Jynarque® (tolvaptan)
Case Name: Otsuka Pharm. Co., Ltd. v. Lupin Ltd., No. 2024-2297, 2026 WL 1429401 (Fed. Cir. May 21, 2026) (Circuit Judges Hughes and Cunningham and District Judge Burroughs presiding; Opinion by Hughes, J.) (Appeal from D. Del., Andrews, J.)
Drug Product and Patent(s)-in-Suit: Jynarque® (tolvaptan); U.S. Pat. Nos. 8,501,730 (“the ‘730 patent”) and 8,273,735 (“the ’735 patent”)
Nature of the Case and Issue(s) Presented: Otsuka owns the patents-in-suit, which claim a highly pure form of tolvaptan, a compound used to treat Autosomal Dominant Polycystic Kidney Disease (ADPKD), and improved methods for synthesizing tolvaptan. Previous methods of synthesizing tolvaptan formed a dechlorinated impurity. Otsuka’s patented method reduces the amount of a key hydrogenating reagent (sodium borohydride) in the synthesis process, which in turn reduces the amount of dechlorinated impurity. Otsuka uses this innovation in manufacturing its ADPKD treatment, Jynarque.
In May 2021, Lupin notified Otsuka that it had submitted an ANDA to the FDA seeking approval to market generic tolvaptan. Otsuka sued for patent infringement, asserting claims 1, 2, 4, and 5 of the ’730 patent and claims 7, 8, and 10 of the ’735 patent. The ‘730 claims are all independent product-by-process claims for the reduction of a benzazepine compound in the presence of a hydrogenating agent. The ‘735 asserted claims are method claims that require the hydrogenating agent be present in the amount of 0.25–1 or 0.25–0.5 molar equivalents per 1 mole of benzazepine precursor compound.
The point of contention centers around the molar equivalents in the ‘735 claims. The claimed process generally uses 1 molar equivalent or less of hydrogenating agent such as sodium borohydride per 1 mole of precursor compound, Lupin's process defined in its DMF uses at least 1.2 molar equivalents of sodium borohydride per 1 mole of precursor. Otsuka contends that the reaction is effectively complete before the excess sodium borohydride matters such that Lupin is practicing the claimed process.
After a bench trial, the district court held that Lupin’s DMF for producing tolvaptan did not infringe the asserted claims, which were also found to be invalid as obvious. Otsuka appealed, and the Federal Circuit affirmed.
Why Lupin Prevailed: The district court construed “amount” to mean a “practical completion,” not an “absolute completion” construction. Otsuka argued that Lupin infringed because the reaction is practically complete before 1 molar equivalent or less of hydrogenating agent is added to the reaction mixture. But the Federal Circuit determined that Otsuka still failed to show infringement for two reasons. First, Otsuka did not show that Lupin’s reaction was practically complete by the time the amount of precursor compound fell to 0.05% of its original level, the point at which Lupin decided to end the reaction by “quenching” it. Second, even assuming the above reaction did reach practical completion, Otsuka failed to demonstrate that no more than 1 molar equivalent or less of sodium borohydride was added at that point in the reaction to fall within the claimed range.
The Federal Circuit also found Otsuka’s expert, Dr. William Roush, unconvincing. Roush relied on (i) two experiments conducted by Lupin and (ii) his scientific expertise to support infringement. The Federal Circuit found the two experiments unreliable and lacking “appropriate quality control.” Additionally, since those experiments were performed under different conditions than Lupin’s DMF process, it did not make sense for Roush to rely upon them. Furthermore, Roush’s testimony shed little light on when the reduction reaction in Lupin’s DMF process was practically complete, the main issue in this case. Even with his “vast experience performing sodium borohydride reactions,” the Federal Circuit was not persuaded by his testimony.
Lastly, the Federal Circuit affirmed the invalidity of the ‘735 patent on obvious grounds. The parties agreed that the “Kondo” prior art reference already taught the overall synthesis of tolvaptan. However, the Federal Circuit affirmed that a POSA would have been motivated to reduce the amount of sodium borohydride to save costs, improve the reaction’s safety profile, simplify downstream process, and minimize wasting sodium borohydride as taught by Kondo. The Federal Circuit also found no clear error in the district court’s analysis of secondary considerations such as commercial success, long-felt need, unexpected results.
