Antecip Bioventures II LLC

Patent Trials and Appeals Board

Jul 28, 2020

PGR2019-00027 (P.T.A.B. Jul. 28, 2020)

Trials@uspto.gov Paper 24
Tel: 571-272-7822 Date: July 28, 2020

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

GRÜNENTHAL GMBH,
Petitioner,
v.
ANTECIP BIOVENTURES II LLC,
Patent Owner.

PGR2019-00027
Patent 10,039,774 B2

Before GRACE KARAFFA OBERMANN, CHRISTOPHER M. KAISER,
and WESLEY B. DERRICK, Administrative Patent Judges.
OBERMANN, Administrative Patent Judge.
JUDGMENT
Final Written Decision
Determining All Claims Unpatentable
35 U.S.C. § 328(a)

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INTRODUCTION
A. Background
Grünenthal GmbH (“Petitioner”) filed a Petition (Paper 2, “Pet.”)
requesting a post-grant review of claims 1–29 of U.S. Patent No. 10,039,774
B2 (Ex. 1002, “the ’774 patent”). Antecip Bioventures II LLC (“Patent
Owner”) did not file a Preliminary Response. We instituted review of all
challenged claims on each of the grounds asserted in the Petition. Paper 6
(“Dec. Inst.”). Following institution, Patent Owner filed a Response (Paper
10, “PO Resp.”), Petitioner filed a Reply (Paper 12, “Reply”), and Patent
Owner filed a Sur-Reply (Paper 15, “PO Sur-Reply”). Patent Owner also
filed a motion to exclude certain evidence. Paper 20 (“Mot. Exclude”).
Petitioner opposed this motion (Paper 21, “Opp. Mot.”), and Patent Owner
filed a Reply (Paper 22, “Reply Mot.”). We held a hearing on April 24,
2020, the transcript of which has been entered into the record. Paper 23.
We have jurisdiction under 35 U.S.C. § 6, and we issue this Final
Written Decision pursuant to 35 U.S.C. § 328(a). We conclude that
Petitioner has established by a preponderance of the evidence that claims 1–
29 of the ’774 patent are unpatentable.
B. Related Matters
The parties do not direct us to any judicial matter that would be
affected by the outcome of this proceeding. Pet. 4–5; Paper 3, 2. Petitioner,
however, challenges patents related to the ’774 patent in additional
administrative petitions for review. Pet. 4; Paper 3, 2. In particular,
according to the parties, the Board has issued final written decisions in
PGR2017-00008 and PGR2017-00022, and petitions are pending in
PGR2018-00001, PGR2018-00062, PGR2019-00003, PGR2019-00026, and
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PGR2019-00028. Id. After the parties identified related matters, the Board
issued a final written decision in PGR2018-00001. See PGR2018-00001,
Paper 48 (PTAB April 29, 2019).
C. The Asserted Grounds of Unpatentability
Petitioner contends that claims 1–29 of the ’774 patent are
unpatentable based on the following grounds (Pet. 22–75):1
35 U.S.C. § References/Basis Challenged Claims
103 Varenna 2011,2 Gatti,3
Muratore,4 Harden,5
Drummond6
1–15

1 Petitioner also relies on a Declaration from Lawrence Poree, M.D., Ph.D.
Ex. 1004.
2 Massimo Varenna, The Clinical Framework of Algodystrophy (Complex
Regional Pain Syndrome Type I), An Update, 37 IT. J. ORTHOPEDICS &
TRAUMATOLOGY 227, 227–34 (Oct. 2011) (Ex. 1006, “Varenna 2011”)
(English translation).
3 Davide Gatti, Ombretta Viapiana, Luca Idolazzi, Elena Fracassi & Silvano
Adami, Neridronic Acid for the Treatment of Bone Metabolic Diseases,
5 EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY 1305, 1305–11
(2009) (Ex. 1008, “Gatti”).
4 M. Muratore, F. Calcagnile, L. Cosentino, M. Serra, C. Circhetta, & E.
Quarta, Neridronate in the Treatment of Reflex Sympathetic Hip
Algodystrophy: Open Comparison with Clodronate, PROGRESS IN
RHEUMATOLOGY (Apr. 2004) (Ex. 1007, “Muratore”) (English translation).
5 R. Norman Harden, Stephen Bruehl, Roberto S.G.M. Perez, Frank
Birklein, Johan Marinus, Christian Maihofner, Timothy Lubenow,
Asokumar Buvanendran, Sean Mackey, Joseph Graciosa, Mila Mogilevski,
Christopher Ramsden, Melissa Chont, & Jean-Jacques Vatine, Validation of
Proposed Diagnostic Criteria (the “Budapest Criteria”) for Complex
Regional Pain Syndrome, 150 PAIN 268, 268–74 (Apr. 2010) (Ex. 1009,
“Harden”).
6 Peter D. Drummond, Sensory Disturbances in Complex Regional Pain
Syndrome: Clinical Observations, Autonomic Interactions, and Possible
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35 U.S.C. § References/Basis Challenged Claims
103 Varenna 2011, Gatti,
Muratore, Harden7
16–29
112 Written Description 1–29
D. The ’774 Patent
The ’774 patent, titled “Neridronic Acid for Treating Complex
Regional Pain Syndrome,” issued on August 7, 2018. Ex. 1002, at (45),
(54). The ’774 patent relates to “[o]steoclast inhibitors, such as neridronic
acid, in an acid or a salt form” that “can be used to treat or alleviate pain or
related conditions, such as complex regional pain syndrome” (“CRPS”). Id.
at (57).
According to the ’774 patent, “[b]isphosphonate compounds are
potent inhibitors of osteoclast activity, and are used clinically to treat bone-
related conditions such as osteoporosis and Paget’s disease of bone,” as well
as “cancer-related conditions including multiple myeloma, and bone
metastases from solid tumors,” but these compounds “generally have low
oral bioavailability.” Id. at 1:38–43. “[O]ral dosage forms of
bisphosphonate compounds . . . can be used to treat or alleviate pain or
related conditions.” Id. at 1:51–54. Two of these conditions are “changes in
skin blood flow” and “abnormal sudomotor activity” associated with CRPS,

Mechanisms, 11 Pain Medicine 1257, 1257–66 (2010) (Ex. 1010,
“Drummond”).
7 This ground advances the same prior art references as the obviousness
ground asserted against claims 1–16. We address this as a distinct ground to
mirror the structure of the Petition.
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which is a “debilitating pain syndrome[] . . . characterized by severe pain in
a limb.” Id. at 13:23–32.
None of the figures or working examples in the specification of
the ’774 patent relate to the use of neridronic acid. Id. at 3:21–4:13
(describing Figs. 1–16), 49:33–65:24 (Examples 1–10); see id. at Figs. 1–16
(all discussing the use of zoledronic acid). Nevertheless, the specification
identifies neridronic acid as a bisphosphonate suitable for use in the
invention and contains information pertaining to daily oral dosing of
neridronic acid. Id. at 3:4–10, 31:40–45. The specification also refers to a
“molecular complex comprising neridronic acid” that “is administered in an
amount that results in” certain disclosed blood plasma concentration curves.
Id. at 26:30–43. Moreover, the specification contains other general
information pertaining to the dosing of neridronic acid. For example,
the ’774 patent describes the administration of “[a]ny suitable amount of an
osteoclast inhibitor, including a bisphosphonate,” from a list that includes
“neridronic acid” and identifies broad dosing ranges (from about 0.005 mg
to about 2000 mg). Id. at 33:25–57. The ’774 patent also describes the
administration of “any amount of osteoclast inhibitor” that is “in a range
bounded by, or between, any of these values.” Id. at 34:12–13. The
specification compares oral forms of bisphosphonates to “parenteral modes
of administration, such [as] intravenous or subcutaneous” modes. Id.
at 26:57–61. The specification explains that “[c]ommonly used measures of
pain intensity include the visual analog scale (VAS) and the numerical rating
scale (NRS).” Id. at 10:9–11.
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E. Illustrative Claims
Claims 1–29 of the ’774 patent are challenged. Claims 1 and 16 are
independent and illustrative; they recite:
1. A method of treating changes in skin blood flow associated
with complex regional pain syndrome, comprising
parenterally administering neridronic acid in a salt form or
an acid form to a human being suffering from changes in
skin blood flow associated with complex regional pain
syndrome, wherein the human being has a pain intensity of
at least 7 cm on the 10 cm visual analogue scale (VAS) or at
least 7 on the 0–10 numerical rating scale (NRS).
Ex. 1002, 90:33–40.
16. A method of treating abnormal sudomotor activity
associated with complex regional pain syndrome,
comprising parenterally administering neridronic acid in a
salt form or an acid form to a human being suffering from
abnormal sudomotor activity associated with complex
regional pain syndrome, wherein the human being has a pain
intensity of at least 7 cm on the 10 cm visual analogue scale
(VAS) or at least 7 on the 0–10 numerical rating scale
(NRS).
Id. at 91:14–21.
ANALYSIS
A. Eligibility of the ’774 Patent for Post-Grant Review
Post-grant reviews are available only for patents “described in section
3(n)(1)” of the Leahy-Smith America Invents Act (“AIA”), Pub L. No. 112-
29, 125 Stat. 284 (2011). AIA § 6(f)(2)(A). These patents are those that
issue from applications “that contain[] or contained at any time . . . a claim
to a claimed invention that has an effective filing date as defined in section
100(i) of title 35, United States Code, that is on or after” “the expiration of
the 18-month period beginning on the date of the enactment of” the AIA.
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Id. § 3(n)(1). Because the AIA was enacted on September 16, 2011, post-
grant reviews are available only for patents that issue from applications that
at one point contained at least one claim with an effective filing date on or
after March 16, 2013, with “effective filing date” having the definition given
to it by 35 U.S.C. § 100(i). The effective filing date of an application for a
patent on an invention is “the filing date of the earliest application for which
the . . . application is entitled, as to such invention, to a right of priority
under section 119, 365(a), 365(b), 386(a), or 386(b) or to the benefit of an
earlier filing date under section 120, 121, 365(c), or 386(c).” 35 U.S.C.
§ 100(i)(1)(B).
Petitioner argues that, although the ’774 patent claims priority to
several applications filed before March 16, 2013, it nevertheless is eligible
for post-grant review because it “contains . . . at least one claim that was not
disclosed in compliance with the written description and enablement
requirements of § 112(a) in the” applications to which it claims priority.
Pet. 19 (quoting Inguran, LLC v. Premium Genetics (UK) Ltd., PGR2015-
00017, Paper 8 at 11 (PTAB Dec. 22, 2015)). Specifically, Petitioner argues
that none of the applications to which the ’774 patent claims priority
sufficiently describes claims 10–13 or 25–28. Id. at 20–22. Those claims
recite limitations regarding the age of patients being treated or the duration
of the patient’s suffering from complex regional pain syndrome. Ex. 1002,
90:65–91:8, 92:16–26. According to Petitioner, none of the priority
applications describe these limitations. Pet. 20–22.
In our Decision on Institution, based on Petitioner’s representations,
we preliminarily found that the ’774 patent was eligible for post-grant
review. Dec. Inst. 8–9. We observed that “Patent Owner may dispute that
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finding in a timely-filed response to the Petition.” Id. at 9. Patent Owner
did not dispute our finding or otherwise argue that the ’774 patent was
ineligible for post-grant review in its Response. PO Resp. 1–25.
Accordingly, we find that the ’774 patent is eligible for post-grant review.
B. Claim Construction
In a post-grant review, we construe claim terms in an unexpired patent
“in accordance with the ordinary and customary meaning of such claim as
understood by one of ordinary skill in the art and the prosecution history
pertaining to the patent,” as the claims would be construed “in a civil action
under 35 U.S.C. 282(b).” 37 C.F.R. § 42.200(b) (2018). Only terms which
are in controversy need to be construed, and then only to the extent
necessary to resolve the controversy. Vivid Techs., Inc. v. Am. Sci. & Eng’g,
Inc., 200 F.3d 795, 803 (Fed. Cir. 1999). On the question of claim
construction, the sole dispute is whether the preambles of the challenged
claims should be treated as limiting the scope of those claims. Pet. 15–18;
PO Resp. 2–4; Reply 1–2; PO Sur-Reply 1. We agree that no other
limitation requires express discussion for our purposes here.
Claim 1 recites “[a] method of treating changes in skin blood flow
associated with complex regional pain syndrome.” Ex. 1002, 90:33–40.
Claim 16 similarly recites “[a] method of treating abnormal sudomotor
activity associated with complex regional pain syndrome.” Id. at 91:14–21.
Petitioner argues that these preambles should not be interpreted as limiting
the scope of the challenged claims. Pet. 13–18; Reply 1–2. Patent Owner
disagrees, arguing that the preambles should be construed as limiting.
PO Resp. 2–4; PO Sur-Reply 1.
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The result of Petitioner’s unpatentability challenges would not change
regardless of whether the preambles are limiting. Even if the preambles are
limiting, their scope is so broad as to be hardly different from no limitation
at all. The specification of the ’774 patent defines “treating” as “includ[ing]
any kind of treatment activity, including the diagnosis, cure, mitigation, or
prevention of disease in man or other animals, or any activity that otherwise
affects the structure or any function of the body of man or other animals.”
Ex. 1002, 7:43–47. This definition exhibits “reasonable clarity,
deliberateness, and precision” and is “‘set out . . . within the patent
disclosure’ so as to give one of ordinary skill in the art notice of the change”
in meaning. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994) (quoting
Intellicall, Inc. v. Phonometrics, Inc., 952 F.2d 1384, 1387–88 (Fed. Cir.
1992)). Accordingly, we give effect to this definition of “treating.”
Under the definition of “treating” in the specification of the ’774
patent, “[a] method of treating” changes in skin blood flow (claim 1) or
abnormal sudomotor activity (claim 16) “associated with complex regional
pain syndrome” means a method of diagnosing, curing, mitigating, or
preventing that condition associated with complex regional pain syndrome,
or otherwise affecting the structure or any function of the body of someone
suffering from the condition associated with complex regional pain
syndrome. To the extent that this requires carrying out the method on a
patient suffering from changes in skin blood flow (claim 1) or abnormal
sudomotor activity (claim 16) associated with complex regional pain
syndrome, this is already part of the method recited in the body of the
claims, Ex. 1002, 90:33–40, 91:14–21, so the preambles provide no
additional limitation. To the extent that the preambles require some
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particular result to be brought about, that result could be the diagnosis, cure,
mitigation, or prevention of the symptom in question, or it could be any
effect at all on the structure or any function of the patient’s body. Thus,
even when construed as limiting, the preambles provide little, if any, further
restriction on the scope of the challenged claims beyond that set forth in the
body of the claims.
Moreover, as discussed below with respect to the asserted grounds of
obviousness, Petitioner directs us to evidence that the prior art teaches or
suggests the subject matter of the preambles, even when those preambles are
construed as limiting in accordance with the meaning of “treating” provided
in the specification.8 Thus, whether or not we treat the preambles as
limiting, the outcome does not change. Given this circumstance, we treat the
preambles of the challenged claims as limiting and assign them a meaning
consistent with the specification’s definition of “treating.”
C. Asserted Obviousness of Claims 1–15 over Harden, Drummond,
and One or More of Varenna 2011, Gatti, and Muratore
Petitioner argues that the subject matter of claims 1–15 would have
been obvious over the combination of Harden, Drummond, and one or more
of Varenna 2011, Gatti, and Muratore. Pet. 22–50.
1. Varenna 2011
Varenna 2011 relates to “[t]he Clinical Framework of
Algodystrophy,” which is also referred to as “Complex Regional Pain
Syndrome Type I” or “Algodystrophic Syndrome.” Ex. 1006, 227, 228.

8 The asserted ground of unpatentability based on lack of written description
support can be resolved without deciding whether the preambles of the
challenged claims are limiting.
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According to Varenna 2011, the “Budapest Criteria” are “used for the
diagnosis of” CRPS:
1. Continuous pain disproportionate to the triggering
event
2. Patient must report the presence of at least one
symptom in three of the following four categories:
• Sensory changes: hyperesthesia and/or
allodynia
• Vasomotor changes: asymmetry of warmth
when touched and/or change and/or asymmetry
of skin color
• Sudomotor changes/edema: edema and/or
perspiration anomalies and/or asymmetry
• Motor/trophic changes: reduced range of
motion and/or motor anomalies (hyposthenia,
tremors, dystonia) and/or trophic changes (skin,
nails, hair follicles)
3. At least one sign in two or more of the following
categories must be objectivized:
• Sensory changes: hyperalgesia and/or allodynia
• Vasomotor changes: evidence of asymmetry in
contact with heat and/or change and/or
asymmetry of skin color
• Sudomotor changes/edema: evidence of . . .
edema and/or perspiration anomalies and/or
asymmetry
• Motor/trophic changes: evidence of: reduced
range of motion and/or motor anomalies
(hyposthenia, tremors, dystonia) and/or trophic
changes (skin, nails, hair follicles)
4. Absence of alternative diagnostic interpretation
Id. at 228 (Table 1).
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In addition, Varenna 2011 teaches that “various studies . . . seem to
demonstrate the efficacy of Bisphosphonates administered intravenously at
high dosages” in treating CRPS. Id. at 233. Among these bisphosphonates,
“the molecule that has most recently demonstrated efficacy is Neridronate
which seems to possess an excellent efficacy profile when administered
intravenously at a dosage of 100 mg per four infusions every fourth day.”
Id.
2. Gatti
Gatti9 reports that “[i]ntravenous high doses of bisphosphonates are
increasingly used for the treatment of reflex sympathetic dystrophy
syndrome or algodystrophy,” which is another term for CRPS. Ex. 1008,
1308; supra 10. According to Gatti, “the most effective dose is 100 mg
diluted in 250 ml of saline solution given intravenously over 4 days,” and,
“[w]ith this treatment regimen, the proportion of patients experiencing rapid
(in 7 – 12 days) > 70% symptomatic improvements is close to 80%.”
Ex. 1008, 1308. Because of these “preliminary observations,” Gatti reports
that “the first formal registrative randomized double-blind clinical trial
comparing 400 mg neridronic acid to placebo in patients with foot or
forearm algodystrophy syndrome has been designed and is underway.” Id.
3. Muratore
Muratore reports the results of a comparison of neridronate and
clodronate “in the treatment of reflex sympathetic hip algodystrophy.”
Ex. 1007, 89. The purpose of the study was “[t]o evaluate the therapeutic

9 Gatti originally was written in Italian, but we refer to the English
translation Petitioner submitted.
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efficacy of Neridronate.” Id. One group of patients in the study “was
administered neridronate 100 mg, intravenously diluted in 250 cc of saline
solution every 4 days 4 times.” Id. Both neridronate and clodronate
“demonstrated being efficacious in the treatment of Reflex Sympathetic
Algodystrophy” (that is, CRPS (Pet. 31–32)), “but the speed of improvement
of pain symptoms with recovery of functional/motor capability . . . was
demonstrated to be statistically more significant in patients treated with
Neridronate.” Ex. 1007, 89.
4. Harden
Harden reports the results of a study that “sought to compare the
relative diagnostic efficiency of [the Budapest Criteria and an alternative,
older set of diagnostic criteria] in discriminating between CRPS and non-
CRPS neuropathic pain patients.” Ex. 1009, 269. The Budapest Criteria are
listed in Harden; they are similar, with minor differences in wording, to the
Budapest Criteria reported in Varenna 2011. Id. at 274 (Appendix II).
Harden teaches that significant numbers of CRPS patients self-reported or
were observed to exhibit changes in skin blood flow (such as skin color
asymmetry) and abnormal sudomotor activity (such as sweating asymmetry).
Id. at 271 (Table 2). In particular, Harden teaches that:
• 69.4% of CRPS patients exhibited symptoms of temperature
asymmetry on examination;
• 83.9% of CRPS patients exhibited symptoms of skin color
asymmetry on examination;; and
• 43.8% of CRPS patients exhibited sweating asymmetry on
examination.
Id.
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5. Drummond
Drummond reports a review of “mechanisms that might contribute to
sensory disturbances and sympathetically-maintained pain in complex
regional pain syndrome (CRPS).” Ex. 1010, 1257. Drummond teaches that
“CRPS is associated with a range of . . . autonomic abnormalities.” Id.
According to Drummond, these “[a]utonomic disturbances . . . range from
signs of sympathetic deficit (warmth and loss of vasoconstrictor reflexes) to
sympathetic overactivity (sweating and coldness).” Id. at 1260. This effect
can “spread beyond the CRPS-affected limb.” Id. “‘Vasomotor’ refers to
changes in the diameter of blood vessels, namely the dilation or constriction
of blood vessels.” Pet. 27 (citing Ex. 1004 ¶ 71). Drummond demonstrates
“that the vasomotor signs and symptoms listed in the Budapest Criteria are
related to changes in skin blood flow.” Id.; see id. at 28–29 (quoting
Ex. 1010, 1260 and citing Ex. 1004 ¶¶ 70–73).
6. Analysis
Petitioner argues that claims 1–15 of the ’774 patent would have been
obvious over the combined teachings of Harden, Drummond, and one or
more of Varenna 2011, Gatti, and Muratore. Pet. 22–50.
Patent Owner argues, with respect to claims 1–15, that the evidence of
record does not show that a person of ordinary skill in the art would have
had a reasonable expectation of success in treating complex regional pain
syndrome with neridronic acid. PO Resp. 17–24; PO Sur-Reply 4–13.
Patent Owner also argues that none of the asserted references qualifies as a
printed publication under 35 U.S.C. § 102. PO Resp. 4–17; PO Sur-Reply
14–21. Finally, with respect to claim 12, Patent Owner argues that none of
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the asserted references teaches or suggests the duration of symptoms recited
in the claim. PO Resp. 20–24; PO Sur-Reply 13–14.
a. Reasonable Expectation of Success
Patent Owner argues that Petitioner has not shown that a person of
ordinary skill in the art would have had “a reasonable expectation of success
in treating complex regional pain syndrome by administering neridronic
acid.” PO Resp. 17. Specifically, Patent Owner argues that none of
Petitioner’s asserted references provides data showing efficacy (namely, that
administering neridronic acid improves the symptoms of CRPS). Id. at 17–
18. Patent Owner also argues that the failure of Petitioner’s Phase III
clinical trials of neridronic acid for treating CRPS demonstrates the lack of
any reasonable expectation of success. Id. at 19–20. Despite these
arguments, we are persuaded that Petitioner has shown by a preponderance
of the evidence the reasonable expectation of success necessary to support
the obviousness of claims 1–15.
As discussed below with respect to claim 1, Petitioner’s position is
that a person of ordinary skill in the art “would have been motivated to
administer neridronic acid to [patients suffering from CRPS] based on the
disclosures of Varenna 2011, Gatti, and/or Muratore, which teach that
neridronic acid is effective for treating CRPS and its symptoms.” Pet. 36.
There is evidence in each of these references that supports a finding that a
person of ordinary skill in the art reasonably would have expected neridronic
acid to treat CRPS successfully. Varenna 2011 describes “Neridronate”10 as
having “recently demonstrated efficacy” and as “seem[ing] to possess an

10 “Neridronate” is the salt form of neridronic acid. Ex. 1004 ¶ 43.
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excellent efficacy profile” in treating CRPS. Ex. 1006, 233. Muratore
describes the treatment of CRPS using “Neridronate” as resulting in faster
“improvement of pain symptoms with recovery of functional/motor
capability, reduction of bone reabsorption markers,” and “statistically more
significant” bone condition restoration, when compared with other drugs.
Ex. 1007, 89. Gatti discloses that a Phase II clinical trial has shown that
neridronic acid, used for treating CRPS, resulted in “close to 80%” of
patients “experiencing rapid (in 7 – 12 days) > 70% symptomatic
improvements.” Ex. 1008, 1308. Because each of these disclosures
suggests successful treatment of CRPS and its symptoms with neridronic
acid, we credit Dr. Poree’s testimony that a person of ordinary skill in the art
“would have known that neridronate is effective to treat CRPS and its
symptoms.” Ex. 1004 ¶ 38.
Against this evidence, Patent Owner first argues that none of
Petitioner’s asserted references provides data showing that administering
neridronic acid improves the symptoms of CRPS. PO Resp. 17–18. But
“[o]bviousness does not require absolute predictability of success. . . . [A]ll
that is required is a reasonable expectation of success.” In re O’Farrell, 853
F.2d 894, 903–904 (Fed. Cir. 1988). It is sufficient that Varenna 2011,
Gatti, and Muratore would have informed the ordinarily skilled artisan that
successful treatment of CRPS and its symptoms was likely; there is no
requirement that Petitioner show that the prior art taught that success was
certain.
Moreover, even if Petitioner’s references insufficiently demonstrate
that administering neridronic acid improves the symptoms of CRPS, it
would be immaterial to the question of whether Petitioner had shown a
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reasonable expectation of success. To show the reasonable expectation of
success necessary to prove obviousness, Petitioner need only show that a
person of ordinary skill in the art would have had “a reasonable expectation
of achieving what is claimed in the patent-at-issue.” Intelligent Bio-Systems,
Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367 (Fed. Cir. 2016).
Here, the claims at issue recite “[a] method of treating changes in skin blood
flow” or “treating abnormal sudomotor activity” that is “associated with
complex regional pain syndrome.” Ex. 1002, 90:33–40, 91:14–21. It might
be possible to interpret the phrases “treating changes in skin blood flow” or
“treating abnormal sudomotor activity” to require some improvement in
those specified symptoms of CRPS, but, as discussed above, that is not the
definition the ’774 patent provides. Instead, as defined in the specification
of the ’774 patent, “[a] method of treating” a symptom associated with
CRPS means a method of diagnosing, curing, mitigating, or preventing a
symptom associated with complex regional pain syndrome, or otherwise
affecting the structure or any function of the body of someone suffering
from that symptom. Ex. 1002, 7:43–47. The disclosures of Varenna 2011,
Gatti, and Muratore certainly suggest that the administration of neridronic
acid to CRPS patients produced some effect in the structure or function of
the patients’ bodies, including structure and function affected by CRPS.
Given the ’774 patent’s broad definition of “treating,” there is no
requirement that the neridronic acid produces any particular effect, much
less achieves any particular degree of efficacy in improving the symptoms of
CRPS.
Patent Owner next argues that the failure of Petitioner’s Phase III
clinical trials of neridronic acid for treating CRPS demonstrates the lack of
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any reasonable expectation of success. PO Resp. 19–20. We are not
persuaded by this argument. The record shows that, in 2019, Petitioner
“decided to discontinue its two ongoing Phase III clinical trials of
Neridronate . . . in patients with Complex Regional Pain Syndrome” because
the “trials were unlikely to meet the primary endpoint.” Ex. 2001, 1–2. At
best, this evidence demonstrates that, in 2019, neridronic acid was known to
be unlikely to achieve some specific result (that is, the primary endpoint of
the trials) when used to treat CRPS. As discussed above, however,
Petitioner need not show that neridronic acid would have been understood to
bring about any particular result; the challenged claims require the
neridronic acid only to produce any effect at all on the structure or function
of a CRPS patient’s body. Thus, the failure to achieve some specific result
weighs little in the reasonable-expectation-of-success inquiry. In addition,
even if we accept that the claims of the ’774 patent require some particular
effect, the record contains no explanation of what was the primary endpoint
of Petitioner’s Phase III clinical trials, much less any evidence that that
endpoint was the same effect required by the challenged claims. For this
reason too, the failure of the Phase III clinical trials to achieve some
particular unspecified result is of little probative value in the reasonable-
expectation-of-success inquiry. In the alternative, even if the failure of the
clinical trials to achieve their endpoint is somehow relevant to the question
of whether a person of ordinary skill in the art reasonably would have
expected success, that failure speaks only to what would have been expected
in 2019, years after the date of the invention of the ’774 patent. Bristol-
Myers Squibb Co. v. Teva Pharm., Inc., 752 F.3d 967, 976 (Fed. Cir. 2014)
(“[T]he skilled artisan’s reasonable expectation of success is measured ‘as of
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the date of the invention.’” (quoting Amgen Inc. v. Hoffman–La Roche, 580
F.3d 1340, 1362 (Fed. Cir. 2009).)).
Accordingly, based on the evidence of record, we find that a person of
ordinary skill in the art at the time of the invention reasonably would have
expected to achieve success in attaining the result claimed in the ’774 patent
(namely, any effect at all on the structure or function of a CRPS patient’s
body due to the administration of neridronic acid).
b. Printed-Publication Status
Patent Owner argues that none of Petitioner’s asserted references
qualifies as a printed publication under 35 U.S.C. § 102. PO Resp. 4–16;
PO Sur-Reply 14–21. “To qualify as a printed publication, a reference ‘must
have been sufficiently accessible to the public interested in the art.’” Blue
Calypso, LLC v. Groupon, Inc., 815 F.3d 1331, 1348 (Fed. Cir. 2016)
(quoting In re Cronyn, 890 F.2d 1158, 1160 (Fed. Cir. 1989)). “A reference
will be considered publicly accessible if it was disseminated or otherwise
made available to the extent that persons interested and ordinarily skilled in
the subject matter or art exercising reasonable diligence, can locate it.” Id.
(quoting Kyocera Wireless Corp. v. Int’l Trade Comm’n, 545 F.3d 1340,
1350 (Fed. Cir. 2008)) (internal quotation marks omitted). Thus, there are
two ways to show that a reference was sufficiently accessible: show it was
disseminated or show it was “otherwise made available to the extent that”
interested people of ordinary skill in the art could have located it after
exercising reasonable diligence. Id. Here, according to Petitioner, the
asserted references “are articles published in periodical journals by an
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identified and reputable publisher.” Reply 3.11 Petitioner argues that the
references were “disseminated on the[ir] stated publication date[s].” Id. at 5.
We agree.
Varenna 2011 includes on its face the notations “Original Article,”
“Received on July 15, 2011,” and “Accepted on August 30, 2011.”
Ex. 1006, 227. It also indicates that the article appeared in the October 2011
publication of “GIOT.” Id. The evidence of record shows that “GIOT”
stands for “Giornale Italiano di Ortopedia e Traumatologia,” which means
“Italian Journal of Orthopedics and Traumatology.” Ex. 1004 ¶ 40;
Ex. 1038, 1. The October 2011 issue of GIOT was disseminated in two
ways, with 150 copies being handed out “at the 96th National Convention of
[the Italian Society of Orthopedics and Traumatology]” on September 26,
2011, and sixty-nine copies being mailed to people on a subscription list.
Ex. 1046.
Gatti, on its face, indicates that it was published in 2009 in the journal
“Expert Opinion on Drug Metabolism & Toxicology.” Ex. 1008, 1305.
Evidence of record shows that the publisher of this journal received,
prepared, and printed this article between May 2009 and September 2009
and that Gatti was made accessible to the public online by September 17,

11 Patent Owner argues that Petitioner was required to submit any evidence
of the printed-publication status of its asserted references with the Petition
rather than with the Reply. PO Resp. 6. That argument is unpersuasive in
view of the decision in Hulu, LLC v. Sound View Innovations, LLC, which
held that, “if the patent owner challenges a reference’s status as a printed
publication, a petitioner may submit a supporting declaration with its reply
to further support its argument that a reference qualifies as a printed
publication.” IPR2018-01039, Paper 29 at 15 (PTAB Dec. 20, 2019)
(precedential).
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2009. Ex. 1044. In view of this corroborating objective proof, we credit
Dr. Poree’s testimony that this article “was published no later than
September 2009.” Ex. 1004 ¶ 46.
Muratore, on its face, indicates that it was published in 2004 in
“Progressi in Reumatologia.” Ex. 1007, 3–4. Evidence of record shows that
the National Library of Medicine received Muratore in July 2004. Id. at 3;
Ex. 1043 ¶ 7. Accordingly, we credit Dr. Poree’s well-supported testimony
that Muratore was disseminated no later than 2004. Ex. 1004 ¶ 50.
Harden includes the notations “Received 18 November 2009,”
“Received in revised form 19 March 2010,” and “Accepted 20 April 2010.”
Ex. 1009, 268. A further notation on the face of Harden indicates that the
article appeared in 2010 in “Pain,” published by the “International
Association for the Study of Pain.” Id. In addition, an article published
in 2012 cites Harden among its references, suggesting that Harden must
have been disseminated no later than 2012. Ex. 1041, 541.
Drummond, on its face, indicates that it appeared in the journal “Pain
Medicine,” published by “Wiley Periodicals, Inc.” in 2010. Ex. 1010, 1257.
Other articles published in the same journal at around the same time appear
in the prosecution history of the ’774 patent. Ex. 1037, 192 (September
2004 publication by Robinson), 216 (September 2016 publication by
Varenna), 231 (August 2010 publication by Coderre). This strongly
suggests that articles published in Pain Medicine, including Drummond,
were disseminated publicly. Against this evidence supporting dissemination
of Drummond, Patent Owner does not direct us to contrary evidence, so we
find that the preponderance of the evidence supports a finding that
Drummond qualifies as a printed publication.
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Accordingly, evidence of record tends to establish that each of the
references Petitioner asserts against claims 1–15 was disseminated publicly
before the critical date, and that each, therefore, qualifies as a prior art
printed publication. Patent Owner does not direct us to any contrary
evidence; therefore, we determine that the preponderance of the evidence
supports a finding that Petitioner’s references are printed publications.
On that point, we are not persuaded by Patent Owner’s argument that
Petitioner fails to show that an interested person of ordinary skill in the art
could have located the asserted references. PO Resp. 13–16. Nor do we
find merit in Patent Owner’s further argument that some of the asserted
references were not available to a person of ordinary skill in the art because
they were written and published in Italian rather than English. PO Sur-
Reply 3–4. These arguments ignore Petitioner’s evidence that each of the
asserted references was disseminated publicly, which is sufficient on its own
to prove printed-publication status, without additional proof that a person of
ordinary skill in the art could have located the references. See Blue Calypso,
815 F.3d at 1348 (quoting Kyocera, 545 F.3d at 1350). Moreover, to the
extent that the ability of a person of ordinary skill in the art to locate a
reference is important to establishing the public dissemination of the
references, we find that an ordinarily skilled artisan interested in the subject
matter could have located the references asserted here through reasonable
diligence. The evidence of record tends to establish that the asserted
references were articles in circulation at the time of the invention; therefore,
a person of ordinary skill in the art could have reviewed them.
In addition, Patent Owner argues that indicia on the face of a non-
patent reference are never sufficient on their own to prove printed-
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publication status. PO Sur-Reply 14–15. As noted above, the evidence of
dissemination of Petitioner’s references comes from the face of the
references,12 from Dr. Poree’s testimony, and from additional evidence
submitted along with Petitioner’s Reply. Accordingly, the question whether
the printed-publication status of a reference may be established solely based
on evidence taken from the face of the document itself is not before us.
Because the preponderance of the evidence of record shows that
Petitioner’s references were disseminated publicly before the critical date,
we find that the asserted references are printed publications.
c. Claim 1
Claim 1 recites,
A method of treating changes in skin blood flow
associated with complex regional pain syndrome,
comprising parenterally administering neridronic
acid in a salt form or an acid form to a human being
suffering from skin blood flow associated with
complex regional pain syndrome, wherein the
human being has a pain intensity of at least 7 cm on
the 10 cm visual analogue scale (VAS) or at least 7
on the 0–10 numerical rating scale (NRS).
Ex. 1002, 90:33–40.
Although changes in skin blood flow are not expressly listed in the
Budapest Criteria, those criteria include “‘vasomotor’ signs and symptoms,”
such as “temperature asymmetry and/or skin color changes and/or
asymmetry.” Ex. 1004 ¶ 71. Petitioner directs us to evidence, moreover,

12 Evidence on the face of a reference may be considered in deciding
whether the reference is a printed publication. Hulu, IPR2018-01039,
Paper 29 at 17–18 (precedential) (evidence taken from the face of a
reference is to be “considered as part of the totality of the evidence”).
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that “‘[v]asomotor’ refers to changes in the diameter of blood vessels,
namely the dilation or constriction of blood vessels.” Id. (citing Ex. 1039,
2093). We are persuaded that a person of ordinary skill in the art “would
have known that the vasomotor signs and symptoms listed in the Budapest
Criteria are related to changes in blood flow.” Id. at ¶ 72; see Pet. 29 (citing
Ex. 1004 ¶¶ 70–73); see also id. at 24–25 (for citations to additional
persuasive information on point).
We also are persuaded that it would have been well known in the art
“to paternally administer neridronic acid to CRPS patients having pain
intensity of at least 7 cm on the VAS, as required by claim 1.” Id. at 34
(citing Ex. 1004 ¶¶ 79–80). To the extent that the claimed VAS limitation is
deemed critical, we find that an ordinarily skilled artisan reasonably would
have expected neridronate to treat successfully changes in skin blood flow
associated with CRPS in patients presenting with the level of pain intensity
required by claim 1. Id. at 34–35 (citing Ex. 1004 ¶¶ 90–93).
Petitioner argues that a person of ordinary skill in the art “would have
been motivated to administer neridronic acid to [patients suffering from
CRPS] based on the disclosures of Varenna 2011, Gatti, and/or Muratore,
which teach that neridronic acid is effective for treating CRPS and its
symptoms.” Pet. 36 (citing Ex. 1004 ¶¶ 81–84). Petitioner argues further
that, having been so motivated, the person of ordinary skill in the art would
have “look[ed] to other references like Varenna 2011, Harden, and
Drummond, which describe the diagnostic criteria, signs, and symptoms of
[CRPS].” Id. at 34 (citing Ex. 1004 ¶ 85). Because these references teach
that neridronate is useful for treating CRPS and its symptoms, and changes
in skin blood flow would have been recognized as such a symptom,
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Petitioner argues that the person of ordinary skill in the art “would have had
a reasonable expectation that neridronic acid or one of its salts could
successfully be administered to a patient suffering from changes in skin
blood flow associated with CRPS.” Id. at 36 (citing Ex. 1004 ¶¶ 81–84).
With the exception of arguments discussed above, pertaining to
reasonable expectation of success and printed-publication status, Patent
Owner does not oppose Petitioner’s arguments. PO Resp. 1–24; PO Sur-
Reply 1–13. Patent Owner, however, contends that the use of the phrase
“and/or” in the asserted obviousness grounds results in an impermissibly
vague challenge. PO Resp. 10–11 n.5; PO Sur-Reply 2. For support, Patent
Owner directs us to the Board’s informative decision in Adaptics Limited v.
Perfect Company, Case IPR2018-01596, Paper 20 at 1 (PTAB Mar. 6, 2019)
(“Adaptics”) (informative). The facts of Adaptics are inapposite. There, the
petitioner strung together ten prior art references by the phrase “and/or,”
resulting in no less than “seventeen possible combinations” of prior art
references, and leading to “voluminous and excessive” grounds nowhere
explained adequately by the patent challenger. Adaptics, Paper 20 at 2, 6,
18–19, 21. Here, by contrast, only three prior art references are combined
by the phrase “and/or,” and the same combination is at issue across both
grounds at hand. Pet. 22, 51. Further, and most significantly, Petitioner
cogently explains the relevant facts underlying both grounds and Patent
Owner does not contest those facts. Id. at 22–71. Accordingly, we are
unpersuaded by Patent Owner’s argument that the grounds presented here
are comparable to those in Adaptics, or result in an impermissibly vague
challenge. PO Resp. 10–11 n.5; PO Sur-Reply 2.
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Based on the full trial record, we find that Petitioner demonstrates by
a preponderance of the evidence that the subject matter of claim 1 would
have been obvious. Varenna 2011 teaches that neridronate “seems to
possess an excellent efficacy profile” in treating CRPS. Ex. 1006, 233. In
the context of reporting the use of “[n]eridronic acid for the treatment of
bone metabolic diseases,” Gatti teaches that “[i]ntravenous high doses of
bisphosphonates are increasingly used for the treatment of [CRPS].”13
Ex. 1008, 1305, 1308. Gatti also reports that a clinical trial of neridronic
acid “is underway.” Id. Muratore teaches that neridronate was “efficacious
in the treatment of [CRPS].” Ex. 1007, 89. Thus, on this record, each of
these references sufficiently teaches the efficacy of neridronic acid or its salt
in treating CRPS, suggesting that a person of ordinary skill in the art would
have been motivated to use neridronic acid in treating CRPS.
With respect to the limitation of claim 1 requiring that the neridronic
acid be “parenterally administer[ed],” each of Varenna 2011, Gatti, and
Muratore teaches intravenous administration of neridronic acid. Ex. 1006,
233; Ex. 1007, 89; Ex. 1008, 1308. Intravenous administration is a type of
parenteral administration. Ex. 1004 ¶ 44.

13 Gatti uses the terms “reflex sympathetic dystrophy syndrome” and
“algodystrophy.” Ex. 1008, 1308. On the present record, we interpret both
of these terms as synonymous with “complex regional pain syndrome,”
“CRPS,” “complex regional pain syndrome type I,” “CRPS I,” “reflex
sympathetic algodystrophy,” “reflex sympathetic dystrophy,” and
“causalgia.” Ex. 1006, 227 (equating “algodystrophy,” “complex regional
pain syndrome type I,” and “CRPS I”); Ex. 1007, 89 (using the term “reflex
sympathetic algodystrophy”); Ex. 1019, 713 (equating “complex regional
pain syndrome,” “CRPS,” “reflex sympathetic dystrophy,” and “causalgia”).
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Harden teaches that the Budapest Criteria are used as “clinical
diagnostic criteria for CRPS” and that they include changes in skin blood
flow, by reference to the symptoms of “temperature asymmetry” and “skin
color asymmetry.” Ex. 1009, 274 (Appendix II). Further, Harden teaches
that 69.4% of patients diagnosed with CRPS were observed on examination
to exhibit temperature asymmetry, and 83.9% were observed on examination
to exhibit skin color asymmetry. Id. at 271 (Table 2). Thus, Harden teaches
that a majority of patient with CRPS suffer from changes in skin blood flow.
Because Varenna 2011, Gatti, and Muratore teach that neridronic acid is
effective in treating CRPS, the combination of any of those references with
Harden14 would have suggested to a person of ordinary skill in the art that
neridronic acid would be effective in alleviating changes in skin blood flow
associated with CRPS.
Thus, the combination of Harden and one or more of Varenna 2011,
Gatti, and Muratore sufficiently teaches or suggests all the limitations of
claim 1. Moreover, Petitioner has shown that a person of ordinary skill in
the art would have had reason to combine the teachings of one or more of
Varenna 2011, Gatti, and Muratore with those of Harden in order to

14 Petitioner further argues that Drummond teaches that CRPS patients may
suffer from changes in skin blood flow. Pet. 56–57. As discussed below,
Patent Owner moves to exclude the evidence of Drummond’s status as prior
art. We need not resolve the issue of whether that evidence should be
excluded, however, because, even without the teachings of Drummond,
Petitioner has shown by a preponderance of the evidence that a person of
ordinary skill in the art would have understood that the defining symptoms
of CRPS include changes in skin blood flow, including temperature
asymmetry and skin color asymmetry. Accordingly, we do not consider the
teachings of Drummond in evaluating this obviousness ground.
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determine the symptoms of CRPS that could be improved by the treatment.
Ex. 1004 ¶¶ 80–84. Accordingly, we conclude that Petitioner has shown by
a preponderance of the evidence that the subject matter of claim 1 would
have been obvious over the combination of Harden and one or more of
Varenna 2011, Gatti, and Muratore.
d. Claims 2 and 3
Claim 2 of the ’774 patent depends from claim 1 and adds a limitation
requiring that “a total of about 200 mg to about 500 mg of the neridronic
acid [be] administered parenterally to the human being.” Ex. 1002, 90:41–
43. Claim 3 depends from claim 1 and adds a limitation requiring that “a
total of about 400 mg of the neridronic acid [be] administered parenterally to
the human being.” Id. at 90:44–46. Petitioner argues that both Varenna
2011 and Muratore teach these limitations. Pet. 39. With the exception of
the arguments discussed above with respect to reasonable expectation of
success, printed-publication status, and impermissible vagueness due to the
use of the phrase “and/or” in the grounds, Patent Owner does not oppose
Petitioner’s arguments. PO Resp. 1–24; PO Sur-Reply 1–13. After
considering the entire record, we determine that Petitioner has shown by a
preponderance of the evidence that claims 2 and 3 would have been obvious.
Muratore teaches administering 100 mg of neridronate per infusion,
with one infusion occurring every four days until four total infusions have
been administered. Ex. 1007, 89. This is a total of 400 mg of neridronate,
which both falls within the recited range of claim 2 and is the specific
amount recited in claim 3. Based on this evidence, we determine that
Petitioner has shown by a preponderance of the evidence that the
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combination of Harden and at least one of Varenna 2011, Gatti, and
Muratore teaches or suggests the limitations of claims 2 and 3.
e. Claim 4
Claim 4 depends from claim 1 and adds a limitation requiring that “a
total of about 100 mg to about 200 mg of the neridronic acid [be]
administered parenterally to the human being within a period of about 1
month.” Ex. 1002, 90:47–50. Petitioner argues that Gatti teaches this
limitation. Pet. 40. With the exception of the arguments discussed above
with respect to reasonable expectation of success, printed-publication status,
and impermissible vagueness due to the use of the phrase “and/or” in the
grounds, Patent Owner does not oppose Petitioner’s arguments. PO Resp.
1–24; PO Sur-Reply 1–13. After considering the entire record, we
determine that Petitioner has shown by a preponderance of the evidence that
claim 4 would have been obvious.
Gatti teaches that “the most effective dose is 100 mg diluted in 250 ml
of saline solution given intravenously over 4 days.” Ex. 1008, 1308. This
statement in Gatti may refer to “bisphosphonates” generally, rather than to
neridronic acid specifically, because the paragraph in which this statement
appears begins with a reference to “high doses of bisphosphonates.” Id. The
following paragraph, however, states that, because of the efficacy of the
specified dose, a clinical trial of neridronic acid “is underway.” Id. This
suggests that the specific bisphosphonate for which “the most effective dose
is 100 mg diluted in 250 ml of saline solution given intravenously over 4
days” is neridronic acid. Id. Moreover, the entirety of Gatti discusses
“[n]eridronic acid for the treatment of bone metabolic diseases,” which also
suggests that the particular bisphosphonate in question is neridronic acid. Id.
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at 1305. Thus, Gatti teaches or suggests the administration of 100 mg of
neridronic acid.15 Accordingly, Petitioner has shown by a preponderance of
the evidence that the combination of Harden and at least one of Varenna
2011, Gatti, and Muratore teaches or suggests the limitations of claim 4.
f. Claim 5
Claim 5 depends from claim 1 and adds a limitation requiring that “a
total of about 250 mg of the neridronic acid [be] administered parenterally to
the human being within a period of about 1 month.” Ex. 1002, 90:54–56.
Petitioner argues that the claimed dose falls within the range of doses that
the prior art describes as effective and that a person of ordinary skill in the
art would have been motivated and able to arrive at the optimum dose of
neridronic acid. Pet. 40–43. With the exception of the arguments discussed
above with respect to reasonable expectation of success, printed-publication
status, and impermissible vagueness due to the use of the phrase “and/or” in
the grounds, Patent Owner does not oppose Petitioner’s arguments. PO
Resp. 1–24; PO Sur-Reply 1–13. After considering the entire record, we
determine that Petitioner has shown by a preponderance of the evidence that
claim 5 would have been obvious.
Gatti teaches that a dose of 100 mg of neridronic acid is effective in
treating CRPS. Ex. 1008, 1308 (this dose reduces symptoms of CRPS by
more than 70% in “close to 80%” of patients). Muratore teaches that a dose
of 400 mg of neridronate is effective in treating CRPS. Ex. 1007, 89
(improvement in several symptoms occurred faster with this dose of

15 Gatti likewise also suggests administration of 100 mg of neridronic acid
by teaching (1) the administration of 100 mg of bisphosphonate and (2) that
neridronic is an exemplary bisphosphonate. Ex. 1008, 1308.
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neridronate than in groups treated with other drugs). The 250-mg dose of
claim 5 falls between these two prior-art values, and there is evidence of
record that an ordinarily skilled artisan would have been motivated and able
to find an optimum dose of neridronic acid within the prior-art range.
Ex. 1004 ¶¶ 102–103. “[I]t is not inventive to discover the optimum or
workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456
(CCPA 1955). Accordingly, Petitioner has shown by a preponderance of the
evidence that the combination of Harden and at least one of Varenna 2011,
Gatti, and Muratore teaches or suggests the limitations of claim 5.
g. Claims 6 and 7
Claim 6 depends from claim 2 and adds a limitation requiring that
“the neridronic acid [be] administered in divided doses.” Ex. 1002, 90:54–
55. Claim 7 depends from claim 6 and adds a limitation requiring that “each
division of the divided parenteral dose contain[] about 10 mg to about 150
mg of the neridronic acid.” Id. at 90:56–58. Petitioner argues that both
Varenna 2011 and Muratore teach these limitations. Pet. 43–44. With the
exception of the arguments discussed above with respect to reasonable
expectation of success, printed-publication status, and impermissible
vagueness due to the use of the phrase “and/or” in the grounds, Patent
Owner does not oppose Petitioner’s arguments. PO Resp. 1–24; PO Sur-
Reply 1–13. After considering the entire record, we determine that
Petitioner has shown by a preponderance of the evidence that claims 6 and 7
would have been obvious.
Varenna 2011 teaches a divided parenteral dose in which each
division falls between 10 mg and 150 mg of neridronate. Ex. 1006, 233
(teaching that neridronate is “administered intravenously at a dosage of 100
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mg per four infusions every fourth day”). This teaches dividing a total dose
into “four infusions,” thus meeting the limitation of claim 6. Id. Regardless
of whether the total dose is 100 mg, as is apparent from the text of Varenna
2011, or 400 mg, as Petitioner argues, the division into four infusions means
that each infusion contains an amount of neridronate between 10 mg and 150
mg as specified in claim 7.
Similarly, Muratore teaches administering 100 mg of neridronate per
infusion, with one infusion occurring every four days until four total
infusions have been administered. Ex. 1007, 89. This teaches dividing a
total dose of 400 mg into four infusions. Id. Thus, Muratore teaches both
the limitation of claim 6 and, because the divided doses contain 100 mg
each, the limitation of claim 7.
Accordingly, Petitioner has shown by a preponderance of the evidence
that the combination of Harden and at least one of Varenna 2011, Gatti, and
Muratore teaches or suggests the limitations of claims 6 and 7.
h. Claim 8
Claim 8 depends from claim 6 and adds a limitation requiring that
“each division of the divided parenteral dose contain[] about 62 mg to about
63 mg of the neridronic acid.” Id. at 90:59–61. Petitioner argues that the
claimed dose falls within the range of doses that the prior art describes as
effective and that a person of ordinary skill in the art would have been
motivated and able to arrive at the optimum dose of neridronic acid.
Pet. 44–45. With the exception of the arguments discussed above with
respect to reasonable expectation of success, printed-publication status, and
impermissible vagueness due to the use of the phrase “and/or” in the
grounds, Patent Owner does not oppose Petitioner’s arguments. PO Resp.
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1–24; PO Sur-Reply 1–13. After considering the entire record, we
determine that Petitioner has shown by a preponderance of the evidence that
claim 8 would have been obvious.
There is evidence of record that a person of ordinary skill in the art
would have been motivated and able to find an optimum dose of neridronic
acid. Ex. 1004 ¶¶ 102–105, 110–111. “[I]t is not inventive to discover the
optimum or workable ranges by routine experimentation.” Aller, 220 F.2d
at 456. Accordingly, Petitioner has shown by a preponderance of the
evidence that the combination of Harden and at least one of Varenna 2011,
Gatti, and Muratore teaches or suggests the limitations of claim 8.
i. Claim 9
Claim 9 depends from claim 1 and adds a limitation requiring that
“the complex regional pain syndrome [be] associated with an inciting
traumatic event.” Ex. 1002, 90:62–64. Petitioner argues that both Harden
and Varenna 2011 teach this limitation. Pet. 45–46. With the exception of
the arguments discussed above with respect to reasonable expectation of
success, printed-publication status, and impermissible vagueness due to the
use of the phrase “and/or” in the grounds, Patent Owner does not oppose
Petitioner’s arguments. PO Resp. 1–24; PO Sur-Reply 1–13. After
considering the entire record, we determine that Petitioner has shown by a
preponderance of the evidence that claim 9 would have been obvious.
Varenna 2011 teaches that “approximately half the cases [of CRPS]
(from 40 to 65%) recognize[] trauma as the triggering event.” Ex. 1006,
229. Harden teaches that traumatic events caused 73.6% of CRPS cases,
with fractures accounting for 41.6% of cases and surgery and crush injuries
causing another 32%. Ex. 1009, 269. Thus, a person of ordinary skill in the
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art would have expected most cases of CRPS to have resulted from a
traumatic triggering event. Because, as discussed above, Petitioner has
shown by a preponderance of the evidence that a person of ordinary skill in
the art would have expected neridronic acid to alleviate changes in skin
blood flow associated with CRPS, that person would have been motivated to
do so in the majority of CRPS cases resulting from a traumatic initiating
event. Ex. 1004 ¶¶ 113–115. Accordingly, Petitioner has shown by a
preponderance of the evidence that the subject matter of claim 9 would have
been obvious in view of the combined disclosures of Harden and at least one
of Varenna 2011, Gatti, and Muratore.
j. Claims 10 and 11
Claim 10 depends from claim 1 and adds a limitation requiring that
“the human being has suffered from complex regional pain syndrome for at
least 6 months.” Ex. 1002, 90:65–67. Claim 11 depends from claim 1 and
adds a limitation requiring that “the human being has suffered from complex
regional pain syndrome for about 6 months to about 12 months.” Id. at
91:1–3. Petitioner argues that these limitations would have been obvious to
a person of ordinary skill in the art. Pet. 46–48. With the exception of the
arguments discussed above with respect to reasonable expectation of
success, printed-publication status, and impermissible vagueness due to the
use of the phrase “and/or” in the grounds, Patent Owner does not oppose
Petitioner’s arguments. PO Resp. 1–24; PO Sur-Reply 1–13. After
considering the entire record, we determine that Petitioner has shown by a
preponderance of the evidence that claims 10 and 11 would have been
obvious.
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The average duration of CRPS symptoms in the study reported in
Muratore was 4.1 months, with some patients having suffered from CRPS
for at least 6.1 months. Ex. 1007, 89. The disease duration of 6.1 months in
Muratore falls within the range recited in claim 10 (“at least 6 months”) and
claim 11 (“about 6 months to about 12 months”). Ex. 1002, 89:56–61. The
ranges of disease duration recited in claims 10 and 11 fall within the range
of 4.1 months to ten years disclosed in the prior art. Accordingly, Petitioner
has shown by a preponderance of the evidence that the combination of
Harden and at least one of Varenna 2011, Gatti, and Muratore teaches or
suggests the limitations of claims 10 and 11.
k. Claim 12
Claim 12 depends from claim 1 and adds a limitation requiring that
“the human being has suffered from complex regional pain syndrome for
about 1 year to about 2 years.” Ex. 1002, 91:4–6. Petitioner argues that this
limitation would have been obvious to a person of ordinary skill in the art.
Pet. 46–48; Reply 19–21. In particular, Petitioner argues that it would have
been obvious to treat patients who had suffered for between one year and
two years because Muratore taught treating patients who had suffered for
more than six months and other art taught that CRPS could last for longer
than one year. Reply 19–21. Patent Owner disagrees, arguing that none of
the asserted references teaches using neridronic acid to treat a patient who
has suffered from CRPS for between one and two years. PO Resp. 20–24;
PO Sur-Reply 13–14. Patent Owner also argues that Petitioner has shown at
most that a person of ordinary skill in the art could have treated patients who
had suffered from CRPS for between one and two years, not that they would
have had a reason to do so. PO Sur-Reply 14. After considering the entire
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record, we determine that Petitioner has shown by a preponderance of the
evidence that claim 12 would have been obvious.
As discussed above with respect to claims 10 and 11, Muratore
teaches treating patients who have suffered from CRPS for up to 6.1 months.
Ex. 1007, 89. Varenna 2011 teaches that symptoms of CRPS often last for
“ten years from the onset of the disease.” Ex. 1006, 230. Accordingly, we
credit the testimony of Dr. Poree that a person of ordinary skill in the art
“would have reasonably expected that neridronate could be used to
successfully treat symptoms of CRPS . . . in patients having CRPS for up to
and including 2 years.” Ex. 1004 ¶ 118. Neither party directs us to evidence
that an ordinarily skilled artisan would have considered it more difficult to
treat patients who had suffered CRPS symptoms for between one and two
years than to treat those who had suffered for shorter periods. Given the
disclosures of Muratore and Varenna 2011, as well as the testimony of
Dr. Poree, we determine that a person of ordinary skill in the art would have
found it obvious to treat patients who had suffered for between one and two
years using the same treatment used for those who had suffered for over six
months. Petitioner has shown by a preponderance of the evidence that the
combination of Harden and at least one of Varenna 2011, Gatti, and
Muratore teaches or suggests the limitations of claim 12.
l. Claim 13
Claim 13 depends from claim 1 and adds a limitation requiring that
“the human being” must have “an age of about 30 years to about 40 years.”
Ex. 1002, 91:10–11. Petitioner argues that Muratore teaches this limitation.
Pet. 48–49. With the exception of the arguments discussed above with
respect to reasonable expectation of success, printed-publication status, and
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impermissible vagueness due to the use of the phrase “and/or” in the
grounds, Patent Owner does not oppose Petitioner’s arguments. PO Resp.
1–24; PO Sur-Reply 1–13. After considering the entire record, we
determine that Petitioner has shown by a preponderance of the evidence that
claim 13 would have been obvious.
Muratore reports the results of a study in which at least one CRPS
patient was 39 years old. Ex. 1007, 89 (disclosing that female patients
ranged in age from 39 to 57). This falls within the range recited in claim 13.
Accordingly, Petitioner has shown by a preponderance of the evidence that
the combination of Harden and at least one of Varenna 2011, Gatti, and
Muratore teaches or suggests the limitations of claim 13.
m. Claims 14 and 15
Claims 14 depends from claim 1 and adds a limitation requiring that
“the human being” have “a pain intensity of at least 8 cm on a 10 cm VAS or
at least 8 on a 0–10 NRS,” whereas claim 15 (which similarly depends from
claim 1) requires a pain intensity “of at least 9 cm on” one of those scales.
Ex. 1002, 91:9–14. Petitioner argues that these limitations would have been
obvious to a person of ordinary skill in the art. Pet. 49–50. With the
exception of the arguments discussed above with respect to reasonable
expectation of success, printed-publication status, and impermissible
vagueness due to the use of the phrase “and/or” in the grounds, Patent
Owner does not oppose Petitioner’s arguments. PO Resp. 1–24; PO Sur-
Reply 1–13. After considering the entire record, we determine that
Petitioner has shown by a preponderance of the evidence that claims 14
and 15 would have been obvious.
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The Budapest Criteria for diagnosing CRPS include “[c]ontinuous
pain disproportionate to the triggering event.” Ex. 1006, 228 (Table I); see
Ex. 1009, 274 (Appendix II). As discussed above, the events that can trigger
CRPS are most often traumatic in nature, including fractures, surgery, and
crush injuries. Ex. 1009, 269. Accordingly, “CRPS is characterized and
defined by severe and continuing pain.” Ex. 1004 ¶ 127. There is evidence
of record that “‘severe’ pain includes patients with high VAS scores, such as
≥7 cm.” Id. As discussed above, the combination of Harden and at least one
of Varenna 2011, Gatti, and Muratore teaches or suggests treating CRPS
with neridronic acid. Thus, the evidence of record shows that a person of
ordinary skill in the art “would reasonably [have] expect[ed] that neridronic
acid could be successfully used to treat . . . CRPS in patients having VAS
scores ≥7 cm, 8 cm, or 9 cm.” Id. Accordingly, Petitioner has shown by a
preponderance of the evidence that the combination of Harden and at least
one of Varenna 2011, Gatti, and Muratore teaches or suggests the limitations
of claims 14 and 15.
D. Asserted Obviousness of Claims 16–29 over Harden and One or
More of Varenna 2011, Gatti, and Muratore
Petitioner argues that claims 16–29 of the ’774 patent would have
been obvious over the combination of Harden and one or more of Varenna
2011, Gatti, and Muratore. Pet. 51–71.
1. The Asserted Prior Art
Our description of Harden, Varenna 2011, Gatti, and Muratore
provided above in connection with the ground against claims 1–15 applies
with equal force here.
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2. Analysis
a. Reasonable Expectation of Success
As it does with respect to the ground of obviousness challenging
claims 1–15, Patent Owner argues that Petitioner fails to show the
obviousness of claims 16–29 because it fails to show that a person of
ordinary skill in the art would have had “a reasonable expectation of success
in treating complex regional pain syndrome by administering neridronic
acid.” PO Resp. 24. We disagree with this argument for the same reasons
discussed above, which apply with equal force here.
b. Printed-Publication Status
As discussed above, despite Patent Owner’s arguments to the
contrary, Petitioner has shown by a preponderance of the evidence that
Varenna 2011, Gatti, Muratore, and Harden qualify as printed publications.
Our reasoning above, regarding the printed-publication status of these
references, applies with equal force to our analysis of this ground.
c. Claim 16
Claim 16 recites,
A method of treating abnormal sudomotor activity
associated with complex regional pain syndrome,
comprising parenterally administering neridronic
acid in a salt form or an acid form to a human being
suffering from abnormal sudomotor activity
associated with complex regional pain syndrome,
wherein the human being has a pain intensity of at
least 7 cm on the 10 cm visual analogue scale (VAS)
or at least 7 on the 0–10 numerical rating scale
(NRS).
Ex. 1002, 91:14–21. “‘Sudomotor activity’ refers to stimulation of the sweat
glands and sweating.” Pet. 53; Ex. 1004 ¶ 68 (citing Ex. 1039, 1861).
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Abnormal sudomotor activity “refers to abnormal sweating changes or
sweating asymmetry in the body parts affected by CRPS.” Ex. 1004 ¶ 68.
Petitioner argues that a person of ordinary skill in the art “would have
been motivated to administer neridronic acid to [patients suffering from
CRPS] based on the disclosures of Varenna 2011, Gatti, and/or Muratore,
which teach that neridronic acid is effective for treating CRPS and its
symptoms.” Pet. 56–57 (citing Ex. 1004 ¶¶ 81–84). Petitioner argues
further that, having been so motivated, the person of ordinary skill in the art
would have “look[ed] to other references like Varenna 2011 and Harden,
which describe the diagnostic criteria, signs, and symptoms of [CRPS].” Id.
at 57 (citing Ex. 1004 ¶ 85). Because Varenna 2011 and Harden both teach
that abnormal sudomotor activity is a common symptom of CRPS, Petitioner
argues that an ordinarily skilled artisan “would have had a reasonable
expectation that neridronic acid or one of its salts could successfully be
administered to a patient suffering from abnormal sudomotor activity
associated with CRPS.” Id. (citing Ex. 1004 ¶¶ 81–84).
With the exception of the arguments discussed above with respect to
reasonable expectation of success, printed-publication status, and
impermissible vagueness due to the use of the phrase “and/or” in the
grounds, Patent Owner does not oppose Petitioner’s arguments. PO
Resp. 1–24; PO Sur-Reply 1–13. After considering the entire record, we
determine that Petitioner has shown by a preponderance of the evidence that
claim 16 would have been obvious.
Petitioner is correct that a person of ordinary skill in the art would
have been motivated to administer neridronic acid to treat CRPS. As
discussed above with respect to claims 1–15, each of Varenna 2011, Gatti,
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and Muratore teaches the efficacy of neridronic acid or its salt in treating
CRPS, suggesting that a person of ordinary skill in the art would have been
motivated to use neridronic acid in treating CRPS. Ex. 1006, 233; Ex. 1007,
89; Ex. 1008, 1305, 1308. In addition, each of these references teaches
intravenous administration of neridronic acid. Ex. 1004 ¶ 42; Ex. 1006, 233;
Ex. 1007, 89; Ex. 1008, 1308.
We further agree with Petitioner that it would have been “widely
known” at the time of the invention “that abnormal sudomotor activity is a
sign and symptom of CRPS” and, in fact, was a defining “criteria” used “to
identify and diagnose CRPS.” Pet. 52 (citing Ex. 1004 ¶ 48). Varenna 2011
and Harden teach that the Budapest Criteria, which are used as clinical
diagnostic criteria for CRPS, include abnormal sudomotor activities,
including sweating changes, temperature asymmetry, and sweating
asymmetry. Ex. 1006, 228; Ex. 1009, 274 (Appendix II); Ex. 1004 ¶ 78.
Further, Harden teaches that CRPS patients were likely to suffer from
abnormal sudomotor activity. Pet. 49; Ex. 1009, 271 (Table 2) (43.8% of
CRPS patients present with sweating asymmetry on examination). Because
each of Varenna 2011, Gatti, and Muratore teaches that neridronic acid is
effective in treating CRPS, the combination of any of those references with
Harden would have suggested to an ordinarily skilled artisan that neridronic
acid would be effective in alleviating abnormal sudomotor activity
associated with CRPS.
The combination of Harden and one or more of Varenna 2011, Gatti,
and Muratore teaches or suggests the limitations of claim 16. Petitioner has
shown sufficiently that a person of ordinary skill in the art would have had
reason to combine the teachings of one or more of Varenna 2011, Gatti, and
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Muratore with those of Harden in order to determine the symptoms of CRPS
that could be improved by the treatment. Ex. 1004 ¶¶ 84–85. Accordingly,
we determine that Petitioner has shown by a preponderance of the evidence
that claim 16 would have been obvious over the combination of Harden and
one or more of Varenna 2011, Gatti, and Muratore.
d. Claims 17–29
Other than their dependency from claim 16 rather than from claim 1,
claims 17–29 of the ’774 patent are identical to claims 2–14. Compare
Ex. 1002, 90:41–91:14, with Ex. 1002, 91:22–92:29. For the same reasons
as discussed above in connection with claims 2–14, we find that Petitioner
has shown by a preponderance of the evidence that claims 17–29 would
have been obvious over the combination of Harden and one or more of
Varenna 2011, Gatti, and Muratore.
E. Asserted Lack of Written Description
Petitioner asserts that claims 1–29 lack written description support in
“[t]he ’774 patent specification.”16 Pet. 74; see id. at 8 (grounds chart). In
our Decision on Institution, we concluded that Petitioner had not shown a
reasonable likelihood of prevailing on this asserted ground of
unpatentability. Dec. Inst. 19–24. After we made that determination,

16 The relevant inquiry is whether the subject matter of the challenged
claims finds written description support “in the originally filed disclosure.”
Purdue Pharm. L.P. v. Faulding Inc., 230 F.3d 1320, 1326–27 (Fed. Cir.
2000). We adopt Petitioner’s convention of referring to the ’774 patent
specification, rather than Application No. 15/782,480, which matured to
issue as the ’774 patent. See Pet. 72–75 (repeatedly referring to, and citing,
the ’774 patent specification); Ex. 1002, code (21) (identification of
Application No. 15/782,480).

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neither party addressed this ground any further. See generally, PO Resp.;
Reply; PO Sur-Reply. Accordingly, the record after trial remains the same
as it was at the time we instituted review, and we repeat our original analysis
here, which remains applicable to our consideration of the record after trial.
“[T]he hallmark of written description is disclosure.” Ariad Pharms.,
Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). A
patent disclosure is sufficient if it “reasonably conveys to those skilled in the
art that the inventor had possession of the claimed subject matter as of the
filing date,” based on an “objective inquiry into the four corners of the
specification.” Id. Petitioner argues that the ’774 patent specification “does
not specifically describe administration of neridronic acid to human beings
to treat changes in skin blood flow” (claims 1–15) or “abnormal sudomotor
activity” (claims 16–20) associated with CRPS. Pet. 73, 74.
We find Petitioner’s information on point insufficient for two
independent reasons. First, the original claims set forth in the patent
application that matured to issue as the ’774 patent are part of the disclosure
that we consider when assessing the question of compliance with the written
description requirement. See Ex. 1036, 145–14717 (prosecution history,
claims as originally filed). It is well settled that “original claims constitute
their own description.” In re Koller, 613 F.2d 819, 823 (CCPA 1980); see
In re Gardner, 475 F.2d 1389, 1391 (CCPA 1973) (“[A]n original claim, in
itself constituted a description in the original disclosure equivalent in scope
and identical in language to the total subject matter now being claimed.”).
Original claim 14 (which depends from original claim 1) appears to support

17 Regarding Exhibit 1036, we cite to page numbers added by Petitioner not
original page numbers assigned during patent prosecution.
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adequately the subject matter of claim 1, as issued. Compare Ex. 1036, 145,
146 (original claims 1 and 14), with Ex. 1002, claims 1 and 14. Similarly,
original claim 30 (which depends from original claim 17) appears to support
adequately claim 16, as issued. Compare Ex. 1036, 146, 147 (original
claims 17 and 30), with Ex. 1002, claim 16. That circumstance, on this
record, appears to us to lay to rest any question that independent claim 1
or 16 lacks written description support.
Petitioner raises no written description argument specific to any
limitation of a dependent claim. Pet. 72–75. In any event, a straightforward
comparison of original claims 1–30 to claims 1–29, as issued, reveals that
they cover essentially identical subject matter. Compare Ex. 1036, 145–147
(original claims 1–30), with Ex. 1002, claims 1–29. On this record,
therefore, the original claims represent “a description in the original
disclosure equivalent in scope” to the subject matter of the challenged
claims. In re Gardner, 475 F.2d at 1391. “Nothing more is necessary for
compliance with the description requirement of the first paragraph of 35
U.S.C. § 112.”18 Id.

18 We do not mean to suggest that original claims always and inevitably
provide their own written description support. When a claim recites a genus
and “use[s] functional language to define the boundaries of [the] claimed
genus,” it “may simply claim a desired result, and may do so without
describing species that achieve that result.” Ariad, 598 F.3d at 1349. When
that is the case, “the specification must demonstrate that the applicant has
made a generic invention that achieves the claimed result and do so by
showing that the applicant has invented species sufficient to support a claim
to the functionally-defined genus.” Id. Petitioner does not allege, however,
that the claims of the ’774 patent take the form described in Ariad.
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Second, we find insufficient Petitioner’s argument that the ’774 patent
specification “contains no working examples of neridronic acid
administration whatsoever.” Pet. 73, 74. Petitioner, in that regard, argues
that the rat tibia fracture model discussed in the examples, and which
involved administration of zoledronic acid to rats, does not support the
claimed feature of claims 1–15 requiring administration of a different
bisphosphonate (neridronic acid) to treat a different animal (a human being).
Id. at 73–74 (asserting that argument in the context of claims 1–15);
compare id. at 74–75 (nowhere advancing that argument in the context of
claims 16–29). Petitioner focuses on those examples in isolation, without
adequately accounting for the disclosure of the specification as a whole.
The specification expressly contemplates the use of neridronic acid to
treat CRPS and contains disclosure adequate to indicate possession of a
method of intravenous administration of neridronic acid to treat the
symptoms of CRPS in human patients. See, e.g., Ex. 1002, 3:4–17, 8:38–53,
69:24–36 (Embodiment 79), 69:56–58 (Embodiment 86). The specification
repeatedly lists neridronic acid alongside zoledronic acid when identifying
bisphosphonate compounds that are suitable for use in the invention. Id.
at 3:5–6, 3:12–13, 4:20, 8:46, 18:17–18, 18:35, 18:32, 33:28, 42:8. As
explained above (supra 6), the specification not only mentions neridronic
acid alongside zoledronic acid when describing the bisphosphonate
compounds useful in the invention, but does so in the context of describing
the administration of a bisphosphonate to a human being suffering from
CRPS. Ex. 1002, 3:4–16, 8:38–48. Those disclosures, on this record,
suggest that the two bisphosphonates behave similarly in the claimed
invention. Id. Further, the specification repeatedly and consistently
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indicates that the inventors were in possession of a treatment applicable to “a
human being” or “a human patient.” Ex. 1002, 2:5, 2:33, 7:24, 8:41, 9:21,
9:30, 9:34, 14:6, 14:12, 14:19, 23:46, 23:59, 24:30, 24:49, 31:19, 37:6,
37:67, 38:61, 39:51, 39:58, 39:63, 40:7.
Although, Examples 1–3 contain data keyed to the efficacy of
zoledronic acid in a rat tibia fracture model (in which CRPS was induced
and evaluated in non-human animals), that fact does not end the inquiry.
Pet. 73–74 (discussing rat tibia model in the context of claims 1–15);
Ex. 1002, Examples 1–3 (describing the efficacy of zoledronic acid in rat
tibia fracture model of CRPS). Each of those examples includes disclosure
that explains how to extrapolate starting dosages for animals to dosages
appropriate for human patients, by reference to FDA guidelines. Ex. 1002,
49:49–55, 50:23–31 (Example 1), 51:20–24 (Example 2), 52:64–67
(Example 3).
Example 3 goes further, citing prior research demonstrating that the
rat tibia fracture model, referenced in the working examples, replicates
CRPS as “observed in human[s].” Id. at 51:30–40 (Example 3, citing a prior
publication). Moreover, “Embodiment 79” in the specification expressly
refers to “[a] method of treating complex regional pain syndrome,
comprising administering neridronic acid to a human being in need thereof.”
Ex. 1002, 69:34–38. As to the limitations that require a patient suffering a
particular intensity of pain, the specification expressly describes VAS and
NRS pain intensity scores required by the claims and, moreover, includes
“Embodiment 86,” which expressly discloses “[a] method of treating pain,
comprising administering neridronic acid to a human being in need thereof.”
Id. at Figs. 10–12, 3:56–67, 10:9–59, 69:56–58 (Embodiment 86).
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Petitioner acknowledges, moreover, that the specification describes
“[s]ome embodiments” that “include administering an osteoclast inhibitor,
such as a bisphosphonate, including zoledronic acid, neridronic acid, etc. to
inhibit the development of pain, unweighting, and abnormal sudomotor
activity when administered early such as when a precipitating event such as
fracture occurs, wherein the precipitating event is associated with CRPS.”
Pet. 74–75 (quoting Ex. 1002, 3:4–10). We find this express disclosure, in
combination with other disclosures discussed above, adequately supports the
administration of “neridronic acid” in a human patient suffering from
“abnormal sudomotor activity” that “is associated with CRPS.” Id.
Petitioner’s attempt to narrowly read that disclosure as relating only to an
administration of neridronic acid that occurs “‘early’ after a bone fracture”
not only reads out of the disclosure the words “such as,” but also myopically
focuses on a phrase in isolation without taking fair account of the totality of
disclosure in the specification. Id. at 75.
In sum, on this record, we find that the claims as originally filed
provide written description support for the claims as issued in the ’774
patent. Compare Ex. 1036, 145–147 (claims 1–30, as originally filed), with
Ex. 1002, claims 1–29 (as issued). But even if we set aside that
circumstance, other disclosures, discussed above, provide written description
support for the claims—support that is addressed inadequately, if at all, by
Petitioner and Dr. Poree. Pet. 72–75 (including citations to Ex. 1004).
Accordingly, we find that Petitioner fails to show that any challenged claim
is more likely than not invalid for lack of written description support.
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F. Motion to Exclude
Patent Owner’s motion to exclude evidence seeks to exclude all or
parts of Exhibits 1004, 1006–1010, 1038, 1040, and 1043–1046. Mot.
Exclude 1. We consider the arguments for each exhibit separately.
1. Exhibit 1004: Declaration of Dr. Poree
Patent Owner moves to exclude any portion of Dr. Poree’s declaration
that relies on Exhibits 1006, 1007, 1008, 1009, or 1010. Mot. Exclude 1–2.
Patent Owner relies on the argument, discussed below, that each of
Exhibits 1006–1010 is itself inadmissible. Id. As discussed below,
however, we are not persuaded that Exhibits 1006–1010 should be excluded
as inadmissible. Accordingly, we deny Patent Owner’s motion to exclude
Dr. Poree’s testimony.
2. Exhibit 1006: Varenna 2011
Patent Owner moves to exclude the phrases “OTTOBRE 2011,”
“ARTICOLO ORIGINALE,” “Ricevuto il 15 luglio 2011,” and “Accettato il
30 agosto 2011,” as they appear on the face of Varenna 2011. Mot.
Exclude 2. The English translations of these phrases are, respectively,
“October 2011,” “Original Article,” “Received on July 15, 2011,” and
“Accepted on August 30, 2011.” Ex. 1006, 227. According to Patent
Owner, each of these phrases is hearsay and should be excluded. Mot.
Exclude 2; Reply Mot. 1–3.
We are not persuaded that “October 2011” should be excluded.
Assuming that “October 2011” is hearsay, it is still admissible evidence
under Rule 807 of the Federal Rules of Evidence. See Opp. Mot. 3–4
(asserting this hearsay exception). Under Rule 807, a statement “is not
excluded,” even if it is hearsay, if it meets two requirements. First, the
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statement must be “supported by sufficient guarantees of trustworthiness—
after considering the totality of circumstances under which it was made and
evidence, if any, corroborating the statement.” Fed. R. Evid. 807(a)(1).
Second, the statement must be “more probative on the point for which it is
offered than any other evidence that the proponent can obtain through
reasonable efforts.” Id. at 807(a)(2). Here, both requirements are satisfied.
The statement “October 2011” on the face of Varenna 2011 is offered
to prove that Varenna 2011 was published in October 2011. This statement
is accompanied by several guarantees of trustworthiness. The statements
“Received on July 15, 2011” and “Accepted on August 30, 2011,” when
offered as corroboration of the October 2011 publication date, are not
hearsay. Fed. R. Evid. 801 (statement is hearsay only if offered in evidence
“to prove the truth of the matter asserted in the statement”). Accordingly,
they may be admitted for this purpose, and they corroborate a publication in
October 2011. Moreover, Exhibits 1038 and 1040 also provide some
evidence that Varenna 2011 was published in October 2011. Ex. 1038, 1
(article with same title as Varenna 2011 published in “Fascicolo 5 2011”);
Ex. 1040, 1 (“Fascicolo 5 2011” published in 2011). Thus, the record
contains sufficient guarantees of trustworthiness of Varenna 2011’s
statement that Varenna 2011 was published in October 2011. See Opp.
Mot. 3 (citing Ex. 1004 ¶¶ 39–40).
We find that Varenna 2011’s statement, indicating that the reference
was published in October 2011, is “more probative on the point for which it
is offered than any other evidence that the proponent can obtain through
reasonable efforts.” Fed. R. Evid. 807(a)(2). It is difficult to imagine
evidence more probative of the publication date of a journal article than the
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article’s own contemporaneous statement about when it was published.19
See Opp. Mot. 2–4 (for well-supported arguments on point). Accordingly,
we determine that the exception of Rule 807 applies, and we conclude that
the statement “October 2011” in Varenna 2011 should not be excluded.
As discussed above, the statements “Received on July 15, 2011,” and
“Accepted on August 30, 2011” in Varenna 2011 are not hearsay, because
they are offered not to prove the date when the article was received or
accepted but, rather, to corroborate the October 2011 publication date.
Accordingly, we conclude that these statements should not be excluded.
In reaching our decision on the unpatentability of the challenged
claims, as well as on the admissibility of the evidence Patent Owner seeks to
exclude, we do not rely on the statement “Original Article” on the face of
“Varenna 2011.” Accordingly, we dismiss Patent Owner’s motion to
exclude this statement as moot.
3. Exhibit 1007: Muratore
Patent Owner moves to exclude the statements “S/2004,” “2004-07-
19,” “Volume 5,” “Supplemento 1/2004,” “2004 ISSUE 1 SUPPLEMENT,”
and “Maratea (PZ), 16-18 aprile 2004,” as they appear on the face of
Muratore. Mot. Exclude 2–3. According to Patent Owner, each phrase is
hearsay and should be excluded. Id.; Reply Mot. 1–3.
As with the statements discussed above on the face of Varenna 2011,
the statements Patent Owner moves to exclude in Muratore include the
statement of the publication date (“Maratea (PZ), 16-18 aprile 2004”) as

19 The authenticity of Varenna 2011 is not in dispute. Paper 8, 4–6
(objections to Ex. 1006, including no objection based on authenticity); Mot.
Exclude 2 (declining to preserve any objection based on authenticity).
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well as several statements offered to corroborate that date. The statements
offered as corroboration are not hearsay, because they are not offered to
prove their own truth. The corroborating statements, moreover, provide
sufficient guarantees of trustworthiness of the reference’s publication date.
Muratore’s own statement about its publication date, “affixed . . . long
before the instant dispute began by wholly disinterested parties,” is more
probative than any other evidence of record. Opp. Mot. 3 (citation omitted).
Accordingly, we conclude that none of the challenged statements in
Muratore should be excluded.
4. Exhibit 1008: Gatti
Patent Owner moves to exclude two statements appearing on the face
of Gatti: “Published online: 17 Sep 2009” and “© 2009 Informa UK Ltd.”
Mot. Exclude 3–4. According to Patent Owner, each of these statements is
hearsay and should be excluded. Id.; Reply Mot. 1–3.
The statement regarding the copyright date is offered as corroboration
of the September 17, 2009, publication date, rather than as proof of the date
when copyright attached, so it is not hearsay. The statement that the article
was published on September 17, 2009, satisfies the hearsay exception of
Rule 807 for the same reasons discussed above with respect to similar
statements in Varenna 2011 and Muratore. The record contains sufficient
guarantees of the trustworthiness of the statement. Ex. 1008, 1305
(copyright date); Ex. 1044 ¶¶ 3–6 (testimony regarding publication process).
In addition, an article’s own statement regarding its publication date is more
probative than any other evidence. Accordingly, we conclude that none of
the challenged statements in Gatti should be excluded.
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5. Exhibit 1009: Harden
Patent Owner moves to exclude several statements appearing on the
face of Harden: “PAIN 150 (2010) 268-274,” “Received 18 November
2009,” “Received in revised form 19 March 2010,” “Accepted 20 April
2010,” and “© 2010 International Association for the Study of Pain.” Mot.
Exclude 4–5. According to Patent Owner, each of these statements is
hearsay and should be excluded. Id.; Reply Mot. 1–3.
The statement “PAIN 150 (2010) 268-274” may be considered to
include a statement that Harden was published in 2010 that is offered to
prove that Harden was published in 2010. Even if we interpret the statement
as being offered for this hearsay purpose, however, it is admissible under
Rule 807 for the same reasons discussed above with respect to the
statements in Varenna 2011, Muratore, and Gatti. See Opp. Mot. 2–4
(Petitioner’s persuasive arguments on point). The remaining statements, all
of which are offered for the non-hearsay purpose of corroborating the 2010
publication date, provide sufficient guarantees of trustworthiness, and there
is no more probative evidence of an article’s publication date than the
article’s own statement on that point. Accordingly, we conclude that none
of the challenged statements in Harden should be excluded.
6. Exhibit 1010: Drummond
Patent Owner moves to exclude the statement “Pain Medicine 2010”
as it appears on the face of Drummond. According to Patent Owner, this
statement is hearsay and should be excluded. Mot. Exclude 5; Reply
Mot. 1–3.
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As noted above (supra 27 n.14), we do not rely on Drummond in
reaching our decision in this case. Accordingly, we dismiss Patent Owner’s
motion to exclude a portion of Drummond as moot.
7. Exhibit 1038: Relevance
Patent Owner moves to exclude the entirety of Exhibit 1038 as
irrelevant because, given the 2015 and 2019 dates on its face, “it has no
bearing upon the determination of what a [person of ordinary skill in the art]
would have known before the priority date of May 14, 2012.” Mot.
Exclude 6.
Evidence is relevant if “it has any tendency to make a fact more or
less probable than it would be without the evidence,” and “the fact is of
consequence in determining the action.” Fed. R. Evid. 401. Here, the fact in
question is whether Varenna 2011 was published before May 14, 2012.
Patent Owner points to the date “1/2/2019” on the face of Exhibit 1038
(apparently the date the exhibit was printed), as well as the year 2015 in a
URL appearing on page 3 of the exhibit, as evidence that the exhibit cannot
bear any relevance to what happened before May 14, 2012. Mot.
Exclude 5–6. But Exhibit 1038 also states multiple times that Varenna 2011
was a part of “Fascicolo 5 2011.” Ex. 1038, 1–3. Accordingly, we do not
agree with Patent Owner that the exhibit does not tend to make a 2011
publication date any more likely. On the contrary, “[r]egardless of when the
websites were retrieved or when the content was uploaded” for purposes of
preparing Exhibit 1038 for this proceeding, the document nonetheless
contains “independent evidence tending to support the fact that Varenna
2011 was, in fact, published in October 2011.” Opp. Mot. 10–11. Thus, we
are not persuaded that Exhibit 1038 should be excluded as irrelevant.
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8. Exhibits 1040, 1043–1046: Reply Evidence
Patent Owner argues that Exhibits 1040 and 1043–1046 should be
excluded as untimely because Petitioner could have submitted them with the
Petition but, instead, elected to submit them with the Reply. Mot.
Exclude 6–10. Each of these exhibits supports the printed-publication status
of Petitioner’s asserted prior-art references, and Petitioner is permitted to file
such evidence with its Reply when responding to an argument in Patent
Owner’s Response, regarding the status of the asserted references as printed
publications. Hulu, IPR2018-01039, Paper 29 at 15 (precedential). Here,
Patent Owner raised such an argument, Response 4–17, so Petitioner’s
submission of Exhibits 1040 and 1043–1046 with the Reply was timely. We
deny Patent Owner’s motion to exclude these references as untimely.
9. Exhibit 1040: Relevance
Patent Owner moves to exclude the entirety of Exhibit 1040 as
irrelevant. Mot. Exclude 10–11. Here, as with Exhibit 1038, the fact in
question is whether Varenna 2011 was published before May 14, 2012.
Patent Owner argues that Exhibit 1040 does not make such a publication
date more or less likely. We disagree. Exhibit 1040 lists “Fascicolo 5 2011”
under the heading “2011” on a page with headings for other years from 2012
through 2019. Ex. 1040, 1. Taken together with the evidence that
Varenna 2011 was published as part of “Fascicolo 5 2011,” Ex. 1038, 1–3,
this supports a finding that Varenna 2011 was published in 2011.
Accordingly, we are not persuaded that Exhibit 1040 should be excluded as
irrelevant.
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10. Exhibit 1043: Relevance
Patent Owner moves to exclude the entirety of Exhibit 1043 as
irrelevant. Mot. Exclude 11–13. Here, the fact in question is whether
Muratore was published before May 14, 2012. Patent Owner argues that
Exhibit 1043 does not make such a publication date more or less likely. We
disagree. Exhibit 1043 contains the declaration testimony of David E.
Cannady, who testifies that he has “nearly forty years of experience
retrieving articles from the [National Library of Medicine],” that the copy of
Muratore he retrieved from the library bore “a date/time stamp of ‘2004-07-
19 10:33:34,’” and that, based on his experience, this stamp “represents the
date/time Muratore was received by the [library].” Ex. 1043 ¶¶ 1, 7. This
testimony tends to establish a publication date before May 14, 2012, because
the article likely was printed and published near the time it was received by
the National Library of Medicine in 2004. Accordingly, we are not
persuaded that Exhibit 1043 should be excluded as irrelevant.
11. Exhibit 1043: Personal Knowledge
Patent Owner also seeks to exclude the statement in Exhibit 1043 that
materials received by the National Library of Medicine are “added to the
[library’s] General Collection—and therefore available and accessible to the
public . . . within 7-10 days of receipt of the publication.” Mot. Exclude 12–
13. Patent Owner argues that this statement is beyond the witness’s personal
knowledge and, therefore, is not admissible under Fed. R. Evid. 602. Id.
We do not rely on this testimony in reaching our decision in this case, so we
dismiss this portion of Patent Owner’s motion to exclude as moot.
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12. Exhibit 1044: Relevance
Patent Owner moves to exclude the entirety of Exhibit 1044 as
irrelevant. Mot. Exclude 12–13. Here, the fact in question is whether Gatti
was published before May 14, 2012. Patent Owner argues that Exhibit 1044
does not make such a publication date more or less likely. We disagree.
Exhibit 1044 contains the declaration testimony of Corinne Militello, Esq.,
who testifies that she investigated the process her employer undertook to
publish Gatti and that her investigation revealed dates for various steps in
the publication process that are consistent with a publication date of
September 17, 2009. Ex. 1044 ¶¶ 1–6. This testimony tends to establish a
publication date before May 14, 2012. Accordingly, we are not persuaded
that Exhibit 1044 should be excluded as irrelevant.
13. Exhibits 1045 and 1046: Relevance
Patent Owner moves to exclude the entirety of Exhibit 1045 and its
English translation, Exhibit 1046, as irrelevant. Mot. Exclude 14–15. Here,
the fact in question is whether Varenna 2011 was published before May 14,
2012. Patent Owner argues that Exhibits 1045 and 1046 do not make such a
publication date more or less likely. We disagree. These exhibits provide
testimony that some copies of Varenna 2011 were distributed to conference
attendees on September 26, 2011, and that other copies were sent to
subscribers in October 2011. Ex. 1046, 3. This testimony tends to establish
a publication date before May 14, 2012, because no copies of an article
published after May 14, 2012, could have been distributed either on
September 26, 2011, or in October 2011. Accordingly, we are not persuaded
that Exhibits 1045 and 1046 should be excluded as irrelevant.
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14. Exhibit 1046: Hearsay
Patent Owner moves to exclude the entirety of Exhibit 1046 as
hearsay. Mot. Exclude 15. We are not persuaded that Exhibit 1046 is
hearsay. The exhibit is offered to corroborate a publication date of
October 2011 for Varenna 2011, rather than as proof of the content of the
statements it contains (that some copies of the article were distributed on
September 26, 2011, or that other copies were sent to subscribers in October
2011). Reply 11. Accordingly, we are not persuaded that Exhibit 1046
should be excluded as hearsay.
15. Conclusion as to Motion to Exclude
We dismiss as moot those portions of Patent Owner’s motion to
exclude that seek to exclude exhibits on which we do not rely in reaching
our decision. Specifically, as discussed above, we deny as moot Patent
Owner’s request to exclude portions of Exhibit 1006 for hearsay and
portions of Exhibit 1010 and Exhibit 1043 for lack of personal knowledge.
We deny the remainder of Patent Owner’s motion to exclude.
CONCLUSION20
Upon consideration of the papers and evidence before us, we
determine that Petitioner has proven by a preponderance of the evidence that

20 Should Patent Owner wish to pursue amendment of the challenged claims
in a reissue or reexamination proceeding subsequent to the issuance of this
Decision, we draw Patent Owner’s attention to the April 2019 Notice
Regarding Options for Amendments by Patent Owner Through Reissue or
Reexamination During a Pending AIA Trial Proceeding, 84 Fed. Reg.
16,654 (Apr. 22, 2019). If Patent Owner chooses to file a reissue application
or a request for reexamination of the challenged patent, we remind Patent
Owner of its continuing obligation to notify the Board of any such related
matters in updated mandatory notices. See 37 C.F.R. § 42.8(a)(3), (b)(2).
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claims 1–29 are unpatentable as obvious over the combination of Harden
and one or more of Varenna 2011, Gatti, and Muratore. We also determine
that Petitioner has not shown that any claim of the ’774 is unpatentable for
lack of written description. Finally, we partially deny and partially dismiss
Patent Owner’s motion to exclude evidence.

Claims
35
U.S.C. §

Reference(s)/Basis
Claims
Shown
Unpatentable
Claims
Not Shown
Unpatentable
1–15 103 Harden. Varenna
2011, Gatti,
Muratore,
Drummond
1–15
16–29 103 Harden, Varenna
2011, Gatti,
Muratore
16–29
1–29 112 Written
Description
1–29
Overall
Outcome
1–29

ORDER
It is hereby
ORDERED that Petitioner has proven by a preponderance of the
evidence that claims 1–29 of U.S. Patent No. 10,039,774 B2 are
unpatentable;
FURTHER ORDERED that, pursuant to 35 U.S.C. § 318(b), upon
expiration of the time for appeal of this decision, or the termination of any
such appeal, a certificate shall issue canceling claims 1–29 of U.S. Patent
No. 10,039,774 B2;
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FURTHER ORDERED that Patent Owner’s motion to exclude
portions of Exhibit 1006 for hearsay and portions of Exhibit 1010 and
Exhibit 1043 for lack of personal knowledge is dismissed as moot;
FURTHER ORDERED that Patent Owner’s motion to exclude is
otherwise denied; and
FURTHER ORDERED that, because this is a Final Written Decision,
parties to the proceeding seeking judicial review of the decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.

PETITIONER:
Daniel J. Minion
Bruce C. Haas
VENABLE LLP
dminion@venable.com
bchaas@venable.com

PATENT OWNER:
Brent A. Johnson
R. Parrish Freeman
MASCHOFF BRENNAN
bjohnson@mabr.com
pfreeman@mabr.com