United Therapeutics Corp. (UTC) and Liquidia Technologies Inc. have been battling for close to a decade over their respective inhaled formulations of treprostinil (UTC's Tyvaso®, Liquidia's Yutrepia™) for treatment of pulmonary hypertension and their dispute is not yet over, both parties filing suits asserting patents against one another.
Treprostinil
In their extensive litigation, UTC has asserted claims in U.S. Patent No. 9,593,066 as well as U.S. Patent No. 10,716,793. The District Court held that the asserted claims of the '066 patent were invalid for anticipation or were not infringed, a decision affirmed in all respects by the Federal Circuit, and that the asserted claims in the '793 patent were infringed and were not invalid (see "United Therapeutics Corp. v. Liquidia Technologies, Inc. (Fed. Cir. 2023)". In an inter partes review proceeding, the Patent Trial and Appeal Board held that the challenged claims of the '793 patent (which the District Court held were infringed) were invalid for obviousness, a decision also affirmed by the Federal Circuit (see "United Therapeutics Corp. v. Liquidia Technologies, Inc. (Fed. Cir. 2024)).
In the more recent cases, UTC asserted (in the Middle District of North Carolina, 1:25CV368, before Judge Thomas Schroeder, complaint filed on May 9, 2025) claims of U.S. Patent No. 11,357,782 (issued June 14, 2022, which expires May 14, 2027) for methods of treating pulmonary hypertension using dry powder formulations; claim 1 is representative:
1. A method of treating pulmonary hypertension comprising:
providing an inhalation device for treating pulmonary hypertension in a human suffering from pulmonary hypertension comprising a powder formulation of treprostinil or a pharmaceutically acceptable salt thereof and a dry powder inhaler configured to administer single event dose of the powder formulation comprising treprostinil or a pharmaceutically acceptable salt thereof,
wherein the single event dose comprises at least 15 micrograms to 90 micrograms of treprostinil or a pharmaceutically acceptable salt thereof delivered in 1 to 3 breaths,
wherein the dry powder inhaler is configured to administer the entire single event dose in less than 5 minutes with at least 5 micrograms of treprostinil or a pharmaceutically acceptable salt thereof being inhaled per breath through coordinated actuation of the dry powder inhaler with each breath, and
administering to a human suffering from pulmonary hypertension with the dry powder inhaler the single event dose comprising at least 15 micrograms to 90 micrograms of treprostinil or a pharmaceutically acceptable salt thereof in 1 to 3 breaths,
wherein the human administers the entire single event dose with the dry powder inhaler in less than 5 minutes by inhaling at least 5 micrograms of treprostinil or a pharmaceutically acceptable salt thereof per breath by coordinating one actuation of the dry powder inhaler for each separate breath, and
wherein administration of an additional single event dose in the same manner occurs at least 3 hours later.
An important distinction is that UTC's product, encompassed by the limitations of the '782 patent is a new formulation of UTC's Tyvaso® product called Tyvaso DPI®, which obtained FDA approval in 2022 and (according to UTC's complaint) "is the first marketed dry powder formulation of treprostinil in the United States." Liquidia's accused product, Yutrepiaä, is also a dry powder formulation of treprostinil approved by FDA on August 19, 2024. However, this approval came with the caveat that Liquidia's product would not get final approval until UTC's 3-year regulatory exclusivity expired on May 23, 2025, which approval was granted when that deadline recently passed (although Liquidia has not yet put its Yutrepiaä product on the market).
UTC alleges that practicing Yutrepia's label will literally infringe claim 1 of the '782 patent, as well as claims 2, 3, 8. UTC's complaint, filed May 9, 2025 asks for a declaratory judgment of inducing infringement under 35 U.S.C. § 271(b) and contributory infringement under 35 U.S.C. § 271(c) based on Liquidia's current failure to launch their product. UTC's allegations are based on "Liquidia's unauthorized development, manufacturing, commercial marketing, distribution, offers for sale, sales and/or use of Yutrepia™ (treprostinil) inhalation powder for the treatment of pulmonary hypertension ("PH")," based on "tentative approval" of Liquidia's Yutrepiaä product. UTC's allegations are illustrated by this cartoon included in the complaint:
Liquidia asserts non-infringement based on UTC's claims requiring coordination between actuation of the dry powder in the inhaler and inhalation by the patient, which is not required by the Yutrepia's device/method. Liquidia further asserts invalidity based on the PTAB's invalidation of the '793 patent based on timing (the Final Written Decision of the IPR in the '793 patent was issued "only weeks after" allowance of the '782 patent), and that a related UTC application (US 2022-0323459 A1) was rejected for obviousness based on the reasoning in the FWD in the '793 IPR.
In a separate litigation, UTC filed suit under the Hatch-Waxman Act in the District of Delaware against Liquidia's earlier Yutrepiaä product when Liquidia amended its NDA (NDA No. 213005, filed under § 505(b)(2)) for this drug to include a new indication, pulmonary hypertension associated with interstitial lung disease ("PH-ILD"). Initially UTC asserted the '793 patent (later invalidated by the PTAB in inter partes review; see above) and U.S. Patent No. 11,826,327, claim 1 being representative:
1. A method of improving exercise capacity in a patient having pulmonary hypertension associated with interstitial lung disease [i.e., PH-ILD], comprising administering by inhalation to the patient having pulmonary hypertension associated with interstitial lung disease an effective amount of at least 15 micrograms up to a maximum tolerated dose of treprostinil or a pharmaceutically acceptable salt thereof in a single administration event that comprises at least 6 micrograms per breath.
Relevant to proceedings in the Middle District of North Carolina case (see below), UTC's motion for preliminary injunction to prevent Liquidia from marketing its Yutrepiaä product was denied in that case. This case is set for trial this month.
In another dispute in inter partes review, the PTAB invalidated UTC's challenged claims in U.S. Patent No. 9,604,901, with claim 1 being a representative claim:
A pharmaceutical batch consisting of treprostinil or a salt thereof and impurities resulting from (a) alkylating a benzindene triol, (b) hydrolyzing the product of step (a) to form a solution comprising treprostinil, (c) contacting the solution comprising treprostinil from step (b) with a base to form a salt of treprostinil, (d) isolating the salt of treprostinil, and (e) optionally reacting the salt of treprostinil with an acid to form treprostinil, and wherein the pharmaceutical batch contains at least 2.9 g of treprostinil or its salt.
This decision was affirmed by the Federal Circuit (see "United Therapeutics Corp. v. Liquidia Technologies Inc. (Fed. Cir. 2024)").
For its part Liquidia sued UTC for infringement of its U.S. Patent No. 10,898,494, which patent issued January 26, 2021 and expires May 5, 2037 and recites representative claim 1:
1. A method for treating a patient, comprising:
administration of a dry powder composition comprising
from about 100 micrograms to about 300 micrograms treprostinil or a pharmaceutically acceptable salt thereof to a patient
by inhalation using a dry powder inhaler over one to four breaths to treat pulmonary hypertension.
Liquidia's complaint mirrors UTC's complaint but is limited to inducement and/or contributory infringement (the patient being the literal infringer by using the inhaler as prescribed). Liquidia interprets UTC's treatment regimen containing on its label to direct patients to administer 112 micrograms (mcg) or 128 mcg at each treatment session for 4 sessions per day, which falls within the scope of UTC's asserted claims.
The most recent activity in these litigations was the District Court's denial in its North Carolina action of UTC's motions for a temporary restraining order and preliminary injunction. In denying these motions, the District Court held that UTC failed to satisfy the requirement for a showing of a likelihood of success on the merits and that Liquidia's Yutrepiaä product market entry would cause irreparable harm. The basis for UTC's failure to satisfy the "likelihood of success" requirement focused on whether the asserted claims were invalid for obviousness. As explained in the opinion, in the preliminary injunction context the burden on the accused infringer is to raise the invalidity issue "that [the patentee] cannot show 'lacks substantial merit,'" citing BlephEx, LLC v. Myco Indus., Inc., 24 F.4th 1391, 1399 (Fed. Cir. 2022). But, the District Court cautioned, "[t]he burden of presenting a substantial question of invalidity at this stage is lower than what is required to prove invalidity at trial," under Entegris, Inc. v. Pall Corp., 490 F.3d 1340, 1351 (Fed. Cir. 2007), and other authority. Here, Liquidia's basis for asserting invalidity was the PTAB's IPR decision that the '793 patent was invalid for obviousness (a decision that issued after the Examiner allowed the application leading to the '782 patent). Liquidia's position is that the disparate decisions create a contradiction, insofar as the '793 invalidation was based on the same prior art as the '782 allowance (a representative claim from each patent shown side-by-side below):
The Examiner for the application that resulted in the '782 patent reasoned that "a person of ordinary skill in the art would be unable to 'predict the dose, the number of breaths, and the timing of taking the drug' based on the relevant prior art," a conclusion not reached by the PTAB Board in invalidating the '793 patent (specifically the dose range, 15-90 micrograms, and delivery in "one to three" breaths). Liquidia's invalidity argument was supported, they contended, by rejection of claims in UTC's U.S. Patent Application No. 17/745,333 for obviousness made after the PTAB's decision invalidating the '793 patent became available. UTC's attempts to distinguish the limitations recited in these claims and the disclosure in the specification were unavailing in attempting to convince the District Court that Liquidia's obviousness arguments were unsupported by the evidence; the District Court supported its decision regarding such arguments by UTC's failure to convince the Examiner during prosecution of the '333 application using similar arguments, the comparison of the three sets of claims shown in this table:
(It being clear that claim 1 of the '782 patent is recited with significantly more specificity (i.e., limitations) than the claims of either the '793 patent or the '333 application; nevertheless these distinctions were not persuasive before the District Court.) And in the denial of UTC's preliminary injunction motion, Judge Schroeder rejected arguments based on any differences in effect regarding the '793 and '782 claims being method of treatment claims and the '333 application claims being directed to pharmaceutical compositions, saying that "[i]f it is not the case that what constitutes an obvious inference from the prior art with respect to a pharmaceutical product is obvious as to a method of treatment, UTC has not persuasively made that case."
Turning to the "irreparable harm" prong of the requirements for a preliminary amendment, the District Court also found a lack of persuasiveness from UTC. Rather, the Court was persuaded in part by UTC's delay in bringing suit on the '782 patent (from June 2022 until May 9, 2025, for purportedly strategic reasons, as well as a six-month delay from the date when FDA established Liquidia's Yutrepiaä product label -- the Court characterized this situation as involving "last-minute filing"). Also relevant was Liquidia's assertion that it was sufficiently "financially viable" to compensate UTC for any monetary losses it might incur after a Yutrepiaä product launch. The Court further expressed doubts about the risk of price erosion argued by UTC, and UTC's cause was not aided by statements by UTC executives minimizing the risk of a Yutrepiaä product launch, in some instances to be less than 5% of their current revenues.
In view of UTC's failures in establishing the first two prongs of the requirements for being granted a preliminary injunction, the District Court's relatively perfunctory analysis of the other two prongs (balance of the hardships and the public interest) did nothing to change the outcome, and the Court denied the injunction of these grounds.
As a consequence of the District Court's decision, within days Liquidia announced that it was preparing for a full commercial launch of its Yutrepiaä product. And UTC's third quarter 2024 projected annual revenues of $3 billion provided important incentives for further litigation over this market.
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