Court Opinion

ID: 4409534
Source: CourtListenerOpinion
Date Created: 2019-06-24 16:00:40.095993+00
Date Added: 2024-06-11T07:49:56.873153
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
                ______________________

  UCB, INC., UCB MANUFACTURING IRELAND
 LIMITED, UCB PHARMA GMBH, LTS LOHMANN
           THERAPIE-SYSTEME AG,
             Plaintiffs-Cross-Appellants

                           v.

     WATSON LABORATORIES INC., ACTAVIS
          LABORATORIES UT, INC.,
              Defendants-Appellants
             ______________________

                 2018-1397, 2018-1453
                ______________________

    Appeals from the United States District Court for the
District of Delaware in No. 1:14-cv-01083-LPS-SRF, Chief
Judge Leonard P. Stark.
                 ______________________

                Decided: June 24, 2019
                ______________________

    JACK B. BLUMENFELD, Morris, Nichols, Arsht & Tun-
nell LLP, Wilmington, DE, argued for plaintiffs-cross-ap-
pellants. Also represented by DEREK J. FAHNESTOCK,
MARYELLEN NOREIKA; JAMES TRAINOR, ROBERT COUNIHAN,
ADAM GAHTAN, KEVIN MCGANN, SILVIA MEDINA, Fenwick &
West LLP, New York, NY.

   JOHN C. O'QUINN, Kirkland & Ellis LLP, Washington,
DC, argued for defendants-appellants. Also represented by
2                      UCB, INC. v. WATSON LABORATORIES INC.

WILLIAM H. BURGESS, CALVIN ALEXANDER SHANK; LEORA
BEN-AMI, THOMAS F. FLEMING, CHRISTOPHER T. JAGOE,
New York, NY.
              ______________________

    Before TARANTO, SCHALL, and CHEN, Circuit Judges.
CHEN, Circuit Judge.
    This appeal concerns UCB, Inc., UCB Manufacturing
Ireland Limited, UCB Pharma GmbH, and LTS Lohman
Therapie-Systeme AG (UCB)’s U.S. Patent Nos. 6,884,434 1
and 8,232,414. 2 The ’434 patent claims a transdermal ther-
apeutic system comprising rotigotine, a drug used for the
treatment of Parkinson’s disease. The ’414 patent claims a
polymorph of rotigotine. The United States District Court
for the District of Delaware found that Watson Laborato-
ries Inc. and Actavis Laboratories UT, Inc. (Actavis)’s ge-
neric products infringed the ’434 patent under the doctrine
of equivalents. The district court also upheld the validity
of the ’434 patent over Actavis’s obviousness and anticipa-
tion challenges. Actavis appeals the district court’s in-
fringement and validity judgments. UCB cross-appeals the
district court’s invalidation of the ’414 patent under 35
U.S.C. § 102(a) as known and used by others in the United
States before the date of invention. For the reasons artic-
ulated below, we affirm.

    1   UCB Manufacturing Ireland Limited and LTS
Lohman Therapie-Systeme AG are assignees of the ’434 pa-
tent. UCB, Inc. is a party to this case because it holds the
approved New Drug Application for brand name drug
Neupro, under which the ’434 patent is listed in the FDA
publication, “Approved Drug Products with Therapeutic
Equivalence Evaluations” (the Orange Book).
    2   UCB Pharma GmbH is an assignee of the ’414 pa-
tent.
UCB, INC. v. WATSON LABORATORIES INC.                     3

                 TECHNICAL BACKGROUND
    The technology at issue relates to a transdermal (via
the skin) form of delivering a drug that treats Parkinson’s
disease. Parkinson’s is a degenerative neurological condi-
tion linked to reduced dopamine levels in the brain, caused
by degeneration and death of “dopaminergic” neurons. The
’434 and ’414 patents relate to the compound rotigotine, a
dopamine receptor stimulator, that has been used to treat
Parkinson’s since the 1990s. Rotigotine comes in two
forms: free base form and hydrochloride salt form.
     Cygnus Therapeutic Systems conducted early attempts
at transdermal rotigotine formulation circa 1994. J.A.
118–19. Its system is described in patent application WO
94/07468 (Cygnus) and a 1995 article entitled “A Two-
Phase Matrix for the Delivery of N-0923, a Dopamine Ago-
nist” by Chiang et al. (Chiang). Rotigotine in the Cygnus
system is present in the hydrochloride salt form, which is
dissolved in water to create an aqueous phase in the patch’s
matrix. Preliminary clinical trials using patches manufac-
tured by Cygnus demonstrated proof of concept that a suf-
ficient amount of rotigotine can be transdermally delivered
for treatment of Parkinson’s. No commercial product re-
sulted from Cygnus’s work.
    UCB developed a rotigotine transdermal patch without
using water and filed the ’434 patent to cover such a patch.
The patent is entitled “Transdermal therapeutic system
which contains a d2 agonist and which is provided for treat-
ing Parkinsonism, and a method for the production
thereof.” The only asserted independent claim reads:
   1. A transdermal therapeutic system comprising a
   self-adhesive matrix layer containing the free base
4                      UCB, INC. v. WATSON LABORATORIES INC.

    [rotigotine 3] in an amount effective for the treat-
    ment of the symptoms of Parkinson’s syndrome,
    wherein the matrix is based on [] an acrylate-based
    or silicone-based polymer adhesive system having
    a solubility of ≧5% (w/w) for the free base [rotigo-
    tine], all of said free base being present in the ma-
    trix in the absence of water; a backing layer inert to
    the components of the matrix layer; and a protec-
    tive foil or sheet covering the matrix layer to be re-
    moved prior to use.
’434 patent, col. 7 ll. 55–67 (emphasis added). The claim
covers administration of rotigotine through a transdermal
patch made of three layers, the most relevant for this ap-
peal being an adhesive layer in which an effective amount
of the free base form of rotigotine is dissolved in an acry-
late- or silicone-based polymer adhesive so that there is no
water and at least 5% rotigotine by weight in the layer. De-
pendent claims cover use of polyvinylpyrrolidone (PVP), a
solubility enhancer, as part of the adhesive system to
achieve the claimed solubility.
    The FDA approved UCB’s rotigotine transdermal
patches in May 2007, and UCB has been selling the product
under the brand name Neupro since July 2007. Neupro’s
polymer adhesive system is silicone-based and contains
PVP.
    Relevant to the other UCB patent in this appeal—the
’414 patent—in June and July 2007, batches of rotigotine
patches were manufactured for distribution in the United

    3     The claim covers the “S” enantiomer of rotigotine,
with the chemical name “(–)-5,6,7,8-tetrahydro-6-[propyl-
[2-(2-thienyl)ethyl]amino]-1-naphthalenol.” ’434 patent,
col 7 ll. 62–63. Enantiomers are two non-superimposable,
mirror-image, three-dimensional structural configurations
of the same molecule.
UCB, INC. v. WATSON LABORATORIES INC.                      5

States. Of particular relevance to the alleged public use of
the ’414 patented product before its date of invention, lam-
inate lot 47808 was produced during this period.
    Until August 2007, UCB manufactured Neupro
patches by dissolving rotigotine in ethanol, among other
steps, to create a rotigotine solution. It then prepared a
coating mass from this solution and other components (in-
cluding a silicone-based polymer), which, after drying, pro-
duced a matrix. The matrix did not contain crystalline
rotigotine, and the rotigotine in the resulting patches, pre-
distribution, was non-crystalline.
    On August 7, 2007, an unknown solid precipitated dur-
ing the dissolution step, causing UCB to halt manufacture
of Neupro patches. Over the next few months, UCB inves-
tigated and determined that the solid was a polymorph of
rotigotine, characterized by unique single-crystal X-ray dif-
fraction parameters. Polymorphs are different three-di-
mensional, solid-state, crystalline structures of the same
chemical compound.
    UCB filed a patent application to cover the newly dis-
covered Form II polymorph of rotigotine. This resulted in
the ’414 patent, entitled “Polymorphic form of rotigotine
and process for production,” with a priority date of Novem-
ber 28, 2007. The claims read:
    1. A polymorphic form of rotigotine characterized
    by at least one parameter selected from the group
    consisting of:
        (a) a powder X-ray diffraction spectrum
        comprising at least one peak at the follow-
        ing °2θ angles (± 0.2): 12.04, 13.68, 17.72,
        and 19.01;
        (b) a Raman spectrum comprising at least
        one peak at the following (±3 cm-1): 226.2,
        297.0, 363.9, 737.3, 847.3, 1018.7, and
        1354.3 cm-1
6                       UCB, INC. v. WATSON LABORATORIES INC.

        (c) a DSC peak with a Tonset at 97°C. ± 2°C.
        measured with a heating rate of 10°/min;
        and
        (d) a melting point of 97°C. ± 2°C.
    2. The polymorphic form of rotigotine of claim 1,
    wherein the polymorphic form of rotigotine is char-
    acterized by at least the following powder X-ray dif-
    fraction peaks at °2θ angles (± 0.2): 12.04, 13.68,
    17.72 and/or 19.01.
    3. A polymorphic form of rotigotine having a pow-
    der X-ray diffraction spectrum substantially as
    shown in FIG. 1.
’414 patent, col. 8 ll. 48–64.
    On November 12, 2007, UCB submitted a Field Alert
Report to the FDA, alerting the FDA that “small crystalline
structure (snowflakes)” had been observed on the active
surface of Neupro patches that had already been manufac-
tured and distributed. J.A. 4833–34. UCB informed the
FDA that “testing confirmed on November 7, 2007 that the
snowflakes contain crystalline structures of a polymorph
variant (Form 2) of the active ingredient Rotigotine.” J.A.
4833. According to its report, many of the examined
patches contained snowflakes; of 29 batches of product,
only one did not have any patches containing visible snow-
flakes. J.A. 4838. For batches manufactured for distribu-
tion in the United States, over 90% of the examined
patches contained crystals by November 12, 2007. J.A.
6144.
     On November 30, 2007, two days after the priority date
of the ’414 patent, a female patient experienced an adverse
event while being treated with Neupro. J.A. 5965. An
Alert Report submitted by UCB states that the patient re-
ceived samples of Neupro in September 2007 and “re-
sponded well” to treatment. Id. In November 2007, she
purchased Neupro patches that were from lot 47808. Id.
UCB, INC. v. WATSON LABORATORIES INC.                      7

While using these patches, the patient began “clearly back-
sliding, experiencing previous symptoms of losing mobility,
shaking and freezing.” J.A. 5966. The Report indicated
that the patient used the lot 47808 patches for “one week,”
implying that she was using the patches before the ’414 pa-
tent’s priority date of November 28, 2007. After experienc-
ing this back-sliding, the patient “was reverted to the
samples of the newer lot number” and “an improvement in
the patient was noted.” Id.
                   PROCEDURAL HISTORY
    Actavis filed an Abbreviated New Drug Application
(ANDA) for generic versions of transdermal rotigotine
patches, and UCB filed suit for infringement of the ’434 and
’414 patents under 35 U.S.C. § 271(e)(2). The case pro-
ceeded to a four-day bench trial on the validity and in-
fringement of claims 1, 5, 7, and 14–15 of the ’434 patent,
and the validity of claims 1–3 of the ’414 patent. 4
    The district court found infringement of all the as-
serted ’434 patent claims by Actavis’s ANDA products (the
Accused Products) under the doctrine of equivalents. Ac-
tavis’s products use a polyisobutylene adhesive, rather
than the claimed acrylate-based or silicone-based polymer
adhesives, but the district court found the adhesives in this
context to be substantially similar and that nothing in this
case barred application of the doctrine of equivalents. J.A.
138–54.
    The district court then upheld the validity of claims 1,
5, 7, 14, and 15 of the ’434 patent, rejecting, in relevant
part, Actavis’s arguments of anticipation under 35 U.S.C.
§ 102 by the Cygnus prior art reference and obviousness

    4   Actavis stipulated to infringement of the ’414 pa-
tent claims.
8                      UCB, INC. v. WATSON LABORATORIES INC.

under 35 U.S.C. § 103 over Cygnus with Lipp 5 or Pfister, 6
and over Timmerman7 with Miranda. 8 J.A. 154–62.
    The district court also found the ’414 patent claims in-
valid under § 102(a) because the Form II polymorph of ro-
tigotine was used by others in the United States before the
invention date—Neupro patches with Form II crystals
were administered to at least one patient before November
28, 2007. J.A. 180–84.
    Actavis appeals the district court’s infringement and
above-listed validity findings on the ’434 patent. UCB
cross-appeals the district court’s invalidation of the ’414
patent. We have jurisdiction pursuant to 28 U.S.C.
§ 1295(a)(1).
                        DISCUSSION
              A. Infringement of the ’434 Patent
    The only infringement issue relevant to this appeal is
whether the Accused Products have a “matrix . . . based on
[]an acrylate-based or silicone-based polymer adhesive sys-
tem.” ’434 patent, col. 7 ll. 59–61. Actavis does not dispute

    5    Canadian Patent No. 2,120,599, entitled “Trans-
dermal Therapeutic Systems Containing Crystallization
Inhibitors,” listing Ralph Lipp et al. as inventors.
     6   European Patent Application EP 0524776, entitled
“Silicone pressure sensitive adhesive compositions for
transdermal drug delivery devices and related medical de-
vices,” listing Willliam Richard Pfister et al. as inventors.
     7   A journal article published by Timmerman et al.,
entitled “Microdialysis and striatal dopamine release: ste-
reoselective actions of the enantiomers of N-0437.”
     8   International Patent Application WO 95/18603, en-
titled “Transdermal Device Containing Polyvinylpyrroli-
done as Solubility Enhancer,” listing Jesus Miranda as an
inventor.
UCB, INC. v. WATSON LABORATORIES INC.                       9

that its Accused Products literally meet every other ele-
ment of the asserted claims. The Accused Products use a
polyisobutylene adhesive, which is different from the
claimed acrylate-based or silicone-based polymer adhe-
sives. But UCB argued that, under the doctrine of equiva-
lents,     polyisobutylene-based      adhesives       are
interchangeable with the claimed adhesives.
              1. Limits to the Application of the
                    Doctrine of Equivalents
    First, we agree with the district court that UCB was
not “barred” from asserting the doctrine of equivalents here
because of prosecution history estoppel, intentional narrow
claiming, vitiation, or ensnarement.
               a. Prosecution History Estoppel
     Prosecution history estoppel can limit application of
the doctrine of equivalents because “[i]f a patentee surren-
ders certain subject matter during prosecution, the pa-
tentee is then barred from using the doctrine of equivalents
to recover for infringement based on that same subject
matter.” Power Integrations, Inc. v. Fairchild Semiconduc-
tor Int’l, Inc., 904 F.3d 965, 975 (Fed. Cir. 2018), cert. de-
nied, 139 S. Ct. 1265 (2019).
    The original patent application for the ’434 patent had
17 claims, which were cancelled in a preliminary amend-
ment prior to any Patent Office action. J.A. 5010. New
claims 18–33 all included an “acrylate-based or silicone-
based polymer adhesive system having a solubility of ≥ 5%
(w/w) for [rotigotine free base].” J.A. 5010–15. That claim
language was never amended during prosecution. New
claims 34–41 were generally directed to processes for pre-
paring a transdermal therapeutic system that included “an
adhesive,” without specifying any particular adhesive. J.A.
5013–15.
    The examiner then issued a restriction requirement,
asking the applicant to elect to prosecute claims from
10                    UCB, INC. v. WATSON LABORATORIES INC.

Group I (claims 18–33) or Group II (claims 34–41). J.A.
5160–62. The applicant elected Group I, but did so “with
traverse,” meaning that it disputed that any election was
necessary. J.A. 5163–65. In response, the examiner ex-
plained the reason for restriction: Group II claims required
use of PVP as a solubility enhancer, but PVP would only be
required for a silicone-based polymer, not acrylate-based
polymer, because rotigotine is soluble enough in the latter
to not need an enhancer. J.A. 5160, 5206. So, “the process
of group II [was] only applicable on silicone-based polymer
and not on acrylate-based polymer,” while “group I read[]
on a matrix based on acrylate polymer or silicone polymer.”
J.A. 5206. Further, the examiner pointed out that “the
product of group I requires the product to be substantially
free from inorganic silicate, while the process of group II
requires the inorganic silicate.” Id. The examiner thus
concluded that “the two groups do not have the same tech-
nical features,” finalized the restriction requirement, and
withdrew the Group II claims from further consideration.
J.A. 5206–07.
    Actavis argued that UCB’s election of the Group I
claims after the examiner issued a restriction requirement
should prevent UCB from now asserting infringement un-
der the doctrine of equivalents. The Group II claims were
not limited to silicone- and acrylate-based polymer adhe-
sive systems. In Actavis’s view, because UCB withdrew
those claims, it gave up claim scope of adhesives that are
not silicates or acrylates and should not be allowed to re-
capture that subject matter through the doctrine of equiv-
alents.
    The district court disagreed with Actavis’s reading of
the prosecution history, and we do as well. J.A. 142–44. A
restriction requirement does not necessarily invoke prose-
cution history estoppel. See Bayer Aktiengesellschaft v. Du-
phar Int’l Research B.V., 738 F.2d 1237, 1243 (Fed. Cir.
1984). Whether a patentee’s actions in the face of a re-
striction requirement give rise to estoppel must be judged
UCB, INC. v. WATSON LABORATORIES INC.                     11

“from the viewpoint of a [skilled artisan], and when the is-
sue includes consideration of formalities of patent practice,
experience in patent law and procedures is presumed.”
Merck & Co. v. Mylan Pharm., Inc., 190 F.3d 1335, 1340
(Fed. Cir. 1999). In Merck, this court determined that the
patentee’s decision to limit the claims to a certain subset—
in response to the examiner’s restriction requirement and
obviousness rejection—“were primarily in consideration of
the patentability rejection under § 103.” Id. at 1340–41.
Thus, this court concluded that Merck’s actions gave rise
to prosecution history estoppel.
     Here, the examiner’s restriction requirement did not
relate to polyisobutylene, and the examiner was not com-
municating anything about the patentability of polyisobu-
tylene-based adhesive systems. UCB never added a
polyisobutylene-excluding limitation by amendment, and
its election cannot be read as such. Moreover, even if UCB
had claimed “an adhesive” in the elected claims, as Actavis
argues it should have done in order to keep polyisobutylene
within the claim scope, the technical differences that trig-
gered the restriction requirement would still have re-
mained and still would have required the same restriction:
the Group II claims required inorganic silicate and applied
only to a subset of adhesives that needed PVP, while Group
I did not have those limitations. Thus, the restriction re-
quirement here, and UCB’s election in response, do not in-
dicate a surrender of polyisobutylene as an equivalent. 9

    9   Actavis also cites to Pacific Coast Marine Wind-
shields Ltd. v. Malibu Boats, LLC, where this court found
that in the prosecution of a design patent on a marine
windshield, “[b]y cancelling figures showing corner posts
with two holes and no holes, the applicant surrendered
such designs and conceded that the claim was limited to
what the remaining figure showed—a windshield with four
12                     UCB, INC. v. WATSON LABORATORIES INC.

    Because we conclude that UCB did not make a narrow-
ing amendment in respect to the restriction requirement,
we reject Actavis’s argument that UCB had the burden to
show that a “narrowing amendment” was unrelated to pa-
tentability.
    Accordingly, we find no good basis in the prosecution
history here to bar the application of the doctrine of equiv-
alents to polyisobutylene-based polymer adhesive systems.
                     b. Narrow Claiming
    Relatedly, Actavis argued to the district court that
UCB had chosen to draft narrow claims and should not be
permitted to expand the scope of those claims through the
doctrine of equivalents. Specifically, Actavis argued that
Dr. Mueller, an inventor of the ’434 patent, knew that pol-
yisobutylene was a polymer that could be used in transder-
mal patches but chose not to prosecute a claim broad
enough to cover polyisobutylene. J.A. 4219. On appeal,
Actavis makes the broader argument that polyisobutylenes
were generally known in the art, citing Dr. Mueller’s
knowledge as an example. The Cygnus prior art reference

holes in the corner post—and colorable imitations thereof.”
739 F.3d 694, 703 (Fed. Cir. 2014); Oral Arg. at 6:35–8:35.
But due to the nature of design patents, the differences be-
tween the figures in that case made the claim scope of each
figure, as to the relevant hole limitation, mutually exclu-
sive. In contrast, as we explain, the inclusion of polyisobu-
tylene under the adhesive claim limitations in the two
groups of claims here is not so clearly mutually exclusive.
In any event, we have never held that a restriction and
election during prosecution of a utility patent application,
without more, can constitute prosecution history estoppel
for claim scope covered by the restricted and then cancelled
claims, and we decline to do so here, given that there were
other reasons for the restriction.
UCB, INC. v. WATSON LABORATORIES INC.                       13

also mentions polyisobutylene as a possible adhesive for
transdermal patches. J.A. 5705, 5708–09.
    The district court disagreed with Actavis, citing this
court’s holding in Ring & Pinion Service Inc. v. ARB Corp.
that “[t]here is not, nor has there ever been, a foreseeability
limitation on the application of the doctrine of equivalents”
as to claim limitations that have never been amended or
relied on during prosecution, because “[e]xcluding equiva-
lents that were foreseeable at the time of patenting would
directly conflict with [prior Supreme Court and Federal
Circuit case] holdings that ‘known interchangeability’ sup-
ports infringement under the doctrine of equivalents.” J.A.
145; 743 F.3d 831, 834 (Fed. Cir. 2014) (citing Warner-Jen-
kinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17, 36
(1997); Graver Tank & Mfg. Co. v. Linde Air Products Co.,
339 U.S. 605, 609 (1950); Abraxis Bioscience, Inc. v. Mayne
Pharma (USA) Inc., 467 F.3d 1370, 1382 (Fed. Cir. 2006);
Interactive Picture Corp. v. Infinite Pictures, Inc., 274 F.3d
1371, 1383 (Fed. Cir. 2001); and Corning Glass Works v.
Sumitomo Elec. U.S.A., Inc., 868 F.2d 1251, 1261 (Fed. Cir.
1989)).
    We understand Ring & Pinion to hold that foreseeabil-
ity at the time of claim drafting is not a per se bar to the
application of the doctrine of equivalents. But, at the same
time, Ring & Pinion does not foreclose consideration of
foreseeability of an asserted equivalent as one factor that
may, in some cases, help show that the facts cannot support
infringement under the doctrine of equivalents.
    Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC is an
example of such a case. 683 F.3d 1356, 1366 (Fed. Cir.
2012). There, Cadbury asserted infringement of U.S. Pa-
tent No. 5,009,893, which claimed a chewing gum that com-
bined menthol with a coolant claimed as an “N-substituted-
p-menthane-carboxamide of [a specific formula].” Id. at
1358. One such carboxamide was called “WS-3.” Id. The
accused infringing product used a coolant called “WS-23,”
14                     UCB, INC. v. WATSON LABORATORIES INC.

which the parties, on appeal, agreed did not fall within the
literal scope of the carboxamides claimed in the ’893 pa-
tent. Id. at 1359, 1365. But the district court ruled on
summary judgment that WS-23 was “not an equivalent of
WS-3 for purposes of the ’893 patent.” Id. at 1365. This
court affirmed, citing several reasons. First, the “disclo-
sure of the ’893 patent focuse[d] narrowly on N-substi-
tuted-p-menthane carboxamides, and not on carboxamides
generally,” because it focused on advantageous character-
istics unique to N-substituted-p-menthane carboxamides
such as its “unexpected[ly] heightened cooling sensation in
edible products” and its structural similarity to menthol it-
self—characteristics not shared by WS-23. Id. at 1365–66.
Second, the claim was drafted to cover only a subset of N-
substituted-p-menthane-carboxamides, indicating a nar-
rowing even beyond the specification. Id. at 1366. Third,
there was clear evidence in the record that the inventors of
the ’893 patent were introduced to WS–3 and WS–23 by a
salesman for the distributor of the compounds during the
same sales call, where they were told that the two com-
pounds were appropriate for the same uses, and yet, the
inventors still drafted their claims narrowly to recite cer-
tain N-substituted-p-menthane carboxamides, as opposed
to a broader category of carboxamides that would include
WS–23. Id.
    The facts are different here. Wrigley does not support
treating the present facts as precluding a finding of equiv-
alence.
     Actavis does not argue that the ’434 patent’s specifica-
tion relies on any unique characteristics of acrylate or sili-
cone-based polymer adhesive systems that would not be
present in a polyisobutylene-based system. The language
in the Summary of the Invention stating that the claimed
system “is essentially characterized by a matrix on the ba-
sis of an acrylate-based or silicone-based non-aqueous pol-
ymer adhesive system having a solubility for [rotigotine
free base] of >5% (w/w), which matrix is substantially free
UCB, INC. v. WATSON LABORATORIES INC.                        15

of inorganic silicate particulates,” is just a recitation of the
qualities of the matrix; the passage does not identify
unique characteristics of acrylate or silicone-based polymer
adhesive systems to the exclusion of other systems. ’434
patent, col. 2 ll. 35–40. And the fact that the specification
repeatedly recites acrylate- and silicone-based polymers is
irrelevant to the issue of whether it describes those poly-
mers in a manner that would suggest to a skilled artisan
that polyisobutylene is not an equivalent. For this inquiry,
the specification states that the “adhesive’s dissolving ca-
pacity for the active substance is an important parameter
for the development of matrix systems, just as the mobility
of the active substance in the matrix, and its transfer via
the contact surface to the skin.” Id. at col. 3 ll. 15–18. As
explained in detail below, the district court found record
evidence that there was no substantial difference between
the claimed adhesive systems and polyisobutylene-based
polymer adhesive systems for these parameters.
    Furthermore, the claims also correspond directly to the
specification by reciting all acrylate-based or silicone-based
polymer adhesive systems, without narrowing to a subset
as in Wrigley.
    Finally, the evidence of the inventor’s knowledge here
at the time of filing is not as clear as in Wrigley. Actavis
points to a feasibility study done by the inventors in Janu-
ary 1996. J.A. 5913–43. The document describes that “[f]or
the formulation of matrix systems with a self-adhesive ma-
trix formulation the following adhesives are most com-
monly used: silicone based adhesive[,] polyacryl resin
based adhesives[,] polyisobutylene based adhesives[, and]
adhesives on the basis of styrene/ isoprene A-8-A blockpol-
ymers.” J.A. 5916 (emphasis added). The inventors ex-
plained that “the suitability of silicone based matrix
formulation was already demonstrated by Cygnus,” so they
chose to concentrate on “polyacrylic resins and styrene/iso-
prene/styrene blockpolymers.” Id. No reason was given for
not testing polyisobutylene-based adhesives. Further, one
16                     UCB, INC. v. WATSON LABORATORIES INC.

inventor testified that he had “limited experience” with pol-
yisobutylene as a liquid but was “not so familiar” with its
polymer form. J.A. 4219.
    Thus, in contrast to Wrigley, there is not enough indi-
cation from the patent specification, claims, or the record
evidence of the inventor’s knowledge here to conclude that
UCB surrendered polyisobutylene as a possible equivalent.
In the absence of such facts, we agree with the district court
that UCB’s claiming of acrylates and silicates does not bar
treating polyisobutylenes as an equivalent for infringe-
ment purposes. J.A. 146–48. 10

     10    Actavis cites two additional cases for this issue:
Carnegie Mellon University v. Hoffmann-La Roche Inc.,
541 F.3d 1115 (Fed. Cir. 2008), and Tanabe Seiyaku Co. v.
International Trade Commission, 109 F.3d 726 (Fed. Cir.
1997). Appellants’ Op. Br. at 48–49. Carnegie Mellon was
decided under the vitiation doctrine, which we address sep-
arately herein. In Tanabe, the applicant “chose to define
its invention in terms of specific base-solvent combinations,
rather than in terms of categories of bases and solvents,”
but also proceeded to define the success of its invention “in
terms of the exact base-solvent combinations” during pros-
ecution such that “a review of the prosecution history by a
competitor would reinforce the suggestion in the claim lan-
guage and specification that using other ketone solvents
. . . is not an insubstantial change [and would suggest] that
other ketone solvents may result in lower yields than the
claimed solvents.” 109 F.3d at 732. In affirming the Inter-
national Trade Commission’s finding of no infringement
under the doctrine of equivalents, the Tanabe court largely
relied on the interchangeability/substantial differences
doctrine and evidence that butanone was not as successful
as the claimed acetone. 109 F.3d at 732–34. Prosecution
UCB, INC. v. WATSON LABORATORIES INC.                        17

    Further, we note as a policy matter that the patent sys-
tem should not incentivize inventors to claim equivalents
that they had not invented or tested, just because they
know of the possibility of an equivalent, and also should
not force inventors to delay filing for a patent on what they
have invented while testing all known possible equivalents
for fear of being unable to assert infringement under the
doctrine of equivalents in the future.
                           c. Vitiation
      “Under the doctrine of equivalents, an infringement
theory . . . fails if it renders a claim limitation inconsequen-
tial or ineffective.” Akzo Nobel Coatings, Inc. v. Dow Chem.
Co., 811 F.3d 1334, 1342 (Fed. Cir. 2016). This vitiation
doctrine ensures that “the application of the doctrine [of
equivalents] . . . is not allowed such broad play as to effec-
tively eliminate that element in its entirety.” Warner-Jen-
kinson, 520 U.S. at 29. Vitiation “is not an exception or
threshold determination that forecloses resort to the doc-
trine of equivalents, but is instead a legal conclusion of a
lack of equivalence based on the evidence presented and
the theory of equivalence asserted.” Cadence Pharm. Inc.
v. Exela PharmSci Inc., 780 F.3d 1364, 1371 (Fed. Cir.
2015). For example, in Carnegie Mellon University v. Hoff-
mann-La Roche Inc., this court concluded that finding Taq
bacteria equivalent to E. coli bacteria would essentially
render the “bacterial source [is] E. coli” claim limitation
meaningless and would thus vitiate that limitation of the

history was a factor in the court’s analysis, but not one that
by itself barred consideration of infringement under the
doctrine of equivalents. Thus, Tanabe does not bar consid-
eration of the doctrine here, even if the prosecution history
was as suggestive in the instant case (which as explained
above, it is not).
18                     UCB, INC. v. WATSON LABORATORIES INC.

claims. 541 F.3d 1115, 1129 (Fed. Cir. 2008) (affirming
summary judgment of noninfringement).
     Here, Actavis argues that UCB’s doctrine of equiva-
lents infringement theory should fail because it vitiates the
“acrylate-based or silicone-base polymer adhesive system”
limitation of claim 1. We do not agree that finding polyiso-
butylene to be an equivalent gives the element “an acry-
late-based or silicone-based polymer adhesive system” such
broad play that the element would disappear entirely. See
Warner-Jenkinson, 520 U.S. at 29. The district court did
not broaden the right to exclude so widely as to cover all
adhesive systems and vitiate the “acrylate-based or sili-
cone-based” claim language. As explained below, the dis-
trict court here conducted a specific analysis as to whether
polyisobutylene would be covered, and it had adequate rea-
sons for why a skilled would understand that polyisobutyl-
ene, specifically, would work just as well as acrylate or
silicone for the claimed transdermal patch. Accordingly,
we agree with the district court that vitiation does not bar
application of the doctrine of equivalents here. J.A. 146–
47.
                       d. Ensnarement
     Actavis also contends that UCB’s infringement theory
is improper because it “ensnares” the prior art. See Inten-
dis GMBH v. Glenmark Pharm. Inc., USA, 822 F.3d 1355,
1363 (Fed. Cir. 2016) (“A patentee may not assert ‘a scope
of equivalency that would encompass, or ensnare, the prior
art.’”) (quoting DePuy Spine, Inc. v. Medtronic Sofamor
Danek, Inc., 567 F.3d 1314, 1322 (Fed. Cir. 2009)). “A help-
ful first step in an ensnarement analysis is to construct a
hypothetical claim that literally covers the accused device.”
DePuy Spine, 567 F.3d at 1324. “Next, the district court
must assess the prior art introduced by the accused in-
fringer and determine whether the patentee has carried its
burden of persuading the court that the hypothetical claim
is patentable over the prior art.” Id. at 1325. “In short,
UCB, INC. v. WATSON LABORATORIES INC.                     19

[the court] ask[s] if a hypothetical claim can be crafted,
which contains both the literal claim scope and the accused
device, without ensnaring the prior art.” Intendis, 822 F.3d
at 1363.
    Actavis argues that a hypothetical claim including pol-
yisobutylene-based polymers would ensnare the prior art.
But the prior art that Actavis points to covers silicone and
acrylate polymers as well; its theory, if correct, would thus
invalidate both the actual and hypothetically broader
claims. Actavis offers no examples of prior art that would
be ensnared by the addition of polyisobutylene to the claim,
in contrast to the claim as is.
    The district court “disagree[d]” with Actavis’s conten-
tion that there is an ensnarement issue here and found
that “UCB’s equivalence theory does not ensnare the prior
art.” J.A. 147–48 (emphasis added). We concur and do not
find that the district court erroneously placed the burden
on Actavis to prove ensnarement. Actavis’s ensnarement
argument is substantively a patent invalidity challenge,
which we address later in this opinion. See Jang v. Boston
Sci. Corp., 872 F.3d 1275, 1288–89 (Fed. Cir. 2017) (ex-
plaining that ensnarement and validity are “two different
concepts”).
                           2. Merits
   Second, we find no clear error with the district court’s
substantive application of the doctrine of equivalents.
    Infringement under the doctrine of equivalents is a fac-
tual question, VirnetX, Inc. v. Cisco Sys., Inc., 767 F.3d
1308, 1322–23 (Fed. Cir. 2014), which we review for clear
error on appeal from a bench trial. Pfizer, Inc. v. Apotex,
Inc., 480 F.3d 1348, 1359 (Fed. Cir. 2007).
    The Supreme Court has set out two frameworks for
evaluating equivalency. Warner-Jenkinson, 520 U.S. at
39–40. The relevant framework here, which the district
court applied, is the (in)substantial differences test, under
20                     UCB, INC. v. WATSON LABORATORIES INC.

which“[a]n element in the accused device is equivalent to a
claim limitation if the only differences between the two are
insubstantial.” Voda v. Cordis Corp., 536 F.3d 1311, 1326
(Fed. Cir. 2008). This court has explained that “the sub-
stantial differences test may be more suitable . . . for deter-
mining equivalence in the chemical arts,” and identified
“structural equivalen[cy]” as particularly relevant when
comparing chemical equivalents. Mylan Institutional LLC
v. Aurobindo Pharma Ltd., 857 F.3d 858, 869 (Fed. Cir.
2017).
     The purpose of the adhesive polymer in the disputed
claim element is to act as a scaffold for the drug and to pro-
vide adhesion to a patient’s skin for the transdermal patch.
The district court found that, at the time the ’434 patent
was filed, silicates, acrylates, and polyisobutylenes were
the most commonly used pressure-sensitive adhesives in
transdermal patches. J.A. 127. The district court then
identified a set of properties that silicates, acrylates, and
polyisobutylenes share: they are pressure-sensitive, adhe-
sive, biologically inert, non-irritating, and non-toxic. J.A.
121–28. Thus, the district court found that a skilled arti-
san “would recognize that polyisobutylene is not substan-
tially different from the classes of adhesives literally
within the scope of the claims.” Id. at 128.
    The district court also made fact findings as to the dif-
ferences between polyisobutylene and silicates/acrylates.
“Polyisobutylene is an organic polymer, consisting exclu-
sively of carbon and hydrogen atoms, forming a non-polar
backbone, without any functional groups,” and accordingly
is non-polar and hydrophobic. Id. Silicates and polyacry-
lates, unlike polyisobutylene, may contain functional
groups that may be polar and/or reactive. So, due to differ-
ences in polarity, polyisobutylene has different adhesive-
ness compared to acrylate- and silicone-based adhesives.
Id. Further, polyisobutylene, unlike silicone- or acrylate-
based polymers, does not allow for crosslinking agents to
be used to increase adhesion or reduce cold-flow. Finally,
UCB, INC. v. WATSON LABORATORIES INC.                     21

rotigotine contains atoms that can interact with certain
functional groups that can be present in silicone- and acry-
late-based polymers, but rotigotine does not interact signif-
icantly with polyisobutylene. Id.
    The district court explained that these differences do
not matter for how the claimed invention works, as evi-
denced by the comparative results between UCB’s Neupro
product and the Accused Products, called PIB Neupro
(Neupro with polyisobutylene substituted for silicone). The
district court noted that permeation results for Neupro and
PIB Neupro were comparable in terms of transdermal de-
livery of rotigotine at the intended wear time of 24 hours,
and that Actavis chose polyisobutylene because it worked
just as well as silicone. J.A. 129. The district concluded
that “[t]hese results show that the polyisobutylene-based
polymer adhesive system did not alter the way rotigotine is
transdermally delivered compared to a silicone-based poly-
mer adhesive system,” nor did it “alter rotigotine transder-
mal delivery rates,” showing that “polyisobutylene is
interchangeable with silicone in the claimed polymer adhe-
sive system.” Id. Accordingly, the district court concluded
that “[t]he polyisobutylene-based adhesive system is an in-
substantial modification of the claimed invention.” Id.
    As for the dependent claims, which recite the use of
PVP as a solubility enhancer, the district court found that
the Accused Products use PVP as a solubility enhancer for
rotigotine—in the same way as the claimed silicone-based
polymer adhesive system. J.A. 130. The district court cited
Actavis’s stability testing (1) confirming that PVP was nec-
essary in the polyisobutylene-based polymer adhesive sys-
tem to fully dissolve the necessary amount of free base and
prevent crystallization and (2) disclosing that this amount
was within the range of PVP claimed in the ’434 patent. Id.
Further, both a polyisobutylene-based polymer adhesive
system and the claimed silicone-based polymer adhesive
system use a hydrophobic adhesive with inherently low sol-
ubility for rotigotine free base in which rotigotine-PVP
22                     UCB, INC. v. WATSON LABORATORIES INC.

complexes are dispersed. Id. So, the district court rea-
soned that just because “polyisobutylene has some differ-
ent properties (e.g., lack of heteroatoms and functional
groups, different polarity, etc.),” this “does not change how
the polymer adhesive system works”: “the polymer func-
tions as a scaffold for the drug,” and “[r]otigotine-PVP com-
plexes form in both silicone polymers and polyisobutylene
to increase drug solubility and allow for drug mobility.”
J.A. 131.
    The district court thus concluded that “[p]olyisobutyl-
ene is interchangeable with silicone in the claimed polymer
adhesive system, resulting in an insubstantially different
system that also uses dispersed rotigotine-PVP to effect
≥5% solubility.” J.A. 132.
    On appeal, Actavis argues that the district court erro-
neously relied on evidence comparing UCB’s branded
Neupro product with (a) Actavis’s ANDA product and
(b) PIB Neupro. Appellants’ Op. Br. at 57. The crux of Ac-
tavis’s argument is that Neupro is not equivalent to the as-
serted claims because it undisputedly contains 5 molecules
of water for every 7 molecules of rotigotine. Id. at 74 (citing
J.A. 4620:23–28:12 (testimony by UCB’s expert); J.A. 5946,
5951–52 (Neupro validation document disclosing ratio and
stating that Neupro patches have final “water content” of
0.3%)). Actavis argues that because it has water, Neupro
does not have free base rotigotine in the patch’s matrix “in
the absence of water” as required by ’434 patent claim 1.
Since it is not equivalent to the claims, Actavis argues that
any comparison between it and the Accused Products is a
legally erroneous basis for infringement.
    But the district court explicitly stated whether Neupro
is or is not an embodiment of the claims is not dispositive
of the infringement question because “infringement re-
quires a comparison of the accused product (the ANDA
product) and the claims.” J.A. 149 n.6.
UCB, INC. v. WATSON LABORATORIES INC.                        23

     And the district court only relied on Neupro and PIB
Neupro for points unrelated to water content. The district
court observed that “[b]oth Neupro itself and the ’434 pa-
tent in exemplary embodiments use silicone adhesives . . .
that have a solubility for rotigotine of less than 0.1%” to
make the point that the low solubility of polyisobutylene
was not a concern that would differentiate it from silicates.
J.A. 151. The district court also pointed out that Actavis
started with Neupro and substituted polyisobutylene for
silicone to make PIB Neupro because it viewed the two as
interchangeable. J.A. 129. And the district court cited the
comparative permeation studies because they showed no
statistical difference in the amount of rotigotine delivered
between the two adhesives. J.A. 152. It is not clear how
any of these conclusions are affected by the water content
of Neupro. Regardless, as summarized above, the district
court had many non-Neupro-related reasons for finding
substantial similarity here.
    We do not find clear error in any of the district court’s
fact findings as to polyisobutylene’s characteristics as com-
pared to silicates and acrylates. We also do not find clear
error in the district court’s fact findings as to what a skilled
artisan would have known about the interchangeability of
polyisobutylene-based adhesives and silicone-based adhe-
sives (i.e., why the similarities matter more than the dif-
ferences for the claimed system). Giving credit to those fact
findings, we affirm the district court’s conclusion that the
Accused Products infringe the claims under the doctrine of
equivalents.
                 B. Validity of the ’434 Patent
    This court reviews legal conclusions from a bench trial
de novo and factual findings for clear error. Pfizer, 480 at
1359. Anticipation is a factual question that we review for
clear error; we review the legal conclusion of obviousness
de novo and the underlying fact findings for clear error. Ge-
netics Inst., LLC v. Novartis Vaccines & Diagnostics, Inc.,
24                     UCB, INC. v. WATSON LABORATORIES INC.

655 F.3d 1291, 1302 (Fed. Cir. 2011) (citations omitted).
Actavis appeals the district court’s rejection of three of its
proposed invalidity grounds: (1) anticipation by Cygnus,
(2) obviousness over Cygnus in combination with Lipp or
Pfister, and (3) obviousness over the combination of Tim-
merman and Miranda.
       1. Cygnus-Based Anticipation and Obviousness
    The Cygnus prior art patent application generally dis-
closes controlled-release drug formulations that can be
used with transdermal patches. J.A. 5704. The application
describes “a novel matrix composed of a continuous hydro-
phobic domain and a dispersed particulate hydrated sili-
cate domain,” “which may be used to administer
hydrophilic drugs in a sustained manner.” J.A. 5706. Ro-
tigotine is listed as an exemplary hydrophilic drug in Ex-
ample 15. J.A. 5717–18. In that example, skin flux (rate
of absorption) studies are presented of patches containing,
in relevant part: rotigotine, a phosphate buffer (which is a
water-based solution), and a silicone-based adhesive. Id.
Example 15’s patches are further described in Chiang. J.A.
155, 4827–28.
    The district court found that Cygnus did not disclose a
crucial element of claim 1: a patch containing rotigotine in
free base form. J.A. 157–58. Cygnus states the chemical
name of rotigotine free base:          S(-)-2-(N-propyl-N-2-
thienylethylamine)-5-hydroxytetralin. J.A. 5717. Rotigo-
tine, however, can exist in free base form or in salt form.
J.A. 157. Actavis presented Example 15 of Cygnus as evi-
dence that Cygnus teaches a free base form existing in a
patch. J.A. 158. In that example, rotigotine is present as
a salt in a phosphate buffer water solution, where most of
the rotigotine would be in charged salt form and only 1.28%
could be present in neutral free base form. Id.
    On appeal, Actavis points to Cygnus’s Example 15 as
teaching a patch with some rotigotine in free base form.
But Actavis’s argument has a fatal flaw: there is nothing
UCB, INC. v. WATSON LABORATORIES INC.                        25

in Cygnus that teaches a water-free patch with rotigotine
in free base form. All the patches in Cygnus’s examples—
including those with rotigotine—contain significant
amounts of water (10–15% w/w) such that even the 1.28%
of rotigotine present in free base form in Example 15 would
necessarily be in the presence of water because of the phos-
phate buffer. 11 Accordingly, it was not clearly erroneous
for the district court to find that “merely providing the
chemical name [in the specification] for the rotigotine free
base” was not enough to disclose that the base was present
in the absence of water. J.A. 158.
    Thus, we agree with the district court’s conclusion that
Actavis did not present “sufficient evidence that rotigotine
free base is present in a patch that is water-free” in Cyg-
nus. Id.
    Neither Lipp nor Pfister fills this gap. Both disclose
transdermal patches containing PVP, but neither discloses
any anti-Parkinson’s drugs, much less rotigotine free base
in the absence of water. 12

    11   Actavis contended at Oral Argument that Cygnus
discloses substituting other solvents for water: “Other hy-
drophilic polar solvents such as ethanol, propylene glycol,
low molecular weight (200 to 400 mw) polyethylene glycol,
isopropyl alcohol, N-butanediol, m-pyrol and benzyl alcohol
may be substituted for water or included in the hydrophilic
domain of the matrix.” Oral Arg. at 3:07 (citing J.A.5209).
But the district court found that “Actavis [] presented no
evidence” that use of such solvents would actually result in
rotigotine free base in a water-free patch. J.A. 158. Actavis
does not show on appeal that the district court erred in that
finding.
    12     Actavis also argues that all of the asserted ’434 pa-
tent     claims are “obvious as claiming well-known
26                     UCB, INC. v. WATSON LABORATORIES INC.

       2. Obviousness over Timmerman and Miranda
     The district court also rejected Actavis’s argument that
the asserted claims of the ’434 patent would have been ob-
vious in light of Miranda combined with Timmerman. Mi-
randa describes (1) transdermal patches based on silicone
or polyacrylate-based polymer adhesives, (2) PVP as a sol-
ubility enhancing agent, (3) an active ingredient present in
concentrations between 3% and 10%, and (4) solvents that
are not water. J.A. 5780, 5787, 5788, 5808–09. Miranda
does not specifically name rotigotine as a suitable drug for
its patches, but it does include a list of other drugs that are
used to treat Parkinson’s disease. J.A. 5797. Timmerman
is a 1988 study in which rats were treated transdermally
on the skin of their necks with a solution containing rotig-
otine free base. J.A. 4811–18. Timmerman deduced that
transdermal application of rotigotine was superior to oral
administration because it induced a much longer duration
of action of the drug (13 hours) in comparison with the oral
mode (5 hours). J.A. 4811, 4816. Timmerman concluded
that “transdermal administration . . . may provide a most
useful way of administering the drug for therapeutic use.”
J.A. 4817.
    The district court found that Actavis did not provide an
adequate rationale for combining the references’ teachings,
noting that Actavis did “not explain why a [skilled artisan]
would have been motivated to start from the patches
taught by Miranda.” J.A. 161–62. The district court then
found that it was not persuaded that a skilled artisan

components.” Appellants’ Op. Br. at 72. But Actavis does
not explain in any detail how a skilled artisan would un-
derstand or combine such evidence to arrive at the claimed
invention. Actavis did not meaningfully develop this argu-
ment below or on appeal, and we do not find it sufficient to
render any of the asserted ’434 patent claims obvious.
UCB, INC. v. WATSON LABORATORIES INC.                      27

would have reasonably expected the combination to be suc-
cessful because: (1) the transdermal patch field was a rel-
atively sparse one at the pertinent date (only 8
transdermal patches were available at the time of the in-
vention of the ’434 patent in 1998, and even now, only 20
drugs are available in patch form), and (2) of the drugs
available as patches, rotigotine is the only active ingredient
that was introduced as a patch without first being availa-
ble in a different type of formulation. J.A. 162. So, even
accepting Actavis’s contention that Miranda provides a
“recipe” or “check list” for making transdermal patches, the
district court reasoned that a skilled artisan “would have
confronted a significant challenge to create a patch that
was successful at treating Parkinson’s disease,” especially
in light of Chiang’s teaching that path formulation can
have a dramatic effect on observed rate of absorption
through the skin (skin flux). Id. Ultimately, the district
court was not persuaded that the claimed invention would
have been, at the time of the invention, “as trivial and
straightforward as simply combining rotigotine free base of
Timmerman with the patch recipe of Miranda.” Id.
     On appeal, Actavis argues that the district court failed
to find obviousness over this combination only because it
applied an “unduly rigid” analysis in concluding that Ac-
tavis had not shown a motivation to combine or reasonable
expectation of success. Appellants’ Op. Br. at 62 (citing
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007)). Ac-
tavis argues that the district court’s concern over why a
skilled artisan would have been motivated to start with Mi-
randa is misplaced because starting with Miranda was not
part of its obviousness theory. As a threshold matter, we
agree with Actavis that, under the flexible framework of
KSR, it should not matter whether a proposed obviousness
combination starts with Timmerman or Miranda. But
even accepting Actavis’s argument that a skilled artisan
would start with Timmerman, there is still an evidentiary
gap as to why a skilled artisan would think of using a
28                    UCB, INC. v. WATSON LABORATORIES INC.

transdermal patch, as taught in Miranda, based on Tim-
merman’s “transdermal administration” disclosure of ap-
plying a liquid dose of the drug on the hairless skin on the
neck of a rat.
     As to lack of reasonable expectation of success, we af-
firm the district court’s finding. Miranda discloses thou-
sands of combinations for making transdermal patches.
First, it discloses huge ranges for the percent by weight of
the rubber, polyacrylate, PVP, co-solvents, and drugs in the
patches. J.A. 5806. Second, it discloses hundreds of drugs,
of which anti-Parkinson drugs are just a small category
and where that category does not even list rotigotine. J.A.
5789–802, 5797. Third, Miranda lists ethanol as just one
of many possible solvents. J.A. 5808. Finally, it teaches
that “[t]he amount of drug to be incorporated in the compo-
sition varies depending on the particular drug, the desired
therapeutic effect, and the time span for which the device
is to provide therapy.” J.A. 5803.
     Based on the above, it was reasonable to conclude that
Miranda is less of a “recipe” for the claimed rotigotine
transdermal patch and more of a list of thousands of possi-
bilities out of which a skilled artisan would have to select
the claimed combination as one to try. Miranda does not
provide a reasonable expectation of success for making a
transdermal patch of rotigotine without undue experimen-
tation, and Timmerman cannot fill in this gap, as it does
not contemplate using a patch to administer rotigotine
transdermally. Chiang’s disclosure that “[o]ne of the major
obstacles for developing a transdermal delivery system is
to deliver sufficient amounts of the drug through the skin,”
J.A. 4827–28, and its conclusion, as summarized by the dis-
trict court, that “path formulation can have a dramatic ef-
fect on observed skin flux,” J.A. 162, further suggest that
transdermal drug administration is not a straightforward
task such that narrowing down Miranda’s teachings to the
claimed invention could be achieved via routine experimen-
tation. J.A. 4827–28. And the district court found that the
UCB, INC. v. WATSON LABORATORIES INC.                      29

transdermal patch field was not a common, widespread one
during the relevant time, and that of the drugs available
as patches, rotigotine was the only active ingredient that
was introduced as a patch without first being available in
a different type of formulation. J.A. 162. All of these facts
support the district court’s conclusion that a skilled artisan
would not have had a reasonable expectation of success in
combining Miranda and Timmerman, even if there was a
motivation to do so.
    Since we find no reversible error in the findings by the
district court about the prior art we have already dis-
cussed, we do not reach Actavis’s arguments challenging
additional findings regarding secondary considerations.
Those considerations are unnecessary here, as they can
only further support the rejection of the obviousness chal-
lenge.
    Accordingly, we affirm the district court’s findings up-
holding the validity of the asserted ’434 patent claims.
                C. Invalidity of the ’414 Patent
    On cross-appeal, UCB asks this court to reverse the
district court’s invalidation of the asserted ’414 patent
claims due to prior public use under § 102(a) because the
record evidence allegedly did not support the district
court’s inferences as to how UCB’s Form II invention was
in actual use before the correct invention date. Cross-Ap-
pellants’ Op. Br. at 62–63.
    A patent may be found invalid if “the invention was
known or used by others in this country” before invention
by the applicant. 35 U.S.C. § 102(a) (pre-AIA). 13 This is

    13 The Leahy-Smith America Invents Act (AIA)
changed 35 U.S.C. § 102. Pub. L. No. 112-29, § 3(b), 125
Stat. 284, 285–86 (2011).      However, because the
30                     UCB, INC. v. WATSON LABORATORIES INC.

because “[i]f the invention was known to or used by others
in this country before the date of the patentee’s invention,
the later inventor has not contributed to the store of
knowledge, and has no entitlement to a patent.” Woodland
Tr. v. Flowertree Nursery, Inc., 148 F.3d 1368, 1370 (Fed.
Cir. 1998). “For prior art to anticipate because it has been
‘used,’ the use must be accessible to the public.” Minnesota
Mining & Mfg. Co. v. Chemque, Inc., 303 F.3d 1294, 1301
(Fed. Cir. 2002). “[P]rior knowledge and use by a single
person is sufficient.” Coffin v. Ogden, 85 U.S. 120, 124
(1873).
    The district court reasonably found that a patient in
the United States used Neupro patches that contained
Form II rotigotine before November 28, 2007—the ’414 pa-
tent’s filing date—and that therefore, the ’414 patent
claims were invalid under § 102(a). 14 J.A. 183. A female

application from which the ’414 patent issued has never
contained a claim having an effective filing date on or after
March 16, 2013, or a reference under 35 U.S.C. §§ 120, 121,
or 365(c) to any patent or application that ever contained
such a claim, the pre-AIA § 102(a) applies. Id. § 3(n)(1), 125
Stat. at 293.
    14   UCB disputes whether November 28, 2007 is the
appropriate date of invention for the ’414 patent. Gener-
ally, “the date of invention [is] presumed to be the filing
date of the application until an earlier date is proved.”
Bausch & Lomb, Inc. v. Barnes-Hind/Hydrocurve, Inc.,
796 F.2d 443, 449 (Fed. Cir. 1986). It is the patentee’s bur-
den to present evidence of an earlier invention date. See
Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1576–78 (Fed.
Cir. 1996). UCB assumed November 28, 2007 as the date
of invention for its arguments against derivation (not on
appeal), was on notice of Actavis’s reliance on the date for
§ 102(a) purposes at least as of the district court’s pre-trial
UCB, INC. v. WATSON LABORATORIES INC.                     31

patient had received samples of Neupro in September 2007
and “responded well” to treatment. J.A. 5965. In Novem-
ber 2007, however, this patient purchased Neupro patches
that were from lot 47808—one of the lots later discovered
to have contained Form II rotigotine. Id.; J.A. 181–82.
While using these lot 47808 patches, the patient began
“clearly back-sliding, experiencing previous [Parkinson’s]
symptoms of losing mobility, shaking and freezing.” J.A.
5966. The patient experienced the adverse event two days
after the priority date of the ’414 patent, but she had been
using the patches for “one week,” necessarily implying that
she was using the patches before the ’414 patent’s priority
date of November 28, 2007. Id. After experiencing this
back-sliding, the patient “was reverted to the samples of
the newer lot number” and “an improvement in the patient
was noted.” Id.
    The district court found that Form II rotigotine was
used in the United States before the November 28, 2007
priority date of the ’414 patent based on (1) record evidence
that most, if not all, of lot 47808’s patches sent to the
United States contained Form II rotigotine, and (2) the pa-
tient’s back-sliding with the lot 47808 patches and subse-
quent improvement on different patches.

order, and failed to raise any issue with the invention date
until post-trial briefing. Under these circumstances, we
find that the district court did not abuse its discretion in
finding that UCB waived any argument of a date of inven-
tion earlier than November 28, 2007. Chimie v. PPG In-
dus., Inc., 402 F.3d 1371, 1376 (Fed. Cir. 2005) (Unless a
procedural ruling raises issues unique to patent law, we
apply the law of the appropriate regional circuit.); Springer
v. Henry, 435 F.3d 268, 275 n.4 (3d Cir. 2006) (The Third
Circuit reviews a district court’s decision that a party has
waived an issue for trial for abuse of discretion.).
32                     UCB, INC. v. WATSON LABORATORIES INC.

     On appeal, UCB first argues that there is insufficient
evidence that there were Form II crystals in the patient’s
Neupro patches before the ’414 patent’s filing date. But the
district court explained that the patient’s patches were
from lot 47808 and concluded that the whole batch had
Form II crystal because so many of the retained and later
tested samples from that lot contained Form II. J.A. 181–
82. The district court also pointed to the patient’s “back-
sliding” symptoms as indicative of the Form II crystals’
presence. J.A. 183. To argue that the patches used by the
patient may not have contained Form II crystals, UCB
points to a report showing that out of the twenty patches
tested in that lot, nine of them did not have crystals ini-
tially. J.A. 4853. But that same report shows that all had
crystals within a month of storage. Id. The patches used
by the patient were stored for far longer than that; they
were made in June/July 2007 and used in November 2007.
J.A. 181; J.A. 5966. UCB further argues that the crystals
observed on the patches may not have necessarily been
Form II, as apparently it is impossible to distinguish Form
I from Form II by sight. Cross Appellants’ Op. Br. at 69
(citing J.A. 4838; J.A. 4282–83). But in this record, all lots
where crystals were observed were confirmed to contain
Form II. J.A. 4852–53.
     Second, UCB argues that the patient’s “back-sliding”
symptoms are not necessarily evidence of Form II use.
Cross-Appellants’ Op. Br. at 69–70. UCB argues that the
patient’s other health issues might have contributed to
those symptoms, citing record evidence that “[t]he impact
of crystals on product efficacy in patients depends on the
extent of drug release, variability at the level of the patient
and product, and psychological patient factors.” J.A. 4850.
We understand this statement to suggest that the “back-
sliding” is different from patient to patient. But it is not
relevant, where, as here, the baseline for the “back-sliding”
is the patient’s own responsiveness to patches she took be-
fore and after the patches likely containing Form II. UCB
UCB, INC. v. WATSON LABORATORIES INC.                      33

also points out that the patient’s physician suspected dif-
ferent causes for the backsliding because the patient was
“checked for co-morbidity, suspecting a cold or lung prob-
lems due to wildfires,” the patient suffered from conditions
other than Parkinson’s, she was on several other medica-
tions, and her improvement after the switch to patches
from a different lot number was temporary, with her con-
ditioning declining again thereafter. J.A. 5966. Finally,
UCB argues that a document the district court relied on
actually shows that there was not enough Form II on the
patches to cause back-sliding. Cross-Appellants’ Op. Br. at
70–71. That document explains that ~one-third of a
patch’s surface area needs to be covered in Form II crystals
to cause back-sliding, and many of the tested samples from
the affected batches had an affected surface area of < 30%.
J.A. 4850. But another report in the record shows affected
areas >40%. J.A. 4848. That there might have been other
causes for the back-sliding or that there may not have been
enough crystals on the patches to cause back-sliding are
speculative facts that are reasonably outweighed by other
evidence in the record.
    Third, UCB argues that Form II cannot penetrate the
skin, so it has no therapeutic function in a patch, and there-
fore, the patches administered to the patient in November
2007 do not count as “use” of the ’414 patent’s invention
under § 102. Cross-Appellants’ Op. Br. at 62–63. But the
’414 patent claims simply cover Form II rotigotine, without
any limitations as to its use. If it was present in the
patches that were administered to the patient, § 102(a)
does not require that the invention be used for a particular
purpose. The case cited by UCB, 3M v. Chemque, 303 F.3d
1294, 1306–07 (Fed. Cir. 2002), stands for the inapposite
proposition that evidence of product samples being sent to
third parties is not sufficient to show that those samples
were actually used by the third parties. The case here is
different; there is evidence that patient actually used the
patches with Form II rotigotine crystals in it. The patient’s
34                     UCB, INC. v. WATSON LABORATORIES INC.

use of the patches fairly counts as public use under
§ 102(a).
     Anticipation under § 102(a) is an issue of fact reviewed
for clear error. Ecolochem, Inc. v. S. Cal. Edison Co., 227
F.3d 1361, 1367 (Fed. Cir. 2000). There is plenty of evi-
dence that most, if not all, of the patches in lot 47808 con-
tained crystals, and that those crystals contained Form II.
There is also evidence that the patient, who reported back-
sliding only after one week of using lot 47808 patches and
who reported improvement (even if short-lived) when a
new set of patches was used thereafter, used patches with
Form II and that her symptoms matched up with use of
Form II. J.A. 5966. We do not find clear error in the dis-
trict court’s finding that Actavis presented clear and con-
vincing evidence of public use before the date of invention
under § 102(a). Accordingly, we affirm the district court’s
invalidation of the asserted ’414 patent claims.
                       CONCLUSION
    We affirm the district court’s judgment of infringement
and validity of the asserted ’434 patent claims, as well as
invalidity of the asserted ’414 patent claims.
                       AFFIRMED
                           COSTS
     No costs.