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Reckitt Benckiser LLC v. Amneal Pharmaceuticals LLC

United States District Court, D. New Jersey, Camden Vicinage

August 22, 2017

RECKITT BENCKISER LLC, Plaintiff,
v.
AMNEAL PHARMACEUTICALS LLC, et al., Defendants. RECKITT BENCKISER LLC, Plaintiff,
v.
DR. REDDYS LABORATORIES, LTD., et al., Defendants.

          OPINION (PUBLIC)

          RENÉE MARIE BUMB, UNITED STATES DISTRICT JUDGE

         Plaintiff Reckitt Benckiser LLC (“Reckitt” or “Plaintiff”) brings this Hatch-Waxman action for patent infringement against Defendants Amneal Pharmaceuticals LLC (“Amneal”) and Dr. Reddy's Laboratories, Inc. (“DRL”) (collectively, “Defendants”) pursuant to 35 U.S.C. § 271(e)(2)(A) and §§ 271(a), (b), and (c).

         I. Reckitt's Guaifenesin Drug Mucinex® and the Patents-in-Suit

         This case involves Reckitt's Mucinex® product, an extended-release guaifenesin tablet used as an expectorant that thins and loosens mucus and relieves chest congestion. Reckitt initially alleged that Amneal's generic 600 mg and 1200 mg guaifenesin sustained-release tablets (“Amneal's ANDA products”) will infringe U.S. Patent Nos. 6, 372, 252 (the “'252 Patent”), 6, 955, 821 (the “'821 Patent”), and 7, 838, 032 (the “'032 Patent”). Similarly, Reckitt initially alleged that DRL's generic 600 mg and 1200 mg guaifenesin and pseudoephedrine hydrochloride sustained-release tablets (“DRL's ANDA Products”) will infringe the '252, '821, and '032 Patents. After the filing of the Complaints, Reckitt dismissed its claims under the '252 Patent as to both Defendants [Docket Nos. 64, 65] and its claims under the '821 Patent against Defendant DRL [Docket No. 64].[1]

         At the heart of the dispute is whether Defendants' ANDA Products have two distinct formulations, an immediate release formulation (“IR formulation”) and a sustained release formulation (“SR formulation”). Reckitt contends that they do. Defendants counter that their ANDA products are single formulation matrix tablets and therefore do not infringe the Patents-in-Suit.

         A. The '821 Patent

         The '821 Patent is entitled “Sustained Release Formulations of Guaifenesin and Additional Drug Ingredients” and is a continuation-in-part of the '252 Patent. Stipulated Facts (“SF”) [Docket No. 157] ¶ 8-9. The named inventors are Robert D. Davis, Ralph W. Blume, and Donald Jeffery Keyser. SF ¶ 10. The '821 Patent was filed on April 15, 2002, as Application No. 10/121, 706. The '821 Patent expires on April 28, 2020. SF ¶ 11. Reckitt is the owner and current assignee of the '821 Patent. SF ¶ 12.

         Claims 30, 35, 36, 41, and 70 of the '821 Patent are asserted against Defendant Amneal only. SF ¶ 20. Amneal has stipulated that its ANDA products satisfy every limitation of the asserted claims of the '821 Patent except for the elements: “modified release drug product;” “first quantity of guaifenesin in an immediate release formulation;” and “second quantity of guaifenesin in a sustained release form/release-delaying matrix.” SF ¶ 24.

         B. The '032 Patent

         The '032 Patent is entitled “Sustained Release of Guaifenesin” and is a continuation-in-part of the '821 Patent, which is a continuation-in-part of the '252 Patent. SF ¶ 14-15. The named inventors are Robert D. Davis, Ralph W. Blume, and Donald Jeffery Keyser. SF ¶ 16. The '032 Patent was filed on April 4, 2003 as Application No. 10/406, 557. The '032 Patent expires on April 28, 2020. SF ¶ 17. Reckitt is the owner and current assignee of the '032 Patent. SF ¶ 18.

         Claims 1, 2, 5, and 6 of the '032 Patent are asserted against both DRL and Amneal. SF ¶ 25. DRL and Amneal have stipulated that their respective 1200 mg ANDA products satisfy every limitation of claims 1 and 2 except for the following claim elements directed to the drug product “having two portions” of guaifenesin: “a first portion comprises guaifenesin in an immediate release form;” and “a second portion comprises guaifenesin in a sustained release form.” SF ¶ 27. DRL and Amneal have also stipulated that their respective 600 mg ANDA products satisfy every limitation of claims 5 and 6 except for the following claim elements directed to the drug product “having two portions” of guaifenesin: “a first portion comprises guaifenesin in an immediate release form;” and “a second portion comprises guaifenesin in a sustained release form.” SF ¶ 28.

         C. Mucinex®

         The FDA approved NDA No. 21-282 in July 2002 for 1200 mg guaifenesin extended-release tablets and in December 2002 for 600 mg guaifenesin extended-release tablets, both of which are marketed by Reckitt under the trademark Mucinex®. SF ¶ 29-30. Mucinex® is approved for use as an expectorant. SF ¶ 30. The FDA approved NDA No. 21-585 in June 2004 for 600 mg/60 mg and 1200 mg/120 mg guaifenesin and pseudoephedrine hydrochloride extended-release tablets, which are marketed by Reckitt under the trademark Mucinex® D. SF ¶ 31-32. Mucinex® D is approved for use as an expectorant and nasal decongestant. SF ¶ 32.

         The claims asserted by Reckitt cover both Mucinex® SE and Mucinex® D. Mucinex® SE products contain guaifenesin as the only active pharmaceutical ingredient (“API”) and Mucinex® D products contain both guaifenesin and pseudoephedrine as the two APIs. SF ¶ 33, 35.

         Both of Reckitt's Mucinex® products are bi-layer tablets, one layer containing guaifenesin in an IR form that provides fast-acting relief, and the other layer containing guaifenesin in a SR form that continues to release guaifenesin for 12 hours. SF ¶ 37. Mucinex® is a preferred example of and is disclosed as Formulation IV in the Patents-it-Suit.[2] Tr. 101:14-102:2; 652:1-6; Tr. 829:22-23.

         D. Amneal's ANDA and ANDA Product

         Amneal filed an Abbreviated New Drug Application (“ANDA”) No. 207342 with the FDA seeking regulatory approval to market guaifenesin extended-release tablets in 1200 mg and 600 mg dosages. SF ¶ 38-39. Amneal's ANDA identifies the listed drug product that is the basis for the submission as Mucinex®. SF ¶ 45. Amneal's ANDA included a paragraph IV certification asserting that the '252, '821, and '032 Patents are invalid, unenforceable, or will not be infringed by the manufacture or sale of its generic extended-release guaifenesin tablets. SF ¶ 44. Amneal's ANDA is currently pending.

         There is no dispute that Amneal intended to develop generic products that are therapeutically equivalent to Mucinex® SE, nor any dispute that Amneal has concluded that its products have comparable dissolution profiles to, and are bioequivalent with, Mucinex® SE products. SF ¶ 53, 60-61. Moreover, the parties have stipulated that the Amneal's ANDA products have the following composition:

         (IMAGE OMITTED)

         E. DRL's ANDA and ANDA Product

         DRL filed ANDA No. 208369 with the FDA seeking regulatory approval to market guaifenesin extended-release tablets. SF ¶ 46-47. DRL's ANDA identifies the listed drug product that is the basis for the submission as Mucinex®. SF ¶ 52. DRL's ANDA included a paragraph IV certification asserting that the '252, '821, and '032 Patents are invalid, unenforceable, or will not be infringed by the manufacture or sale of its generic extended-release guaifenesin tablets. SF ¶ 51. DRL's ANDA is currently pending.

         As with Amneal, there is no dispute that DRL intended to develop generic products that are therapeutically equivalent to Mucinex® D, nor any dispute that DRL has concluded that its products have comparable dissolution profiles to, and are bioequivalent with, Mucinex® SE products. SF ¶ 66-68. The parties have also stipulated that DRL's ANDA products have the following composition:

         (XXXXX)

         II. Procedural History Before This Court

         On August 14, 2015, and September 25, 2015, Amneal and DRL each filed motions for judgment on the pleadings under Rule 12(c) arguing that their ANDA products do not infringe the Patents-in-Suit because their products are single-formulation matrix tablets that were disclaimed during the prosecution of the '252 Patent. On January 15, 2016, the Court denied the motions on the ground that Reckitt should be afforded limited discovery regarding the actual structure of the Defendants' ANDA products.[3]

         On May 11, 2016, Defendants, contending their products were single formulation release tablets, filed a summary judgment motion of non-infringement. They argued that the disclaimer of single formulation sustained release tablets that Reckitt had made during the prosecution of the '252 Patent should also apply to the '821 and '032 Patents. On December 22, 2016, the Court denied the motions, without opinion, and thereafter scheduled a trial on the merits.[4]

         On March 28, 2017, the Court issued an Order adopting the claim constructions of Judge Stark set forth in Reckitt Benckiser LLC v. Aurobindo Pharma Ltd., C.A. No. 14-1203-LPS, 2016 U.S. Dist. LEXIS 152337 (D. Del. Nov. 3, 2016) (“Aurobindo I”) and Reckitt Benckiser LLC v. Aurobindo Pharma Ltd., C.A. No. 14-1203-LPS, 2017 U.S. Dist. LEXIS 31985 (D. Del. Mar. 6, 2017) (“Aurobindo II”), appeal docketed, No. 17-1895 (3d Cir. Apr. 12, 2017). [Docket No. 127]. The Court set the matter down for trial, limiting the trial to the issue of infringement only.

         III. Prior Related Litigation

         The case that comes before this Court is not Reckitt's first challenge against a manufacturer of a generic Mucinex®. Three other courts have found no infringement by three other manufacturers of generic single formulation matrix tablets. Reckitt contends that Defendants' reliance on prior litigation is misplaced because the prior cases involve a different patent (the '252 Patent), different claim construction, and different products. The Court disagrees, in part. While it is true that the '252 Patent is no longer part of this case, Defendants' products must have a discrete IR formulation and SR formulation to infringe. Reckitt has rehashed some of its earlier arguments and the prior courts' discussions of those arguments are instructive. Moreover, whether or not Reckitt adequately addressed the deficiency of proof identified by the Aurobindo court (infra) requires analysis of that court's decision whose claim construction this Court has adopted.

         A. Watson Litigation

         On April 24, 2009, Reckitt filed an infringement lawsuit against Watson Laboratories, Inc. - Florida and Watson Pharmaceuticals, Inc. (“Watson”) for infringement of the '252 and '821 Patents, subsequently dismissing the '821 Patent claim. Plaintiff's Responses to Defendants' Proposed Findings of Fact (“PRDFF”), ¶ 12 (citing Reckitt Benckiser, Inc. v. Watson Laboratories, Inc. Florida, Case No. 09-60609 (S.D. Fla. 2009)).[5]The District Court held that Watson did not infringe the '252 Patent, either literally or under the doctrine of equivalents. Reckitt Benckiser, Inc. v. Watson Laboratories, Inc. Florida, Case No. 09-60609, 2011 U.S. Dist. LEXIS 83090, ¶ 238 (S.D. Fla. Feb. 18, 2011). In relevant part, that Court found that Watson's products were prepared from a single uniform blend. Id.at ¶ 143. Moreover, the Court found that the “guaifenesin granules that touch the surface are not part of a separate structure from the balance of the guaifenesin and the other ingredients; all are part of a single structure. Watson's ANDA products do not have two structural portions.” Id.at ¶ 204. On July 7, 2011, the Court of Appeals for the Federal Circuit affirmed the District Court's judgment of non-infringement, holding that “[t]he district court correctly concluded that Watson's products do not have two structural portions and that guaifenesin granules on the surface of Watson's tablets do not constitute the claimed first portion of guaifenesin in an IR form.” Reckitt Benckiser Inc. v. Watson Laboratories, Inc., Florida, 430 Fed.Appx. 871, 877 (Fed. Cir. 2011).

         B. Perrigo Litigation

         In 2007, Adams Respiratory Therapeutics, Inc., Reckitt's predecessor-in-interest, and related entities filed an infringement lawsuit against Perrigo Company (“Perrigo”) and related entities for infringement of the '252 Patent. Adams Respiratory Therapeutics, Inc. et al v. Perrigo Co., Case No. 1:07-CV-993 (W.D. Mich. 2007). The Perrigo District Court granted summary judgment of non-infringement. In relevant part the Court held that “[i]n spite of its attempts to distinguish Watson, [Reckitt] made substantially the same argument to the Federal Circuit in Watson (including that the Guaifenesin on the surface of Watson's tablets was uninhibited by polymer) that it now makes in this case with regard to Perrigo's tablet.” Perrigo, Case No. 1:07-CV-993, 2012 U.S. Dist. LEXIS 3288, at *16 (W.D. Mich. Jan. 11, 2012). In short, the Court held that Perrigo, like Watson, made a single formulation tablet which was disclaimed in the '252 Patent.

         C. Aurobindo Litigation

         On September 14, 2014, Reckitt filed an infringement suit against Aurobindo Pharma Ltd. (“Aurobindo”) for infringement of the '821, '032 and '252 Patents, later dismissing the '252 Patent from its suit. See generally Aurobindo I, 2016 U.S. Dist. LEXIS 152337 and Aurobindo II, 2017 U.S. Dist. LEXIS 31985. The Court found that the asserted claims of the '821 and '032 Patents require “two distinct formulations.” See Aurobindo I, 2016 U.S. Dist. LEXIS 152337, at *6-8. The Court then granted summary judgment of non-infringement concluding that “a reasonable factfinder could only conclude that Aurobindo seeks FDA approval of a single-formulation, extended-release product.” Aurobindo II, 2017 U.S. Dist. LEXIS 31985, at *15. (The Aurobindo decisions will be discussed in greater detail infra.)

         IV. Trial Before This Court

         Trial on the issue of infringement commenced on May 15, 2017, and lasted four days. Closing arguments were heard on June 29, 2017. Defendants' invalidity claims were stayed pending the outcome of the infringement trial. Reckitt presented the testimony of Dr. Martyn C. Davies, a professor of biomedical surface chemistry at the University of Nottingham School of Pharmacy.[6] In general, relying on his Raman analyses, Dr. Davies opined that Defendants' ANDA Products have two distinct formulations of guaifenesin, an IR formulation without rate-controlling polymers on the surface and a SR formulation including rate-controlling polymers in the interior.

         Defendants presented five experts at trial. Dr. Harry Brittain and Dr. Richard Gemeinhart, two experts in pharmaceutical formulation, generally testified that Defendants' ANDA products are matrix tablets made from a single uniformly distributed blend of ingredients.[7] Two experts, Dr. Robin Rogers and Dr. Neil Spingarn, generally testified about the flaws and weaknesses of Dr. Davies's Raman analyses.[8] Finally, Dr. Jeffrey Rodriguez, a computer imaging expert called by DRL testified about his count of the guaifenesin and (XXXXX) pixels in Dr. Davies's Raman maps.[9]

         After considering all the evidence, and the parties' submissions, for the reasons set forth herein, the Court finds that Amneal and DRL will not infringe the '032 and '821 Patents. The Court declines to exercise jurisdiction over the counterclaims asserting invalidity. This Opinion constitutes the Court's findings of fact and conclusions of law pursuant to Federal Rule of Civil Procedure 52(a).

         V. Literal Infringement

         To prove infringement, the patentee 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, 1289 (Fed. Cir. 2010); 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); Laitram Corp. v. Rexnord, Inc., 939 F.2d 1533, 1535 (Fed. Cir. 1991) (“To establish infringement, every limitation set forth in a patent claim must be found in an accused product . . . .”). 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 patent claims and then compare the accused product to the properly construed claims. Id.

         A. The Asserted Claims and Claim Construction

         Reckitt asserts claims 30, 35, 36 and 41 of the '821 Patent against Amneal, and claims 1 and 5 of the '032 Patent against Amneal and DRL.[10] The claims are as follows:

29. A modified release drug product comprising a first quantity of guaifenesin in an immediate release formulation wherein the guaifenesin becomes bioavailable in a subject's stomach; a second quantity of guaifenesin in a sustained release form, . . .
30. The modified release drug product according to claim 29, wherein a total quantity of guaifenesin is from about 600 mg to about 1200 mg.
35. The modified release drug product according to claim 30, wherein the guaifenesin has a Cmax of about 800 to 1250 ng/ml and an AUCinf of about 2800 to 4375 hr*ng/ml.
36. The modified release drug product according to claim 30, wherein the guaifenesin has a Cmax of least 1000 ng/ml and an AUCinf of at least 3500 hr*ng/ml.
41. The modified release drug product according to claim 29, wherein the drug product is approximately equally effective when administered to the human subject with an empty or full stomach.

'821 Patent (emphasis added).

1. A drug product comprising guaifenesin and having two portions, wherein a first portion comprises guaifenesin in an immediate release form, which releases guaifenesin in a human's stomach, and a second portion comprises guaifenesin in a sustained release form.
5. A drug product comprising guaifenesin and having two portions, wherein a first portion comprises guaifenesin in an immediate release form, which releases guaifenesin in a human subject's stomach, and a second portion comprises guaifenesin in a sustained release form, . . .

'032 Patent (emphasis added).

         As noted, this Court adopted Judge Stark's claim construction from Aurobindo I as follows:

Disputed Word

Meaning

“Portion”

“a distinct formulation” ('032 Patent)

“Modified release drug product”

“a dosage form comprising a sustained release quantity and an immediate release quantity, and having both immediate release and sustained release properties” ('821 Patent)

“Immediate release formulation wherein the guaifenesin becomes bioavailable in a subject's stomach”

“a form intended to rapidly release in the stomach guaifenesin for absorption” ('821 Patent)

“Release-delaying matrix”

“a combination of hydrophilic and water insoluble polymers of the sustained release formulation which gels in the stomach” ('821 patent)

         Although the two formulations need not be physically separate - except where there is a limitation regarding the spatial orientation of them, like a bi-layered tablet - they must be “inherently physically ‘separate'” because they are distinct formulations.[11] This construction is in line with the Federal Circuit's decision that construed the same term in the context of the related (not asserted here) '252 Patent. See Watson, 430 Fed.Appx. at 875-77.

         The Aurobindo court, much like the Perrigo court, turned to the Federal Circuit's construction of the “portion” limitation in the '252 Patent. See Aurobindo I, 2016 U.S. Dist. LEXIS 152337, at *6-8. The Federal Circuit construed “portion” as a discrete part of the product. Watson, 430 Fed.Appx. at 875-77. Based on the nearly-identical language of the '032 Patent, the Aurobindo court construed “portion” to mean “distinct formulation.” Aurobindo I, 2016 U.S. Dist. LEXIS 152337, at *6, *8 n.5 (“[I]n order to avoid confusion . . . the Court has (non-substantively) modified the Federal Circuit's construction of “portion” by substituting “distinct formulation” for “discrete part of the product.”) Similarly, regarding the '821 Patent, as Judge Stark found and this Court adopted, the plain language of the claim - a “modified release drug product” comprising a “first quantity”[12] and “second quantity” of guaifenesin - imposes a requirement that the product comprises two distinct formulations. Id. at *12-13.

         The parties squabble over whether “discrete” means “distinct.” Reckitt contends that the words have different meanings and, thus, the Federal Circuit's construction of “portion” in Claim 1 as a “discrete part of the product” cannot be squared under the doctrine of claim differentiation with Claim 3 which provides “the drug product according to claim 1, wherein the first and second portions are discrete.” See Watson, 430 Fed.Appx. at 876 (construing '252 Patent). The Watson case involved a bi-layered tablet. As the Watson court explained, the two-portion limitation distinguished the product from the defendant's non-layered tablet.[13] The Aurobindo case, like this case, however, did not involve a bilayer tablet. The Aurobindo court modified the construction by substituting “distinct formulation” for “discrete part of the product.” Aurobindo I, 2016 U.S. Dist. LEXIS 152337, at *8 n.5. Notably, the Aurobindo court declined to impose a construction that required any particular spatial relationship. Id. at *13. The Court ruled

To the extent the parties' dispute centers on whether the IR and SR formulations must be “physically separate, ” as in, for example, a bi-layered tablet . . . the Court finds that the claims do not impose limitations regarding the spatial orientation of the two. The Court recognizes that the two different formulations of guaifenesin in the claimed products are inherently physically “separate” because they are distinct formulations. However, the intrinsic record does not support additional structural or spatial limitations being imposed by the word “portion.”

Id. (emphasis in original) (citation omitted).

         As the court explained in its second opinion

In discussing spatial relationships, the Court considered, and rejected, Aurobindo's suggestion that the claims require the two distinct formulations to exist in a particular relationship, such as being layered. But the Court's rejection of any particular spatial relationship simply means that the two distinct formulations can be put together into a tablet in any physical combination. See, e.g., '821 [P]atent col. 4 ll. 8-16 (describing tablet embodiments composed of two types of beads or granules mixed together; a sustained-release core with immediate-release outer coating; or two layers). It does not eliminate the requirement for two distinct formulations, which are defined in the patents by their ingredients. See, e.g., '821 [P]atent col. 20 l. 54-col. 21 l. 37 (defining IR and SR formulations by listing components).

Aurobindo II, 2017 U.S. Dist. LEXIS 31985, at *24 (emphasis in original).

         In this Court's view, the Aurobindo court recognized that Claims 1 and 3 used the terms “distinct” and “discrete” with somewhat different meanings. Although the words are often used interchangeably, the Court finds that “discrete” in Claim 3 means “separate and distinct.” See Webster's New World College Dictionary 411 (Michael Agnes eds., 4th ed. 2010). Thus, Claim 3 added a particular spatial relationship, see '821 Patent col. 4:10-12 (“beads or granules of both immediate release formulation and beads or granules of sustained release formulation”), not present in Claim 1.[14] Cf. Claim 4 (“The drug product according to claim 3, which is in a form of a bi-layer tablet”).[15]

         B. Infringement Analysis

         The Court must next 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), abrogated on other grounds by Teva Pharm. USA, Inc. v. Sandoz, Inc., 135 S.Ct. 831 (2015).[16] Thus, the relevant question is whether the Defendants' ANDA Products contain two distinct formulations, an IR Formulation and a SR Formulation. Because Reckitt believed that the Aurobindo court had granted summary judgment against it due to Reckitt's failure to present any evidence of structural or spatial limitations, [17] the trial before this Court primarily involved testimonial evidence focused on that issue.

         1. Dr. Davies's Raman Imaging

         Reckitt introduced the testimony of Dr. Davies who relied on Raman chemical imaging maps of Defendants' Products to attempt to show that the accused products have a distinct IR formulation on the surface and a distinct SR formulation below the surface. Tr. 98:24 - 99:7. In general, Dr. Davies identified a region where there was guaifenesin and other excipients, without (XXXXX) (a rate-changing polymer), on and near the surface of the tablets from which guaifenesin would rapidly release, i.e., an IR portion. He then identified another region beneath the surface of the tablets where the rate of guaifenesin would be slower, i.e., an SR portion, because (XXXXX) is present, which effects the release of guaifenesin. Dr. Davies then testified how the IR and SR portions were, in his opinion, distinct in location, composition, and in release properties.

         Defendants argue that the analyses done by Dr. Davies are flawed for numerous reasons. Principally, Defendants aver that Dr. Davies's images merely portray what is well known, that in a non-coated tablet there is always guaifenesin on the surface that rapidly dissolves in the stomach before the rate-controlling polymers have swelled to exert a rate-controlling effect. Defendants also contend that Dr. Davies equated two distinct formulations with dissolution behavior, a theory rejected by the Aurobindo court. See Aurobindo II, 2017 U.S. Dist. LEXIS 31985, at *18, 19-23 ("[That the drugs have similar dissolution profiles] is unsurprising, as bioequivalence to an already-approved product is a requirement for ANDA approval”). The Court now turns to the parties' analyses of the evidence.

         As an initial matter, the parties do not dispute that Raman microscopy testing is used in the pharmaceutical industry as a means to characterize the structure of solid oral dosage forms. Tr. 134:17-20. Raman spectroscopy and microscopy produces unique chemical fingerprints which may enable a person skilled in the art to identify the molecules at any given position. Id. at 134:21-23.

         As part of his Raman analysis, Dr. Davies cut a single tablet of each of the Defendants' products in half and then used a microtome to obtain an extremely thin and flat substrate for imaging. Id. at 135:6-12. The spot size of the laser used for imaging was two microns. Id. at 139:9. After a spectrum was obtained the laser moved to a new spot five microns away to repeat the process. Id. at 139:14-16. For each spectrum, the acquisition time was 400 milliseconds. Id. at 139:21-22. This process was repeated 230, 000 times and each spectrum was matched to a compound, using K-means cluster analysis, and a corresponding location in order to create a colored Raman map. Id. at 145:21; 176:17-177:10.

         a. Imaging of DRL Tablet

         Dr. Davies generated the following two maps which he testified are representative of the structure of DRL's tablets (PTX 35). (XXXXX) In the third demonstrative map (PDX 237), the red arrows illustrate where, allegedly, guaifenesin is present on the surface.

         (IMAGE OMITTED)

         (PTX 35)

         (IMAGE OMITTED)

         (PDX 237)

         According to Dr. Davies, the surface of DRL's tablet was “dominated” by guaifenesin. Tr. 147:25-148:15. He explained that regions on and near the surface of DRL's tablet dominated by guaifenesin and other excipients, but without the rate-controlling (XXXXX) polymers, constitute the first portion of guaifenesin in IR form. Id. at 148:15-20. Because the guaifenesin present in the IR region is uninhibited by (XXXXX) (which is rate-controlling), it rapidly releases in the gastric fluid upon contact. Id. at 148:21-23. The consistent release rate in the first hour is about 23%. Id. at 118:20-24. In his opinion, this is a distinct immediate release formulation within the meaning of the asserted claims. Id. at 118:22-25; 191-198. Dr. Davies further testified that DRL's products contain a second portion of guaifenesin in SR form, which is guaifenesin in the interior of the tablet in the presence of the rate- controlling polymers, a second formulation within the asserted claims. Id. at 118:25-119:4; 191-198.

         b. Imaging of Amneal Tablet

         Dr. Davies also generated the following map (PTX 36), which he testified is representative of the structure of Amneal's tablets:

         (IMAGE OMITTED)

         (PTX 36)

         (IMAGE OMITTED)

         (PDX 241)

         Similar to the DRL tablet, the red arrows in the demonstrative map above, (PDX 241), illustrate where guaifenesin is present on the surface of the Amneal tablet. According to Dr. Davies, the surface is dominated by guaifenesin and other excipients without Methocel, which constitutes the IR formulation. Id. at 160:6-10. Dr. Davies testified that Amneal's tablets provide a consistent release in the first hour, about 20% and 24% for the 1200 mg and 600 mg products, respectively. Id. 422:6-10. In his opinion, this is a distinct immediate release formulation. Id. at 160:7-9. He further provided that, similar to the DRL tablet, the guaifenesin below the surface is inhibited by the rate-controlling polymers and is the SR distinct formulation.

         2. Dr. Davies's Analysis is Flawed and Unreliable

         Because the parties spent a considerable amount of time either defending or attacking Dr. Davies's Raman analyses, the Court first turns to some of the parties' specific arguments. In the Court's final analysis, however, it is not so much that Dr. Davies's images were flawed - as they were for the reasons set forth herein - but that his interpretation of those images was fundamentally flawed. Defendants argue as a general principle that Dr. Davies's Raman maps should be given no evidentiary weight because they are nothing more than “window dressing.” They essentially rely on an exchange between Dr. Davies and the Court:

The Court: But it seems to me, correct me if I'm wrong, that if you have to do content blending, uniformity blending, you are going to get this mixture. You know the significant percentages of guaifenesin going into it. It seems to me that that picture could have been painted without the imaging.
The Witness: Your Honor, to me it could because . . . I think looking at the dissolution and the PK data, somebody of ordinary skill in the art would know thatsuch formulations would be able to achieve that because they have the first portion and an immediate-release portion and they have a sustained-release portion that can give you that long term effect. It's - I guess ...

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