approved active ingredients is not eligible for a PTE, regardless of “any enhanced effect of the combination.”  In addition, in 2004, the U.S. Court of Appeals for the Federal Circuit stated in its decision in Arnold Partnership v. Dudas – a case concerning a PTE for VICOPROFEN (ibuprofen; hydrocodone bitartrate) – 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.”

As with the previous SYMBICORT PTE denial, the PTO ruled that the ‘045 patent is not eligible for a PTE, and that Glaxo’s reliance on the MPEP statement above “is misplaced:”  

The synergistic effect of the active ingredients salmeterol xinafoate and fluticasone propionate has no relevance in determining "first permitted commercial marketing or use of the product" as required by 35 U.S.C. § 156(a)(5)(A).  The term "product" as used in 35 U.S.C. § 156 includes any new drug or antibiotic drug, "as a single entity or in combination with another active ingredient."  35 U.S.C. § 156 (f)(2).  Section 156(f)(2) says nothing about if a combination of active ingredient is synergistic, it is treated as a single entity.  See Arnold Partnership v. Dudas, 362 F.3d 1338, 1343 (Fed. Cir. 2004). . . .

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 patent term extension 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 patent term extension purposes.  The USPTO construes 35 U.S.C. § 156(f)(2) by giving the plain meaning to each and every term of the provision.  A "drug product" exists as a single entity, i.e., a drug product having one active ingredient, or the drug product is a combination of two or more active ingredients.  No statutory language, regulation, court decision or legislative history account for synergy in the patent term extension context.  As such, Applicant cannot point to any precedent which would require finding that a drug product having two active ingredients, which exhibit a synergistic effect, is a single entity within the meaning of section 156.

So, absent another long-lingering PTE application (or a court challenge), the PTO’s latest decision shoud be the last we hear about this issue.