Skinny Label Avoids Infringement

by Dennis Crouch

H. Lundbeck A/S v. Lupin Ltd., Nos. 2022-1194, 2022-1208, 2022-1246 (Fed. Cir. Dec. 7, 2023) (Opinion by Judge Dyk, joined by Judges Prost and Hughes).

The Federal Circuit recently affirmed a district court judgment finding that Abbreviated New Drug Applications (“ANDAs”) submitted by generic drug manufacturers did not infringe patents rights held by H. Lundbeck A/S and its licensee Takeda relating to the antidepressant drug Trintellix (vortioxetine). The court also affirmed the lower court’s finding that one of the generic manufacturer’s processes for making the drug would infringe a Lundbeck patent directed to methods of manufacture.

Lundbeck’s patents on vortioxetine as well as methods of using the drug to treat major depressive disorder (“MDD”) have expired. However, Lundbeck holds newer patents claiming additional methods of use, including U.S. Patent No. 9,278,096 (“the ‘096 patent”), which claims using Trintellix to treat patients who previously took other antidepressants but ceased use due to sexual side effects, and U.S. Patent No. 9,125,910 (“the ‘910 patent”), which claims treating MDD patients’ cognitive impairment with Trintellix.

When the generic manufacturers filed ANDAs seeking approval for only the initial approved use of Trintellix to treat MDD, Lundbeck sued for infringement, arguing that approval should be blocked because Trintellix would likely later be prescribed for the uses claimed in the ‘096 and ‘910 patents. The Federal Circuit largely rejected this argument — holding that filing the ANDA in this situation cannot constitute infringement under Hatch-Waxman.

The Patent Act does define a form of patent infringement that consists of filing an ANDA with the FDA seeking to manufacture a drug covered by someone else’s patent. But, as relevant for this case, 35 U.S.C. § 271(e)(2)(A) limits the infringement to circumstances where “the use . . . claimed in a patent” be the use for which FDA approval is sought, not merely any use for which the drug may eventually be prescribed.   Thus, the court reaffirmed that ANDA applicants may use section viii statements to carve out patented methods of use and obtain FDA approval for only non-patented uses.

Inducement: The patent holder also alleged that the skinny-label serves as an inducement to doctors to prescribe the drug off-label in a way that infringes the new patents.

I want to note here that the facts in this case are different from prior carve-out cases such as GlaxoSmithKline LLC v. Teva Pharmaceuticals USA, Inc., 7 F.4th 1320, 1333 (Fed. Cir. 2021). In GSK, the patentee provided additional evidence beyond the skinny label, such as communications to the doctors in the form of advertising or promotional materials, etc.  Here, “plaintiffs’ inducement case relied solely on defendants’ proposed ANDA labels as the inducing conduct.”

Still, the patentee argued that the generics would be inducing infringement because physicians would naturally ignore the label carve-outs and prescribe the drug in ways that infringe.  Lundbeck argued that even though the generic labels carved out references to this patient population and patented method of treatment, other information remaining in the labels, particularly data on rates of treatment-emergent sexual dysfunction (TESD), would still encourage doctors to prescribe the generics for the patented use.  The district court (Judge Stark) found no inducement, holding that the proposed labels have carved out all references to treatment based on prior medications and sexual side effects, as well as data from Lundbeck’s clinical studies related to TESD rates. On appeal, the Federal Circuit agreed that a generic cannot be liable for inducement if it has carved out all sections of the label relating to the patented method of treatment, even if doctors may  use their background knowledge to prescribe the drug off-label for that use.  Allowing inducement in that situation would indefinitely generics after compound patents expire, undermining the Hatch-Waxman scheme.

The court also held that for contributory infringement under § 271(c), substantial noninfringing uses refer to uses not covered by the asserted patents. Somewhat controversially, uses potentially infringing other unasserted patents qualify as noninfringing uses in the analysis. “[S]ubstantial noninfringing use in section 271(c) refers to uses that do not infringe the patent in question, not other patents.”  To reach this determination, the court looked to the statutory text of 271(c) and concluded that the non-infringing use requirement was tied only to the asserted patents.  Arguing for the accused infringers, David Abramowitz (Locke Lord) explained at oral arguments: “There is no statute or case law that a substantial amount of infringing use can’t be covered by some other patent. The statute’s patent specific.”

Overall, the court ruling places a hard stop against a potential form of evergreening that brand drug companies could have used to prevent generic entry through method-of-use patents obtained later in a drug’s lifecycle.  At the same time, this ruling may significantly hamper innovators ability to effectuate their exclusive rights in their newer method of use patents that can be infringed by off-label prescriptions.

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One note here is that the courts sided with the patentee on one patent, a method of manufacture of the drug. The appeal focused on claim construction of the term “reacting” – that the district court had properly broadly construed.  Although it is not entirely clear to me, this might be enough to forestall generic entry.