United Therapeutics asserted that Liquidia infringed its U.S. Patent No. 10,716,793 directed to methods of treatment of pulmonary hypertension (PH) with Tyvaso (an inhaled solution of a vasodilator treprostinil). Liquidia counterclaimed that the claims are invalid as not failing to comply with the enablement and written description requirements.

A representative claim reads:

1.         A method of treating pulmonary hypertension comprising administering by inhalation to a human suffering from pulmonary hypertension a therapeutically effective single event dose of a formulation comprising treprostinil or a pharmaceutically acceptable salt thereof with an inhalation device, wherein the therapeutically effective single event dose comprises from 15 micrograms to 90 micrograms of treprostinil or a pharmaceutically acceptable salt thereof delivered in 1 to 3 breaths.

The ‘793 Patent discloses the results of a clinical trial of Tyvaso demonstrating short term efficacy and adverse effects of the drug. The clinical trial did not include patients with PH type 2 – one of the five types of PH which, unlike the types included in the trial, is not normally treated with vasodilators, such as treprostinil.

The district court found the claims valid.

Claim construction

On Appeal, Liquidia raised a claim construction issue with respect to the term “treating pulmonary hypertension.” Liquidia argued that the term requires a showing of safety and efficacy, which the United Therapeutics’ clinical trial did not show for patients with PH type 2. Liquidia’s expert testified that a skilled person would have concerns about administering inhaled treprostinil to PH type 2 patients because related drugs cause increased mortality in these patients. Liquidia asserted that, for these reasons, the specification does not provide an adequate written description for the term “treating pulmonary hypertension” and does not enable the full scope of the claims.

In response, United Therapeutics argued that the clinical trial demonstrated that treprostinil improves hemodynamics and hence would treat a patient’s elevated pulmonary blood pressure, including in PH type 2 patients; that nothing in the specification requires the importation of safety and efficacy limitations into the claims; and that safety concerns in treating type 2 PH may factor into the FDA approval of the drug, but do not factor into claim interpretation.

The Federal Circuit held that the specification encompasses all five PH types when describing “pulmonary hypertension” and, therefore, the term includes treating all five groups of patients. However, the court found that despite this claim construction the claims are both enabled and comply with the written description requirement.

Enablement

The court held that the district court properly relied on expert testimony and record evidence to conclude that a skilled artisan would understand that the claimed administration of treprostinil would dilate the pulmonary vasculature, improve hemodynamics, and thus treat a patient’s elevated pulmonary blood pressure independent of the PH type.

The court further explained that a study showing that drugs similar to treprostinil failed in PH type 2 patients due to increased mortality yet showed improvement in a patient’s hemodynamics may be an issue for the FDA whereas the court’s focus is on the claimed invention.

Written Description

The court reiterated that questions of drugs safety and efficacy fall under the purview of the FDA.

The court explained that Liquidia essentially asks to treat patients with PH type 2 as a claimed species within a larger genus, but analogizing a subset of patients having a variant of a particular disease to traditional genus and species claims is inapt. It would be incorrect to fractionate a disease or condition and to require a separate disclosure in the specification for each variant in order to satisfy the provisions of 35 U.S.C. § 112, unless these variants are specified in the claims. For any given method of treatment, there may be a subset of patients who would not benefit from or should not take said treatment. However, a subset of unresponsive patients is not analogous to unsupported species in a generic claim to a chemical compound. Further, since safety and efficacy are not recited in the claims, the court need not deal with Liquidia’s arguments.

Takeaways

Disease subtypes are not equivalent to traditional species of a genus for the purposes of § 112. Applicant does not need to show efficacy and safety for a representative number of disease subtypes or a representative sample of patients in order to claim a method of medical treatment. Just because treatment may not be efficacious for every disease subtype or even dangerous for certain patients, does not mean that the written description and enablement requirements are not satisfied for claims of treating the disease.