Court Opinion

ID: 820521
Source: CourtListenerOpinion
Date Created: 2013-02-14 16:49:37.343285+00
Date Added: 2024-06-11T09:03:05.721938
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
              __________________________

      CEPHALON, INC. AND CIMA LABS, INC.,
             Plaintiffs-Appellants,
                           v.
  WATSON PHARMACEUTICALS, INC., WATSON
  LABORATORIES, INC. AND WATSON PHARMA,
                   INC.,
            Defendants-Appellees.
              __________________________

                      2011-1325
              __________________________

    Appeal from the United States District Court for the
District of Delaware in No. 08-CV-0330, Judge Sue L.
Robinson.
              ___________________________
               Decided: February 14, 2013
              ___________________________
    CAROLYN JACOBS CHACHKIN, Wilmer Cutler Pickering
Hale and Dorr, LLP, of Washington, DC, argued for
plaintiffs-appellants. With her on the brief were WILLIAM
G. MCELWAIN and JACOB S. OYLE; and WILLIAM F. LEE
and MARK C. FLEMING, of Boston, Massachusetts.

   JAMES K. STRONSKI, Crowell & Moring, LLP, of New
York, New York, argued for defendants-appellees. With
CEPHALON   v. WATSON PHARMA                              2

him on the brief were CHIEMI D. SUZUKI and JACOB Z.
ZAMBRZYCKI.
               __________________________
 Before REYNA, BRYSON, ∗ and WALLACH, Circuit Judges.
WALLACH, Circuit Judge.
    This action arises out of the filing of an Abbreviated
New Drug Application (“ANDA”) by Watson Pharmaceuti-
cals, Inc., Watson Laboratories, Inc., and Watson Pharma,
Inc. (collectively, “Watson”) for a generic version of
FENTORA®. In response to Watson’s ANDA filing,
Cephalon, Inc. and CIMA Labs, Inc. (collectively, “Cepha-
lon”) instituted this patent infringement suit at the
United States District Court for the District of Delaware
asserting U.S. Patent Nos. 6,200,604 (“the ’604 patent”)
and 6,974,590 (“the ’590 patent”). After a bench trial, the
district court found that Watson’s ANDA products did not
infringe and held the asserted patents invalid for lack of
enablement. Cephalon, Inc. v. Watson Pharms., Inc., 769
F. Supp. 2d 729, 761 (D. Del. 2011). We reverse on the
issue of enablement because Watson failed as a matter of
law to show with clear and convincing evidence that
Cephalon’s patents require undue experimentation to
practice the invention. As to the noninfringement finding,
the district court did not clearly err. Thus, we reverse–
in–part and affirm–in–part.
                              I.
             A. Background of the Invention
    The ’604 and ’590 patents (“Khankari patents”) gen-
erally relate to a method of drug delivery. The most
common method of drug delivery occurs through the

       ∗
            Judge Bryson assumed senior status on Janu-
ary 7, 2013.
3                              CEPHALON   v. WATSON PHARMA

gastrointestinal system upon oral administration. The
Khankari patents, however, utilize a different route—
drug delivery via the mucous membrane lining or mucosa
in the oral cavity.
     Oral mucosal drug delivery offers advantages. For in-
stance, the oral mucosal route provides direct access to
the bloodstream without having to travel through the
gastrointestinal tract, which allows the drug to avoid the
“first pass effect”—the percentage of drug lost to metabo-
lization in the liver. As a result, drug delivery across the
oral mucosa potentially provides patients with rapid onset
of action at a lower dosage.
                B. The Claimed Invention
     The Khankari patents 1 disclose methods to adminis-
ter a tablet (or other dosage form) comprising fentanyl 2 or
other pharmaceutical agents. Such tablets include effer-
vescent agents used as penetration enhancers, which
influence drug absorption across the buccal, sublingual,
and gingival mucosae. 3 ’590 patent col. 2 ll. 13–15. The
Khankari patents also disclose the use of an additional
pH adjusting substance in combination with an efferves-
cent agent for promoting the absorption of drugs. Id. col. 3
ll. 18–20.

       1
            The inventors of the Khankari patents are as
follows: Drs. Sathasivan Indiran Pather, Rajentra K.
Khankari, Jonathan D. Eichman, Joseph R. Robinson,
and John Hontz.
     2
        Fentanyl is an opioid analgesic or painkiller and a
Schedule II controlled substance, 21 U.S.C. § 812(c)
Schedule II(b)(6), with high lipophilicity.
        3
            Different areas of the mouth are given differ-
ent names. For example, the buccal mucosa is along the
inside of the cheek, the sublingual mucosa is under the
tongue, and the gingival mucosa is between the lips and
gum.
CEPHALON    v. WATSON PHARMA                                4

    An “effervescent agent” includes at least one com-
pound that evolves gas. Id. col. 2 ll. 44–45. The preferred
effervescent agents evolve gas by means of a chemical
reaction triggered by exposure of the effervescent agent
(an effervescent couple) to water and/or saliva in the
mouth. Id. col. 2 ll. 45–48. This reaction is most often the
result of a soluble acid source, like citric acid, reacting
with a source of carbon dioxide that is mostly basic, like
an alkaline carbonate or bicarbonate. 4 Id. col. 2 ll. 48–51,
59. Carbon dioxide gas is evolved as a result of this
reaction. Id. col. 2 ll. 51–52. The dosage form preferably
includes an effervescent couple comprising both the acid
source and a source for carbon dioxide. Id. col. 4. ll. 23–27.
     The effervescent reaction occurring in the mouth af-
fects the pH level of the saliva. Generally, pH levels can
influence the relative concentrations of the ionized and
un-ionized forms of the drug, which in turn, affects the
dissolution of the drug in the saliva and absorption of the
drug across the oral mucosa. Id. col. 3 ll. 20–24. The pH
of solutions in which an effervescent agent has dissolved
is slightly acidic due to the evolution of carbon dioxide. Id.
col. 3 ll. 24–25. Specifically, when carbon dioxide dis-
solves in saliva, it forms a weak acid (carbonic acid) that
reduces salival pH. The carbonic acid thereafter dissoci-
ates into carbon dioxide and water; the carbon dioxide is
released as gas, causing the pH to slowly rise providing
        4
            The acid sources may be any which are safe
for human consumption and generally include food acids,
acid, and hydrite antacids such as: citric, tartaric, amalic,
fumeric, adipic, and succinics. ’590 patent col. 2 ll. 56-60.
Carbonate sources include dry solid carbonate and bicar-
bonate salt such as, preferably, sodium bicarbonate,
sodium carbonate, potassium bicarbonate, potassium
carbonate, magnesium carbonate, and the like. Id. col. 2
ll. 60–64. Reactants which evolve oxygen or other gasses
and which are safe for human consumption are also
included. Id. col. 2 ll. 64–65.
5                               CEPHALON   v. WATSON PHARMA

for the initial low pH level suitable for dissolution and the
eventual high pH level ideal for absorption. Thus, incor-
porating a pH adjusting substance in combination with
effervescent agents may lead to an increase in the rate
and extent of absorption of an active drug. Id. col. 3 ll. 18–
20. According to the Khankari patents, suitable pH-
adjusting substances include, but are not limited to, any
of the acids or bases disclosed as effervescent compounds.
Id. col. 3 ll. 47–55.
    Other pharmaceutical ingredients are preferably in-
corporated into the dosage form of the invention for a
variety of purposes, including aiding disintegration.
“Disintegrants may comprise up to about 20 weight
percent” of the composition and, preferably, between 2%
and 10% of the composition. Id. col. 4 ll. 41–51.
“[S]uitable non-effervescent disintegration agents” may be
used. Id. col. 4 l. 43. Excipient fillers “desirably will also
assist in the rapid dissolution of the dosage form in the
mouth.” Id. col. 5 ll. 28–32. Mannitol is listed among the
(non-limiting) examples of such excipient fillers. Id.
    The ’604 patent was filed on June 8, 1999 and issued
on March 13, 2001. Priority is claimed to its provisional
patent application (No. 60/079,652) filed on March 27,
1998. The ’590 patent was filed on February 20, 2002 and
issued on December 13, 2005. The ’590 patent claims
priority to the ’604 patent’s application, and as a result,
the patents share a common disclosure.
    Claim 1 of the ’604 patent is the sole independent
claim of that patent, and reads as follows:
    1. A method of administering at least one systemi-
    cally distributable pharmaceutical agent across
    the oral mucosa comprising:
    a) providing a solid oral dosage form including a
    pharmaceutically effective amount of an orally
CEPHALON   v. WATSON PHARMA                              6

   administerable medicament; and at least one ef-
   fervescent agent in an amount sufficient to in-
   crease absorption of said orally administerable
   medicament across the oral mucosa; wherein said
   orally administerable medicament is not substan-
   tially encompassed by or dispersed in a material
   that prevents absorption of said medicament
   across the oral mucosa;
   b) placing said solid oral dosage form in the mouth
   of a patient so that saliva in said patient’s mouth
   activates said at least one effervescent agent in
   said tablet; and
   c) holding said solid oral dosage form and the dis-
   solving contents of said solid oral dosage form in
   the mouth of a patient whereby said at least one
   effervescent agent promotes absorption of said
   orally administerable medicament across the oral
   mucosa.
’604 patent col. 7 ll. 11–31 (emphasis added). The ’590
patent expressly discloses fentanyl as the pharmaceutical
agent. The ’590 patent recites one independent claim as
follows:
   1. A method of administration of fentanyl to a
   mammal across the oral mucosa thereof, said
   method comprising:
   providing a solid oral dosage form comprising fen-
   tanyl or a pharmaceutically acceptable salt there-
   of and at least one saliva activated effervescent
   agent in an amount sufficient to increase absorp-
   tion of said fentanyl or pharmaceutically accepta-
   ble salt thereof across said oral mucosa, at least
   one pH adjusting substance, and wherein said
   amount of said at least one effervescent agent is
   between about 5% by weight and about 80% by
7                              CEPHALON   v. WATSON PHARMA

    weight; and buccally, sublingually or gingivally
    administrating said solid oral dosage form to said
    mammal.
’590 patent col. 7 ll. 2–13 (emphasis added).
                  C. Procedural History
     Cephalon is the holder of the New Drug Application
for fentanyl buccal tablets, sold under the trade name
FENTORA® 5 for the treatment of breakthrough cancer
pain. The Khankari patents were listed in the FDA’s
Orange Book in connection with this New Drug Applica-
tion. See 21 U.S.C. § 355(b)(1). On July 10, 2007, Watson
filed an ANDA for FDA approval to sell a generic counter-
part of FENTORA® (“ANDA product”). 6 Watson’s actions
invoked the Hatch–Waxman Act, which establishes a
procedure called a “Paragraph IV certification,” 21 U.S.C.
§ 355(j)(2)(A)(vii)(IV), by which an entity that seeks to
market a generic counterpart of a patented drug product
or method of use, before the patent has expired, may
challenge the patent before actually marketing the drug. 7
    In response, on June 2, 2008, Cephalon instituted the
underlying action in district court against Watson, first
asserting the Khankari patents, and in a subsequent
        5
            FENTORA® contains fentanyl citrate, manni-
tol, sodium starch glycolate, magenesium stearate, citric
acid, sodium bicarbonate, and sodium carbonate. The
sodium bicarbonate and citric acid are an effervescent
couple that react to evolve carbon dioxide.
        6
            Watson’s ANDA products contain the active
ingredient fentanyl citrate and the inactive ingredients
mannitol, sodium starch glycolate, potassium bicarbonate,
and magnesium stearate.
        7
            A Paragraph IV certification “is defined as an
act of infringement for litigation purposes.” Sanofi-
Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1078 (Fed. Cir.
2008); see 21 U.S.C. § 355(j)(2)(A)(vii)(IV); 35 U.S.C. §
271(e).
CEPHALON   v. WATSON PHARMA                                   8

Complaint filed on September 25, 2009, asserting U.S.
Patent No. 6,264,981 (“the ’981 patent”). The two actions
were consolidated, and the district court held a bench trial
between May 10 and May 17, 2010. 8
    In an opinion issued on March 11, 2011, the district
court concluded that Cephalon did not prove, by a pre-
ponderance of the evidence, that Watson’s ANDA products
infringe either of the Khankari patents under the district
court’s claim construction. Cephalon, 769 F. Supp. 2d at
761. The district court also held that Watson proved, by
clear and convincing evidence, that the Khankari patents
were invalid for lack of enablement. Id. Further, the
district court determined that Watson failed to show that
the asserted patents were invalid as anticipated or obvi-
ous in view of prior art. Id. Cephalon timely appeals.
This court has jurisdiction under 28 U.S.C. § 1295(a)(1).
                              II.
     Cephalon raises the following issues on appeal: (1)
whether the district court erred in ruling that Watson had
carried its burden of proving by clear and convincing
evidence that the asserted patents were invalid for lack of
enablement; and (2) whether the district court erred in
failing to consider Cephalon’s literal infringement conten-
tions and ruling that Watson does not infringe the assert-
ed claims. This court addresses these issues seriatim.
     A. The District Court Committed Error in Holding
   That the Khankari Patents Were Invalid for Lack of
                      Enablement
    Enablement is a question of law that we review with-
out deference, based on underlying factual inquiries that
we review for clear error. MagSil Corp. v. Hitachi Global
Storage Techs., Inc., 687 F.3d 1377, 1380 (Fed. Cir. 2012).

       8
            The ’981 patent is not at issue in this appeal.
9                               CEPHALON   v. WATSON PHARMA

To satisfy section 112 of the 1952 Patent Act, the specifi-
cation must enable a person of ordinary skill in the art to
make and use the invention. 35 U.S.C. § 112, ¶1. 9 This
requirement is met when at the time of filing the applica-
tion one skilled in the art, having read the specification,
could practice the invention without “undue experimenta-
tion.” In re Wands, 858 F.2d 731, 736–37 (Fed. Cir. 1988).
Whether undue experimentation is required “is not a
single, simple factual determination, but rather is a
conclusion reached by weighing many factual considera-
tions.” ALZA Corp. v. Andrx Pharms., LLC, 603 F.3d 935,
940 (Fed. Cir. 2010) (citing Wands, 858 F.2d at 737).
   The following factors may be considered when deter-
mining if a disclosure requires undue experimentation:
    (1) the quantity of experimentation necessary, (2)
    the amount of direction or guidance presented, (3)
    the presence or absence of working examples, (4)
    the nature of the invention, (5) the state of the
    prior art, (6) the relative skill of those in the art,
    (7) the predictability or unpredictability of the art,
    and (8) the breadth of the claims.
Wands, 858 F.2d at 737 (“Wands factors”); Enzo Biochem,
Inc. v. Calgene, Inc., 188 F.3d 1362, 1372 (Fed. Cir. 1999)
(“The Wands factors, when applied from the proper tem-
poral perspective . . . are a useful methodology for deter-
mining enablement . . . .”).          These factors while
illustrative are not mandatory. Enzo Biochem, Inc., 188
F.3d at 1371. What is relevant depends on the facts, and
although experimentation must not be undue, a reasona-

        9
            Paragraph 1 of 35 U.S.C. § 112 was replaced
with newly designated § 112(a) when § 4(c) of the Leahy–
Smith America Invents Act, Pub. L. No. 112–29, took
effect on September 16, 2012. Because this case was filed
before that date, we will refer to the pre-AIA version of §
112.
CEPHALON   v. WATSON PHARMA                             10

ble amount of routine experimentation required to prac-
tice a claimed invention does not violate the enablement
requirement. Id. The burden of proof here is on Watson to
show that the Khankari patents are invalid for lack of
enablement by clear and convincing evidence. See Auto.
Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274,
1281 (Fed. Cir. 2007).
    The district court construed “effervescent agent” as
recited in claim 1 of both Khankari patents to require, in
part, “at least one compound that evolves gas by means of
an effervescent reaction.” Cephalon, 769 F. Supp. 2d at
744 (emphasis added). In particular, the district court
acknowledged the “singularity” of the term “agent” and
concluded that “effervescent agent” referred to a single
compound. Id. at 743–44. Watson argued against this
construction contending that the asserted patents de-
scribe “effervescent agent” synonymously with “efferves-
cent couple.” Id. at 737. Focusing on “couple,” Watson
posited that “effervescent agent” therefore requires a
combination of two or more compounds that evolve gas.
Id. While the parties do not appeal the district court’s
claim construction, contentions surrounding the distinc-
tion between effervescent “agent” and “couple” persist.
    Specific to the enablement inquiry, the parties do not
dispute that the Khankari patents are enabling as to an
effervescent “couple” generating the claimed effervescent
reaction, where the soluble acid source and the efferves-
cent agent (carbonate source) are in the same tablet or
other dosage form. Instead, the dispute arises from the
district court’s claim construction requiring effervescent
“agent” to be “at least one compound” that evolves gas.
This “single compound effervescent agent” construction
requires the soluble acid source to be in a separate tablet
or dosage form from the effervescent agent. In addition,
in order to achieve the claimed effervescent reaction, this
11                             CEPHALON   v. WATSON PHARMA

construction requires these separate dosage forms to be
co-administered.
    The district court held that the Khankari patents
lacked enabling disclosures illustrating a dosage form
having only the single compound effervescent agent.
Cephalon, 769 F. Supp. 2d at 753–54. Specifically, it held
that the disclosures lacked teachings directed to formulat-
ing and co-administering two separate dosage forms—one
including a soluble acid source and the other containing
the effervescent agent—to achieve an effervescent reac-
tion. Id. at 753. The lack of disclosure of such methods of
co-administration would, according to the court, necessi-
tate undue experimentation to practice the invention. Id.
    Cephalon on appeal contends that its expert, Dr. Rob-
ert O. Williams, testified that a skilled artisan could
easily calculate the required amount of acid and co-
administer a soluble acid source, which may be a separate
tablet, a film, or a liquid, with the tablet containing the
effervescent agent. Likewise, Cephalon argues that the
Khankari patents describe multiple embodiments using
effervescent formulations for fentanyl citrate along with
different amounts of sodium carbonate. According to
Cephalon, the specification also discloses many different
soluble acid sources and many different sources of car-
bonate, which can be combined into a nearly limitless
number of acid/carbonate pairs that would generate the
desired effervescent reaction. Indeed, Cephalon pro-
pounds Dr. Williams’s testimony that “it would be routine
given what’s in the patent[s] about how to actually create
the effervescence to use in the invention.” J.A. 6424,
1383:20–22.
    Watson argues that the district court properly consid-
ered all the evidence and credited its expert, Dr. Russell
Mumper. In addition, Watson contends the Khankari
patents do not provide specific parameters to conduct
CEPHALON   v. WATSON PHARMA                              12

experiments to calculate a method of co-administration
and that Cephalon failed to produce evidence showing a
successful co-administration method. Specifically, accord-
ing to Watson, Cephalon should have produced evidence
showing a successful effervescent reaction in the same
area of the mouth between two co-administered tablets
containing the acid and base compounds.
    As an initial matter, the district court determined
that Watson established a “prima facie” case of lack of
enablement and that Cephalon failed to “rebut” Watson’s
prima facie case. Cephalon, 769 F. Supp. 2d at 751, 754.
Actually, the burden of proof was Watson’s alone. Be-
cause we must presume a patent enabled, the challenger
bears the burden, throughout the litigation, of proving
lack of enablement by clear and convincing evidence.
Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464,
1469–70 (Fed. Cir. 1993). Hence, there is no formal
burden-shifting framework when addressing the issue of
enablement. Accordingly, we examine whether Watson
met its burden of proof and determine that it did not.
     Watson’s evidence on enablement was based heavily
on Dr. Mumper’s testimony. Dr. Mumper stated that
“formulation of fentanyl with some couple in a tablet that
would be administered into the mouth and must react
with some externally applied acid . . . would be very
difficult” and “complicated” and “would require I think the
partnering with a clinician to talk about the timing effects
and volume effects and how this would actually be trans-
lated to a patient actually doing this. I don’t know.” J.A.
6337–38, 1184:17–1186:19.        Dr. Mumper’s ipse dixit
statements that co-administration would be “difficult” and
“complicated,” however, cannot be enough to constitute
clear and convincing evidence. See Ashland Oil, Inc. v.
Delta Resins & Refractories, Inc., 776 F.2d 281, 294 (Fed.
Cir. 1985) (“Lack of factual support for expert opinion
going to factual determinations, however, may render the
13                              CEPHALON   v. WATSON PHARMA

testimony of little probative value in a validity determina-
tion.”). Despite the district court’s finding according
credibility to Dr. Mumper, his testimony is largely unsup-
ported, and therefore, carries little weight in this analy-
sis.
    The district court’s reliance on Cephalon’s expert tes-
timony does not rescue Dr. Mumper’s unsubstantiated
statements. Referring to inventor testimony regarding
“drinking orange juice [as the soluble acid source] follow-
ing administration of a[n effervescent agent],” Dr. Wil-
liams testified:
     I think one of skill in the art, knowing in that ex-
     ample orange juice contains citric acid, would be
     able to calculate the amount of citric acid and put
     . . . [an effervescent agent] in a second, fast-
     dissolve film or quick-dissolve tablet or something,
     to do a concomitant administration of [the] two
     dosage forms . . . .
J.A. 6424, 1383:1–2, 5–10. He further posited that creat-
ing an effervescent reaction by co-administering the two
dosage forms would require “routine” experimentation.
J.A. 6424, 1383:20–22. On cross examination, Dr. Wil-
liams explained the potential need for in vitro experi-
ments and a formulator to work with a clinician to
determine the parameters for co-administering a soluble
acid source with an effervescent agent. J.A. 6424–25,
1384:25–1385:7. According to the district court, Dr.
Williams’s testimony regarding the potential need for
experiments provided additional support for Dr.
Mumper’s opinion that undue experimentation was
required. Cephalon, 769 F. Supp. 2d at 753. The district
court’s emphasis on the mere fact that experimentation
may be necessary is misplaced, however.
   The question of undue experimentation is a matter of
degree, and what is required is that the amount of exper-
CEPHALON   v. WATSON PHARMA                                  14

imentation not be “unduly extensive.” Chiron Corp. v.
Genentech, Inc., 363 F.3d 1247, 1253 (Fed. Cir. 2004)
(quoting PPG Indus., Inc. v. Guardian Indus., Corp., 75
F.3d 1558, 1564 (Fed. Cir. 1996)). For example, the fact
that a clinician’s involvement may be necessary to deter-
mine effective amounts of the single compound efferves-
cent agent and its corresponding soluble acid source does
not itself constitute undue experimentation. See Ortho-
McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F.3d 1358,
1365–66 (Fed. Cir. 2008) (“[E]ven if clinical trials in-
formed the anticonvulsively effective amount, this record
does not show that extensive or ‘undue’ tests would be
required to practice the invention.”). In addition, exten-
sive experimentation does not necessarily render the
experiments unduly extensive where the experiments
involve repetition of known or commonly used techniques.
See Johns Hopkins Univ. v. CellPro, Inc., 152 F.3d 1342,
1360 (Fed. Cir. 1998) (finding that the difficulty in pro-
ducing certain antibodies could not be attributed to the
shortcomings in the disclosure of the patent at issue, but
rather, the difficulty was attributed to the technique
commonly used during experimentation that generally
required repetition). Thus, the focus “is not merely quan-
titative, since a considerable amount of experimentation
is permissible, if it is merely routine, or if the specification
in question provides a reasonable amount of guidance . . .
.” PPG Indus., Inc., 75 F.3d at 1564 (citation and quota-
tion omitted).
    Permissible experimentation is, nevertheless, not
without bounds. This court has held that experimenta-
tion was unreasonable, for example, where it was found
that eighteen months to two years’ work was required to
practice the patented invention. See, e.g., White Consol.
Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791
(Fed. Cir. 1983). Likewise, we have held that the amount
of experimentation would be undue where: (1) the specifi-
15                              CEPHALON   v. WATSON PHARMA

cation lacks guidance by teaching away from the subject
matter that was eventually claimed; and (2) there is
evidence of the patentee’s own failures to make and use
the later claimed invention at the time of the application.
See, e.g., AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244
(Fed. Cir. 2003). Hence, the mere potential need for
clinical work, without more, is not dispositive in this case.
    Rather, Watson had the burden to show by way of tes-
timony or documentary evidence the amount of experi-
mentation needed to calculate a formulation for co-
administering a soluble acid source in one form of dosage
with a carbonate source in another form to achieve the
claimed effervescent reaction. See Moba, B.V. v. Diamond
Automation, Inc., 325 F.3d 1306, 1321 (Fed. Cir. 2003)
(finding that there was no record evidence recounting the
amount of experimentation one of skill in the art would
require to develop the claimed invention based on the
patent’s disclosure). As Cephalon avers, the Khankari
patents describe multiple embodiments using effervescent
formulations for fentanyl citrate (acid) alongside different
amounts of sodium carbonate (base). Nonetheless, Wat-
son has not presented evidence showing why these formu-
lations for a “couple” do not provide sufficient guidance for
a skilled artisan to calculate formulations for single
compound effervescent agents. See United States v. Telec-
tronics, Inc., 857 F.2d 778, 786 (Fed. Cir. 1988) (“Since
one embodiment is admittedly disclosed in the specifica-
tion, along with the general manner in which its current
range was ascertained, we are convinced that other per-
mutations of the invention could be practiced by those
skilled in the art without undue experimentation.”). Nor
does Watson show that the resulting experimentation in
this case would be excessive, e.g., that it would involve
testing for an unreasonable length of time. See White
Consol. Indus., Inc., 713 F.2d at 791. Unsubstantiated
statements indicating that experimentation would be
CEPHALON     v. WATSON PHARMA                             16

“difficult” and “complicated” are not sufficient. In light of
the lack of evidence on the record of undue experimenta-
tion, the district court erred as a matter of law in holding
that Watson proved its case on enablement by clear and
convincing evidence. 10
     Watson had the burden of proof to show that the
Khankari patents lacked enabling disclosures. Watson
failed to carry its burden. 11 The evidence on the record
does not sufficiently show that the experimentation

        10
             The district court also predicated its decision
on the inventors’ testimony that they could not “name any
single-compound effervescent on the stand” and that they
were “only in possession of a method for creating efferves-
cence using a formulation containing both an acid and a
base.” Cephalon, 769 F. Supp. 2d at 751. These state-
ments nevertheless do not contradict the fact that the
record lacks evidence directed to whether the experimen-
tation necessary would be unduly extensive. Accordingly,
they carry little probative value here.
         11
             The district court focused on the evidence
Watson presented on enablement—Dr. Mumper’s testi-
mony. As the district court acknowledged, Dr. “Mumper
did not specifically analyze many of the Wands factors at
trial.” Cephalon, 769 F. Supp. 2d at 752 n. 29. Rather, Dr.
Mumper’s testimony was limited to the opinion that the
necessary experimentation would be “difficult” and “com-
plicated.” Nevertheless, the district court mentions that
“there is no genuine question as to the lack of direction or
guidance (on co-administration) in the patent or the
absence of working examples (factors 2 and 3).” Id. The
district court also states that “[t]he nature of the inven-
tion, state of the art, relative skill in the art and claim
scope (factors 4 to 7) were addressed by Watson within
the context of its obviousness arguments and Markman
briefing.” Id. Although analysis of the Wands factors is
instructive, the district court’s cursory consideration of
these factors is not dispositive in this case. Even assum-
ing the district court’s findings were accurate, the record
still lacks evidence of undue experimentation.
17                             CEPHALON   v. WATSON PHARMA

necessary to co-administer a soluble acid source with a
single compound effervescent agent would be unduly
extensive. Thus, we reverse the district court’s nonena-
blement determination.
     B. The District Court Did Not Clearly Err in Finding
        Noninfringement of the Khankari Patents
    Infringement is a question of fact that, after a bench
trial, we review for clear error. Alza Corp. v. Mylan Labs.,
Inc., 464 F.3d 1286, 1289 (Fed. Cir. 2006). A factual
finding is clearly erroneous when, despite some support-
ing evidence, we are left with a definite and firm convic-
tion that the district court was in error. Id. To prove
infringement, the patentee must show that an accused
product embodies all limitations of the claim either liter-
ally or by the doctrine of equivalents. TIP Sys., LLC v.
Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1379
(Fed. Cir. 2008); see also Tech. Licensing Corp. v. Vide-
otek, Inc., 545 F.3d 1316, 1327 (Fed. Cir. 2008) (stating
that, to prove infringement, the patentee has the burden
of persuasion by a preponderance of the evidence). If any
claim limitation is absent from the accused device, there
is no literal infringement as a matter of law. TIP Sys., 529
F.3d at 1379.
    To support a finding of infringement under the doc-
trine of equivalents, a patentee must provide particular-
ized testimony and linking argument with respect to the
“function, way, result” test. Tex. Instruments Inc. v.
Cypress Semiconductor Corp., 90 F.3d 1558, 1566–67
(Fed. Cir. 1996). The “essential inquiry” in any determi-
nation under the equivalents doctrine is whether “the
accused product or process contain[s] elements identical
or equivalent to each claimed element of the patented
invention.” Warner-Jenkinson Co., Inc. v. Hilton Davis
Chem. Co., 520 U.S. 17, 40 (1997). We have assessed the
insubstantiality of an alleged equivalent by applying the
CEPHALON   v. WATSON PHARMA                               18

function-way-result test as set forth in Union Paper–Bag
Machine Co. v. Murphy, 97 U.S. 120, 125 (1877), which
asks whether an element of an accused product “performs
substantially the same function in substantially the same
way to obtain the same result” as an element of the pa-
tented invention. See, e.g., TIP Sys., 529 F.3d at 1376.
     With respect to the disputed limitation, “at least one
[saliva activated] effervescent agent in an amount suffi-
cient to increase absorption . . . across [the] oral mucosa,”
the district court found Cephalon failed to prove that
Watson’s ANDA products meet this limitation. Cephalon,
769 F. Supp. 2d at 748 (brackets in original). Significant-
ly, the district court’s construction of this limitation
required that the effervescent agent is “saliva activated,”
and the parties’ dispute centered on whether potassium
bicarbonate and mannitol in the ANDA products reacted
to generate an effervescent reaction. Id. at 743, 748. In
particular, the district court noted that Cephalon’s expert,
Dr. Bernard Olsen, testified that he conducted pH exper-
iments on the ANDA products and found mannitol to be
acidic in water; the more concentrated the mannitol, the
more acidic the solution. Id. at 748. The district court
however found that Cephalon presented no evidence
regarding the acidity of mannitol in artificial saliva—that
there is no evidence of record regarding the properties of
human saliva and how, for example, mannitol may react
in it. Id.
    Cephalon argues that it focused on water and not sa-
liva because the Khankari patents explicitly state that
the preferred effervescent agents evolve gas upon expo-
sure to water and/or to saliva. Cephalon also argues that
at various points during the course of litigation Watson
represented that the reaction required of the effervescent
agent may occur in either saliva or in water. The district
court nevertheless credited Dr. Mumper, Watson’s expert,
who concluded that:
19                               CEPHALON   v. WATSON PHARMA

     I looked at Dr. Olsen’s data of mannitol in water
     where he showed that increasing concentrations of
     mannitol in water led to a correspondingly de-
     crease in pH. And I think the important point
     that I’ll make on here is that . . . it’s in water.
     And so what Dr. Olsen has showed is that manni-
     tol is acidic in water; and Dr. Williams asserts
     that mannitol is therefore the acidic agent and is
     reacting with potassium bicarbonate. I think the
     important piece of information that is missing [in
     this case] is what the potential or alleged acidity
     of mannitol in either artificial saliva or, even more
     important, in the human mouth . . . and there is
     no evidence that mannitol would be acidic under
     those conditions.”
J.A. 6335, 1174:1–16. Cephalon does not dispute this fact,
and we find no clear error in the district court’s finding of
noninfringement based on Watson’s expert testimony.
Therefore, Cephalon has failed to prove that this limita-
tion is practiced by the ANDA product, either literally or
under the doctrine of equivalents. Because Cephalon has
failed to prove the ANDA products infringe the “at least
one [saliva activated] effervescent agent . . .” limitation,
we need not discuss the remaining disputed limitations.
Accordingly, the district court’s noninfringement finding
is affirmed.
                             III.
    Because this court concludes that Watson failed to
prove by clear and convincing evidence that the Khankari
patents—covering a dosage form having a single com-
pound effervescent agent—were invalid for lack enable-
ment, we reverse that portion of the district court’s
decision. As to the district court’s finding of noninfringe-
ment, we affirm.
 REVERSED–IN–PART and AFFIRMED–IN–PART
CEPHALON   v. WATSON PHARMA            20

Each party shall bear its own costs.