CAFC Affirms Mixed Ruling on Pulmonary Hypertension Drug Patent, Noting ‘Safety and Efficacy’ is for FDA

The U.S. Court of Appeals for the Federal Circuit (CAFC) on Monday issued a precedential decision affirming a district court’s mixed ruling in a patent infringement case involving two patents owned by United Therapeutics on the pulmonary hypertension drug, Tyvaso.

U.S. Patent 10,716,793 and U.S. Patent 9,593,066 cover methods of treating pulmonary hypertension and pharmaceutical compositions comprising treprostinil—Tyvaso is an inhaled solution formulation of treprostinil. United Therapeutics also owns a new drug application (NDA) for Tyvaso, No. 022387.

The five subgroups of pulmonary hypertension, according to the CAFC decision, are: “Group 1, pulmonary arterial hyper- tension (“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.”

Liquidia Technologies, Inc. filed NDA No. 213005 for Yutrepia—a dry powder inhalation formulation of treprostinil. United Therapeutics subsequently sued Liquidia for infringement of the ‘066 patent in the District of Delaware, and, following issuance of its ‘793 patent, also added the latter to the infringement suit.

At the same time, Liquidia filed an inter partes review (IPR) with the Patent Trial and Appeal Board (PTAB) and the PTAB ultimately found all claims of the ‘793 patent invalid as obvious. An appeal to the CAFC on that decision is pending.

The district court found that United Therapeutics had proven by a preponderance of the evidence that the administration of Yutrepia will directly infringe claims 1, 4, and 6–8 of the ’793 patent; that Liquidia will induce infringement of claims 1, 4, and 6–8 of the ’793 patent; that the asserted claims were not invalid for lack of enablement or written description; and therefore stayed approval of Liquidia’s NDA for Yutrepia until May 5, 2027, the expiration date of the ’793 patent.

As to the ‘066 patent, the district court held that United Therapeutics also successfully proved that Liquidia’s Yutrepia would infringe claims 1–3, but said that claims 1–3, 6, and 9 were invalid as anticipated by the asserted prior art. The court also said claims 6 and 9 were invalid and not infringed and that claim 8 was not invalid and not infringed.

On appeal, Liquidia made five arguments: 1) that the district court erred in construing the claim limitation “treating pulmonary hypertension” in claim 1 of the ’793 patent not to include safety and efficacy; 2) that the court erred in finding the asserted claims of the ’793 patent enabled; 3) that the court clearly erred in finding the asserted claims of the ’793 patent supported by written description; 4) that the court clearly erred in finding Liquidia liable for induced infringement of claims 1, 4, and 6–8 of the ’793 patent; and 5) that the court clearly erred in finding claims 1–3 of the ’066 patent to be infringed.

In its cross-appeal, United Therapeutics argued that the district court clearly erred in finding that Liquidia does not infringe claims 6 and 8 of the ’066 patent and  that the court clearly erred in finding that claims 1–3, 6, and 9 of the ’066 patent are invalid.

Looking at Liquidia’s first argument, the CAFC rejected its contention that the district court erred in determining that the meaning of “treating pulmonary hypertension” does not require a showing of safety and efficacy, explaining that “[q]uestions of safety and efficacy in patent law have long fallen under the purview of the FDA.” The CAFC added: “We decline to insert the FDA’s responsibilities into claims by importing requirements where they do not recite such limitations.”

The court also agreed with the district court that that “treating pulmonary hypertension” includes treating all five groups of pulmonary hypertension patients.

The CAFC next agreed with United Therapeutics that the claims were adequately enabled and supported by adequate written description. “While the court credited expert testimony concluding that a physician may have safety concerns in treating Group 2 PH patients with treprostinil and other vasodilators…the court also found 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,” wrote the CAFC. Thus, the district court properly relied on expert testimony and the evidence to determine that the claimed process would be effective, independent of the type of patient, and “[t]hat was all that the claims require under the district court’s construction,” added the court. “‘That a study—administering treprostinil-like prostacyclins to Group 2 PH patients—failed due to increased mortality, yet showed ‘improvement in a patient’s hemodynamics,’ may be an issue for the FDA. But our focus is on the claimed invention.”

Turning to Liquidia’s argument challenging written description, the court said that “Liquidia essentially asks us to treat Group 2 PH as a claimed species within a larger genus (i.e., all five groups of pulmonary hypertension).” But that analogy is “inapt,” said the CAFC. The opinion underscored its point again:

“Again, because safety and efficacy are not recited in the claims, we need not deal with Liquidia’s arguments. Disease-specific treatment requirements are matters for the FDA and medical practitioners…. [F]or any given method of treatment claim, there may be a subset of patients who would not benefit from or should not take the claimed treatment…. That does not mean that such claims are not sufficiently enabled or supported by written description. A subset of unresponsive patients is not analogous to unsupported species in a generic claim to chemical compounds.”

The CAFC similarly affirmed the district court’s finding as to Liquidia’s liability for induced infringement of the ‘793 patent. Even though the patent was found invalid by the PTAB, “[a] pending, non-final litigation does not negate an intent to infringe that is otherwise supported by evidence,” wrote the CAFC. “And we have previously held that an IPR decision does not have collateral estoppel effect until that decision is affirmed or the parties waive their appeal rights.” Furthermore, claims that are invalidated in an IPR are not cancelled until “the Director issues a certificate confirming unpatentability, which occurs only after ‘the time for appeal has expired or any appeal has terminated.’”

On the remaining arguments, the court found that the issue of Liquidia’s infringement of claims 1-3 of the ‘066 patent is moot since the district court correctly found those claims invalid; that the district court did not clearly err in finding that claims 1–3, 6, and 9 are invalid as anticipated; and that the district court did not clearly err in finding that Liquidia does not infringe claims 6 and 8 of the ’066 patent.

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