Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center v. Eli Lilly & Co.

United States Court of Appeals
for the Federal Circuit
______________________
LOS ANGELES BIOMEDICAL RESEARCH
INSTITUTE AT HARBOR-UCLA MEDICAL
CENTER,
Appellant
v.
ELI LILLY AND COMPANY,
Appellee
______________________
2016-1518
______________________
Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board, in No. IPR2014-
00752.
______________________
Decided: February 28, 2017
______________________
EWA M. DAVISON, Fenwick & West LLP, Seattle, WA,
argued for appellant. Also represented by DAVID KEITH
TELLEKSON, ELIZABETH B. HAGAN; VIRGINIA KAY
DEMARCHI, AMY HAYDEN, Mountain View, CA.
MARK J. FELDSTEIN, Finnegan, Henderson, Farabow,
Garrett & Dunner, LLP, Washington, DC, argued for
appellee. Also represented by JOSHUA GOLDBERG, YIEYIE
YANG; CHARLES E. LIPSEY, Reston, VA; MARK STEWART,
Eli Lilly and Company, Indianapolis, IN.
2 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
______________________
Before NEWMAN, BRYSON, and MOORE, Circuit Judges.
Opinion for the court filed by Circuit Judge BRYSON.
Opinion concurring in part, dissenting from the judg-
ment filed by Circuit Judge NEWMAN.
BRYSON, Circuit Judge.
Appellant Los Angeles Biomedical Research Institute
at Harbor-UCLA Medical Center (“LAB”) seeks review of
a decision of the Patent Trial and Appeal Board holding
all claims of U.S. Patent No. 8,133,903 (“the ’903 patent”)
unpatentable as obvious. We vacate the Board’s order
and remand for further proceedings.
I
A
The ’903 patent claims a method of “arresting or re-
gressing” a condition known as penile fibrosis. The meth-
od entails the long-term, daily administration of drugs
known as type 5 phosphodiesterase (“PDE5”) inhibitors.
The drugs function by inhibiting the enzymatic action of
PDE5, which is found in the human penis. See ’903
patent, col. 6, line 51, through col. 7, line 15.
The penis contains two cylindrical chambers called
the corpora cavernosa. Those chambers fill with blood
during an erection. The corpora cavernosa are surround-
ed by a membrane called the tunica albuginea. Penile
fibrosis is characterized by the buildup of excess collagen.
It includes two conditions: penile tunical fibrosis, which
results from the buildup of excess collagen in the tunica
albuginea, and corporal tissue fibrosis, which results from
a buildup of excess collagen in the corpora cavernosa. See
’903 patent, col. 68, ll. 22-32, 37-39; see also id., col. 9, ll.
45-46.
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 3
The two fibrotic conditions can cause erectile dysfunc-
tion, although they do not always do so. Tunical fibrosis
can manifest itself as Peyronie’s disease, a condition that
“usually leads to penile deformation (curved penis during
erection), pain, and quite frequently erectile dysfunction.”
’903 patent, col. 1, ll. 33-34. Corporal tissue fibrosis,
which results from the death of smooth muscle cells in the
corpora cavernosa and a corresponding buildup of colla-
gen, can cause dysfunction of the mechanism that retains
blood in the corpora cavernosa during an erection. In a
healthy male, the relaxation of the smooth muscle cells in
the penis increases the flow of blood to the corpora caver-
nosa. The flow of blood into the corpora cavernosa in turn
compresses the veins of the penis against the tunica
albuginea to block the flow of blood from the penis. The
compression of those veins is known as the veno-occlusive
mechanism. Disruption of that mechanism, known as
corporal veno-occlusive disorder (“CVOD”), can lead to
erectile dysfunction. Id., col. 2, ll. 23-31.
In addition to the two types of penile fibrosis, there
are many other causes of erectile dysfunction. Some
causes of erectile dysfunction, such as those of psychologi-
cal origin, are entirely unrelated to fibrosis.
In the early 2000s, PDE5 inhibitors such as sildenafil
(Viagra) and tadalafil (Cialis) were well known and com-
monly used for the on-demand treatment of erectile
dysfunction. See ’903 patent, col. 10, line 59, through col.
11, line 3. The use of sildenafil and tadalafil for that
purpose was not restricted to cases of erectile dysfunction
resulting from penile fibrosis. Individuals with erectile
dysfunction of varying causes were instructed to take
PDE5 inhibitors before sexual activity in order to obtain
an erection at the desired time. As the ’903 patent ex-
plains, that use of PDE5 inhibitors was “not addressed to
the long-term cure of underlying tissue fibrosis.” Id., col.
10, line 67, through col. 11, line 3.
4 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
At that time, according to the patent, there was a
need for adequate non-surgical treatments for Peyronie’s
disease and other fibrotic conditions. ’903 patent, col. 2,
ll. 2-7 (noting that surgery was “the only option” available
in most cases of Peyronie’s disease). Erectile dysfunction
resulting from those conditions could be treated sympto-
matically with on-demand PDE5 inhibitors, but there was
“[n]o effective method of treatment . . . directed towards
the molecular pathways underlying excessive collagen
deposition” to address penile fibrosis. Id., col. 2, ll. 44-46.
The ’903 patent, owned by LAB, claims such a treat-
ment. Claim 1, the only independent claim, recites:
1. A method comprising:
a) administering a cyclic guanosine 3’, 5’-
monophosphate (cGMP) type 5 phos-
phodiesterase (PDE5) inhibitor accord-
ing to a continuous long-term regimen
to an individual with at least one of a
penile tunical fibrosis and corporal tis-
sue fibrosis; and
b) arresting or regressing the at least one
of the penile tunical fibrosis and cor-
poral tissue fibrosis, wherein the PDE-
5 inhibitor is administered at a dosage
up to 1.5 mg/kg/day for not less than 45
days.
’903 patent, col. 68, ll. 23-32.
The remaining four claims depend from claim 1 and
concern the type of drug (claim 2), the type of fibrotic
condition (claim 3), the mode of administration (claim 4),
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 5
and the duration of treatment (claim 5). Id., col. 68, ll. 33-
45. 1
B
In 2013, LAB filed an infringement action in the
United States District Court for the Central District of
California against Eli Lilly & Company (“Lilly”), alleging
that Lilly’s marketing of the drug Cialis induced in-
fringement of the ’903 patent. Los Angeles Biomed.
Research Inst. v. Eli Lilly & Co., No. 2:13-cv-08567-JAK-
JCG (C.D. Cal. filed Nov. 20, 2013). Lilly subsequently
filed multiple petitions requesting that the Patent Trial
and Appeal Board conduct inter partes review of the ’903
patent. The Board instituted inter partes review on the
petition in which Lilly contended that all the claims of the
’903 patent were unpatentable as obvious in light of three
references. The cited references were: Francesco Montorsi
et al., The Ageing Male and Erectile Dysfunction, 20
World J. Urology 28-53 (2002) (“Montorsi”); International
Patent Application No. WO 01/80860 (published Nov. 1,
2001) (John S. Whitaker et al., applicants) (“Whitaker”);
and Hartmut Porst et al., Daily IC351 Treatment of ED,
12 Int’l J. Impotence Research (Supp. 3) S76, B13 (2000)
(“Porst”). 2
1 LAB has not presented separate arguments for
the patentability of any of the dependent claims.
2 The Board also instituted inter partes review on
the petition in which Lilly argued that all the claims of
the ’903 patent were unpatentable as anticipated by
Whitaker. The Board conducted that inter partes review
in a separate proceeding, No. IPR2014-00693. At the
conclusion of that proceeding, the Board ruled that the
claims were not anticipated. That decision, which Lilly
appealed, is addressed in the related case, Eli Lilly &
Company v. Los Angeles Biomedical Research Institute at
6 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
The ’903 patent claims priority from Provisional Ap-
plication No. 60/420,281, which was filed on October 22,
2002. ’903 patent, col. 1, ll. 12-15. The Board rejected
LAB’s argument for the earlier priority date and deter-
mined that the specification of the provisional application
did not disclose the dosage limitation of “up to 1.5
mg/kg/day,” i.e., a dosage of up to 1.5 milligrams of PDE5
inhibitor per kilogram of the patient’s body weight each
day.
The Board also construed several claim limitations
that are now at issue on appeal. First, the Board con-
strued the phrase “an individual with at least one of
penile tunical fibrosis and corporal tissue fibrosis” to
mean an “individual hav[ing] symptoms that may be
associated with penile fibrosis, such as [erectile dysfunc-
tion], but not that the patient be specifically diagnosed as
having penile tunical fibrosis or corporal tissue fibrosis.”
Second, the Board construed the phrase “arresting or
regressing the at least one of the penile tunical fibrosis
and corporal tissue fibrosis” as having no limiting role,
but merely stating the intended result of administering a
PDE5 inhibitor at a dosage of up to 1.5 mg/kg/day for at
least 45 days.
Third, in the Decision on Institution, the Board con-
strued the term “continuous long-term regimen” to mean
“the administration of drug over a certain period of time
without intermission such that the treatment is therapeu-
tically effective.” In its final decision, the Board conclud-
ed that the claim limitation requiring the delivery of a
dosage of up to 1.5 mg/kg/day for at least 45 days “would
meet the claim requirement of a continuous, long-term
regimen.”
Harbor-UCLA Medical Center, No. 2016-1547, decided
together with this case but in a separate opinion.
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 7
The Board then addressed the three prior art refer-
ences: Montorsi, Whitaker, and Porst.
Montorsi is a review article that addresses the treat-
ment of erectile dysfunction in the aging male population.
Montorsi states that male erectile dysfunction is associat-
ed with aging; that atherosclerosis (the buildup of plaque
in the arteries) is common in the elderly; and that athero-
sclerosis is associated with CVOD and corporal fibrosis,
which can cause erectile dysfunction. Montorsi at 28, 30-
31. Montorsi concludes that “it seems reasonable to
hypothesise that the [erectile dysfunction] from ageing is
the result of atherosclerosis-induced cavernosal ischaemia
leading to cavernosal fibrosis and [CVOD].” Id. at 31.
Montorsi discusses several relevant studies of erectile
dysfunction. It begins by reviewing a group of studies on
sildenafil as a treatment for erectile dysfunction in elderly
patients. The patients in that study were instructed to
take up to 100 mg of sildenafil on demand (one hour
before sexual activity) but no more than once daily over a
12 week to 6 month period. Those studies showed that
sildenafil was well tolerated and that it ameliorated the
treated condition. Montorsi at 32-33. Another study
reported that administering a 100 mg dose of sildenafil at
bedtime to male patients between 40 and 68 years old
with erectile dysfunction produced an increase in noctur-
nal erections. Id. at 31 (citing Francesco Montorsi et al.,
Sildenafil Taken at Bedtime Significantly Increases
Nocturnal Erections: Results of a Placebo-Controlled
Study, 56 Urology 906, 907 (2000)). Montorsi concludes
that this study “opened the door to further study investi-
gating the possible dosage of sildenafil to be administered
daily at bedtime to prevent or treat [erectile dysfunction]
in the elderly patient.” Montorsi at 31.
Whitaker is an abandoned patent application that
claims the chronic use of low-dose PDE5 inhibitors to
treat erectile dysfunction. Whitaker defines “chronic” as
8 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
“the regular administration of the [PDE5 inhibitor] in
intervals unrelated to the onset of sexual activity,” and
states that “chronic administration generally refers to
regular administration for an extended period, preferably
daily for three or more days, and still more preferably
daily for as long as the patient suffers from erectile dys-
function (in the absence of therapy).” Whitaker at 7.
Whitaker defines “daily” as “administration of the [PDE5
inhibitor] one or more times, generally one to three times,
still more preferably one time, per about 24-hour period.”
Id.
Example 6 of Whitaker combines data from five clini-
cal studies to show that chronic administration of low
doses (5 mg or 10 mg) of tadalafil improved erectile func-
tion in a population of patients with male erectile dys-
function. Whitaker at 34. The study population included
four subgroups, in which tadalafil was taken (1) less than
30% of the time, (2) 30-50% of the time, (3) 50-70% of the
time, and (4) more than 70% of the time. Id. Example 6
states that tadalafil “was administered ‘daily’ to [these]
patients.” Id.; accord id. at 35 (“The Study Drug was
administered in 5 mg and 10 mg doses, ‘daily’ and not
more than once every 24 hours.”). Whitaker notes “a
trend toward better response with increased frequency of
dose.” Id. at 36 (referring to results showing better erec-
tile function in subgroups 3 and 4 than in subgroups 1
and 2). In Example 7, tadalafil was administered daily
for three weeks to men 21-72 years old with erectile
dysfunction, in subgroups receiving either a placebo or
one of four dosages (10, 25, 50, and 100 mg). The results
showed that “[a]dverse events [side effects] were dose-
related, and attenuated with continued daily treatment.”
Id. at 38.
Whitaker states that “[t]he enhanced efficacy demon-
strated by low daily dosing of a PDE5 inhibitor in treating
erectile dysfunction . . . results from improved vascular
responsiveness when the PDE5 inhibitor is present con-
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 9
tinuously, or essentially continuously, in plasma.” Whit-
aker at 12. Whitaker terms that effect “vascular condi-
tioning,” an effect that had not been reported or observed
in treatments with PDE inhibitors generally, nor more
specifically in the case of on-demand dosing of PDE5
inhibitors. Id. Whitaker concludes that “[i]t is expected
that vascular conditioning occurs after chronic admin-
istration of the PDE5 inhibitor, for example, after about
three daily doses of up to 10 mg, preferably after five days
of daily dosing, and more preferably after seven days of
daily dosing. In addition, after about three days of daily
dosing, intermittently missing one chronic dose may lead
to a reduction in vascular conditioning, but not a complete
loss of conditioning.” Id. at 13. Whitaker then posits: “It
is theorized, but not relied upon herein, that vascular
conditioning is caused by a partial or complete reversal of
circulatory dysfunctions in penile circulation arising from
conditions such as diabetes, atherosclerosis, smoking,
hypertension, or a combination of such factors.” Id. at 13.
Porst is a published abstract of a study showing that
100 mg of tadalafil administered daily for three weeks to
men with erectile dysfunction having a mean age of 52.4
years was safe and well tolerated, and that it improved
erectile function.
The Board found that Montorsi and Whitaker taught
administering a PDE5 inhibitor to an individual with
erectile dysfunction, as required by its construction of “an
individual with at least one of a penile tunical fibrosis and
corporal tissue fibrosis.” The Board also found that
Montorsi taught that erectile dysfunction in the aging
male is associated with atherosclerosis, which in turn is
associated with the development of corporal fibrosis, and
that Whitaker taught that long-term treatment with a
PDE5 inhibitor can cause reversal of circulatory dysfunc-
tions caused by diabetes, atherosclerosis, smoking, hyper-
tension, or a combination of such factors.
10 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
The Board further found that the three references to-
gether taught daily dosing of up to 1.5 mg/kg/day for at
least 45 days, and therefore met the “continuous long-
term regimen” limitation of the ’903 patent. In particular,
the Board found that Montorsi taught dosing of up to 100
mg of sildenafil per day. According to the ’903 patent, col.
45, ll. 7-12, a dosage of 100 mg per day is roughly equiva-
lent to 1.5 mg/kg for an average weight adult male.
Although the Board acknowledged that Whitaker’s Ex-
ample 6 did not specifically disclose dosing every day, it
noted that Whitaker taught that better results are ob-
tained with increased frequency of dosing, that adverse
effects are attenuated with daily administration, and that
treatment should continue for as long as the erectile
dysfunction persists. Finally, the Board found that Porst
taught that a dosage of 100 mg of tadalafil per day is safe
and well tolerated.
In response to Lilly’s arguments based on the prior
art references, LAB argued that its treatment method
produced unexpected results, because at the time of the
invention the scientific community believed that PDE5
inhibitors would exacerbate fibrosis, not treat it. That
belief, according to LAB, was based on the understanding
that the enzyme inductible nitric oxide synthase (“iNOS”)
and its product, nitric oxide, which have a mechanism of
action similar to that of PDE5 inhibitors, were profibrotic.
The Board rejected that argument on the ground that the
claims of the ’903 patent do not require a particular
mechanism of action and that any antifibrotic effect
resulting from the administration of PDE5 inhibitors,
whether expected or not, is inherent.
The Board ultimately concluded that the combination
of references satisfies each of the limitations of the ’903
patent, as construed, and that the combination provides a
reasonable expectation of success in treating erectile
dysfunction.
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 11
On appeal, LAB argues that the Board erred (1) in
denying LAB’s claim of priority to the October 2002 filing
date of the inventors’ provisional application, (2) in con-
struing the three disputed claim terms, (3) in deciding
that claim 1 of the ’903 patent would have been obvious
based on incorrect claim constructions, and (4) by failing
to adequately consider the prevailing beliefs in the field
and the unexpected results achieved by the inventors.
II
A
In order for a patent to be entitled to priority based on
an earlier application or chain of applications, each previ-
ous application in the chain must comply with the written
description requirement of 35 U.S.C. § 112(a). Bradford
Co. v. Conteyor N. Am., Inc., 603 F.3d 1262, 1269 (Fed.
Cir. 2010). To satisfy the written description require-
ment, the disclosure in each application must “reasonably
convey[]” to those skilled in the art that as of the claimed
priority date the inventor was in possession of the later
claimed subject matter. Vas-Cath Inc. v. Mahurkar, 935
F.2d 1555, 1563 (Fed. Cir. 1991). A disclosure in a parent
application is not sufficient if it “merely renders the later-
claimed invention obvious . . . ; the disclosure must de-
scribe the claimed invention with all its limitations.”
Tronzo v. Biomet, Inc., 156 F.3d 1154, 1158 (Fed. Cir.
1998).
In this case, the inventors filed a provisional applica-
tion in October 2002 to which the ’903 patent claims
priority. Lilly argues on appeal that the three prior art
references were published before the provisional applica-
tion was filed and are thus prior art under 35 U.S.C. §
102(a) even with the priority date of October 2002. LAB
responds that Lilly asserted Whitaker and Montorsi as
prior art only under 35 U.S.C. § 102(b) before the Board
and that Whitaker and Montorsi do not qualify as prior
art under that provision. We decline to address the
12 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
question of Lilly’s waiver, as we conclude on the merits
that the ’903 patent is not entitled to the priority date of
the provisional application because of a lack of adequate
written description.
The provisional application does not explicitly disclose
a dosage of “up to 1.5 mg/kg/day.” LAB, however, con-
tends that the dosage level is disclosed by a rat study
described in the provisional application. In that study,
rats were provided with 100 mg/L (milligrams per liter) of
sildenafil in drinking water. LAB argues that a person of
skill in the art would be able to calculate the correspond-
ing human dosage according to a conversion method
devised by E. J. Freireich, and that the result of that
computation would be a dosage of approximately 1.5
mg/kg/day. See Emil J. Freireich, Quantitative Compari-
son of Toxicity of Anticancer Agents in Mouse, Rat, Ham-
ster, Dog, Monkey, and Man, 50 Cancer Chemotherapy
Reports 219-44 (1966).
LAB’s argument depends on several assumptions re-
garding the knowledge of a person of skill in the art.
Such a person would have to know the average daily
water intake of the rat model used in the ’903 patent, the
average weight of the rat model used in the ’903 patent,
the average weight of an adult human male, and the
average height of an adult human male. Moreover, that
person would need to know of the Freireich method for
calculating the rat-to-human interspecies dosage conver-
sion and have a reason to apply it. The Board held that
the first four variables were not knowable from the disclo-
sure in the application, but would at best require persons
of skill to look to the prior art and make assumptions.
That is not enough to establish priority. See Lockwood v.
Am. Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997)
(“It is not sufficient for purposes of the written description
requirement of § 112 that the disclosure, when combined
with knowledge in the art, would lead one to speculate as
to modifications that the inventor might have envisioned,
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 13
but failed to disclose.”). Moreover, the underlying as-
sumptions for LAB’s expert’s derivation were themselves
faulty. For example, LAB’s expert assumed an adult male
weight of 86.1 kg to calculate the 1.5 mg/kg/day human
dosage from the rat study. He relied on an uncited, non-
prior art reference for that data. Lilly’s expert showed
that the dosage would have been approximately 1.7
mg/kg/day if 67 kg—the weight disclosed in the ’903
patent—had been used instead. 3
As for the fifth assumption, LAB presented no evi-
dence as to why a person of skill would choose to rely on
the Freireich method to calculate a human dosage for
therapeutic treatment of fibrosis with PDE5 inhibitors.
That reference was not disclosed in the provisional appli-
cation, is nearly half a century old, and was based on
measurements of toxicity of anticancer agents. More
importantly, LAB cannot rely on standalone references
that it failed to incorporate in the provisional application
in order to make out its priority claim. “[I]t is the disclo-
sures of the [provisional] application[] that count,” not
those of uncited references. Allergan, Inc. v. Sandoz Inc.,
796 F.3d 1293, 1309 (Fed. Cir. 2015) (holding that it was
error to rely on a clinical protocol to show earlier posses-
sion because the protocol was not disclosed in the specifi-
cations of the asserted patents).
Because proof of priority requires written description
disclosure in the parent application, not simply infor-
mation and inferences drawn from uncited references, the
Board correctly held that LAB’s expert’s calculation did
not satisfy the requirements for priority and that the ’903
3 The patent states that “1.5 mg/kg . . . is about the
dose ingested by men with an on demand single 100 mg
tablet.” ’903 patent, col. 45, ll. 7-12. That passage as-
sumes that an adult man weighs approximately 67 kg.
14 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
patent was therefore not entitled to the October 2002
priority date of the provisional application.
B
In an inter partes review proceeding, the Board gives
claims their broadest reasonable interpretation consistent
with the specification. In re Cuozzo Speed Techs., LLC,
793 F.3d 1268, 1276, 1279 (Fed. Cir. 2015), aff’d, 136 S.
Ct. 2131, 2142 (2016). We review the Board’s claim
construction de novo except for subsidiary fact findings,
which we review for substantial evidence. Id. at 1280.
1. The broadest reasonable interpretation of the
phrase “an individual with at least one of penile tunical
fibrosis and corporal tissue fibrosis” is its plain meaning:
an individual with penile tunical fibrosis and/or corporal
tissue fibrosis. 4 The Board’s construction (“an individual
hav[ing] symptoms that may be associated with penile
fibrosis, such as [erectile dysfunction], but not that the
patient be specifically diagnosed as having penile tunical
fibrosis or corporal tissue fibrosis”) reads that limitation
out of the claim. That is because erectile dysfunction can
have causes other than penile fibrosis, and because penile
fibrosis does not necessarily result in erectile dysfunction.
Because erectile dysfunction is merely a symptom that
4 Although Lilly claims that any “plain meaning”
argument was waived below, LAB adequately preserved
that argument when it stated in its Response to the
Petition for Institution that “a person of ordinary skill in
the art would understand the claims of the ’903 patent to
concern treatment of fibrosis, a disease.” See Phillips v.
AWH Corp., 415 F.3d 1303, 1313 (Fed. Cir. 2005) (en
banc) (“[T]he ordinary and customary meaning of a claim
term is the meaning that the term would have to a person
of ordinary skill in the art in question at the time of the
invention.”).
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 15
may be, but is not necessarily, associated with penile
fibrosis, erectile dysfunction cannot be equated with
tunical fibrosis and corporal tissue fibrosis.
The patent makes clear that penile fibrosis and erec-
tile dysfunction are not the same thing and do not neces-
sarily accompany one another. The specification makes
clear that penile fibrosis may result in erectile dysfunc-
tion, but it may not. E.g., ’903 patent, col. 1, ll. 29-34, 43-
44 (“Peyronie’s disease is a fibromatosis of the tunica
albuginea” that “[c]linically . . . quite frequently leads to
erectile dysfunction” but “is not always associated with
erectile dysfunction”). Conversely, the specification
acknowledges that erectile dysfunction has alternative
causes and may present without underlying penile fibro-
sis. See, e.g., id., col. 2, ll. 23-26 (“aging associated [erec-
tile dysfunction] . . . is mostly related to the loss of
[smooth muscle cells] in the penile corpora cavernosa by
apoptosis [cell death], with a corresponding increase in
collagen fibers”); id., col. 2, ll. 28-31 (“clinical result of this
aging process in the penis is defective cavernosal [smooth
muscle cell] relaxation leading to [CVOD], the most
common cause of [erectile dysfunction]” in aging males).
The patented invention targets the treatment of fibro-
sis, whether or not the fibrosis causes erectile dysfunction
in a particular case. For example, the invention treats
Peyronie’s disease even in a patient with no symptoms of
erectile dysfunction. The point is that the claimed treat-
ment method is intended to decrease the level of fibrotic
tissue, without regard to whether the patient’s fibrosis is
accompanied by erectile dysfunction.
The Board relied on a statement in the Background
section of the patent that notes that “[a] need exists for
effective methods to treat and/or ameliorate the symp-
toms of a variety of fibrotic disease, such as [Peyronie’s
disease], [erectile dysfunction] and arteriosclerosis.” ’903
patent, col. 2, ll. 42-44. But that statement plainly refers
16 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
to instances of erectile dysfunction that arise from fibrosis
(a “symptom[] of . . . fibrotic disease”), not to all cases of
erectile dysfunction. The next sentence in the specifica-
tion clarifies that the focus of the treatment method is
fibrosis, not the possible symptoms of fibrosis, such as
erectile dysfunction. That sentence states: “No effective
method of treatment currently exists that is directed
towards the molecular pathways underlying excessive
collagen deposition [fibrosis].” Id., col. 2, ll. 44-46.
This court’s decision in Rapoport v. Dement, 254 F.3d
1053 (Fed. Cir. 2001), is closely analogous to this case.
There, the appellant argued that the claim term “treat-
ment of sleep apneas” encompassed treatment of the
symptoms associated with sleep apnea. Id. at 1059. This
court disagreed, noting that the plain meaning of the term
sleep apnea and the specification made clear that the
patent was directed to treatment of the underlying sleep
apnea condition, even though the written description
noted that the claimed “treatment [also] alleviates the
sleep apnea-related symptoms of anxiety, depression,
fatigue, malaise, irritability, anger and hostility.” Id.
(citing patent application).
In this case, similarly, the ’903 specification mentions
various fibrotic conditions and their possible symptoms.
See, e.g., ’903 patent, col. 2, ll. 13-22 (arteriosclerosis, or
fibrosis of the media of the arterial wall, is one of the
underlying causes of hypertension). But the claims are
narrower and are clearly aimed at penile fibrosis—not
other types of fibrosis, and not at symptoms such as
erectile dysfunction. See Rapoport, 254 F.3d at 1059
(“[t]he plain language . . . unambiguously refers to ‘treat-
ment of sleep apneas’ narrowly defined, and does not also
include by its plain terms ‘treatment of symptoms associ-
ated with sleep apneas.’”). The specification’s references
to erectile dysfunction as a possible symptom of penile
fibrosis do not broaden the phrase “an individual with at
least one of penile tunical fibrosis and corporal tissue
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 17
fibrosis” beyond its ordinary meaning. As in Rapoport,
the ordinary meaning “narrowly refers to . . . the underly-
ing disorder itself.” Id.
The Board’s construction would make the patent
claims applicable to individuals with erectile dysfunction
not caused by penile fibrosis. Yet for patients suffering
from erectile dysfunction without penile fibrosis, the
claimed method would have no effect on the treatment of
penile fibrosis. The Board’s construction is therefore not
the broadest reasonable interpretation of the disputed
claim language; rather, it is overly broad. Given the
relationship between erectile dysfunction and penile
fibrosis, it is unreasonable to use the symptom of erectile
dysfunction as a proxy for penile fibrosis.
On the other hand, there is no support in the patent
or the prosecution history for LAB’s contention that the
phrase “an individual with at least one of penile tunical
fibrosis and corporal tissue fibrosis” requires an individu-
al to have “clinically significant” penile tunical or corporal
tissue fibrosis. Both parties’ experts agreed that some
physicians would treat fibrosis even if it was not deemed
“clinically significant.” We see no reason to import such a
limitation here, and we conclude that “an individual with
at least one of penile tunical fibrosis and corporal tissue
fibrosis” includes an individual with one or both of those
conditions, even if the condition is not deemed “clinically
significant.”
2. The limitation “arresting or regressing the at least
one of the penile tunical fibrosis and corporal tissue
fibrosis” requires halting the progression of, or reversing,
penile fibrosis. Lilly contends that the phrase “arresting
or regressing the [penile fibrosis]” has no patentable
weight. We conclude, however, that the phrase is more
than a statement of the intended result of administering
the PDE5 inhibitor within the dosage limits, with the
18 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
frequency, and for at least the minimum period prescribed
in the patent.
The full text of the limitation in which the “arresting
or regressing” language appears reads: “arresting or
regressing the [penile] fibrosis, wherein the PDE-5 inhibi-
tor is administered at a dosage up to 1.5 mg/kg/day for not
less than 45 days.” ’903 patent, col. 68, ll. 29-32. While
not dispositive, it is significant that the phrase “arresting
or regressing the [penile] fibrosis” is drafted as part of a
separate step of the method, not as the preamble or
introduction to a process carried out by the administra-
tion of the drug. The structure of the ’903 patent claim 1
is therefore not comparable to the structure of patent
claims in which statements of general purpose in the
preambles of method claims have been held to carry no
patentable weight. E.g., Bristol-Myers Squibb Co. v. Ben
Venue Labs., Inc., 246 F.3d 1368, 1375 (Fed. Cir. 2001)
(preamble phrase “for reducing hematologic toxicity” was
“non-limiting, and merely expressing a purpose”); see also
In re Montgomery, 677 F.3d 1375, 1380 (Fed. Cir. 2012)
(expressing “skeptic[ism]” that the phrase “for the treat-
ment or prevention of stroke” in a claim preamble was
more than an expression of purpose for the claimed meth-
od).
Other intrinsic evidence shows that the “arresting or
regressing” limitation does not merely duplicate the
wherein clause that follows. “Arresting or regressing”
demands efficacy; the wherein clause does not. As ex-
plained in the specification, “arresting” means “halt[ing]
the progression” or “prevent[ing] the further develop-
ment” of the fibrotic condition, and “regressing” means
“reduc[ing] in size” or “reversing” the fibrotic condition.
’903 patent, col. 3, ll. 8-13; id., col. 9, ll. 13-15; see also id.,
col. 2, ll. 53-61. In Example 3 of the specification, the
inventors demonstrated the arrest or regression of fibrosis
when administering a PDE5 inhibitor to rats daily for 45
days at a dosage equivalent to 1.5 mg/kg/day for an adult
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 19
human male. ’903 patent, col. 36, line 25, through col. 37,
line 5 (Example 3); id., col. 45, ll. 7-12.
The wherein clause sets forth the minimum duration
supported by the disclosure (45 days) for the arrest or
regression of fibrosis at a high dosage of the PDE-5 inhibi-
tor. But the reference to a minimum duration period of 45
days says nothing about the efficacy of the method if a
lower dosage of PDE5 inhibitor is administered. As the
inventors explained during prosecution, “it is likely that if
the dose [administered to the rats in Example 3] is re-
duced to 1/2 of the current dose to adapt it to the clinic
and minimize side effects, the duration of the antifibrotic
treatment may take 2 to 6 months or longer.” 5
Because the ’903 patent claims specify only a maxi-
mum dosage level and a minimum treatment period, it is
different from cases in which the claims contain express
dosage amounts as material claim limitations, and in
which efficacy is “inherent in carrying out the claim
steps.” Dawson v. Dawson, 710 F.3d 1347, 1355 (Fed. Cir.
2013) (citing Bristol-Myers Squibb, 246 F.3d at 1375, and
In re Montgomery, 677 F.3d at 1381). We therefore con-
clude that “arresting or regressing” the fibrosis adds an
efficacy requirement that is not otherwise found in the
claim language.
Nor do LAB’s infringement contentions in the ongoing
district court case render the “arresting or regressing”
5 The inventors also stated during prosecution that,
“like in the aging rat model [Example 3], it takes at least
45 days of treatment with sildenafil to ameliorate the
CVOD and underlying corporal fibrosis,” which “was done
with daily doses equivalent to 2.5 fold the doses currently
applied in the clinic to elicit an erection.”
20 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
limitation irrelevant. 6 LAB alleged that the “[l]ong-term
administration of Cialis on a once daily basis for the
treatment of [erectile dysfunction] results in the arrest or
regression of penile tunical fibrosis (i.e., [Peyronie’s
disease]) and corporal tissue fibrosis (i.e., [CVOD]).”
[LAB]’s Disclosure of Asserted Claims and Preliminary
Infringement Contentions, Ex. A at 5, Los Angeles Bio-
med. Research Inst. v. Eli Lilly & Co., No. 2:13-cv-08567-
JAK-JCG (C.D. Cal. filed May 19, 2014). But LAB did not
define “long-term” in that context. In order to prove
infringement, LAB may need to show, for example, that
Lilly induces the administration of 2.5 mg or 5 mg of
Cialis daily by patients with penile tunical or corporal
tissue fibrosis for a period of time that is long enough,
given the dosage levels, to result in the arrest or regres-
sion of fibrosis. In any event, LAB does not contend that
the Cialis label induces infringement by instructing the
daily administration of 2.5 mg or 5 mg of Cialis, regard-
less of the duration of the treatment.
3. Claim 1 of the ’903 patent contains a limitation
providing for a “continuous long-term regimen” in addi-
tion to the limitation providing for administering a PDE5
inhibitor in an amount “up to 1.5 mg/kg/day for not less
than 45 days.” The 45-day requirement makes clear that
the “continuous long-term regimen” must be at least 45
days in length.
6 We deny LAB’s motion to strike Lilly’s references
to those filings. We can properly take judicial notice of
the records of related court proceedings. See Function
Media, L.L.C. v. Google, Inc., 708 F.3d 1310, 1316 n.4
(Fed. Cir. 2013). Because we take judicial notice of those
records, we do not reach Lilly’s conditional objection to
LAB’s reliance on the Final Written Decision in the
related IPR proceeding on anticipation. See note 2 supra.
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 21
LAB argues that the term “continuous long-term reg-
imen” adds a requirement that the drug concentration in
the patient’s body attain a “constant level,” i.e., maintain
a “steady state” plasma concentration. The patent, how-
ever, never mentions the “steady state” of a drug or other
agent. As for “constant level,” LAB points to a single
sentence buried in the middle of the 68-column disclosure
that states:
A distinction exists between long-term (weeks,
months, years) continuous treatment with, for ex-
ample, a PDE5 inhibitor such as sildenafil to
maintain a constant level of these agents in order
to arrest or regress a fibrotic condition, versus on
demand (prior to the sexual act) single pill, short-
term treatment with sildenafil or other PDE5 in-
hibitors to obtain smooth muscle vasodilation in
the penis (male penile erection) or vagina/clitoris
(female sexual arousal) upon sexual stimulation.
’903 patent, col. 10, ll. 59-67. In that passage, the term
“constant level” is not presented as a definition of “contin-
uous long-term regimen,” or its equivalent. Rather, the
passage simply confirms that long-term continuous PDE5
inhibitor treatment excludes an “on demand . . . single
pill, short-term treatment”; the passage does not exclude
any treatment that fails to maintain an unvarying level of
the drug within the patient’s body.
Nor is “a constant level” required by anything else in
the specification. If an applicant intends to ascribe a
meaning to a claim term different from its ordinary
meaning, he must “set out the different meaning in the
specification in a manner sufficient to give one of ordinary
skill in the art notice of the change from ordinary mean-
ing.” Innova/Pure Water, Inc. v. Safari Water Filtration
Sys., Inc., 381 F.3d 1111, 1117 (Fed. Cir. 2004). Because
the patentees in this case have not “demonstrated a clear
intention to limit the claim scope,” id., in a manner incon-
22 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
sistent with the ordinary meaning of the term “continu-
ous,” it would be improper to construe the claim language
in the manner that LAB suggests.
Although LAB argues that the term “continuous long-
term regimen” should be construed to require a “constant
level of the administered PDE-5 inhibitor,” the position
LAB took before the Board and takes in its briefs before
this court makes clear that LAB is not using the word
“constant” in its conventional sense. In its opening brief,
LAB argues that a “constant level” of a PDE5 inhibitor
refers to “the average plasma concentration of that drug
upon reaching steady state,” even though the actual
concentration “peaks and then declines.” LAB Opening
Br. 36. In its reply brief, LAB departs even farther from
the ordinary meaning of “constant” and argues that “a
meaningful steady state (‘constant level’) requires a dose
interval that allows drug concentration to stay within its
therapeutic range.” LAB Reply Br. 16.
LAB cites its expert’s report and a pharmacology text
to support its argument that frequent dosages of a drug
with a short half-life are required to maintain a high, if
varying, level of plasma drug concentration. However,
LAB points to nothing in the patent that supports the
construction of the term “continuous long-term regimen”
to require dosing frequency sufficient to maintain the
level of drug concentration within what LAB refers to as
“its therapeutic range.”
The prosecution history also undercuts LAB’s argu-
ment. In the provisional application, claim 16 required
both a “continuous long term regimen” and “maintaining
a constant level.” It provided: “The method of claim 1,
wherein said administering comprises long term continu-
ous treatment for weeks, months or years to maintain a
constant level of the inhibitor.” But in the 2004 applica-
tion that matured into the ’903 patent, the claims did not
include the language “maintaining a constant level.” The
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 23
separate use of those terms in the provisional application
gives rise to the inference that “maintaining a constant
level” is not implicit in the term “continuous long-term
regimen.” And the omission of the reference to “maintain-
ing a constant level” from the non-provisional application
strongly suggests that the claims in the patent were not
meant to require that a constant level of the PDE5 inhibi-
tor be maintained.
LAB points out that during prosecution the inventors
distinguished “continuous long-term” treatment from on-
demand treatment. While that is true, the inventors drew
that distinction based on the duration of the treatment
regimen, not on the plasma level of the drug. For exam-
ple, in addressing the prior art, the inventors “predict[ed]
that 21 days of even a daily or twice a day treatment with
a PDE5 inhibitor would be totally insufficient . . . to
prevent or ameliorate CVOD, since in our unpublished
study on the time course of CVOD in the rat after caver-
nosal nerve damage, . . . once CVOD is established, . . . it
takes at least 45 days of treatment with sildenafil to
ameliorate CVOD and underlying corporal fibrosis.”
There is no suggestion in the prosecution history that a
“constant level” of the drug is required for patentability or
efficacy.
Finally, LAB argues that the Board’s construction im-
permissibly renders the term “continuous long-term
regimen” superfluous in light of the limitation requiring
administration of the PDE5 inhibitor “at a dosage up to
1.5 mg/kg/day for not less than 45 days.” While the two
limitations clearly overlap, the more general reference to
a “continuous long-term regimen” limitation serves to
emphasize that the treatment is continuous and not
sporadic. The fact that the limitations overlap is not
fatal, nor does it compel us to adopt an otherwise unsup-
ported construction of the claims. See SimpleAir, Inc. v.
Sony Ericsson Mobile Commc’ns AB, 820 F.3d 419, 429
(Fed. Cir. 2016) (Although “interpretations that render
24 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
some portion of the claim language superfluous are disfa-
vored,” that “preference for giving meaning to all
terms . . . is not an inflexible rule that supersedes all
other principles of claim construction.”). The overlap in
the limitations that results from giving them their plain
meaning does not justify importing a “constant level” or
“steady state” limitation into the claims where such a
limitation has no support in the specification or the
prosecution history.
C
Determining whether an invention would have been
obvious requires consideration of the scope and content of
the prior art, differences between the prior art and the
patent claims, the level of ordinary skill in the art, and
any secondary considerations. KSR Int’l Co. v. Teleflex
Inc., 550 U.S. 398, 406 (2007). In the case of a combina-
tion of references that together disclose all the limitations
of the claimed invention, the adjudicator must determine
whether there was an “apparent reason to combine the
known elements in the fashion claimed by the patent at
issue,” id. at 418, and whether a person of skill in the art
at the time of the invention would have had a “reasonable
expectation of success” in pursuing that combination, see
Genzyme Therapeutic Prods. Ltd. P’ship v. Biomarin
Pharm. Inc., 825 F.3d 1360, 1373 (Fed. Cir. 2016).
LAB contends that the Board’s findings are insuffi-
cient to establish obviousness under the correct construc-
tions of “an individual with at least one of a penile tunical
fibrosis and corporal tissue fibrosis” and “arresting or
regressing the at least one of a penile tunical fibrosis and
corporal tissue fibrosis.” We agree. The Board concluded
that the references on which it relied rendered obvious
the treatment of erectile dysfunction via the claimed
method, but it did not determine whether those references
showed that it would have been obvious to use long-term
continuous treatment with a PDE5 inhibitor to treat
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 25
individuals with penile fibrosis and to achieve the arrest
or regression of that condition.
1. The Board found that Montorsi and Whitaker
taught the treatment of erectile dysfunction, a symptom
sometimes associated with penile fibrosis, and that the
combination of Montorsi, Whitaker, and Porst gave rise to
a reasonable expectation of success in treating erectile
dysfunction. What the Board did not do, however, was to
find that those references taught treating a patient with
penile tunical fibrosis or corporal tissue fibrosis. Nor did
the Board find that those references provided the basis for
a reasonable expectation of success in treating those
conditions. See Institut Pasteur & Universite Pierre et
Marie Curie v. Focarino, 738 F.3d 1337, 1346 (Fed. Cir.
2013) (“Importantly, without a sound explanation for
doing otherwise, . . . the expectation-of-success analysis
must match the highly desired goal, not switch to a differ-
ent goal that may be a less challenging but also less
worthwhile pursuit.”). As indicated above, the correct
construction of the pertinent claim language requires
more than simply treating erectile dysfunction. 7
To be sure, Montorsi teaches that corporal fibrosis is
associated with erectile dysfunction in atherosclerotic or
aging patient populations. Montorsi, however, is directed
7 The dissent states that the Board found that the
method of claim 1 was used in the prior art. The Board’s
findings, however, rest on its erroneous claim construc-
tions, including equating erectile dysfunction with penile
fibrosis. The Board found in the prior art the method of
long-term administration (i) to an individual with erectile
dysfunction (ii) to symptomatically treat the erectile
dysfunction. It did not find in the prior art the method of
claim 1: long-term administration (i) to an individual with
penile fibrosis (ii) in an effective amount to arrest or
regress the fibrosis.
26 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
to on-demand dosing of PDE5 inhibitors; it does not teach
long-term daily treatment. The only statement in Mon-
torsi relating in any way to long-term treatment appears
in Montorsi’s discussion of a study showing that a one-
time administration of sildenafil at bedtime increased
nocturnal erections in men between 40 and 68 years of
age with erectile dysfunction. Montorsi comments that
the study “opened the door to further study investigating
the possible dosage of sildenafil to be administered daily
at bedtime.” Montorsi at 31. The study discussed by
Montorsi, however, was not limited to a population of
patients suffering from erectile dysfunction caused by an
underlying fibrotic condition (or even aging or atheroscle-
rotic patients who have a higher likelihood of an underly-
ing fibrosis).
The Board found that Whitaker taught the chronic
administration of PDE5 inhibitors to individuals with
erectile dysfunction and, in particular, that it taught
treating individuals with erectile dysfunction that is
associated with atherosclerosis. The first of those find-
ings is supported by substantial evidence, but the second
is not.
Whitaker mentions atherosclerosis only once in its 39-
page disclosure. It does so when addressing an effect that
Whitaker refers to as “vascular conditioning,” which was
not previously seen in patients treated with PDE5 inhibi-
tors. Whitaker at 12-13. Upon observing that effect in
the case of chronic treatment of patients with erectile
dysfunction, Whitaker states that “[i]t is expected that
vascular conditioning occurs after chronic administration
of the PDE5 inhibitor, for example, after about three daily
doses of up to 10 mg, preferably after five days of daily
dosing, and more preferably after seven days of daily
dosing.” Id. at 13. Whitaker then states that “[i]t is
theorized, but not relied upon herein that vascular condi-
tioning is caused by a partial or complete reversal of
circulatory dysfunctions in penile circulation arising from
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 27
conditions such as diabetes, atherosclerosis, smoking,
hypertension, or a combination of such factors,” conditions
that “result in thickening of the arterial wall, decreased
arterial compliance, and decreased responsiveness to
endogenous vasodilators, such as nitric oxide.” Id.
Whitaker, however, provides no data to support this
“vascular conditioning” causation theory. None of the
studies reported in Examples 5, 6, and 7 of Whitaker were
expressly limited to atherosclerotic, or even aging, patient
populations. E.g., Whitaker at 34 (PDE5 inhibitor in
Example 6 was administered to “patients with male
erectile dysfunction”). Nor can the presence of an under-
lying fibrotic condition be inferred, because the Board
pointed to no findings regarding the rate of incidence of
atherosclerosis in males with erectile dysfunction. In
sum, Whitaker provides no information about whether the
vascular conditioning effect was observed in erectile
dysfunction patients with atherosclerosis and associated
corporal fibrosis.
Indeed, Whitaker makes clear that the observation
about “vascular conditioning” and its cause is speculative.
Whitaker states that the “vascular conditioning” effect
was not previously observed, and notes that its relation-
ship to circulatory dysfunctions such as atherosclerosis is
merely “theorized.” Whitaker at 12-13. As such, Whita-
ker’s observation cannot serve as an express or implicit
teaching. See, e.g., Star Scientific, Inc. v. R.J. Reynolds
Tobacco Co., 655 F.3d 1364, 1375-76 (Fed. Cir. 2011)
(prior art’s “speculative and tentative disclosure of what
‘might’ or ‘may’ [explain the cause of a desired effect] does
not sufficiently direct or instruct one of skill in this art”);
Alza Corp. v. Mylan Labs., Inc., 464 F.3d 1286, 1290 (Fed.
Cir. 2006) (“[L]egal determinations of obviousness, as
with such determinations generally, should be based on
evidence rather than on mere speculation or conjecture.”).
28 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
Following its analysis of Whitaker, the Board found
that persons of skill in the art would have had a reasona-
ble expectation of success in treating erectile dysfunction
in fibrotic patients, as in Montorsi, and doing so through
long-term treatment, as in Whitaker. In so finding,
however, the Board summarily dismissed LAB’s counter-
argument that those references would not have given rise
to a reasonable expectation of success in treating erectile
dysfunction in the subpopulation suffering from penile
fibrosis.
According to LAB’s expert, it was widely believed at
the time of the invention that the enzyme iNOS and its
product nitric oxide were profibrotic, i.e., they exacerbated
fibrotic conditions and the accompanying symptom of
erectile dysfunction. It was known that nitric oxide
activates guanylate cyclase, which increases intracellular
cyclic guanosine monophosphate (“cGMP”). It was also
known that PDE5 inhibitors operate similarly: They
inhibit the enzyme PDE5, which breaks down cGMP, so
inhibiting PDE5 also leads to an increase in intracellular
cGMP. LAB contends that the prevailing view in the field
at the time of the invention was that PDE5 inhibitors
would also be profibrotic. Therefore, according to LAB,
persons of skill in the art would not have prescribed a
PDE5 inhibitor on a long-term basis to treat erectile
dysfunction in patients with penile fibrosis.
The Board dismissed LAB’s argument as addressed
only to the mechanism of action inherent in the claimed
method, which it found was taught by the combination of
Montorsi and Whitaker. That answer, however, does not
address LAB’s point that even if the combination of
Montorsi and Whitaker teach long-term treatment with a
PDE5 inhibitor of individuals with some forms of erectile
dysfunction, a person of skill in the art would not have
been motivated to combine those references to treat
individuals with fibrosis-related erectile dysfunction
because, according to LAB, the results would have been
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 29
expected to be detrimental. See Institut Pasteur, 738 F.3d
at 1346 (error to disregard prior art evidence of toxicity,
which was relevant to question of whether skilled artisan
would have a reasonable expectation of success in achiev-
ing the claimed invention).
To be sure, LAB’s evidence is not undisputed. At the
time of the invention, according to Lilly, the biochemical
pathway was under study by those in the field as a way of
addressing CVOD. And Whitaker, in discussing the
possibility of such a treatment, does not single out athero-
sclerotic individuals (or others with an underlying penile
fibrosis) and specifically warn against the profibrotic
effects of long-term treatment with a PDE5 inhibitor.
The question remains whether a person of skill in the
art would have had a reason to combine Montorsi, Whita-
ker, and Porst to treat penile fibrosis with a long-term
regimen of a daily dosage of a PDE5 inhibitor, and would
have had a reasonable expectation of success from doing
so. Because the Board’s obviousness analysis was based
on an erroneous construction of the claim language and
an overly broad interpretation of Whitaker, and because
the Board did not address the record evidence summa-
rized above, we remand for the Board to make new find-
ings as to whether there was an apparent reason to
combine the prior art references and whether that combi-
nation would have rendered obvious the long-term admin-
istration of PDE5 inhibitors to treat penile fibrosis. 8
8 LAB contends (LAB Opening Br. 60-62) that the
Board failed to consider the evidence of unexpected re-
sults as objective evidence of nonobviousness. As indicat-
ed above, the issue of unexpected results (and the related
question of a reasonable expectation of success) is tied to
the proper construction of the claim language. We there-
30 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
2. The Board also made no findings as to whether any
reference or combination of references rendered obvious
the claim limitation “arresting or regressing the at least
one of a penile tunical fibrosis and corporal tissue fibro-
sis,” because the Board erroneously concluded that arrest-
ing or regressing fibrosis is an inherent effect of any
regimen exceeding 45 days regardless of the dosage. The
Board did not consider, for example, whether the chronic
low dose of tadalafil (5 mg or 10 mg administered “daily”
for 8 or 12 weeks) in Whitaker’s Example 6 would arrest
or regress penile fibrosis, including the relevant inventor
statements during prosecution that administration for 45
days of an extremely high dose of sildenafil was required
to achieve the arrest or regression of penile fibrosis, see
supra note 5. On remand, the Board should make the
findings necessary to determine whether the references
render the “arresting or regressing” limitation obvious.
3. LAB also challenges the Board’s findings regarding
the limitation “at a dosage up to 1.5 mg/kg/day for not less
than 45 days.” But the Board’s findings on that issue are
well founded. Porst discloses that taking up to 1.5
mg/kg/day of a PDE5 inhibitor for three weeks is safe,
well-tolerated, and effective as a treatment for erectile
dysfunction. Whitaker teaches chronic dosing of PDE5
inhibitor for at least 45 days. Whitaker does not explicitly
disclose that dosing must occur every day, but it suggests
as much, noting that a “better response” was obtained
“with increased frequency of dose.” Whitaker at 36 (bet-
ter results reported with closer to daily compliance, in the
context of comparing the subgroups in Example 6); see
also id. at 38 (“Adverse events were . . . attenuated with
continued daily treatment.”). And those remarks are
supported by Montorsi’s observation that the study re-
fore leave it to the Board on remand to address that issue
in the first instance.
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 31
viewed by Montorsi “opened the door to further study
investigating the possible dosage of sildenafil to be admin-
istered daily at bedtime to prevent or treat [erectile
dysfunction] in the elderly patient.” Montorsi at 31.
In sum, Whitaker teaches long-term chronic treat-
ment for more than 45 days, Montorsi and Whitaker
suggest daily administration, and Porst and Montorsi
teach a dosage of up to 1.5 mg/kg/day. The Board’s find-
ings regarding the dosage and treatment period limitation
are therefore supported by substantial evidence.
4. Because we agree with the Board that the “contin-
uous long-term regimen” limitation is satisfied by the
administration of a PDE5 inhibitor “up to 1.5 mg/kg/day
for not less than 45 days,” we conclude that the same
references teach “continuous long-term regimen.” The
Board’s findings regarding that limitation are therefore
supported by substantial evidence as well.
III
Because the Board’s obviousness determination was
predicated on an erroneous claim construction of two of
the limitations of claim 1, and because the Board did not
make factual findings as to whether there was an appar-
ent reason to combine the prior art references to treat
penile fibrosis and whether a person of skill in the art
would have had a reasonable expectation of success from
such a combination, we remand this case to the Board.
We also remand for the Board to make findings bearing
on the obviousness of the “arresting or regressing” limita-
tion. 9 The Board’s order is vacated, and the case is re-
9 Although the dissent urges that we should resolve
the obviousness question without a remand, it would be
improper for us to do so in the absence of the necessary
factual findings by the Board. Personal Web Techs., LLC
v. Apple, Inc., No. 2016-1174, at 8-9 (Fed. Cir. Feb. 14,
32 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
manded for further proceedings consistent with this
opinion.
VACATED AND REMANDED
2017) (discussing the “basic principle[] of administrative
law” that an agency must provide a full and reasoned
explanation for its decision, which is necessary to both
enable judicial review and “prevent judicial intrusion on
agency authority”); Ariosa Diagnostics v. Verinata Health,
Inc., 805 F.3d 1359, 1365 (Fed. Cir. 2015) (“[W]e must not
ourselves make factual and discretionary findings that
are for the agency to make.”) (citing SEC v. Chenery
Corp., 332 U.S. 194, 196-97 (1947)); see also, e.g., Bilstad
v. Wakalopulos, 386 F.3d 1116, 1126 (Fed. Cir. 2004)
(“vacat[ing] the Board’s decision with respect to the
written description requirement and remand[ing] for
reconsideration under the proper test” because the court’s
“resolution of the [written description] question” previous-
ly decided by the Board under an incorrect legal standard
would “require[] fact findings this court is not permitted
to make.”).
United States Court of Appeals
for the Federal Circuit
______________________
LOS ANGELES BIOMEDICAL RESEARCH
INSTITUTE AT HARBOR-UCLA MEDICAL
CENTER,
Appellant
v.
ELI LILLY AND COMPANY,
Appellee
______________________
2016-1518
______________________
Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board, in No. IPR2014-
00752.
______________________
NEWMAN, Circuit Judge, concurring in part, dissenting
from the judgment.
I agree generally with the court’s discussion of the
’903 patent and the prior art. However, I conclude that
the Patent Trial and Appeal Board correctly held the
claim invalid on grounds of obviousness and inherency.
No dispositive error of law, no absence of support of
dispositive findings by substantial evidence, has been
shown. I would affirm the Board’s decision, and thus I
respectfully dissent from the ruling of vacatur and re-
mand.
2 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
DISCUSSION
The subject claim of the ’903 patent is:
1. A method comprising:
a) administering a cyclic guanosine 3’,5’-
monophosphate (cGMP) type 5 phosphodiesterase
(PDE 5) inhibitor according to a continuous long-
term regimen to an individual with at least one of
a penile tunical fibrosis and corporal tissue fibro-
sis; and
b) arresting or regressing the at least one of the
penile tunical fibrosis and corporal tissue fibrosis,
wherein the PDE-5 inhibitor is administered at a
dosage up to 1.5 mg/kg/day for not less than 45
days.
’903 Patent, col. 68, lines 23–32. The references cited by
the PTAB show the subject cGMP products for treatment
of erectile dysfunction, and discuss the mode of action in
erectile dysfunction. The cited references are in the same
field of endeavor, and include a review article. I outline
some relevant PTAB findings:
• the prior art shows that the cGMP products of
claim 1 were known PDE-5 inhibitors, and known
to relieve erectile dysfunction;
• the prior art shows use of these cGMP products
in the claimed dosages and over extended time pe-
riods.
• the prior art shows that penile fibrosis was
known to be a cause of erectile dysfunction.
The PTAB held trial, with evidence and expert witnesses
from both sides. The Board concluded that the subject
matter of claim 1 would have been obvious in view of the
cited references. Reversible error in this conclusion has
not been shown, and the Board’s findings on which its
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 3
conclusion was based are supported by substantial evi-
dence.
The court’s extensive opinion sets forth the relevant
facts, which I repeat only as needed to explain why I
conclude that our proper action is to affirm the decision of
the PTAB.
PDE-5 inhibitors were known to treat erectile
dysfunction, which was known to be caused
by penile fibrosis.
That penile fibrosis is a cause of erectile dysfunction,
and that erectile dysfunction is relieved by treatment
with these PDE-5 inhibitors, was known before the filing
of the ’903 application. LABio stresses that erectile
dysfunction was known to have other causes, such as
diabetes, atherosclerosis, and psychological problems.
However, on the prior art and expert testimony that when
penile fibrosis was present it was affected by the PDE-5
inhibitors, the Board found that this effect was inherent
in the use of these products to treat erectile dysfunction.
There was no claim that the ’903 inventors discovered
that penile fibrosis is a cause of erectile dysfunction.
Their work is described as relating to understanding the
production of nitric oxide, and other scientific aspects of
the mechanism of erectile dysfunction and how PDE-5
inhibitors work. I do not diminish the scientific value of
their investigations. However, this does not diminish the
evidence and the Board’s findings that PDE-5 inhibitors
were known and used by others under the conditions set
forth in claim 1.
Claim 1 is directed to use of the cGMP PDE-5 inhibi-
tors in dosages and for periods shown in the prior art; and
the Board found that this use existed in the prior art,
with the effect on penile fibrosis inherent in this use.
This finding is supported by substantial evidence. In
Atlas Powder Co. v. Ireco, Inc., 190 F.3d 1342, 1346 (Fed.
4 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
Cir. 1999), the court explained that “if granting patent
protection on the disputed claim would allow the patentee
to exclude the public from practicing the prior art, then
that claim is anticipated, regardless of whether it also
covers subject matter not in the prior art.”
We are reminded of the truism that “that which in-
fringes if later anticipates if earlier.” Polaroid Corp. v.
Eastman Kodak Co., 789 F.2d 1556, 1573 (Fed. Cir. 1986)
(quoting Peters v. Active Mfg. Co., 129 U.S. 530, 537
(1889)). Both parties have advised that LABio has
charged Lilly with “willfully inducing infringement of the
’903 patent by marketing Cialis®, whose active ingredient
is the PDE-5 inhibitor tadalafil, to erectile dysfunction
patients for daily use, knowing and intending that it
would be used to treat the penile fibrosis of those erectile
dysfunction patients suffering from that underling condi-
tion.” LABio Br. 12. 1 I agree with the court that this
representation is relevant to the issues of obviousness and
inherency, for the prior art shows such daily use and at
the claimed dosages.
The cited references lead to the PTAB’s rul-
ing of obviousness
The Montorsi reference is a review article published
in April 2002, entitled “The Ageing Male and Erectile
Dysfunction.” The Whitaker reference is an international
application published November 1, 2001, entitled “Daily
Treatment for Erectile Dysfunction Using a PDE5 Inhibi-
tor.” The Porst reference is an article entitled “Daily
IC351 [tadalafil] Treatment of ED,” published in Septem-
ber 2000. 2
1 The district court action has been stayed pending
resolution of the PTAB proceedings.
2 LABio appeals the PTAB’s denial of priority to
LABio’s provisional application, filed on October 22, 2002.
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 5
At the PTAB trial, witnesses discussed the mecha-
nism whereby penile fibrosis is related to erectile dysfunc-
tion, and the mechanism of these cGMP compounds in
PDE-5 inhibition. The PTAB found that “treatment of ED
in elderly patients or patients with atherosclerosis, as
suggested by both Montorsi and Whitaker, would result in
treatment of patients with the fibrosis, as Montorsi teach-
es that corporal fibrosis is associated with ED in those
patient populations.” PTAB Op. at 22. Substantial
evidence supports this finding.
The PTAB cited Montorsi, which is a review of the
causes of erectile dysfunction, an ailment that had been
extensively studied over the years. Montorsi reports on
the use of cGMP compounds as PDE-5 inhibitors, and
compiles information from many scientific publications.
Montorsi describes studies investigating the causes of
erectile dysfunction in aging men, summarizing that “it
seems reasonable to hypothesize that the ED from ageing
is the result of atherosclerosis-induced cavernosal is-
chaemia leading to cavernosal fibrosis and veno-occlusive
dysfunction.” Montorsi at 31.
Montorsi describes a study “wherein sildenafil was
taken as required, but no more than once daily, over a 12
week to 6 month period,” relied on by the PTAB to show
“that sildenafil is an effective treatment of ED in elderly
men.” PTAB Op. at 20. The court observes that “Montor-
si teaches that corporal fibrosis is associated with erectile
dysfunction in atherosclerosis of aging patient popula-
tions,” Maj. Op. at 25, and finds that substantial evidence
Lilly points out, without apparent dispute, that the rele-
vant prior art would not be eliminated by LABio’s provi-
sional application’s filing date of October 22, 2002,
because all the references are prior art within the mean-
ing of 35 U.S.C. § 102(a), even if they do not qualify under
§ 102(b). Lilly Br. at 18.
6 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
supports “the Board[s] f[inding] that Whitaker taught the
chronic administration of PDE5 inhibitors to individuals
with erectile dysfunction.” Id. at 26. I agree. Whitaker
states that “[t]o receive the full benefit of the present
invention, chronic administration generally refers to
regular administration for an extended period, preferably
daily for three or more days, and still more preferably
daily as long as the patient suffers from erectile dysfunc-
tion (in the absence of therapy).” Whitaker at 7. Lilly’s
expert testified that “it would take ‘months’ to resolve ED
based on circulatory dysfunction due to diabetes, athero-
sclerosis, smoking hypertension or a combination of those
factors (i.e., Whitaker’s patient population).” Goldstein
Decl. at 73.
The court cites Whitaker’s statement that “[i]t is ex-
pected that vascular conditioning occurs after chronic
administration of the PDE5 inhibitor, . . .” Maj. Op. at 26,
citing Whitaker at 13. My colleagues criticize Whitaker’s
lack of data on vascular conditioning. Id. at 27. However,
that does not erase Whitaker’s teaching of chronic admin-
istration; and I point out that claim 1 does not mention or
require vascular conditioning. The PTAB found that
“Whitaker expressly teaches once daily dosing, teaches
that treatment should last as long as the erectile dysfunc-
tion continues, and expressly teaches time periods of eight
to twelve weeks.” PTAB Op. at 21. These findings are
supported by substantial evidence.
On this appeal LABio argues, as it did during prose-
cution, that “[t]he pending claims are directed to a ‘cura-
tive’ effect as opposed to a ‘palliative’ effect . . . for a long-
term result (e.g., years), not a pathophysiology (function)
for a very short-term result of a vasodilation (e.g., hours,
maximum 2-3 days.” LABio Br. 10. However, the refer-
ences show use longer than hours or 2-3 days. The Porst
reference shows clinical trials in which tadalafil was
administered for three weeks to “men with mild to mod-
erate erectile dysfunction.” The dosages were in the
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 7
range shown in claim 1. The PTAB considered this refer-
ence in combination with the references to Montorsi and
Whitaker; no error has been shown in this combination
for the treatment of erectile dysfunction.
The PTAB’s decision accords with precedent
Precedent has dealt with a variety of factual situa-
tions in which a purported new use or property has been
discovered for a known product, and patentability is
sought on various premises. In Bristol-Myers Squibb Co.
v. Ben Venue Laboriatories, Inc., 246 F.3d 1368 (Fed. Cir.
2001), the court held that “[n]ewly discovered results of
known processes directed to the same purpose are not
patentable because such results are inherent,” having
observed that the claimed term “for reducing hematologic
activity” “merely express[ed] a purpose” and is “non-
limiting.” Id. at 1375, 1376.
Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362
(Fed. Cir. 2012), involved a claim to a method comprising
“stabilizing conjunctival mast cells by topically adminis-
tering” olopatadine in a known composition. Id. at 1364.
The prior art described the known composition used as an
antihistamine. Id. This court reversed the district court’s
finding that a person would not have used the composi-
tion to stabilize mast cells because “a person of ordinary
skill in the art at the time of the invention would have
been motivated to use olopatadine to treat human eye
allergies as claimed for its established antihistaminic
efficacy.” Id. at 1369.
A contrary result was reached in Allergan, Inc. v.
Sandoz Inc., 726 F.3d 1286 (Fed. Cir. 2013), where the
proposed claim was for “reducing the number of daily
topical ophthalmic doses.” Id. at 1289. The court held
that the enhanced efficacy was not taught in or suggested
in the prior art or inherent in the prior dosage regimen,
Id. at 1294, and allowed claims to the multiple daily
doses. In Alcon Research, the court allowed claims to a
8 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
specific high concentration of a known product for treat-
ment of allergic eye disease, finding that the prior art only
taught lower concentrations, and that the higher concen-
tration would not be obvious to try. Id. at 1370. And in
Rapoport v. Dement, 254 F.3d 1053 (Fed. Cir. 2001), the
court upheld claims to the use of a known product to treat
sleep apnea, holding that the prior use to treat anxiety
“did not address treatment of the underlying sleep apnea
disorder” because the sleep apnea treatment was not
inherent in the prior art’s anxiety treatment. Id. at 1060,
1062–63. While LABio states that Allergan and Rapoport
support its position, each of those cases relies on facts
missing here.
Precedent thus illustrates that the later discovery of a
new and unobvious use of a known product may be pa-
tentable when the standards of unobviousness are met.
Here, however, penile fibrosis was known in the prior art
to be a mechanism of causing erectile dysfunction. A
person of ordinary skill would, as the PTAB found, use
the claimed compounds at the claimed doses for the
claimed duration, for the purpose of treating erectile
dysfunction in patients with penile fibrosis. The PTAB’s
findings are supported by substantial evidence, and its
conclusions based thereon are in accordance with law.
See Alcon Research, 687 F.3d at 1369 (“Given that the
patent defines, and expressly claims, olopatadine concen-
trations that are ‘therapeutically effective’ to stabilize
conjunctival mast cells, Kamei’s disclosure of overlapping
concentrations, even if for a different purpose, meets
these claim limitations.”). The PTAB’s decision should be
affirmed.
Finality and the America Invents Act
I respectfully dissent from my colleagues’ judgment of
vacatur and remand, for such further proceedings fail the
policy and purpose of the America Invents Act, and should
be invoked only when there are major defects in the PTAB
LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY 9
proceeding, requiring activity and redetermination that is
not available on the appellate record.
The court at its footnote 9 takes issue with my posi-
tion that our appellate obligation is to decide the appeal
on the record on which the appeal reaches us. The court
states that if an aspect is insufficiently established in the
PTAB proceeding, our appellate role is to remand, despite
the usual protocol that when sufficient basis has not been
provided to support a necessary ruling, the side with the
burden of establishing that position, loses. When, as
here, the dispositive facts are not in dispute, it is not
customary to authorize the deficient party to return to the
trial tribunal to try again.
The America Invents Act adds rigor to this protocol,
for the AIA created an expedited administrative proce-
dure with strict time limits. Within these time limits, the
parties must present their case and the PTAB must make
its decision. It negates a foundation of the AIA for the
appellate tribunal simply to remand for further proceed-
ings after the statutory deadline. Our obligation is to
decide the appeal as it reaches us.
According to the majority, the Board did not find that
the prior art taught “long-term administration (i) to an
individual with penile fibrosis (ii) in an effective amount
to arrest or regress the fibrosis.” Maj. Op. at 25 n.7, 31.
Respectfully, the majority is incorrect, because the Board
expressly found that the Whitaker reference taught long-
term administration to patients with erectile dysfunction,
and the Board expressly found that in some of those
patients erectile dysfunction is caused by penile fibrosis.
It is not necessary to return to the Board to find whether
the prior art administered “an effective amount to arrest
or regress the fibrosis,” id. at 25 n.7, because LABiomed
has conceded that it does; that is the basis for its litiga-
tion position.
10 LOS ANGELES BIOMEDICAL v. ELI LILLY AND COMPANY
Our obligation is to review the rulings of law and fact
on the record presented. On this record, preponderant
evidence is on the side of obviousness. Thus the decision
in this IPR proceeding should be affirmed, not vacated
and remanded.
The America Invents Act was enacted to remedy the
lack of expedition and to add predictability in infringe-
ment disputes, by assigning to an expert administrative
tribunal and presumed expert federal court the resolution
of some major patentability issues, with tight procedural
rules and deadlines. It was expected that in the normal
course questions of patentability under Section 102 and
103 would be reliably and speedily resolved. Implement-
ing this policy, when we find analytic lapses by the PTAB,
it appears that the statute contemplates that we will
make the determination, on the record that was made at
the Board. Indeed, the depth of briefing by the parties
suggests that this was their understanding, too.
I don’t say that remands are never appropriate, but
remands should be rare. Here the issues were fully
developed, with eloquent argument all around, and an
extensive Board opinion in which my colleagues find only
slight gaps. Finality is available; it is our obligation to
decide the merits.