No Safety Requirement, No Process Shield: Fed. Cir. on Treprostinil Patents

The Federal Circuit in United Therapeutics v. Liquidia affirmed a Delaware court’s ruling that Liquidia’s NDA for Yutrepia™ would infringe United Therapeutics’ patents, although one (the ’066 patent) fell on anticipation grounds.

The court underscored three familiar principles: (1) safety and efficacy belong to the FDA, not the USPTO; (2) product-by-process claims rise or fall on the product itself, not the process; and (3) method-of-treatment claims do not require disclosure of every disease subtype unless the claims themselves demand it.

United Therapeutics holds a New Drug Application (NDA) for Tyvaso®, a treprostinil solution used for the treatment of pulmonary hypertension. Liquidia filed an NDA for its drug Yutrepia™, an inhalation formulation of treprostinil that is also indicated for the treatment of pulmonary hypertension. Liquidia’s NDA was filed under § 505(b)(2) of the Hatch-Waxman act, which is an abbreviated approval pathway allowing United Therapeutics to bring this suit.

Pulmonary hypertension, characterized by abnormally high blood pressure in the lungs, is comprised of five subgroups. Each of Groups 1, 3, 4, and 5 are caused by conditions affecting the pulmonary arteries or precapillary vessels of the lungs, while Group 2 typically develops because of a cardiac-based etiology.

United sued within the Hatch-Waxman window on the ’066 patent, later adding the ’793 patent when it issued. The district court concluded that claims 1, 4, and 6-8 of ’793 patent are not invalid and are infringed; claims 1-3 of the ‘066 patent are invalid as anticipated, but otherwise infringed; claims 6 and 9 of the ‘066 patent are invalid as anticipated; and that claims 6, 8, and 9 of the ‘066 patent are not infringed. The CAFC affirmed.[1]

The ‘793 patent claims a method of treating pulmonary hypertension by administering by inhalation a therapeutically effective single dose of treprostinil at a specific dosage. Liquidia responded that the asserted claims of the ‘793 patent were invalid as lacking adequate enablement and written description under, arguing that the claim limitation “treating pulmonary hypertension” should be construed to include safety and efficacy.

As a threshold issue, the CAFC agreed with the district court that while “treating pulmonary hypertension” should be construed as treating all five groups of pulmonary hypertension patients, “the claim language ‘treating pulmonary hypertension’ does not import any additional efficacy limitations or any safety limitations.” [2] The court concluded that “absent incorporation of safety and efficacy requirements in the claims, Liquidia’s argument concerning the safety and efficacy of treating Group 2 PH patients is not before us.” [2] The CAFC reiterated that questions of safety and efficacy in patent law have long fallen under the purview of the FDA and declined to insert the FDA’s requirements into claims where they do require such limitations. [3]

Turning to Liquidia’s written description and enablement arguments, the CAFC agreed with United Therapeutics that the claims are adequately enabled as they were construed by the district court. Liquidia argued that the ‘793 patent did not describe treating Group 2 PH patients with inhaled treprostinil. While the court acknowledged that expert testimony concluded that a physician may have safety concerns in treating Group 2 PH patients with treprostinil, the CAFC credited the district court’s finding that the record demonstrates that the claimed administration of treprostinil vasodilates the pulmonary vasculature and reduces pulmonary blood pressure even in Group 2 PH patients. [4] The CAFC also agreed with the district court’s finding of adequate written description. The CAFC declined to treat Group 2 PH as a claimed species within a larger genus (i.e., all five groups of pulmonary hypertension), stating:

It would be incorrect to fractionate a disease or condition that a method of treatment claim is directed to, and to require a separate disclosure in the specification for each individual variant of the condition (here, an individual group of pulmonary hypertension patients) in order to satisfy the enablement and written description provisions of 35 U.S.C. § 112, unless these variants are specified in the claims.

[5]The CAFC further agreed with the district court’s conclusion that Liquidia induced infringement of the ‘793 patent by instructing doctors and patients to administer a therapeutically effective single event dose.[6]

Turning to the ‘066 patent claims, which are directed to a pharmaceutical composition comprising treprostinil, prepared by alkylation and hydrolysis steps, i.e., product-by-process claims. These claims were affirmed as anticipated by a disclosure of the same product, irrespective of the processes by which they were made.

In sum, the Federal Circuit reaffirmed two principles: safety and efficacy are for the FDA, not the PTO, and product-by-process claims live or die on the product itself. For patentees, the lesson is that method-of-treatment claims will not be invalidated for lack of safety data if not recited in the claim, and product claims cannot hide behind process language when the prior art shows the same compound.

[1] United Therapeutics Corporation v. Liquidia Technologies, Inc., No. 2022-2217 and 2023-1021, Fed. Cir. July 24, 2023, at p. 5.

[2] Id. at p. 13.

[3] Id. at p. 14.

[4] Id. at p. 16.

[5] Id. at p. 17.

[6] Id. at p. 18.