United Therapeutics Corp. v. Liquidia Technologies, Inc.

Case Name: United Therapeutics Corp. v. Liquidia Technologies, Inc., Civ. No. 20-755-RGA, 2022 WL 3910252 (D. Del. Aug. 31, 2022) (Andrews, J.)

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

Nature of the Case and Issue(s) Presented: UTC holds the NDA for Tyvaso, an inhaled solution formulation of treprostinil approved to treat pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. The ’066 and ’793 patents are Orange Book-listed patents. The ’066 patent claims an improved process for preparing treprostinil. The ’793 patent claims a method of administering treprostinil by inhalation. Liquidia filed an NDA pursuant to § 505(b)(2) to make and sell Yutrepia™, a dry powder formulation of treprostinil sodium. FDA tentatively approved Yutrepia to treat pulmonary arterial hypertension. Liquidia’s NDA contains Paragraph IV certifications alleging invalidity and/or non-infringement of the patents-in-suit. UTC initiated suit. The court presided over a four-day bench trial and found the ’066 patent invalid, and therefore not infringed, and further found that the ’793 patent was not invalid and would be infringed by Liquidia’s NDA product.

Why UTC Prevailed: The asserted ’066 claims are product-by-process claims where the product is a “pharmaceutical composition … comprising treprostinil or a pharmaceutically acceptable salt thereof.” Liquidia argued that those claims are invalid because the claimed product is the same product previously disclosed in the prior art Moriarty publication. Moriarty teaches the synthesis of treprostinil free acid by alkylation and hydrolysis of benzindene triol. UTC argued that Moriarty could not invalidate the product-by-process claims because it only disclosed treprostinil, not a “pharmaceutical composition comprising treprostinil.” But the patent makes no such distinction. The specification only describes the steps for synthesizing treprostinil or treprostinil salt. There is no description of combining treprostinil or treprostinil salt with excipients.

No UTC expert or fact witness rebutted Liquidia’s expert’s opinion that there was no structural or functional difference between the Moriarty Treprostinil free acid and the claimed treprostinil free acid product. The inventor testified that the ’066 process greatly reduced the 3AU90 impurity (an isomer of treprostinil) as compared to UTC’s former Chicago process. But the inventor did not compare the Moriarty treprostinil free acid prepared in Chicago and the claimed treprostinil free acid product. Instead, he compared the treprostinil free acid prepared at the Chicago facility and the Treprostinil diethanolamine salt prepared by the ’066 process. Thus, the court found that the inventor’s testimony failed to identify any structural or functional differences between the treprostinil products.

UTC also focused on the process limitations to distinguish the Moriarty reference. The court found this was improper. “The storage and stability limitations in claims 6 and 9 relate to the intermediate salt generated during the process steps, not the final composition product. The claims do not cover any stability or storage of the final treprostinil product. Nor is this ‘capability’ a structural or functional difference which appears in the claimed product.” Therefore, claims 1, 2, 3, 6, and 9 of the ’066 patent were invalid as anticipated.

Next, the court addressed Liquidia’s arguments that the ’793 patent was not infringed. Liquidia argued that UTC failed to prove that Yutrepia would be administered in “a therapeutically effective single event dose.” Put another way, Liquidia argued that claim 1 is limited to one single event dose per day rather than multiple doses per day. The court disagreed, finding that the term “single” modifies “event,” not “dose.” The experts agree that “single event dose” refers to a dose that is delivered in a single treatment session (i.e., a “single event”), including a session that involves multiple breaths, and that the claim language did not limit the number of single event doses per day. The “therapeutically effective” limitation was also met because UTC proved by a preponderance of the evidence that Yutrepia is a vasodilator that reduces vasoconstriction in the pulmonary vasculature, causing vasodilation (widening of vasculature). The direct infringement prong for induced infringement is met.

Liquidia then argued that it lacked specific intent to induce infringement because the Yutrepia’s label does not encourage administration of a “therapeutically effective single event dose.” The label does not contain any hemodynamic data or instruction to doctors to measure hemodynamic changes after a single event dose. But the label does not need to provide hemodynamic data to induce infringement. “It just needs to instruct doctors and patients to administer a single event dose that is therapeutically effective.” Instructing doctors to administer Yutrepia is sufficient because those instructions will “inevitably lead” to the administration of a “therapeutically effective single event dose.” Therefore, UTC has met its burden to show intent to induce infringement.

Liquidia raised various Section 112 defenses that the court considered and rejected. Given the disclosures in the specification, the court found that the asserted claims were enabled and were supported by adequate written description.