How a Treatment Claim Without Reciting Safety and Efficacy Requirements May Survive the Disclosure Requirement Challenge: United Therapeutics Corp. v. Liquidia Technologies,Inc.

Abstract

This article analyzes a case representing an issue of the disclosure requirement under 35 U.S.C. § 112 where the claimed invention used a single active ingredient to treat several variants of the targeted disease. In United Therapeutics Corp. v. Liquidia Techs., Inc., 74 F.4th 1360 (Fed. Cir. 2023), one disputed treatment patent survived the disclosure requirement challenge. United Therapeutics indicates that a treatment claim without reciting a safety or efficacy limitation is generally not construed to include safety and efficacy requirements. This case also suggests a strategy of patent drafting where the specification of a treatment patent should focus on how the patented treatment improves targeted subjects’ biological data rather than their symptoms, functions, or survival rates.

INTRODUCTION

35 U.S.C. § 112(a) provides that “[t]he specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same[.]”¹ This language represents two separate requirements: written description and enablement.² These two requirements together constitute the disclosure requirement.³

The disclosure requirement plays a significant role in the patent system.⁴ The public can learn technological knowledge from a patent as long as the specification explains the details of the invention.⁵ In addition, by teaching how to make and use the invention, the specification allows others to replicate the invention.⁶

On the litigation side, a defendant may bring an invalidation challenge against certain claims violating the disclosure requirement. For instance, in Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., the Federal Circuit held that the disputed claims reciting a method for the treatment of a hepatitis C virus (“HCV”) infection were invalid for lack of enablement and written description.⁷ There, the disputed claims required a specific group of nucleosides as medicines for the claimed treatment, but the specification failed to demonstrate the feasibility of producing every claimed nucleoside that can treat HCV.⁸ The specification was also found not to provide sufficient embodiments to support the invention of using the claimed nucleosides to treat HCV.⁹

For a treatment claim challenged under the disclosure requirement, Idenix Pharmaceuticals falls within a line of cases where the claimed invention uses many variants of the active ingredient to cure a single disease.¹⁰ On the contrary, United Therapeutics Corp. v. Liquidia Technologies, Inc. represents the opposite because the claimed invention used a single active ingredient to treat several variants of the targeted disease.¹¹

In United Therapeutics, the Federal Circuit held that one disputed patent survived the disclosure requirement challenge.¹² There, the defendant sought to persuade the Federal Circuit to import safety and efficacy requirements into the treatment claims in dispute.¹³ However, the Federal Circuit denied the defendant’s approach and, therefore, affirmed that the disputed claims satisfied the enablement and written description requirements.¹⁴ This case was petitioned to the Supreme Court, which in 2024 decided not to grant certiorari.¹⁵

The article is intended to analyze United Therapeutics. Next, Part II introduces the technological background and the disputed claims relevant to the disclosure requirement. Part II also describes the Federal Circuit’s reasoning for upholding the district court’s decision on patent validity. Finally, Part III provides a practical implication drawn from United Therapeutics, focusing on the claim construction issue that may affect the outcome of the case.

ANALYSIS OF UNITED THERAPEUTICS CORP. v. LIQUIDIA TECHNOLOGIES, INC

Patented technology

In United Therapeutics, the patent-in-suit relevant to the disclosure requirement issue was U.S. Patent No. 10,716,793 (“793 Patent”) involving a method of treating pulmonary hypertension (“PH”).¹⁶ When the blood pressure in the lungs is higher than normal, PH develops to affect the blood vessels there and causes the heart to work harder than normal to pump blood into the lungs.¹⁷ The PH-related symptoms include shortness of breath, chest pain, and lightheadedness.¹⁸

There are five different groups of PH.¹⁹ Group 1 PH is known as pulmonary arterial hypertension (“PAH”), where PH develops on its own.²⁰ Group 2 PH or pulmonary venous hypertension (“PVH”) is PH caused by left-sided heart disease.²¹ Group 3 PH stands for PH due to lung disease or hypoxia.²² Group 4 PH means PH arising from pulmonary artery obstructions, including chronic thromboembolic pulmonary hypertension (“CTEPH”).²³ Group 5 PH includes PH with unknown causes or PH that does not fall within those four categories.²⁴

The second way to divide PH is to examine whether “the underlying pathology is predominantly in the pulmonary arterioles and small pulmonary arteries[.]”²⁵ If so, the PH is classified as precapillary PH.²⁶ If not, the next question is whether raised pulmonary artery pressure (“PAP”) is caused by left heart disease; if so, the PH is termed isolated postcapillary PH.²⁷ Postcapillary PH involves no intrinsic pathology in pulmonary circulation.²⁸

Groups 1, 3, 4, and 5 of PH generally fall within the precapillary PH class because they “are caused by conditions affecting the pulmonary arteries or precapillary vessels of the lungs[.]”²⁹ Group 2 PH is postcapillary PH because it “typically develops as a result of a cardiac-based etiology[.]”³⁰

Among those major medications used to treat PH are vasodilators or blood vessel dilators, which widen the blood vessels by causing the muscle in the vessel walls to relax, such that blood can flow through the vessel better.³¹ The patented method used inhalation of treprostinil, a synthetic prostacyclin analogue functioning as a vasodilator to reduce vasoconstriction in the pulmonary vasculature, thereby widening vasculature and decreasing PAP and pulmonary vascular resistance (“PVR”).³²

The patentee United Therapeutics Corp. (“UTC”) holds New Drug Application (“NDA”) No. 022387 for Tyvaso®, an inhaled solution formulation of treprostinil, and NDA No. 214324 for Tyvaso DPI®, a dry inhalation powder of treprostinil, approved for the treatment of PH.³³ Because different PH groups arise from different causes, each PH group requires group-specific treatment.³⁴ The U.S. Food and Drug Administration (“FDA”) has approved Tyvaso® and Tyvaso DPI® for treating PAH and PH associated with interstitial lung disease (“PH-ILD”).³⁵

Disputed claims

On appeal, the defendant challenged the district court’s determination that claims 1, 4, and 6–8 of the 793 Patent were not invalid for lack of enablement and written description.³⁶ Claim 1 was an independent claim reciting:

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. ³⁷

Claim 4 dependent on claim 1 designated the inhalation device as a dry powder inhaler.³⁸ Claim 6 dependent on claim 4 recited that “the formulation is a powder.”³⁹ Claim 7 dependent on claim 6 further defined the powder as “compris[ing] particles less than 5 micrometers in diameter.”⁴⁰ Finally, claim 8 dependent on claim 1 included a negative limitation reciting that “the formulation contains no metacresol.”⁴¹

Issue I: Claim interpretation

The key issue related to the disclosure requirement was whether the recitation of “treating pulmonary hypertension” in claim 1 requires “a showing of safety and efficacy.”⁴² This issue was triggered primarily by two contentions brought by the defendant.⁴³ First, both parties’ experts agreed that Group 2 PH patients would not benefit from treprostinil treatment.⁴⁴ Second, the defendant’s expert highlighted the safety concern of treprostinil treatment by citing one earlier study indicating that the administration of a treprostinil-like prostacyclin to Group 2 PH patients failed due to increased mortality.⁴⁵

These contentions implied that if “safety and efficacy” had been read into the disputed claims, the district court would have invalidated the 793 Patent for lack of enablement and written description.⁴⁶ However, the Federal Circuit ruled out “safety and efficacy” as requirements in the disputed claims.⁴⁷ Thus, the Federal Circuit rejected the defendant’s argument regarding the safety and efficacy of using treprostinil in Group 2 PH treatment.⁴⁸

Although not describing any governing law for claim construction, the Federal Circuit reviewed the district court’s claim construction de novo with applying a “clear error” standard to any underlying facts.⁴⁹ Initially, the Federal Circuit affirmed the district court’s interpretation of “treating pulmonary hypertension” as treating all five groups of PH patients.⁵⁰ The Federal Circuit pointed out that the use of both “precapillary pulmonary hypertension” and “pulmonary hypertension” in the specification as representing the inventor’s view of precapillary PH as a subset of PH.⁵¹

In addition, the Federal Circuit considered the phrase “treating pulmonary hypertension” in claim 1 as “not import[ing] any additional efficacy limitations or any safety limitations.”⁵² This notion rested on the district court’s interpretation of “a therapeutically effective single dose” as “a dose given in a single treatment session that causes an improvement in a patient’s hemodynamics (reduced PAP or PVR).”⁵³ The Federal Circuit was reluctant to construe the term “a therapeutically effective single dose” here because the defendant did not question the district court’s construction.⁵⁴

Finally, the Federal Circuit emphasized its traditional view that “[q]uestions of safety and efficacy in patent law have long fallen under the purview of the FDA.”⁵⁵ Thus, the Federal Circuit opined that it “decline[s] to insert the FDA’s responsibilities into claims by importing requirements where they do not recite such limitations.”⁵⁶

Issue II: Enablement

Without referring to any case law governing enablement, the Federal Circuit simplified the issue of enablement as whether “the claims [of 793 Patent] are adequately enabled as they were construed by the district court.”⁵⁷ The Federal Circuit also reviewed this issue de novo.⁵⁸

In affirming the district court’s enablement holding, the Federal Circuit first observed that the specification described the treatment of PH patients with inhaled treprostinil and illustrated a study concerning acute safety, tolerability, and hemodynamic effects of inhaled treprostinil.⁵⁹ Thus, the Federal Circuit opined that the specification “sufficiently enables the scope of the claims.”⁶⁰

In addition, while acknowledging that the district court credited expert testimony mentioning the safety issue of treating Group 2 PH patients with treprostinil, the Federal Circuit noted that the record also supported the district court’s finding that the claimed administration of treprostinil widened the pulmonary vasculature and even lowered the pulmonary blood pressure of Group 2 PH patients.⁶¹ Therefore, the Federal Circuit agreed with the district court that a skilled artisan would view the claimed administration of treprostinil as a measure to broaden the pulmonary vasculature (i.e., better hemodynamics) and treat with a single dose a patient suffering elevated pulmonary blood pressure regardless of what causes it.⁶²

Finally, the Federal Circuit emphasized that the district court’s enablement determination “was all that the claims require under the district court’s [undisputed] construction [regarding the] ‘therapeutically effective single event dose’ [limitation.]”⁶³ The Federal Circuit explained that “[its] focus is on the claimed invention” and left FDA to consider the study showing the mortality issue of administering treprostinil-like prostacyclins to Group 2 PH patients.⁶⁴ As a result, the Federal Circuit held that “the claims are adequately enabled.”⁶⁵

Issue III: Written description

The issue concerning written description was whether “the district court did not clearly err in finding that the claims of the [793 Patent] are supported by an adequate written description.”⁶⁶ Unlike its approach to other issues, the Federal Circuit resolved the written description issue by bringing out a standard “requir[ing] that the specification reasonably convey to those skilled in the art that the inventor had possession of the claimed invention as of the filing date.”⁶⁷

The Federal Circuit agreed with the district court’s holding.⁶⁸ The reasoning again centered on the claim language “treating pulmonary hypertension comprising administering … a therapeutically effective single event dose of a formulation containing treprostinil[.]”⁶⁹ The Federal Circuit found that the specification described the claim language and, therefore, concluded that the “possession of the claimed invention under the district court’s construction” had been shown.⁷⁰

In addition, the Federal Circuit responded to the defendant’s attempt to urge it to “treat Group 2 PH as a claimed species within a larger genus (i.e., all five groups of pulmonary hypertension).”⁷¹ The Federal Circuit criticized that “analogizing a subset of patients having a variant of a particular disease to traditional genus and species claims is inapt.”⁷²

Regarding treatment claims, the Federal Circuit further declared an incorrect standard for either enablement or written description which “fractionate[s] a disease or condition that a method of treatment claim is directed to” and “require[s] a separate disclosure in the specification for each individual variant of the condition (here, an individual group of pulmonary hypertension patients)[.]”⁷³ However, the Federal Circuit noted that this incorrect standard may become a correct one as long as those “variants are specified in the claims.”⁷⁴

Moreover, the Federal Circuit again pointed to the key fact that “safety and efficacy are not recited in the claims[.]”⁷⁵ Thus, the Federal Circuit refused to examine the defendant’s assertions concerning Group 2 PH patients.⁷⁶

Ultimately, the Federal Circuit held that “[a] subset of unresponsive patients is not analogous to unsupported species in a generic claim to chemical compounds.”⁷⁷ On the one hand, the Federal Circuit reaffirmed its view that it is best for FDA and medical practitioners to determine disease-specific treatment requirements where the practitioners may rely on FDA’s findings to avoid therapeutically ineffective treatment of certain patients.⁷⁸ On the other hand, the Federal Circuit assured that whether a treatment claim is “not sufficiently enabled or supported by written description” is independent of a concern that “a subset of patients [] would not benefit from or should not take the claimed treatment.”⁷⁹

TREATMENT CLAIMS AND SAFETY AND EFFICACY REQUIREMENTS

United Therapeutics indicates that use of “treating” or “therapeutically effective” in a treatment claim does not automatically import safety and efficacy limitations into the claim. However, it is a matter of claim construction.

The district court in United Therapeutics characterized the defendant’s enablement arguments as imposing on the disputed claims a limitation requiring “safely and effectively treating pulmonary hypertension.”⁸⁰ But in fact, the defendant did not propose a claim construction containing safety and efficacy requirements.⁸¹ Instead, the defendant’s strategy for claim construction focused on the scope of the claimed PH.⁸²

The defendant argued that the scope covered all five PH groups, while the patentee sought to exclude Group 2 PH from the scope.⁸³ The premise of the defendant’s version of claim construction was, for example, that the specification would not enable treating patients of all five PH groups.⁸⁴ Ultimately, the district court agreed with the defendant’s claim construction but objected to the defendant’s enablement theory.⁸⁵

Nonetheless, the district court identified a phrase “therapeutically effective single event dose” in claim 1 as a limitation related to efficacy.⁸⁶ Both parties indeed disputed the meaning of “therapeutically effective single event dose.”⁸⁷ But, this dispute was associated with the issue of direct infringement.⁸⁸

In determining whether an alleged patent is infringed, courts generally perform “a two-step analysis [by] first determin[ing] the scope and meaning of the claims asserted[] and then [comparing] the properly construed claims [] to the allegedly infringing device (for an apparatus claim) or allegedly infringing act (for a method claim).”⁸⁹ The district court in United Therapeutics also embraced this two-step analysis.⁹⁰

The dispute concerning the meaning of “therapeutically effective single event dose” was divided into two issues.⁹¹ The first issue involved “single event dose,” a phrase the district court interpreted as “not [being] limited to one single event dose per day.”⁹²

The second issue involving a phrase “therapeutically effective” is more relevant to efficacy, where the district court ultimately construed the phrase as “a dose given in a single treatment session that causes an improvement in a patient’s hemodynamics (reduced PAP or PVR).”⁹³ To reach this interpretation, the district court relied on both parties’ expert testimony and the specification of the 793 Patent.⁹⁴

To perform claim construction, courts primarily rely on intrinsic evidence including claim language itself, the specification, and prosecution record.⁹⁵ The secondary evidence is extrinsic evidence covering “expert testimony, articles, and inventor testimony[,]” and the extrinsic evidence “may not be used to vary, contradict, expand, or limit the claim language from how it is defined, even implicitly, in the specification or file history.”⁹⁶ Although the district court in United Therapeutics did not expressly illustrate a legal standard for claim construction, the way it interpreted the disputed claims implied a result of applying those legal propositions concerning claim construction.⁹⁷

The district court’s analysis of “therapeutically effective” began with acknowledging expert testimony offered by both parties.⁹⁸ Comparing different versions of the disputed term, the district court sided with the patentee’s expert, testifying that “a therapeutically effective single event dose is one that causes a positive change in a patient’s hemodynamics—i.e., [] a reduction in pulmonary artery pressure and cause a reduction in pulmonary vascular resistance.”⁹⁹

The district court did not simply accept the patent’s expert testimony.¹⁰⁰ Rather, the district court reviewed “[t]he examples in the specification [which] studied the hemodynamic effects after a single event dose of treprostinil.”¹⁰¹ These studies demonstrated that the administration of inhaled treprostinil sodium reduced PVR for a period of time.¹⁰² Therefore, the district court interpreted “therapeutically effective” as a situation where “a single event dose [] improves a patient’s hemodynamics.”¹⁰³

Contrarily, the defendant’s expert viewed “therapeutically effective” as a situation where “a single event dose [] causes an ‘improvement in symptoms, in function, and/or in survival.’”¹⁰⁴ That is, the defendant’s version of “therapeutically effective” focuses on a PH patient’s recovery. Although not explaining why it disagreed with the defendant’s expert, the district court indeed mentioned that “[t]he examples in the patent do not report long-term measures like patient survival rate.”¹⁰⁵ This statement indicates that the defendant’s expert testimony was unsupported by the specification.

The district court’s reasoning may reflect some strategy for patent drafting of a medical treatment invention to avoid importing safety and efficacy requirements into a treatment claim. That is, a specification supporting a treatment claim should disclose and emphasize how the claimed treatment improves biological data related to the targeted disease (such as here hemodynamic data) rather than symptoms, functions, or survival rates of targeted subjects.

Finally, it is unclear why on appeal the defendant did not allege that the district court erred in its claim construction of “therapeutically effective.” Without the defendant’s challenge to the district court’s interpretation of “therapeutically effective,” the Federal Circuit was then silent on whether the specification truly limits the meaning of “therapeutically effective” to an improvement of a patient’s hemodynamics.¹⁰⁶

CONCLUSION

Under United Therapeutics, a treatment claim without reciting a safety or efficacy limitation is generally not construed to include safety and efficacy requirements. United Therapeutics also reaffirms a long-standing principle that the patent authority is not responsible for examining safety or efficacy of a treatment claim. Lastly, from the district court’s claim construction, the United Therapeutics case indicates a strategy of patent drafting where the specification of a treatment patent should focus on how the patented treatment improves targeted subjects’ biological data rather than their symptoms, functions, or survival rates.