United Therapeutics Corporation v. Liquidia Technologies, Inc. ( 2023 )

Case: 22-2217 Document: 61 Page: 1 Filed: 07/24/2023
United States Court of Appeals
for the Federal Circuit
______________________
UNITED THERAPEUTICS CORPORATION,
Plaintiff-Cross-Appellant
v.
LIQUIDIA TECHNOLOGIES, INC.,
Defendant-Appellant
______________________
2022-2217, 2023-1021
______________________
Appeals from the United States District Court for the
District of Delaware in No. 1:20-cv-00755-RGA-JLH, Judge
Richard G. Andrews.
______________________
Decided: July 24, 2023
______________________
SANYA SUKDUANG, Cooley LLP, Washington, DC, ar-
gued for defendant-appellant. Also represented by
JONATHAN DAVIES; DEEPA KANNAPPAN, Palo Alto, CA; ERIK
BENTON MILCH, Reston, VA.
WILLIAM M. JAY, Goodwin Procter LLP, Washington,
DC, argued for plaintiff-cross-appellant. Also represented
by WILLIAM COVINGTON JACKSON, JAIME SANTOS,
ROHINIYURIE TASHIMA, JENNY J. ZHANG; GERARD JUSTIN
CEDRONE, Boston, MA; ADAM WILLIAM BURROWBRIDGE.
McDermott Will & Emery, LLP, Washington, DC;
DOUGLAS H. CARSTEN, ARTHUR PAUL DYKHUIS, Irvine, CA;
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2 UNITED THERAPEUTICS CORPORATION v.
LIQUIDIA TECHNOLOGIES, INC.
SHAUN R. SNADER, United Therapeutics Corporation,
Washington, DC.
______________________
Before LOURIE, DYK, and STOLL, Circuit Judges.
LOURIE, Circuit Judge.
Liquidia Technologies, Inc. (“Liquidia”) appeals from a
decision of the United States District Court for the District
of Delaware holding that (1) claims 1, 4, and 6–8 of U.S.
Patent 10,716,793 (“the ’793 patent”) are not invalid and
are infringed by Liquidia and (2) claims 1–3 of U.S. Patent
9,593,066 (“the ’066 patent”) are invalid as anticipated, but
are otherwise infringed by Liquidia. United Therapeutics
Corporation (“United Therapeutics”) cross-appeals from
the court’s decision holding that (1) claims 1–3, 6, and 9 of
the ’066 patent are invalid as anticipated and (2) claims 6,
8, and 9 of the ’066 patent are not infringed by Liquidia.
See United Therapeutics Corp. v. Liquidia Techs., Inc., 624
F. Supp. 3d 436 (D. Del. 2022) (“Decision”). For the reasons
provided below, we affirm.
BACKGROUND
United Therapeutics holds New Drug Application
(“NDA”) No. 022387 for Tyvaso®, an inhaled solution for-
mulation of treprostinil approved for the treatment of pul-
monary hypertension (“PH”). Pulmonary hypertension is a
potentially life-threatening condition characterized gener-
ally by abnormally high blood pressure in the lungs. For
many patients, treprostinil is used in treating pulmonary
hypertension because it is a vasodilator that reduces vaso-
constriction in the pulmonary vasculature, thereby de-
creasing blood pressure.
Experts consider that there are five subgroups of pul-
monary hypertension: Group 1, pulmonary arterial hyper-
tension (“PAH”); Group 2, pulmonary venous hypertension,
i.e., pulmonary hypertension related to left-heart disease;
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Group 3, pulmonary hypertension associated with disor-
ders damaging the lungs; Group 4, pulmonary hyperten-
sion 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. Groups 1, 3, 4, and 5 are
caused by conditions affecting the pulmonary arteries or
precapillary vessels of the lungs (“precapillary PH”), while
Group 2 typically develops as a result of a cardiac-based
etiology (“postcapillary PH”). Due to differing etiologies,
each group may require group-specific treatment.
United Therapeutics owns the ’793 and ’066 patents,
which are generally directed to methods of treating pulmo-
nary hypertension and to pharmaceutical compositions
comprising treprostinil. The ’793 and ’066 patents are
listed in the FDA’s Orange Book for Tyvaso.
Liquidia filed NDA No. 213005 for Yutrepia™ under
§ 505(b)(2) of the Food, Drug, and Cosmetic Act (codified at
21 U.S.C. § 355(b)(2)). 1 Yutrepia is a dry powder
1 Under the Drug Price Competition and Patent
Term Restoration Act of 1984 (the Hatch-Waxman amend-
ments to the Food, Drug, and Cosmetic Act), an NDA filed
under § 505(b)(2) contains full reports of investigations of
safety and effectiveness, where at least some of the infor-
mation used for approval comes from studies that were not
conducted for or by the applicant. Such an NDA is one of
two abbreviated approval pathways introduced by the
Hatch-Waxman amendments, the other being an abbrevi-
ated new drug application (“ANDA”) filed under § 505(j)
(codified at 21 U.S.C. § 355(j)). 35 U.S.C. § 271(e)(2), the
statutory provision delineating acts of infringement, covers
both types of applications: “It shall be an act of infringe-
ment to submit . . . an application under section 505(j) of
the Federal Food, Drug, and Cosmetic Act or described in
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4 UNITED THERAPEUTICS CORPORATION v.
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inhalation formulation of treprostinil but is not a generic
version of any currently marketed drug. Pursuant to §
505(c)(3)(C) (codified at 21 U.S.C. § 355(c)(3)(C)), United
Therapeutics sued Liquidia within 45 days of receipt of no-
tice of Liquidia’s NDA in the United States District Court
for the District of Delaware alleging infringement of the
’066 patent. J.A. 171, 190. In addition, after Liquidia filed
its NDA, United Therapeutics filed another patent applica-
tion that eventually issued as the ’793 patent, which was
subsequently added to the district court litigation. J.A.
208.
In parallel, Liquidia filed a petition for inter partes re-
view (“IPR”) of the ’793 patent, alleging that all claims
would have been unpatentable as obvious over prior art at
the time of the invention. On July 19, 2022, the Board is-
sued a Final Written Decision finding all claims of the ’793
patent unpatentable as obvious. Liquidia Techs., Inc. v.
United Therapeutics Corp., No. IPR2021-00406, 2022 WL
2820717 (P.T.A.B. July 19, 2022). United Therapeutics
filed a Request for Rehearing, challenging whether various
asserted references qualified as prior art. J.A. 36648. In
its Rehearing Decision, the Board found that the references
were prior art, again holding the claims of the ’793 patent
unpatentable as obvious. United Therapeutics filed a No-
tice of Appeal in that case on April 26, 2023. Liquidia filed
a motion for expedited appeal, which has been denied. The
appeal is currently pending in this court.
I. The ’793 Patent
The ’793 patent is directed to a method of treating pul-
monary hypertension comprising inhalation of treprostinil.
Asserted claim 1 of the ’793 patent is the only independent
claim and reads as follows:
section 505(b)(2) of such Act for a drug claimed in a patent
or the use of which is claimed in a patent[.]”
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1. A method of treating pulmonary hyper-
tension comprising administering by inhala-
tion to a human suffering from pulmonary
hypertension a therapeutically effective sin-
gle 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 pharmaceu-
tically acceptable salt thereof delivered in 1 to
3 breaths.
’793 patent at col. 18 ll. 23–31.
The additional asserted dependent claims include lim-
itations directed to dry powder inhalers (claim 4), powder
formulations (claim 6), powder formulations comprising
particles less than 5 micrometers in diameter (claim 7), and
formulations containing no metacresol (claim 8). See id. col.
18 ll. 36–37, 40–45.
In the district court, United Therapeutics argued that,
although Liquidia’s proposed product had not yet been
marketed, when marketed, it (1) would directly infringe
claims 1, 4, and 6–8 of the ’793 patent and (2) would also
induce infringement of those claims. Liquidia responded
that the asserted claims were invalid as lacking adequate
enablement and written description under 35 U.S.C. § 112.
The district court found that United Therapeutics
showed that a single administration of treprostinil, as re-
quired by claim 1, improves a patient’s hemodynamics, es-
tablishing that administration of Liquidia’s Yutrepia,
comprising treprostinil, at the claimed doses will also im-
prove a patient’s hemodynamics. The court concluded that
United Therapeutics thus proved by a preponderance of the
evidence that the administration of Yutrepia will directly
infringe claims 1, 4, and 6–8 of the ’793 patent.
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The district court also concluded that Liquidia’s argu-
ment that it lacked specific intent to induce infringement
lacked merit. Liquidia argued that, because the Yutrepia
label does not encourage administration of a therapeuti-
cally effective single event dose, it does not induce infringe-
ment. The court noted that the label does not need to
provide hemodynamic data to constitute inducement of in-
fringement; instead, it merely needs to instruct doctors and
patients to administer a therapeutically effective single
event dose. The court found that the label’s instructions
will inevitably lead to the administration of a therapeuti-
cally effective single event dose. The court thus concluded
that United Therapeutics proved by a preponderance of the
evidence that Liquidia will induce infringement of claims
1, 4, and 6–8 of the ’793 patent.
The district court further found that the asserted
claims were not invalid for lack of enablement or written
description. First, the court construed “treating pulmo-
nary hypertension” as encompassing all five groups of pul-
monary hypertension, noting that the specification of
the ’793 patent expressly includes all five groups when de-
scribing “pulmonary hypertension.” Second, the court
found that a skilled artisan would not need to engage in
undue experimentation to practice the full scope of the
claimed treatment of pulmonary hypertension, despite po-
tential safety concerns in treating Group 2 PH patients,
and that the claims did not require safety and efficacy.
Third, the court found that the claims were not invalid for
lack of written description, finding that a skilled artisan
would, based on the specification, understand that trepros-
tinil would effectively vasodilate the pulmonary vascula-
ture, improve hemodynamics, and treat a patient’s
elevated pulmonary blood pressure. As a result of the
court’s findings that the claims were not invalid but were
infringed, the court stayed approval of Liquidia’s NDA for
Yutrepia until May 5, 2027, the expiration date of the ’793
patent.
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II. The ’066 Patent
The ’066 patent is directed to a pharmaceutical compo-
sition comprising treprostinil and a process of preparing a
pharmaceutical product comprising treprostinil.
Asserted claim 1 of the ’066 patent reads as follows:
1. A pharmaceutical composition compris-
ing treprostinil or a pharmaceutically ac-
ceptable salt thereof, said composition
prepared by a process comprising providing a
starting batch of treprostinil having one or
more impurities resulting from prior alkyla-
tion and hydrolysis steps, forming a salt of
treprostinil by combining the starting batch
and a base, isolating the treprostinil salt, and
preparing a pharmaceutical composition com-
prising treprostinil or a pharmaceutically ac-
ceptable salt thereof from the isolated
treprostinil salt, whereby a level of one or
more impurities found in the starting batch of
the treprostinil is lower in the pharmaceutical
composition, and wherein said alkylation is
alkylation of benzindene triol.
’066 patent at col. 17 ll. 51–63.
Asserted claim 6 of the ’066 patent reads:
6. The pharmaceutical composition of
claim 1, wherein the isolated salt is stored at
ambient temperature.
Id. col. 18 ll. 34–35.
Asserted claim 8 of the ’066 patent reads:
8. A process of preparing a pharmaceutical
product comprising treprostinil or a pharma-
ceutically acceptable salt thereof, comprising
alkylating a triol intermediate of the formula:
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hydrolyzing the resulting compound to form
treprostinil, forming a salt of treprostinil sta-
ble at ambient temperature, storing the
treprostinil salt at ambient temperature, and
preparing a pharmaceutical product from the
treprostinil salt after storage, wherein the
pharmaceutical product comprises treprosti-
nil or a pharmaceutically acceptable salt
thereof.
Id. col. 18 ll. 38–61.
Additional asserted dependent claims are directed to
crystalline forms (claim 2), a base selected from the group
consisting of sodium, ammonia, potassium, calcium, etha-
nolamine, diethanolamine, N-methylglucamine, and cho-
line (claim 3), and a pharmaceutical product prepared by
the process recited in claim 8 (claim 9). See id. col. 17 ll.
64–67; col. 18 ll. 27–28, 62–63.
In the district court, United Therapeutics argued that
Liquidia infringed claims 1–3, 6, 8, and 9 of the ’066 patent.
Liquidia responded that claims 1–3, 6, and 9 were invalid
as anticipated by Moriarty 2 and that claims 1–3 and 6 were
invalid as lacking written description support. Liquidia did
not challenge the validity of claim 8, which is a chemical
2 R.M. Moriarty et al., The Intramolecular Asymmet-
ric Pauson-Khand Cyclization as a Novel and General Ste-
reoselective Route to Benzindene Prostacyclins: Synthesis of
UT-15 (Treprostinil), 69 J. ORGANIC CHEM. 1890 (2004).
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process claim, in contrast to the other claims that are di-
rected to compositions.
The district court found that United Therapeutics
showed by a preponderance of the evidence that Liquidia’s
Yutrepia would infringe claims 1–3 of the ’066 patent be-
cause Yutrepia met the impurities limitations of claim 1.
But the court also found that claims 1–3, 6, and 9 were in-
valid as anticipated by Moriarty. Moriarty discloses the
synthesis of analogues of benzindene prostacyclins, includ-
ing treprostinil, which is designated in the publication as
UT-15. Moriarty at 1890, 1892. The court also found that
Liquidia showed by clear and convincing evidence that the
claimed treprostinil product is functionally and structur-
ally the same as the UT-15 treprostinil disclosed in Mori-
arty. The court thus concluded that claims 1–3 would have
been infringed by Liquidia, but for the finding of anticipa-
tion, and that claims 6 and 9 were invalid as anticipated by
Moriarty but not infringed by Liquidia.
In finding a lack of infringement of claim 6, the court
construed the terms “ambient temperature” as room tem-
perature (equal to or less than the range of 15°C to 30°C)
and “stored”/“storing”/“storage” to have its plain and ordi-
nary meaning. Using these constructions, the court deter-
mined that United Therapeutics failed to show by a
preponderance of the evidence that Liquidia’s Yutrepia
production process stored treprostinil at ambient tempera-
ture, and therefore found that claims 6, 8, and 9 were not
infringed. The court further found that any storage be-
tween steps of Liquidia’s manufacturing process did not
meet the limitations of claims 8 and 9, which require stor-
age of treprostinil before preparing a pharmaceutical prod-
uct.
The district court also found that the specification pro-
vided adequate written description support for the impuri-
ties limitation in claim 1, and that a skilled artisan would
understand that the inventors were in possession of the
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composition with the claimed impurities. The court thus
concluded that Liquidia did not prove by clear and convinc-
ing evidence that claims 1–3 and 6 of the ’066 patent were
invalid for lack of written description.
In summary, the district court concluded that (1)
claims 1, 4, and 6–8 of the ’793 patent were not invalid and
were infringed by Liquidia; (2) claims 1–3 of the ’066 patent
were invalid as anticipated by Moriarty and would have
been infringed by Liquidia but for the finding of anticipa-
tion; (3) claims 6 and 9 of the ’066 patent were invalid as
anticipated by Moriarty and not infringed by Liquidia; and
(4) claim 8 of the ’066 patent was not invalid and not in-
fringed by Liquidia. Liquidia appealed, and United Ther-
apeutics cross-appealed. We have jurisdiction under 28
U.S.C. § 1295(a)(1).
DISCUSSION
Liquidia raises five issues on appeal. First, Liquidia
contends 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.
Second, Liquidia argues that the court erred in finding the
asserted claims of the ’793 patent enabled. Third, Liquidia
contends that the court clearly erred in finding the asserted
claims of the ’793 patent supported by written description.
Fourth, Liquidia contends that the court clearly erred in
finding Liquidia liable for induced infringement of claims
1, 4, and 6–8 of the ’793 patent. Fifth, Liquidia argues that
the court clearly erred in finding claims 1–3 of the ’066 pa-
tent to be infringed.
United Therapeutics raises two issues on cross-appeal.
First, United Therapeutics asserts that the district court
clearly erred in finding that Liquidia does not infringe
claims 6 and 8 of the ’066 patent. Second, United Thera-
peutics contends that the court clearly erred in finding that
claims 1–3, 6, and 9 of the ’066 patent are invalid as
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anticipated by Moriarty. We address each appeal and
cross-appeal argument in turn.
Infringement is a question of fact that we review, after
a bench trial, for clear error. Eli Lilly & Co. v. Teva Paren-
teral Meds., Inc., 845 F.3d 1357, 1364 (Fed. Cir. 2017). A
patent is directly infringed when a person “without author-
ity makes, uses, offers to sell, or sells any patented inven-
tion, within the United States or imports into the United
States any patented invention during the term of the pa-
tent.” 35 U.S.C. § 271(a). “Whoever actively induces in-
fringement of a patent shall be liable as an infringer.” Id.§ 271(b).
We review district court findings of anticipation under
35 U.S.C. § 102 and satisfaction of the written description
requirement under 35 U.S.C. § 112 for clear error. Nuvo
Pharms. (Ir.) Designated Activity Co. v. Dr. Reddy’s Lab’ys
Inc., 923 F.3d 1368, 1376 (Fed. Cir. 2019) (written descrip-
tion); Forest Lab’ys, Inc. v. Ivax Pharms., Inc., 501 F.3d
1263, 1268 (Fed. Cir. 2007) (anticipation). Enablement “is
a question of law” that we review de novo after a bench trial.
Auto. Techs. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d
1274, 1281 (Fed. Cir. 2007). We review questions of claim
construction de novo but review any underlying facts for
clear error. Markman v. Westview Instruments, Inc., 52
F.3d 967, 979, 991 (Fed. Cir. 1995); Eli Lilly & Co. v. Hos-
pira, Inc., 933 F.3d 1320, 1328 (Fed. Cir. 2019).
I. The ’793 Patent
A.
We first consider Liquidia’s challenge to the district
court’s determination that the meaning of “treating pulmo-
nary hypertension” does not require a showing of safety
and efficacy. It asserts that a skilled artisan would under-
stand the plain and ordinary meaning of “treating pulmo-
nary hypertension” to encompass a method that
accomplishes that goal safely and effectively. It asserts
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that the parties’ experts agreed that treatment with
treprostinil, a vascular dilator, would not benefit Group 2
PH patients. It further asserts that while the specification
of the ’793 patent states that the treatment does not result
in significant side effects, ’793 patent at col. 5 ll. 16–20, and
that administration of treprostinil is safe, id. col. 9 ll. 30–
31, its expert testified that a skilled artisan would have
concerns about administering inhaled treprostinil to Group
2 PH patients and that at least one earlier study, in which
a treprostinil-like prostacyclin was administered to Group
2 PH patients, failed due to increased mortality.
United Therapeutics responds that the district court
did not err in finding that the claimed administration of
treprostinil would improve hemodynamics and hence treat
a patient’s elevated pulmonary blood pressure, including
Group 2 PH patients. It asserts that Liquidia attempts to
import limitations into the claims and that nothing in the
specification requires the importation of safety and efficacy
limitations into the claims. Finally, United Therapeutics
asserts that while Liquidia’s statements that a skilled ar-
tisan would have safety concerns in treating Group 2 PH
patients with treprostinil may factor into Food and Drug
Administration (“FDA”) approval, they do not factor into
claim interpretation.
As a threshold matter, we agree with the district court
that “treating pulmonary hypertension” includes treating
all five groups of pulmonary hypertension patients. The
court did not err in finding that the specification encom-
passes all five groups when describing “pulmonary hyper-
tension.” In fact, the specification does not limit the scope
of “pulmonary hypertension” to any particular subset of
pulmonary hypertension patients. It refers to both “preca-
pillary pulmonary hypertension” and “pulmonary hyper-
tension,” which, as the court found, demonstrates that the
inventors view precapillary PH only as a subset of the
broadly claimed “pulmonary hypertension.” Thus, “treat-
ing pulmonary hypertension” includes treating all five
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groups of pulmonary hypertension. See ’793 patent at col.
9 ll. 36–37, col. 12 ll. 64–65, col. 16 ll. 64–65.
While the claims require “treating pulmonary hyper-
tension comprising administering . . . a therapeutically ef-
fective single event dose of a formulation comprising
treprostinil,” Decision, at 467, the district court gave the
phrase “therapeutically effective” a limiting construction.
The district court held, and Liquidia does not challenge on
appeal, that a person of ordinary skill in the art “would un-
derstand the plain and ordinary meaning of ‘therapeuti-
cally effective single dose’ to be a dose given in a single
treatment session that causes an improvement in a pa-
tient’s hemodynamics (reduced PAP or PVR).” Id. at 461;
Appellee’s Br. 39. We need not address whether the district
court’s construction was correct because Liquidia, on ap-
peal, does not challenge that construction. Read in context,
the claim language “treating pulmonary hypertension”
does not import any additional efficacy limitations or any
safety limitations.
Absent incorporation of safety and efficacy require-
ments in the claims, Liquidia’s argument concerning the
safety and efficacy of treating Group 2 PH patients is not
before us. Questions of safety and efficacy in patent law
have long fallen under the purview of the FDA. In re Brana,
51 F.3d 1560, 1567 (Fed. Cir. 1995) (noting that “the re-
quirements under the law for obtaining a patent” are dif-
ferent from “the requirements for obtaining government
approval to market a particular drug for human consump-
tion”); Scott v. Finney, 34 F.3d 1058, 1063 (Fed. Cir. 1994)
(“Testing for the full safety and effectiveness . . . is more
properly left to the [FDA]. Title 35 does not demand that
such human testing occur within the confines of Patent and
Trademark Office (PTO) proceedings.”); In re Anthony, 414
F.2d 1383, 1395 (CCPA 1969) (“Congress has given the re-
sponsibility to the FDA, not to the Patent Office, to deter-
mine in the first instance whether drugs are sufficiently
safe for use that they can be introduced in the commercial
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market . . . .”). We decline to insert the FDA’s responsibil-
ities into claims by importing requirements where they do
not recite such limitations.
B.
We next turn to Liquidia’s challenge to the district
court’s finding that the claims of the ’793 patent are ade-
quately enabled and supported by written description.
Liquidia argues that the specification of the ’793 patent
provides no guidance or examples of treating Group 2 PH
patients, and thus that a skilled artisan would have to en-
gage in undue experimentation to practice the full scope of
the claimed invention (i.e., treating Group 2 PH patients).
Liquidia further argues that, even if the district court’s
construction of “treating pulmonary hypertension” as not
requiring safety was proper, the claims of the ’793 patent
would still not be enabled because any changes in hemody-
namics caused by inhalation of treprostinil would provide
no benefit to Group 2 PH patients. Thus, a skilled artisan
would not conclude that the ’793 patent claims are enabled
to the full scope of the claimed invention.
United Therapeutics responds that the district court
did not err in concluding that Liquidia failed to show a lack
of enablement. It contends that Liquidia failed to show by
clear and convincing evidence that enablement would re-
quire undue experimentation with respect to Group 2 PH.
Further, even if the specification fails to describe how
to treat Group 2 PH patients with treprostinil, United
Therapeutics asserts, claims are not required to carve out
all possible inoperative embodiments in a claim in order to
avoid that claim being found not to be enabled. United
Therapeutics asserts that if a skilled artisan has the infor-
mation to limit the claims to operative embodiments, then
the claims are not invalid. Here, United Therapeutics as-
serts, the skilled artisan has that information.
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Liquidia also challenges the district court’s finding that
the claims are supported by an adequate written descrip-
tion. Liquidia argues that the ’793 patent never describes
treating Group 2 PH patients with inhaled treprostinil, but
only Group 1, 3, and 4 patients, all of whom have precapil-
lary PH. Thus, Liquidia contends, there is no information
in the ’793 patent specification sufficient for a skilled arti-
san to conclude that the inventors were in possession of a
method of treating Group 2 PH patients with inhaled
treprostinil.
Liquidia further argues that, even if the district court
correctly construed “treating pulmonary hypertension” not
to require a showing of safety, the claims still are not sup-
ported by written description because vasodilation of the
pulmonary vasculature is not effective in treating Group 2
PH patients. Thus, Liquidia contends, a skilled artisan
would have understood that the inventors did not invent or
possess a method of treating Group 2 PH patients.
United Therapeutics responds that the district court
did not clearly err in finding the claims of the ’793 patent
supported by an adequate written description. United
Therapeutics argues that Liquidia’s written description ar-
guments fail for largely the same reasons as its enablement
arguments. In particular, United Therapeutics asserts
that the court did not err in holding that a skilled artisan
would understand a therapeutically effective dose to be one
that improves a patient’s hemodynamics. United Thera-
peutics further contends that, although a physician may or
may not decide to administer treprostinil to a Group 2 PH
patient, that decision would be informed by FDA guidance,
not the written description in the specification.
We agree with United Therapeutics that the claims are
adequately enabled as they were construed by the district
court. The specification of the ’793 patent sufficiently ena-
bles the scope of the claims. See, e.g., ’793 patent at col. 7
ll. 7–67 (providing details on administration,
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concentrations, and dosages of inhaled treprostinil for
treating patients with pulmonary hypertension); id. col. 9
ll. 5–49 (describing an open label study upon acute safety,
tolerability, and hemodynamic effects of inhaled treprosti-
nil delivered over the course of a few seconds). While the
court credited expert testimony concluding that a physi-
cian may have safety concerns in treating Group 2 PH pa-
tients with treprostinil and other vasodilators, see Decision,
at 466–67, the court also found that the record demon-
strates that the claimed administration of treprostinil vas-
odilates the pulmonary vasculature and reduces
pulmonary blood pressure even in Group 2 PH patients, id.
at 468. The court properly relied on expert testimony and
record evidence to conclude that a skilled artisan would un-
derstand that the claimed administration of treprostinil
would vasodilate the pulmonary vasculature, improve he-
modynamics, and in this way for a single dose, treat a pa-
tient’s elevated pulmonary blood pressure independent of
the type (i.e., group) of pulmonary hypertension patient. Id.
That was all that the claims require under the district
court’s construction because, again, the parties do not dis-
pute that a “therapeutically effective single event dose” is
defined by “an improvement in a patient’s hemodynamics
(reduced PAP or PVP).” That a study—administering
treprostinil-like prostacyclins to Group 2 PH patients—
failed due to increased mortality, yet showed “improve-
ment in a patient’s hemodynamics,” may be an issue for the
FDA. But our focus is on the claimed invention. And on
this record, with the district court’s claim construction, the
claims are adequately enabled.
We also agree with United Therapeutics that the dis-
trict court did not clearly err in finding that the claims of
the ’793 patent are supported by an adequate written de-
scription. Written description requires that the specifica-
tion reasonably convey to those skilled in the art that the
inventor had possession of the claimed invention as of the
filing date. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d
Case: 22-2217 Document: 61 Page: 17 Filed: 07/24/2023
UNITED THERAPEUTICS CORPORATION v. 17
LIQUIDIA TECHNOLOGIES, INC.
1336, 1351 (Fed. Cir. 2010) (en banc). As the court noted,
the ’793 patent claims require “treating pulmonary hyper-
tension comprising administering . . . a therapeutically ef-
fective single event dose of a formulation containing
treprostinil,” Decision, at 466–67, and the specification de-
scribes that. In other words, the specification shows pos-
session for the claimed invention under the district court’s
construction.
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 analogizing a subset of
patients having a variant of a particular disease to tradi-
tional genus and species claims is inapt. It would be incor-
rect 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 hy-
pertension 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.
Again, because safety and efficacy are not recited in the
claims, we need not deal with Liquidia’s arguments. Dis-
ease-specific treatment requirements are matters for the
FDA and medical practitioners. They are best suited to
make these determinations because practitioners are in-
formed by the findings of the regulatory agency to avoid
treatment of patients who will not properly respond. And
every claim to a method of treatment of an ailment has re-
finements. That is, for any given method of treatment
claim, there may be a subset of patients who would not ben-
efit from or should not take the claimed treatment. See
Oral Arg. at 4:28–4:58, https://oralargu-
ments.cafc.uscourts.gov/default.aspx?fl=22-2217_0503202
3.mp3. That does not mean that such claims are not suffi-
ciently enabled or supported by written description. A sub-
set of unresponsive patients is not analogous to
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18 UNITED THERAPEUTICS CORPORATION v.
LIQUIDIA TECHNOLOGIES, INC.
unsupported species in a generic claim to chemical com-
pounds.
C.
We next turn to Liquidia’s challenge to the district
court’s finding that Liquidia was liable for induced in-
fringement. Liquidia argues that it cannot be held liable
for induced infringement because the ’793 patent was
found to be unpatentable in an IPR, and an unpatentable
or invalid patent cannot be infringed. To support this as-
sertion, Liquidia cites Commil USA, LLC v. Cisco Systems,
Inc., 575 U.S. 632, 644 (2015) (stating that if “an act that
would have been . . . an inducement to infringe pertains to
a patent that is shown to be invalid, there is no patent to
be infringed”). Liquidia contends that Commil should be
read as stating that knowledge of actual unpatentability
determined in an IPR precludes having the necessary in-
tent to induce infringement.
United Therapeutics responds that the Board’s deci-
sion on the ’793 patent is not final, and a non-final Board
decision does not defeat Liquidia’s liability for inducing in-
fringement of the ’793 patent. United Therapeutics con-
tends that unpatentability is relevant to infringement
liability only once a final adjudication of unpatentability or
invalidity rules that there is no such patent to infringe.
We agree with United Therapeutics that the district
court did not clearly err in finding that Liquidia induced
infringement of the ’793 patent. The court did not clearly
err in finding that the label on Yutrepia, Liquidia’s product,
does not need to provide hemodynamic data to constitute
inducement of infringement; it merely needs to instruct
doctors and patients to administer a therapeutically effec-
tive single event dose, which it does. Decision, at 462–63.
The court also did not clearly err in concluding that United
Therapeutics proved that a single administration of Yutre-
pia will be therapeutically effective, as required by the
claims of the ’793 patent and constituting inducement.
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UNITED THERAPEUTICS CORPORATION v. 19
LIQUIDIA TECHNOLOGIES, INC.
Liquidia’s reliance on Commil, 575 U.S. at 632, re-
quires the ’793 patent to have been invalidated, but as
United Therapeutics argues, the corresponding IPR pro-
ceeding of the ’793 patent is pending on appeal in this court.
A pending, non-final litigation does not negate an intent to
infringe that is otherwise supported by evidence. 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. XY, LLC v. Trans
Ova Genetics, L.C., 890 F.3d 1282, 1294 (Fed. Cir. 2018)
(“[A]n affirmance of an invalidity finding, whether from a
district court or the Board, has a collateral estoppel effect
on all pending or co-pending actions.”). Further, as the
court noted, the Board’s final written decision does not can-
cel claims; the claims are cancelled when the Director is-
sues a certificate confirming unpatentability, which occurs
only after “the time for appeal has expired or any appeal
has terminated.” 35 U.S.C. § 318(b). The ’793 IPR decision
thus has no impact here on a finding of induced infringe-
ment.
II. The ’066 Patent
A.
We next turn to Liquidia’s assertion on appeal that the
district court clearly erred in finding that it infringed
claims 1–3 of the ’066 patent. Liquidia argues that United
Therapeutics failed to meet its burden of proving infringe-
ment. In particular, Liquidia argues that United Thera-
peutics identified the starting batch as the treprostinil salt
and the pharmaceutical composition as the bulk powder.
Liquidia thus contends that a comparison between the im-
purities in the treprostinil salt and bulk powder would
have been required to establish infringement of claims that
require a lowering of impurities.
United Therapeutics responds that the district court
did not clearly err in finding that Liquidia infringed claims
1–3 of the ’066 patent. United Therapeutics contends that
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20 UNITED THERAPEUTICS CORPORATION v.
LIQUIDIA TECHNOLOGIES, INC.
the court based its conclusion on well-supported facts in
finding that a skilled artisan would understand the rele-
vant impurities to be those generated during the alkylation
and hydrolysis steps used to create the starting batch of
treprostinil.
We need not evaluate this argument that claims 1–3 of
the ’066 patent are not infringed, because Liquidia cor-
rectly argues that the district court did not clearly err in
finding those claims invalid as anticipated by Moriarty.
See Part II.B. Because unpatentable or invalid claims can-
not be infringed, Commil, 575 U.S. at 644 (“To say that an
invalid patent cannot be infringed . . . is in one sense a sim-
ple truth, both as a matter of logic and semantics.”), the
issue of infringement of claims 1–3 of the ’066 patent has
been rendered moot.
B.
Accordingly, we forthwith turn to United Therapeutics’
argument on cross-appeal concerning the validity of claims
1–3. United Therapeutics argues that Moriarty does not
teach the purification of treprostinil through salt formation
and discloses no information on specific alkylation and hy-
drolysis impurities. United Therapeutics argues that it
added the relevant impurities claim language to overcome
validity challenges raised during prosecution, and the
court failed to recognize the structural features that are
imparted by the claimed salt-formation purification.
United Therapeutics further contends that Moriarty dis-
closes treprostinil with a purity of 99.7%, which does not
establish that the product of Moriarty had the same level
of alkylation or hydrolysis impurities of the claimed prod-
uct.
Liquidia responds that the district court did not err in
finding that claims 1–3, 6, and 9 of the ’066 patent are an-
ticipated by Moriarty. Liquidia argues that the claimed
composition in Moriarty is the same as the claimed
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UNITED THERAPEUTICS CORPORATION v. 21
LIQUIDIA TECHNOLOGIES, INC.
composition in the ’066 patent, and that United Therapeu-
tics demonstrated no clear error in the court’s findings.
We agree with Liquidia that the district court did not
clearly err in finding that claims 1–3, 6, and 9 are invalid
as anticipated by Moriarty. The claims of the ’066 patent
are directed to a pharmaceutical composition comprising,
inter alia, treprostinil, prepared by alkylation and hydrol-
ysis steps. It is thus referred to as a product-by-process
claim. But a product-by-process claim is a product claim,
even if claimed by a process by which it can be made. The
claims also recite the presence of impurities.
We conclude that the district court did not clearly err
in finding that these claims are anticipated by the Moriarty
reference, which discloses treprostinil with impurities.
The specification of the ’066 patent discloses an impurity
level of 99.7%–99.9%, ’066 patent col. 14, table, whereas
Moriarty similarly discloses the synthesis of impure
treprostinil, designated in the publication as UT-15, hav-
ing 99.7% purity, Moriarty at 1890, 1892, 1902. As these
claims are product claims, they are anticipated by a disclo-
sure of the same product irrespective of the processes by
which they are made. Further, United Therapeutics did
not provide any expert or fact witness rebutting Liquidia’s
expert’s opinions or providing testimony identifying any
structural or functional differences between the Moriarty
treprostinil and the claimed treprostinil. Decision, at 456.
The court thus did not err in finding that claims 1–3, 6, and
9 of the ’066 patent are anticipated by Moriarty.
C.
United Therapeutics also argues on cross-appeal that
the district court clearly erred in finding that Liquidia does
not infringe claims 6 and 8 of the ’066 patent. United Ther-
apeutics contends that claims 6 and 8 require that the
treprostinil salt be stored at ambient temperature, and
that Liquidia stores treprostinil salt at ambient tempera-
ture during production, thus infringing the claims. United
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22 UNITED THERAPEUTICS CORPORATION v.
LIQUIDIA TECHNOLOGIES, INC.
Therapeutics contends that Liquidia’s promise not to make
its product with batches of treprostinil salt that were
stored at ambient temperature is insufficient to avoid a
finding of infringement.
United Therapeutics also contends that the district
court erred in construing the term “storage” in claims 6 and
8 as excluding storage during manufacturing but including
storage during shipment of the product. United Therapeu-
tics further contends that Liquidia also infringes claim 8
through ambient storage that occurs after the composition
recited in claims 1–6 is prepared and before the drug prod-
uct of claim 8 is prepared.
Liquidia responds that the district court did not clearly
err in finding that it does not infringe claims 6 and 8 of the
’066 patent. In particular, Liquidia notes that the court
based its findings of non-infringement on several clear
findings of fact, including that (1) Liquidia’s NDA requires
the treprostinil salt to be stored at a temperature of 2–8°C;
(2) Liquidia asserted that it would not use treprostinil salt
batches that have been stored at ambient temperature; and
(3) Liquidia begins preparing a pharmaceutical product
during step 1 of its production process. Liquidia further
asserts that the NDA storage specifications are regulatory
requirements, not mere recommendations or promises.
Liquidia further responds that the district court did not
err in its construction of the term “storage.” Liquidia as-
serts that United Therapeutics mischaracterizes Liquidia’s
production process, and that its production process is a sin-
gle production process, not two stages separated by a pe-
riod of ambient storage.
We agree with Liquidia that the district court did not
clearly err in finding that it does not infringe claims 6 and
8 of the ’066 patent. The court credited Liquidia’s repre-
sentations to the FDA that it would store treprostinil so-
dium between 2°C and 8°C. The court also found that
United Therapeutics provided no evidence showing that
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UNITED THERAPEUTICS CORPORATION v. 23
LIQUIDIA TECHNOLOGIES, INC.
Liquidia used ambient-temperature-stored batches of
treprostinil in its manufacturing process in making a phar-
maceutical composition as required by claim 6 or claim 8.
Without a showing that Liquidia stores treprostinil at am-
bient temperature, there can be no infringement of the
claims.
CONCLUSION
We have considered the parties’ remaining arguments
but find them unpersuasive. For the foregoing reasons, the
decision of the United States District Court for the District
of Delaware is affirmed.
AFFIRMED
COSTS
No costs.