Supernus Pharmaceuticals, Inc. v. TWi Pharmaceuticals, Inc. (265 F. Supp. 3d 490, 2017)

United States District Court for the District of New Jersey 2017-09-21

Food and Drugs Patents

Citations

Full opinion text

OPINION FOR PUBLIC VIEWING

BUMB, UNITED STATES DISTRICT JUDGE:

TABLE OF CONTENTS

I. INTRODUCTION ... 493

II. BACKGROUND ... 494

A. The Drug Approval Process ... 494

B. The Patents-in-Suit ... 495

i. The ’898 Patent ... 495

ii. The ’131 Patent ... 495

iii. The ’930 Patent ... 495

C. Oxtellar XR® ... 496

D. TWi’s ANDA ... 496

III. LEGAL ANALYSIS ... 496

A. Claim Construction ... 497

i. Homogeneous Matrix ... 498

ii. Agent that Enhances the Solubility of Oxcarbazepine ... 498

B. Infringement ... 499

i. The Patents-in-Suit ... 499

ii. The TWi ANDA Product ... 500

C. Invalidity ... 519

i. Written Description ... 519

ii. Indefiniteness ... 523

IV.CONCLUSION ... 525

I. INTRODUCTION

This is an action for patent infringement brought by Plaintiff Supernus Pharmaceuticals, Inc. (“Supernus” or the “Plaintiff’) against Defendants TWi International LLC and TWi Pharmaceuticals, Inc. (together, “TWi” or the “Defendants”), pursuant to 35 U.S.C. § 271(e)(2)(A) and 35 U.S.C. §§ 271(a), (b), and (c).

This case involves Supernus’s Oxtellar XR® product, a once-a-day extended release oxcarbazepine tablet for the treatment of partial epilepsy seizures in adults and children above the age of six. Super-nus seeks to prevent TWi from selling a generic version of Oxtellar XR®, in connection with TWi’s submission of Abbreviated New Drug Application (“ANDA”) No. 206576, seeking the approval of the United States Food & Drug Administration (“FDA”) to market its generic version of Oxtellar XR® (the “ANDA Product” or the “TWi Tablets”) prior to the expiration of certain patents held by Supernus. Specifically, Supernus alleges that, in selling its ANDA Product, TWi will infringe U.S. Patent Nos. 7,722,898 (the “’898 Patent”), 7,910,131 (the “’131 Patent”), and 8,821,930 (the “’930 Patent”) (collectively, the “Su-pernus Patents” or the “Patents-in-Suit"). Supernus asserts Claims 1 and. 11 of the ’898 Patent, Claims 1, 11, and 21 of the 131 Patent, and Claims 1 and 19 of the ’930 Patent. The asserted claims all require a homogeneous matrix comprising the active pharmaceutical ingredient (“API”), oxcarbazepine, a matrix-forming polymer, a solubility-enhancing agent, and a release-promoting agent.

Claim 1 of the ’898 Patent provides:

1. A pharmaceutical formulation for once-a-day administration of oxcarbaze-pine comprising a homogeneous matrix comprising:

(a) oxcarbazepine;

(b) a matrix-forming polymer selected from the group consisting of cellulosic polymers, alginates, gums, cross-linked polyacrylic acid, carrageenan, polyvinyl pyrrolidone, polyethylene oxides, and polyvinyl alcohol;

(c) at least one agent that enhances the solubility of oxcarbazepine selected from the group consisting of surface active agents, complexing agents, cydodext-rins, pH modifying agents, and hydration promoting agents; and

(d)- at least one release promoting agent comprising a polymer having pH-depéndent solubility selected from- the group consisting of cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, ethylhydroxy-cellulose phthalate, polyvinylacetate phthalate, polyvinylbutyrate acetate, vinyl acetate-maleic anhydride copolymer, styrene-maleic mono-ester copolymer, and Eudragit L 100-55 (Methacrylic Acid-Ethyl Acrylate Copolymer (1:1)), and methyl acrylate-methacrylic acid co-polymers.

The dependent claims of the Patents-in-Suit include additional limitations, generally specifying the types of excipients for the matrix-forming polymer, solubility enhancing agent, and release promoting agent, and/or the nature of the dosage form.

The Court conducted a four-day bench trial from April 3, 2017 through April '6, 2017. It then permitted the parties to submit post-trial briefing.

After considering all the evidence, as well as the parties’ submissions, and for the reasons set forth herein, the Court finds that: (1) TWi’s ANDA Product will infringe each of the Patents-in-Suit; and (2) each of the Patents-in-Suit is valid. Accordingly, the Court enters judgment against TWi and in favor of Supernus as to the ’898 Patent, the ’131 Patent, and the ’930 Patent. This Opinion constitutes the Court’s findings of fact and conclusions of law pursuant to Federal Rule of Civil Procedure 52(a).

II. BACKGROUND

A. The Drug Approval Process

Under the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 301, et seq., the FDA must approve all new drugs before they may be distributed in interstate commerce, 21 U.S.C. § 355(a). To secure approval for a new drug, an applicant may file a New Drug Application (“NDA”) that includes, inter alia, the number and expiration date of any patents which claim the drug or a method of using the drug if a claim of patent infringement could reasonably be asserted. Id. § 355(b)(2). “The FDA publishes the names of approved drugs and their associated* patent information in the Approved Drug Products with Therapeutic Equivalence Evaluations list, commonly referred to as the ‘Orange Book.’” AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1045 (Fed. Cir. 2010). An applicant seeking approval to market a generic version of a drug that has already been approved by the FDA may file an ANDA, which “allows an applicant to rely on the safety and efficacy information for the listed drug if the applicant can show that the generic drug is ‘bioequivalent’ to the listed drug.” Id. (citing 21 U.S.C. §§ 355(b)(2), 355(j)).

“[F]or each patent listed,in the Orange Book that claims either the listed drug or a use of the listed drug for which the applicant is requesting approval, an ANDA must include either one of four certifications or a ‘section viii statement.’ ” AstraZeneca LP, 633 F.3d at 1046. If an applicant submits a certification, the applicant must certify “(I) that ... patent information has not been filed, (II) that such patent has expired, (III) ... the date on which such patent will expire, or (IV) that such patent is invalid or will not be infringed by the manufacture, use, or sale of the new drug.” 21 U.S.C. § 356(3)(2)(A)(yii)(I)—(IV). The last of these is known as a “paragraph IV certification.” If an ANDA applicant submits a paragraph IV certification and a patent infringement suit is commenced within 45 days, then the FDA -may not approve the ANDA until the expiration of a 30-month statutory -period. Id § 355(c)(3)(C).

B. The Patents-in-Suit

The Patents-in-Suit describe and claim a specific type of oxcarbazepine formulation for the treatment of seizures with a “homogeneous matrix” containing the active ingredient, oxcarbazepine, and certain categories of excipients; The “homogeneous matrix” is central to the claimed invention.

i. The ’898 Patent

On May' 25, 2010, the United States Patent and Trademark Office (the “PTO”) issued the ’898 Patent, entitled “Modified-Release Preparations Containing Oxcar-bazepine and Derivatives Thereof.”' PTX 1(A). The named inventors are Dr. Pad-manabh P. Bhatt, Dr. Argaw Kidane, and Dr. Kevin Edwards; The ’898 Patent was filed oh April 13, 2007 as Application No. 11/734,874 and is related to Provisional Application No. 60/794,837, filed on April 26, 2006. The ’898 Patent expires on April 13, 2027. PTX 1(A); Joint Final Pretrial Order, Stipulated Facts' (“SF”) ¶-12. The ’898 Patent covers an oxcarbazepine formulation administered once-daily for the treatment of seizures. PTX 1(A).

ii. The ’131 Patent

The ’131 Patent, entitled “Method of Treating Seizures Using Modified Release Formulations of Oxcarbazepine,” was filed on August 27, 2008 as Application No. 12/230,276,. which was, a continuation of Application No. 11/734,874, filed on April 13, 2007. PTX 2(A). The 131 Patent is also related to Provisional Application No. 60/794,837, filed on April 26, 2006. The 131 Patent was issued by the PTO on March 22, 2011 and expires on. April 13, 2027. PTX 2(A); SF ¶ 13. The 131 Patent covers a method of treating seizures by administrating an oxcarbazepine pharmaceutical formulation. PTX 2(A).

iii. The ’930 Patent

The ’930 Patent/ entitled “Modified Release Preparations Containing Oxcarbaze-pine and Derivatives Thereof,” was filed on December 11, 2013 as Application No. 14/103,103, which was a continuation of Application No. 13/476,337, filed on May 21, 2012, which is, in turn, a continuation of Application Ño, 13/137,382, filed on August 10, 2011, which is a division of Application No. 12/230,275, filed on August 27, 2008, which is a continuation of Application No. 11/734,874, filed on April 13, 2007. It is also related to Provisional Application No. 60/794,837, filed on April 26, 2006. PTX 4(A); SF ¶ 14. The ’930 Patent issued on September 2, 2014 and expires on April 13, 2027. The ’930 Patent covers an oxcarbaze-pine formulation for the treatment of seizures. Its terms are largely similar to those of the ’898 Patent, but also include, in relevant part, certain percentages by weight of the formulation limitations.

TWi disputes Supernus’s claims relating to each of the Patents-in-Suits on the grounds of non-infringement and invalidity.

C. Oxtellar XR®

In October 2012, the FDA approved NDA No. 202810 for an oxcarbazepine extended-release oral tablet, which Supernus markets under the name Oxtellar XR®. Its sole active ingredient is oxcarbazepine. Oxtellar XR® is indicated for use as a once-daily adjunctive therapy in the treatment of partial seizures in adults and children 6 to 17 years of age. SF ¶¶ 1, 6.

D. TWi’s ANDA

On December 30, 2013, TWi filed ANDA No. 206576 with the FDA seeking regulatory approval to market extended-release oxcarbazepine oral tablets in 150 mg, 300 mg, and 600 mg dosages. SF ¶ 27. TWi’s ANDA identifies the listed drug product that is the basis for the submission as Oxtellar XR®. PTX 88.5. TWi’s ANDA included a paragraph IV certification asserting that the ’898, ’131, and ’930 Patents are invalid, unenforceable, or will not be infringed by the manufacture or sale of its generic extended-release oxcarbazepine tablets. SF ¶ 27. On January 18, 2017, TWi submitted an ANDA amendment to the FDA, which included changes to the formulation of TWi’s 150 mg and 300 mg tablets only. SF ¶ 28. [redacted]

III. LEGAL ANALYSIS

To prove infringement, the pat-entee must show that it is more likely than not that the proposed ANDA product would, if commercially marketed, meet all of the claim limitations of the Patents-in-Suit. See Adams Respiratory Therapeutics, Inc. v. Perrigo Co., 616 F.3d 1283, 1287 (Fed. Cir. 2010) (en banc); Abbott Labs. v. TorPharm, Inc., 300 F.3d 1367, 1373 (Fed. Cir. 2002) (infringement analysis turns on whether accused product satisfies every limitation of the claim in question). In other words, the patentee “has the burden of proving infringement by a preponderance of the evidence.” Kegel Co., Inc. v. AMF Bowling, Inc., 127 F.3d 1420, 1425 (Fed. Cir. 1997); SmithKline Diagnostics, Inc. v. Helena Labs. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988). Determining whether an accused product infringes the patent involves a two-step analysis. Kegel, 127 F.3d at 1425. The Court must first construe the scope and meaning of the asserted claims and then compare the accused product to the properly construed claims. Id.

Before beginning this two-step analysis, the Court observes that, although the parties do not agree on the exact definition of a person of ordinary skill in the art, sometimes referred to as a POSA, their respective definitions are fairly similar and they have made no arguments as to which definition the Court should adopt. More importantly, the parties have not identified how the Court’s analysis would differ depending on the definition adopted. Nonetheless, the Court sees no material difference between the definitions put forth by the parties and finds that its claim construction, infringement, and validity analy-ses would be the same under either definition.

A. Claim Construction

As for the first step, on August 31, 2015, the parties filed their Joint Claim Construction and Prehearing Statement, pursuant to Local Patent Rule 4.3 and the Court’s July 17, 2015 Scheduling Order [Docket No. 64], On October 7, 2015, the Court conducted a Markman hearing [Docket No. 81]. The Court construed several terms, of which the only disputed claim term that remains • contested at this juncture is “agent that enhances the solubility of oxcarbazepine.” The parties stipulated to the Court’s construction of the term “homogeneous matrix” in a related action, Supernus Pharm., Inc. v. Actavis, Inc., Civil Action Nos. 13-4740, 14-1981 (the “Actavis Matter”). Joint Claim Construction Br. at 5 [Docket No. 64].

Claim construction is a question of law. See Markman v. Westview Instruments, Inc., 517 U.S. 370, 391, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996). The Court determines the meaning of disputed claim terms as understood by one of ordinary skill in the art at the time of invention. See Phillips v. AWH Corp., 415 F.3d 1303, 1312-13 (Fed. Cir. 2005) (en banc). Claim terms generally should be given their ordinary and customary meaning to a person of skill in the art at the time of the invention. See id. To determine the ordinary meaning, the Court first looks to the intrinsic evidence, which includes the claims, the specification, and the prosecution history. Id. at 1312-17 (“Like the specification, the prosecution history provides evidence of how the PTO and the inventor understood the patent.”).

The starting point for claim interpretation is the claim language itself, which can “provide substantial guidance as to the meaning of particular claim terms.” Id. at 1314. Thus, the language of the claims is paramount. Pass & Seymour, Inc. v. Int’l Trade Comm’n, 617 F.3d 1319, 1324 (Fed. Cir. 2010); see Chef Am., Inc. v. Lamb-Weston, Inc., 358 F.3d 1371, 1374 (Fed. Cir. 2004) (“in accord with our settled practice we construe the claim as written, not as the patentees wish they had written-it”). The claims, however, “must be read in view of the specification, of which they are a part.” Markman v. Westview Instruments, Inc., 52 F.3d 967, 979 (Fed Cir.), aff'd, 517. U.S. 370, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996). Extrinsic evidence, such as dictionaries, may be consulted to assist in understanding disputed terms. Phillips, 415 F.3d at 1318. Extrinsic evidence, however, must be “considered in the context of the intrinsic evidence.” Id. at 1317-19.

i. Homogeneous Matrix

The parties agreed to adopt the. Court’s construction of the term “homogeneous matrix” in the Actavis Matter. Joint Claim Construction Br. at 5. In the Actavis Matter, the Court construed the term “homogeneous -matrix” as “a matrix in which the ingredients or constituents are uniformly dispersed.” Markman Order, civ. Action No. 13-4740 [Docket No. 244]. The Court incorporates its reasoning for -this claim construction as set forth in fits February 5, 2016 Opinion in the Actavis Matter Supernus Pharm. Inc. v. Actavis Inc., 2016 WL 527838, at *6-8 (D.N.J. Feb. 5, 2016), aff'd, 665 Fed.Appx. 901 (Fed. Cir. 2016).

ii. Agent that Enhances the Solubility of Oxcarbazepine

The Court construed the term “an agent that enhances the solubility of oxcarbaze-pine” as “an agent, other than oxcarbazep ine, that enhances the solubility of oxcar-bazepine, which agent cannot also serve as the sole matrix-forming polymer in 1(b) or the sole release promoting agent in 1(d) -in claim 1.” Markman Order ¶ 2 [Docket No. 84]/ The parties had proposed the following constructions:

Joint Claim Construction Br., Ex.A.

The parties did not genuinely dispute that the plain and ordinary meaning of the term “agent that enhances the solubility of oxcarbazepine” was an “agent that functions to increase the aqueous solubility of oxcarbazepine.” That is evident from their respective proposed constructions. TWi, however, wished to further limit the term in two ways. First, TWi sought the addition of essentially a materiality provision, requiring that the increase in aqueous solubility of oxcarbazepine be “to a point where it impacts the availability of the drug for systemic absorption in patients.” At the Markman hearing, however, the parties agreed that-the-solubility enhancing agent must result in an increase in the solubility of .oxcarbazepine that wás more than de minimis. Markman Tr, 66:22-68:1 [Docket No. 85], In light of the parties’ agreement on this issue, the Court declined to expressly supplement the claim language in this fespect.

Second, TWi argued that the solubility enhancing agept cannot be oxcarbazepine, a matrix-forming polymer, or a release promoting agent. TWi expressed concerns regarding a construction that permitted a single excipient that serves several different functions to satisfy multiple claim elements. The Court agreed that such “double duty” was not envisioned by the inventors or in th.e specifications or claim language of the Patents-in-Suit. For example, the specifications state that a “combination, of solubility and release promoters is contemplated in this invention.” ’898 Patent, col. 4,' 11. 14-16 (emphasis added).- In this Court’s view, it is clear that a person skilled in the art would understand the claim language to require that a single excipient cannot serve, for example, as both the only solubility enhancing agent and the only release promoting agent in the formulation. TWi’s proposed construction, however, is unnecessarily restrictive. Nothing in the claim language, the specifications, or the prosecution history suggests that an ex-cipient cannot function as an agent that enhances the solubility of oxcarbazepine just because it also can function as a matrix-forming polymer or a release promoting agent, so long as the formulation also contains a distinct matrix-forming polymer and release promoting agent. Accordingly, the Court adopted a variation of TWi’s proposed construction that eliminated the possibility of improper “double duty,” while recognizing that ex-cipients may serve several functions ’ at once.

At trial, however, the parties conveyed to the Court that its construction of the term “agent that enhances the solubility of oxcarbazepine” was no longer relevant to the infringement theories or defenses advanced by the parties. Tr. 28:8-30:13.

B. Infringement

i. The Patents-in-Suit

As for the second step of the infringement analysis, the Court must determine whether the accused product contains every limitation of the properly construed claims. Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448, 1467 (Fed. Cir. 1998).

The Patents-in-Suit are directed to “controlled-release preparations of ox-carbazepine and derivatives thereof for once-a-day administration.” ’898 Patent, col. 1, 11. 14-16; 131 Patent, col. 1, 11. 16-18; ’930 Patent, col. 1,11. 22-24. Supernus asserts that TWi will infringe Claims 1 and 11 of ’898 Patent, Claims 1, 11, and 21 of the 131 Patent, and Claims 1 and 19 of the ’930 Patent. Claim 1 of each of the Patents-in-Suit, the only independent claim, requires a “pharmaceutical formulation comprising a homogeneous matrix,” which in turn comprises four constituents:

(a) oxcarbazepine;

(b) a matrix-forming polymer selected from the group consisting of cellulosic polymers, alginates, gums, cross-linked polyacrylic acid, carrageenan, polyvinyl pyrrolidone, polyethylene oxides, and polyvinyl alcohol;

(c) at least one agent that enhances the solubility of oxcarbazepine selected from the group consisting of surface active agents, complexing agents, cyclodext-rins, pH modifying agents, and hydration promoting agents; and

(d) at least one release promoting agent comprising a polymer having pH-dependent solubility selected from the group consisting of cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, ethylhydroxy-cellulose phthalate, polyvinylacetate phthalate, polyvinylbdtyrate acetate, vinyl acetate-maleic anhydride copolymer, styrene-maleic mono-ester copolymer, and Eudragit L 100-55 (Methacrylic Acid-Ethyl Acrylate Copolymer (1:1)), and methyl acrylate-methacrylic acid co-polymers.

Claim 1 of the ’898 Patent also requires that the pharmaceutical formulation be for “for once-a-day administration,” Claim 1 of the ’131 Patent discloses a “method of treating seizures” through the administration of the pharmaceutical formulation described above. Claim 1 of the ’930 Patent largely replicates Claim 1 of the ’898 Patent. It also, however, includes percent by weight of the formulation limitations, as follows:

(a) oxcarbazepine;

(b) 1-50%, by weight of the formulation, a matrix-forming polymer;

(c) 1-80%, by weight of the formulation, at least one agent that enhances the solubility of oxcarbazepine; and

(d) 10-90%, by weight of the formulation, at least one release promoting agent comprising a polymer having pH-dependent solubility selected from the group consisting of cellulose acetate phthalate, cellulose acetate succinate, methylcellulose phthalate, ethylhydroxy-cellulose phthalate, polyvinylacetate phthalate, polyvinylbutyrate acetate, vinyl acetate-maleic anhydride copolymer, styrene-maleic mono-ester copolymer, Eudragit L100-55 (Methacrylic Acid— Ethyl Acrylate Copolymer (1:1)), and methyl acrylate-methacrylic acid copo-lymers.

The remaining asserted claims are all directly or indirectly dependent on Claim 1, meaning that they include all of the limitations of Claim 1 as well as additional limitations, generally related to the type of dosage form.

ii. The TWi ANDA Product

The parties have stipulated that the TWi Tablets have the following composition:

[redacted]

Stipulation ¶ 8 [Docket No. 195-1].

Supernus contends that the TWi Tablets infringe Claim 1 of each of the Patents-in-Suit and certain claims that depend upon Claim 1 of the Patents-in-Suit. TWi does not dispute that its tablets contain certain elements of Claim 1. Specifically, TWi admits that its tablets are meant for once-a-day administration for the treatment of seizures. SF ¶43. Further, there is no dispute that TWi’s label and prescribing information state that the TWi Tablets are to be used to treat seizures. PTX 101.1. TWi also admits for purposes of this litigation that its tablets contain element 1(a), oxcarbazepine, at least one element 1(b) matrix-forming polymer, and at least one element 1(d) release promoting agent comprising a polymer with pH-dependent solubility. Stipulation ¶¶ 1, 8.

The parties’ infringement dispute centers on the remaining two claim elements: the presence of a “homogeneous matrix” and an element 1(c) “agent that enhances the solubility of oxcarbazepine.” The Court’s infringement analysis shall, therefore, be limited to these two claim elements.

1. Claim 1

(a) Homogeneous Matrix

All of the asserted claims require a pharmaceutical formulation of oxcarbaze-pine “comprising a homogeneous matrix .... ” ’898 Patent, Claim 1; ’131 Patent, Claim 1, ’930 Patent, Claim 1. As noted above, the Court construed “homogeneous matrix” to mean a “matrix in which the ingredients or constituents are uniformly dispersed.” Markman Order, Civ. Action No. 13-4740. As demonstrated by the prosecution history, the term “homogeneous matrix” was added to Claim 1 through two consecutive Office Action responses to overcome prior references that purportedly disclosed element 1(d) release promoting agents in the tablet coating. Stated differently, the term “homogeneous matrix” was added to the claims to distinguish Supernus’s invention, which has all four matrix components in the tablet core, from the prior art references, which contained certain matrix constituents solely in the coating, which the Patent Examiner viewed to be part of the matrix. The term was not added to describe the degree of uniformity or homogeneity of the Supernus invention or to distinguish the degree of uniformity of Supernus’s invention from that of prior art formulations. See PTX 5.206-07, 262-70, 281, 290-300; Tr. 566:15-569:5, 572:18-574:13 (Little Direct).

To carry its burden of proving infringement as to the “homogeneous matrix” limitation, Supernus presented evidence regarding (1) the manufacturing process by which TWi creates its ANDA Product, (2) FDA-réquired uniformity testing, and (3) chemical imaging. The Court addresses each in turn.

Manufacturing Process

Supernus contends that TWi’s manufacturing process establishes that the TWi Tablets comprise a homogeneous matrix in which the constituents are uniformly dispersed. In support of this position, Plaintiff presented the testimony of several expert witnesses.

Plaintiffs experts credibly testified that the default objective of a person skilled in the art when developing a matrix-based formulation would be to form a homogeneous matrix. PTX 5.298; Tr. 567:5-19, 589:9-14 (Little Direct). Indeed, absent a specific objective not to be homogeneous, the default objective of a skilled formulator is to create a homogeneous matrix formulation comprising a uniform dispersion of ingredients. .Tr. 589:9-14,-590:2-12 (Little Direct); Tr. 170:21-172:16 (Bugay Direct). Moreover, TWi’s expert witness, Dr. Elder, did not genuinely dispute this proposition. Tr. 819:20-820:3 (Elder Direct); Tr. 910:4-23 (Elder Cross). No evidence in the record indicates that TWi’s. formulators sought to stray from this default objective in formulating its ANDA' product. Tr. 589:9-14 (Little Direct); see also icL 577:19-583:23. In fact, for the reasons , set forth below, the Court finds that TWi’s manufacturing process establishes that its tablets comprise a homogeneous matrix.

TWi’s manufacturing process involves several steps. The parties have stipulated that the TWi Tablets are manufactured according to the following process, set forth in TWi’s Quality Overall Summary, included in its ANDA:

[redacted]

Stipulation ¶ 9.

Dr. Little testified extensively regarding the manufacturing process utilized, by TWi. The process involves five stages: (1) premixing/wet granulation; (2) drying; (3) milling; (4) blending; and (5) tablet-ing/compression. PTX 364.9; Tr.. 577:19-578:19 (Little Direct). Dr. Little explained that “[t]he purpose of these steps [is] to mix all of the ingredients together uniformly.” Tr. 578:15-19 (Little Direct).

The first step, pre-mixing or wet granulation, involves “takfing] all of th[e] ingredients, and that includes the [redacted], ánd mix[ing] them up really well, and then essentially you’re forming granules.” Id 582:10-15. [redacted] Id. 579:5-11, 586:5-10; PTX 367.17.

[redacted] M. Tr. 579:12-20, 586:12-19 (Little Direct); PTX 367.18. [redacted] Tr. 581:15-24 (Little Direct). Thereafter, the ingredients are wet granulated to “ensure content, uniformity.” PTX 88.16; PTX 364.6. In its ANDA, TWi explained that [redacted]

[redacted]

TWi, however, contends that its manufacturing process does not result in tablets that comprise a homogeneous -matrix, due to the “paradox” of high-shear granulation. Dr. Elder, TWi’s expert, explained this concept as> follows: -

It’s utilized to indicate in this case that high-shear granulation can result in non-homogeneous granules. Many people would expect mixing processes, especially high shear, to make things uniform, when in reality that term — the conundrum or paradox is that some of the materials are nonhomogeneous.

Tr. 819:20-820:4 (Elder Direct). Relying upon relevant scientific literature, Dr. Elder explained that “[a] major disadvantage is that granulation can introduce inhomogeneity. ... The inhomogeneity is expressed as a granule size dependent variation in composition.” Jd. 820:4-12. Critically* however, there is no evidence whatsoever in' the record that the so-called paradox actually resulted in the formation of non-homogeneous granules .in the TWi Tablets. Indeed, as Supernus correctly notes, TWi specifically explained to the FDA that it had optimized its high-shear wet granulation manufacturing process for the express purpose of achieving “a better granulation,” i,e. obtaining “more uniform granules.” PTX 88.16 (“Granulation using high shear mixer directly impacted wet granule size, granule density and compressibility of the final blend.... A slow impeller and a low chopper speed lead to unevenly wetted granules. The setting of the parameter is optimized for a better granulation.”); Tr. 587:9-14 (Little Direct) (quoting TWi’s ANDA, “an additional two minutes of mixing after this point, after the addition of the' granulation solution Ml result in more-uniform granules.”).

. Given TWi’s own description of the purpose of each step in its manufacturing process, the Court gives TWi’s arguments about granule inhomogeneity no weight. See, e.g„ PTX 88.16 (“Granulation was required to improve flow and ensure content uniformity.-High shear mixer was selected due-to intimate mixing of API and other excipients are [sic] rapidly achieved.); PTX 88.17 (impeller/chopper speed “optimized for a better granulation. Adequate speed is important for well mixing and distribution of raw .materials.”). Furthermore, the Patents-in-Suit clearly contemplated the formation of granules and did not view the formation of such granules to be an impediment to the creation of .a homogeneous matrix. See, e.g.,. ’898 Patent, col. 5,11.1-9,22.

Moreover, the Court agrees with Super-nus that “the homogeneity or inhomogeneity of a discrete granule has no bearing on TWi’s infringement .of the ‘homogeneous matrix’ claim .limitation.” PI. Br. at 12 [Docket No, 272] (emphasis in original). Claim 1 of the Patents-in-Suit addresses the homogeneity of the tablet matrix, not the homogeneity of any individual granules within the matrix. Each TWi Tablet contains tens of thousands of granules. Tr. 919:25-920:19 (Little Direct). As Dr. Little testified, the proper scale of scrutiny in assessing whether thé ANDA Product satisfies the homogeneous matrix limitation of Claim 1 of the Patents-in-Suit is the scale of the tablet, not the granules. Id, 925:6-926:3. Dr. David Bugay, Supernus’s expert in spectroscopy,, also focused on the homogeneity of the tablet matrix, rather than the granules. Nonetheless, he. concluded based upon the Raman chemical images he created of the sample TWi-Tablet, discussed in detail below, that the granules themselves are uniformly dispersed- across the-.tablet' matrix. Tr. 168:13-19, 174:2-7 (Bugay Direct). Thus, the Court finds that there is no evidence that suggests that TWi’s- manufacturing- process resulted in inhomogeneous granules in' its -tablets. Furthermore, as the granules in the TWi Tablets are themselves -uniformly dispersed across the tablet matrix, any theoretical granule inhomogeneity introduced by high-shear wet granulation- does not résult in an inhomogeneous matrix.

[redacted] Tr. 584:20-25 (Little Direct); PTX 367.38. Dr. Little persuasively testified that [redacted] does not affect the blend uniformity achieved throughout the previous steps. Tr. 583:3-8 (Little Direct). Likewise, Dr. Elder did not identify any evidence of de-mixing between [redacted], Tr. 899:9-13 (Elder Cross). Based on his review of the Quality Overall Summary, manufacturing batch records, and product development report included in TWi’s ANDA, Dr. Little opined that TWi’s high shear wet granulation manufacturing process results in a homogeneous matrix tablet in which all constituents are uniformly dispersed. Tr. 565:6-566:2 (Little Direct).

Dr. Bugay,- Supernus’s expert .in spectroscopy, also reviewed TWi’s manufacturing process as set forth in its ANDA. Based upon his review of TWi’s manufacturing process and his knowledge of and experience with wet granulation processes, Dr. Bugay concluded that TWi’s manufacturing process results in a homogeneous matrix in its ANDA Product. Tr. 170:21-172:16 (Bugay Direct). Moreover, the inventors of the Patents-in-Súit stated during prosécution that' “[o]ne of ordinary skill in the art would appreciate that the formulations derived according to the [manufacturing] protocol set forth in.the Examples would necessarily comprise a homogeneous matrix.” PTX 5.298; Tr. 567:5-19 (Little Direct). Example 4 in the ’898 Patent sets forth a manufacturing process that involves blending and high shear granulation prior to tableting, as does TWi’s manufacturing process. ’898 Patent, col. 10,11. 35-56.

For the foregoing reasons, based upon the testimony of Dr. Little and Dr. Bugay, as well as.TWi’s own representations as to the purposes - of the various steps of its manufacturing process, the Court finds that TWi’s manufacturing process results in a homogeneous matrix in the TWi Tablets.

FDA Uniformity Testing

. Pursuant to FDA' regulation, all pharmaceutical formulations must pass a series of uniformity tests, including blend uniformity, content uniformity, and dissolution testing, prior to being administered to humans or animals. See 21 C.F.R. § 211.110. These controls are required to ^assure batch- uniformity and integrity of drug products.” Tr. 592:4-593:15 (Little Direct). The FDA has issued guidance, entitled “Powder Blends and Finished Dosage Units — Stratified In-Process Dosage Unit Sampling and Assessment,” “to assist manufacturers of human drug products in meeting the requirements of 21 C.F.R. § 211.110.” Id. 596:3-16. This guidance explains that uniformity testing is required to “demonstrat[e] the adequacy of mixing to ensure uniformity of in-process powder blends and finished dosage units.” Id. Additionally, the FDA ¾⅛0 recommends that manufacturers “assess the uniformity of the powder blend, the in-process dosage ■units, and the finished product.” Id 597:8-598:3.

As required, TWi conducted blend and content uniformity tests and in vitro dissolution tests on its ANDA Product, [redacted] PDX 8 at 93:24-94:7, 96:2-5, 101:3-8 (S. Chen Dep.); PTX 364.14-16, 21; Tr. 599:25-600:2, 652:25-653:4, 659:1-2 (Little Direct). For .the following reasons, the Court finds that the results of TWi’s uniformity testing further demonstrate that the ANDA Product comprises a homogeneous matrix in which its constituents are uniformly dispersed.

Blend Uniformity Testing

Prior to receiving FDA approval, all pharmaceutical formulations must also pass blend uniformity testing. The FDA requires that blend uniformity testing be performed on all pharmaceutical formulations to ensure the adequacy of mixing. Specifically, the purpose of such testing is to verify that the API is uniformly distributed throughout the final blend during the manufacturing process. Tr. 601:13-602:13 (Little Direct). Blend uniformity testing is performed prior to tableting and assesses the adequacy of mixing. This testing confirms the uniformity of all blended ingredients by determining whether samples from various locations within the blender contain the same amount of the API. Id. 595:6-13, 601:17-603:22.

While blend uniformity testing only directly measures the uniformity of the API, the results serve as a proxy for the uniformity of all ingredients, as the testing is designed to assess the adequacy of mixing. Id. 601:17-603:22. This concept is well-established in the literature. For example, the Journal of Drug Development and Industrial Pharmacy, a journal for which Dr. Elder serves on the editorial advisory board, published an article acknowledging that: “The homogeneity of a pharmaceutical blend is usually determined by assessing the uniformity of the active ingredient distribution throughout the mixture, while the uniformity of the excipients is assumed.” DTX 9.3 (emphasis added). Dr. Little also persuasively testified that excip-ients that are not uniformly dispersed would result in a non-uniform distribution of the API, which would be apparent in the testing. His thorough and helpful explanation bears repeating:

Q. Does blend uniformity testing have any relevance to ingredients within a tablet, other than the active ingredient, in your opinion?

A. Yeah. This is a good question. So blend uniformity explicitly measures the active [ingredient], but it is understood that since you are mixing all of the rest of the ingredients alongside and in the same process as the active, that all the rest of those ingredients are mixed as well.

Another way to think about this logically is that if you have, for instance, a heterogeneity in one of your excipients, that heterogeneity is going to take up space and is going to displace the active ingredient.

So if you have a heterogeneity of an [excipient], you are going to have a heterogeneity in your API, or your active pharmaceutical ingredient.

So all said, what’s understood is that the blend uniformity measurement of the uniformity of the active is a proxy for the uniformity of the other excipients.

Q. In your opinion, would a person of ordinary skill in the art view blend uniformity as applicable to all of the ingredients in a tablet?

A. Yes.

Tr. 601:17-602:13 (Little Direct). The Court is persuaded that once the uniformity of oxcarbazepine has been established through blend uniformity testing, a person of ordinary skill in the art would assume that the inactive excipients are also uniformly dispersed.

Additionally, although blend uniformity testing assesses the adequacy of the blend, rather than the finished tablet, the properties of the blend “largely dictate the final product’s properties.” Id. 598:4-599:20. Indeed,. Dr. Elder, TWi’s expert, admitted that “blend uniformity testing is the first in-process check to make sure that the product is uniform.” Tr. 908:3-7 (Elder Cross) (emphasis added).

TWi conducted two sets of blend uniformity testing — one on the blend in the blender and the second on the blend in the drum — “to make sure that any blend uniformity observed in the blender carries through to the drum.” PDX 8 at 92:10-14 (S. Chen Dep.). It is undisputed that TWi’s ANDA Product passed FDA blend uniformity testing in both the blender and drum. Id. 91:18-92:14. As Dr. Little explained, the Court finds that this establishes that oxcarbazepine and the inactive excipients are uniformly dispersed in the blend. Furthermore, the Court is persuaded that the properties of the blend carry over to the final dosage unit. Accordingly, the Court finds that the results of TWi’s blend uniformity tests establish that its ANDA Product comprises a homogeneous matrix in which the constituents are uniformly dispersed.

Content Uniformity Testing

'TWi’s ANDA product also passed the required content uniformity testing. PDX 8 at 96:2-5 (S'. Chen Dep.). Whereas blend uniformity refers to the uniformity of the blend prior to tableting, content uniformity testing is conducted after the blend has been compressed into tablets. Content uniformity testing assesses whether each finished tablet contains the same amount of active ingredient. Dr. Little testified that in-process dosage unit testing, such as content uniformity testing, “is an accurate and reflective measure of homogeneity of the product,” which “account for potential segregation after blending.” Tr. 653:25-654:20 (Little Direct). As with blend uniformity testing, the results of content uniformity testing serve as a direct proxy for the uniformity of all ingredients. Tr. 602:4-6, 653:25-654:20 (Little Direct). The Court is persuaded that the results of TWi’s content uniformity testing also confirm that TWi’s ANDA product comprises a matrix in which its constituents are uniformly dispersed.

In Vitro Dissolution Testing

Finally, TWi performed in vitro dissolution tests on twelve tablets from each of its 150 mg, 300 mg, and 600 mg strengths. PTX 364.21; PTX 382; Tr. 658:1-7 (Little Direct). It is undisputed that the dissolution values for each of the TWi Tablets tested fell within the stated acceptance criteria for the in vitro dissolution tests. PTX -364:21; PTX 382; Tr. 657:7-660:21 (Little Direct); PDX 8 at 101:3-8 (S. Chen Dep:). Plaintiff contends that the results of TWi’s in vitro dissolution tests further indicate that the TWi Tablets comprise a homogeneous matrix. For the following reasons, the Court agrees.

As Dr. Little testified, in vitro dissolution testing involves’ testing the final dosage form, i.e. the tablet, and measuring the “drug coming out of the dosage form.” Tr. 656:13-19 (Little Direct). Dr. Little further explained how in vitro dissolution testing serves as ¾ proxy for homogeneity of the tablet matrix:

Dissolution testing is where you take the final tablet, and this is typically the tablet that has even the coating on the outside of it, and you put it into a vial that has media. So you’re putting it in high degradation conditions, dissolution testing conditions. And then what you’re measuring is the drug coming out’of the dosage form. Okay?

So, the drug coming out of the dosage form is dependent on the drug and the solubility of the drug, and it’s also heavily dependent on the excipients and the mixture of the excipients. So if you have a[n] inhomogeneity in either the API, active pharmaceutical ingredient, or the excipients, what you’re going to see is that the tablets are going to sort of fall apart funny, and one will be different than another. So what you’ll see is overall what I refer to as, and many people refer to as a dissolution profile which is the rate of dissolution over time, well see that in a minute, will be different from tablet to tablet. So that’s why it gives you information about the uniformity of the. product.

Id. 656:13-657:6, Stated differently, values within the stated acceptance criteria confirm that the TWi Tablets comprise a homogeneous matrix because, if there were heterogeneities in the distribution of ox-carbazepine or the excipients from tablet to tablet, the tested TWi Tablets would have fallen apart inconsistently and, thus, would not have consistent release profiles. As the results of TWi’s in vitro dissolution tests demonstrate, the TWi Tablets exhibited the same release profiles, confirming that the tablets each comprise a homogeneous matrix. Tr. 656:6-660:21 (Little Direct); PTX 382; PTX 364.21.

The results of TWi’s in vitro dissolution tests show low variability between tablets, indicating that the TWi Tablets “performed uniformly” from tablet to tablet, as described by Dr. Little. Tr. 660:14-21 (Little Direct). Additionally, as Dr. Little testified, “nothing” in the in vitro dissolution test results “indicate[s] that there were heterogeneities in the system.” Id. The Court is persuaded by Dr. Little’s expert testimony that in vitro dissolution testing measures and confirms tablet matrix homogeneity by demonstrating that the TWi Tablets perform consistently with each other.

In sum, based upon the testimony and evidence presented-at trial, the Court finds that the results of the, FDA-required blend uniformity, content uniformity, and in vitro dissolution testing confirm that TWi’s manufacturing process results in a uniform dispersion of ingredients and, therefore, establish that the TWi Tablets comprise a homogeneous matrix.

Raman Chemical Imaging

In further support of its position that the TWi Tablets comprise a homogeneous matrix, Supernus offers evidence of Ra-man chemical imaging of the TWi Tablets. Dr. Bugay testified at length regarding the Raman imaging tests he performed on the TWi Tablets, as well as the Oxtellar XR® tablets, and his conclusions regarding the presence of a homogeneous matrix.

Dr. Bugay first microtomed and analyzed a 600 mg TWi Tablet. To prepare the sample, Dr. Bugay mounted the sample tablet and performed microtomy to expose a flat, interior surface of the tablet for analysis. Tr. 155:19-157:5 (Bugay Direct), Dr. Bugay explained that he was able to qualitatively (i.e. non-statistically) analyze the homogeneity of the ANDA Product based on a single slice of one tablet because TWi uses a standard high-shear wet granulation manufacturing process and the TWi Tablets passed FDA uniformity testing. Id. 170:21-173:3, 174:14-25. Next, Dr. Bugay performed Raman spectroscopy to identify the different constituents present in the sample tablet surface based upon the constituents’ distinct vibrational frequencies and resultant spectra when irradiated with a beam of monochromatic light. Id, 157:7-158:14. Each constituent’s Ra-man spectrum is like a “fingerprint,” which is unique to the particular constituent. This allowed Dr. Bugay to compare the spectra he obtained from the sample TWi Tablet to individual reference spectra that he collected from standard samples of each ingredient, in order to identify the different components on the sample surface. Id.

Dr. Bugay then repeated this procedure for more than 35,000 data points, covering over 70% of the tablet’s surface. Id. 158:15-168:7. By processing and compiling thousands of data points, Dr. Bugay created color-coded Raman chemical images that indicate both the presence and location of the various constituents in the tablet sample. Id. 164:2-165:9. Dr. Bugay then confirmed this data using extensive validation procedures. Id. 168:20-170:17. Dr. Bugay credibly testified that a person of ordinary skill in the art would know that homogeneity must be assessed, in the context of the Patents-in-Suit, at the scale of the tablet as a whole. Id. 153:19-154:2. Dr. Little confirmed that a person of skill in the art would understand that the proper scale of scrutiny in this context is at the level of the tablet. Tr. 931:10-21 (Little Direct). Given the relevant scale of scrutiny identified in the asserted claims in the Patents-in-Suit, the Court believes that Dr. Bugay’s Raman chemical images properly assess the vast majority of the tablet surface.

Dr. Bugay created the following Raman chemical images of the sample TWi Tablet, which show the presence of [redacted]

Tr. 165:10-158:10 (Bugay Direct); PTX 246:3-14.

Based upon his visual analysis of the Raman chemical images, Dr. Bugay concluded that, each of the constituents in the sample TWi Tablet is uniformly dispersed throughout the tablet and, therefore, that the TWi tablet comprises a homogeneous matrix. Tr. 164:1-168:19 (Bugay Direct); Tr. 660:22-662:6 (Little Direct). As evidenced by the Raman chemical images of the sample TWi Tablet, the constituents are not localized in one area of the tablet surface alone, but rather are found throughout the tablet surface. Dr. Bugay persuasively testified that a person of ordinary skill in the art would not expect to obtain perfect molecular uniformity using standard high-shear wet granulation processes. Tr. 154:3-15 (Bugay Direct). Instead, he explained, such a person would understand that a lack of localization of excipients across the tablet matrix indicates that the matrix constituents are homogeneous and uniformly dispersed. Id. 165:10-168:10; PTX 246.3-14; Tr. 661:9-662:6 (Little Direct). Dr. Bugay testified that a person of- ordinary skill in the art would not “require that a matrix be perfectly molecularly uniform in order to qualify as a homogeneous matrix in the context of [the Patents-in-Suit] and specifically this Court’s construction of ‘homogeneous matrix.’” Tr. 154:3-8 (Bugay Direct). He elaborated:

I would not expect that a perfect homogeneous matrix such as how a mason builds a sidewalk in a herringbone pattern or builds a'brick wall with the' bricks in exact orientation and such. Our pharmaceutical procedures don’t get down to that level of precision, okay, so it wouldn’t be the perfect homogeneity, yet we are able to easily discern as to whether a homogeneous matrix exists or not for that particular tablet.

Id. 154:8-15.

Moreover, Dr. Little reviewed Dr. Bu-gays Raman chemical images and agreed with Dr. Bugay’s determination that the images confirm the presence of a homogeneous matrix in the sample TWi Tablet. Tr. 661:9-662:6 (Little Direct). Dr. Little reiterated that matrix homogeneity in this context is measured by lack of localization of any excipient, testifying that the Raman chemical images verify that the ANDA Product comprises a homogeneous matrix because there is no localization of any of the excipients. Id. at 661:23-662:6. Specifically, he testified regarding the Raman chemical images of the TWi Tablet as follows:

And what I observed in these [Raman chemical images] is that the results that we see here [are] not surprising at all because these were made by high-shear wet granulation. So, what you would see is that all these excipients that are listed here are mixed up in the tablet, so you can just see that’s the case. There’s not a particular excipient that is located in one particular location, like a coating or a Mayer or a core or something like that. What this confirms is that these are homogeneous matrix tablets.

Id. In Dr. Little’s expert opinion, this lack of localization is not only the expected result of TWi’s high-shear wet granulation manufacturing process, but also establishes that each TWi Tablet comprises a matrix in which all of the constituents are uniformly dispersed.

Based upon his assessment of the 600 mg TWi Tablet, Dr. Bugay concluded, in his expert opinion, that the 150 mg and 300 mg TWi Tablets also comprise homogeneous matrices in which all the constituents are uniformly dispersed since each tablet is created through the same manufacturing process. Tr. 170:21-173:3, 174:14-25 (Bugay Direct). The only difference is in the amount- of each constituent. This does not affect the homogeneity of the tablets. Id. 174:14-25. Additionally, as Dr. Little and Dr. Bugay testified, the objective of any formulator creating a standard pharmaceutical formulation is to achieve a homogeneous matrix. See, e.g., id. 170:21-172:16; Tr. 590:2-16 (Little Direct).

TWi levels two main critiques against Dr. Bugay’s testimony. First, TWi claims that “[i]t is undisputed that Dr. Bugay tested expired samples of TWi’s product,” which “calls the testing into question, as it was not conducted on the actual product TWi will sell, because FDA regulations do not permit the sale of expired product.” Def. Br. at 44 n.7 [Docket No. 275]. Yet, the TWi Tablets do not currently have an expiration date approved by the FDA, but merely a proposed expiration date based only upon accelerated stability studies, which may be extended by the FDA after review of TWi’s full-term stability data. Tr. 241:15-243:6 (Bugay Redirect). In any event, Dr. Bugay credibly testified that he did not observe any evidence of degradation or impurities in the sample TWi Tablet that would have impacted the accuracy of his Raman chemical images. Tr. 213:13-17, 217:5-9 (Bugay Cross); 243:10-244:11 (Bugay Redirect). He further testified that any degradation or impurities in the sample TWi Tablet would have been readily apparent to him when he conducted his Raman chemical imaging. Tr. 213:13-17 (Bugay Cross); Tr. 243:15-21 (Bugay Redirect). At this stage, the TWi Tablets are only subject to a proposed expiration date. There is no evidence that the TWi Tablet tested by Dr. Bugay was not representative of the TWi Tablets that TWi submitted to the FDA for approval and that TWi intends to market. More importantly, there is simply no evidence in the record that Dr. Bugay’s analysis was impaired, altered, or otherwise inaccurate because he tested a sample tablet beyond its proposed expiration date. Accordingly, the Court finds that Dr. Bugay’s Raman chemical images are relevant to its infringement determination.'Moreover, the Court finds no reason to discredit Dr. Bugay’s analy-ses or conclusions simply because the sample tablet may have been tested beyond its proposed expiration date.

Second, TWi argues that the Raman chemical images of the TWi Tablet do not establish that the constituents are uniformly dispersed because Dr. Bugay assessed only the relative concentration of the constituents in the sample TWi Tablet, as opposed to the absolute concentration or quantity of the constituents. According to TWi’s expert witness, Dr. Elder, Dr. Bugay’s Raman chemical images do' not establish that the TWi Tablet tested comprises a homogeneous matrix in which its constituents are uniformly dispersed “because the images do not provide an absolute concentration of the active — or any of the ingredients in that evaluation, the images do not quantitatively describe the ingredients that are being measured” and “[fit’s not possible to determine uniformity without determining the concentration^]” Tr. 860:6-10 (Elder Direct). In. other words, Dr. Elder opined that Dr. Bugay’s qualitative analysis was inappropriate for assessing homogeneity and that a quantitative analysis should have been undertaken. Id. 861:5-14. Despite this testimony, Dr. Elder did not perform any testing in connection with this litigation. Tr. 869:9-10 (Elder Cross).

Dr. Bugay agrees that his Raman chemical analysis was a qualitative study; however, he credibly testified that, in his expert opinion, a quantitative analysis is not necessary to determine whether the matrix constituents in the TWi Tablet are uniformly dispersed or localized in a discrete area of the tablet. Tr. 165:10-23 (Bugay Direct); Tr. 222:10-14, 223:8-224:4 (Bugay Cross). He further testified that'“quantitative presentation of chemical images is very rare” and is “not routinely performed at all by spectroscopists as [hinfiself in the industry.” Tr. 223:13-19 (Bugay Cross). This was confirmed by Dr. Elder, who testified that he has only performed one “semi-quantitative” Raman chemical analysis in his thirty years’ of experience in this field. Tr. 869:12-870:1 (Elder Cross) (emphasis added). Having considered the testimony of Dr. Bugay and Dr. Elder on this issue, the Court finds no reason to discredit Dr. Bugay’s qualitative chemical imaging or the conclusions drawn from it. The record simply does not support a finding that a qualitative Raman chemical analysis is inappropriate for assessing or confirming the homogeneity of the tablet matrix or that a quantitative analysis should have been performed. The Court is persuaded by Dr. Bugay’s testimony that quantitative Raman chemical analyses are rarely, if ever, used by persons of ordinary skill in the art and that his Raman chemical imaging confirms that the constituents of the' sample TWi Tablet are uniformly dispersed across the tablet matrix.

Having considered Dr. Bugay’s testimony, as well as the Raman chemical images of the sample TWi Tablet, and haying rejected TWi’s critiques of Dr. Bugay’s anal-yses and conclusions, the Court concludes that the Raman chemical images of the sample TWi Tablet confirm that TWi’s ANDA Product comprises a homogeneous matrix. In sum, based upon TWi’s manufacturing process, the results of the FDA uniformity testing on the TWi Tablets, and the Raman chemical imaging of the sample TWi Tablet, the Court finds that the TWi Tablets comprise a homogeneous matrix, as construed by this Court and as understood by a person of ordinary skill in the art.

(b) Agent that Enhances the Solubility of Oxcarbazepine

. Supernus contends that [redacted] in the TWi Tablets satisfies element 1(c) of claim 1 of the Patents-in-Suit. Claim element 1(c) of the ’898 and ’131 Patents requires “at least one agent that enhances the solubility of oxcarbazepine selected from the group consisting of surface active agents, com-plexing agents, cyclodextrins, pH modifying agents, and hydration promoting agents.” Claim element 1(c) of the ’930 Patent requires “1-80%, by weight of the formulation, at least one agent that enhances the solubility of oxcarbazepine.” [redacted] Tr. 353:23-354:8, 365:1-6 .(Berk-land Direct).

To establish whether [redacted] is an agent that enhances the solubility of oxcar-bazepine, Dr. Leonard Chyall, Supernus’s expert in analytical testing of pharmaceutical compositiqns, performed solubility tests on oxcarbazepine in the presence of [redacted], Tr. 250:11-251:4 (Chyall Direct). He did not perform solubility or dissolution tests on the TWi Tablets themselves. Dr. Chyall employed the shake-flask test in his solubility studies, an industry standard method, which he described as “the most reliable and widely used method for solubility measurement today.” Id. 252:14-19. His testing .protocol tracked the solubility testing protocol set forth in Example 3 of the Patents-in-Suit. Id. 251:10-19. In performing the solubility testing, Dr. Chyall prepared four solutions with varying percent concentrations of [redacted] to assess how- the presence of [redacted] impacted the solubility of oxcarbazepine. The various solutions included a control solution with [redacted]. Id. 253:4-254:5. Dr. Chyall added crystalline oxcarbazepine to the various solutions. The samples were then shaken to facilitate dissolution of the oxcarbazepine crystals into the solution. Id.. 254:6-255:11. Thereafter, Dr. Chyall separated the undissolved solid oxcarbaze-pine from the solutions, first using centri-fugation and then filtration through a 0.2 micron.filter. Id. 255:12-257:1. Due to the high viscosity of the 10% [redacted] solution, Dr. Chyall was unable to obtain results from this sample. Id. 261:21-262:2. This, however, did not affect his ability to form and offer an opinion as to whether [redacted] enhances the solubility of oxear-bazepine. Id. 262:3-7,

Dr. Chyall’s solubility testing presented the following results:

[redacted]

The results of Dr. Chyall’s tests show that the solubility of oxcarbazepine increased from an average of 0.0521 mg/mL in the control solution to an average of 0.66498 mg/mL in the 1% [redacted] solution and an average of 0.1554 mg/mL in the 5% [redacted] solution. These values demonstrate an average 26% increase in the solubility of oxcarbazepine in the 1% [redacted] solution versus the control solution and an average 195% increase in the solubility of oxcarbazepine in the 5% [redacted] solution versus the control solution. PTX 259.2. Clearly, Dr. Chyall’s solubility test results indicate that as the concentration of [redacted] increases, so does the solubility of oxcarbazepine. PTX 259.2; Tr. 270:19-24 (Chyall Direct).

TWi apparently does not dispute that Dr. Chyall’s solubility testing demonstrates an increase in the solubility of ox-carbazepine in the presence of [redacted]. See Def. PPOP ¶ 173 [Docket No. 275-1]. Rather, TWi argues that such minor increases in solubility are insignificant and insufficient to establish that [redacted] is an agent that enhances the solubility of oxcarbazepine. The- Court disagrees. Dr. Chyall testified that he performed statistical analyses on his solubility testing results and that he concluded, based upon these "analyses, that the increase in solubility evidenced by his tests is statistically significant. Tr. 270:4-17 (Chyall Direct). Additionally, as Supernus correctly points out, there is simply nothing in the Patents-in-Suit that requires an ingredient to increase the solubility of oxcarbazepine by a particular amount or percentage before it is considered an- “agent that enhances the solubility of oxcarbazepine,” as claimed in element 1(c).

In challenging Dr. Chyall’s opinions, TWi presents the testing and opinions of Dr. Cory Berkland, an expert in the field of pharmaceutical formulations and particulates, who independently conducted shake-flask testing to assess the solubility of oxcarbazepine in various [redacted]solutions. Like Dr. Chyall, Dr. Berkland also prepared solutions with varying percent concentrations of [redacted], added solid crystalline oxcarbazepine to the samples, separated the solid oxcarbazepine particles from the solutions using centrifugation and filtration through a 0.22 micron filter, and then measured the solubility of ox'carbaze-pine in the different solutions. DTX 46.1, 8-11. Each value obtained by Dr. Berkland established that the solubility of oxcar-bazepine increased as the percent concentration of [redacted] increased. Id.

Despite such findings and despite having independently employed the same shake-flask testing method as Dr. Chyall to assess solubility, see Tr. 423:2-7 (Berkland Direct), at trial, Dr. Berkland testified that the results of Dr. Chyall’s shake-flask solubility tests were flawed and inaccurate. According to Dr. Berkland, Dr. Chyall’s results overestimated the increase in the solubility of oxcarbazepine because they did not account fo