United Therapeutics Corp. v. Liquidia Technologies, Inc.

Tyvaso® (treprostinil)

July 24, 2023

GENERICally Speaking

Case Name: United Therapeutics Corp. v. Liquidia Technologies, Inc., Nos. 2022-2217, 2023-1021, 2023 WL 4695903 (Fed. Cir. July 24, 2023) (Circuit Judges Lourie, Dyk, and Stoll presiding; Opinion by Lourie, J.) (Appeal from D. Del., Andrews, J.)

Drug Product and Patent(s)-in-Suit: Tyvaso® (treprostinil); U.S. Patents Nos. 10,716,793 (“the ’793 patent”) and 9,593,066 (“the ’066 patent”)

Nature of the Case and Issue(s) Presented: UTC holds and NDA for Tyvaso, an inhaled solution formulation of treprostinil approved for the treatment of pulmonary hypertension (“PH”). There are five subgroups of PH: Group 1, pulmonary arterial hypertension (“PAH”); Group 2, pulmonary venous hypertension, i.e., pulmonary hypertension related to left-heart disease; Group 3, pulmonary hypertension associated with disorders damaging the lungs; Group 4, pulmonary hypertension caused by chronic thrombotic or embolic disease, including chronic blood clots in the lungs; and Group 5, a miscellaneous category for conditions that do not fit well into the other four subgroups. Each group may require group-specific treatment. The patents-in-suit claim methods of treating PH and pharmaceutical compositions comprising treprostinil. Liquidia filed a 505(b)(2) application for Yutrepia™, a dry powder inhalation formulation of treprostinil, referencing UTC’s NDA. UTC sued Liquidia in district court. The district court found held the ’793 patent claims valid and infringed and the ’066 patent claims invalid. The parties cross appealed and the Federal Circuit affirmed.

In parallel, Liquidia filed a petition for IPR of the ’793 patent, alleging that all claims would have been unpatentable as obvious. On July 19, 2022, the PTAB issued a Final Written Decision finding all claims of the ’793 patent unpatentable as obvious. UTC’s appeal of that decision is currently pending and not the subject of this opinion.

Why UTC Prevailed: Liquidia raised five issues on appeal: the district court erred (i) in construing the claim limitation “treating pulmonary hypertension” in claim 1 of the ’793 patent not to include safety and efficacy; (ii) in finding the asserted claims of the ’793 patent enabled; (iii) in finding the asserted claims of the ’793 patent supported by written description; (iv) in  finding Liquidia liable for induced infringement of claims 1, 4, and 6–8 of the ’793 patent; and (v) in finding claims 1–3 of the ’066 patent to be infringed. UTC raised two issues on appeal: the district court erred (i) in finding that Liquidia did not infringe claims 6 and 8 of the ’066 patent; and (ii) in finding that claims 1–3, 6, and 9 of the ’066 patent were invalid as anticipated by Moriarty.

The ’793 patent. The Federal Circuit agreed with the district court that “treating PH” included treating all five groups of PH patients. “Questions of safety and efficacy in patent law have long fallen under the purview of the FDA” and therefore the Federal Circuit declined to insert the FDA’s responsibilities into claims by importing requirements where they do not recite such limitations.

Next, Liquidia argued that the ’793 patent specification provided no guidance or examples of treating Group 2 PH patients, and thus a skilled artisan would have had to engage in undue experimentation to practice the full scope of the claimed invention. Liquidia further argued that the ’793 patent never described treating Group 2 PH patients with inhaled treprostinil, but only Group 1, 3, and 4 patients, all of whom have precapillary PH. Thus, a skilled artisan would have understood that the inventors did not invent or possess a method of treating Group 2 PH patients. The Federal Circuit disagreed. While the record showed that a physician may have safety concerns in treating Group 2 PH patients with treprostinil and other vasodilators, the district court properly relied on the record evidence showing that the claimed administration of treprostinil vasodilates the pulmonary vasculature and reduces pulmonary blood pressure even in Group 2 PH patients.

Turning to the induced infringement argument, Liquidia contended that it could not be held liable for induced infringement because the ’793 patent was found to be unpatentable in an IPR, and an unpatentable or invalid patent cannot be infringed. The Federal Circuit agreed with the district court that a pending, non-final litigation does not negate an intent to infringe that is otherwise supported by evidence. An IPR decision does not have collateral estoppel effect until that decision is affirmed or the parties waive their appeal rights.

The ’066 patent. UTC argued that Moriarty did not anticipate the ’066 patent because Moriarty did not teach the purification of treprostinil through salt formation and did not disclose any information on specific alkylation and hydrolysis impurities. Those limitations were added to overcome validity challenges and the district court failed to recognize the structural features that are imparted by the claimed salt-formation purification. The asserted claims are product-by-process claims. “But a product-by-process claim is a product claim, even if claimed by a process by which it can be made.” The specification of the ’066 patent discloses an impurity level of 99.7%-99.9%, and Moriarty similarly discloses the synthesis of impure Treprostinil having 99.7% purity.

Next, claims 6 and 8 require that the treprostinil salt be stored at ambient temperature. UTC argued that Liquidia’s promise not to make its product with batches of treprostinil salt that were stored at ambient temperature is insufficient to avoid a finding of infringement. But the district court properly credited Liquidia’s representations to the FDA that it would store Treprostinil sodium between 2°C and 8°C. There was no evidence showing that Liquidia used ambient-temperature-stored batches of treprostinil in its manufacturing process in making a pharmaceutical composition as required by claim 6 or claim 8.

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