# United States Court of Appeals **for the Federal Circuit**

__________________________ CEPHALON, INC. AND CIMA LABS , INC., Plaintiffs -A ppellant s,

v.
WATSON PHARMACEUTICA LS, 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

___________________________ C AROLYN J ACOBS C HACHKIN , Wilmer Cutler Pickering Hale and Dorr, LLP, of Washington, DC, argued for plaintiffs

- appellants. With her on the brief were W ILLIAM G. M C E LWAIN and J ACOB S. O YLE ; and W ILLIAM F. L EE and M ARK C. F LEMING , of Boston, Massachusetts.

J AMES K. S TRONSKI , Crowell & Moring, LLP, of New York, New York, argued for defendants

- appellees. WithCEPHALON v. WATSON PHARMA 2

him on the brief were C HIEMI D. S UZUKI and J ACOB Z. Z AMBRZYCKI

.

__________________________

Before R EYNA , B RYSON , ∗ and W ALLACH , Circuit Judges

. W ALLACH , Circuit Judge

. This action arises out of the filing of an Abbrevi ated New Drug Ap plication (“ANDA”) by Watson Pharm aceut icals, Inc., Watson Labora to ries, Inc., and Watson Pharma, Inc. ( collectively, “Watson”) for a generic version of FENTORA ®. In re sponse to Watson’s ANDA filing, Cephalon, Inc. and CIMA Labs, Inc. (collectively, “Ceph alon” ) 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, t he district court found that Watson’s ANDA products did not infringe and held the asserted patents invalid for lack of enablemen t. Cephalon, Inc. v. Watson Pharms., Inc.

, 769 F. Supp. 2d 729, 761 (D. Del. 2011). We reverse on the issue of enablement because Wa tson failed as a matter of law to show with clear and convincing evidence that Cephalon’s patents require undue experim entation to practice the invention

. As to the noni n fringement 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” ) ge nerally relate to a method of drug delivery

. The most common method of d rug delivery occurs through the

∗ Judge Bryson assumed senior status on Jan uary 7, 2013.CEPHALON v. WATSON PHARMA 3

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.

O ral mucosal drug delivery offers advantages

. For i nstance, t he oral mucosal route provide s direct access to the bloodstream without having to travel through the gast ro intestinal tract, which allows the drug to avo id the “first pass effect ”—t he percentage of drug lost to metab olization 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

T he Khankari patents 1 disclo se methods to admini ster a tablet ( or other dosage form ) comprising fentanyl 2 or other pharmaceutical agents . Such tablets include effe rvescent agent s used as penetration enhancers , which influence drug absorption across t he buccal, su blingual

, and gingival mucosa e. 3 ’590 patent col. 2 ll. 13

– 15

. The Khankari patents also disclose t he use of an additional pH adjusting s ubstance in combination with an effervescent agent for promoting the absorption of drugs

. Id. col. 3 ll. 18

– 20.

1 The inventors of the Khankari patents are as fo l lows: Drs. Sathasivan Indiran Pather

, Rajentra K. Khankari

, Jonathan D. Eichman, Joseph R. Robinson, and John Hontz. 2 Fentanyl is an opioi d 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 diffe rent 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 co mpound that evolve s gas. Id. col. 2 ll. 44

– 45. The pref erred effervescent agent s evolve gas by mea ns 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 oft en the result of a soluble ac id 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 effervesc ent 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 a ffect s t he pH level of the saliva

. Generally, pH levels ca n influenc e 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 efferv escent agent has dissolved is slightly acidic due to the evolution of carbon dioxide. Id. col. 3 ll. 24

– 25. Specifically , when carbon dioxide di ssolves in saliva, it forms a weak acid (carbonic aci d) that reduces salival pH. The carbonic acid there after dissoc iates 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 saf e for human consumption and generally include food acids, acid

, and hydrite antacids such as: citric, tartaric, ama lic, fumeric, adipic, and succinics. ’590 patent col. 2 ll. 56

- 60. Carbonate sources include dry solid carbonate and bica rbonate salt such as, preferably, sodium bicarbonate, sodium carbonate, potassium bicarbonate

, potassium carbonate, magnesium carbonat e, and the like. Id. col. 2 ll. 60

– 64. Reactants which evolve oxygen or other gasses and which are safe for h u man consumption are also included. Id. col. 2 ll. 64

– 65.CEPHALON v. WATSON PHARMA 5

for the initial low pH level suitable for dissolution and the eventual high pH level ideal for absorption

. Thus, inco rporating a pH a djusting 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, s uitable pH

adjusting substances include, but are not limit ed to, a ny of the acids or bases disclosed as effervescent compounds. Id. col. 3 ll. 47

– 55. Other pharmaceutical ingredients are prefer ably i ncorporated into the dosage form of the inven tion for a variety of p urposes, including aiding disin tegration. “D isintegrants may comprise up to about 20 weight percent” of the composition and, preferably, between 2% and 10% o f the composition. Id. col. 4 ll. 41

– 51

. “[S]uitable non

- efferv escent disintegra ti on agents” may be used. Id. col. 4 l. 43. Excipient fillers “de sirably 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) examp les 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 prio rity to the ’604 patent’s applicati on, and as a result, the patents share a common disclosure.

Claim 1 of the ’ 604 patent is the sole inde pendent claim of that patent, and reads as follows :
1. A method of adm inistering at least one system ically distributable pharmaceutical agent across the oral mucosa comprising:
a) providing a solid oral dosage form inclu d ing a pharmaceutically effective amount of an orallyCEPHALON v. WATSON PHARMA 6

administerable medicament; and at least one effervescent agent in an amount sufficient to i ncrease absorption of said orally administe rable medicament across the oral mucosa ; wherein said orally administerable medicament is not substa ntially enco m passed by or dispersed in a material that prevents absorption of said med icament across the oral mucosa;
b) placing said solid oral dosage for m in the mouth of a patient so that saliva in said p a tient’ s mouth activates said at least one efferve scent agent in said tablet; and
c) holding said solid oral dosage form and the di ssolving contents of said solid oral dosage form in the mouth of a patie nt whereby said at least one effervescent agent promotes absorption of said orally administerable m e dicament 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 a s follows:
1. A method of administration of fentanyl to a mammal across the oral mucosa t hereof, said method comprising:
providing a solid oral dosage form comprising fe ntanyl or a pharmaceutically acceptab le salt ther eof and at least one saliva activated effervescent agent in an amount sufficient to increase absorption of said fentanyl or pharmaceutically accept able 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% byCEPHALON v. WATSON PHARMA 7

weight; and buccally, sub lingually or gingivally admini s trating said solid oral dosage form to said mammal.
’590 patent col. 7 ll. 2

– 13 (emphasis added)

. C. Pro cedural 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 Or ange Book in connection with this New Drug Applic ation. See 21 U.S.C. § 355(b)(1). On July 10 , 2007, Watson filed an ANDA for FDA approval to sell a generic counte rpa rt 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 marketin g the drug. 7
In response, o n June 2, 2008, Cephalon instituted the underl ying action in district court against Watson, firs t asserting the Khankari patents, and in a subsequent

5 FENTORA® contains fentanyl citrate, mann itol, s o dium starch glycolate, magenesium ste arate, 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 ingr e dient fentanyl citrate and the inactive ingredients

mann i tol, sodium starch glycolate, potassium bicarb onate, and ma g nesium 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

C omplaint 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 Ce phalon did not prove , by a pr eponderan ce of the evidence, that Watson’ s AND A product s infringe either of the Khankari patent s under the district court’ s claim construct ion. Cephalon , 769 F. Supp. 2d at 761. The district court also held that Watson proved , by clear and convincing evidence, that the Khan kari 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 obv ious in view of prior art. Id. Cephalon timely appeals. This court has ju risdiction under 28 U.S.C. § 1295(a)(1).

II.
Cephalon raises the f ollowing issues on appeal: (1)

w hether the district court erred in ruling that Watson had carried its burden of proving by clear and convincing evidence that the asserted patents were inva lid for lack of enablement ; and (2) w hether the district court erred in failing to consider Cepha lon’s literal infringement conte ntions and ruling that Watson does not infringe the asser ted claims. Th is court addresses these issues seriatim.

A. The District Court Committed Error in Holding T hat the Khankari Patents Were Invalid for Lack of Enablement

Enablement is a question of law that we review wit hout deference , based on underlying factual inquiries that we review for clear error. MagSil Corp. v. H itachi Global Storage Techs., Inc. , 687 F.3d 1377, 1380 (Fed. Cir. 2012).

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

To satisfy section 112 of the 1952 Patent Act, the specification must enable a person of ordinary skill in the art to make and use the invention. 35 U.S.C. § 112, ¶ 1. 9 This require ment is met when at the time of filing the applic ation one skilled in the art, having read the specif i cation, could practice the invention without “undue experiment ation.” In re Wands , 858 F. 2d 731, 736

– 37 (Fed. Cir. 1988). Whether undue experimentation i s required “is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual consider ations.” ALZA Corp. v. Andrx Pharms., LLC , 603 F.3d 935, 940 (Fed. Cir. 2010) (citing Wands , 858 F.2d at 737).

T he following fa ctors may be considered when dete rmining if a disclosure requires undue experimentation:
(1) the quantity of experimentation nece s sary, (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 pr e dictability 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 te mporal perspective . . . are a useful methodology for dete rmining enablement . . . .”). These factors while illustr a tive are not mandatory

. Enzo Biochem, Inc. , 188 F.3d at 1371

. What is relevant depends on the facts, and al t hough experimentation must not be undue, a reason a9 Paragraph 1 of 35 U.S.C . § 112 was replace d with newly designated § 112(a ) when § 4(c) of the Leahy

– Smith Ame rica 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 pra ctice a claimed invention does not violate the enabl e ment

re quirement. Id. The burden of p roo f 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).

T he district court construed “ef ferves cent 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 acknowledge d 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 d escribe “effervescent agent” synonymously with “eff erve scent couple

. ” Id. at 737

. Focusing on “couple,” Watson posited that “effervescent agent” therefore require s a combination of two or more compounds that evolve gas. Id

. While t he parties do not appeal the district court’s claim construction

, contenti ons surrounding the distin ction 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 claim ed effervescent

re action, where the soluble acid source and the efferve scent 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 co mpound ” 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, t hisCEPHALON v. WATSON PHARMA 11

construction re quires t hese separate dosage forms to be

co

- administered.

T he district court held that the Khankari patents lacked enabling disclosure s illustrating a dosage form having only the single compound effervescent agent. Cephalon , 769 F. Supp. 2d at 753

– 54. Specifically , it held that the d isclosures lacked teachings directed to formula ting and co

- administ ering two separate dosage forms —one including a soluble acid source and the other containing the effervescent agent

— to achieve an effervesce nt rea ction. Id. at 753. The lack of disclosure of s uch method s of

co

- administration would

, ac cording to the court, necess itate undue experimentation to practice the invention. Id.
Cephalon on appeal contends that its expert, Dr. Ro bert O. Williams, test i fied 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 table t con taining the effervescent agent. Likewise, Cephalon argues that the Khankari patents describe multiple embodiments using effervescent for mulations for fentanyl citrate along with different amounts of sodium carbon ate. According to Cephalon, the specification also discloses many different soluble acid sources and many different sources of ca rbonate, which can be combined into a nearly limitless number of acid/carbonate pairs that would generate the desired effervescent reaction. Indeed, Cephalon pr opounds 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 considered all the evidence and credi ted its expert, Dr. Ru s sell Mumper. In addition, Watson co ntends the Khankari patents do not provide specific parameters to conductCEPHALON v. WATSON PHARMA 12

experiments to calculat e a method of co

- administration and tha t Cephalon failed to produce evidence showing a successful co

- administration method

. Specifically, accor ding to Watson, Cephalon should have produced evidence showing a successful effervescen t 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 est ablished 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. Because we must presume a patent enabled, the chal lenger 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, 14 69

– 70 (Fed. Cir. 199 3). Hence, there is no formal burden

- shifting framework when a ddressing 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 fentany l 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 e ffects and volume effects and how this would actually be tran slated to a pat i ent actual ly 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. S ee 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 theCEPHALON v. WATSON PHARMA 13

testimony of little probative value in a validity determin ation.”). Despite the district court’s finding accor ding credibility to Dr. Mumper

, his testimony is largely unsu pported , and therefore

, carries little weight in this anal ysis

. T he district cou rt ’s reliance on Cephalon’s expert te stimony does not rescue Dr. Mumper’s unsubstantiated
statements. Referring to inventor testimony regarding “drinking orange juice [as the soluble acid source] follo wing administration of a[n effervescent agent],” Dr. W i lliams testified:
I think one of skill in the art, knowing in that e xample orange juice contains citric acid, would be able to calculate the amoun t of citric acid and put . . . [an effervescent agent] in a second, fast

dissolve film or quick

- dissolve tabl et or something, to do a con comitant administration of [the] two dosage forms . . . .
J.A. 6424, 1383: 1– 2, 5– 10. He further posited that crea ting an effe rvescent reaction by co

- administering the two dosage forms would require “routine” experimentation. J .A. 6424, 1383:20

– 22. On cross examination, Dr. Wi lliams explained the potential need for in vitro exper iments and a formulator to work with a clinician to dete r mine 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 undu e experimentation was required. Cephalon , 769 F. Supp. 2d at 75 3. T he district court’s emphasis on the mere fact that experimentation

may b e necessary is misplaced , however.

T he question of undue experimentation is a matter of degree, and what is required is that the amount of expe r-CEPHALON v. WATSON PHARMA 14

imentation not be “unduly extensiv e.” 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 dete rmine effective amounts of the single compound efferve scent 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 clinica l trials i nformed the anticonvulsively effective amount, this record d oes not show that extensive or ‘ un due’ tests would be required to practice the invention.”). In addition, exte nsive experimentation do es not necessarily render the experiments unduly ex tensive 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 pr oducing certain antibodies could not be attributed to th e shortcomings in the disclosure of the patent at issue, but rather, the difficulty was attributed to the technique commonly used during experimentation that g enerally required repetition). Thus, t he focus “is not merely qua ntitative

, 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 quot ation omitted)

. P ermissible experimentation is

, nevertheless, not without bounds. This court has held that experiment ation 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 specif i-CEPHALON v. WATSON PHARMA 15

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 , wit hout more, is not dispositive in this case

. Rather

, Wa tson had the burden to show by way of te stimony or documentary evidence the amount of exper imentation needed to calculate a formulation for co

administering a soluble acid source in one form of dosage

w ith 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) along side different

amoun ts of sodium carbonate (base). Nonetheless

, Wa tson has not presented evidence showing why the se form ulations for a “couple” do not provide sufficient guidance f or a skilled artisan to calculate formulations for single compound effervescent agents. See Uni ted States v. Tele ctronics, Inc.

, 857 F.2d 778, 786 (Fed. Cir. 1988) (“Since one embodiment is admittedly disclosed in the specific ation, along with the general manner in which its current range was ascertained, we are convinced that other pe rmutations of the invention could be practiced by those skilled in the art without undue experimentation.”). N or does Watson show that the resultin g 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 experiment ation would beCEPHALON v. WATSON PHARMA 16

“difficult” and “complicated” are not sufficient. In light of
t he lack of evidence on the record of undue experiment ation

, the district court erred as a matter of law in holdin g 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 lack ed enabling disclosures. Watson failed to carry its burden

. 11 Th e 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 efferve scence using a formulation containing both an acid and a base .” Cephalon , 769 F. Supp. 2d at 751. These stat ements nevertheless do not contradict t he fact that the record lacks evidence directed to whether the experime ntation 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. Mump er’s test imony. As the district court acknowledged, Dr. “Mumper did not specif i cally analyze many of the Wands factors at trial.” Cephalon , 769 F. Supp. 2d at 752 n. 29. Rather, Dr. Mumper’s test i mony was limited to the opinion that the necessary experim entation would be “difficult” and “co mplicated.” 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 inve ntion, state of the art, relative skill in the art and claim scope (factors 4 to 7) were a d dressed by Watson within the context of its obviousness arguments and Markman briefing.” Id. Al though analysis of the Wands factors is instructive, the district court’s cursory consideration of these factors is not dispositive in this case. Even assu ming the district court’s findings were accurate, the record still lacks evidence of undue experimen tation.CEPHALON v. WATSON PHARMA 17

necessary to co

- administer a soluble acid source with a sin gle compound effervescent agent would be unduly extensive. Thus, we reverse the district court’s nonen ablement determin ation.

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 suppor ting evidence, we are left with a definite and firm convi ction 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 eith er lite rally or by the doctrine of e qu ivalents

. TIP Sys., LLC v. Phillips & Brooks/Gladwin, Inc. , 529 F.3d 1364, 1379 (Fed. Cir. 2008); see also Tech. Licensing Corp. v. Vid eotek, 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 137 9. To support a finding of infringement under the do ctrine of equivalents, a patentee must provide particula rized 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 determ ination 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.” Warne r- 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 theCEPHALON 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 p atented 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 sufficient to increase absorption . . . across [the] oral mucosa ,” the district court found Cephalon failed to prove that Watson’s ANDA product s meet this limitation. Cephalon

, 769 F. Supp. 2d at 748 (brackets in original)

. Significan tly, the district court’s construction of this limitation required that the efferves cent agent is “saliva activated, ” and the parties’ dispute centered on whether potassium bicarbonate and man nitol 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 expe riments 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 Cephalo n 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 s aliva because the Kh ankari patents explicitly state that the preferred effervescent agents evolve gas upon exp osure to water and/or to saliva. C ephalon 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 neverthe less credited Dr. Mumper, Watson’s expert

, who concluded that :CEPHALON v. WATSON PHARMA 19

I looked at Dr. Olsen’s data of mannitol in water where he showed that increasing co n centrations of mannitol in water led to a correspondingly d ecrease in pH. And I think the important point
t hat I’ll make on here is that . . . it’s in water. And so what Dr. Olsen has showed is that mann itol is acidic in water; and Dr. Williams asserts that mannitol is therefore the acidic agent and is reacting with potassium bicarbonate. I think the im portan t 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 mou th . . . and there is no evidence that mannitol would be acidic under those cond i tions.”
J.A. 6335, 1174:1

– 16. Cephalon does not disput e this fact, and we find no clear error in the district court’s finding of

no n infringemen t based on Watson’s expert testimony

. Therefore, Cephalon has failed to prove that this limit ation is practiced by the ANDA product , either literally or unde r 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 di sputed limitations

. Accordingly, the district cour t’s noninfringement finding is affirmed

. III.

Because this court concludes that Watson failed to prove by clear and convincing evidence that the Khankari patent s— covering a d osage form having a singl e co mpound effervescent agent

— were invalid for l ack enabl ement, we reverse that portion of the district court’s dec i sion. As to the district court’s finding of noninfring ement, we affirm.

REVERSED

– IN

– PART and AFFIRMED

– IN

– PARTCEPHALON v. WATSON PHARMA 20

Each party shall bear its own c osts.