By Kurt R. Karst –
The U.S. Patent and Trademark Office (“PTO”) recently indicated in a letter to FDA that U.S. Patent No. RE 41,571 (“the ‘571 patent”), a method-of-use patent listed in the Orange Book covering BUTRANS (buprenorphine) Transdermal System is not eligible for a Patent Term Extension (“PTE”) because the product does not meet the first permitted commercial marketing prong of the PTE statute at 35 U.S.C. § 156(a)(5)(A). The PTO letter brings this case one step closer to what could ultimately be a showdown in court.
As we previously reported, the ‘571 patent PTE application was submitted to the PTO in August 2010, following the June 30, 2010 approval of BUTRANS under NDA No. 021306, and just a few months after the U.S. Court of Appeals for the Federal Circuit’s May 10, 2010 decision in Photocure v. Kappos, 603 F.3d 1372 (Fed. Cir. 2010).
In Photocure, the Federal Circuit interpreted the term “product” in the PTE statute at 35 U.S.C. § 156(a)(5)(A) to mean “active ingredient” rather than “active moiety.” In reaching its decision in Photocure, the Federal Circuit relied on its 1990 decision in Glaxo Operations UK Ltd. v. Quigg, 894 F.2d 392 (Fed. Cir. 1990) (“Glaxo II”) (which affirmed a 1989 district court decision in Glaxo v. Quigg, 706 F. Supp 1224 (E.D. Va. 1989) (“Glaxo I”)) where the Court construed the term “product” in 35 U.S.C. § 156(a)(5)(A) to mean “active ingredient.” The Federal Circuit also pointed out that according to the Court’s 1997 decision in Hoechst-Roussel Pharms. Inc. v. Lehman, 109 F.3d 756 (Fed. Cir. 1997), “[f]or purposes of patent term extension, [the] active ingredient must be present in the drug product when administered.” Photocure also contains dicta to the effect that a patent – in that case, U.S. Patent No. 6,034,267 covering the drug product METVIXIA (methyl aminoevulinate HCl) – is eligible for a PTE not only because methyl aminoevulinate HCL is a different chemical compound from previously approved aminolevulinic acid, but because “it is not disputed that they differ in their biological properties, warranting separate patenting and separate regulatory approval, although their chemical structure is similar.”
FDA has approved several applications for drug products containing buprenorphine, and specifically buprenorphine HCl, a salt of buprenorphine, including BUPRENEX (NDA No. 018401), SUBUTEX (NDA No. 020732), and SUBOXONE (NDA No. 020733). Nevertheless, the ‘571 patent PTE applicant claims eligibility for a PTE because “[i]n contrast to these three products, the active ingredient for Butrans™ is buprenorphine base, which has never before been approved by the FDA.” Moreover, says the PTE applicant citing to Photocure, “buprenorphine base was required to undergo full FDA review, and has pharmacological properties that set it apart from buprenorphine hydrochloride. Accordingly, the ‘571 patent that covers Butrans™ remains eligible for a patent term extension under 35 U.S.C. § 156.”
The PTO initially says in its October 12th letter that “based on a plain reading of the statute, the approval of BUTRANS® does not comply with §156(a)(5)(A).” “Here, a salt of the active ingredient, buprenorphine hydrochloride, was the first permitted commercial marketing or use of the ‘product’ as that term is defined in § 156(f).” The PTO then delves into the Photocure decision and the related Hoechst and Glaxo decisions.
Applying the Hoeschet [sic] and Glaxo I analyses here, the active ingredient of BUTRANS® is buprenorphine. The question to ask is what substance is physically present in the product; here, it is burprenorphine. The next step is to ask whether any salt or ester of buprenorphine has been previously approved by FDA. Because a salt of buprenorphine, buprenorphine hydrochloride, has been approved first, before the approval of BUTRANS®, the grant of permission to commercially market or use BUTRANS® is NOT the first permitted commercial marketing or use of the product/active ingredient as required by section 156(a)(5)(A) in light of the approvals of Buprenex, Subutex and Suboxone. Accordingly, the ‘571 patent is ineligible for extension under the provisions of section 156.
The PTO also addresses the dicta in Photocure that the METVIXIA patent was eligible for a PTE because of different “biological properties, warranting separate patenting and separate regulatory approval.” According to the PTO, “[w]hile true that the Photocure court discussed different biological properties, nothing in section 156 requires analyzing biological properties to determine eligibility. Additionally, any 'new drug,' as defined in 21 U.S.C. § 321(P), must undergo separate regulatory approval as per 21 U.S.C. § 355.” Thus, says the PTO, “[s]ince the additional circumstances discussed by the Photocure court in finding that the approval of Metvixia could support an extension of Photocure’s patent are not statutory requirements, alleging similar circumstances fails to confer eligibility here.”
The next step is for FDA to respond to the PTO’s letter. Once that happens and the PTO issues a final determination, the stage will be set for a face-off.