Full opinion text
OPINION SUE L. ROBINSON, District Judge. I. INTRODUCTION This action arises out of the filing of an Abbreviated New Drug Application (“ANDA”) by defendants Watson Pharmaceuticals, Inc., Watson Laboratories, Inc., and Watson Pharma, Inc. (collectively, “Watson”) in 2008 for a generic version of Fentora® (fentanyl buccal tablets), used to treat breakthrough pain in cancer patients. Plaintiff CIMA Labs, Inc. (“CIMA”) is the assignee of U.S. Patent Nos. 6,200,604 (“the '604 patent”) and 6,974,590 (“the '590 patent”), directed to a sublingual buccal effervescent pharmaceutical dosage form. Plaintiff Cephalon, Inc. (“Cephalon”) is the exclusive licensee of the '604 and '590 patents (hereinafter, collectively the “Khankari patents”) and is also the owner of U.S. Patent No. 6,264,-981 (“the '981 patent”). Cephalon is the holder of an approved New Drug Application (“NDA”) for the manufacture and sale of fentanyl buccal tablets for the treatment of breakthrough cancer pain. Cephalon listed with the Food and Drug Administration (“FDA”) the '604 and '590 patents in the Orange Book in connection with its NDA. In response to Watson’s ANDA filing, which contained a paragraph IV certification as to the '604 and '590 patents, plaintiffs filed a patent infringement suit on June 2, 2008. (Civ. No. 08-330, D.I. 1) The court denied defendants’ (renewed) motion to dismiss certain counts of the complaint on April 3, 2009, 629 F.Supp.2d 338 (D.Del.2009). On September 25, 2009, plaintiffs filed a second complaint of patent infringement against defendants seeking a declaratory judgment of infringement of U.S. Patent No. 6,264,981 (“the '981 patent”), directed to a method for oral transmucosal drug delivery. (Civ. No. 09-724, D.I. 1) In both cases, defendants asserted defenses and counterclaims of noninfringement and invalidity. The two actions were consolidated for purposes of discovery and tried together in a bench trial held between May 10 and 17, 2010. (Civ. No. 09-724, D.I. 23) The issues of infringement and invalidity have been fully briefed post-trial. Having been advised that the 30-month stay on the FDA’s approval of defendants’ ANDA (triggered by plaintiffs’ first suit) expired, the court recently enjoined defendants’ launch of generic fentanyl buccal tablets pending the issuance of its decision. (Civ. No. 08-330, D.I. 157) The court has jurisdiction pursuant to 28 U.S.C. §§ 1331, 1338(a) and 1400(b). Having considered the documentary evidence and testimony, the court makes the following findings of fact and conclusions of law pursuant to Fed.R.Civ.P. 52(a). II. FINDINGS OF FACT AND CONCLUSIONS OF LAW A. The Technology at Issue 1.Drug delivery across the oral mucosa 1. There are several methods by which a drug may be delivered to the human bloodstream. In traditional oral administration, a dosage form is swallowed and drug absorption occurs across the gastrointestinal mucosa (the stomach or intestines). (D.I. 282 at 108:22-109:10) By contrast, when a drug is administered by an oral transmucosal route, the drug is absorbed across the mucous membranes of the mouth and directly into the blood stream. (Id. at 116:2-21) 2. The inventions at bar relate to oral transmucosal drug delivery. The oral mucosa are the mucous membranes lining the mouth, and include the buccal, sublingual, and gingival mucosa. (Id. at 109:17-110:10) The buccal mucosa is along the inside of the cheek; the sublingual mucosa is under the tongue; and the gingival mucosa is between the upper lip and gum. (Id.) 3. Cells in the intestinal tract, an area naturally designed for absorption, are present in a single layer lining the intestinal wall. (Id. at 114:8-115:11) Between these cells are “tight junctions,” or certain proteins that act as a gate controlling what substances may pass through the intestine into the body. (Id.) Tight junctions are generally not present in the oral mucosa, however, the oral mucosa lining comprises multiple, staggered layers of cells such that a “molecule has to take a tortuous path to get to the other end.” (Id.) The surface area for absorption of the oral mucosa is also small. (Id.) Despite these disadvantages, drug delivery across the oral mucosa offers the advantage of a faster onset of action. This is because the drug need not travel through the gastrointestinal tract and the liver prior to blood absorption, and the “first-pass effect” — a percentage of drug lost to metabolization in the liver — is avoided. (Id. at 115:14-116:21) Consequently, the same therapeutic effect can be achieved with a lower dose of drug administered across the oral mucosa. (Id.) Rapid entry of the drug into the bloodstream benefits the treatment of conditions requiring fast relief, such as breakthrough cancer pain. 4. For both the traditional oral and transmucosal routes of administration, the drug traverses the relevant mucosa and can reach the bloodstream primarily by two pathways: paracellular or transcellular. (Id. at 110:11-15.) With paracellular absorption, the drug moves between cells to reach the bloodstream. (Id. at 110:16-23) With transeellular absorption, the drug moves across the mucosa by passing through cells until reaching the bloodstream. (Id. at 110:24-111:8; 112:23-113:7) In doing so, the drug must breach the cell membrane wall. (Id. at 113:5-7) 5. Fentanyl is a lipophilic drug, meaning that it dissolves much more readily in lipid (fats and oils) than in water. (Id. at 113:13-17) Highly lipophilic compounds like fentanyl are absorbed primarily through the transcellular route. (Id. at 120:9-20; 154:10-20) Lipophilicity and, thus, the ability to absorb via the transcellular route, is increased by increasing the pH. At a higher pH, unionized (lipophilic) species of the drug are favored. (Id. at 122:2-124:7) 6. A high starting pH level is impracticable, however, because a high pH hinders the dissolution of the drug. (Id. at 124:8-16) Herein lies the formulator’s quandary; while a high pH is favored for absorption, a low pH is favored for solubility. Put in terms of ionization, when a weakly acidic or basic drug dissolves, it becomes ionized. The ionized form is hydrophilic while the dissolved, unionized form is favored for transcellular absorption. (Id. at 123:9-13; 124:4-7) Therefore, the “holy grail” is to provide a drug designed for oral mucosal delivery having both improved solubility and absorption. 2. The Khankari patents: overview 7. A method for achieving this result is claimed by Drs. Sathasivan Indiran Pather (“Dr. Pather”), Rajentra K. Khankari (“Dr. Khankari”), Jonathan D. Eichman (“Dr. Eichman”), Joseph R. Robinson (“Dr. Robinson”), and John Hontz (“Dr. Hontz”): using an effervescent agent to enhance the penetration of the medicament across the buccal, sublingual and gingival mucosa. ('590 patent, col. 2:13-15) 8. Dr. Khankari testified that the inventors achieved a dynamic change in pH — a low starting pH, promoting dissolution, followed by an increase in pH, favoring absorption — by incorporating effervescent agents that react to form carbon dioxide (C02). (D.I. 282 at 120:9-23) When C02 dissolves in saliva, it forms a weak acid (carbonic acid) that reduces the salival pH. (Id. at 121:1-11) The carbonic acid thereafter dissociates into C02 and water; C02 is released as gas, causing the pH to slowly rise. (Id. at 121:13-20) In this manner, a balance between dissolution and absorption is achieved. The inventors believed that effervescence increases the rate and extent of absorption of an active drug by “one or all of the following mechanisms: (1) reducing the mucosal layer thickness and/or viscosity; (2) tight junction alteration; (3) inducing a change in the cell membrane structure; and (4) increasing the hydrophobic environment within the cellular membrane.” ('590 patent, col. 2:23-31) 9. The Khankari patents characterize the invention as the use of “an effervescent agent effective to aid penetration of the drug across the oral mucosa.” (Id., col. 2:32-34) To this end, specific quantities of an effervescent agent (between 5% and 95% by weight and, preferably, 30% to 80% by weight) are provided for formulation purposes. (Id., col. 2:34-38) This quantity, in turn, should be sufficient to provide “about 5 cm3 to but less than about 30 cm3 [of evolved gas] upon exposure of the tablet to an aqueous environment.” (Id., col. 2:38-41) While most often a soluble acid source and a carbonate source (such as potassium bicarbonate) will be used, which reaction produces C02 gas, reactants may also be used which evolve other gases. (Id., col. 2:48-col. 3:3) 10. Other pharmaceutical ingredients are preferably incorporated 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. 4:41-51) “[S]uitable non-efferveseent disintegration agents” may be used. (Id.) Excipient fillers “desirably will also assist in the rapid dissolution of the dosage form in the mouth.” (Id., col. 5:28-32) Mannitol is listed among the (non-limiting) examples of such excipient fillers. (Id.) 11. The Khankari patents also disclose the use of suitable pH-adjusting substances that permit a sufficient concentration of the drug to be present in the unionized (and more absorbable) form. (Id., col. 3:40-46) “Suitable pH-adjusting substance[s] for use in the present invention include any weak acid or weak base in amounts additional to that required for the effervescence or, preferably, any buffer system that is not harmful to the oral mucosa. Suitable pH-adjusting substance[s] for use in the present invention include, but are not limited to, any of the acids or bases previously mentioned as effervescent compounds[.]” (Id., col. 3:47-55) (emphasis added) 12. The '604 patent was filed (as U.S. Patent Application No. 09/327,814, hereinafter, “the '814 application”) on June 8, 1999 and issued March 13, 2001. Priority is claimed to a provisional patent application (No. 60/079,652) filed March 27, 1998. The '590 patent was filed on February 20, 2002 (as U.S. Patent Application No. 10/080,616, hereinafter, “the '616 application”) and issued on December 13, 2005. It is a grandchild, continuation application claiming priority to the '814 application. As such, the Khankari patents share a common disclosure. 13. 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 systemically distributable pharmaceutical agent across the oral mucosa comprising: a)providing a solid oral dosage form including a pharmaceutically effective amount of an orally administerable medicament; and at least one effervescent agent in an amount sufficient to increase absorption of said orally administerable medicament across the oral mucosa; wherein said orally administerable medicament is not substantially 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 dissolving 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. (emphasis added) 14.The '590 patent discloses fentanyl as the pharmaceutical agent, and contains 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 fentanyl or a pharmaceutically acceptable salt thereof and at least one saliva activated effervescent agent in an amount sufficient to increase absorption of said fentanyl or pharmaceutically acceptable 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 weight; and buccally, sublingually or gingivally administrating said solid oral dosage form to said mammal. (emphasis added) B. Claim Construction 1. Standards 15. Claim construction is a matter of law. Phillips v. AWH Corp., 415 F.3d 1303, 1330 (Fed.Cir.2005) (en banc). Claim construction focuses on intrinsic evidence — the claims, specification and prosecution history — because intrinsic evidence is “the most significant source of the legally operative meaning of disputed claim language.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed.Cir.1996); Markman v. Westview Instruments, Inc., 52 F.3d 967, 979 (Fed.Cir.1995) (en banc), aff'd, 517 U.S. 370, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996), Claims must be interpreted from the perspective of one of ordinary skill in the relevant art at the time of the invention. Phillips, 415 F.3d at 1313. 16. Claim construction starts with the claims, id. at 1312, and remains centered on the words of the claims throughout. Interactive Gift Express, Inc. v. Compuserve, Inc., 256 F.3d 1323, 1331 (Fed.Cir.2001). In the absence of an express intent to impart different meaning to claim terms, the terms are presumed to have their ordinary meaning. Id. Claims, however, must be read in view of the specification and prosecution history. Indeed, the specification is often “the single best guide to the meaning of a disputed term.” Phillips, 415 F.3d at 1315. 2. Issues at bar 17. While the parties have separately addressed the “effervescent agent” and “amount sufficient to increase absorption” terms of the claims, the court finds it more appropriate to address the “at least one [saliva activated] effervescent agent in an amount sufficient to increase absorption ... across [the] oral mucosa” term as a whole. The court, however, will briefly frame the parties’ arguments on each portion of the term prior to addressing the intrinsic record. 18. There is no dispute among the parties that an “effervescent agent” must generally “evolve gas” “by means of a reaction.” (D.I. 187; D.I. 253 at 39) The claim construction issue before the court, therefore, is whether two (or more) compounds are required to do so. Specifically, Cephalon asserts that “at least one effervescent agent” means “at least one compound that evolves gas by means of a reaction,” without limitation as to the nature of the reaction, Watson argues that, while “at least one” has its ordinary meaning, “effervescent agent” is “synonymous with effervescent couple, which is a combination of two or more compounds that evolve gas by means of a reaction” upon exposure to saliva. (D.I. 187) 19. With respect to the “in an amount sufficient” portion, the parties agree that the term means, at least, “in an amount sufficient to increase the rate and/or extent of absorption of [an orally administer-able medicament/fentanyl or pharmaceutically acceptable salt thereof] across [said/ the] oral mucosa.” (D.I. 187) Watson proposes the additional limitation that the amount sufficient be “an amount greater than the amount required for tablet disintegration” and “not include any amount of pH-adjusting substance present in the tablet.” (Id.) 3. Intrinsic evidence 20. The Khankari patents’ specification provides that “effervescent agents can be used alone or in combination with other penetration enhancers, which leads to an increase in the rate and extent of absorption of an active drug.” ('590 patent, col. 2:21-23) The preferred effervescent agents evolve gas by means of a chemical reaction which takes place upon exposure of the effervescent agent (an effervescent couple) to water and/or to saliva in the mouth. The reaction is most often the result of a soluble acid source and a source of carbon dioxide such as an alkaline carbonate or bicarbonate. The reaction of these two general compounds produces carbon dioxide gas upon contact with water or saliva. ('590 patent, col. 2:44-53) (emphasis added) 21. Further, “[t]he dosage form preferably includes an effervescent couple, in combination with the other ingredients to enhance the absorption of the pharmaceutical ingredient across the oral mucosa and to improve the disintegration profile and the organoleptic properties of the dosage form.” (Id, col. 4:23-27) a. '604 patent 22. The parties do not dispute that the meaning of the claim term “at least one effervescent agent” was not addressed during prosecution of the '604 patent (from 1999 to 2001). 23. The phrase “and at least one effervescent agent in an amount sufficient to increase absorption of said orally administerable medicament across the oral mucosa” was added to the claims during prosecution of the '604 patent in response to an anticipation and obviousness rejection by U.S. Patent No. 5,178,878 (“Wehling”). (JA-146-47) The applicants provided that: Both rejections appear to be based on the fact that the use of effervescents as disintegration agents or taste masking agents in solid oral dosage forms was known in the art. Although the prior art’s teachings of the use of effervescents in this manner is acknowledged, the present invention, as recited in claims 9-10, is directed to a new use for effervescent agents. Namely, the present invention is directed to the use of effervescent agents alone or in combination with pH adjusting substances to promote the absorption of medicaments across the oral mucosa. The claimed invention therefore provides improvements in the field of the oral delivery of medicaments, including, for example, by increasing the onset of action of some orally administerable drugs, improving the bioavailability of some orally administerable drug, and enabling delivery of drugs across the oral mucosa that were previously not suited for this route of administration due to their poor absorption properties. (JA-147) (emphasis added) These arguments were deemed unpersuasive, and a final rejection issued. (JA-351) In response, the applicants added additional limitations to the independent claim, specifically, the “wherein said orally administerable medicament is not substantially encompassed by or dispersed in a material that prevents absorption of said medicament across the oral mucosa” and the requirement that the patient hold the oral dosage form in the mouth as it dissolves and as absorption is improved (issued claim 1, subpart (e)). (JA-393) The claims were thereafter allowed in view of the latter amendment, as the prior art taught swallowing of the dosage form and absorption in the stomach. (JA-404) b. '590 patent 24.The “effervescent agent” term was addressed while the later-filed '590 patent was pending (as the '016 application). Claim 1 of the '016 application (filed in 2002) was drawn to a pharmaceutical dosage form comprising fentanyl and “at least one saliva activated effervescent agent.” (JA-2310) (emphasis added) Dependent claims 2 to 4 added the requirements for a pH-adjusting substance, a basic pH-adjusting substance, and more specific bases to be used. (Id.) Claims 2 to 4 were provisionally rejected for obviousness-type double patenting over copending U.S. Patent Application No. 09/661,693 (“the '693 application”) — the parent to the '016 application, and the child to the '604 patent in the chain of continuation applications. (JA-2508) The examiner identified two sets of overlapping claims in a provisional obviousness-type double patenting rejection: '693 application claim 95 with '016 application claim 2, and '693 application claims 85 and 86 with '016 application claim 4. (JA-2508-09) 25. In this same rejection, the examiner also rejected the pending claims as obvious in view of the combination of U.S. Patent No. 6,071,539 to Robinson et al. (“Robinson”) and U.S. Patent No. 4,671,-953 to Stanley et al. (“Stanley”). (JA-2509) The examiner stated that Robinson taught oral formulations containing effervescent granules containing “an effervescent couple (i.e., an acidic agent such as citric acid, tartaric acid, fumaric acid and an alkaline agent such as sodium bicarbonate, sodium dihydrogen phosphate, potassium carbonate) and a binder.” (Id.) (emphasis added) 26. The applicants traversed the rejection by arguing, inter alia, that Robinson discussed an effervescent couple in the context of disintegration and did not disclose adjusting the amount of effervescence to increase absorption across the oral mucosa. (JA-2599-600) Robinson did not disclose or recognize that “adjusting the amount of effervescent couple, or the pH, [would] improve penetration of an [API] across the oral mucosa[.]” (JA-2599, JA-2600) In particular, there is nothing in Robinson to suggest that the amount of effervescent couple required for substantially complete disintegration of the tablet and a positive organoleptic sensation to a patient is anything more than that required to just cause the tablet to disintegrate. Clearly, an effervescent couple, when activated in the mouth, will cause “fizzing” and thereby be perceived by the patient. It is only the present invention that teaches that the amount of effervescent couple should be greater than that required for disintegration in order to achieve an improvement in transport of the active ingredient across the oral mucosa. It is only as a consequence of applicants’ teaching regarding this effect that the examiner has extrapolated the teachings of Robinson in order to suggest that it is desirable to increase the amount of the effervescent couple and the pH of the composition in order to achieve the effect taught by applicants; Robinson contains no such teaching or suggestion. (JA-2600-01) (emphasis added) In sum, Robinson did not teach the “critical limitations” of the present invention, that is, improving the transport of an API across the oral mucosa “by appropriate control of the amount of effervescent couple and, additionally, the pH achieved by the composition.” (JA-2601) 27.Thereafter, the examiner rejected claims 1-19 of the '016 application over claims 22, 23, 25-28, 83-91 and 93-95 of the '693 application. (JA-2618) While the '016 application contained “effervescent agent” in the claims, claim 22 of the '693 application, the independent claim from which the others in this group depend, included a limitation to “at least one saliva activated effervescent couple.” The examiner stated that the conflicting claims were “not identical, [but] not patentably distinct.” (Id.) Furthermore, the provisional double-patenting rejection was forged on the ground that the claims of the '693 application were “directed to a tablet for oral administration across the oral mucosa comprising a pharmaceutically effective amount of a medicament, at least one pH adjusting substance and at least one saliva activated effervescent couple present in an amount which is greater than the amount necessary for tablet disintegration and which is sufficient to increase absorption of the medicament across the oral mucosa,” which encompassed the '016 fentanyl dosage form. (JA-2619) (emphasis added) 28. The obviousness rejection of Robinson and Stanley was replaced with a rejection of the claims over a combination of Robinson and either U.S. Patent No. 5,958,458 to Norling et al. (“Norling”), teaching the use of analgesics in effervescent tablets, or U.S. Patent No. 5,073,374 to McCarty, teaching non-effervescent but fast dissolving buccal medicaments. (JA-2620-24) 29. In response, the applicants added oral administration limitations and weight percent limitations to the independent claims of the '016 application. Independent claims 1 and 10 of the '016 application were amended to require “wherein said amount of said at least one effervescent couple is between about 5% by weight and about 80% by weight.” (JA-2645) At the time the amendment was entered, “effervescent couple” had as its antecedent basis only “at least one saliva activated effervescent agent” as recited previously in the claim. (Id.) 30.Following a final rejection, in which the double patenting and obviousness rejections based on Robinson and Norling were maintained, a terminal disclaimer was filed by the applicants. (JA-2671, 2678) The applicants cancelled claims 1 through 9. (JA-2680) Then-pending claim 10 of the '016 application read as follows: 10. (previously presented) A method of administration of fentanyl to a mammal across the oral mucosa thereof, said method comprising: providing a solid oral dosage form comprising fentanyl or a pharmaceutically acceptable salt thereof and at least one saliva activated effervescent agent in an amount sufficient to increase absorption of said fentanyl or pharmaceutically acceptable salt thereof across said oral mucosa, at least one pH-adjusting substance, and wherein said amount of said at least one effervescent couple is between about 5% by weight and about 80% by weight; and buccally, sublingually or gingivally administering fentanyl or a pharmaceutically acceptable salt thereof to said mammal across said oral mucosa. (JA-2680) (emphasis added) Claim 10 (and dependent claims 11-15 and 17-19) were subsequently allowed by the PTO, however, the applicants filed a request for continued examination (“RCE”) in order to make additional art of record in the application. The applicants provided the following remarks in their RCE request transmittal: On June 10, 2005 the undersigned received a telephone call from Examiner Lamm during which the Examiner advised that pursuant to a quality review by the Patent Office of the allowed claims following mailing of the above-identified Notice of Allowance, further amendments to the claims were being requested. As stated by the Examiner, the requested amendments were directed to making the claim language in the terminal part of independent claim 10 consistent with that used in the earlier part of the claim and are considered by the Office to be minor changes not affecting the scope of the claim. In particular, it was requested that the word “couple” be changed to “agent” and that the phrase “fentanyl or a pharmaceutically acceptable salt thereof’ be changed to “said solid oral dosage form.” These changes are acceptable to Applicants and the amendment submitted herein is consistent with that request. Furthermore, Applicants have also amended the last line of claim 10 to conform the overall claim language to be consistent with the amendments proposed as a consequence of the quality review. Respectfully, this amendment is not intended to narrow the scope of the claim and no narrowing has occurred, either as a result of this amendment or those proposed by the Office. Entry of these claim amendments is respectfully requested. (JA-2911) (emphasis added) A Notice of Allowance followed and the issue fee for the '016 application was paid. A Certificate of Correction was later issued in which the term “agents” was added to the Detailed Description of the Invention, to read; “One aspect of this invention is to use effervescent agents as penetration enhancers for influencing oral drug absorption.” ('590 patent, col. 2:19-20) (emphasis added) Two Certificates of Correction were filed for the '604 patent; neither contained this addition to the specification. c. '693 application 31. The '693 application was filed (as a continuation of the '604 patent application) in September 2000 and was ultimately abandoned in 2009. As a continuation, the '693 application shares the same specification as the Khankari patents. 32. The originally presented claims of the '693 application were drawn to a solid pharmaceutical dosage form comprising “at least one saliva activated agent present in an amount sufficient to increase absorption ... across the oral mucosa.” (JA-450-51) The claims were later amended to require “at least one saliva activated effervescent agent present in an amount 5% by weight and about 80% by weight.” (JA-791) The claims were rejected over U.S. Patent No. 6,117,912 (“DiSanto”), teaching an effervescent selegiline tablet for sublingual or buccal administration. (JA-788) Specifically, DiSanto provided that “[t]he amount of sodium bicarbonate (effervescent) present in example 3 is more than 61%[.]” (JA-787-88) In response to the examiner’s 102(b) and 103 rejections, the applicants provided: Claim 22 referred to an effervescent “agent.” As explained at page 5 of the specification, the term “effervescent agent” includes compounds that evolve gas. The preferred effervescent agents evolve gas by means of a chemical reaction, which takes place upon exposure of the effervescent agent (an effervescent couple) to water and/or to saliva in the mouth. Accordingly, it is inconsistent with both applicants’ definition and the common definition of effervescence to consider only the weight percentage of the sodium bicarbonate without also consideration of, at the very least, the citric acid recited within example 3. If citric acid is considered, then the amount of effervescent material is well above 80% as claimed. Therefore, the DiSanto reference cannot anticipate the claim. To alleviate any possible ambiguity, applicants have amended claim 22 to delete the term “agent” and to specifically refer to an effervescent “couple.” As noted above, these terms are of identical scope and are clearly supported by at least the specification at page 5 quoted above. (JA-792) The claims were amended to recite “at least one saliva activated effervescent couple present in an amount between about 5% by weight and about 80% by weight.” (JA-791, 796) 33. After receiving a new matter objection to the amendment (JA-885), the inventors reiterated to the PTO (in October 2002) that an effervescent agent is “identical in scope” in this context to an “effervescent couple.” (JA-950) 34. The applicants also added a limitation that the “at least one saliva activated effervescent couple” is “present in an amount which is greater than the amount necessary for tablet disintegration and which is sufficient to increase either the rate [or] the extent of absorption of said medicament across the oral mucosa.” (JA-948-49) The applicants’ comments on this limitation were as follows: To further accentuate the differences between the present invention and the prior art, applicants have amended claim 22 to make it clear that in the invention, a saliva activated effervescent couple is present in an amount that is greater than the amount necessary for tablet disintegration. Indeed, the amount of saliva activated effervescent disintegration couple present must be sufficient to increase either the rate or the extent of absorption of the medication across the oral mucosa. Applicants have found that effervescents can be used for far more than merely allowing for disintegration of the tablet. While rapid disintegration exposes the drug such that it may be used by the body, unless an effervescent couple is present in sufficient amounts, amounts greater than that necessary for disintegration, it does not significantly participate in the drug absorption process. By providing effervescents in an amount that is greater than that necessary for achieving disintegration of the dosage form, it is possible to obtain these benefits. Nothing in DiSanto teaches or suggests the need for such additional amounts of effervescent agent. (JA-951) 35.The examiner responded to the applicants’ remarks on DiSanto as follows: Applicant asserts that the term “effervescent agent” is synonymous with “effervescent couple” and therefore it is improper to consider only one component (as shown in the prior art) to determine the amount of effervescent in the composition. Whereas “effervescent couple” is referred to in the instant specification, it is not evidence that the “effervescent couple” refers to an agent containing multiple components. The specification does not state the reaction is most often the result of a[n] acid source and carbon source, but it is the examiner’s position that this is a preferred reaction and not a necessary one. Therefore, the effervescent couple can be one agent or multiple agents. As such, the teachings of DiSanto anticipate claim 22, and the rejection is maintained. (JA-958) The applicants responded: The examiner asserts that sodium bicarbonate in the formulation qualifies as the claimed “effervescent couple” on its own. Since sodium bicarbonate cannot be an effervescent couple, i.e., comprising two components, it appears, without there being an explicit statement in the office action, that the examiner is suggesting that, even if citric acid were not present in the formulation, sodium bicarbonate would produce effervescence by reacting with the hydrochloric acid in the selegiline salt .... It is respectfully suggested that the examiner misconstrues “effervescent couple.” First of all, the instant claims recite a “couple,” not just one “agent.” Clearly, sodium bicarbonate cannot, by itself, be a “couple.” Even if, as the examiner argues, the “effervescent couple” could be produced in situ by hydrochloric acid in the drug and sodium bicarbonate, the citric acid, as well as the fumaric acid present in the formulation cannot be ignored and must also be part of such “couple.” If anything, since the HCI adds more acid, it accentuates the fact that DiSanto does not teach or suggest the range of claim 22.... [T]he instant claims also require that the amount of the effervescent couple be sufficient for tablet disintegration. If the examiner’s view is adopted that, e.g., the citric acid in selegiline is the source of acid for the effervescent couple, the example is inadequate to anticipate the instant claims ... Even if the reaction between sodium bicarbonate and the trivial amount of hydrochloric acid in the selegiline salt does take place, the effervescent effect would be minimal. The amount of gas evolved from such a reaction would be very small, and thus insufficient for noticeable effervescence, let alone for tablet disintegration. When the claims of the instant application are read on DiSanto’s example 3, the combination of citric acid (and, additionally, the fumaric acid also present) and sodium bicarbonate could qualify as an “effervescent couple.” Considering the combined weight of citric acid and sodium bicarbonate, or both citric acid and fumaric acid plus sodium bicarbonate, the amount of effervescent couple in the example 3 is substantially greater than 80% and thus outside the range of claim 22. (JA-975-77) (first emphasis in original) The examiner found the arguments persuasive 36. The prosecution continued for several more years and claim 22 (among others) was ultimately allowed with additional limitations presented in Markush form. That is, claim 22 required “at least one saliva activated effervescent couple” comprising an acid selected from a specified group and a base selected from a specified group, wherein the amount of said at least one effervescent couple is present in an amount greater than necessary for tablet disintegration, and is between 20% and 80% by weight. (JA-2151) As noted previously, the '693 application was abandoned prior to issuance. 4. Discussion 37. For the reasons discussed infra, the court construes the disputed claim language consistent with the tenets of claim construction set forth above as follows: “[A]t least one [saliva activated] effervescent agent in an amount sufficient to increase absorption ... across [the] oral mucosa” means that at least one compound that evolves gas by means of an effervescent reaction is present in an amount sufficient to increase the rate and/or extent of absorption of an orally administerable medicament across the oral mucosa. This amount is greater than that required for disintegration and does not include the pH-adjusting substance separately claimed. a. Singularity of “agent” 38. The term “agent” is, on its face, a singular term distinguishable from the plural “couple.” “When construing terms in the body of a claim, the general assumption is that different terms have different meanings[.]” Symantec Corp. v. Computer Associates Intern., 522 F.3d 1279, 1289 (Fed.Cir.2008) (citation omitted). Notwithstanding that the Khankari patents’ specification does not disclose a single-compound effervescent “agent” that could produce gas on its own upon exposure to water or saliva, there is no indication that the court should ignore the applicants’ choice of language. See SEB S.A. v. Montgomery Ward & Co., Inc., 594 F.3d 1360, 1369 (Fed.Cir.2010) (stating that the presumption simply “carries less weight” where the specification only describes one embodiment). Put another way, the specification does not contain a “clear and unambiguous” disavowal of a single effervescent compound. See Microsoft, 357 F.3d at 1350. 39.The reference to “the effervescent agent (an effervescent couple)” is a general one. That the claims of the '590 patent briefly contained the term “effervescent couple” is also not compelling. The term “effervescent couple” was introduced to the claims by the amendment adding the 5-80% limitation to the '590 patent. (JA-2645) As explained supra, the claims were internally inconsistent and the PTO recommended changing “couple” to “agent.” The inventors characterized the change as minor and non-narrowing (JA-2911), a view consistent with the court’s construction insofar as the term “at least one effervescent agent” is broader than “effervescent couple.” 40. Most notably, during prosecution of the '693 application, the applicants explicitly rejected the examiner’s view that the “effervescent couple” of the claims could be “one agent or multiple agents.” The applicants emphasized that “couple” is plural while one “agent,” such as the sodium bicarbonate in DiSanto example 3, cannot itself be considered an effervescent “couple.” (JA-975-77) The examiner withdrew the DiSanto rejections based on this understanding of “couple.” 41. In view of the foregoing, the claims are broad enough to encompass at least one compound that evolves gas by means of an effervescent reaction. While the claims do not require that the oral dosage form contain both halves of the effervescent couple, leaving open the possibility that the other reactant be present in the oral cavity, effervescence (as compared to a reaction of a different nature) is required. b. The quantity of effervescent agent is distinct 42. The court is next tasked with determining the nature of the “effervescent agent” of the invention. Watson argues all pH-adjusting substances present in the tablet cannot be subsumed by the “effervescent agent” limitation or the related requirement that the effervescent agent be present “in an amount sufficient to increase absorption” across the oral mucosa. (D.I. 187) Cephalon admits that the concepts of effervescence and pH-adjustment are different, but that one component (namely, the potassium bicarbonate present in Watson’s tablets) can perform both functions. (D.I. 193 at 20) While both parties agree that the “amount [of effervescent agent] sufficient to increase absorption” requires the “rate and/or extent” of absorption to be increased, Watson argues that the amount of effervescent agent must be greater than that required for tablet disintegration. (D.1.187) 43. The court agrees with Watson’s position. As set out supra (¶¶ 9-11), the inventors distinguished the effervescent agent(s) from the other ingredients of the composition. The claims separately require at least one “effervescent agent in an amount sufficient to increase absorption” and “at least one pH-adjusting substance.” While one compound may both adjust pH and participate in effervescence, only the quantity of effervescent agent above that needed for effervescence may be considered the “pH adjusting substance.” ('590 patent, col. 3:47-55) The inventors noted a distinction between the effervescent agent and pH-adjusting substance during the prosecution of the '590 patent in distinguishing Robinson, wherein they stated: “[C]laim 1 of the present application, in addition to an effervescent couple-, requires the use of a pH-adjusting substance ... There is no parallel structure or function in Robinson, nor does Robinson teach or suggest the use of an effervescent couple and, as a separate agent, a pH-adjusting substance.” (JA-2637-38) (emphasis added) 44.A similar conclusion is warranted with respect to disintegration. The court has previously described the applicants’ argument with respect to Robinson made during prosecution of the '590 patent. (supra, ¶24) The applicants argued, inter alia, that “[i]t is only the present invention that teaches that the amount of effervescent couple should be greater than that required for disintegration in order to achieve an improvement in transport of the active ingredient across the oral mucosa.” (JA-2601) (emphasis added) Although the emphasized language is not unequivocal, the applicants’ comments are consistent with the specification’s separate treatment of effervescents and disintegrants. While the “effervescent agent” is provided in an amount between 5% and 90% and, preferably, 30% and 80% by weight, “disintegrants” may comprise up to 20% by weight and, preferably, between about 2% and about 10% of the total weight of the composition. ('590 patent, col. 2:34-38; col. 4:49-51) In further acknowledgment of the difference between effervescents and disintegrants, the Khankari patents’ specification states that “effervescents have been employed to obtain rapid dissolution and/or dispersion of the medicament in the oral cavity” but, “[d]e-spite these and other efforts toward increasing the permeation of medicaments across the oral mucosa, there have been unmet needs for improved methods of administering medicaments across the oral mucosa” until the present invention. (Id., col. 1:42-45, col. 2:5-8) Thus, although the “effervescent couple in combination with the other ingredients” will “improve the disintegration profile” of the dosage form (id. at col. 4:22-31), and while a certain (surplus) amount of effervescents will also confer pH-adjusting benefits to the formulation, Watson is correct that these are distinct ingredients. c. Amount sufficient to increase absorption 45. With the exceptions adopted above, the parties agree that the effervescent agent must be present in “an amount sufficient to increase the rate and/or extent of absorption of an orally administerable medicament across the oral mucosa.” Watson does not contend, therefore, that the “amount sufficient” is ambiguous or indefinite or that a person of ordinary skill in the art could not determine the appropriate amount without undue experimentation. (D.I. 59 at 21-22) C. Infringement 1. Standards 46. A patent is infringed when a person “without authority makes, uses or sells any patented invention, within the United States ... during the term of the patent.” 35 U.S.C. § 271(a). A two-step analysis is employed in making an infringement determination. See Markman v. Westview Instruments, Inc., 52 F.3d 967, 976 (Fed.Cir.1995). First, the court must construe the asserted claims to ascertain their meaning and scope. See id. Construction of the claims is a question of law subject to de novo review. See Cybor Corp. v. FAS Techs., 138 F.3d 1448, 1454 (Fed.Cir.1998). The trier of fact must then compare the properly construed claims with the accused infringing product. See Markman, 52 F.3d at 976. This second step is a question of fact. See Bai v. L & L Wings, Inc., 160 F.3d 1350, 1353 (Fed.Cir.1998). 47. “Direct infringement requires a party to perform each and every step or element of a claimed method or product.” BMC Res., Inc. v. Paymentech, L.P., 498 F.3d 1373, 1378 (Fed.Cir.2007). “If any claim limitation is absent from the accused device, there is no literal infringement as a matter of law.” Bayer AG v. Elan Pharm. Research Corp., 212 F.3d 1241, 1247 (Fed.Cir.2000). If an accused product does not infringe an independent claim, it also does not infringe any claim depending thereon. See Wahpeton Canvas Co. v. Frontier, Inc., 870 F.2d 1546, 1553 (Fed.Cir.1989). However, “[o]ne may infringe an independent claim and not infringe a claim dependent on that claim.” Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 1359 (Fed.Cir.2007) (quoting Wahpeton Canvas, 870 F.2d at 1552) (internal quotations omitted). A product that does not literally infringe a patent claim may still infringe under the doctrine of equivalents if the differences between an individual limitation of the claimed invention and an element of the accused product are insubstantial. See Warner-Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17, 24, 117 S.Ct. 1040, 137 L.Ed.2d 146 (1997). The patent owner has the burden of proving infringement and must meet its burden by a preponderance of the evidence. See SmithKline Diagnostics, Inc. v. Helena Lab. Corp., 859 F.2d 878, 889 (Fed.Cir.1988) (citations omitted). 2. Discussion 48. To prove infringement under the court’s construction, Cephalon must demonstrate that Watson’s ANDA product contains at least one compound that evolves gas by means of an effervescent reaction and that is present in an amount sufficient to increase the rate and/or extent of absorption of an orally administerable medicament across the oral mucosa. 49. Watson’s ANDA product contains fentanyl citrate, potassium bicarbonate, mannitol, sodium starch glyeolate, and magnesium stearate. (D.I. 283 at 280:17-281:1; DTX-1456 at 9992) Potassium bicarbonate is a carbonate (or C02) source listed in the Khankari patents as capable of effervescence. ('590 patent, col. 2:62) Cephalon admits that potassium bicarbonate will not react without an acid source. (D.I. 244 at 25 (citing D.I. 282 at 188:21-192:9; PTX-379); see also id. at 31 (citing D.I. 283 at 464:22-465:4)) The question at bar, therefore, is whether Cephalon demonstrated at trial that the potassium bicarbonate in Watson’s ANDA product reacts with an acid source to evolve C02 and, ultimately, increases the absorption of fentanyl across the oral mucosa. ('590 patent, col. 2:33-60) 50. Cephalon devoted all of one sentence to the standard for determining infringement: “ ‘Direct infringement requires a party to perform or use each and every step or element of a claimed method or product,’ ” citing (as did the court) BMC Resources, Inc. v. Paymentech, L.P., 498 F.3d at 1378, a case in which the Federal Circuit reviewed the proper standard for joint infringement by multiple parties of a single claim. The Federal Circuit in BMC Resources went on to state that “[i]ndirect infringement requires, as a predicate, a finding that some party amongst the accused actors has committed the entire act of direct infringement,’ ” citing Dynacore Holdings Corporation v. U.S. Philips Corp., 363 F.3d 1263, 1272 (Fed.Cir.2004). In Dynacore Holdings, the Federal Circuit reiterated that, to establish the underlying direct infringement, a plaintiff must show that the accused infringer “meet[s] each limitation of the [asserted] claims, either literally or under the doctrine of equivalents.” Id. 51.There is no specific discussion by Cephalon of either literal infringement or infringement by equivalents. Indeed, Cephalon’s summary of its infringement analysis does not use the word “infringement” at all: “The foregoing evidence— that Watson’s tablets evolve C02 gas, exhibit a dynamic pH, and are bioequivalent to Fentora® — demonstrates that the amount of effervescent agent in Watson’s tablets is an amount sufficient to increase the rate and/or extent of fentanyl absorption across the oral mucosa.” (D.I. 244 at 27) Nevertheless, because Cephalon depends at least in part on the bioequivalence of Watson’s tablets to Fentora® and uses the word “equivalent” in various of its discussions, the court will proceed on the understanding that Cephalon is asserting infringement by equivalents only. 52. With respect to the disputed limitation, that is, “at least one [saliva activated] effervescent agent in an amount sufficient to increase absorption ... across [the] oral mucosa,” both parties have used the evolution of C02 gas as the benchmark for determining whether effervescence occurs. (D.I. 244; D.I. 253 at 40) For instance, video evidence was introduced at trial with respect to the release (or non-release) of gas bubbles by Watson’s ANDA product. (DTX-721) Given the court’s claim construction, however, it is not enough to argue (as Cephalon does) that if it looks like effervescence, and produces C02 like effervescence, then there must be effervescence. 53. In this regard, Cephalon has not provided any affirmative proof regarding the precise nature of the chemical reaction allegedly occurring. Although the parties agree that the potassium bicarbonate in the ANDA product (the “at least one effervescent agent” according to Cephalon) requires the presence of a soluble acid source in order to evolve C02 gas, Cephalon states only that said acid source is “at least” the mannitol contained the ANDA product (D.I. 244 at 31) and does not identify any external acid source. 54. More specifically, Cephalon’s analytical chemist expert, Dr. Bernard Olsen (“Olsen”), testified that he conducted pH experiments and found mannitol to be acidic in water; the more concentrated the mannitol, the more acidic the solution. (D.I. 283 at 328:23-330:10; PTX-431) Cephalon presents no evidence regarding the acidity of mannitol in artificial saliva. Notably, there is no evidence of record regarding the properties of human saliva. As Watson’s expert put it, “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.” (D.I. 286 at 1174:11-16) Even were the court to assume that Olsen’s data translates to human saliva, Cephalon’s infringement expert, Dr. Robert O. Williams III (“Williams”), stated that he did not “do any testing to determine definitively whether it was the mannitol that was reacting with the potassium bicarbonate [in the ANDA product] as opposed to a different excipient.” (D.I. 283 at 406:11-15) 55.Had Cephalon demonstrated effervescence in the first instance, nevertheless, the court finds that Cephalon did not meet its burden to demonstrate that the effervescent reaction increases the rate and/or extent of absorption of an orally administerable medicament across the oral mucosa. Cephalon emphasizes Williams’ testimony that, like Fentora®, the ANDA products exhibit a dynamic pH profile, or a gradual increase from a more acidic to a more basic pH. (D.I. 244 at 33-34 (citing D.I. 150 at 410:20-411:24; 445:14-17; 455:6-456:22; 459:20-460:2)) Williams based his opinion on both pH data and Olsen’s C02-emission data. Regardless of how the ANDA product may be working, the only proffered evidence that the ANDA product actually results in an increase in the rate and/or extent of absorption across the oral mucosa is the fact that the ANDA product is “bioequivalent” to Fentora® (and Fentora® has proven improved bioavailability over Actiq® and non-effervescent fentanyl citrate tablets). (D.I. 244 at 33; id. at 35 (citing D.I. 150 at 462:8-13); see also D.I. 150 at 410:15-19 (Williams’ explaining that the basis of his opinion is bioequivalence)) 56. As the Federal Circuit has recently explained, [w]hile bioequivalency may be relevant to the function prong of the function-way-result test, bioequivalency and equivalent infringement are different inquiries. Bioequivalency is a regulatory and medical concern aimed at establishing that two compounds are effectively the same for pharmaceutical purposes. In contrast, equivalency for purposes of patent infringement requires an element-by-element comparison of the patent claim and the accused product, requiring not only equivalent function but also equivalent way and result. Different attributes of a given product may thus be relevant to bioequivalency but not equivalent infringement, and vice versa. As the Northern District of Illinois observed in the Sandoz case, “[i]f bioequivalency meant per se infringement, no alternative to a patented medicine could ever be offered to the public during the life of a patent.” Thus, while potentially relevant, the bioequivalency of an accused product with a product produced from the patent at issue is not sufficient to establish infringement by equivalents. Abbott Labs. v. Sandoz, Inc., 566 F.3d 1282, 1298 (Fed.Cir.2009) (internal citations omitted); compare Johns Hopkins Univ. v. Datascope Corp., 543 F.3d 1342, 1349 (Fed.Cir.2008) (“FDA equivalence is irrelevant to patent law because it involves fundamentally different inquiries.”). Bioequivalence, therefore, is insufficient to establish infringement under the doctrine of equivalents. As the foregoing indicates, the inquiry is not identicality to Fentora®, it is whether the ANDA product meets the limitations of the asserted Khankari patent claims. 57. Cephalon did not perform any absorption testing, or experiments comparing the rate and/or extent of absorption of the fentanyl citrate (API) in the ANDA product across the oral mucosa to the rate and/or extent of absorption of the fentanyl citrate from any non-effervescent delivery system. There were no experiments comparing the rate and/or extent of absorption of the fentanyl citrate in the ANDA product to the rate and/or extent of absorption of the APIs from the Khankari patents’ examples. Cephalon cites no testimony regarding rates of absorption at all. There is no comparator that the court can use to determine whether the potassium bicarbonate in the ANDA product is present in “an amount sufficient to increase absorption” upon effervescence. In its reply papers, Cephalon argues that it had no “obligation to perform any testing at all, let alone a particular kind of testing” in order to establish infringement. (D.I. 262 at 10) Although Cephalon is correct that a plaintiff may rely upon circumstantial evidence as proof of direct infringement, the record at bar does not contain sufficient (i.e., a preponderance of) circumstantial evidence in this regard. 3. Conclusion on infringement 58. For the foregoing reasons, Cephalon has not demonstrated, by a preponderance of the evidence, that an effervescent agent in the Watson ANDA product (potassium bicarbonate) participates in an effervescent reaction (with mannitol or with citric acid, whether present in the tablet or in the mouth) such as to increase absorption of fentanyl across the oral mucosa. The court does not address the additional contested limitations in view of its holding. D. Validity The court next determines whether, under the foregoing construction of “effervescent agent,” the Khankari patents are invalid. 1. 35 U.S.C. § 112, first paragraph a. Standards 59. The statutory basis for the written description and enablement requirements is found in 35 U.S.C. § 112, paragraph 1, which provides in relevant part: The specification shall contain a written description of the invention and of the manner and process of making and using it, in such full, clear, concise and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same. The Federal Circuit has explained that “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.... Tossing out the mere germ of an idea does not constitute enabling disclosure.” Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed.Cir.1997). 60. To satisfy the enablement requirement, a specification must teach those skilled in the art how to make and to use the full scope of the claimed invention without undue experimentation. Genentech, 108 F.3d at 1365. ‘While every aspect of a generic claim certainly need not have been carried out by the inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at 1366. The specification need not teach what is well known in the art. Hybritech v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1384 (Fed.Cir.1986). 61. Enablement is determined as of the filing date of the patent application. In re Brana, 51 F.3d, 1560, 1567 n. 19 (Fed.Cir.1995). The use of prophetic examples does not automatically make a patent non-enabling. The burden is on one challenging validity to show, by clear and convincing evidence, that the prophetic examples together with the other parts of the specification are not enabling. Atlas Powder Co. v. E.I. Du Pont de Nemours & Co., 750 F.2d 1569, 1577 (Fed.Cir.1984). 62. Some experimentation may be necessary in order to practice a claimed invention; the amount of experimentation, however, “must not be unduly extensive.” Id. at 1576. The test for whether undue experimentation would have been required is not merely quantitative, 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 with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the invention claimed. PPG Indus. Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed.Cir.1996) (quoting Ex parte Jackson, 217 U.S.P.Q. 804, 807 (1982)). 63. The enablement requirement is a question of law based on underlying factual inquiries. In re Wands, 858 F.2d 731, 737 (Fed.Cir.1988). A court may consider several factors in determining whether undue experimentation is required to practice a claimed invention, including: (1) the quantity of experimentation necessary; (2) the amount of direction or guidance disclosed in the patent; (3) the presence or absence of working examples in the patent; (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 of the art; and (8) the breadth of the claims. Wands, 858 F.2d at 737. These factors are sometimes referred to as the “Wands factors.” A court need not consider every one of the Wands factors in its analysis. Rather, a court is only required to consider those factors relevant to the facts of the case. See Amgen, Inc. v. Chugai Pharm. Co., Ltd., 927 F.2d 1200, 1213 (Fed.Cir.1991). b. Discussion 64. The question at bar is whether the full scope of the Khankari patent claims as the court has construed them— covering a drug form having a single compound effervescent agent — is enabled by the specification. Watson asserts that persons of ordinary skill in the art could not practice the invention of the Khankari patents without undue experimentation. Watson’s arguments in this regard are best described against a backdrop of Cephalon’s validity position. Cephalon argues that claims to a single-compound effervescent are enabled because a person of ordinary skill in the art could easily “co-administer” a soluble acid source to react with a tablet containing a single compound effervescent agent. According to Cephalon’s expert (Williams), a person of skill in the art would know that orange juice contains citric acid and would be able to put citric acid in a “second, fast-dissolve film or quick-dissolve tablet” to accompany the administration of the effervescent agent. (D.I. 287 at 1382:17-1383:22) 65. As Watson points out, inventors Hontz and Pather both testified that only sodium bicarbonate (a base) and citric acid were used to create effervescence in their formulations. Neither could recall any other acid-base formulations they used, or even used in the industry — nor could they name any single-compound effervesce