Spruce Biosciences, Inc.

Patent Trials and Appeals Board

Dec 10, 2021

PGR2021-00088 (P.T.A.B. Dec. 10, 2021)

Trials@uspto.gov Paper 11
571-272-7822 Entered: December 10, 2021

UNITED STATES PATENT AND TRADEMARK OFFICE
________________________________________
BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________________________________
NEUROCRINE BIOSCIENCES, INC.,
Petitioner,
v.
SPRUCE BOSCIENCES, INC.,
Patent Owner.
________________________________________
PGR2021-00088
Patent 10,849,908 B2
________________________________________

Before JOHN G. NEW, SUSAN L. C. MITCHELL, and ZHENYU YANG,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION
Denying Institution of Post-Grant Review
35 U.S.C. § 324

PGR2021-00088
Patent 10,849,908 B2

2

I. INTRODUCTION
Petitioner Neurocrine Biosciences, Inc. (“Petitioner”) has filed a
Petition (Paper 3, “Pet.”) seeking post-grant review of claim 1–25 of
US Patent 10,849,908 B2 (Ex. 1001, the “’908 patent”). Patent Owner
Spruce Biosciences, Inc. (“Patent Owner”) timely filed a Preliminary
Response. Paper 8 (“Prelim. Resp.”).
Under 35 U.S.C. § 324, the Board “may not authorize a post-grant
review to be instituted unless … the information presented in the petition
… if such information is not rebutted would demonstrate that it is more
likely than not that at least 1 of the claims challenged in the petition is
unpatentable.” Upon consideration of the Petition, the Preliminary
Response, and the evidence presently before us, we determine that Petitioner
has failed to demonstrate that it is more likely than not that it would prevail
in establishing the unpatentability of at least one challenged claim of the
’908 patent. We consequently deny institution of post-grant review.

II. BACKGROUND
A. Real Parties-in-Interest
Petitioner identifies Neurocrine Biosciences, Inc. as the real party-in-
interest. Pet. 79. Patent Owner identifies Spruce Biosciences, Inc. as the
real party-in-interest. Paper 6, 2.

B. Related Matters
Petitioner states that it is not aware of any disclaimers, reexamination
certificates, or petitions for inter partes or post grant review for the ’908
Patent, nor is Petitioner aware of any pending civil actions involving the
PGR2021-00088
Patent 10,849,908 B2

3

’908 patent. Pet. 80. Patent Owner similarly states that it is not aware of
any related matters involving the ’908 patent. Paper 6, 2.

C. The Asserted Grounds of Unpatentability
Petitioner contends that claims 1–25 of the ’908 patent are
unpatentable, based upon the following grounds:

Ground Claim(s)
Challenged 35 U.S.C. § Reference(s)/Basis
I 1–4, 7–9, 11–14,
17–19, 21–24
102 Grigoriadis1
II 4, 10, 14, 20–22,
25
103 Grigoriadis
III 5–6, 15–16 103 Grigoriadis, Romano2
IV 1–25 112 Lack of written
description
V 1–25 112 Lack of enablement

Petitioner also relies upon the Declaration of Dr. Robert M. Carey (the
“Carey Declaration,” Ex. 1005).

1 Grigoriadis et al. (US 2017/0020877 A1, January 26, 2017) (“Grigoriadis”)
Ex. 1006.

2 Romano (US 2005/0209250 A1, September 22, 2005) (“Romano”) Ex.
1007.

PGR2021-00088
Patent 10,849,908 B2

4

D. The ’908 Patent
The ’908 patent is directed to pharmaceutical compositions
comprising -(4-chloro-2-(morpholin-4-yl) thiazol-5-yl)-7-(1-ethylpropyl)-
2,5-dimethylpyrazolo (1,5-α) pyrimidine (“Compound 1”), and to methods
of using the same for the treatment of congenital adrenal hyperplasia
(“CAH”). Ex. 1001, Abstr. Relevantly, the ’908 patent is directed to the
administration of Compound 1, or another antagonist of the corticotropin
releasing factor (“CRF”) receptor type 1 (“CRF1”), and thus inhibiting
release of adrenal corticotropic hormone (“ACTH”) by the secretory cells of
the adenohypohysis, for the treatment of CAH. Ex. 1001, cols. 10–12, ll.
47–26.

E. Representative Claims
Independent claims 1 and 11 of the ’908 patent recite:
1. A method of treating congenital adrenal hyperplasia
(CAH) in a human comprising administering to the human a
therapeutically-effective amount of a CRF receptor antagonist or
a pharmaceutically acceptable salt thereof, wherein an
adrenocorticotropic hormone (ACTH) level in the human is
reduced by at least 10% from baseline.

11. A method of treating congenital adrenal hyperplasia in a
human comprising administering to the human a therapeutically-
effective amount of a CRF receptor antagonist or a
pharmaceutically acceptable salt thereof, wherein a 17-
hydroxyprogesterone (17-OHP) level is reduced in the human by
at least about 10% from baseline.

Ex. 1001 col. 48, ll. 6–42.

PGR2021-00088
Patent 10,849,908 B2

5

F. Prosecution History of the ’908 Patent
The ’908 patent issued from U.S. Application Ser. No. 16/388,620
(the “’620 application”), filed on April 18, 2019, and claims the priority
benefit of, inter alia, provisional Application Ser. No. 62/545,406, which
was filed on August 14, 2017. Ex. 1001, codes (21–22, 60).
Claims 1–25 of the ’908 patent were allowed on September 30, 2020,
and the patent issued on December 1, 2020. Ex. 1002, 186; Ex. 1001, code
(45). The Petition is consequently eligible for post-grant review. See 35
U.S.C. § 324.

III. ANALYSIS
A. Claim Construction
The Board applies the same claim construction standard that would be
used to construe the claim in a civil action under 35 U.S.C. § 282(b). See
37 C.F.R. § 100(b) (2020). Under that standard, claim terms “are generally
given their ordinary and customary meaning” as understood by a person of
ordinary skill in the art at the time of the invention. Phillips v. AWH Corp.,
415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc). “In determining the
meaning of the disputed claim limitation, we look principally to the intrinsic
evidence of record, examining the claim language itself, the written
description, and the prosecution history, if in evidence.” DePuy Spine, Inc.
v. Medtronic Sofamor Danek, Inc., 469 F.3d 1005, 1014 (Fed. Cir. 2006)
(citing Phillips, 415 F.3d at 1312–17). Extrinsic evidence is “less significant
than the intrinsic record in determining ‘the legally operative meaning of
PGR2021-00088
Patent 10,849,908 B2

6

claim language.’” Phillips, 415 F.3d at 1317 (quoting C.R. Bard, Inc. v. U.S.
Surgical Corp., 388 F.3d 858, 862 (Fed. Cir. 2004)).
Petitioner proposes constructions for the claim terms “baseline/from
baseline,” “human,” “maintained at a reduced level post 24 hours,” and
“administered 4 hours prior to sleeping.” Pet. 23–28. Patent Owner
responds that, of these claim terms, the Board need only construe the claim
term “from baseline” for the purposes of institution. Prelim. Resp. 19–20
(citing Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co., 868 F.3d
1013, 1017 (Fed. Cir. 2017)).
Having reviewed the pleadings and evidence of record, we conclude
that we need only construe the claim term “from baseline” as part of our
Decision to deny institution of post-grant review.

1. “from baseline”
Independent claims 1 and 11 recite a reduction of ACTH or 17-OHP
by at least 10% “from baseline” after administering a CRF1 receptor
antagonist to a CAH patient. See Ex. 1001 col. 48, ll. 6–42. Petitioner
argues that, based upon the ordinary meaning of the claim language,
“baseline” refers to a measurement prior to the administration of a CRF1
receptor antagonist. Pet. 24 (citing Ex. 1005 ¶¶ 36–43). Petitioner observes
that the only clinical data in the ’908 patent relating to ACTH and 17-OHP
describe measuring ACTH and 17-OHP levels “at baseline,” i.e. ACTH and
17-OHP levels before the administration of tildacerfont (i.e., Compound 1),
a CRF1 receptor antagonist, and ACTH and 17-OHP levels after the
administration of the first dose of tildacerfont. Id. (citing Ex. 1001 col. 42,
ll. 1–16, col. 43, ll. 49–67, Figs. 2–3; Ex. 1005 ¶ 38). Petitioner points to
PGR2021-00088
Patent 10,849,908 B2

7

Figures 2 and 3 of the ’908 patent as demonstrating a reduction of ACTH
and 17-OHP due to the administration of tildacerfont. Id. (citing Ex. 1001,
col. 43, ll. 49–67, Figs. 2–3; Ex. 1005 ¶ 39). Petitioner contends that
Figures 2 and 3 thus depict the change in ACTH and 17-OHP levels from
“baseline,” consistent with the ordinary meaning of the term. Id.
Petitioner contends that the claims do not require that the
measurement be made at any particular point in time. Pet. 24. Therefore,
argues Petitioner, the baseline measurement for ACTH and 17-OHP levels
may be made at any point in time prior to CRF1 receptor antagonist
administration, and then compared to those levels post-CRF1 receptor
antagonist administration, measured at the same time of day. Id. at 24–25
(citing Ex. 1005 ¶¶ 41–42).
Petitioner also argues that a person of ordinary skill in the art would
have understood that “baseline” and “from baseline” allow for
glucocorticoid administration during baseline measurements. Pet. 25.
Acceding to Petitioner, when studying a new CAH drug like a CRF1
receptor antagonist, a skilled artisan would have allowed the patient to
continue his or her usual glucocorticoid treatments during and after baseline
measurements to avoid endangering the patient’s health. Id. (citing Ex. 1005
¶ 40). Petitioner contends that this is consistent with the clinical example in
the ’908 patent, which tracked the patients’ “background glucocorticoid
regimens.” Id. (citing Ex. 1001 col. 42, ll. 26–32; Ex. 1005 ¶ 40).
Patent Owner urges the Board to construe the claim term “from
baseline” at least to the extent necessary to determine whether to reject
Petitioner’s argument on the merits that the claimed reduction “from
baseline” is no different than a reduction relative to a placebo. Prelim. Resp.
PGR2021-00088
Patent 10,849,908 B2

8

11. Patent Owner argues that the prosecution history of the ’908 patent is
part of the intrinsic evidence of the claims’ meaning, if it is in evidence. Id.
(citing Phillips, 415 F.3d at 1317).
Patent Owner notes that Petitioner acknowledges that, during
prosecution of the ’908 patent, Applicants asserted that ACTH and 17-OHP
levels “relative to placebo” as used in Grigoriadis were different from
reduction of levels “from baseline.” Prelim. Resp. 12 (citing Pet. 19).
Petitioner contends that, subsequent to the Final Office Action of November
25, 2019, Applicant submitted a Declaration by Dr. Chris N. Barnes, filed
June 15, 2020 (the “Barnes Declaration”). Id. (see Ex. 1002, 34). In the
Barnes Declaration, Dr. Barnes attested that, in the Specification, the
hormone levels in the patent “were assessed at baseline, which includes a
pre-dose overnight set of serial assessments and a post-dose overnight set of
serial assessments following the administration of the first dose at day 1.”
Id. at 12–13 (quoting Ex. 1002, 36–37) (emphasis omitted). Patent Owner
contends that Applicants explained that, whereas the prior art reference cited
by the Examiner (Grigoriadis) compared ACTH and 17-OHP levels relative
to placebo, it failed to demonstrate a reduction by at least 10% from
baseline. Id. at 13 (citing Ex. 1002, 100).
The Specification expressly teaches that, with respect to the clinical
phase 2 trial described in Example 4, “Patients will have overnight
[pharmacokinetic/pharmacodynamics] PK/PD assessments performed at
baseline, which include an [sic] pre-dose overnight assessment and a post-
dose overnight assessment for PK/PD following administration of the first
dose.” Ex. 1001 col. 42, ll. 12–16. This is the same quotation and clinical
trial relied upon by Dr. Barnes in his Declaration, and is the only definition
PGR2021-00088
Patent 10,849,908 B2

9

of a “baseline” in the ’908 patent. See Ex. 1002, 36–37. We note that
placebos were evidently not employed in the phase 2 clinical study of
Example 4.3
Given the sole exemplary description of “baseline” in Example 4 of
the Specification, we construe the claim term reciting “reduced by at least
10% from baseline” as meaning “a reduction of at least 10% in the level of
ACTH (claim 1) or 17-OHP (claim 11) compared to measurements of
ACTH or 17-OHP made prior to, and/or at the beginning of, administration
of the drug.”

B. A Person of Ordinary Skill in the Art
Petitioner contends that a person of ordinary skill in the art would
typically possess a medical degree or a Ph.D. in a field related to
endocrinology, and would have knowledge of hormone regulation and
disorders, as well as knowledge of the treatment regimens employed to treat
such disorders. Pet. 60 (citing Ex. 1005 ¶ 34). Petitioner argues that such a
person of ordinary skill would also have at least three years of experience
conducting research concerning endocrine disorders, including CAH or other
adrenal disorders. Id.
Patent Owner does not expressly contest this definition of a person of
ordinary skill in the art in its Preliminary Response. For the purposes of this
Decision, because we find Petitioner’s definition to be consistent with the
demonstrable level of skill in the art (see, e.g., Exs. 1009, 1025, 2003, 2004,

3 We note that placebos were to be employed in the yet-to-be-performed
phase 3 clinical trial described in Example 7 of the Specification. See
Ex. 1001 col. 46, ll. 29–34.
PGR2021-00088
Patent 10,849,908 B2

10

2005), and in the absence of a different proposed definition of the level of
skill in the art by Patent Owner, we adopt Petitioner’s definition.

C. Ground I: Alleged Anticipation of Claims 1–4, 7–9, 11–14, 17–19,
21–24 by Grigoriadis

1. Overview of Grigoriadis
Grigoriadis is directed to methods for treating CAH by administering
to a subject in need thereof an effective amount of a CRF1 receptor
antagonist, including (but not limited to) bedtime administration. Ex. 1006
¶ 7. Grigoriadis teaches that CAH is a group of autosomal recessive genetic
disorders that result in little or no cortisol biosynthesis. Id. at ¶ 4.
Grigoriadis teaches that:
Corticotropin-releasing factor (CRF)4 activates the CRF1
receptor, a class B G protein-coupled receptor (GPCR), and that
CRF1 receptor antagonists have the potential to directly inhibit
ACTH release in patients with CAB, thereby allowing
normalization of androgen production while using lower, more
physiologic doses of hydrocortisone, and reducing treatment-
associated side effects.

Id. at ¶ 6.
Relevantly, Example 6 of Grigoriadis teaches a clinical study, entitled
“A Phase 1, Single-Blind, Placebo-Controlled, Fixed-Sequence, Single-Dose
Study to Evaluate the Safety and Tolerability of NBl-77860 in Adult
Females with Congenital Adrenal Hyperplasia (IND 117, 388).” Id. at ¶ 90.
The study comprised a single-blind, placebo-controlled, single center, fixed-

4 The terms “corticotropin releasing factor” (CRF) and “corticotropin
releasing hormone” (CRH) as used herein are synonymous.
PGR2021-00088
Patent 10,849,908 B2

11

sequence single-dose clinical trial in adult female classical CAH patients,
designed to “assess the safety, tolerability, and plasma exposure of
verucerfont (NBI-77860), a CRF1 receptor antagonist, as well as the effect
of this compound on endogenous levels of [hypothalamic-pituitary-adrenal]
axis hormones.” Id.
The dosage regiment and experimental design of this study is depicted
in Figure 4 of Grigoriadis, which is reproduced below:

Figure 4 of Grigoriadis depicts the dosage regimen and
experimental design of the clinical phase 1 study of Example 6

In the study, a total of eight female subjects, ages 19 to 58, with a medical
diagnosis of classical 21-hydroxylase deficiency AH were administered
single bedtime doses (hs) of placebo and verucerfont 300 mg, and 600 mg
during three separate treatment periods. Id. at ¶ 91. The results of the study
are depicted in Figure 5 of Grigoriadis, reproduced below:
PGR2021-00088
Patent 10,849,908 B2

12

Figure 5 of Grigoriadis depicts levels of 17-OHP and ACTH in
response to placebo and 300 mg and 600mg doses of
verucerfont during the 24-hour, post-dose periods

Grigoriadis teaches:
Consistent and clinically meaningful reductions from predose
levels of both 17-OHP and ACTH were observed throughout the
postdose period following administration of NBI-77860 relative
to placebo in these CAH patients. In addition to the group mean
data, individual responses were evaluated and treatment
“responders” were conservatively defined as those subjects with
at least a 50% decrease in 17-OHP and ACTH under active NBI-
77860 relative to placebo during the peak morning period. This
responder analysis yielded a sizeable responder rate of 50% in
PGR2021-00088
Patent 10,849,908 B2

13

the study (none of these subjects were responders during the
initial placebo treatment period). Furthermore, the 300 mg dose
yielded nearly identical effects on 17-OHP and ACTH as the 600
mg dose.

Ex. 1006 ¶ 93.

2. Anticipation of Claims 1–4, 7–9, 11–14, 17–19, and 21–24 by
Grigoriadis
a. Independent claims 1 and 11
Petitioner argues that Grigoriadis teaches crinecerfont (SSR-125543),
a CRF1 receptor antagonist, as useful for the treatment of CAH. Pet. 47
(citing Ex. 1006 ¶ 54). Petitioner contends that Grigoriadis also discloses a
range of therapeutically acceptable amounts of a CRF1 receptor antagonist,
of about 50–1000 mg. Id. (citing Ex. 1006 ¶ 63). According to Petitioner,
the administration of a therapeutically effective amount of crinecerfont to a
patient, as taught by Grigoriadis necessarily, and thus inherently, results in
an at least 10% reduction of the patient’s levels of ACTH and 17-OHP,
compared to the patient’s baseline. Id. (citing Ex. 1005 ¶¶ 53–62; Ex. 1009,
10, 13–19, Figs. 1–2, Table 2).
The factual basis of this inherency, argues Petitioner, is demonstrated
by R.J. Auchus et al., Crinecerfont Lowers Elevated Biomarkers of Disease
Control in Adults with Congenital Adrenal Hyperplasia due to 21-
Hydroxylase Deficiency, (“Auchus”) a manuscript that has been submitted
for review for publication in The Lancet. Ex. 1009. According to Petitioner,
Auchus teaches a Phase 2 clinical study demonstrating that the
administration of crinecerfont to patients with CAH resulted in at least a
PGR2021-00088
Patent 10,849,908 B2

14

10% reduction in ACTH and 17-OHP compared to the patient’s baseline
levels prior to administration of crinecerfont. Pet. 30 (citing Ex. 1005
¶¶ 54–62; Ex. 1009, 11, 13–19, Figs. 1–2, Table 2. Petitioner contends that
the clinical study tested four dosing regimens, with patients in four cohorts
receiving between 50 mg and 200 mg of crinecerfont per day, administered
for 14 consecutive days. Id. at 30–31 (citing Ex. 1005 ¶ 55; Ex. 1009, 10).
Petitioner argues that the Auchus study measured the patients’ baseline
ACTH and 17-OHP levels over a 24-hour period beginning in the evening of
the seventh day before the study began (Day -7 to Day -6). Id. at 31 (citing
Ex. 1005 ¶ 56; Ex. 1009, 10–11, Fig. 1). After 14 days of repeated dosing of
crinecerfont, the patients’ ACTH and 17-OHP levels were measured over a
24-hour period beginning in the evening of Day 14 and ending on Day 15.
Id.
Petitioner asserts that the reduction in ACTH and 17-OHP levels
compared to baseline exceeded 10% for patients in all four cohorts after
receiving crinecerfont for 14 days. Pet. 31 (citing Ex. 1005 ¶ 57; Ex. 1009,
13–19, Figs. 1–2, Table 2). Petitioner points to Figure 1 of Auchus, which,
Petitioner argues, presents 24-hour profiles of median patient ACTH and 17-
OHP by cohort, at baseline and at Day 14. Id. (citing Ex. 1005 ¶ 58;
Ex. 1009, Fig. 1). Petitioner asserts that the results of the Auchus study
show that “[t]reatment with crinecerfont for 14 days led to substantial
median reductions for ACTH, 17-OHP, and androstenedione relative to
baseline, especially during the morning window, across all cohorts
(Figure 1).” Id. (citing Ex. 1005 ¶ 58; Ex. 1009, 14).
Petitioner asserts that the “morning window” is clinically relevant
because the body’s natural circadian release of ACTH occurs in the early
PGR2021-00088
Patent 10,849,908 B2

15

morning hours. Pet. 32 (citing Ex. 1005 ¶ 19; Ex. 1006 ¶ 66). According to
Petitioner, in the absence of treatment, the highest ACTH and 17-OHP levels
in CAH patients are observed in the morning; reducing ACTH and 17-OHP
during this time period is an important objective of any CAH treatment. Id.
(citing Ex. 1005 ¶¶ 19, 59; Ex. 1009, 11).
Petitioner argues further that Auchus also examined median percent
reductions in patient ACTH and 17-OHP levels during the clinically relevant
morning window (6–10 a.m.) after 14 days of receiving crinecerfont
compared to baseline morning window measurements. Pet. 34 (citing
Ex. 1005 ¶ 59; Ex. 1009, 11, 14, Fig. 2, Table 2). Petitioner contends that
Auchus reports that in all cohorts, median ACTH and 17-OHP “were
reduced from baseline to Day 14 whether based on samples collected during
the morning window or the 24-hour sampling period. Id. (citing Ex. 1009,
Supplementary Table 1). Petitioner asserts that the ACTH and 17-OHP,
median percent decreases from baseline were generally similar across
cohorts, ranging from -53% to -66%. Id. (citing Ex. 1005 ¶ 60; Ex. 1009,
14, Fig. 2).
Petitioner also notes that Auchus reports the number of patients with a
greater than 50% reduction in ACTH and 17-OHP at Day 14 compared to
baseline levels. Pet. 36 (citing Ex. 1005 ¶ 62; Ex. 1009, Table 2). Petitioner
argues that Table 2 of Auchus demonstrates that 50% of patients in
Cohort 1, 71% of patients in Cohort 2, 63% of patients in Cohort 3, and 75%
of patients in Cohort 4 demonstrated a greater than 50% reduction in ACTH
at Day 14 compared to the patient’s baseline level. Id. (citing Ex. 1005 ¶ 62;
Ex. 1009, Table 2).
PGR2021-00088
Patent 10,849,908 B2

16

Summarizing, Petitioner asserts that administration of a
therapeutically effective amount of crinecerfont to a patient, as taught by
Grigoriadis, would necessarily result in an at least 10% reduction in a
patient’s ACTH level from baseline, and necessarily results in an at least
10% reduction in a patient’s ACTH level from baseline, and therefore
inherently anticipates claims 1 and 11 of the ’908 patent. Pet. 48.

b. Analysis
We are not persuaded that Petitioner has established that it is more
likely than not that independent claims 1 and 11 are anticipated by
Grigoriadis. “For a claim to be anticipated, each claim element must be
disclosed, either expressly or inherently, in a single prior art reference, and
the claimed arrangement or combination of those elements must also be
disclosed, either expressly or inherently, in that same prior art reference.”
Therasense, Inc. v. Becton, Dickinson and Co., 593 F.3d 1325, 1332–33
(Fed. Cir. 2010).
The single clinical trial taught by Example 6 of Grigoriadis does not
establish a baseline value for patients against which to compare the data
obtained from patients receiving 300 mg or 600 mg of the test drug, NBI-
77860 (verucerfont). See Ex. 1006 ¶¶ 90–94. Specifically, Example 6 does
not establish a baseline “which include[s] an [sic] pre-dose overnight
assessment and a post-dose overnight assessment for PK/PD following
administration of the first dose,” as disclosed by the ’908 patent. See
Ex. 1001, col. 42, ll. 12–16. We therefore conclude that Grigoriadis fails to
disclose expressly the limitations of claims 1 and 11 severally reciting
PGR2021-00088
Patent 10,849,908 B2

17

“wherein [the] … hormone … level in the human is reduced by at least 10 %
from baseline.”
Petitioner argues that Grigoriadis inherently discloses this limitation.
A reference may anticipate if a claim limitation that is not expressly
disclosed is inherently disclosed because it “is necessarily present, or
inherent, in the single anticipating reference.” Verizon Servs. Corp. v. Cox
Fibernet Va., Inc., 602 F.3d 1325, 1337 (Fed. Cir. 2010); see also Agilent
Techs., Inc. v. Affymetrix, Inc., 567 F.3d 1366, 1383 (Fed. Cir. 2009)
(holding that the “very essence of inherency is that one of ordinary skill in
the art would recognize that a reference unavoidably teaches the property in
question”).
In support of its argument that Grigoriadis inherently teaches the
limitation in question, Petitioner points to Auchus. Auchus discloses a
phase 2 study that orally administered crinecerfont (NCT03525886/ NBI-
74788) to a mixed-gender group of 18 patients for 14 consecutive days as
follows: 50 or 100 mg once-daily at bedtime (Cohorts 1 and 2, respectively);
100 mg once-daily in the evening (Cohort 3); 100 mg twice-daily (BID,
Cohort 4). Ex. 1009, 5. Participants could enroll in more than one cohort.
Id.
In the Auchus clinical trial, changes from baseline to Day 14 in
adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP),
androstenedione, and testosterone were evaluated. Ex. 1009, 5. Auchus
further discloses that baseline is established for the participant subjects via
admitting them to the study center “from Day -7 to -6 [i.e. from day 7 to day
6 prior to the initial administration of the drug] for serial blood sampling to
establish baseline ACTH, 17-OHP, androstenedione, and testosterone
PGR2021-00088
Patent 10,849,908 B2

18

concentration profiles.” Id. at 12. Although this method of establishing a
baseline is somewhat different than that employed by Grigoriadis, the effect
is essentially the same, to establish for each patient the metabolic baseline
levels of the concentration of each of the hormones measured, to be
compared against the same hormones subsequent to administration of the
test drug.
However, the Auchus and Grigoriadis clinical trials vary in several
important ways. Most significantly, the two trials employ different CRF1
receptor antagonists: Grigoriadis discloses administration of verucerfont
((NBI-77860), whereas Auchus discloses administration of crinecerfont
(NBI-74788/ SSR-125543). Ex. 1006 ¶ 90; Ex. 1009, 5. Table 1 of Patent
Owner’s Preliminary Response, reproduced below, outlines other significant
differences between the studies:

Prelim. Resp. 32.
PGR2021-00088
Patent 10,849,908 B2

19

Given these differences, and particularly the difference in the study
drugs employed in Grigoriadis and Auchus, we cannot agree with Petitioner
that the results of the Auchus clinical trial demonstrate that the single
clinical trial of a different drug, as disclosed by Grigoriadis, necessarily
discloses “at least 10% reduction in a patient’s ACTH level from baseline,
and therefore inherently anticipates claims 1 and 11 of the ’908 patent.”
Pet. 48. A persuasive demonstration of inherency would seem to require a
study replicating that of Grigoriadis (and at least employing the identical
study drug) and including baseline measurements against which to compare
the Grigoriadis results. The Auchus clinical trial, for the reasons we have
explained above, does not provide such proof of inherency.
To be sure, Grigoriadis discloses crinecerfont, the study drug
employed in the Auchus clinical trial. See Ex. 1006 ¶ 54. But Grigoriadis
discloses crinecerfont ([4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(l S)-2
cyclopropyl-1-(3-fluoro-4-methylpbenyl) ethyl]-5-mcthyl-N-(2-propyn-l-yl)-
2-thiazolamine) as an example of a CRF1 receptor antagonist. However,
crinecerfont is not disclosed by Grigoriadis as being a study drug in any
clinical trial similar to its Example 6; it is mentioned only as being one of a
class of CRF1 receptor antagonists. And although Grigoriadis discloses that
crinecerfont is a species of CRF1 receptor antagonist, Petitioner may not
attempt to import experimental results from Auchus that are not prior art to
the ’908 patent in an attempt to show that crinecerfont inherently has clinical
properties that were not already demonstrated in Grigoriadis.5

5 We also note that this reasoning was expressly employed by the Examiner
during prosecution of the ’908 patent, who stated in both the Non-Final
Office Action of July 15, 2019 and the Final Office Action of October 4,
PGR2021-00088
Patent 10,849,908 B2

20

Nor is Petitioner’s inherency argument commensurate with the scope
of the claims. Claims 1 and 11 recite administering to a human “a
therapeutically-effective amount of a CRF receptor antagonist or a
pharmaceutically acceptable salt thereof.” Petitioner’s declarant, Dr. Carey,
acknowledges that “[b]ased on my review of the published literature, over
100 CRF1 receptor antagonists had been characterized or were in clinical
development prior to the filing of the ’908 patent, including NBI34041,
verucerfont, and pexacerfont. Ex. 1005 ¶ 99 (citing Ex. 1029; Ex. 1018;
Ex. 1030; Ex. 1031). Petitioner has not demonstrated that all, or even a
representative number of this genus have necessarily demonstrated an “at
least 10% reduction in a patient’s ACTH level from baseline.”
Grigoriadis may well support an obviousness challenge to claims 1
and 11, however Petitioner has not made that argument, or challenged
independent claims 1 and 11 as unpatentable under 35 U.S.C. § 103. And
because we find that: (1) Grigoriadis does not expressly disclose all of the
limitations of claims 1 and 11; and (2) Auchus does not support Petitioner’s
argument that Grigoriadis inherently discloses the non-expressly taught
limitations of claims 1 and 11, we conclude that Petitioner has failed to

2019, that “The prior art is not anticipatory insofar as these combinations
must be selected from various lists/locations in the reference.” Ex. 1002,
113, 87. Although we need not reach Patent Owner’s arguments with
respect to 35 U.S.C. § 325(d), we find this finding of the Examiner to be
relevant here, because we agree that the disclosure of crinecerfont as a
CRF1 receptor antagonist, but the lack of any clinical showing of
crinecerfont’s efficacy, demonstrates that Grigoriadis does not anticipate
claims 1 and 11.
PGR2021-00088
Patent 10,849,908 B2

21

establish that it is more likely than not that Grigoriadis anticipates claims 1
and 11 of the ’908 patent.

c. Dependent claims 2–4, 7–9, 12–14, 17–19, 21–24
Claims 2–4, 7–9, and 21 depend, directly or indirectly, from claim 1.
Claims 12–14, 17–19, and 22 depend, directly or indirectly, from claim 11.
Claims 23 or 24 depend from either claims 1 or 11. Petitioner makes
arguments that these dependent claims are also anticipated by Grigoriadis.
See Pet. 51–58. However, because we conclude, for the reasons explained
supra, that Petitioner is not reasonably likely to prevail in proving at trial
that Grigoriadis anticipates the independent claims, we similarly conclude
that Petitioner has not established a likelihood of similarly prevailing with
respect to the dependent claims.

D. Ground II: Obviousness of Claims 4, 10, 14, 20–22, and 25 by
Grigoriadis
These claims depend, directly or indirectly, from independent claims
1 or 11. Petitioner argues that, because:
[A]dministering a CRF1 receptor antagonist at a dose of 200
mg/day is inherently anticipated by Grigoriadis’s disclosure of
crinecerfont to treat CAH, and Neurocrine’s Phase II clinical data
reported in Auchus 2021 demonstrating that administration of
200 mg/day crinecerfont results in the claimed ACTH and 17-
OHP reductions from baseline. These [dependent] claims are
also obvious in view of the disclosure of NBI-77860 in
Grigoriadis.

PGR2021-00088
Patent 10,849,908 B2

22

Pet. 61 (citing Ex. 1005 ¶¶ 72–73). In effect, Petitioner argues that these
dependent claims are obvious variations of the allegedly anticipated claims 1
and 11. See id.
However, as we have explained supra, we have concluded that
Petitioner has failed to establish that it is more likely than not that
independent claims 1 and 11 are anticipated by Grigoriadis. Petitioner
makes no argument that independent claims 1 and 11 are obvious over
Grigoriadis. Because Petitioner’s arguments with respect to Ground II rely
in principal part in showing that dependent claims 4, 10, 14, 20–22, and 25
are obvious in view of the alleged anticipation of claims 1 and 11 by
Grigoriadis, Petitioner’s arguments must again fail. We therefore conclude
that Petitioner has failed to establish that it is more likely than not that
dependent claims 4, 10, 14, 20–22, and 25 are obvious over Grigoriadis.

E. Ground III: Obviousness of Claims 5–6 and 15–16 by Grigoriadis and
Romano

1. Overview of Romano
Romano is directed to:
[A] pharmaceutical compositions [sic] for treating, for example,
mood disorders or conditions, psychotic disorders or conditions,
or a combination thereof, in a mammal such as a human, the
composition comprising (a) an atypical antipsychotic, a prodrug
thereof or a pharmaceutically acceptable salt of the atypical
antipsychotic or prodrug thereof, (b) a corticotropin releasing
factor antagonist, a prodrug thereof, or pharmaceutically
acceptable salt of said corticotropin releasing factor antagonist
or prodrug thereof, and optionally (c) a pharmaceutically
acceptable vehicle, carrier or diluent.

PGR2021-00088
Patent 10,849,908 B2

23

Ex. 1007, Abstr. Specifically, Romano teaches that “[i]n particular, CRF
antagonists have been described as effective in the treatment of, for example,
stress-related illnesses; mood disorders such as depression, including, for
example, depression in cancer patients, depression in Parkinson’s patients.”
Id. at ¶ 10.
With response to its formulations, Romano teaches:
The pharmaceutical compositions of the present invention can
consist of a combination of immediate release and controlled
release characteristics. Such compositions can take the form of
combinations of the active ingredients that range in size from
nanoparticles to microparticles or in the form of a plurality of
pellets with different release rates. The tablet or capsule
composition of the present invention can contain an atypical
antipsychotic in sustained or controlled release form and the CRF
antagonist in an immediate release form. Alternatively, the
atypical antipsychotic can be in immediate release form and the
CRF antagonist can be in sustained or controlled release form.

Ex. 1007 ¶ 531 (emphasis added).

2. Alleged obviousness of claims 5–6 and 15–16 over Grigoriadis
and Romano

a. Petitioner’s contentions

Dependent claim 5 is representative of these claims, and recites “the
method of claim 1, wherein said CRF receptor or a pharmaceutically
acceptable salt thereof is in the form of microparticles.” Ex. 1001 col. 48,
ll. 22–26. Claims 6 and 16 further define the size range of the microparticles
as being between 1 m and 20 m. Id. at col. 48, ll. 27–28, 57–58.
PGR2021-00088
Patent 10,849,908 B2

24

Petitioner acknowledges that Grigoriadis does not explicitly disclose
administering the CRF1 receptor antagonist in the form of microparticles.
Pet. 68. According to Petitioner, however, it would have been obvious to
formulate the CRF1 receptor antagonists disclosed by Grigoriadis as
microparticles with an average size of between about 1–20 μm, as taught by
Romano. Id. Petitioner contends that Romano expressly teaches that the
active ingredients of Romano’s claimed compositions, a CRF1 receptor
antagonist and an atypical antipsychotic, can range in size from
nanoparticles to microparticles. Id. at 68–69 (citing Ex. 1005 ¶¶ 76–77;
Ex. 1007 ¶ 531). According to Petitioner, a person of ordinary skill in the
art would have understood Romano as teaching the use of small particle
sizes with CRF1 receptor antagonists, such as the claimed range of between
about 1–20 μm. Id. at 69.
Petitioner argues further that a person of ordinary skill in the art
would have been motivated to combine the teachings of Grigoriadis with
Romano because both relate to pharmaceutical compositions comprising a
CRF1 receptor antagonist. Pet. 69 (citing Ex. 1005 ¶ 77; Ex. 1006 ¶ 61;
Ex. 1007 ¶ 531). Furthermore, argues Petitioner, a skilled artisan would
have known that microparticles could be used to create sustained release
formulations, and would have been motivated to combine Grigoriadis and
Romano because both disclose using a CRF1 receptor antagonist in a
sustained release formulation. Id. (citing Ex. 1005 ¶ 77; Ex. 1006 ¶ 73;
Ex. 1007 ¶ 531; Ex. 1023, 2; Ex. 1035, 309–310, 349–350). Petitioner
asserts that Grigoriadis teaches that CRF1 receptor antagonist compositions
could generally be prepared using well-known technology, and a person of
ordinary skill would have been familiar with microparticles as a common
PGR2021-00088
Patent 10,849,908 B2

25

form of administering a pharmaceutical active ingredient. Id., 69–70 (citing
Ex. 1005 ¶ 77; Ex. 1006 ¶ 73; Ex. 1023, 2; Ex. 1035, 309–310, 349–350).

b. Analysis
We conclude that Petitioner’s argument with respect to Ground III
must fail, because, again, Petitioner has made no argument or showing with
respect to this Ground, or with respect to Grounds I and II, that any of the
limitations of independent claims 1 and 11, from which claims 5–6 and 15–
16 depend, and each of which therefore incorporate the limitations of the
independent claims, are obvious over Grigoriadis. See Robotic Vision Sys.,
Inc. v. View Eng’g, Inc., 189 F.3d 1370 1376 (Fed. Cir. 1999) (holding that
dependent claims are to be construed to incorporate by reference all of the
limitations of the claims from which they depend (citing 35 U.S.C. § 112)).
Petitioner advances no ground or basis that the limitations of independent
claims 1 and 11 are obvious over Grigoriadis, but argues only that these
claims are anticipated.
We have explained in Section III.C.2.b, supra, why we have
concluded that Petitioner has failed to establish that it is more likely than not
that independent claims 1 and 11, from which claims 5–6 and 15–16 depend,
are anticipated by Grigoriadis. The Petition makes no argument, and
adduces no evidence of record, to show that the limitations of the
independent claims, which must be construed as being incorporated by
reference into claims 5–6 and 15–16, are obvious over Grigoriadis. See
Robotic Vision, 189 F.3d at 1376. Absent any such argument, Petitioner has
failed to demonstrate that it is more likely than not that these dependent
claims are obvious over Grigoriadis.
PGR2021-00088
Patent 10,849,908 B2

26

F. Ground IV: Claims 1–25 Lack of Written Descriptive Support

1. Petitioner’s Contentions
Petitioner argues that the claims of the ’908 patent fail the written
description requirement because the ’908 patent does not show possession of
the claimed subject matter. Pet. 72. Petitioner contends that the claims are
broad and recite methods of treating CAH that employ a “CRF1 receptor
antagonist or a pharmaceutically acceptable salt thereof” that reduces ACTH
or 17-OHP by at least 10% from baseline. Id. Petitioner asserts that these
are “functionally defined” claims that are unbounded structurally and are
limited only by the achieved effect on ACTH and/or 17-OHP. Id. Petitioner
points to our reviewing court’s opinion in Ariad Pharm., Inc. v.
Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010) (en banc), as requiring that
the patent must disclose either a representative number of species or
common structural features. Id. at 72–73 (citing Ariad, 598 F.3d 1350).
Petitioner notes that CRF1 receptor antagonists represent a large,
structurally diverse class of over 100 compounds, but asserts that the ’908
patent discloses only a single CRF1 receptor antagonist, tildacerfont
(Compound 1). Pet. 73 (citing Ex. 1005 ¶¶ 98–100). Furthermore, argues
Petitioner, all of the Examples and clinical data in the ’908 patent relate to
tildacerfont. Id. (citing Ex. 1001, cols. 34–47, ll. 5–58, Tables 5–8).
Petitioner contends that the ’908 patent does not disclose the use of any
other CRF1 receptor antagonist to treat CAH, or disclose structural features
common to the members of the genus so that one of skill in the art could
visualize or recognize the members of the genus. Id. at 73–74.

PGR2021-00088
Patent 10,849,908 B2

27

2. Patent Owner’s Preliminary Response
Patent Owner responds that Petitioner incorrectly assumes there is a
per se rule that a claim is invalid if there is only one working example in the
specification. Prelim. Resp. 39. Patent Owner argues that Ariad states no
such rule, noting that Ariad involved a patent application that disclosed no
example of any species actually being used to achieve the claimed result. Id.
(citing Ariad, 598 F.3d at 1356). Patent Owner argues that there is no rule
categorically requiring disclosure of using more than one antagonist from a
known class to provide written description support for a method directed to
using that class, and points to a recent Board decision rejecting the same
arguments made by Petitioner. Id. (citing Merck Sharp & Dohme Corp. v.
Genentech, Inc., PGR2021-00039, Paper 10 at 7, 13–22 (July 24, 2021)
(denying institution challenging, inter alia, written description of claims to a
method for treating cancer by administering a PD antagonist together with a
TIGIT antagonist)).
Patent Owner contends that the ’908 patent is directed to a method of
treatment using a CRF1 receptor antagonist that is exemplified by actual
reduction to practice—a working example demonstrating the inventors were
in possession of the claimed invention. Prelim. Resp. 41. According to
Patent Owner, the Specification of the ’908 patent discloses using a CRF1
receptor antagonist, in the manner claimed, to achieve the claimed results.
Id. Patent Owner points out that Petitioner’s declarant acknowledges that a
person of ordinary skill in the art would, at the time of filing, have been in
possession of a discrete class of approximately 100 CRF1 receptor
antagonists that had already “been characterized or were in clinical
PGR2021-00088
Patent 10,849,908 B2

28

development prior to the filing of the ’908 patent.” Id. (quoting Pet. 73; see
also Ex. 1005 ¶ 99).
Patent Owner therefore distinguishes the present case from Ariad
because the Specification of the ’908 patent discloses an example practicing
the invention, and referred to a known class of CRF1 receptor antagonists
that would have been recognized by a skilled artisan. Id. (citing Pet. 71).

3. Analysis
We conclude that Petitioner has not established that it is more likely
than not that any claim in Ground IV is unpatentable upon this Ground.
“The essence of the written description requirement is that a patent
applicant, as part of the bargain with the public, must describe his or her
invention so that the public will know what it is and that he or she has truly
made the claimed invention.” AbbVie Deutschland GmbH & Co., KG v.
Janssen Biotech, Inc., 759 F.3d 1285, 1298 (Fed. Cir. 2014) (citing Festo
Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 736 (2002)).
According to our reviewing court:
[W]e have repeatedly indicated that the written description
requirement does not demand either examples or an actual
reduction to practice. Ariad, 598 F.3d at 1352. What it does
demand is that one of skill in the art can “visualize or recognize”
the claimed antibodies based on the specification’s disclosure.
Eli Lilly, 119 F.3d at 1568. In other words, the specification must
demonstrate constructive possession…. Ariad, 598 F.3d at 1352.

Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 1353
(2011); see also, e.g., Abbvie, 759 F.3d at 1299:
One particular question regarding the written description
requirement has been raised when a genus is claimed but the
PGR2021-00088
Patent 10,849,908 B2

29

specification only describes a part of that genus that is
insufficient to constitute a description of the genus.
….

“For generic claims, we have set forth a number of factors for
evaluating the adequacy of the disclosure, including ‘the existing
knowledge in the particular field, the extent and content of the
prior art, the maturity of the science or technology, [and] the
predictability of the aspect at issue.’”
…..

Here, the claimed invention is a class of fully human antibodies
that are defined by their high affinity and neutralizing activity to
human IL–12, a known antigen. AbbVie’s expert conceded that
the ’128 and ’485 patents do not disclose structural features
common to the members of the claimed genus. The question
therefore is whether the patents sufficiently otherwise describe
representative species to support the entire genus.

(Internal references and citations omitted).
The challenged claims recite a genus (“a CRF1 receptor antagonist or
pharmaceutically acceptable salt thereof) that is not itself claimed. The
claims, rather, are directed to a method of using that genus in the treatment
of CAH. The prior art cited by Petitioner acknowledges that the genus of
CRF1 receptor antagonists was well known in the art at the time of
invention. See Ex. 1006, e.g., ¶¶ 20, 21, 25, 26, 52–55. Furthermore, the
Specification of the ’908 patent discloses that CRF1 receptor antagonists
were known in the art, identifies an example of a CRF1 receptor antagonist,
and provides an exemplary embodiment by which a CRF1 receptor
antagonist is administered to achieve the claimed effect. See Ex. 1001
col. 10, ll. 47–64, col. 12, ll. 27–30; Ex. 4. Finally, Petitioner’s declarant,
Dr. Carey, acknowledges that this genus would have been well known to a
PGR2021-00088
Patent 10,849,908 B2

30

person of ordinary skill in the art. See Ex. 1005 ¶ 99 (citing Ex. 1029;
Ex. 1018; Ex. 1030; Ex. 1031) (“Based on my review of the published
literature, over 100 CRF1 receptor antagonists had been characterized or
were in clinical development prior to the filing of the ’908 patent, including
NBI34041, verucerfont, and pexacerfont”).
We consequently conclude that Petitioner’s argument has not
established that the Specification fails to “reasonably convey[] to those
skilled in the art that the inventor had possession of the claimed subject
matter as of the filing date.” Ariad, 598 F.3d at 1351. We further conclude
that Petitioner has not demonstrated that it is more likely than not that any
claim in Ground IV is unpatentable.

G. Ground V: Claims 1–25 Lack of Enablement

1. Petitioner’s Contentions
Petitioner argues that the Specification of the ’908 patent fails to
enable the full scope of the claims, because the claims recite CRF1 receptor
antagonists broadly, but the patent provides only a single example,
tildacerfont (Compound 1). Pet. 76. Petitioner contends that, during
prosecution, Patent Owner singled out tildacerfont by alleging that
tildacerfont’s ability to maintain the claimed ACTH and 17-OHP reductions
were unexpected. Id. (citing Ex. 1002, 30–38). Petitioner further contends
that Patent Owner relied on this argument to distinguish another CRF1
receptor antagonist, Neurocrine’s NBI-77860. Id.
Petitioner argues that the genus of CRF1 receptor antagonists included
over 100 structurally diverse compounds prior to the filing of the ’908
PGR2021-00088
Patent 10,849,908 B2

31

patent. Pet. 76 (citing Ex. 1005 ¶ 99). Petitioner asserts that, given the large
scope of the CRF1 receptor antagonist genus, and given Patent Owner’s
arguments that the ability of a single agent (tildacerfont) to perform the
claimed reduction was unexpected relative to a different CRF1 receptor
antagonist, Spruce fails to enable the full scope of the claims. Id. According
to Petitioner, it would require undue experimentation to determine which
CRF1 receptor antagonists from among the members of this large genus
could achieve the claimed reductions. Id. at 76–77.

2. Patent Owner’s Preliminary Response
Patent Owner responds that Petitioner offers only the conclusory
assertion that the claims would require undue experimentation, but presents
no evidence to support this assertion. Prelim. Resp. 44. Patent Owner
asserts that Petitioner’s declarant fails to address the issue of whether the
claims would require undue experimentation. Id.
Patent Owner asserts that the Specification of the ’908 patent provides
an explanation of the mechanism of action, a working example, and clinical
trial protocols used to verify efficacy. Prelim. Resp. 46. Patent Owner
argues that Petitioner ignores the Specification’s explanation that CAH is
treated by “reducing the elevated ACTH levels from the pituitary,” its
identification of CRF1 as “the major physiological regulator of the basal and
stress-induced release of adrenocorticotropic hormone (‘ACTH’),” and its
description of the development of “biologically-active small molecules
having significant CRF receptor binding activity and which are capable of
antagonizing the CRF1 receptor” to reduce ACTH levels by reducing CRF
PGR2021-00088
Patent 10,849,908 B2

32

secretion. Id. at 46–47 (citing Ex. 1001 cols. 10–11, ll. 66–9, col. 11, ll. 49–
64).
Patent Owner further contends that Petitioner ignores the ’908
patent’s provision of the protocols used for evaluating CRF1 receptor
antagonists for treatment of CAH. Prelim. Resp. 47 (citing Ex. 1001 cols.
36–48, ll. 35–3). According to Patent Owner, Petitioner unduly minimizes
the importance of the working example and the fact that a relatively small
number (approximately 100) of known compounds were already available.
Id. Patent Owner argues that the ’908 patent “disclosure provides
considerable direction and guidance on how to practice their invention and
presents working examples” and thus “leads to the conclusion that undue
experimentation would not be required to practice the invention.” In re
Wands, 858 F.2d 731, 740 (Fed. Cir. 1988). Patent Owner asserts that the
petition provides no reason that a skilled artisan, equipped with the protocols
of the ’908 patent and the discrete genus of CRF1 receptor antagonists,
would require undue experimentation to make and use the claimed
invention. Prelim. Resp. 47. Patent Owner notes that the Specification is
not required to demonstrate experimentally every possible embodiment that
falls within the scope of a claim in order to be enabling. Id. (citing Amgen
Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1336 (Fed. Cir. 2003)).
Finally, Patent Owner argues, Petitioner contends that the art was
unpredictable because one CRF1 receptor antagonist performed differently
relative to another CRF1 receptor antagonist. Prelim. Resp. 48 (citing
Pet. 76). However, argues Patent Owner, differing levels of performance for
one compound does not undermine enablement. Id. Patent Owner asserts
that “[e]ven if some of the claimed combinations were inoperative, the
PGR2021-00088
Patent 10,849,908 B2

33

claims are not necessarily invalid.” Id. (quoting Atlas Powder Co. v. E.I. du
Pont De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984)) (alteration
in original).

3. Analysis
Section 112 requires that the patent specification enables “those
skilled in the art how to make and use the full scope of the claimed invention
without ‘undue experimentation’” in order to extract meaningful disclosure
of the invention and, by this disclosure, advance the technical arts. Koito
Mfg. Co., Ltd. v. Turn-Key-Tech, LLC, 381 F.3d 1142, 1155 (Fed. Cir. 2004)
(quoting Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1365 (Fed.
Cir. 1997)). Furthermore:
The scope of [patent] claims must be less than or equal to the
scope of the enablement. The scope of enablement, in turn, is that
which is disclosed in the specification plus the scope of what
would be known to one of ordinary skill in the art without undue
experimentation.

Nat’l Recovery Techs., Inc. v. Magnetic Separation Sys., Inc., 166 F.3d
1190, 1196 (Fed. Cir. 1996); see also In re Goodman, 11 F.3d 1046, 1050
(Fed. Cir. 1993) (holding that “the specification must teach those of skill in
the art ‘how to make and how to use the invention as broadly as it is
claimed’”). Furthermore, “the scope of the claims must bear a reasonable
correlation to the scope of enablement provided by the specification to
persons of ordinary skill in the art.” In re Fisher, 427 F.2d 833, 839
(C.C.P.A. 1970).
Petitioner argues that the claims of the ’908 patent are not enabled
because a person of ordinary skill in the art would be required to perform
PGR2021-00088
Patent 10,849,908 B2

34

“undue experimentation” in order to practice the invention. Pet. 76–77
(citing In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988)).6 Petitioner
provides no evidence of record to support this allegation, beyond noting that,
during prosecution, Patent Owner contended that tildacerfont’s ability to
maintain the claimed ACTH and 17-OHP reductions was unexpected,
distinguishing it from another CRF1 receptor antagonist, Petitioner’s NBI-
77860. Id. at 76.
We do not find this persuasive. In the Notice of Allowance, filed
September 30, 2020, the Examiner provided two reasons why the
Specification of the ’908 patent discloses unexpected results: (1) hormone
reductions were maintained over a 6-week period in the treatment of
congenital adrenal hyperplasia; and (2) maintaining the reduced hormone
levels beyond 24 hours post-treatment. See Ex. 1002, 12. Nevertheless, the
Examiner made no finding that the claims of the ’908 patent were not
enabled by the Specification.
More importantly, Petitioner adduces no evidence of record that
practicing the invention claimed by the ’908 patent would require undue
experimentation. To the contrary, Petitioner’s declarant, Dr. Carey, testifies
that the genus of CRF1 receptor antagonists was known in the art. The prior
art reference principally relied upon by Petitioner, Grigoriadis, expressly
teaches significant reduction of ACTH and 17-OHP levels in humans in
response to administration of another known CRF1 receptor antagonist,
verucerfont, compared to placebo. See Ex. 1006 ¶¶ 90–95. The

6 We also note here that, although Petitioner cites to Wands, the Petition
provides no systematic analysis of, or even addresses, the Wands factors in
the context of this case.
PGR2021-00088
Patent 10,849,908 B2

35

Specification of the ’908 patent discloses, as Patent Owner points out, an
explanation of the mechanism of action, a working example, and clinical
trial protocols used to verify efficacy. See Prelim Resp. 46. Against these
disclosures, we find that Petitioner’s argument that practicing the claimed
invention of the ’908 patent would require undue experimentation, without
further evidentiary support, would be unsustainable at trial. We
consequently conclude that Petitioner has failed to establish that it is more
likely than not that any claim in Ground V is unpatentable. We therefore
deny institution of post grant review.

IV. CONCLUSION
For the reasons we have explained, we conclude that Petitioner has
failed to establish a sufficiently persuasive showing that the cited prior art
references disclose, teach, or suggest at least one claim of the ’908 patent, as
set forth in the asserted Grounds I–III or that the claims lack written
descriptive support or are not enabled as set forth in the asserted Grounds IV
and V respectively. 35 U.S.C. § 314. Because we decline to institute post-
grant review on the merits, we do not reach Patent Owner’s arguments with
respect to our discretion to deny institution under 35 U.S.C. § 325(d).

V. ORDER
In consideration of the foregoing, it is hereby:
ORDERED, pursuant to 35 U.S.C. § 314(a), that the Petition for post-
grant review of the challenged claims of US Patent 10,849,908 B2 is
DENIED with respect to all Grounds in the Petition; and
FURTHER ORDERED that post-grant review is not instituted.
PGR2021-00088
Patent 10,849,908 B2

36

For PETITIONER:
Dorothy Whelan
Robert Oakes
FISH & RICHARDSON P.C.
whelan@fr.com
oakes@fr.com

For PATENT OWNER:

Michael T. Rosato
Jad A. Mills
WILSON SONSINI GOODRICH & ROSATI
mrosato@wsgr.com
jmills@wsgr.com