ERFINDERGEMEINSCHAFT UROPEP GbR v. Eli Lilly and Company et al

Filing 149

MEMORANDUM OPINION AND ORDER. Signed by Judge William C. Bryson on 10/21/2016. (ch, )

IN THE UNITED STATES DISTRICT COURT
FOR THE EASTERN DISTRICT OF TEXAS
MARSHALL DIVISION

ERFINDERGEMEINSCHAFT UROPEP
GbR,
Plaintiff,
v.
ELI LILLY AND COMPANY, and
BROOKSHIRE BROTHERS, INC.,
Defendants.

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Case No. 2:15-CV-1202-WCB

MEMORANDUM OPINION AND ORDER
In this patent case, the plaintiff, Erfindergemeinschaft UroPep GbR (“UroPep”), has
alleged that the defendants, Eli Lilly and Company and Brookshire Brothers, Inc., have infringed
U.S. Patent No. 8,791,124 (“the ’124 patent”), owned by UroPep. Before the Court are two
motions for summary judgment filed by the defendants: a motion for summary judgment of noninfringement, Dkt. No. 119, and a motion for partial summary judgment that claims 1 and 3 of
the ’124 patent are invalid for failure to meet the written description requirement of 35 U.S.C.
§ 112 ¶ 1, Dkt. No. 120.
Following a hearing on June 23, 2016, the Court entered an order construing several
disputed terms of the ’124 patent. Dkt. No. 131 (construing the terms “administering,” “a person
in need thereof,” and “an effective amount”). In that order, the Court did not construe the term
“an inhibitor of phosphodiesterase (PDE) V,” which appears in the ’124 patent, but instead
postponed the construction of that term until summary judgment motions were filed. In addition,
prior to issuing its claim construction order, the Court entered an amended docket control order
setting forth a schedule for expedited briefing of the defendants’ summary judgment motions.

Dkt. No. 117. In accordance with that schedule, the defendants filed motions for summary
judgment of non-infringement and for partial summary judgment of invalidity. Those motions
focus on the phrase “an inhibitor of phosphodiesterase (PDE) V.”
In their non-infringement motion, the defendants argue that the disputed phrase should be
construed under 35 U.S.C. § 112 ¶ 6 and that the scope of the claims should therefore be limited
to certain specifically disclosed PDE V inhibitors. The necessary result of such an interpretation
of the phrase, according to the defendants, would be a judgment of non-infringement. In their
invalidity motion, the defendants argue that if the phrase “an inhibitor of phosphodiesterase
(PDE) V” were construed to include all compounds capable of inhibiting PDE V (other than
those specifically excluded by the claim language), the claims would lack the written description
required under 35 U.S.C. § 112 ¶ 1, and therefore would be invalid.
UroPep responds that the phrase “an inhibitor of phosphodiesterase (PDE) V” should not
be construed under 35 U.S.C. § 112 ¶ 6 and that construing the phrase without reference to
35 U.S.C. § 112 ¶ 6 does not give rise to a written description problem under 35 U.S.C. § 112
¶ 1.
In this order, the Court construes the term “inhibitor of phosphodiesterase (PDE) V” and
DENIES the defendants’ two motions for summary judgment.
BACKGROUND
The ’124 patent is directed to a method of treatment or prophylaxis of a person affected
with benign prostatic hyperplasia (“BPH”), a condition associated with an enlarged prostate,
leading to difficulty in urination and associated problems.

By 1983, it was known that a

significant improvement in the condition could be achieved by the administration of drugs that
trigger the relaxation of the prostatic muscle cells. However, prior art treatments that relaxed
those cells, such as the use of alpha-receptor blockers, were characterized by low effectiveness,
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slow onset of action, or significant side effects. As an improvement over the prior art, the ’124
patent purports to “have examined a completely different pharmacological principle of action,
namely the affection of a key enzyme within the smooth muscle cells of the prostate gland,
phosphodiesterase.” ’124 patent, col. 1, ll. 9-35.
The specification explains that the relaxation of smooth muscle cells is caused by the
transmission of information through either hormones or neurotransmitters. That passage of
information causes an increase in the levels of cyclic adenosine monophosphate (“cAMP”) and
cyclic guanosine monophosphate (“cGMP”) in the muscle, which promotes the relaxation of
those cells. The level of those compounds is reduced by the presence of phosphodiesterases
(“PDEs”), which hydrolyze cAMP and cGMP. ’124 patent, col. 1, ll. 36-52. To promote muscle
relaxation, “[i]nhibitors of the PDEs in turn reduce the digestion of cAMP and cGMP, resulting
in an increase of these molecules within the cell and thus in a relaxation of the smooth muscle
cell.” Id., col. 1, ll. 44-47. The ’124 patent states that this mechanism of action had been
described by a number of publications in the early 1990s. Id., col 1, ll. 48-52.
The ’124 patent notes that the cited prior publications describe PDEs in the body as
consisting of at least five categories of subesterases of PDE (i.e., PDE I to PDE V), and that the
various PDEs are distributed differently throughout different organs and organ systems. 1 The
specification asserts that the side effects and low effectiveness of the prior art prostate treatments
suggests that “a well-aimed affection of the prostatic muscles by inhibiting a functionally
important sPDE [specific PDE] isoenzyme appears to be superior to conventional therapy
1

The specific PDEs were initially identified by Roman numerals, the convention
followed in the ’124 patent. It is now more common to use Arabic numerals to describe the
specific PDEs. The current practice is to refer, for example, to PDE V as PDE5. For
consistency, except where quoting record materials, the Court will use the Roman numeral
convention that was commonly employed as of the July 1997 priority date of the’124 patent.

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methods.” ’124 patent, col. 2, ll. 3-5. The specification states that PDE I, PDE IV, and PDE V
have been found in prostate tissue and that a “well-aimed inhibition of these isoenzymes will
result in relaxation of the [prostatic] muscles even when minute doses of a specific inhibitor are
administered, with no appreciable effects in other organ strips.” Id., col. 2, ll. 3-5. It then
concludes that the “subject matter of the invention is the use of specific inhibitors of sPDE I,
sPDE IV, and sPDE V in the prophylaxis and treatment of prostatic diseases, in particular
[BPH] . . . .” Id., col. 2, ll. 17-20.
The ’124 patent has one independent claim. It reads as follows:
1. A method for prophylaxis or treatment of benign prostatic
hyperplasia comprising administering to a person in need thereof
an effective amount of an inhibitor of phosphodiesterase (PDE) V
excluding a compound selected from the group consisting of
dipyridamole,
2-(N-(4-carboxypiperidine)-6-chloro-4(3,4(methylendioxy)benzyl)amino)quinazoline,
2,3-dihydro-8-hydroxy-7-nitro-1,4-benzodioxine-2methanol, alpha-nitrate.
4((3,4-(methylendioxy)benzyl)amino)-6,7,8-trimethoxyquinazoline,
1-methyl-3-propyl-6-(5-(N-(4-methylmorpholino)sulfonyl)2-ethoxyphenyl)pyrazole[4,5]pyrimidin-4(5H)one,
2-n-butyl-5-chloro-1-(2-chlorobenzyl)-4-methylacetateimidazole,
1-cyclopentyl-3-methyl-6-(4-pyridinyl)pyrazolo(3,4d)pyrimidin-4(5H)-one,
7-(3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-2-hydroxypropoxy)-2-carboxy-2,3-didehydro-chronan-4-one,
and pharmacologically compatible salts thereof.

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’124 patent, col. 8, ll. 18-41 (emphasis added and duplicate compound removed). 2 In other
words, the inventors “claimed a method of treatment for BPH by administering an effective
amount of a PDE5 inhibitor” that is not one of the eight listed compounds or their
pharmacologically compatible salts. Pl. UroPep’s Combined Sur-Reply to Defs.’ Mots. for
Summ. J., at 11, Dkt. No. 141. Claim 3, which depends from claim 1, reads as follows:
3. The method of claim 1 wherein the compound in combination
with a pharmacologically acceptable excipient is administered in a
unit dose form.
’124 patent, col. 8, ll. 45-48.
The structure of claim 1, which covers all inhibitors of PDE V except for certain
specifically listed compounds, is not common in the Court’s experience.

As UroPep

acknowledges “there are not a lot of claims that are drafted in this way.” Claim Construction
Hr’g Tr., at 62:22-25, Dkt. No. 125.
The application for the ’124 patent was a continuation of the application that matured into
U.S. Patent No. 8,106,061 (“the ’061 patent”). The ’061 patent includes claims that cover
methods of treating of BPH and prostatic disease or relaxing prostatic muscles by administering
a selective inhibitor of PDE IV and/or PDE V selected from a group of specific compounds.
’061 patent, col. 8, ll. 4-59. The specific compounds identified in the claims of the’061 patent
include most of the compounds that are specifically excluded from the claims of the ’124 patent.
During the prosecution of the application that led to the ’124 patent, the examiner
rejected the claims on the ground of nonstatutory double patenting. The patentees then amended
claim 1 to exclude from the scope of the claim most of the PDE inhibitors recited in the ’061
2

Claim 1, as set forth in the ’124 patent, contains a duplicate listing of 1-methyl-3propyl-6-(5-(N-(4-methylmorpholino)sulfonyl)-2-ethoxyphenyl)pyrazole[4,5]pyrimidin4(5H)one, which is one of the eight excluded compounds.

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patent. Dkt. No. 106-08, at 115. When the examiner nonetheless rejected the new claims as
being anticipated by the claims of the ’061 patent, id. at 121-23, the patentees entered a terminal
disclaimer with respect to the’061 patent, id. at 126-28. The claims were then allowed.
DISCUSSION
The matters presently before the Court raise three issues: (1) whether the term “an
inhibitor of phosphodiesterase (PDE) V” in claim 1 of the ’124 patent is governed by 35 U.S.C.
§ 112 ¶ 6; (2) how that term should be construed if it is not governed by section 112 paragraph 6;
and (3) whether the specification of the ’124 patent satisfies the written description requirement
of 35 U.S.C. § 112 ¶ 1.
I. The Motion for Summary Judgment of Non-Infringement
UroPep’s theory of infringement is that the defendants infringe, directly or indirectly, by
the administration of the drug tadalafil (the active ingredient in Lilly’s commercial product
Cialis) to treat BPH. According to UroPep, tadalafil is “an inhibitor of phosphodiesterase (PDE)
V” that is effective for prophylaxis or treatment of BPH, and its administration for that purpose
therefore infringes UroPep’s ’124 patent.
The defendants’ motion for summary judgment of non-infringement turns on the
construction of the term “an inhibitor of phosphodiesterase (PDE) V.” As noted, when the Court
entered its claim construction order in this case, see Dkt. No. 131, it postponed construction of
that term until briefing on the defendants’ motions for summary judgment was complete. The
Court will now construe that term.
UroPep proposes that the phrase “an inhibitor of phosphodiesterase (PDE) V” should be
construed to mean a “compound able to inhibit phosphodiesterase (PDE) V.” See Pl. UroPep’s
Corrected Opening Claim Constr. Br., at 21, Dkt. No. 105. In addition, UroPep asserts that the
intrinsic record requires that the phrase should be understood to contain three additional
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limitations: the PDE V inhibitor must be “selective”; it must consist of a small molecule; and it
must be therapeutically effective. 3 See id. at 22-25; Pl. UroPep’s Reply Claim Constr. Br., at 810, Dkt. No. 109.
The defendants argue that the term “an inhibitor of phosphodiesterase (PDE) V” is “an
element in a claim for a combination” that recites function without reciting structure and
therefore is governed by 35 U.S.C. § 112 ¶ 6. See Defs. Eli Lilly and Company and Brookshire
Brothers, Inc.’s Resp. Claim Constr. Br., at 7-8, Dkt. No. 106. For that reason, they contend,
only those compounds that are specifically described in the specification and not otherwise
excluded would be covered by the claims. Construed in that manner, the patent would read only
on zaprinast and MY5445, the only two non-excluded compounds that are specifically identified
in the ’124 specification as PDE V inhibitors and are not expressly excluded from the scope of
the claims.
A. Analysis of the Term “an inhibitor of phosphodiesterase (PDE) V” Under
35 U.S.C. § 112 ¶ 6
The Court first addresses the question whether the term “an inhibitor of
phosphodiesterase (PDE) V” is governed by 35 U.S.C. § 112, ¶ 6, the “means- (or step-) plusfunction” clause of section 112 of the Patent Act. 4 Whether that clause applies to a particular
claim element is a matter of claim construction and is therefore a question of law. Personalized
Media Commc’ns, LLC v. Int’l Trade Comm’n, 161 F.3d 696, 702 (Fed. Cir. 1998).
3

A selective inhibitor is one that inhibits a particular compound significantly more than it
does others. For example, a selective inhibitor of PDE V would inhibit PDE V significantly
more than it inhibits other PDEs, such as PDE II or PDE III. The parties dispute how selective a
selective inhibitor must be in order to qualify as a “selective” inhibitor.
4

Under the America Invents Act (“AIA”), section 112 paragraph 6 was recodified as 35
U.S.C. § 112(f). Although the AIA did not make any change in the substance of the provision,
this opinion refers to it as section 112 paragraph 6, since the pre-AIA version of the provision
governs cases involving the ’124 patent.
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Section 112 paragraph 6 was first enacted as part of the 1952 Patent Act “in response to
Halliburton Oil Well Cementing Co. v. Walker, 329 U.S. 1 (1946), which rejected claims that do
not describe the invention but use conveniently functional language at the exact point of
novelty.” Warner-Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17, 27 (1997) (quoting
Halliburton, 329 U.S. at 8); see also Gen. Elec. Co. v. Wabash Appliance Corp., 304 U.S. 364,
371 (1938). The statute allows functional claiming subject to certain restrictions. It provides as
follows:
An element in a claim for a combination may be expressed as a
means or step for performing a specified function without the
recital of structure, material, or acts in support thereof, and such
claim shall be construed to cover the corresponding structure,
material, or acts described in the specification and equivalents
thereof.
35 U.S.C. § 112 ¶ 6 (2006).
1. Section 112 paragraph 6 as applied to method claims
The Federal Circuit has held that for method claims, such as the claims of the ’124 patent,
section 112 paragraph 6 “is implicated only when steps plus function without acts are present.”
Epcon Gas Sys., Inc. v. Bauer Compressors, Inc., 279 F.3d 1022, 1028 (Fed. Cir. 2002). As the
Federal Circuit has explained, the word “means” in the statute refers to an apparatus element,
which is implemented by structure or material, while the word “step” refers to a process element,
which is implemented by an act. O.I. Corp. v. Tekmar Co., 115 F.3d 1576, 1582-83 (Fed. Cir.
1997). In other words, “structure and material go with means, acts go with steps.” Id. at 1583.
Overall, section 112 paragraph 6 is “implicated only when means plus function without definite
structure are present, and that is similarly true with respect to steps, that the paragraph is
implicated only when steps plus function without acts are present.” Id. “The statute thus in
effect provides that an element in a combination method or process claim may be recited as a

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step for performing a specified function without the recital of acts in support of the function.”
Id.
Based on those Federal Circuit decisions, the Court concludes that means-plus-function
analysis is not applicable to the method claims at issue in this case. The statutory provision
permits a description of a claim “element” by function instead of structure, material, or act. 35
U.S.C. § 112, ¶ 6; see also Cole v. Kimberly-Clark Corp., 102 F.3d 524, 531 (Fed. Cir. 1996)
(“[The Court] decide[s] on an element-by-element basis, based upon the patent and its
prosecution history, whether § 112, ¶ 6 applies.”); In re Fuetterer, 319 F.2d 259, 1460 n.11
(C.C.P.A. 1963) (“[Section 112, paragraph 6] in reality will give statutory sanction to
combination claiming as it was understood before the Halliburton decision. All the [individual]
elements of a combination now will be able to be claimed in terms of what they do as well as in
terms of what they are.”) (emphasis added) (quoting H.R. 3760, 82d Cong., 1st Sess., § 112
(1951) (statements of Representative Joseph R. Bryson, chairman of the subcommittee in charge
of the legislation that resulted in the Patent Act of 1952)).
For method claims, the “elements” are acts; for apparatus claims, the “elements” are
structures or materials. While a method element may describe the use of a structure or material,
the “use” is still an act. Here, the reference to a PDE V inhibitor is not an element of the claims
of the ’124 patent; the element in question is the step of administering an effective amount of a
PDE V inhibitor to a patient. Thus, even if means-plus-function analysis would apply to a
product claim to “an inhibitor of PDE V,” it does not apply to a method claim reciting a method
of administering that substance to a patient. See O.I. Corp., 115 F.3d at 1583 (“[E]ven if we
were to hold that the word ‘passage’ in the apparatus claims meets the section 112, ¶ 6, tests, we
would not agree with [defendant] that the parallelism of the claims means that the method claims

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should be subject to the requirements of section 112, ¶ 6”; instead, “[e]ach claim must be
independently reviewed in order to determine if it is subject to the requirements of section 112, ¶
6.”); Epcon, 279 F.3d at 1028 (same). 5
The inventive contribution of the patent is not the discovery or invention of PDE V
inhibitors, which were both numerous and well-known at the time of the invention. Instead, the
invention is based on the discovery that PDE V inhibitors can be effective in treating BPH. It is
thus not the point of the patent to disclose or claim particular PDE V inhibitors; the point is to
disclose and claim that PDE V inhibitors can be used to treat BPH. The patent is agnostic as to
what PDE V inhibitor is used. It simply recites that by using an appropriate amount of a PDE V
inhibitor, a therapeutic effect on BPH can be obtained.
In this respect, the reference in the ’124 patent to a PDE V inhibitor is analogous to a
reference, in a patent on a novel surgical procedure, to a cutting device that is used to begin the
procedure. In such a patent, it is irrelevant what particular cutting device is used; that is not the
point of the invention. In that setting, the reference to a cutting device would not implicate

5

Notwithstanding the decisions in O.I. Corp. and Epcon, the Federal Circuit
subsequently applied means-plus-function analysis to a method claim in On Demand Machine
Corp. v. Ingram Industries, Inc., 442 F.3d 1331 (Fed. Cir. 2006). In that case, the claim
limitation at issue recited “providing means for a customer to visually review said sales
information.” Id. at 1341. The Federal Circuit approved the district court’s instruction to the
jury that the “providing” limitation should be applied to the customer computer module disclosed
in the specification plus its equivalents.
Although the defendants argue that the On Demand case shows that in appropriate cases
means-plus-function analysis can be applied to method claims as well as apparatus claims, the
Court disagrees. The parties in that case did not dispute that means-plus-function analysis was
applicable, so the O.I. Corp. and Epcon decisions were never argued to the court. Moreover, the
claims in the On Demand case expressly used the “means for” construction; the claims in that
case could therefore be viewed as hybrid claims to which means-plus-function analysis might be
applicable. No such “means for” language is present in the method claims of the ’124 patent.

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section 112 paragraph 6, and would not require that the patent be interpreted to read only on the
particular cutting device or devices that may have been referred to in the specification.
Another similar example would be a patent that claimed a novel method for treating a
particular type of cardiac arrhythmia by administering a blood thinner. Although the claim could
be viewed as referring to the blood thinner by its function, the claim would not invoke section
112 paragraph 6, because the invention would be directed not to a new blood thinner, but to the
use of the blood thinner (of whatever type) to treat a disease in a novel way. For that reason, the
patentee would not be limited to any particular type of blood thinner that may have been referred
to in the specification.
The same is true in this case. The point of the patent is not the invention of compounds
that inhibit PDE V, but the invention of a treatment using compounds that have that effect. Thus,
the ’124 patent does not contain the flaw that led to the enactment of section 112 paragraph 6, by
“us[ing] conveniently functional language at the exact point of novelty.” Warner-Jenkinson, 520
U.S. at 27; Halliburton, 329 U.S. at 8; Gen. Elec., 304 U.S. at 371. For that reason, the use of the
term “an inhibitor of phosphodiesterase (PDE) V” does not convert the claims of the ’124 patent
into the sort of claims to which section 112 paragraph 6 was meant to apply.
2.
Section 112 paragraph 6 as applied to an “inhibitor of
phosphodiesterase (PDE) V”
Even if means-plus-function analysis can apply to method claims in some instances, the
Court concludes that the method claims at issue in this case are not in means-plus-function form.
The question whether section 112 paragraph 6 applies to a particular claim element turns
on whether the words of the claim element would be understood by persons of ordinary skill in
the art to have a sufficiently definite meaning as the name for a structure or an act. Williamson
v. Citrix Online, LLC, 792 F.3d 1339, 1349 (Fed. Cir. 2015) (en banc). The use of the word

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“means” in a claim element “creates a rebuttable presumption that § 112, para. 6 applies.” Id. at
1347. On the other hand, “[w]hen a claim term lacks the word ‘means,’ the presumption can be
overcome and § 112, para. 6 will apply if the challenger demonstrates that the claim term fails to
‘recite sufficiently definite structure’ or else recites ‘function without reciting sufficient structure
for performing that function.’” Id. at 1349. When section 112 paragraph 6 applies, it limits the
functional term “to only the structure, materials, or acts described in the specification as
corresponding to the claimed function and equivalents thereof.” Id. at 1347.
Because the claims of the ’124 patent do not contain the words “means for” (or “step
for”), there is a rebuttable presumption that section 112 paragraph 6 does not apply to the term
“an inhibitor of phosphodiesterase [PDE] V.”

For the reasons set forth below, the Court

concludes that the defendants have not overcome that presumption by presenting evidence
showing that a person of ordinary skill in the art as of the 1997 priority date of the ’124 patent
would have regarded “an inhibitor of phosphodiesterase [PDE] V” to be a purely functional
limitation.
The defendants’ position is that the term “an inhibitor of phosphodiesterase [PDE] V”
describes the compound by what it does—i.e., it inhibits PDE V by any means—rather than by
reference to a specific chemical structure. It is true that the term “inhibitor of phosphodiesterase
(PDE) V” is described in part by its function. However, the fact that a thing is defined in part by
its function does not necessarily compel the conclusion that a person of ordinary skill would not
have a sufficiently definite idea of what that thing is. To the contrary, “[f]unctional language
may [] be employed to limit the claims without using the means-plus-function format.”
Microprocessor Enhancement Corp. v. Tex. Instruments Inc., 520 F.3d 1367, 1375 (Fed. Cir.
2008); see also Lighting World, Inc. v. Birchwood Lighting, Inc., 382 F.3d 1354, 1360 (Fed. Cir.

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2004) (“[T]he fact that a particular mechanism . . . is defined in functional terms is not sufficient
to convert a claim element containing that term into a ‘means for performing a specified
function’ within the meaning of section 112(6).”). That is because it is not uncommon for
functional language to be used to describe particular structural objects, such as a brake, a drill, a
lock, a putter, or a post-hole digger. In such cases, the name of the object is not congruent with
the function suggested by the name: thus, for example, a driver is not a putter simply because a
golfer decides to use his driver to putt, and a trowel is not a post-hole digger just because a
gardener chooses to use the trowel to dig a post hole.
The “essential inquiry” in such cases is “whether the words of the claim are understood
by persons of ordinary skill in the art to have a sufficiently definite meaning as the name for
structure.” Williamson, 792 F.3d at 1348; see also Greenberg v. Ethicon Endo-Surgery, Inc., 91
F.3d 1580, 1583 (Fed. Cir. 1996) (“What is important is not simply that [the term in question] is
defined in terms of what it does, but that the term, as the name for structure, has a reasonably
well understood meaning in the art.”); Personalized Media Commc’ns, 161 F.3d at 704
(concluding that section 112 paragraph 6 did not apply to the term “detector” because, although
defined in terms of its function, it “had a well-known meaning to those of skill in the art
connotative of structure.”). Moreover, it is not necessary that a term “connote a precise physical
structure in order to avoid the ambit of [section 112 paragraph 6].” CCS Fitness, Inc. v.
Brunswick Corp., 288 F.3d 1359, 1370 (Fed. Cir. 2002).
Based on the evidence of record, the Court finds that the defendants have failed to rebut
the presumption that the term “inhibitor,” which is used in the ’124 patent without the word
“means,” does not invoke section 112 paragraph 6. In particular, the Court finds that the term

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“an inhibitor of [PDE] V” is not merely the description of a function, but would convey structure
to a person of skill in the art at the time of the invention.
The evidence before the Court shows that PDE V inhibitors have been “under
investigation since around 1985” and “were well-understood by the time of the invention.”
Corrected Decl. of Nicholas K. Terrett, Ph.D., Regarding Claim Constr. of U.S. Patent No.
8,791,124 (“Terrett Decl.”), at ¶ 21, Dkt. No. 105-1. By 1997, evidence of the general structure
of the PDE V enzyme, as well as that of its cGMP-specific catalytic site, were reported in the
literature. E.g., Michael Czarniecki et al., Inhibitors of Types I and V Phosphodiesterase:
Elevation of cGMP as a Therapeutic Strategy, 31 ANN. REPORTS

IN

MED. CHEM. 61, 61-62

(1996) (“Czarniecki”) (Phosphodiesterase “classes [including PDE V] share several common
structural features and the amino acid sequences in the putative hydrolytic sites are highly
conserved”; and the cDNA of PDE V, which “binds and selectively hydrolyzes cGMP,” encodes
“an 875 amino acid polypeptide with a homologous catalytic segment that is conserved across
PDE types.”), Dkt. No. 99-34; Kate Loughney & Ken Ferguson, 1. Identification and
Quantification of PDE Isoenzymes and Subtypes by Molecular Biological Methods, in
PHOSPHODIESTERASE INHIBITORS 1, 2 (Christian Schudt et al., eds., 1996) (PDEs, including PDE
V, “share in common an arrangement of structural domains,” including a “catalytic region [that]
is localized in the carboxy-terminal portion of the protein.”), Dkt. No. 99-35.
It is undisputed that, as understood in the art, “inhibitors” act by binding to the enzyme in
a way that “inhibits,” or suppresses, its catalytic activity. Nicholas Terrett, Ph.D., Dep., at 22:919 (May 26, 2016) (agreeing that “to inhibit an enzyme like PDE . . . a molecule binds to that
enzyme and decreases its [catalytic] activity”), Dkt. No. 106-9; Decl. of David P. Rotella, Ph.D.
in Support of Defs.’ Mot. for Partial Summ. J. Regarding the Written Description of U.S. Patent

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No. 8,791,124 (“Rotella Decl.”), at ¶ 8(e) (“[an inhibitor of PDE V] encompasses compounds
that may interact with the active site of the enzyme or some other site on the enzyme to inhibit
activity”), Dkt. No. 121-4; see also Terrett Dep. at 15:25-16:22 (to inhibit the PDE V enzyme
“means that the compound, the inhibitor, would [(a)] bind to the enzyme to make specific
interactions with the catalytic site of the enzyme, and, thereby, prevent the phosphodiesterase
from undertaking its normal catalytic activity,” or (b) “bind to another site on the protein surface,
a so-called allosteric site, … [to] block the [catalytic] activity of the enzyme.”); David P. Rotella
Dep. (“Rotella Dep.”), at 71:12-72:16 (Aug. 24, 2016) (acknowledging PDE V inhibitors bind to
the enzyme), Dkt. No. 130-1.
By the time of the invention, artisans had developed hundreds of PDE V inhibitors that
bound competitively to the enzyme’s catalytic site. Corrected Decl. of Dr. Andrew Bell in
Support of Corrected Pl. UroPep’s Combined Opp’n to Defs.’ Mots. for Summ. J. (“Bell Decl.”),
at ¶¶ 45-47, 49 (noting that a review article published in 1995 contains evidence of more than
100 PDE V inhibitors, a 1995 patent now owned by Lilly lists 119 PDE V inhibitors, and a 1996
patent includes 55 examples of PDE V inhibitors), Dkt. No. 137-2. Indeed, it is undisputed even
today that all known PDE V inhibitors bind competitively to the catalytic site of the enzyme.
Bell Decl., at ¶ 50 (stating that, to his knowledge, “all PDE5 inhibitors bind to the same catalytic
site on PDE5.”); Terrett Dep., at 17:7-9 (“[A]ll of the PDE V inhibitors known do bind to the
catalytic site.”); Rotella Dep., at 71:12-16 (admitting that “all of the approved PDE5 inhibitors
bind competitively with substrate [cGMP].”); see also Sharron R. Francis et al., Inhibition of
Cyclic Nucleotide Phosphodiesterases by Methylxanthines and Related Compounds, 200
HANDBOOK OF EXP. PHARMACOL. 93, 94 (2011) (“Francis”) ( “All known PDE inhibitors contain

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one or more rings that mimic the purine in the [cyclic nucleotide] substrate and directly compete
with [the cyclic nucleotide] for access to the catalytic site.”), Dkt. No. 99-37.
According to UroPep’s expert, Dr. Andrew Bell, a review of the large numbers of PDE V
inhibitors that were known in the art reveals “the overall structural similarity that [these]
inhibitors have.” Bell Decl., at ¶ 50. He concluded that all of the known PDE V inhibitors
“share common physical structural features which include a planar region and typically a
neighboring moiety capable of donating or accepting a hydrogen bond.” Id. This result is
unsurprising for two reasons. First, persons of skill in the art used known PDE inhibitors, such
as zaprinast, “as the conceptual starting point for the design of new compounds.” Terrett Decl.,
at ¶ 21 (quoting Czarniecki, at 62). For example, defendants’ expert, Dr. David P. Rotella, used
that approach in developing PDE V inhibitors.

David P. Rotella et al., N-3-Substituted

Imidazoquinazolinones: Potent and Selective PDE5 Inhibitors as Potential Agents for Treatment
of Erectile Dysfunction, 43 J. MED. CHEM., no. 7, 2000, at 1257 (“[u]sing the prototypical PDE5
inhibitor zaprinast . . . as a template” to screen other potential PDE5 inhibitors), Dkt. No. 121-9;
see also Rotella Dep., at 71:12-16 (noting use of a “template upon which inhibitors are based”).
Second, persons of skill in the art at the time explored inhibitors that would mimic the structure
of, and therefore compete with, cGMP to occupy the catalytic site of PDE V. E.g., Nicholas K.
Terrett et al., Sildenafil (Viagra™), a Potent and Selective Inhibitor of Type 5 cGMP
Phosphodiesterase with Utility for the Treatment of Male Erectile Dysfunction, 6 BIOORG. MED.
CHEM. LETT., no. 15, 1996 at 1819, 1820-21 (in synthesizing potential PDE V inhibitors, relying
on “[m]odelling studies [that] suggested that the nucleus may mimic the guanosine base of
cGMP, as both are of similar size, shape and have a similar dipole moment,” and considering
that “extending the 3-substituent might fill a space in the enzyme active site occupied by ribose,

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and substituents on the 5’-position of the phenyl ring could, depending on the conformation of
cGMP in the enzyme active site, reproduce the role of the phosphate in binding”), Dkt. No. 12112; see also Francis, at 94 (reporting that “[a]ll known PDE inhibitors contain one or more rings
that mimic the purine in the [cyclic nucleotide] substrate and directly compete with [the cyclic
nucleotide] for access to the catalytic site.”), Dkt. No. 99-37.
This is not to say that “an inhibitor of PDE V” describes a fixed structure, or even a small
subset of structures. Indeed, many authorities explain that PDE V inhibitors vary widely in
structure. Terrett Decl., at ¶ 23; see also, e.g., Czarniecki, at 62 (“Significant structural latitude
is possible while retaining potent inhibition of Type V PDE,” and “there appears to be a wide
tolerance for substitution [at certain positions of the inhibitor molecule]”), Dkt. No. 99-34. For
that reason, Dr. Terrett stated that “[n]o one could know the range of compounds that could be
included in that class.” Terrett Dep., at 15:9-17. And, in response to counsel’s question whether
a person of skill in the art would “understand or know of a common chemical structure or feature
for all inhibitors of PDE V,” Dr. Terrett said no, as “[t]he PDE V inhibitors . . . represent a fairly
diverse collection of different chemical structures.” Id. at 25:17-22.
Yet even though PDE V inhibitors constitute a “diverse collection of different chemical
structures,” the evidence shows that they fall within the class of compounds designed to compete
with cGMP to occupy the enzyme’s catalytic site. Bell Decl., at ¶ 50. That class is not a small
one, as Dr. Bell explained, because “the active site of the PDE5 enzyme accommodates such
diversity.” Id. at ¶ 51; see also id. at ¶¶ 51-55 (pointing out that the catalytic sites of some
enzymes, such as COX and NMT, accommodate structurally diverse inhibitors, while those of
other enzymes, such as CYP51, do not); Rotella Dep., at 78:1-14 (giving several examples of
other enzyme inhibitors that show structural diversity similar to that of PDE V inhibitors). But

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“[t]he fact that these [fundamental] physical structures can be accomplished through diverse
chemical structures and that PDE5 inhibitors permit a variety of substituents does not take away
from the overall structural similarity that inhibitors have, and must have, in order to bind to the
catalytic site of the PDE5 enzyme.” Bell Decl., at ¶ 50.
As such, “the words of the claim are understood by persons of ordinary skill in the art to
have a sufficiently definite meaning as the name for structure.” Williamson, 792 F.3d at 1349.
Artisans understood that “an inhibitor” is a compound with a structure that can bind to a key site
on the enzyme to inhibit its catalytic activity, and therefore developed inhibitors with structures
complementary to particular portions of the enzyme’s structure. In the case of PDE V, the
artisans targeted the catalytic site and designed inhibitors with structures complementary to that
site.
Put another way, the term “inhibitor of phosphodiesterase (PDE) V,” as used in the ’124
patent, is not simply a term that refers to any substance that will inhibit the chemical activity of
PDE V. It does not apply, for example, to a very strong acidic solution which, when added to a
solution containing PDE V, could be expected to destroy the PDE V molecules in a way that
would disable their ability to hydrolyze cGMP. See also Terrett Decl., at ¶ 30 (noting that one of
ordinary skill would not understand the patent to encompass techniques that “reduce the levels of
PDE V enzyme in the cell” or that “insert a mutation into the gene(s) encoding the PDE V
enzyme” to “disrupt its structure,” as that would be inconsistent with the understanding of the
term “inhibitor”). Instead, as both parties’ experts attest, “an inhibitor” refers to a category of
compounds with certain physical structures that bind to PDE V molecules in a way that prevents
them from hydrolyzing cGMP.

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In construing claims in light of section 112 paragraph 6, it is important to confine that
statutory provision to cases for which it was designed to apply, and not to apply it mechanically
whenever any seemingly functional term appears anywhere in a claim. That provision allows
drafters to describe a structure, material, or act by its function, with the understanding that the
structure, material, or act will be limited by what is disclosed in the specification. Drafters
should not, however, be confined by section 112 paragraph 6 when they use a term that is
understood by persons of skill in the art to have a meaning that denotes structure, even though
the term may also describe the function performed by the object in question. Instead, in such
cases the conventional tools of claim construction should be applied to discern the scope of the
term. See Hill-Rom Servs., Inc. v. Stryker Corp., 755 F.3d 1367, 1374-75 (Fed. Cir. 2014);
Greenberg, 91 F.3d at 1583.
For example, in Personalized Media Communications, LLC v. International Trade
Commission, which involved a patent claiming a receiver system that detects and manipulates
digital control signals in a broadcast or cablecast transmission, the Federal Circuit rejected the
Commission’s argument that “detector” should be read as a means-plus-function limitation. 161
F.3d 696, 704 (Fed. Cir. 1998). The term was “not a generic structural term such as ‘means,’
‘element,’ or ‘device,’” and it “had a well-known meaning to those of skill in the electrical arts
connotative of structure.” Id. The court acknowledged “the fact that a ‘detector’ is defined in
terms of its function” and “does not connote a precise physical structure in the minds of those of
skill in the art.” Id. at 705. But, “[e]ven though the term ‘detector’ does not specifically evoke a
particular structure, it does convey to one knowledgeable in the art a variety of structures known
as ‘detectors.’” Id. Therefore, the term “detector” was “a sufficiently definite structural term to
preclude the application of § 112, ¶ 6.” Id.

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Like the term “detector” in Personalized Media Communications, the term “inhibitor” in
this case presents a good example of an instance in which a seemingly functional term does not
play the role in the claim that section 112 paragraph 6 was directed to and therefore does not
trigger the application of that provision.

See also, e.g., CCS Fitness, 288 F.3d at 1369

(concluding that section 112 paragraph 6 did not apply to “reciprocating member” because a
person of ordinary skill in the art would understand the term to connote beam-like structures
encompassing more than the “single-component, straight bar structures (and their equivalents)
shown in the patents’ drawings.”).
The observations of the defendants’ expert, Dr. Rotella, are not inconsistent with this
conclusion. Dr. Rotella agreed that all known PDE V inhibitors bind to the enzyme’s cGMP
catalytic site. Rotella Dep., at 71:12-16; 6 see also Rotella Decl., at ¶¶ 101, 103 (describing the
method of determining how an inhibitor binds to PDE V by combining the inhibitor with a
fragment of the PDE V molecule that includes the cGMP catalytic site, rather than the whole
enzyme), Dkt. No. 121-3. He then explained that inhibitors may vary in structure and have
different binding interactions with PDE V. Rotella Decl., at ¶ 33; see also, e.g., Rotella Decl., at
¶ 102 (comparing how structural features of tadalafil and sildenafil bind to various pockets
within the catalytic site of PDE V). Dr. Rotella focused on minute differences in binding
interactions and made the general statement that “there is no structure that would be common to
all compounds able to inhibit PDE5.” Rotella Decl., at ¶ 19. But he never described any
particular PDE V inhibitor as lacking the fundamental structures identified by Dr. Bell that
6

Dr. Rotella mentioned “one paper” that he “believe[d]” was “published in 2005 that
illustrates that it is possible to inhibit PDE V by binding at a site distinct from the active site.”
Rotella Dep., at 71:18-22. But he could not remember the name of the lead author on the paper,
id. at 72:6-16, and the defendants have submitted nothing to supplement that statement. Dr. Bell
stated that he was not aware of any such paper or similar evidence. Bell Decl., at ¶ 50.

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account for “the overall structural similarity that [PDE V] inhibitors have, and must have, in
order to bind to the catalytic site of the PDE5 enzyme.” Bell Decl., at ¶ 50. More importantly,
Dr. Rotella’s review of how certain inhibitor molecules may differ—for example, by including
other components that bind to additional regions of the catalytic site—does not undermine the
experts’ agreement that all PDE V inhibitors bind to the enzyme and therefore have structures
that correspond to that of PDE V.
The evidence, of course, does not show—nor does UroPep attempt to argue—that simply
stating that a compound is a PDE V inhibitor would resolve all the questions that might have
come to the mind of a person of ordinary skill about its nature. Clearly there are issues as to
additional properties of the compound that a person of ordinary skill would consider, such as its
precise chemical composition, its toxicity, its selectivity, and its kinetics. Thus, a person of skill
in the art would need to have additional information in order to describe a particular PDE V
inhibitor in detail, just as a golfer would need additional information beyond the term “putter” to
describe a particular type of putter in detail. However, the Court finds that those additional
questions do not rise to a level such that a person of ordinary skill would lack a reasonably
definite understanding of the structure in question.
In sum, a person of ordinary skill in the art as of the priority date of the ’124 patent would
have had a reasonably certain understanding of the structural features necessary for a particular
compound to be an inhibitor of PDE V, as that term was used in the field. For that reason, the
Court finds that the defendants have not carried their burden to overcome the presumption that
35 U.S.C. § 112 ¶ 6 does not apply to the term “an inhibitor of phosphodiesterase (PDE) V.”

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B. Construction of the Term “an inhibitor of phosphodiesterase (PDE) V”
The parties agree that if section 112 paragraph 6 does not apply to the term “an inhibitor
of phosphodiesterase (PDE) V,” the term should be construed to mean “a compound able to
inhibit PDE V.” However, UroPep argues that the term should be given an even narrower
construction in three respects: first, the compound must be a “small molecule” compound;
second, it must be “therapeutically effective”; and third, it must be “relatively selective” as to
PDE V. The defendants disagree and argue that the term is not limited in any of those three
additional respects.
1. Small molecule compound
The Court agrees with the parties that “an inhibitor of phosphodiesterase (PDE) V” refers
to a compound, as is clear from the claim language.

The phrase “an inhibitor of

phosphodiesterase (PDE) V” is followed by the limitation that it “exclud[es] a compound
selected from the group” of eight listed compounds. That formulation, although unusual, is a
modified form of a claim to a Markush group, which is “a listing of specified alternatives of a
group in a patent claim, typically expressed as “a member selected from the group consisting of
A, B, and C.” Abbott Labs. v. Baxter Pharm. Prods., Inc., 334 F.3d 1274, 1280 (Fed. Cir. 2003).
Because the term “an inhibitor of phosphodiesterase (PDE) V” is defined, albeit in negative
form, by reference to a group of compounds, the claim language suggests that “an inhibitor of
phosphodiesterase (PDE) V” must be a compound, like the compounds that are excluded from its
coverage. Moreover, as the defendants have noted, “the specification of the ’124 Patent . . . uses
the terms ‘inhibitor,’ ‘compound’ and ‘substance’ interchangeably.”

Defs. Eli Lilly and

Company and Brookshire Brothers, Inc.’s Resp. Claim Constr. Br., at 8, Dkt. No. 106.

- 22 -

The dispute between the parties centers on whether the term “inhibitor” is limited to a
compound of a particular size. UroPep argues that “inhibitor,” as used in the ’124 patent, is
limited to a “small molecule compound.” UroPep adopts that position based on the testimony of
its expert, Dr. Terrett, who stated in his declaration that the “inhibitor of phosphodiesterase
(PDE) V” referred to in the ’124 patent must be a compound whose molecular weight does not
exceed about 600 Daltons. He stated:
Small molecule compounds are formed by the combination of
multiple atoms in a specifically defined structural arrangement.
Such compounds are referred to as small molecules if the total
molecular weight does not exceed around 600 Daltons. The
definition also distinguishes the compounds from larger molecules
such as peptides, proteins or polymers. An individual compound
has a unique chemical structure that confers the compound’s
pharmacological and physical properties, and no alteration of the
connections between atoms is permitted as such change would
redefine the identity of the compound.
Terrett Decl., at ¶ 22. While Dr. Terrett’s definition of “small molecule compounds” may be
consistent with the definition of a small molecule compound in the art, nothing in the record
suggests that the term “inhibitor,” as used in the ’124 patent, is limited to a compound having a
molecular weight under a particular limit, such as 600 Daltons. The Court therefore does not
adopt UroPep’s contention that the term “an inhibitor of phosphodiesterase (PDE) V” is limited
to “small molecule” compounds, as defined by Dr. Terrett.
2. Therapeutically effective
UroPep next argues that the term “an inhibitor of phosphodiesterase (PDE) V” requires
that the inhibitor be therapeutically effective.

The Court disagrees.

The “inhibitor of

phosphodiesterase (PDE) V” is simply a compound that inhibits PDE V. Of course, claim 1 of
the ’124 patent describes a “method of prophylaxis or treatment of [BPH] comprising
administering . . . an effective amount of an inhibitor of phosphodiesterase (PDE) V.” Therefore,

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the claim separately requires that the administration of the PDE V inhibitor be “effective” in the
“prophylaxis or treatment of [BPH].” For that reason, a particular inhibitor of PDE V may be
insufficiently potent to be effective in treating BPH, in which case a treatment using that
inhibitor would not satisfy the “effective amount” limitation of the claims. But nothing in the
record supports UroPep’s contention that the requirement of effectiveness in treating BPH is
inherent in the definition of the term “inhibitor of phosphodiesterase (PDE) V.”
3. Selective inhibitor
Finally, UroPep argues that the claimed inhibitor of PDE V must be a selective inhibitor,
i.e., a compound that inhibits PDE V to a significantly greater extent than other specific PDEs.
UroPep’s position is that “statements made during the prosecution of the ’124 patent family
confirm that the claims cover the use of selective inhibitors.” Pl. UroPep’s Corrected Opening
Claim Constr. Br., at 23 (citing portions of the prosecution history of the parent application and
stating that “patentees thus distinguished its invention over the prior art by emphasizing the
selective nature of the PDE V inhibitors”), Dkt. No. 105; see also Pl. UroPep’s Reply Claim
Constr. Br., at 2 n.2 (citing statements made during the prosecution of the parent application),
Dkt. No. 109.
The defendants respond to UroPep’s argument by pointing out that the patentees claimed
“a selective inhibitor” in the patent that issued from the parent application and therefore knew
how to claim that the inhibitors in the ’124 patent were “selective” if that is what was intended.
The failure to include the term “selective” in the claims of the ’124 patent, according to the
defendants, is a clear indication that the reference to “an inhibitor of phosphodiesterase (PDE)
V” in that patent was not intended to be limited to “selective” inhibitors of PDE V, as was the

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case for the earlier patent. Defs. Eli Lilly and Company and Brookshire Brothers, Inc.’s Resp.
Claim Constr. Br., at 15-16, Dkt. No. 106.
The Court finds that the term “inhibitor of phosphodiesterase (PDE) V” in the ’124 patent
refers to a selective inhibitor of PDE V. The specification of the ’124 patent makes clear that a
PDE V inhibitor is a member of the class of specific PDE inhibitors, or sPDEs. ’124 patent, col.
1, line 53, through col. 2, line 16; col. 7, line 35, through col. 8, line 27. The specification
further explains that a substance is considered an inhibitor of a specific PDE if the amount of that
substance needed to hydrolyze the specific PDE is much less than the amount needed to
hydrolyze other specific PDEs. Id., col. 8, ll. 5-9.
In addition, the prosecution history supports the conclusion that the term “inhibitor of
phosphodiesterase (PDE) V” refers to a selective PDE inhibitor. The application for the ’124
patent was a continuation of application number 10/443,870, which matured into the ’061 patent.
As noted, the ’061 patent claimed many of the compounds that were expressly excluded from the
claims of the ’124 patent. In the prosecution of that application, the applicants distinguished the
claimed compounds from the compounds disclosed in a prior art reference on the ground that the
prior art reference did not teach the use of a specific PDE V inhibitor for treating prostate
hypertrophy, see Oct. 27, 2009, Am. and Remarks, at 10, Dkt. No. 99-26. The applicants
asserted that “[t]he compounds of the currently pending claims are selective inhibitors,” unlike
the compounds disclosed in the prior art, see Mar. 7, 2010, Am. and Remarks, at 10, Dkt. No.
99-27.

Thus, in the course of the prosecution of the ’061 patent, the applicants clearly

disclaimed non-selective inhibitors (and amended the claims in accordance with that disclaimer).
The question is whether the disclaimer that the applicants made during the prosecution of the
’061 patent applies to the continuation application that led to the ’124 patent.

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In general, a prosecution disclaimer “will only apply to a subsequent patent if that patent
contains the same claim limitation as its predecessor.” Regents of Univ. of Minn. v. AGA Med.
Corp., 717 F.3d 929, 943 (Fed. Cir. 2013). Where the limitations are different, the question
whether the disclaimer is to be carried forward turns on whether there is a material difference
between the earlier and later claim limitations. Id. at 944. However, there is “an exception [to
that rule] where an amendment to a related limitation in the parent application distinguishes prior
art and thereby specifically disclaims a later (though differently worded) limitation in the
continuation application.” Invitrogen Corp. v. Clontech Labs., Inc., 429 F.3d 1052, 1078 (Fed.
Cir. 2005) (citing Elkay Mfg. Co. v. EBCO Mfg. Co., 192 F.3d 973, 978-79 (Fed. Cir. 1999)).
Here, the patentees amended their claims during the prosecution of the parent ’061 patent to
overcome a prior art rejection by arguing that its inhibitors of PDE IV and/or PDE V were
“selective.”

Therefore, it does not matter that UroPep did not affirmatively include that

limitation in the ’124 patent; the limitation was included through the earlier disclaimer and
amendment. Even if that were not true, it would be difficult to imagine one of ordinary skill
reading the specification of the ’124 patent and concluding that the reference to an inhibitor of
PDE V was not meant to be limited to a selective inhibitor. See, e.g., ’124 patent, col. 2, ll. 3-4
(“a well-aimed affection of the prostatic muscles by inhibiting a functionally important sPDE
isoenzyme”); col. 2, line 28 (“[p]referred selective inhibitors of PDE I, IV, and V”). 7

7

The defendants assert that Housey Pharms., Inc. v. Astrazeneca UK Ltd., 366 F.3d
1348 (Fed. Cir. 2004), stands for the proposition that the inhibitor claimed in the ’124 patent
cannot be selective because the claim language does not include the terms “selective” or
“relatively selective.” Housey does not stand for such a broad proposition. In determining the
correct construction of the term at issue in that case, the Housey court considered both the
prosecution history and the specification, and it concluded that they did not support the argument
that the claim term in question should be given a restrictive construction. Id. at 1354-55. Having
considered both the prosecution history and the specification in this case, the Court concludes
- 26 -

The parties also dispute how great the differential effect must be for a compound to be
considered a “selective” inhibitor. On this issue, the specification of the’124 patent provides
helpful guidance. The specification states that an inhibitor is a considered an inhibitor of a
specific PDE “if the concentration thereof which is necessary for inhibiting 50% of the substrate
hydrolysis (IC50) is at least 20 times lower in the respective peak fraction containing the specific
phosphodiesterase than in other peak fractions.” ’124 patent, col. 8, ll. 6-9. The parties do not
appear to dispute that this “20 times” standard represents the general understanding of a person
of ordinary skill in the art. The Court therefore finds that a selective inhibitor of a specific PDE
is at least 20 times more effective in inhibiting that specific PDE as compared to all other
specific PDEs.
In summary, the Court finds that “an inhibitor of phosphodiesterase (PDE) V” is “a
compound that selectively inhibits PDE V.”
C. The Motion for Summary Judgment of Non-Infringement Is Denied
As noted earlier, the defendants’ motion for summary judgment of non-infringement was
predicated on their assertion that the claims of the ’124 patent are governed by 35 U.S.C. § 112 ¶
6. In the course of construing the term “inhibitor of phosphodiesterase (PDE) V,” the Court has
found otherwise. The Court therefore DENIES the motion for summary judgment of noninfringement.
II. The Motion for Summary Judgment of Invalidity
The defendants argue that if the ’124 patent claims are not restricted to the specific
compounds disclosed in the specification, the specification fails to satisfy the “written
description” requirement of 35 U.S.C. § 112 ¶ 1, and the asserted claims are invalid.
that those sources of guidance as to the meaning of the claims indicate that the claim language
must be construed to refer to a selective inhibitor of PDE V.

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Section 112 paragraph 1 provides, in pertinent part:
The specification shall contain a written description of the
invention, and of the manner and process of making and using it, in
such full, clear, concise, and exact terms as to enable any person
skilled in the art to which it pertains, or with which it is most
nearly connected, to make and use the same . . . .
35 U.S.C. § 112 ¶ 1 (2006). That provision has remained largely unchanged since the Patent Act
of 1793. 8
The written description clause has been interpreted to require that the specification
“describe the invention sufficiently to convey to a person of skill in the art that the patentee had
possession of the claimed invention at the time of the application, i.e., that the patentee invented
what is claimed.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010)
(en banc). 9 The level of detail required to satisfy the written description requirement “varies
depending on the nature and scope of the claims and on the complexity and predictability of the
relevant technology.” Id. at 1351; see also Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir.
8

See Act of Feb. 21, 1793, 1 Stat. 318, 319 (the applicant “shall deliver a written
description of his invention, and of the manner of using, or process of compounding the same, in
such full, clear and exact terms, as to distinguish the same from all other things before known,
and to enable any person skilled in the art or science . . . which it is most nearly connected, to
make, compound and use the same”).
9

As the Federal Circuit explained in Ariad, 598 F.3d at 1351, the possession inquiry is
an objective one that is viewed from the perspective of a person of ordinary skill in the art:
The term “possession” . . . has never been very enlightening. It
implies that as long as one can produce records documenting a
written description of a claimed invention, one can show
possession. But the hallmark of written description is disclosure.
Thus, “possession as shown in the disclosure” is a more complete
formulation. Yet whatever the specific articulation, the test
requires an objective inquiry into the four corners of the
specification from the perspective of a person of ordinary skill in
the art. Based on that inquiry, the specification must describe an
invention understandable to that skilled artisan and show that the
inventor actually invented the invention claimed.

- 28 -

2005) (what is required “varies with the nature and scope of the invention at issue, and with the
scientific and technologic knowledge already in existence”). In the case of a claim to a genus,
the Federal Circuit has held that “a sufficient description of the genus . . . requires the disclosure
of either a representative number of species falling within the scope of the genus or structural
features common to the members of the genus so that one of skill in the art can ‘visualize or
recognize’ the members of the genus.” Ariad, 598 F.3d at 1350.
Whether the written description requirement is satisfied is a question of fact. Scriptpro,
LLC v. Innovation Assocs., Inc., 762 F.3d 1355, 1359 (Fed. Cir. 2014). The failure to satisfy the
requirements of 35 U.S.C. § 112 ¶ 1 must be proved by clear and convincing evidence. AbbVie
Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1297 (Fed. Cir. 2014).
The defendants argue that they are entitled to summary judgment on the written
description issue.

Summary judgment is appropriate when there are no genuine issues of

material fact and when, drawing all factual inferences in favor of the nonmoving party, no
“reasonable jury could return a verdict for the nonmoving party.” Anderson v. Liberty Lobby,
Inc., 477 U.S. 242, 248 (1986); accord Scriptpro, 762 F.3d at 1359. Even under the clear and
convincing evidence standard, the defendants contend, a reasonable jury would be compelled to
find that the specification of the ’124 patent provides an inadequate written description of the
invention set forth in the claims.
In particular, the defendants argue that UroPep’s proposed construction of the term
“inhibitor” encompasses a great number of compounds, including many that are not disclosed in
the patent or in the prior art, and many that have not even been discovered.

UroPep’s

“overreaching construction,” according to the defendants, “far exceeds the disclosure of the ’124
patent and if adopted, renders claims 1 and 3 of the ’124 patent invalid.” Eli Lilly & Co.’s and

- 29 -

Brookshire Brothers, Inc.’s Mot. for Partial Summ. J. that Claims 1 and 3 of U.S. Patent No.
8,791,124 Are Invalid for Failure to Meet the Written Description Requirement of 35 U.S.C.
§ 112 ¶ 1 and Mem. of Law in Support Thereof, at 10, Dkt. No. 120.
The Court concludes that there is at least a disputed issue of material fact as to whether
the ’124 patent specification satisfies the written description requirement. In the first place, the
claims of the ’124 patent are directed to the use of PDE V inhibitors to treat BPH, not to the
discovery of PDE V inhibitors themselves. As UroPep explains, the “inventors did not purport
to, and did not, contribute novel PDE V inhibitors” to the art. See Pl. UroPep’s Combined
Opp’n to Defs.’ Mots. for Summ. J., at 22, Dkt. No. 129. Given the nature of the claims, the
proper inquiry under the written description requirement is whether the disclosure in the
specification shows that the inventors possessed the invention that administering an effective
amount of a PDE5 inhibitor would treat BPH. Thus, given that at least some PDE V inhibitors
were known and were disclosed in the ’124 specification, the written description issue does not
turn on whether the patentees were in possession of the entire genus of PDE V inhibitors.
In re Herschler, 591 F.2d 692 (C.C.P.A. 1979), presented a similar issue. In that case, the
court found adequate written description support for broad claims for topically administering a
steroidal agent by administering the steroidal agent together with dimethyl sulfoxide. Even
though the specification disclosed only a single example of a steroidal agent, the court found that
the disclosure was sufficient because the claim was drawn to the method of administering the
steroidal agent, and numerous active steroidal agents were known to persons of skill in the art.
591 F.2d at 701. The court noted that “[w]ere this application drawn to novel ‘steroidal agents,’
a different question would be posed.” Id.; see also Rochester, 358 F.3d at 928 (discussing
Herschler).

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To the same effect is In re Fuetterer, 319 F.2d 259 (C.C.P.A.) (Rich, J.), in which the
application was directed to a combination of substances used to make rubber tire tread stock,
including “an inorganic salt that is capable of holding a mixture of . . . carbohydrate and protein
in colloidal suspension in water.” Id. at 261. The Patent Office Board of Appeals rejected the
representative claim on the ground that it was functional and because the specification included
only four examples of such salts. Id. at 262. The court reversed the Board. In his opinion,
Judge Rich explained that the “invention is the combination claimed and not the discovery that
certain inorganic salts have colloid suspending properties.” Id. at 265. He continued, in words
applicable here by analogy,
We see nothing in patent law which requires appellant to discover
which of all those salts have such properties and which will
function properly in his combination. If others in the future
discover what inorganic salts additional to those enumerated do
have such properties, it is clear appellant will have no control over
them per se, and equally clear his claims should not be so restricted
that they can be avoided merely by using some inorganic salt not
named by appellant in his disclosure.
Id.
UroPep’s evidence shows that PDE V inhibitors were not unknown as of the July 9,
1997, priority date of the ’124 patent. To the contrary, there were hundreds of known PDE V
inhibitors at that time.

Accordingly, the written description requirement is satisfied if the

specification shows that the inventors possessed the method of treating BPH by administering an
inhibitor of PDE V.
Relying on language from Rochester and AbbVie, the defendants assert that the written
description requirement applies “[r]egardless whether a compound is claimed per se or a method
is claimed that entails the use of the compound[].” See Rochester, 358 F.3d at 926. That
statement was made in a different context, however. The claims at issue in that case were

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directed to methods “for selectively inhibiting PGHS-2 activity in a human host.” 358 F.3d at
918. In that context, it made sense for the court to say that the written description requirement
was the same whether the claims were directed to inhibitors of PGHS-2 activity or to methods of
inhibiting PGSH-2 activity, as the essence of the invention was the same in both cases—the
identification of compounds that would inhibit PGHS-2 activity.
In this case, by contrast, the invention is not a method for inhibiting PDE V, which would
be analogous to the invention in the Rochester case. Instead, the invention is a method of
treating BPH by using inhibitors of PDE V. Because the invention is not the identification of
particular inhibitors, but the use of compounds having the inhibiting feature for a particular
therapeutic purpose, the particular risk presented in Rochester—that the inventor is seeking
claim coverage for a genus of compounds that perform a particular function, while only
disclosing a small and unrepresentative subset of such compounds—is not directly presented
here. 10
These distinctions of the Rochester and AbbVie cases might not have much force if the
specification of the ’124 patent had disclosed very little information about PDE V inhibitors, or
had provided no examples of such inhibitors. In that setting, it could be argued that, absent
knowledge of the substances to be used in the claimed treatment, the inventors were not shown
to be in possession of the invention.

10

The same distinction applies to the AbbVie case on which the defendants rely. 759
F.3d 1285. The claims in that case were drawn to isolated antibodies that would neutralize the
activity of human interleukin 12, and the patent purported to teach how to make such antibodies.
The examples given in the patent, however, were limited to certain species of the claimed
antibodies, even though the claims were not so limited, and the specification did not disclose
structural features common to the members of the claimed genus of antibodies. 759 F.3d at
1299. Under these circumstances, the Federal Circuit upheld the jury’s verdict that the written
description requirement was not satisfied.

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Indeed, the patent in Rochester did “not disclose any compounds that [could] be used in
its claimed methods”; the court explained that “[w]ithout such disclosure, the claimed methods
cannot be said to have been described.” 358 F.3d at 927. The court distinguished the case
before it from other cases in which the specification also failed to cite examples but was
nevertheless held sufficient because persons of skill in the art “could recognize what was being
claimed” based on the prevailing knowledge. Id. at 928 (discussing, e.g., Union Oil Co. v.
Atlantic Richfield Co., 208 F.3d 989 (Fed. Cir. 2000), where “evidence was adduced . . . that
artisans skilled in petroleum refining were aware of the properties of raw petroleum sources and
knew how to mix streams of such sources to achieve a final product with desired
characteristics.”). In Rochester, the lack of examples and anything beyond a “vague functional
description” meant that the patent was drawn to no more than “a mere wish or plan for obtaining
the claimed chemical invention.” Id. at 927.
In this case, however, the disclosures in the specification regarding PDE V inhibitors go
beyond merely providing a functional description, or only a single example, of a PDE V
inhibitor. As noted above, the ’124 specification contains a description of the biochemistry
underlying the invention. It discloses that the relaxation of smooth muscle cells in the prostate
can result in a distinct improvement in the symptoms of BPH. It discloses the physiological
mechanism by which information is transmitted that causes the relaxation of smooth muscle
cells, explaining that hormones or neurotransmitters cause an increase in cAMP and cGMP in the
smooth muscle cells, resulting in relaxation of those cells. It explains that because cAMP and
cGMP are hydrolyzed by phosphodiesterases, inhibitors of PDEs reduce the digestion of cAMP
and cGMP, “resulting in an increase in these molecules within the cell and thus in a relaxation of
the smooth muscle cell.” ’124 patent, col. 1, ll. 36-47.

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The specification teaches that three specific PDEs—PDE I, PDE IV, and PDE V—“are of
particular importance in human prostatic muscles.” Id., col. 2, ll. 6-8. The specification then
concludes that a “well-aimed inhibition of these isoenzymes will result in relaxation of the
prostatic muscles even when minute doses of a specific inhibitor are administered, with no
appreciable effects in other organ strips, particularly vessels, being observed. Therefore, they
have an excellent efficiency in the treatment of prostatic diseases.” Id., col. 2, ll. 11-16. The
specification lists 12 “preferred selective inhibitors” of PDE I, IV, and V: 10 compounds and two
general names of compounds. The journal articles cited in the specification (and the sources
cited in those journal articles) disclose other PDE V inhibitors. See C. David Nicholson & M.
Shadid, Inhibitors of Cyclic Nucleotide Phosphodiesterase Isoenzymes–Their Potential Utility in
the Therapy of Asthma, 7 PULM. PHARMACOL., no. 1, 1994, at 1-17; T. J. Torphy et al.,
Identification, Characterization and Functional Role of Phosphodiesterase Isoenzymes in Human
Airway Smooth Muscle, 265 J. PHARMACOL. EXP. THER., no. 3, 1993, at 1213-23; W. J.
Thompson, Cyclic Nucleotide Phosphodiesterases: Pharmacology, Biochemistry and Function,
51 PHARMACOL. THER., no. 1, 1991, at 13-33.
Beyond that, the specification describes in some detail pharmacological studies that were
used to determine the potency of specific PDE inhibitors. ’124 patent, col. 7, ll. 14-34. Those
studies involved the use of samples of human prostatic tissue in a solution of a specific PDE
inhibitor to measure the degree of muscle relaxation caused by particular test compounds. The
results of those studies showed that “the inhibitors of PDE I, IV and V proved to have the
strongest prostatic tissue relaxing effect.” Id., col. 7, ll. 32-34.
The specification also states that “the proof of whether a compound is suitable for the
purpose according to the invention” is furnished by known methods, citing references from 1989

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and 1990.

’124 patent, col. 7, ll. 35-39.

The specification then describes an assay for

determining if a substance is an inhibitor of a specific PDE and determining the potency of that
inhibitor. Id., col. 7, line 35, through col. 8, line 16. UroPep points to record evidence that the
information provided by that assay would be sufficient to show that the particular inhibitor under
examination would have the necessary potency to be therapeutically effective against BPH. Bell
Dep., at 111:2-6, 114:15-20 (Aug. 11, 2016), Dkt. No. 140-1.

The information provided

regarding PDE inhibitors in general, and PDE V inhibitors in particular, is considerably more
detailed than the information disclosed regarding the genus of PGSH-2 inhibitors in Rochester
and antibodies that could neutralize interleukin 12 in AbbVie.
To be sure, there is much that the ’124 specification does not describe. For example, it
does not separately discuss the characteristics of the three identified specific phosphodiesterases,
PDE I, PDE IV, and PDE V. Other than the general statement that specific PDEs are distributed
differently throughout the body, the specification provides no explanation of how or why one of
those three PDEs should be targeted differently within prostate tissue. That is to say, despite the
fact that the claims of the ’124 patent are directed only to PDE V, the specification provides no
suggestion as to why a person of ordinary skill would single out PDE V rather than the other two
PDE inhibitors of interest, PDE I and PDE IV. See Defs. Eli Lilly & Co. and Brookshire
Brothers, Inc.’s Consolidated Reply Br. in Support of their Mots. for Summ. J. of
Noninfringement and for Invalidity for Failure to Meet the Written Description Requirement of
35 U.S.C. § 112, ¶6, at 15, Dkt. No. 139. The specification also provides no substantive results
for the tests it discusses or the results of any testing demonstrating actual prophylaxis or
treatment of BPH in animals or humans.

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In response to the defendants’ criticisms of the disclosure in the ’124 specification,
UroPep points out that in assessing the adequacy of a specification’s disclosure for written
description purposes, the Court must view the disclosure as would one of skill in the art. See
Ariad, 598 F.3d at 1351 (Possession means possession as shown in the disclosure and “requires
an objective inquiry into the four corners of the specification from the perspective of a person of
ordinary skill in the art.”); In re Alonso, 545 F.3d 1015, 1019 (Fed. Cir. 2008); Intel Corp. v.
VIA Techs., Inc., 319 F.3d 1357, 1365-66 (Fed. Cir. 2003). Because “the patent specification is
written for a person of skill in the art, and such a person comes to the patent with the knowledge
of what has come before . . . it is unnecessary to spell out every detail of the invention in the
specification; only enough must be included to convince a person of skill in the art that the
inventor possessed the invention . . . .” LizardTech, Inc. v. Earth Res. Mapping, Inc., 424 F.3d
1336, 1345 (Fed. Cir. 2005).
UroPep points to evidence in the record that persons of skill in the art would have been
aware of hundreds of PDE V inhibitors in addition to the exemplary compounds set forth in the
’124 specification, see the evidence cited at pages 15-16, supra. UroPep also points to evidence
that persons of skill in the art would have been aware of the structure of tadalafil, the compound
used in the defendants’ accused method, and the fact that tadalafil is a PDE V inhibitor, see
Rotella Decl., at ¶ 64; Bell Decl., at ¶ 46; Rotella Dep., at 48:18-22.
It was not necessary for the patentees to include in the specification a catalog of all thenknown PDE V inhibitors, UroPep argues, because persons of skill in the art were aware of the
studies listing large number of such inhibitors. In light of the knowledge of persons in the field
at the time, according to UroPep, the particular PDE V inhibitors that were described in detail in
the specification constitute “a representative number of species falling within the scope of the

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genus,” AbbVie, 759 F.3d at 1299, even if the genus is viewed as all compounds capable of
inhibiting the catalytic action of PDE V.
Whether the omissions from the specification, viewed in light of the facts known to
persons of skill in the art as of the priority date of the ’124 patent, render the specification
insufficient to provide the necessary written description of the inventions of the ’124 patent is a
factual issue. The Court is persuaded that what is disclosed in the specification, when viewed in
light of what a person of ordinary skill in the art would have known at the time, is sufficient to at
least raise a question of fact sufficient to take the written description issue to a jury. The Court
therefore DENIES the defendants’ motion for partial summary judgment of invalidity based on
35 U.S.C. § 112 ¶ 1.
IT IS SO ORDERED.
SIGNED this 21st day of October, 2016.

_____________________________
WILLIAM C. BRYSON
UNITED STATES CIRCUIT JUDGE

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