In H. Lundbeck A-S v. Lupin Ltd., Case No. 2022-1194 (Fed. Circ. December 7, 2023), Plaintiffs, H. Lundbeck A/S (“Lundbeck”) and Takeda Pharmaceutical Company Ltd., Takeda Pharmaceuticals U.S.A., Inc., Takeda Pharmaceuticals International AG, and Takeda Pharmaceuticals America, Inc. (collectively “Takeda”) appealed a District of Delaware ruling that several generic pharmaceutical company defendants’ Abbreviated New Drug Applications would not infringe its U.S. Patent No. 9,278,096 (“the ’096 patent”) and U.S. Patent No. 9,125,910 (“the ’910 patent”). One defendant, Lupin Pharmaceuticals, Inc., also cross-appealed the district court’s finding that Lupin’s ANDA product would infringe U.S. Patent No. 9,101,626 (“the ’626 patent”), which claims a method of manufacturing. The Federal Circuit affirmed on all issues.

Facts

Takeda holds the New Drug Application (“NDA”) for Trintellix®, a drug used for the treatment of major depressive disorder (“MDD”) in adults. Slip Op. at 6. The active ingredient is a salt of vortioxetine. Id. Takeda holds patents for Trintellix® covering the drug compound and methods of using it to treat depression, which have expiration dates of June 17, 2026 and October 2, 2022, respectively. Id.

Lundbeck and Takeda also own the ’096 and ’910 patents, both of which are listed in the Orange Book. Slip Op. at 6-7. The ’096 patent covers the use of the drug vortioxetine in patients who have previously used certain other antidepressant medications and had to cease or reduce their use due to adverse events. Id. at 3. The ’910 patent covers the use of the drug vortioxetine to treat cognitive impairment. Id. Plaintiffs also own the ’626 patent which claims a process for manufacturing vortioxetine. Id. at 9.

The generic defendants sought approval to market a generic product after the expiration of the compound patent, and only for the treatment of MDD in adults. Slip Op. at 6. The defendants’ ANDAs contained section viii statements which attempted to “carve out” methods covered by the plaintiffs’ patents: the treatment of MDD in patients who had previously taken certain other drugs but had to cease or reduce use due to sexually related adverse events and the treatment or cognitive impairment. Id. at 11. Plaintiffs sued defendants alleging induced and contributory infringement of the ’096 patent and contributory infringement of the ’910 patent. Id. at 7-9. Plaintiffs also sued Lupin for infringement of the ’626 patent. Id. at 10.

Following a bench trial, the district court determined that the defendants’ ANDAs did not infringe the ’096 and ’910 patents. Slip Op. at 9. The district court, however, agreed with Plaintiffs’ construction of the disputed term “reacting” and found that Lupin infringed the ’626 patent under that construction. Id. at 10.

Issues on Appeal

Plaintiffs raised five issues on appeal. Whether the district court erred in:

1. “[N]ot finding infringement of the ’096 and ’910 patents because section 271(e)(2)(A) [of the Hatch-Waxman Act] creates a separate cause of action that does not require a showing of direct, induced, or contributory infringement by the ANDA filer.” Slip Op. at 10.
2. Finding that there was no induced infringement of claim 7 of the ’096 patent.Slip Op. at 13.
3. Finding that the ANDA label does not induce infringement if physicians will prescribe the drug based on their background knowledge and information on the carved-out label.Slip Op. at 17.
4. Failing to properly credit dosage limits and record evidence in its infringement analysis.Slip Op. at 1.
5. Failing to find contributory infringement for the ’096 and ’910 patents.Slip Op. at 19.

In its cross-appeal Lupin argued that the district court erred in its construction of the term “reacting” and its finding of infringement of the ’626 patent. Slip Op. at 10.

The Federal Circuit affirmed the district court’s rulings on all issues. Slip Op. at 23.

Holding

The Federal Circuit first rejected Plaintiffs’ argument that 35 U.S.C. §271(e)(2)(A) makes the submission of an ANDA seeking approval before the expiration of any patent covering a use of the reference drug an act of infringement regardless of whether the ANDA holder is seeking approval for the use(s) claimed in the asserted patents. Slip Op. at 11. The Court found that this statutory interpretation already had been rejected in Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1365 (Fed. Cir. 2003) and that Federal Circuit precedent established that “the use . . . claimed in a patent” referred to in §271(e)(2)(A) “must be the use for which an [ANDA] applicant is seeking marketing approval.” Id. at 11-12. Here, the Court found that “[d]efendants solely seek approval to market the drug for the treatment of MDD pursuant to the methods of expiring patents—that is the ‘purpose’ of the ANDA submissions. Thus, the patented uses are not those for which ANDA approval is sought” and there was no infringement under §271(e)(2)(A). Id. at 13.

Next, the Court addressed Plaintiffs’ arguments regarding induced infringement of the ’096 patent. Slip Op. at 13. The asserted claim of the ’096 patent covered use of vortioxetine to treat MDD in patients that had received a prior treatment that had to be ceased or reduced due to sexually related adverse events. Id. at 3. The Court noted that Plaintiffs’ inducement evidence focused exclusively on the defendants’ proposed labeling, unlike other recent cases involving evidence concerning advertising and promotional materials. Id. at 14 (citing GlaxoSmithKline LLC v. Teva Pharmaceuticals USA, Inc., 7 F.4th 1320, 1333 (Fed. Cir. 2021)). While defendants’ labeling did contain an indication for the treatment of MDD, the Court found that alone could not support a finding of inducement seeing as that use already had been claimed in an expired patent and described in Plaintiffs’ product labeling in effect prior to the issuance of the ’096 patent. Id. at 14-15. The court stated that “it cannot be, as plaintiffs suggest, that a patentee can bar the sale of a drug for a use covered only by patents that will have expired simply by securing a new patent for an additional, narrower use, as we recognized in Warner-Lambert.” Id. at 14. The Court also held that certain adverse event data in the proposed generic labeling did not support a finding of inducement. Id. at 15. The data relied upon by Plaintiffs was present in the Trintellix label since it was first approved, years before the issuance of the ’096 patent. Id. Furthermore, the generic applicants had explicitly “carved out” certain superiority data and their labeling expressly instructed physicians not to compare rates of adverse reaction between vortioxetine and other drugs. Id. at 16-17. All these facts supported affirmance of the district court decision. Id. at 17.

The Federal Circuit also rejected Plaintiffs’ argument that physicians may prescribe the Defendants’ drug for uses claimed by the ’096 patent “based on their background knowledge together with information in the carved-out label.” Slip Op. at 17. The Court noted that in the Hatch-Waxman context, “mere knowledge of possible infringement by others does not amount to inducement; specific intent and action to induce infringement must be proven.” Id. at 18. Plaintiffs’ argument that the district court ignored the dosage limitations in its infringement analysis also failed. Slip Op. at 18. The Court found that the lower court’s ruling relied on multiple sources of evidence, including label instructions and recommended dosage information. Id.

The Court also affirmed the district court finding of no contributory infringement for the ’096 and ’910 patents. Slip Op. at 19. The Federal Circuit affirmed the district court’s finding that the existence of substantial noninfringing uses -- specifically uses such as prescribing vortioxetine to patients with no prior treatment or prescribing to patients without cognitive impairment – precluded a finding of contributory infringement under 35 U.S.C. § 271(c). Id. The Court rejected Plaintiffs’ argument that these uses were not noninfringing because they were covered by patents other than the ’096 and ’010 patents. Id. at 19-20. The Court noted that “substantial noninfringing use in section 271(c) refers to uses that do not infringe the patent in question, not other patents” Id. at 19. Considering patents aside from those asserted would “impermissibly expand the exclusive [patent] grant Congress provided.” Id. at 20. On this basis, the Court affirmed the district court decision.

The Federal Circuit dismissed Defendants’ cross-appeal, affirming the district court’s construction of the term “reacting” and its finding infringement of the ’626 patent. Slip Op. at 21. The Court rejected Defendants’ argument that the district court had discounted evidence from the prosecution history, stating that the examiner had said nothing about the scope of the term “reacting” and “the examiner’s use of the word ‘starting compound’ in isolation does not suggest that he defined reacting as referring only to starting materials.” Id. at 22.

Key Takeaway

1. Section 271(e)(2)(A) of the Hatch-Waxman Act does not create a separate cause of action where a plaintiff may establish infringement without a showing of direct, induced, or contributory infringement by the ANDA filer.
2. Absent other facts, a label required to market a drug for a use covered by an expired patent does not demonstrate the required specific intent to encourage infringement of new patents covering a narrower use or subset of patients.
3. The potential for substantial noninfringing uses of narrowly claimed methods of treatment should be considered during prosecution as they may preclude a finding of contributory infringement.