Court Opinion

ID: 4381862
Source: CourtListenerOpinion
Date Created: 2019-03-28 16:00:59.329894+00
Date Added: 2024-06-11T12:04:21.949815
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
                ______________________

         ENDO PHARMACEUTICALS INC.,
               Plaintiff-Appellant

               MALLINCKRODT LLC,
                     Plaintiff

                           v.

  TEVA PHARMACEUTICALS USA, INC., BARR
   LABORATORIES, INC., ACTAVIS LLC, FKA
 ACTAVIS INC., ACTAVIS SOUTH ATLANTIC LLC,
     TEVA PHARMACEUTICALS USA, INC.,
               Defendants-Appellees

 ACTAVIS PHARMA, INC., ACTAVIS ELIZABETH
      LLC, ACTAVIS HOLDCO U.S., INC.,
                  Defendants
            ______________________

            2017-1240, 2017-1455, 2017-1887
                ______________________

    Appeals from the United States District Court for the
District of Delaware in Nos. 1:14-cv-01381-RGA, 1:14-cv-
01382-RGA, 1:14-cv-01389-RGA, Judge Richard G. An-
drews.
                 ______________________

                Decided: March 28, 2019
                ______________________
2                ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.

   MARTIN JAY BLACK, Dechert LLP, Philadelphia, PA, ar-
gued for plaintiff-appellant. Also represented by SHARON
K. GAGLIARDI; BLAKE GREENE, Austin, TX; JONATHAN
LOEB, Mountain View, CA; ROBERT RHOAD, Princeton, NJ.

    WILLIAM H. BURGESS, Kirkland & Ellis LLP, Washing-
ton, DC, argued for defendants-appellees Actavis LLC, Ac-
tavis South Atlantic LLC, Teva Pharmaceuticals USA, Inc.
Also represented by JOHN C. O’QUINN; JAMES F. HURST,
Chicago, IL; LESLIE M. SCHMIDT, New York, NY; HOWARD
S. SUH, CHARLES A. WEISS, ERIC H. YECIES, Holland &
Knight, LLP, New York, NY.

    HUIYA WU, Goodwin Procter LLP, New York, NY, for
defendants-appellees Teva Pharmaceuticals USA, Inc.,
Barr Laboratories, Inc.
                ______________________

Before WALLACH, CLEVENGER, and STOLL, Circuit Judges.
STOLL, Circuit Judge.
    Endo Pharmaceuticals Inc. appeals the district court’s
decision holding the claims of U.S. Patent No. 8,808,737 in-
eligible under 35 U.S.C. § 101. See Endo Pharms. Inc. v.
Actavis Inc., No. 14-cv-1381-RGA, 2015 WL 7253674
(D. Del. Nov. 17, 2015) (“District Court Op.”), adopting re-
port and recommendation, 2015 WL 5580488 (D. Del.
Sept. 23, 2015) (“Magistrate Op.”). Because the district
court incorrectly concluded that the claims at issue are di-
rected to a natural law, we reverse.
                        BACKGROUND
                             I
    Endo owns the ’737 patent, entitled “Method of treat-
ing pain utilizing controlled release oxymorphone pharma-
ceutical compositions and instruction on dosing for renal
impairment.” ’737 patent Title. As explained in the
ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.                3

specification, the patent covers a method of using oxy-
morphone to treat pain in patients with impaired kidney
function. Id. at col. 1 ll. 19–32. Controlled-release dosage
forms that maintain optimal levels of pain relief for longer
periods are useful to patients and clinicians. Id. at col. 2
ll. 13–16. Patients’ pain relief levels can be impacted by
the way their body processes oxymorphone. For example,
patients with impaired kidney function, also known as re-
nal impairment, can experience buildup of waste products
and some drugs that are typically filtered out by the kid-
neys. Id. at col. 2 ll. 17–24.
    The inventor of the ’737 patent studied the effect of re-
nal impairment on the pharmacokinetics—including me-
tabolism—of oxymorphone. Id. at col. 27 ll. 60–67. The
’737 patent relates to his discovery that patients with renal
impairment in need of pain relief can be treated in a new,
different way than other patients. Specifically, the inven-
tor discovered that patients with moderately or severely
impaired kidney function need less oxymorphone than
usual to achieve a similar level of pain management.
Id. at col. 10 ll. 15–19. Accordingly, the inventor’s treat-
ment method advantageously allows patients with renal
impairment to ingest less oxymorphone while still treating
their pain. Stated somewhat differently, the inventor de-
veloped a method that allowed renally impaired pain pa-
tients to be treated safely and effectively notwithstanding
their impaired kidney function.
    In technical terms, the inventor found that there was a
statistically significant correlation between plasma AUC1
for oxymorphone and a patient’s degree of renal

    1    “AUC” stands for Area Under the Curve—that is,
the area underneath the concentration versus time curve,
which measures the total amount of drug observed in a pa-
tient’s bloodstream over time since administration of the
drug. AUC is indicative of drug in the body over time.
4                 ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.

impairment, as indicated by their creatinine clearance
rate. 2 Id. at col. 46 ll. 38–40. The subjects were separated
into four groups based on their creatinine clearance rates:
               Group            Creatinine Clearance Rate
    [Healthy] Controls                   > 80 mL/min
    Mild Renal Impairment            51 to 80 mL/min
    Moderate Renal Impairment        30 to 50 mL/min
    Severe Renal Impairment              <30 mL/min

Id. at col. 30 ll. 30–35. These four groups were studied for
their pharmacokinetic responses to oxymorphone as meas-
ured by their AUC levels. There was relatively little
change in oxymorphone AUC until the subjects had moder-
ate-to-severe renal impairment (creatinine clearance rates
below 50 mL/min). Subjects with severe renal impairment
(creatinine clearance rates below 30 mL/min) had the high-
est AUC values. See id. at col. 46 ll. 38–46, col. 30 ll. 30–
35.

     2   Creatinine is a waste byproduct. The kidneys filter
creatinine out of the bloodstream and excrete it in urine. A
patient’s creatinine clearance rate measures how effec-
tively the kidneys are able to remove creatinine, and thus
reflects how well the kidneys are functioning.
ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.                    5

Id. at Fig. 16 (excerpted, annotated). “Because of this, the
oxymorphone levels in the blood of a patient with [] renal
impairment are higher than the levels that would be seen
in a healthy patient receiving the same dose.” Id. at col. 10
ll. 19–22. For example, subjects with severe renal impair-
ment had a mean oxymorphone AUC, on average, 1.7 times
greater than healthy subjects. Id. at col. 46 ll. 25–30.
           Mean Plasma Pharmacokinetic Results
                            Level of renal impairment
 Analyte/Variable                                   Healthy
                      Severe   Moderate      Mild
                                                    controls
 Oxymorphone AUC
                      32.46      27.93     21.68      18.86
    (ng·hr/mL)

Id. at col. 38 Table 33 (excerpted).
     Armed with this discovery, the inventor developed a
new method of using oxymorphone to treat patients with
renal impairment, claimed in the ’737 patent. As the spec-
ification explains, “the present invention provides methods
using oxymorphone in the treatment of pain,” including
“providing a patient [with renal impairment] with a thera-
peutically effective amount of oxymorphone.” Id. at col. 3
ll. 33–36. The specification further explains that the
method “avoid[s] possible issues in dosing” and allows for
treatment with “the lowest available dose” for patients
with renal impairment. Id. at col. 10 ll. 26–27, 41. Claim 1
of the ’737 patent is representative and reads:
    1. A method of treating pain in a renally impaired
    patient, comprising the steps of:
    a. providing a solid oral controlled release dosage
    form, comprising:
        i. about 5 mg to about 80 mg of oxymorphone or
        a pharmaceutically acceptable salt thereof as
        the sole active ingredient; and
        ii. a controlled release matrix;
6                ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.

    b. measuring a creatinine clearance rate of the pa-
    tient and determining it to be
        (a) less than about 30 ml/min,
        (b) about 30 mL/min to about 50 mL/min,
        (c) about 51 mL/min to about 80 mL/min, or
        (d) above about 80 mL/min; and
    c. orally administering to said patient, in depend-
    ence on which creatinine clearance rate is found, a
    lower dosage of the dosage form to provide pain re-
    lief;
    wherein after said administration to said patient,
    the average AUC of oxymorphone over a 12-hour
    period is less than about 21 ng·hr/mL.
Id. at col. 48 ll. 7–26 (emphases added).
                              II
     Endo and Mallinckrodt LLC sued Actavis LLC, Actavis
South Atlantic LLC, Actavis Pharma, Inc., Actavis Eliza-
beth LLC, Actavis Holdco U.S., Inc. (collectively, “Actavis”)
and Teva Pharmaceuticals USA, Inc. and Barr Laborato-
ries, Inc. (collectively, “Teva”) for allegedly infringing the
’737 patent’s claims 1−6. Actavis moved to dismiss Endo’s
patent infringement claims, arguing that the patent claims
were ineligible under § 101. The magistrate judge recom-
mended granting Actavis’s motion. The magistrate judge
first analyzed step 1 of the Alice/Mayo test, reasoning that
the claims are directed to the natural law that the bioavail-
ability of oxymorphone is increased in people with severe
renal impairment. Magistrate Op., 2015 WL 5580488,
at *6.
    The magistrate judge then considered step 2 of the Al-
ice/Mayo test, analyzing whether the ’737 patent claims,
though directed to a law of nature, added enough to qualify
as a patentable method that applies the law of nature.
ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.                7

Id. at *7–9 (citing Mayo Collaborative Servs. v. Prometheus
Labs., Inc., 566 U.S. 66, 77 (2012)). The magistrate judge
separated claim 1 into three steps: (1) a “providing” step,
(2) a “measuring” step, and (3) an “administering” step.
Id. at *7. First, the magistrate judge reasoned that the
“providing” step is similar to the administering step in
Mayo because it “merely identifies the specific drug for ad-
ministration.” Id. Second, the magistrate judge concluded
that the measuring/determining step, like Mayo, “just di-
rects one to use a well-known method to measure creati-
nine levels to obtain the necessary information to apply a
law of nature.” Id. Finally, the magistrate judge concluded
that the “administering step” is indistinguishable from
Mayo:
    The administering step simply limits the relevant
    audience to patients and prescribing physicians,
    who treat chronic or acute pain with oxymorphone,
    and instructs the administration of the correct dos-
    age of oxymorphone depending on the severity of
    the renal impairment, a step very similar to Mayo,
    which limited the relevant audience to “doctors
    who treat patients with certain diseases with thio-
    purine drugs.”
Id. at *7 (quoting Mayo, 566 U.S. at 78). According to the
magistrate judge, “[t]he administering step merely in-
structs physicians to dispense oxymorphone for the treat-
ment of pain in a well-know[n] manner, while utilizing the
natural law to manage the dosage.” Id. at *8. Based on
this analysis, the magistrate judge concluded that the pa-
tent was not directed to a patent-eligible application of a
natural law.
    The district court adopted the magistrate judge’s rec-
ommendation, finding the patent claims ineligible. District
Court Op., 2015 WL 7253674, at *4. The district court
agreed with the magistrate judge that the claims are di-
rected to “‘the connection between the severity of renal
8                 ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.

impairment and the bioavailability of oxymorphone,’ or, in
other words, the reaction of the human body of a renally
impaired individual to oxymorphone, which is unquestion-
ably a natural law.” Id. at *3 (quoting Magistrate Op.,
2015 WL 5580488, at *6). Moreover, the district court
agreed that the magistrate judge properly analogized the
’737 patent claims to the patent-ineligible representative
claim in Mayo and rejected Endo’s attempts to distinguish
Mayo.
    Having held the patent ineligible, the district court dis-
missed Endo’s claims in the Actavis case. Based on that
order, Endo stipulated that the patent claims were ineligi-
ble (subject to Endo’s right to appeal) in the Teva case,
which was before the same district court judge. Accord-
ingly, the district court entered partial, and later, final
judgment of ineligibility. In the Actavis case, the court en-
tered a Rule 54(b) partial judgment of ineligibility. Endo
appealed.      We have jurisdiction under 28 U.S.C.
§ 1295(a)(1).
                         DISCUSSION
                               I
     “We apply regional circuit law to the review of motions
to dismiss for failure to state a claim under Rule 12(b)(6),”
In re TLI Commc’ns Patent Litig., 823 F.3d 607, 610
(Fed. Cir. 2016), here, the Third Circuit. The Third Circuit
“review[s] de novo a district court’s grant of a motion to dis-
miss for failure to state a claim under Federal Rule of Civil
Procedure 12(b)(6).” Ballentine v. United States, 486 F.3d
806, 808 (3d Cir. 2007). To survive a motion to dismiss for
failure to state a claim, a complaint must allege “enough
facts to state a claim to relief that is plausible on its face.”
Bell Atl. Corp. v. Twombly, 550 U.S. 544, 570 (2007). “We
review issues unique to patent law, including patent eligi-
bility under § 101, consistent with our circuit’s precedent.”
Smart Sys. Innovations, LLC v. Chi. Transit Auth.,
873 F.3d 1364, 1367 (Fed. Cir. 2017) (internal quotation
ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.               9

marks and citation omitted). A district court’s determina-
tion of patent eligibility under § 101 is an issue of law,
which we review de novo, and may contain underlying is-
sues of fact. Berkheimer v. HP Inc., 881 F.3d 1360, 1365
(Fed. Cir. 2018).
                             II
    Section 101 of the Patent Act states that “[w]hoever in-
vents or discovers any new and useful process, machine,
manufacture, or composition of matter, or any new and
useful improvement thereof, may obtain a patent therefor,
subject to the conditions and requirements of this title.”
35 U.S.C. § 101. However, § 101 “contains an important
implicit exception”: “‘laws of nature, natural phenomena,
and abstract ideas’ are not patentable.” Mayo, 566 U.S.
at 70 (alteration omitted) (quoting Diamond v. Diehr,
450 U.S. 175, 185 (1981)).
    The Supreme Court has established a two-step frame-
work to determine subject matter eligibility under § 101.
Alice Corp. Pty. v. CLS Bank Int’l, 573 U.S. 208, 217–18
(2014) (citing Mayo, 566 U.S. at 72–73, 75–80). If the
claims are not directed to a patent-ineligible concept at
step one, we need not address step two of the inquiry. See
Enfish, LLC v. Microsoft Corp., 822 F.3d 1327, 1339
(Fed. Cir. 2016). That is the case here. Accordingly, our
analysis focuses solely on step one.
    Step one requires determining “whether the claims at
issue are directed to one of those patent-ineligible con-
cepts.” Alice, 573 U.S. at 217; see also Enfish, 822 F.3d
at 1334–35. The Supreme Court has cautioned that “too
broad an interpretation of” ineligible subject matter “could
eviscerate patent law” because “all inventions at some level
embody, use, reflect, rest upon, or apply laws of nature,
natural phenomena, or abstract ideas.” Mayo, 566 U.S.
at 71. Accordingly, at step one, “it is not enough to merely
identify a patent-ineligible concept underlying the claim;
we must determine whether that patent-ineligible concept
10               ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.

is what the claim is ‘directed to.’” Rapid Litig. Mgmt. Ltd.
v. CellzDirect, Inc., 827 F.3d 1042, 1050 (Fed. Cir. 2016).
     Applying this law, we conclude that the asserted claims
are not directed to patent-ineligible subject matter. 3 On
the contrary, the claims are directed to a patent-eligible
method of using oxymorphone or a pharmaceutically ac-
ceptable salt thereof to treat pain in a renally impaired pa-
tient. 4 Our conclusion is supported by the claim language
itself and confirmed by the specification. The claims recite
“[a] method of treating pain in a renally impaired patient.”
’737 patent col. 48 ll. 7–9. Claim 1 also requires specific
steps: (a) providing a pharmaceutical (5–80 mg of oral con-
trolled-release oxymorphone or one of its pharmaceutically
acceptable salts), (b) testing the patient for a disease state
(reduced kidney function based on creatinine clearance
rate), and then (c) administering the pharmaceutical (a
lower dose of oxymorphone) based on the creatinine clear-
ance rate to achieve an average AUC of oxymorphone over
a 12-hour period of less than 21 ng·hr/mL. Consistent with
the claims, the abstract, patent title, and summary of the
invention all describe the invention as a “method of treat-
ing pain” in patients with renal impairment. Id. at Ab-
stract, col. 1 ll. 1–5; see id. at col. 2 ll. 35–43.      The
specification predominantly describes the invention as a
method that treats renally impaired pain patients with less
oxymorphone while still treating their pain. Indeed, the

     3   The parties did not argue the claims separately, so
they rise or fall together with representative claim 1.
    4    We acknowledge that when the district court held
the claims ineligible, it did not have the benefit of consid-
ering Vanda Pharmaceuticals Inc. v. West-Ward Pharma-
ceuticals International Ltd., 887 F.3d 1117 (Fed. Cir.
2018), CellzDirect, 827 F.3d at 1050, and Natural Alterna-
tives International v. Creative Compounds, LLC, No. 2018-
1295, 2019 WL 1216226 (Fed. Cir. Mar. 15, 2019).
ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.               11

specification explains that the method “avoid[s] possible is-
sues in dosing” and allows for treatment with “the lowest
available dose” for patients with renal impairment. Id.
at col. 10 ll. 26–27, 40–41.
    We held similar claims patent-eligible in Vanda Phar-
maceuticals Inc. v. West-Ward Pharmaceuticals Interna-
tional Ltd, 887 F.3d 1117 (Fed. Cir. 2018). The patent at
issue in Vanda related to a method of treating schizophre-
nia patients with a drug (iloperidone), where the adminis-
tered dose is adjusted based on whether or not the patient
is a “CYP2D6 poor metabolizer.” 887 F.3d at 1121. Pa-
tients who are CYP2D6 poor metabolizers can be subject to
serious cardiac problems when treated with drugs such as
iloperidone. One such cardiac problem is QTc prolonga-
tion, an abnormality in the patient’s heart rhythm. The
Vanda inventors discovered that the treatment of CYP2D6
poor metabolizers “can be accomplish[ed] more safely by
administering a lower dose of the drug than would be ad-
ministered to a person who has normal CYP2D6 enzyme
activity.” Id. (alteration in original) (quoting U.S. Patent
No. 8,586,610 col. 2 ll. 15–21). Thus, the Vanda patent
claims refer to a reduced dose of iloperidone for poor me-
tabolizers compared to typical metabolizers. Id.
     The claims at issue here are legally indistinguishable
from the representative claim in Vanda. Both claims recite
a method for treating a patient. The Vanda patent claims
recite the steps of carrying out a dosage regimen based on
the results of genetic testing. Id. at 1135. Here, the claims
similarly recite the steps of carrying out a dosage regimen,
though the steps are based on the results of kidney function
testing. Additionally, the claims in both cases require spe-
cific treatment steps. In Vanda, the claims require doctors
to “internally administer[] iloperidone to the patient in an
amount of 12 mg/day or less” if the patient has a CYP2D6
poor metabolizer genotype; and “internally administer[]
iloperidone to the patient in an amount that is greater
than 12 mg/day, up to 24 mg/day” if the patient does not
12               ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.

have a CYP2D6 poor metabolizer genotype. Id. (alterations
in original) (quoting ’610 patent col. 17 ll. 13–20). Here,
the claims require doctors to “orally administer[] to said
patient, in dependence on which creatinine clearance rate
is found, a lower dosage of the dosage form to provide pain
relief” in such a way that after administering the dose, the
patient’s “average AUC of oxymorphone over a 12-hour pe-
riod is less than about 21 ng·hr/mL.” ’737 patent col. 48
ll. 7–26. Like the claims in Vanda, the claims here “are
directed to a specific method of treatment for specific pa-
tients using a specific compound at specific doses to achieve
a specific outcome.” See Vanda, 887 F.3d at 1136.
    Also like the claims in Vanda, the claims here differ
from those in Mayo in material respects. Although the rep-
resentative claim in Mayo recited administering a thiopu-
rine drug to a patient, the claim as a whole was not directed
to the application of a drug to treat a particular disease.
See Mayo, 566 U.S. at 74, 87; Vanda, 887 F.3d at 1134.
Furthermore, the administering step in Mayo is distin-
guishable from the administering step in the ’737 patent
because the administering step in Mayo is the first step in
the method that simply describes giving the drug to a pa-
tient with a certain disorder. By contrast, the administer-
ing step in the ’737 patent is the step that describes giving
a specific dose of the drug based on the results of kidney
function testing. The Supreme Court in Mayo underscored
the distinction between such method of treatment claims
and those in Mayo, noting that “[u]nlike, say, a typical pa-
tent on a new drug or a new way of using an existing drug,
the patent claims do not confine their reach to particular
applications of those laws.” Mayo, 566 U.S. at 87; Vanda,
887 F.3d at 1135. In Vanda, the inventors recognized the
relationship between iloperidone dosage and the patient’s
CYP2D6 poor metabolizer genotype, but that was not what
they claimed. Similarly, the inventor here recognized the
relationship between oxymorphone and patients with renal
impairment, but that is not what he claimed. Rather, he
ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.                13

claimed an application of that relationship—specifically, a
method of treatment including specific steps to adjust or
lower the oxymorphone dose for patients with renal impair-
ment. The claims are thus directed to more than just recit-
ing the natural relationship.
     Nor is preemption a valid concern. While the claim in
Mayo could “tie up the doctor’s subsequent treatment deci-
sion,” the claims here do not. Mayo, 566 U.S. at 86. The
representative claim in Mayo stated that the metabolite
level in blood simply “indicates” a need to increase or de-
crease dosage, without prescribing a specific dosage regi-
men or other added steps to take as a result of that
indication. Id. at 75. In contrast, the claims here recite the
steps of carrying out a dosage regimen based on the results
of kidney function testing. The claims require doctors to
“orally administer[] to said patient, in dependence on
which creatinine clearance rate is found, a lower dosage of
the dosage form to provide pain relief” in such a way that
after administering the dose, the patient’s “average AUC of
oxymorphone over a 12-hour period is less than about
21 ng·hr/mL.” ’737 patent col. 48 ll. 7–26. These are spe-
cific treatment steps. The claims prescribe a specific dos-
age regimen through the wherein clause, under which the
physician administers oxymorphone to achieve a specific
range of AUC of oxymorphone based on the patient’s creat-
inine clearance rate. Id. at col. 48 ll. 20–26.
    Actavis argues that the court in Vanda emphasized the
particularity of the claimed method’s “specific steps”—a
specificity Actavis alleges is not found in the ’737 patent’s
claims.     Appellee Br. 34–35 (citing Vanda, 887 F.3d
at 1134). According to Actavis, unlike the claims in Vanda,
the method steps in Endo’s claims offer no “practical assur-
ance that the process is more than a drafting effort de-
signed to monopolize the law of nature itself.” Vanda,
887 F.3d at 1134 (quoting Mayo, 566 U.S. at 77). We disa-
gree. As addressed above, the ’737 patent claims are very
similar to those in Vanda and any differences in specificity
14               ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.

are not of a sufficient degree to convince us to conclude that
the claims here should be ineligible as compared to the
claims in Vanda.
     We nonetheless address each of Actavis’s alleged points
of distinction between the ’737 patent claims and those in
Vanda. First, Actavis argues that, unlike the Vanda
claims, the ’737 patent claims do not require that a biolog-
ical sample be obtained or assayed in any particular way to
determine the patient’s creatinine-clearance rate. Appel-
lee Br. 35 (citing Vanda, 887 F.3d at 1121). But this is a
distinction without a difference. The court in Vanda rea-
soned that the claim was directed to “specific patients,”
without explicitly emphasizing the precise methods used to
identify those specific patients.
    Second, Actavis argues that, unlike Vanda, the ’737 pa-
tent’s claims do not specify an amount or frequency of oxy-
morphone to be administered after patients are categorized
by creatinine-clearance rate. We disagree with Actavis’s
interpretation of the claims in this regard. The wherein
clause that immediately follows the orally administering
step limits the scope of the orally administering step. In
particular, the wherein clause requires that the dosage and
schedule administered in the “orally administering step”
must achieve a target average AUC of oxymorphone less
than about 21 ng·hr/mL over a 12-hour period. In other
words, the wherein clause identifies the appropriate sched-
ule and dose of oxymorphone to administer, as a function
of how much oxymorphone is in the patient’s system. It is
the combination of the administering step and wherein
clause claim language, taken together, that make the
claims-at-issue as specific as those in Vanda such that the
patent claims do not “tie up the doctor’s subsequent treat-
ment decision.” Vanda, 887 F.3d at 1135 (quoting Mayo,
566 U.S. at 86). Like the administering step in Vanda, the
administering step and wherein clause in the present
claims allow the claims to do more than just recognize a
need to lower or decrease a dose. See id.
ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.                15

     At bottom, we conclude that the ’737 patent claims are
like those in Vanda. They are eligible because they are “di-
rected to a specific method of treatment for specific patients
using a specific compound at specific doses to achieve a spe-
cific outcome.” Id. at 1136. Our precedent leaves no room
for a different outcome.
     CellzDirect further supports our decision that the
claims are patent eligible. The claims in CellzDirect were
directed to a method of freezing hepatocytes. There, we
held that “a method of producing a desired preparation of
multi-cryopreserved hepatocytes cells” was patent eligible.
827 F.3d at 1046−47. We explained that “[t]he end result
of the . . . claims is not simply an observation or detection
of the ability of hepatocytes to survive multiple freeze-thaw
cycles. Rather, the claims [were] directed to a new and use-
ful method of preserving hepatocyte cells.” Id. at 1048. We
further emphasized that “the natural ability of the subject
matter to undergo the process does not make the claim ‘di-
rected to’ that natural ability.” Id. at 1049 (emphasis in
original). Otherwise, claims directed to actually “treating
cancer with chemotherapy” or “treating headaches with as-
pirin” would be patent ineligible. Id. Just like the claims
in CellzDirect, the result of the claims here is not simply an
observation or detection. The claims in CellzDirect are di-
rected to a new and useful method of preserving hepatocyte
cells. Similarly, the claims here are directed to a new and
useful method of treating pain in patients with impaired
renal function.
    Nor does Ariosa Diagnostics, Inc. v. Sequenom, Inc.,
788 F.3d 1371 (Fed. Cir. 2015) compel a different outcome.
This court in Ariosa held that “where claims of a method
patent are directed to an application that starts and ends
with a naturally occurring phenomenon, the patent fails to
disclose patent eligible subject matter if the methods them-
selves are conventional, routine and well understood appli-
cations in the art.” Id. at 1378. The representative claim
16                ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.

in Ariosa was directed to a method for detecting paternally
inherited cell-free fetal DNA 5:
     1. A method for detecting a paternally inherited nu-
     cleic acid of fetal origin performed on a maternal
     serum or plasma sample from a pregnant female,
     which method comprises
     amplifying a paternally inherited nucleic acid from
     the serum or plasma sample and
     detecting the presence of a paternally inherited nu-
     cleic acid of fetal origin in the sample.
Id. at 1373–74 (quoting U.S. Patent No. 6,258,540 col. 23
ll. 61–67). There, we determined that the claims were di-
rected to a natural phenomenon. We also determined that
the only new and useful subject matter claimed “was the
discovery of the presence of [cell-free fetal DNA] in mater-
nal plasma or serum,” and that the “method at issue here
amounts to a general instruction to doctors to apply rou-
tine, conventional techniques when seeking to detect [cell-
free fetal DNA].” Id. at 1377. In contrast, the claims here
are directed to a treatment method, not a detection method.
The ’737 patent does not “start[] and end[] with a naturally
occurring phenomenon.” Id. at 1378. Instead, the claims
are directed to more—they recite a specific method of treat-
ment based on the recognition that patients with severe re-
nal impairment have a mean oxymorphone AUC, on
average, 1.7 times greater than healthy subjects.
    Athena Diagnostics, Inc. v. Mayo Collaborative Servs.,
LLC, 915 F.3d 743 (Fed. Cir. 2019), also does not require a
different outcome. In Athena, our court held that the claim
“recite[d] a natural law and conventional means for

     5 Cell-free fetal DNA (“cffDNA”) is non-cellular fetal
DNA that circulates freely in the blood stream of a preg-
nant woman. Id. at 1373.
ENDO PHARMS. INC. v. TEVA PHARMS. USA, INC.               17

detecting it.” Id. at 752. There, the court concluded that
the claims at issue were like the claims in Mayo, and that
“claiming a natural cause of an ailment and well-known
means of observing it is not eligible for patent because such
a claim in effect only encompasses the natural law itself.”
Id. at 752−53. At the same time, the court acknowledged
that “claiming a new treatment for an ailment, albeit using
a natural law, is not claiming the natural law”—that is ex-
actly the situation we have here. Id. at 753. The claims in
this case are directed to a new treatment for an ailment,
albeit using a natural law or phenomenon. The claims are
not directed to the ineligible subject matter itself and, as
such, are eligible.
                       CONCLUSION
     We have considered the appellees’ remaining argu-
ments but do not find them persuasive. Because the
’737 patent claims are not directed to patent-ineligible sub-
ject matter, we reverse the district court’s decision.
                       REVERSED