The Federal Circuit Weighs in On Hatch-Waxman “Skinny” Label Infringement Dispute


This article was republished at IP Litigator in the January/February 2024 issue.

The Hatch-Waxman Act allows a generic drugmaker to rely on a branded drugmaker’s Food and Drug Administration-approved New Drug Application if the generic drugmaker can show that the generic drug has the same active ingredient and is bioequivalent to the branded drug. Generally, a generic drug label must copy the branded drug label. But there are some exceptions. A generic drugmaker may propose a label that attempts to “carve out” a patented use. See Caraco Pharm. Lab’ys, Ltd. v. Novo Nordisk A/S, 566 U.S. 399, 406 (2012) (citing 21 U.S.C. § 355(j)(2)(A)(viii)). Over the past decade, so-called “skinny” labels have been a topic of interest when it comes to patent infringement.

Last week, the United States Court of Appeals for the Federal Circuit weighed in again on the issue of skinny labels in H. Lundbeck A/S et al. v. Lupin Ltd. et al., No. 2022-1194, 2023 WL 8462010 (Fed. Cir. Dec. 7, 2023). In a precedential opinion, Judge Dyk (joined by Judges Prost and Hughes) wrote for the court addressing important considerations for asserting infringement of method of treatment patents in view of a generic skinny label under the Hatch-Waxman statutory framework.

Key takeaways from H. Lundbeck v. Lupin

  • The Federal Circuit reaffirmed that “the use . . . claimed in a patent” under 35 U.S.C. § 271(e)(2)(A) must be the use for which an applicant is seeking marketing approval, and thus, there is no separate act of infringement of a drug for just “any use” of the drug.
  • Carve-outs or skinny labels that remove the indications covered by a patent remain viable avenues for supporting a finding of non-infringement of method of treatment patents but may be overcome by additional evidence of intent or lack of substantial non-infringing uses.
  • For contributory infringement, “substantial non-infringing uses” refers to uses that do not infringe the patent in question, not other unasserted patents.

H. Lundbeck A/S, Takeda Pharmaceutical Co. Ltd., Takeda Pharmaceuticals U.S.A. Inc., Takeda Pharmaceuticals Int’l AG, and Takeda Pharmaceuticals Am. Inc. (together, “Takeda”) (collectively, “plaintiffs”) market and hold patents covering Trintellix® (vortioxetine). Trintellix® 5 mg, 10 mg, and 20 mg tablets are indicated for the treatment of major depressive disorder, as reflected in its product label.

The plaintiffs listed several patents covering Trintellix® in FDA’s Orange Book, including patents on the drug compound and on a method of use for treating depression. After FDA’s approval of Trintellix®, the plaintiffs obtained two additional method of use patents: U.S. Patent Nos. 9,278,096 (“the ’096 patent”) and U.S. Patent No. 9,125,910 (“the ’910 patent”). The ’096 patent generally covers the use of the drug vortioxetine in patients who have previously taken certain other antidepressant medications and had to cease or reduce use due to sexually related adverse events (called Treatment Emergent Sexual Dysfunction), whereas the ’910 patent generally covers the use of vortioxetine to treat cognitive impairment. In seeking FDA approval for their respective Abbreviated New Drug Applications, the generic defendants sought approval of generic Trintellix® to treat major depressive disorder in adults and not the specific uses covered by the ’096 and ’910 patents.

In 2019, the plaintiffs brought Hatch-Waxman actions under 35 U.S.C. § 271 in the District of Delaware before former Chief Judge Leonard Stark alleging induced infringement of the ’096 patent and contributory infringement of the ’096 and ’910 patents against several generic drugmakers for their submission of ANDAs to FDA for approval of generic Trintellix®.1 The plaintiffs also included a claim against Lupin for infringing the plaintiffs’ U.S. Patent No. 9,101,626 (“the ’626 patent”), covering a process for making vortioxetine.2 After a 10-day remote bench trial, Judge Stark found, among other things, that the defendants neither induced infringement of the ’096 patent nor contributorily infringed both the ’096 and ’910 patents. The plaintiffs appealed the District Court’s final judgment of no induced or contributory infringement, and also raised for the first time a statutory interpretation argument for § 271(e)(2)(A).3

Section 271(e)(2)(A) does not create a separate act of infringement for “any use”

The plaintiffs, for the first time on appeal, asked the Federal Circuit to interpret 35 U.S.C. § 271(e)(2)(A) as providing for a separate cause of action for infringement that does not require a showing of direct, induced, or contributory infringement by the ANDA filer. The plaintiffs argued that the defendants infringed the ’096 and ’910 patents under the plain text of § 271(e)(2)(A) because (1) the defendants filed ANDAs seeking approval to market vortioxetine; (2) some uses of vortioxetine are covered by the ’096 and ’910 patents; and (3) the defendants’ ANDA product labels do not prohibit clinicians from prescribing vortioxetine for those patented uses, even though the defendants do not propose to market the drug for those patented uses.

The Federal Circuit disagreed. Relying on its previous decisions in Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1365 (Fed. Cir. 2003), and its progeny, the court explained that “it is not an act of infringement under 35 U.S.C. § 271(e)(2)(A) to submit an ANDA for a drug if just any use of that drug were claimed in a patent,” but rather, actions for infringement of method of use patents under § 271(e)(2)(A) “are limited to patents that claim an indication of the drug for which indication the applicant is seeking approval.” H. Lundbeck, 2023 WL 8462010 at *5. The Federal Circuit found that the “[d]efendants solely seek approval to market the drug for the treatment of [major depressive disorder] pursuant to the methods of expiring patents—that is the ‘purpose’ of the ANDA submissions.” Id. In other words, the court found that the patented uses of the ’096 and ’910 patents were not those for which ANDA approval was sought, and thus, the “[p]laintiffs [] failed to establish that section 271(e)(2)(A) provides an independent basis for infringement.” Id.

No induced infringement

The plaintiffs argued that the District Court erred in finding no induced infringement of claim 7 of the ’096 patent, which further recites limitations on the dosage range and a pharmaceutically acceptable salt of vortioxetine.

As an initial matter, the court reiterated the requirements for induced infringement, focusing on the specific intent requirements for demonstrating active steps to encourage, recommend, or promote infringement (e.g., advertising an infringing use). In this case, the plaintiffs relied solely on the defendants’ proposed ANDA labels as evidence of inducement, particularly the “Adverse Reactions” section of the label, which was unchanged since FDA’s first approval of Trintellix® and prior to the ’096 patent. Id. at *6. Notably, Judge Dyk distinguished this case from GlaxoSmithKline LLC v. Teva and others where the Federal Circuit “found infringement based on communications outside the ANDA label,” among other things. Id. And, in particular, the court noted that the indication on the GSK label used to support induced infringement did not describe or relate to a use claimed in an expired patent. Id. at n.7.

The Federal Circuit affirmed the District Court’s ruling, focusing primarily on two aspects — the particular portions of the ANDA label relied upon and specific intent. The court highlighted that FDA approved the “Adverse Reactions” section of the label for the purpose of selling the drug to treat major depressive disorder before the ’096 patent issued. In rejecting the plaintiffs’ contention that the defendants induced infringement because the ’096 patent exists and thus clinicians will prescribe the ANDA products for its claimed uses, the Federal Circuit relied again on Warner-Lambert. Notably, the court said “we do not see how, in the normal course, a label required to market the drug for a use covered by expired patents could demonstrate the required specific intent to encourage infringement of new patents covering different uses.” Id. Despite this finding, the Federal Circuit made clear that there may be situations where the owner of expired compound or method of treatment patents makes a new discovery and FDA requires that the new method of use must be included on the label to ensure patient safety.

Unlike cases where “there is an ‘express direction’ in the label to review data about the class of patient for whom the drug is indicated to achieve the stated objective of a new patent,” the Federal Circuit credited the defendants having labels with information relating to the ’096 patent carved out. Id. at *7 (quoting Sanofi v. Watson Lab'ys Inc., 875 F.3d 636, 645 (Fed. Cir. 2017)). Namely, the court found persuasive the defendants’ removal of the relevant clinical study data from their labels, that the labels did not reference the patient class recited in claim 7 of the ’096 patent, and that the label included instructions for clinicians not to compare rates of adverse reactions of sexual dysfunction between vortioxetine and other drugs. Id. The court was not persuaded, however, by “the fact that some individuals may have been influenced by one piece of information from a label required to sell the drug for other purposes.” Id. at *8.

No contributory infringement due to substantial non-infringing uses

The plaintiffs argued that the District Court erred in not finding contributory infringement of the ’096 and ’910 patents due to substantial non-infringing uses of vortioxetine. The plaintiffs maintained that the other uses for vortioxetine were not non-infringing uses because those uses infringed other patents owned by the plaintiffs.

But the Federal Circuit clarified that “substantial noninfringing use in section 271(c) refers to uses that do not infringe the patent in question, not other patents.” Id. at *8. The Federal Circuit explained that “[t]o consider patents other than those asserted against a defendant . . . would impermissibly expand the exclusive grant Congress provided.” Id. The plaintiffs also argued the District Court erred in requiring the plaintiffs to show that the defendants possess the intent required to prove contributory infringement. In response, the Federal Circuit confirmed that contributory infringement has a scienter requirement even though the statute does not use the word “intent.” Id. at *9. The Federal Circuit found no error in the District Court’s contributory infringement analysis.

  1. The generic drugmakers included Lupin Ltd and Lupin Pharmaceuticals Inc. (together, “Lupin”); Macleods Pharma USA Inc. and Macleods Pharmaceuticals Ltd. (together, “Macleods”); Sandoz Inc. and Lek Pharmaceuticals d.d. (together, “Sandoz”); Sigmapharm Labs. LLC; Zydus Pharmaceuticals (USA) Inc.; Alembic Global Holding S.A., Alembic Pharmaceuticals Inc., and Alembic Pharmaceuticals Ltd. (together, “Alembic”); and Cadila Healthcare Ltd. (collectively, “Defendants”).

  2. Lupin also cross appealed the District Court’s determination that Lupin will infringe the plaintiffs’ process patent based on the District Court’s construction of the term “reacting.” The Federal Circuit affirmed, explaining that nothing in the claims, specification, or file history required Lupin’s proposed narrow reading of the term. Id. at *9.

  3. The defendants conditionally cross appealed the District Court judgment that the ’096 and ’910 patents are invalid, which the Federal Circuit did not reach in light of its affirmance of non-infringement. Id. at *10.