Full opinion text
MEMORANDUM OPINION ROBINSON, District Judge I. INTRODUCTION This action arises out of the filing of an Abbreviated New Drug Application (“ANDA”) by defendant Glenmark Pharmaceuticals Limited (“Glenmark Pharmaceuticals”) seeking to market a- generic azelaic acid hydrogel. Plaintiff Bayer Healthcare Pharmaceuticals Inc. (“Bayer”) is the holder of approved New Drug Application (“NDA”) No. 21-470 for Finacea® Gel, 15%, indicated for topical treatment of inflammatory papules and pustules of mild to moderate rosacea. Plaintiff Intraserv GmbH & Co., KG (“Intraserv”) is the as-signee of U.S. Patent No. 6,534,070 (“the '070 patent”) (“the patent-in-suit”) entitled “Composition with Azelaic Acid.” (D.I, 118, ex. 1 at ¶ 13) The '070 patent is listed in the Food and Drug Administration’s (“FDA’s”) publication titled “Approved Drug Products with Therapeutic Equivalence Evaluations” (known as the “Orange Book”) for Finacea®. (Id. at ¶ 16) Plaintiff Intendis GmbH (“Intendis”) (together with Bayer and Intraserv, “plaintiffs”) holds an exclusive license under the '070 patent. (Id. at ¶ 14) Bayer is the exclusive distributor of Finacea®. (Id. at ¶ 22) On July 27, 2012, pursuant to 21 U.S.C. § 355 (j), Glenmark Pharmaceuticals submitted ANDA No. 204637, seeking approval to commercially manufacture, use, sell, offer for sale and/or import a generic Aze-laic Acid Gel, 15% formulation with a paragraph IV certification stating that the '070 patent is not infringed and is invalid. (D.I. 1 at ¶¶ 18-20) On January 30, 2013, defendant Glenmark Pharmaceuticals Inc., U.S.A. (together with Glenmark Pharma-eeuticals, “defendants”) informed plaintiffs that an ANDA had been filed and alleged that the ANDA product would not infringe the '070 patent. (D.I. 118, ex. 1 at ¶ 39) Plaintiffs responded on March 14, 2013 by filing this suit for infringement of the '070 patent. The court held a Markman hearing and a final pretrial conference on January 21, 2015. The court held a five-day bench trial from February 5-11, 2015 on the issues of infringement and validity, and the parties have since completed their post-trial briefing. The 30-month stay of FDA final approval on Glenmark Pharmaceutical’s ANDA expires on July 31, 2015. The court has jurisdiction over, this matter 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 Federal Rule of Civil Procedure 52(a). II. FINDINGS OF FACT AND CONCLUSIONS OF LAW A. The Technology at Issue 1. Azelaic acid Azelaic acid has the following chemical structure: o Q HO' OH By the year 1998, azelaic acid formulations were being used as topical treatments for various skin disorders, including acne vul-garis,' melisma, arid rosacea. (D.I. 126 at 300:17-301:4; D.I. 127 at 524:18-20, 525:1-8; D.I. 128 at 695:23-696:1; D.I. 125 at 60:5-13; '070 patent, col. 1:24-26) Prior to Fina-cea®, Bayer marketed and sold a topical 20% azelaic'acid cream, marketed abroad as Skinoren® and in the United States as Azelex. (D.I. 125 at 60:2-10; D.I. 127 at 525:1-8; D.I. 128 at 761:7-18) 2. Bayer’s Finacea® Gel Finacea® Gel is a composition that contains azelaic acid as the therapeutically active ingredient as well as at least one triacylglyceride, propylene glycol, at least one polysorbate, at least one polyacrylic acid, lecithin, purified water, edetate diso-dium and benzoic acid. (D.I. 118, ex. 1 at ¶¶ 24-37) Bayer’s development of Fina-cea® Gel unfolded as follows: a., Skinoren® Cream Prior to developing Finacea® Gel, Sehering marketed and sold azelaic acid in the form of Skinoren®, a facial cream containing 20%' azelaic acid. (D.I. 125 at 59:20-60:13) Dr. Patrick Franke (“Dr. Franke”), one of the. named inventors on the '070 patent, testified that Skinoren® cream suffered from unwanted agglomeration and phase separation. (D.I. 125 at 60:22-25) Because the “cream formulation has a pretty high load of azelaic acid, 20 percent, there was a risk and a problem that certain particles concentrated in so-called agglomerates, so there was ... an inhomogeneity within th[e] cream emulsion” that caused a patient to “feel particles or agglomerates on the skin.” (D.I. 125 at 61:4-18) Dr. Franke testified that' the agglomeration “caused ■ some stability problems due to ... liquid separation ... so we had to reject batches.” (D.I. 125 at 61:14-18) As for phase separation, Dr. Franke explained that it “may occur when you have an emulsion and one of the phases separates, so liquid may not disperse anymore and it’s what we saw partly connected with the agglomeration.” (D.I. 125 at 62:5-8) b. Formulation of Finacea® Gel Dr. Karin -Hoffman (“Dr. Hoffman”), de--fendants’ non-infringement ’ and invalidity expert, testified that Schering opted to develop a gel formulation because it “had Skinoren® cream on the market and a gel formulation was a line extension.” (D.1.128 at 760:24-761:4) Dr. Hoffman explained that “[t]o develop the brand further [through a line extension], it’s usual to come up with a second formulation on the market” in order “to increase sales.” (D.I. 128 at 761:3-6) In-contrast, Dr. Franke opined that the decision to reformulate Skinoren® was based on a desire to solve the “agglomerate instability problem” and to cure “disadvantages of the cream regarding the ... application properties and cosmetic properties”, such as a whitening effect, while still “maintaining] the same efficacy of the cream.” (D.I. 125 at 63:8-15, 77:4-10) Because an azelaic acid concentration of 20 percent carried a risk of agglomeration, Dr. Franke and his colleagues first “thought of reducing the azelaic acid in content” to 15 percent. (Id. at 61:4-7, 63:19-64:6) Dr. Franke testified that the researchers “discussed on the one hand to keep close to the cream emulsion, SMno-ren® cream, and reformulate the cream in terms of thinking of 'how we can modify ingredients in quantity or quality, and on the other side we also thought about a hydrogel formulation type.” (Id. at 64:18-22) Between the cream emulsiqn and the hydrogel, “[t]here was certainly preference towards the .cream formulation.” (Id. at 65:13-17) The clinicians on the team “were afraid ... that reformulated or new formulation would lose efficacy,” and the team “thought that we might have to: cope with an efficacy problem.” (Id. at 66:2-9) Specifically, “there [was] the possibility that active ingredients are held back through this [hydrogel] matrix and interact.” (D.I. 125 at 66:12-18) Dr. Franke testified that the team ultimately selected the hydrogel formulation for further testing because the hydrogel solved the “agglomeration problem and phase separation” and it also offered “an improvement of the cosmetic properties” regarding the “whitening effect and spreadability problems with the cream.” (Id. at 66:19-21) After settling on a hydrogel formulation, the researchers initially “concentrated on being very similar, to the cream”- and later “switched to other ingredients and left out ingredients from the cream composition.”, (Id. at 68:4-21) In order to narrow down, the list of potential formulations, the team began “characterizing and analyzing the stability of the compounds ... also .taking care of the rheological behavior” and additionally “assess[ing] the [cosmetic] application properties.” (Id. at 70:21-71:5) According to Schering’s formulation development report, “[a] framework recipe based on a polyacrylate gel was available from an earlier acne therapeutic development using a related active ingredient,” and “[t]he gel has already been clinically tested as placebo control ‘ in the indication acne and should be changed as little as possible ... because of its high acceptance and tolerance.” (JTX- 20 at BAYER0434130) The report stated that “[f]urther development work concentrated on the choice and optimization of the moisture-retaining/re-greasing complex.” (Id.) Dr. Franke explained that after “we -saw that we [were] successfully on the track of solving the problems,” the question' remained of whether “there [was] still efficacy having now reduced azelaic acid and taken care of all other formulation parameters.” (D.I. 125 at 71:8-12) Eventually, the researchers selected two 15% azelaic acid hydrogels, hydrogel ■ A and hydrogel B, for further testing “[b]ased'on the results in our lab.” (Id. at 71:13-20, 72:17-22) Dr. Franke agreed that the two gel formulations “were based, on the same formulation concept” and they differed only in the kind of moisture-retaining/regreasing complex that was used. (D.I., 125 at 97:2-7; JTX 20 at BAYER0434141) Dr. Franke further agreed that hydrogel A “took ... ingredients from the cream formulation but made it into a gel.” (D.I. 125 at 97:2-5) Specifically, the moisture-retaining/re-greasing complex of the hydrogel A formulation included arlatone and cetearyl octonoate while the hydrogel B 'formulation-which would later become Finacea®-contained lecithin, triglycerides and poly-sorbate 80. (Id. at 95:11-17, 153:2-3; D.I. 128 at 757:4-10; JTX 20 at 9) Dr. Franke testified that lecithin was chosen for the hydrogel B formulation because of its “am-phiphilic structure” that allowed it to “interact in the skin layers,” and because- it “fit in” with “oils and active ingredients.” (D.I. 125 at 69:3-23) Triglycerides were selected because they have “a caring effect on the skin” and “in terms of its polarity as an oil, [it is] very suitable being together with lecithin.” (Id. at 70:4-10) • c. Franz diffusion cell test In the next phase of Finacea® development, Dr. Clemens Gunther (“Dr. Gunther), a named inventor on the '070 patent, “performed in vitro percutaneous penetration studies,” otherwise referred to as Franz diffusion cell tests or Franz cell tests. (D.I. 125 at 142:16-21; D.I. 127 at 518:2-519:18; JTX 16 at BAYER0384907) Defendants’ expert, Dr. Bozena Michniak-Kohn (“Dr. Michniak-Kohn”), testified that Franz cell tests are popular for ethical reasons as well as for the reason that researchers “don’t want a complicated screening method” in the initial stages of testing. (D.I. 127 at 518:21-519:16) Insofar as the goal is to ultimately use the product on living human skin, Franz cell testing is “just a model” that is “used to predict what might happen when a drug is given to humans.” (D.I. 125 at 183:20-25; see also id. at 184:24-185:5; D.I. 127 at 516:18-518:19; D.I. 128 at 764:22-765:10) The ability to use Franz cell testing to predict the efficacy in vivo on human skin is limited by the fact that in vitro skin is dead, it is “treated in some way” such as cutting the fat layer, and “there’s no blood supply.” (D.I. 127 at 517:13-518:8; see also D.I. 129 at 998:25-999:5) The goal of-the Franz cell test was to assess the “distribution of azelaic acid in the skin and the absorption across the skin” after treatment with the two hydro-gel formulations and Skinoren® cream. (D.I. 125 at 142:24-143:1, 143:17-20) To measure absorption, Dr. Gunther used a “Franz diffusion cell consisting] of a donor chamber and a receptor chamber, which both are separated by the [mouse] skin samplé acting as a membrane.” (Id. at 145:17-20) Mouse skin was the “established routine skin” used in the laboratory, and they “did not have access at that time to human skin vivo,” the “gold standard” for Franz cell testing. (D.I. 125 at 146:1-8, 156:20-24; D.I. 127 at 515:14) Because “hairless mouse skin is'much thinner than human skin ... [it] overexaggerat'es the numbers you see when you use chemical penetration enhancers.” (D.I. 127 at 516:18-517:9; see also D.I. 125 at 146:9-13) After selecting skin type and assembling the apparatus, “a thin layer of formulation [is] placed on the skin” and “the drug enters the stratum corneum and diffuses across the skin” then “partitions ... into the receptor chamber” and “excess flow-through” is captured and studied. (D.I. 125 at 148:1-149:4) Dr. Gunther explained that “[t]he concentrations in the receptor fluid resembled systemic absorption and thus might correlate or indicate systemic side effects.” (Id. at 156:20-24) At the end of the 24-hour period, Dr. Gunther measured “the distribution of azelaic acid in various skin layers” including the stratum corneum and the underlying layers.- (D.I. 125 at 151:10-16; JTX 16 at BAY-ER384907, -23) Dr. Gunther performed two experiments for the Skinoren® cream and two experiments for each of the hydrogel formulations, with four samples apiece for a total of eight data points per formulation. (D.I. 125 at 178:9-17; JTX 16 at BAY-ER0384916) However, Dr. Gunther decided to only “use the results of the second [hydrogel] experiment” as the “results of both experiments were not in agreement.” (D.I. 125 at 179:1-25) Dr. Gunther “did not perform any statistical analysis of the results of [the] study,” although he testified that it is not “standard practice in this type of pharmacokinetic investigation” to perform statistical analysis. (D.I. 125 at 174:25-175:2; D.1.126 at 371:5-372:21) Dr. Franke was “surprised to see such a good penetration behavior into living skin tissue with one of oúr gel candidates” containing lecithin and triglycerides (hydrogel B). (D.I. 125 at 73:2-21) Dr. Franke testified that they did not “see similar results with the hydrogel formulation containing thé arlatone and cetearyl octonoate ingredients [hydrogel A] that had been carried over from the cream.” (D.I. 125 and 73:22-5, 95:1-17, 152:9-153:4; JTX 16 at BAY-ER384923) More specifically, Dr. Gunther explained that, “after accounting] for the fact that there was only 15 percent azelaic acid in the hydrogels and 20 percent in the cream to begin with,” the azelaic acid remaining in the skin after treatment with hydrogel B was five' times higher than compared to Skinoren® cream. (D.I. 125 at 154:16-155:16; 174:15-22) Dr. Gunther “expected that the concentration in the skin and recéptor fluid would point in the same .. i direction,” but “[i]n this case, it appeared to be vice-versa, meaning that the fraction of dose present at the end of experiment in the skin was lower for Ski-noren® cream versus the hydrogel B.” (D.I. 125 at 158:14-19) In the words of plaintiffs’ expert, Dr. Norman Weiner (“Dr. Weiner”), “the inventive formulation had more of the ... azelaic acid going into the skin, but the prior art had more formulation going out of the skin.” (D.I. 128 at 917:23-918:13) Dr. Franke testified that, following the Franz diffusion cell test, “we again collected our data from the pharmaceutical technology lab and took the results of Dr. Gunther, and ... proposed this new candidate” for clinical trials. (D.I. 125 at 74:3-.7) Defendants propose that finances were the true motivator behind the decision to pursue hydrogel B, citing Sobering's formulation development report which stated that the “decisive” difference leading to a preference for hydrogel B over hydrogel A was that “[t]he components of the moisture-retaining/regreasing complex in [hydrogel B] can be processed cold, melting is unnecessary and makes large-scale production cheaper.” (JTX 20 at BAYER0434146) d. Clinical tests Next, a double-blind scarification test was performed “to detect small differences in irritation potential,” wherein hydrogel A and hydrogel B and Skinoren® cream “were applied once daily for 4 days in 20 [healthy human] subjects” and ,skin reactions were assessed (hereinafter “the scarification test”). (DTX 92; DTX 111 at BAYER0384619) Prior to application, the subject’s skin is “predamaged” by scarification to “mimic[] the situation found in lesional skin.’" • (DTX 111 at BAY-ER0384630) The reaction score for hydro-gel B was significantly higher than that for Skinoren® (DTX 111 at BAY-ER38.4644; DTX 93; D.I. 129 at 1037:17-1039:8), thus “confirm[ing] the results of the hairless mouse Franz flow-through diffusion cell study” (D.I. 129 at 1038:23-1039:3). Following the scarification test, an 8-week double-blind pilot study measuring percutaneous absorption was conducted to directly compare the initial clinical effect of hydrogel B to Skinoren®. (D.I. 125 at 162:22-25; D.I. 129 at 1003:14-17; JTX 11 at BAYER154358) According to the Scher-ing clinical study report, “[t]he aim of this exploratory pilot study was to investigate the effect of [hydrogel B] on acne lesions during an 8-week treatment period, as compared with that of [Skinoren®].” (JTX 11 at BAYER0154358) The study looked at “the relative decrease in the sum of facial papules and pustules,” ■ as well as “the amounts of [azelaic acid] excreted with the urine.” (JTX 11 at BAYER0154358) Dr. Guntheb testified that “there was no significant treatment difference between the Skinoren® cream and Finacea® or later on Finacea® hydrogel with regard to the efficacy in reducing the number of acne lesions.” (D.I. 125 at 167:19-22; D.I. 126 at 193:19-24, 373:23-374:1; JTX 11 at BAY-ER154393) Additionally, Dr. Weiner admitted that “the- progression of the efficacy over time was similar for both treatments.” (D.I. 127 at 443:23-444:4) According to Dr, Gunther, there was also “no statistical significance in urinary excretion of azelaic acid ... and this is certainly positive in terms of the point that this does not give rise to concerns related to systemic safety.” (D.I. 125 at 166:2-6; JTX 11 at BAYER0154360) Dr. Gunther opined that a study with only 30 patients (15 per treatment group) means it is “likely that such [a] study does not bring statistical power.” (D.I. 125 at 165:4-7; JTX 11 at BAY-ER0154370) The company proceeded with full-scale clinical trials comparing Finacea® to placebo formulations as “required by regulator purpose for submission.” (D.I. 126 at 206:3-8) In 2002, Dr. Franke gave a presentation to the marketing and management members of the project team detailing the benefits of Finacea® over Ski-noren®. (JTX 3) In the presentation, Dr. Franke identified three benefits of hydro-gel B: (1) no agglomeration or phase separation; (2) good results in the clinics and maintenance of efficacy; and (3) cosmetic benefits. (D.I. 125 at 76:2-22; JTX 3 at BAYER6527-530) Eventually, FDA approval was sought and Finacea® gel was approved and indicated for treating rosa-cea. (D.I. 125 at 74:8-15, 168:18-25) 3. The asserted patent The ’070 patent issued on March 18, 2003, and claims priority to U.S. Provisional Application No. 60/074,850 (“the '850 provisional”), filed on February 12, 1998. Plaintiffs assert independent claim 1 and dependent claims 2-12. The '070 patent claims azelaic hydrogel compositions, including Finacea®, as well as methods for treating rosacea and other skin conditions. ('070 patent, cols. 6:27-8:9) Independent claim 1 reads: 1. A composition that comprises: (i) azelaic acid as a therapeutically active ingredient in a concentration of 5 to 20% by weight, (iii) at least one triacylglyceride[] in a concentration of 0.5 to 5% by weight, (iv) propylene glycol, and • (v) at least one polysorbate, in an aqueous phase that further comprises water and salts, and-the composition further comprises (ii) at least one polyacrylic acid, and (vi) lecithin, wherein the composition is in the form of a hydrogel. (Id. at col. 6:28-38) The specification of the '070 patent identifies Skinoren® cream and EP 0 336 880 as relevant prior art cream formulations that contain azelaic acid. ('007 patent, col. 1 at 16-36) Skinoren® cream is described as “the closest prior art.” (Id. at col. 1:36) The specification also' identifies non-azelaic acid prior art “emulsions” or “nanoemul-sions” such as the composition disclosed in International Application WO 96/11700. ('070 patent, col. 1:37-49) Example 1 describes the formulation and processing steps for producing the claimed hydrogel. ('070 patent, col. 5:20-39) Specifically, a “pre-emulsion” is formed from a mixture of benzoic acid, EDTA, triglycerides, polysorbate 80, lecithin, and propylene glycol. (Id. at col. 5:20-32) The “pre-emulsion” is homogenized, and then polyacrylic acid and azelaic acid are added. ('070 patent, col. 5:32-34) Finally, a gel is formed by adding sodium hydroxide, which raises the pH of the solution. (Id. at col. 5:34-36) The specification emphasizes that “[t]he presence of polyacrylic acid is essential” and “decisive for the production of the hydrogel.” (Id. at col. 2:51 :52) The specification defines polyacrylic acid as “an anion-active polymerizate of acrylic acid, which is only partially water-soluble” where “[t]he one-percent aqueous suspension has a pH of 3 and approximately the same viscosity as water.” (Id. at col. 3:42-45) The specification states that “gel formation and the production of highly viscous products” only occurs during neutralization (raising the pH) of polyacrylic acid. (Id. at col. 3:46-48) One named advantage of the claimed composition is that it “allows a larger amount of pharmaceutical active ingredient to penetrate into living skin layers and/or cutaneous organs.” (Id. at col. 2:29-40) Dr. Weiner, Dr. Michniak-Kohn and Dr. Gunther all testified' that the claim of “increased bioavailability” is solely supported by the results from the, Franz diffusion cell test, as described in example 2 of the specification. (D.I. 125 at 170:21-717:8; D.I. 128 at 932:2-8; D.I. 129 at 1013:4-6; '070 patent, 5:40-6:26) Another named advantage of the claimed composition is that when lecithin is 1% or less by weight, the composition “does not form any standard nanoemulsion” but rather forms a gel “that comprises a homogenous mass with virtually no vesicles” as detected by a scanning electron microscope. ('070 patent, cols. 2:61-3:3) Dr. Franke testified that the electron microscopy was performed on Finacea® by Dr. Rolf Schubert (“Dr. Schubert”) at the Albert Ludwig Universitat. (D.I. 125 at 111:1-19) In a report submitted to Dr. Hoffman, Dr. Schubert wrote that “the examinations have proven to be particularly difficult” as “the processing methods you recommended for us were not optimally suited to separate and identify structures to a sufficient extent.” (D.I. 125 at 112:22-113:3; DTX 16 at BAYER0524392) Dr. Schubert stated that “[further examinations will have to be performed,” although no further examinations were conducted following the initial report. (D.I. 125 at 113:7-114:4; DTX 16 at BAY-ER0524392) Dr. Schubert concluded that, given the heterogeneity of the samples, “more images must be used for interpretation.” (D.I. 125 at 115:5-9; DTX 16 at BAY-ER0524404) 4. The accused ANDA product a. Overview Defendants’ ANDA product (“the accused product” or “the accused formulation”) is a composition for topical administration to treat rosacea that contains azelaic acid as the therapeutically active ingredient at a concentration of 15% by weight, isopropyl myristate at a concentration of 2% by weight, propylene glycol at a concentration of 12% by weight, at least one polysorbate,, at least one po-lyacrylic acid at a concentration of 0.85% by weight, purified water, benzoic acid at a concentration of 0.10% by weight, and edetate disodium at a concentration of 0.10% by weight. (D.I. 118, ex. 1 at ¶¶ 44-59) b. Formulation of the accused product Mr. Kamal Mehta (“Mehta”), defendants’ corporate witness, testified that defendants used, inter alia, “details about Finacea® [that] are available in the public domain” such as the Finacea® label to develop the accused formulation. (D.I. 126 at 214:11-16; PTX 214 at GMG-710) For the first experimental batch, Mehta agreed that defendants used “the formulation that was listed in the patent.” (D.I. 126 at 220:12-19; see also JTX 54 at GMG_VP1266-67) Like the procedure described in example 1 of the '070 patent, defendants’ manufacturing process involved dissolving EDTA and benzoic acid in water, adding additional excipients to create a homogenized “pre-emulsion,” adding polyacrylic acid and azelaic acid, and finally neutralizing with sodium hydroxide to achieve “orientation of the gel.” (JTX 39 at GMG-0014878; JTX 53 at GMG-VP798-800; '070 patent, col. 5:22-39) In their original ANDA submission, defendants detailed experimental trials in which triglyceride and lecithin were swapped for alternate excipients, with the goal of “match[ing] the appearance ... and chemical stability of the [experimental] gel with the reference-listed drug Fi-nacea® Gel 15%.” (JTX 53 at GMG-VP000776; D.I. 126 at 220:21-227:10) Defendants’ overall “[objective was to develop a formulation which doesn’t fall in the [scope of] the patent claims.” (D.I. 126 at 217:14-23) Defendants' determined that batch 540/03-08/036 (“batch 036”) and batch 540/03-08/041 (“batch 041”) were “satisfactory” formulations. ’(JTX 53 at GMG_YP000776) In batch 036, PPG-20Methyl glucose ether distearate was substituted for triglyceride and lecithin. (Id.) In batch 041 — which would later become the accused formulation — isopropyl myris-tate was substituted for triglyceride and lecithin “to improve the penetration.” (Id.; JTX 54 at GMG-VP001272; D.I. 126 at 225:14-226:13) In their original ANDA submission, defendants listed the “function” of isopropyl myristate, lecithin and medium chain triglyceride as “penetration enhancer.” (JTX 53 at GMG-VP000775) With the exception óf the substitution of isopropyl myristate for triglyceride and lecithin, all other excipients in the accused product remained “exactly the same” as those in Finacea®. (D.I. 126 at 313:18-21; JTX 53 at GMG-VP000775; JTX 54 at GMG_VP001266) c. Franz diffusion cell and clinical testing Defendants performed Franz diffusion cell tests with human cadaver, skin, comparing the rate of penetration of azelaic acid across the skin layers between batch 036, batch 041 and Finacea® gel. (D.I. 126 at 233:18-235:12; JTX 54 at GMG_VP1271-73; JTX 38 at GMG-12942-45, -949) In the Franz diffusion cell test, defendants applied a finite dose of product, then measured penetration and absorption of azelaic acid over a period of 48 hours. (JTX 38 at GMG-12942, 44-49) For both batch 041 and Finacea®, “more azelaic acid stayed in the epidermis skin layer than what went through to the reservoir.” (D.I. 128 at 720:9-12; JTX 38 at GMG-0012948) Compared to one another, nearly twice as much azelaic acid remained in the epidermis following treatment with Finacea® than following treatment with batch 041. (JTX 38 at BMB-0012947) Both batch 041 and Fi-nacea® reached a peak flux between 1 to 5 hours after application, although the absorption levels declined more rapidly for batch 041 than for Finacea®. (JTX 38 at BMB_0012947; D.I. 127 at 581:9-17) Mehta admitted that defendants selected batch ■ 041 over batch 036 because it was “close[r] to the reference product, Finacea®.” (D.I. 126 at 214:8-11, 241:8-10)) The study concluded that “there were no statistically significant differences” across the parameters, and “the flux profiles suggest that the test formulations are similar to, but not identical to, the Finacea® reference formulation.” (JTX 38 at GMG-0012949) Meh-ta agreed that “once [defendants] got the results from the cadaver study with the isopropyl-myristate containing formulation, [they] didn’t investigate ... any other alternative formulations.” (D.I. 126 at 227:6-11) Defendants then performed a large-scale clinical trial comparing batch 041 to Finacea®, and concluded that “the test product was bioequivalent” to - Finacea® and superior to placebo. (Id. at 259:13-20, 261:7-11; PTX 219 at GMG-002365-68, 2412) B. Claim Construction 1. Standard 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. Conceptronie, 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. 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 The parties agree that a “hydrogel” is a semi-solid dosage form wherein the gel structure contains water and a gelling agent to form a gel, which may contain dispersed particles such as undissolved azelaic acid. The crux of the parties’ disagreement is whether, as defendants propose, hydrogels may also contain insoluble liquids. Regarding the term “lecithin,” the parties dispute whether construction of the term is necessary given that the construction may not alter the outcome of the court’s validity or infringement analysis. Substantively, the parties dispute whether lecithin is equivalent to phosphatidylcho-line or whether, lecithin is a complex mixture of compounds that is characterized by the presence of phosphatidylcholine. 3. “Hydrogel” Plaintiffs admit that claim 1 calls for the addition of a small amount of oil-triacylglyceride.in a concentration of 0.5 to 5%-by w;eight-which is insoluble in liquid water. ('070 patent, claim 1) Plaintiffs also recognize that example 1 of the '070 patent describes* a homogenized mixture containing liquid water and triacylglycerides as a “pre-emulsion.” (Id. at col. 5:20-32) Plaintiffs contend, however, that no more than a trace amount of triacylglyceride would remain in the solution following addition of polyacrylic acid and neutralization of the solution to form a gel, arguing that droplets of triacylglyceride would be .adsorbed onto the surface of any solid aze-laic acid particles. Although the issue is most narrowly framed as whether the claimed hydrogel contains insoluble liquid vesicles, the ;parties somewhat confusingly present the issue as,whether the claimed hydrogel “contains” a nanoemulsion. Plaintiffs argue that defendants blur the line between a gel and an emulsion in order to advance their invalidity position, while defendants respond that they do not blur any lines insofar as they do not argue that gels are equivalent to emulsions. As such, the parties appear to accept the premise that a gel differs from an emulsion in that, at least bn the macro level, a gel is a single-phase semisolid and an emulsion is a mixture of two liquids. With this framework in mind, the court considers the following intrinsic evidence: Under the heading of “advantages,” the specification states that [i]t has unexpectedly proven that the composition according to the invention in the case of concentrations in lecithin of 1% by weight and less does not form ahy standard nanoemulsions according to the prior art. Rather a gel is present that comprises a homogenous mass with virtually no vesicles, but does have membrane fragments. The fact that azelaic acid and the remainder of the solution do not form any nanoemulsions was not expected. Only with the aid of scanning electron microscope recordings was it possible to provide clarity. It turned out that no nanoemulsions could be identified in microscopic examination. ('070 patent, cols. 2:61-3:7) By stating that the claimed hydrogel “unexpectedly” fails to form a “standard nanoemulsions” as in the prior art, the drafters belie an expectation that gel compositions will typically form nanoemulsions. Moreover, in using the word “nanoemulsion,” it is evident that the drafters envisaged a “gel” present as a “homogenous mass” that contains vesicles. Indeed, as explained in the final two sentences of the passage, the inventors imaged samples of the claimed composition with a scanning electron microscope for the purpose of verifying the absence of a nanoemulsion (a.k.a. vesicles). Importantly, the absence of a nanoemulsion was ■ only observed in formulations containing less than 1% lecithin by weight. Although the embodiment disclosed in example 1 and .claimed in dependent claim 4 contains lecithin in the vesicle-free range of 0-1 %, independent claim 1 does not specify a concentration and dependent, claim 11 claims a concentration in the range of 0-3%. Interpreting claim 1 as being limited to the vesicle-free embodiment would run afoul of the doctrine of claim differentiation and would improperly read a single embodiment from the specification into the claims. See Phillips, 415 F.3d at 1323. The court’s construction ,is further bolstered by the prosecution history. The '850 provisional application, to which the '070 patent claims priority, describes a method of making a “nanoemulsion gel” wherein the gel is made in the same manner as the method disclosed in example 1 of the '070 patent. (DTX 15 at 11-14) The concentrations disclosed in the two methods are not identical, but are overlapping. (DTX 15 at 11; '070 patent, col. 5:26-40) For example, the '850 application calls for 1-5 parts lecithin, whereas the '070 patent calls for 1 part lecithin. (DTX 15 at 11; '070 patent, col. 5:30-31) The '850 application goes on to state that “detection of the nanoemulsion” is achieved by measuring “vesical [sic] sizes using zeta sizers.” (DTX 15 at 11) The issued '070 patent substitutes the phrase “nanoemulsion gel” with “gel,” and omits the language regarding detection of vesicles,, presumably because at a lecithin concentration of less than 1%, no vesicles were .detected. Nonetheless, the example provided by the '850 application reinforces the concept that, when, lecithin is in a range of .1-5%, a “nanoemulsion gel” will form that contains measurable nanovesi-cles. For the foregoing reasons, the court construes “hydrogel” as “a semisolid dosage form that contains water and a gelling agent to form a gel, which may contain dispersed particles and/or insoluble liquids.” 4. “Lecithin” The parties dó not dispute the meaning of the term lecithin in the context of literal infringement, nor do plaintiffs allege that defendants’ generic product contains lecithin. (D.I. 91, ex. 15 at 230:15-232:23) Moreover, defendants do not allege that the construction of lecithin impacts the court’s analysis regarding validity. (See D.I. 97 at 18-28) Rather, defendants propose that the construction of lecithin is relevant to the court’s analysis of infringement under the doctrine of equivalents. Specifically, defendants object to the portion of plaintiffs’ proposed construction equating lecithin with phosphatidylcholine. Defendants’ counsel argues that limiting what is allegedly a mixture of compounds to a single pure compound makes lecithin appear more like isopropyl myristate, the compound allegedly substituted for lecithin and triglycerides in the generic compound. However, this non-infringement posture is not adopted by defendants’ expert, who stated that the difference between the two proposed constructions “doesn’t make any difference to my opinion” as to whether the accused composition meets the limitations of the claims. (D.I. 91, ex. 15 at 236:17-237:7) Because construing “lecithin” will not impact the court’s analysis, the court declines to issue a construction'. See Jang v. Boston Sci. Corp., 532 F.3d 1330, 1336-37 (Fed.Cir.2008) (cautioning that “[t]he Supreme Court has explicitly held that Article Ill does not permit the courts to resolve issues when it is not clear that the resolution of the question will resolve-a concrete controversy between interested parties.”). C. Infringement 1. Standard 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). To prove direct infringement, the patentee must establish, by a preponderance of the evidence, that one or more claims of the patent read on the accused device literally or under the doctrine of equivalents. See Advanced Cardiovascular Sys., Inc. v. Scimed Life Sys., Inc., 261 F.3d 1329, 1336 (Fed.Cir.2001). A two-step analysis is employed in making an infringement determination. See Markman, 52 F.3d at 976. 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). “Direct infringement requires a party to perform each and every step or element of a claimed method or product.” Exergen Corp. v. Wal-Mart Stores, Inc., 575 F.3d 1312, 1320 (Fed.Cir.2009) (internal quotation marks omitted). “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, 1558 (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). One test used to determine “insubstantiality” is whether the element performs substantially the same function in substantially the same way to obtain substantially the- same result as the claim limitation. Graver Tank & Mfg. Co. v. Linde Air Products Co., 339 U.S. 605, 608, 70 S.Ct. 854, 94 L.Ed. 1097 (1950). This test is commonly referred to as the “function-way-result” test. The mere showing that an accused device is equivalent overall to the claimed invention is insufficient to establish infringement under the doctrine of equivalents. The patent owner has the burden of proving literal infringement and/or infringement under the' doctrine of equivalents by a preponderance of the evidence. See SmithKline Diagnostics, Inc. v. Helena Lab. Corp., 859 F.2d 878, 889 (Fed.Cir.1988) (citations omitted). The doctrine of equivalents is limited by the doctrine of prosecution history estoppel. In Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., Ltd., 535 U.S. 722, 122 S.Ct. 1831, 152 L.Ed.2d 944 (2002) (“Festo I”), the Supreme Court stated: Prosecution history estoppel ensures that the doctrine of equivalents remains tied to its underlying purpose. Where the original application once embraced the purported equivalent but the patentee narrowed his claims to obtain the patent or to protect its validity, the patentee cannot assert that he lacked the words to-describe the subject matter in question. The doctrine of equivalents is premised on language’s inability to capture the essence of innovation, but a prior application describing the precise element at issue undercuts that premise. In that instance the prosecution history has established that the inventor turned his attention to the subject matter in question, knew the words for both the broader and narrower claim, and affirmatively chose the latter. Id. at 734-735, 122 S.Ct. 1831. In other words, the prosecution history of a patent, as the public record of the patent proceedings, serves the important function of identifying the boundaries of the patentee’s property rights. Once a patentee has narrowed the scope of a patent claim as a condition of receiving a patent, the paten-tee may not recapture the subject matter surrendered. In order for prosecution history estoppel to apply, however, there must be a deliberate and express surrender of subject matter. See Southwall Techs., Inc. v. Cardinal IG Co., 54 F.3d 1570, 1580 (Fed.Cir.1995). Once a court has determined that prosecution history estoppel applies, it must determine the scope of the estoppel. See id. at 1580. This requires an objective examination into the reason for and nature of the surrendered subject matter. Id.; see also Augustine Med., Inc. v. Gaymar Indus., Inc., 181 F.3d 1291, 1299 (Fed.Cir.1999). If one of ordinary skill in the art would consider the accused product to be surrendered subject matter, then the doctrine of equivalents cannot be used to claim infringement.by the accused product; i.e., prosecution history estoppel necessarily applies. Augustine Med., 181 F.3d at 1298. In addition, a “patentee may not assert coverage of a ‘trivial’ variation of the distinguished prior art feature as an equivalent.” Id. at 1299 (quoting Litton Sys., Inc. v. Honeywell, Inc., 140 F.3d 1449, 1454 (Fed.Cir.1998)). “[A] narrowing amendment made to satisfy any requirement of the Patent Act” creates a presumption that “the patentee surrendered ah subject matter between the broader and the narrower language” and bars any equivalents. Festo I, 535 U.S. 722, 736, 740, 122 S.Ct. 1831, 152 L.Ed.2d 944 (2002); see also Honeywell Int’l, Inc. v. Hamilton Sundstrand, 370 F.3d 1131, 1139 (Fed.Cir.2004) (prosecution history estoppel “bar[s] the paten-tee from asserting equivalents if the scope of the claims has been narrowed' by an amendment during prosecution.”). Thus, a presumption of prosecution history estop-pel is established by showing that the pat-entee made a narrowing amendment and that “the reason for that amendment was a substantial one relating to patentability.” Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 344 F.3d 1359, 1366 (Fed.Cir.2003) (en banc) (“Festo II”). There are three exceptions to this presumption: (1) the equivalent was “unforeseeable at the time of the narrowing amendment”; (2) the rationale for the amendment “bore no more than a tangential relation to the equivalent in question”; or (3) “some other reason suggested that the patentee could not reasonably have been expected to describe the alleged equivalent.” Festo I., 535 U.S. at 740-41, 122 S.Ct. 1831. To establish. indirect infringement, a patent owner has available two theories: active • inducement of infringement and contributory infringement. See 35 U.S.C. § 271 (b) & (c). To establish active inducement of infringement, a patent owner must show that an accused in-fringer “knew or . should have known [their], actions would induce actual infringements.” DSU Med. Corp. v. JMS Co., Ltd., 471 F.3d 1293, 1306 (Fed.Cir.2006). To establish contributory infringement, a patent owner must show that an accused infringer sells “a .component of a patented machine .,. knowing the same to be especially- made or especially adapted for use in an infringement of such patent, and not a staple article or commodity of commerce suitable for substantial nonin-fringing use.” Golden Blount, Inc. v. Robert H. Peterson Co., 365 F.3d 1054, 1061 (Fed.Cir.2004) (quoting 35 U.S.C. § 271 (o))'. Liability under either theory, however, depends on the patent owner having first shown direct infringement. Joy Technologies, Inc. v. Flakt, Inc., 6 F.3d 770, 774 (Fed.Cir.1993). 2. Doctrine of equivalents Plaintiffs allege that defendants infringe claims 1-12 of the '070 patent (“the asserted claims”) under the doctrine of equivalents. Defendants do not dispute that the accused product meets the azelaic acid, propylene glycol, polysorbate, aqueous phase with water and salts, and polyacrylic ácid limitations, as well as the concentration ranges specified in claims'1, 5, 6 and 10. Defendants also do not dispute that the accused product meets the additional limitations recited in dependent claims 2, 7, 8, • 9 and 12. (D.I. 118, ex. 1 at ¶¶ 53, 57, 58) Defendants contend, however, that the accused product does not fully satisfy the limitations of the asserted claims insofar as the accused product does not physically contain triacylglycerides, lecithin or soybean lecithin. {Id. at. ¶¶ 46-47) Plaintiffs argue that defendants’ substitution of iso-propyl myristate for triglycerides and lecithin raises a question of legal equivalency under the “function-way-result” test, a. Function (1) Evidence Dr. Weiner testified that lecithin and triglycerides function as penetration enhancers in the claimed formulation. '(D.I. 126 at 320:15-323:16) In support of this conclusion, Dr. Weiner examined the results of the Franz diffusion study and found that “the inventive formulation was much more effective than the prior art in allowing the penetration of the azelaic acid into ... the skin.” (D.L 126 at 321:19-21) Dr. Weiner explained that, because “the amount of propylene glycol in [Skinoren® cream and Finacea®] were [sic] essentially the same,” the increased penetration could not be explained by differing amounts of azelaic acid and, therefore, must be explained by the addition of lecithin and triglycerides. {Id. at 323:4-17) Dr. Michn-iak-Kohn agreed that “a person of ordinary skill in the art [would] understand that lecithin contributed to the reportedly better results for the claimed gel function.” (D.I. 127 at 563:9-12) Indeed, Dr. Franke testified that he originally selected lecithin for its “penetration enhancement” qualities in that it could “interact in the skin layers” which are “also double membrane structures with a similar chemistry” to lecithin. (D.I. 126 at 69:11-19) Dr. Franke testified that he selected triglycerides due, in part, to their “polarity as an oil” which makes them “suitable being together with lecithin.” (Id. at 70:2-10) Defendants argue that Dr. Weiner’s analysis should be-, disregarded because he was mistaken in concluding that Skino-ren® cream does not contain triglycerides (D.I, 127 at 453:22-455:20), and he did not offer an opinion as to whether lecithin alone could.act as a penetration enhancer. Defendants also argue that the Franz diffusion test is unreliable because one of the experimental data sets was discarded (JTX 16 at BAYER0384920; D.I. 125 at 178:9-179:17) and because Dr. Gunther “did not perform any- statistical analysis of the results of [the] study” (D.I. 125 at 174:25-175:2; D.I. 126 at 371:5-372:21).. . Plaintiffs argue i that in defendants’ ANDA filings and formulation development report, defendants repeatedly stated that the function'of lecithin and triglyceride in the claimed formulation and isopro-pyl myristate in the accused formulation is identical; to wit, all three excipients enhance penetration of the skin. (JTX 53 at GMG-VP765, -774-76; JTX 54 at GMG_VP1241, -252, -253, -272; PTX 312 at GMG_137769; D.I. 126 at 217:1-10, 226:2-5, 228:19-229:4, 323:25-325:22) As detailed supra, defendants performed Franz cell diffusion tests comparing the accused product to Finacea® and found that the two formulations have statistically similar penetration profiles in terms of the amount and rate of skin penetration. ■ (JTX 38 at GMG-0012947-49) In response to a query by the FDA regarding defendants’ selection of penetration enhancer in the accused product, defendants wrote that the penetration studies “demonstrate the equivalence” between Finacea® and the accused product. (PTX 312 at GMG_0137769) Defendants respond that plaintiffs are in the best -position to understand the' function of lecithin and triglycerides in the claimed formulation.. {See D.I. 126 at 369:24-370:5) In this vein, defendants cite several documents from plaintiffs suggesting that an increased percentage of dissolved azelaic acid, not the presence of lecithin and triglycerides, is responsible for the increased penetration observed in the claimed hydrogel. (JTX 3 at BAY-ER0006537 (a marketing presentation by Dr. Franke reports the percentage of dissolved azelaic acid as -25% for Finacea® and -3% for Skinoren® cream); DTX 92 (a poster from two scientists involved in clinical development of Finacea® states that the hydrogel “contains a higher dissolved fraction of azelaic acid than the cream, leading to improved drug release and bioa-vailability”)) Indeed, Dr. Franke admitted that, none of plaintiffs’ documents describes the function of lecithin and triglycerides as penetration enhancers. (D.I. 125 at 88:23-89:10; see also D.I. 126 at 369:7-11) Instead, plaintiffs’ development reports and NOA submissions affirmatively describe the function of lecithins and triglycerides as either moisturizers, emollients or emulsifiers. (See JTX 20 at BAY-ER0434132; DTX 19 at BAYER0157202; JTX 11 at BAYER0154373) Defendants also cite various publications to support the conclusion that lecithin or triglycerides are not penetration enhancers, including a publication by Dr. Weiner in which he wrote that “when phospholipid based lipo-somes are incorporated in an emulsion, the delivery of the drug is greatly diminished because phospholipids do not function as permeation enhancers.” (D.I. 126 at 430:9-19; see also JTX 49 (the Handbook of Pharmaceutical Excipients does not identify either lecithin or triglycerides as being a penetration enhancer); JTX 29 at BAY-ER0544905; D.I. 126 at 395:14-396:1) The '070 patent itself is silent on the question of whether lecithins or triglycerides function as penetration enhancers. (D.I. 126 at 368:3-6) Plaintiffs offer that their failure to include “penetration enhancer” as a potential function of lecithin and triglycerides is not fatal given that an excipient may have multiple relevant functions. In support of this position, plaintiffs cite Dr. Weiner’s testimony that “lecithin can be an emollient ... and the triglyceride can act as a humectant or emollient [skin softener]” in addition to acting as penetration enhancers. (D.I. 126 at 320:7-18) Additionally, Dr. Michniak-Kohn testified that isopropyl myristate may act as an emollient or as a penetration enhancer. (D.I. 127 at 552:15-553:4) Plaintiffs also cite Mehta’s testimony that isopropyl myristate, lecithin and triglycerides each perform multiple functions, and that they share at least the qualities of penetration enhancer and emulsifying agent. (D.I. 126 at 229:24-230:4, 232:24-233:10) (2) Discussion The parties agree that two factors could contribute to the increased penetration observed in plaintiffs’ Franz cell study: (1) increased dissolution of azelaic acid; or (2) the presence of chemical penetration enhancers. The '070 patent does not specify the role of lecithin and triglycerides in the claimed composition, and plaintiffs’ Franz cell test was not designed to control for the potential contribution of either factor. As such, Dr. Weiner artificially held one variable constant by assuming that the amount of dissolved azelaic acid did not differ between samples, and he was then able to attribute the observed increase in penetration to the presence of lecithin and triglycerides. (D.I. 126 at 323:4-17) The court is troubled by Dr. Weiner’s method of deduction, especially given that Dr. Weiner did not realize that Skinoren® cream also contains triglycerides and given that plaintiffs’ scientific representatives twice reported an increased percentage of dissolved azelaic acid in Finacea® as compared to Skinoren® cream. (JTX 3 at BAYER0006537; DTX 92) Nonetheless, although plaintiffs’ position lacks scientific rigor, the court discerns nothing in the record that indicates that lecithin and triglycerides cannot act as penetration enhancers. Indeed, Dr. Michaniak-Kohn admitted that a person of ordinary skill in the art would understand that lecithin contributed to the better results of the claimed gel (D.I. 127 at 563:9-12), and Mehta acknowledged that lecithin and triglycerides could function as penetration enhancers (D.I. 126 at 232:24-233:10). Additionally, Dr. Franke testified that he initially selected lecithin for its “penetration enhancement” properties and triglyceride for its compatibility with lecithin. {Id. at 70:2-10) Similarly, the fact that plaintiffs did not identify lecithin and triglycerides as penetration enhancers in their own filings and internal documents does not exclude the possibility that they function as such in the claimed composition. Plaintiffs provided testimony from both sides’ witnesses to support the common-sense proposition that a given excipient may perform more than one function. (D.I. 126 at 320:7-18; D.I. 127 at 552:15-553:4) It logically follows that listing the function of lecithin and triglyceride as “moisturizer” or “emollient” does not mean that the excipients cannot also act as penetration enhancers. The court is also swayed by defendants’ repeated statements in their ANDA filings that lecithin, triglyceride and isopropyl myristate function as penetration enhancers. {See, e.g., JTX 53 at GMG-VP765, -774-76) The Federal Circuit has held that, “[b]ecause drug manufacturers are bound by strict statutory provisions to sell only those products that comport with the ANDA’s description of the drug, an ANDA specification defining a proposed generic drug in a manner that directly addresses the issue of infringement will control the infringement inquiry.” Abbott Labs. v. TorPharm, Inc., 300 F.3d 1367, 1373 (Fed.Cir.2002). Moreover, “[i]f an ANDA specification defines a property of a compound such that it must meet a limitation of an asserted claim, then there will almost never be a genuine dispute of material fact that the claim is infringed with respect to that limitation.” Id. Here, the infringement inquiry hinges on the question of whether the claimed and accused excipients both act as penetration enhancers. Throughout their ANDA filings, defendants repeatedly answered that question in the affirmative. Defendants should not be permitted to liken their product to the claimed composition to support their bid for FDA approval, yet avoid the consequences of such a comparison for purposes of infringement. b. Way (1) Evidence At trial, Dr. Weiner opined that lecithin, triglyceride, and isopropyl myris-tate enhance penetration by “temporarily altering -the structural properties of the lipid bilayers in the stratum corneum.” (D.I. 126 at 332:7-336:25) For support, Dr. Weiner relied on a 1987 article entitled “Mode of Action of Penetration Enhancers in Human Skin” by B.W. Barry (“Barry”). (JTX 29) Barry proposed that penetration enhancers “interact [ ] in some way with the stratum corneum lipid structure, disrupting its organization and increasing its fluidity.” (D.I. 126 at 334:12-21; JTX' 29) Barry reported that non-polar materials, such as oleic acids, “enter the lipid regions ... where they disrupt the structure.” (JTX 29 at BAYER0544916) Dr. Weiner admitted' that Barry discloses a “general theory of skin accelerant activity” in which if does not directly “identify lecithin or triglyceride as penetration enhancers.” (D.I. 126 af 395:15-396:1) Dr.' Weiner opined that Barry is nonetheless applicable to the instant case because-like oleic acid-lecithin,' triglycerides, and ispropyl myris-tate are large non-polar materials. (D.I. 127 at 481:19-23) Dr. Weiner explained that lecithin, triglycerides, isopropyl myr-istate, and the lipids in the stratum corne-um are all hydrophobic and, as such, are “very soluble in oils.” (D.I. 126 at-335:5-17) Like the lipids in the stratum corneum, lecithin and isopropyl myristate are amphi-philic and, therefore, are likely to “enter into the lipid portion of the .stratum corneum.” (D.I. 128 at 715:23-716:2) Triglycerides are compatible with the lipids in the' stratum corneum by virtue of being insoluble and “extremely compatible, with lecithin ” (D.I. 126 at 335:22-335:20) Plaintiffs argue that the exact location of integration is irrelevant as Dr. Michniak Kohn agreed that a disruptive “interaction of a penetration enhancer can be with the polar heads of the lipid, in between those lipid heads, or between the hydrophobic tails of the lipids in the stratum corneum.” (D.I. 128 at'715:23-716:2) Although Dr, Weiner did not opine on the relationship between chemical class and penetration ability, defendants' expert acknowledged that lecithin,. triglyceride, and isopropyl myristate contain ■ a fatty ester group (id. at 705:2-706:1), a feature that defendants linked to absorption capacity in their ANDA submission. (JTX 53 at GMG-VP774 (isopropyl myristate was selected “as [a] penetration enhancer instead of lecithin and medium chain triglyceride because isopropyl myristate has a good absorption capacity due to [its] fatty ester group ...,); D.I. 126 at 275:9-276:20; D.I. 128 at 706:2-23) Moreover, defendants do not dispute that an article cited by Dr. Michniak-Kohn categorizes chemical penetration enhancers and their mechanism of action by class. (DTX 83 at GMG-137198 (listing isopropyl myristate under the category of “fatty acid esters”) Although Dr. Michniak-Kohn relied on several publications to support her opinions at trial, defendants’ post-trial briefing focuses on a single article entitled “An Attempt to Clarify the Mechanism of the Penetration Enhancing Effects of Lipo-philic Vehicles with Differential Scanning Calorimetry (DSC)” by Claudia S. Leopold et al. (“Leopold”). (DTX 84) Leopold used DSC to test the' ability of various excipi-ents to “alter the structure of the stratum corneum,” including caprylic/capric acid triglycerides and phospholipids and iso-propyl myristate. (DTX 84 at GMG-0136577-78) Leopold concluded that “the observed- decrease of only the phase-transition enthalpy by the ... caprylic/ca-pric acid triglycerides with phospholipids is due to dissolution or extraction of the stratum corneum lipids.” (DTX 84 at GMG-0136581) However, “[v]ehicles which cause both a reduction of the enthalpy and a decrease of the phase-transition temperatures” such as isopropyl myristate, “are thought to fluidize the lamellar-gel phase of the stratum corneum lipids, and possibly also partially dissolve the lipids.” (Id.; D.I. 127 at 568:19-23) Defendants argue that fluidization of the stratum corneum lipids is materially different from dissolution of the stratum corneum lipids. The court disagrees, given that Leopold itself concedes that “[t]he observed enthalpy decrease caused by dissolution or extraction of the intercellular lipids cannot be distinguished from enthalpy changes caused by fluidization of the lipid bilayers.” (DTX 84 at GMG-0136580) Plaintiffs argue that, even if DSC could distinguish between fluidization and dissolution, such a difference is insignificant where Dr. Miehniak-Kohn agreed that both .types of penetration enhancers are “lipophilic liquids” that may enhance drug penetration by causing a “specific alteration of the. stratum corneum lipids.” (D.I. 128 at 709:9-710:2; DTX 84 at GMG-136577) -The parties - agree 'that defendants’ Franz cell study demonstrated no statistically-significant differences in the flux profiles between batch 041, batch 036 and Finacea®. (JTX 38 at GMG_0012949) The parties also agree that batch 041 was selected for further development because its flux profile was “more similar to Fina-cea®.” (Id.; JTX 38 at BMB-0012949; JTX 41 at GMG-0015047) Defendants-propose two somewhat incongruous interpretations of-the data: (1) lecithin and triglyceride enhance penetration differently than iso-propyl myristate because the flux curves are not “very, very close or overlapping” (D.I. 127 at 581:18-582:2); and (2) a penetration enhancer cannot be responsible for increased absorption because the flux curve for b