Nuedexta® (dextromethorphan hydrobromide / quinidine sulfate)
Case Name: Otsuka America Pharm., Inc. v. Hetero Labs Ltd., No. 2025-2016, 2026 WL 1884666 (Fed. Cir. July 1, 2026) (Circuit Judges Bryson, Stoll, and Dyk presiding; Opinion by Bryson, J.; Dyk, J., dissenting-in-part and concurring-in-part) (Appeal from D. Del., Williams, J.)
Drug Product and Patent(s)-in-Suit: Nuedexta® (dextromethorphan hydrobromide / quinidine sulfate); U.S. Pat. No. 7,659,282 (“the ’282 patent”)
Nature of the Case and Issue(s) Presented: The ’282 patent claims methods of treating pseudobulbar affect or emotional lability, which is the inability to control emotions exhibited by patients with neurodegenerative diseases or after a stroke or other brain injury, by administering dextromethorphan in combination with quinidine. Independent claim 1 requires administration of about 20-80 mg/day of dextromethorphan and about 10 mg/day to less than about 30 mg/day of quinidine, with the additional limitation that the weight-to-weight ratio of dextromethorphan to quinidine be 1:0.5 or less. Nuedexta is marketed as capsules containing 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate. In 2024, the FDA approved Hetero’s ANDA for a generic version of Nuedexta containing the same salt forms and nominal dosage strengths. After Hetero announced its intent to launch before expiration of the ’282 patent, Otsuka sought and obtained a preliminary injunction. The district court concluded that Otsuka was likely to succeed on infringement under its proposed claim construction and waived the Rule 65(c) bond requirement. Hetero appealed both rulings.
Why Otsuka Prevailed: The principal dispute concerned whether the claim terms “dextromethorphan” and “quinidine,” as used in the claimed weight-to-weight ratio, referred to the compounds as administered—including their pharmaceutically acceptable salt forms—or instead required conversion to the weights of the active moieties. Hetero argued that the ratio should be calculated using only the free-base portions of dextromethorphan hydrobromide and quinidine sulfate, which would place its ANDA product outside the claimed ratio. The Federal Circuit rejected that argument, holding that the intrinsic evidence demonstrated that the patent consistently used “dextromethorphan” and “quinidine” to encompass both the free-base and salt forms of those compounds. Dependent claims expressly referred to pharmaceutically acceptable salts, the specification repeatedly described doses of the salt forms as doses of dextromethorphan and quinidine, and the prosecution history reflected the examiner’s understanding that those claim terms included the salt forms. The Federal Circuit also found it highly unlikely that the patentees intended to draft claims excluding Nuedexta itself, the product the patent was designed to protect.
The Federal Circuit further rejected Hetero’s indefiniteness arguments, concluding that under Otsuka’s construction there remained only one straightforward method for calculating the claimed ratio based on the particular form of the actually-administered compounds. The possibility that different salt combinations might satisfy or fall outside the claims did not render the claims indefinite because each formulation presents only one measurable ratio. Accordingly, the Federal Circuit affirmed the district court’s determination that Otsuka was likely to succeed on the merits.
The Federal Circuit nevertheless vacated the district court’s decision to waive the Rule 65(c) bond requirement. Applying Third Circuit law, it explained that waiver of a bond is appropriate only in limited circumstances and that commercial patent disputes involving potential lost profits generally do not qualify. Because the injunction prevented Hetero from engaging in commercial market entry, the district court was required to reconsider an appropriate bond amount on remand.
Judge Dyk dissented from the majority’s claim construction and infringement analysis but agreed that the district court improperly waived the Rule 65(c) bond requirement. In Judge Dyk’s view, the claimed weight-to-weight ratio should be calculated using only the weights of the active moieties rather than the total weight of their administered salt forms. He reasoned that the invention’s objective was to optimize the therapeutic relationship between the active compounds while minimizing quinidine exposure, making comparison of the salt weights scientifically inconsistent with the patent’s purpose. Judge Dyk also concluded that the specification’s conversion tables and the prosecution history supported measuring only the active ingredients. Under that construction, Hetero raised a substantial question of noninfringement, and Judge Dyk would have reversed the preliminary injunction while still vacating the bond waiver.
