PTO Dismisses PTE Application in “Reverse Photocure” Case; Moves One Step Closer to a Showdown in Court?

By Kurt R. Karst –       

In what appears to be the first dismissal (Docket No. FDA-2012-E-0491) of a Patent Term Extension (“PTE”) application in what has been referred to as a “reverse Photocure” scenario, the Patent and Trademark Office (“PTO”) has determined that U.S. Patent No. 6,132,766 (“the ‘766 patent”) covering Pacira Pharmaceuticals, Inc.’s (“Pacira’s”) EXPAREL (bupivacaine), approved on October 28, 2011 under NDA No. 022496, is ineligible for a PTE, as well as an interim PTE.  The decision likely foreshadows another “reverse Photocure” case pending before the PTO that may ultimately end up in court.

By way of a refresher, 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, among other things, “the permission for the commercial marketing or use of the product . . . is the first permitted commercial marketing or use of the product under the provision of law under which such regulatory review period occurred” (35 U.S.C. § 156(a)(5)(A)) (emphasis added).   The term “product” is defined at 35 U.S.C. 156(f)(2) to mean, in relevant part, “the active ingredient of – a new drug, antibiotic drug, or human biological product . . . including any salt or ester of the active ingredient, as a single entity or in combination with another active ingredient.” 

For several years, the PTO interpreted the term “product” to mean “active moiety” rather than “active ingredient.”  In PhotoCure v. Kappos, 603 F.3d 1372 (Fed. Cir. 2010), the Federal Circuit interpreted the term “product” in the PTE statute to mean active ingredient rather than active moiety.  In reaching this decision, 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.”

Post-Photocure, the PTO has framed PTE eligibility as a three-part inquiry applying the analyses used in Hoechst and Glaxo I: (1) Has the active ingredient been previously approved?; (2) Has a salt of the active ingredient been approved?; and (3) Has an ester of the active ingredient been approved?  A “yes” to any of these questions means that permission does not meet the first permitted commercial marketing prong of the statute.

Applying this analysis to the ‘766 patent PTE request for EXPAREL, the PTO determined that a PTE is not available:

Applying the Hoescht [sic] and Glaxo I analyses here, the active ingredient of EXPAREL® is bupivacaine.  The first question to ask is what active ingredient is physically present in the drug product; here, it is bupivacaine.  The next question to ask is whether bupivacaine has been previously approved.  The answer to that question is no.  Although bupivacaine itself has not been previously approved, a complete analysis requires asking whether any salt or ester of bupivacaine has been previously approved by FDA.  The answer to that question is yes.  Because a salt of bupivacaine, bupivacaine hydrochloride, has been approved first, i.e., before the approval of EXPAREL®, the grant of permission to commercially market or use EXPAREL® 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 approval of Marcaine hydrochloride in 1972. . . .  Accordingly, the ‘766 patent is ineligible for extension under the provisions of section 156.

In addition, the PTO addressed the comments in Photocure, and raised in the PTE application for EXPAREL, concerning separate patenting:

Notwithstanding the statutory requirements, the comments of the Photocure court serve to buttress the conclusion that the approval of Metvixia complied with § 156(a)(5)(A), but did not provide additional criteria to confer eligibility.  Applicant appears to attempt to garner support for an extension for EXAREL® by indicating that a “bupivacaine liposome injectable suspension warrants separate patenting and separate regulatory approval.”  Application at 4.  Although the court in Photocure commented that Metvixia was separately patented [from Levulan] and underwent separate regulatory review [from Levulan], nothing in section 156 requires analyzing biological properties of a drug product 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 (stating that no person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application filed pursuant to subsection (b) or (j) is effective with respect to such drug).  Since 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 of 35 U.S.C. 156, similar circumstances cannot confer eligibility.

Finally, the PTO determined that because the ‘766 patent, which expired on November 16, 2013, is ineligible for a PTE, an interim extension of up to one year pursuant to 35 U.S.C. § 156(e)(2) is also not available.

Although the PTO has not been challenged on its decision with respect to a PTE for the ‘766 patent covering EXPAREL (and will not be because the patent has expired), the Office’s decision foreshadows a final decision for another pending PTE application.  As we previously reported, the PTO has signaled that U.S. Patent No. RE 41,571, a method-of-use patent listed in the Orange Book covering BUTRANS (buprenorphine) Transdermal System, approved on June 30, 2010 under NDA No. 021306, is not eligible for a PTE because the product does not meet the first permitted commercial marketing prong of the PTE statute.  That PTE docket (Docket No. FDA-2012-E-0152) has remained relatively silent since FDA, in June 2012, sent a letter to the PTO stating that the Agency’s record “indicate that BUTRANS does not represent the first permitted commercial marketing or use of the product, as defined under 35 U.S.C. § 156(f)(1).”  In November 2011, in a letter submission to the PTO, the PTE applicant addressed the Office’s initial, non-final determination of PTE ineligibility, saying that the PTO’s initial determination is erroneous and contrary to the PTE statute and Federal Circuit decisions.