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Warner Chilcott Laboratories Ireland Limited, et al v. Impax Laboratories

April 30, 2012

WARNER CHILCOTT LABORATORIES IRELAND LIMITED, ET AL.,
PLAINTIFFS,
v.
IMPAX LABORATORIES, INC., ET AL., DEFENDANTS. WARNER CHILCOTT LABORATORIES IRELAND LIMITED, ET AL., PLAINTIFFS,
v.
MYLAN PHARMACEUTICALS INC., ET AL., DEFENDANTS. WARNER CHILCOTT LABORATORIES IRELAND LIMITED, ET AL.,
PLAINTIFFS,
v.
IMPAX LABORATORIES, INC., DEFENDANT.



The opinion of the court was delivered by: William J. Martini, U.S.D.J.:

OPINION

TABLE OF CONTENTS

I.JURISDICTION, VENUE, AND APPLICABLE LAW..........2

II.BACKGROUND..........................3

A.THE DORYX® CAPSULE.....................3

B.THE '161 PATENT AND THE DORYX® TABLET.........4

C.PROCEDURAL HISTORY....................6

III.INFRINGEMENT..........................7

A.MOTIONS FOR JUDGMENT AS A MATTER OF LAW........8

B.MYLAN'S ANDA PRODUCT DOES NOT INFRINGE THE '161 PATENT...........................8

1.Plaintiffs Failed to Prove That Mylan's ANDA Products Has "A Layer Of Material(s) Between Each Core Element And Its Modified Release Coating" ................9

a.Mylan Does Not Apply a Stabilizing Coat to its ANDA Product........................9

b.Five Widely-Accepted Scientific Testing Methods Did Not Show the Presence of a Stabilizing Coat in Mylan's Product...10

i.Raman Spectroscopy..............10

ii.ToF-SIMS Testing...............18

iii.ATR-FTIR Testing...............24

iv.AFM Testing..................24

v.SEM Testing..................25

c.Dr. Davies's Humidity Test Does Not Support a Finding that There Is a Stabilizing Coat in Mylan's Product........25

i.Dr. Davies's Humidity Test: Methodology, Testing, and Results.....................26

ii.Dr. Davies's Humidity Test Does Not Meet the Daubert Standard.....................27

iii.Even if Dr. Davies's Humidity Test Met the Daubert Standard, the Test Would Not Support a Finding that there Is a Stabilizing Coat in Mylan's Product....31

2.Plaintiffs Failed to Prove that the Alleged Stabilizing Coat "Keeps Migration of Core Materials to a Minimum Such That the Interaction of Core Materials With Coating Materials Is Reduced or Prevented" .......................34

C.IMPAX'S ANDA PRODUCT DOES NOT INFRINGE THE '161 PATENT.............................36

1.Plaintiffs Failed to Prove That Impax's ANDA Product Has "A Layer Of Material(s) Between Each Core Element And Its Modified Release Coating" .......................36

a.Impax Does Not Apply a Stabilizing Coat to its ANDA Product.................................................37

b.Five Widely-Accepted Scientific Testing Methods Did Not Show the Presence of a Stabilizing Coat in Impax's Unaltered Seeds....................................................38

i.ATR-FTIR Testing ............................................38

ii.ToF-SIMS Testing ............................................39

iii.SEM/EDS Testing .............................................41

iv.Optical Microscopy...........................................41

v.AFM Testing......................................................41

c.Dr. Davies's Acetone Wash Test Does Not Support a Finding that There Is a Stabilizing Coat in Impax's Product................42

i.Dr. Davies's Acetone Wash Test: Methodology, Testing, and Results........................................................42

ii.Dr. Davies's Acetone Wash Test Does Not Meet the Daubert Standard .............................................43

iii.Even if Dr. Davies's Acetone Wash Test Met the Daubert Standard, the Test Would Not Support a Finding that there Is a Stabilizing Coat in Impax's Product....45

2.Plaintiffs Failed to Prove that the Alleged Stabilizing Coat "Keeps Migration of Core Materials to a Minimum Such That the Interaction of Core Materials With Coating Materials Is Reduced or Prevented" ....................................................................48

3.Plaintiffs Met Their Burden of Proving that Impax's Product Provides the Required Dissolution Storage Stability.....................49

IV.VALIDITY.............................................................................................50

A.ANTICIPATION..........................................................................................50

1.The '777 Patent Does Not Inherently Disclose the Dissolution Storage Stability Limitations........................................................51

2.The '777 Patent Does Not Anticipate the Migration Limitation...........................................................................55

3.The '777 Patent Does Not Anticipate the Limitations that Require that the Active Ingredient Be an Acid Salt of Doxycycline..........56

4.The '777 Patent Anticipates the Tablet Limitation.......................56

B.OBVIOUSNESS...........................................................................................57

1.Level of Ordinary Skill in the Art...................................................58

2.Scope and Content of the Prior Art................................................58

3.Differences Between the Claimed Subject Matter and Prior

ii

Art.......................................................................................................59

a.The Dissolution Storage Stability Limitations Are Not Rendered Obvious by the Prior Art............................................59

b.The Stabilizing Coat Limitation Is Not Rendered Obvious by the Prior Art................................................................................60

i.A Person of Ordinary Skill in the Art Attempting to Solve the Dissolution Stability Problem Faced Many Possible Choices.............................................................................61

ii.The '777 Patent Does Not Render the Stabilizing Coat Limitation Obvious...........................................................62

iii.JP '926 Does Not Render the Stabilizing Coat Limitation Obvious............................................................................63

iv.WO '453 Does Not Render the Stabilizing Coat Limitation Obvious............................................................................64

v.EP '536 Does Not Render the Stabilizing Coat Limitation Obvious............................................................................64

c.The Limitations Relating to the Percentage of Coated Cores in the Tablet Are Not Rendered Obvious by the Prior Art............65

4.Secondary Factors (Objective Indicia of Non-Obviousness)........66

C.DEFENDANTS' REMAINING INVALIDITY ARGUMENTS.................66

V.DEFENDANTS' EXCEPTIONAL CASE CLAIMS.........................................67

VI.CONCLUSION.....................................................................................................67

iii

Plaintiffs Warner Chilcott Company, LLC and Warner Chilcott (US), LLC (collectively, "Warner Chilcott") and Mayne Pharma International Pty. Ltd. ("Mayne") are pharmaceutical companies that develop or market brand name drug products. Mayne was formerly known as F. H. Faulding & Co., Ltd. ("Faulding"). Mayne is the owner of United States Patent No. 6,958,161 ("the '161 Patent"), entitled "Modified Release Coated Drug Preparation." The '161 Patent covers a modified release preparation of doxycycline hyclate that helps to maintain the drug's intended rate of release over time. Warner Chilcott has exclusive rights to market and sell products covered by the '161 Patent in the United States. Warner Chilcott sells such products under the brand name Doryx® Delayed Release Tablets ("Doryx Tablets").

Defendants Mylan Pharmaceuticals Inc. and Mylan Inc. (collectively "Mylan") and Impax Laboratories, Inc. ("Impax") are generic pharmaceutical companies. Mylan and Impax each filed Abbreviated New Drug Applications ("ANDAs") with the Food and Drug Administration ("FDA"), seeking approval to market generic versions of Doryx Tablets. In response to Defendants' ANDA filings, Plaintiffs filed these Hatch-Waxman actions, alleging that Mylan and Impax infringed the '161 Patent. Mylan and Impax assert that their generic products do not infringe the '161 Patent. Mylan and Impax also assert that the '161 Patent is invalid on the grounds of anticipation and obviousness.

The Court conducted a seven-day bench trial between February 1, 2012 and February 9, 2012. The parties submitted post-trial briefs and proposed findings of fact and conclusions of law on February 21, 2012. After carefully considering the record evidence and the parties' submissions, the Court makes the following findings.

First, the Court finds that Plaintiffs failed to prove, by a preponderance of the evidence, that Mylan's ANDA product infringes the '161 Patent. More specifically, the Court finds that Plaintiffs failed to prove that Mylan's ANDA product has a stabilizing coat, as required by the '161 Patent. Mylan does not apply a stabilizing coat to its ANDA product. And five widely-accepted scientific testing methods failed to show the presence of a stabilizing coat in Mylan's product. The one, novel "humidity test" relied on by Plaintiffs does not meet the Daubert standard for admissibility. Even if the "humidity test" met the Daubert standard, Plaintiffs still failed to prove that there was a stabilizing coat in Mylan's product. The Court also finds that Plaintiffs failed to prove that the alleged stabilizing coat in Mylan's product kept the migration of core materials to a minimum, such that the interaction of core materials with coating materials was reduced or prevented.

Second, the Court finds that Plaintiffs failed to prove, by a preponderance of the evidence, that Impax's ANDA product infringes the '161 Patent. The Court finds that Plaintiffs failed to prove that Impax's ANDA product has a stabilizing coat. Impax does not apply a stabilizing coat to its ANDA product. And five widely-accepted scientific testing methods failed to show the presence of a stabilizing coat in the unaltered seeds in Impax's tablet. The one, novel "acetone wash test" relied on by Plaintiffs does not meet the Daubert standard for admissibility. Even if the "acetone wash test" met the Daubert standard, Plaintiffs still failed to prove that there was a stabilizing coat in Impax's product. The Court also finds that Plaintiffs failed to prove that the alleged stabilizing coat in Impax's product kept the migration of core materials to a minimum, such that the interaction of core materials with coating materials was reduced or prevented. The Court finds that Plaintiffs met their burden of proving that Impax's product provided the required level of dissolution storage stability. However, this does not change the Court's overall finding that Impax's ANDA product is non-infringing.

Third, the Court finds that Defendants failed to prove, by clear and convincing evidence, that the '161 Patent is invalid as anticipated by United States Patent No. 5,413,777 ("the '777 Patent"). The Court finds that the '777 Patent does not inherently disclose the dissolution storage stability limitations of the '161 Patent. The Court also finds that the '777 Patent does not anticipate the stabilizing coat limitation of the '161 Patent. Lastly, the Court finds that the '777 Patent does not anticipate the limitations that require that the active ingredient be an acid salt of doxycycline. The Court finds that the '777 Patent anticipates the tablet limitation of the '161 Patent. However, this does not change the Court's overall finding that the '161 Patent is not invalid as anticipated.

Fourth, the Court finds that Defendants failed to prove, by clear and convincing evidence, that the '161 Patent is obvious in light of prior art. The Court finds that the dissolution storage stability limitations of the '161 Patent are not rendered obvious by the prior art. The Court also finds that the stabilizing coat limitation of the '161 Patent is not rendered obvious by the prior art. Lastly, the Court finds that the limitations of the '161 Patent relating to the percentage of coated cores in the tablet are not rendered obvious by the prior art.

Finally, the Court finds that Defendants failed to establish their exceptional case claims by clear and convincing evidence. Accordingly, Mylan and Impax are not entitled to an award of attorneys' fees and expert fees under 35 U.S.C. § 285.

This Opinion constitutes the Court's findings of fact and conclusions of law pursuant to Federal Rule of Civil Procedure 52(a). All proposed findings of fact and conclusions of law inconsistent with those set forth herein are rejected.

I.JURISDICTION, VENUE, AND APPLICABLE LAW

This Court has subject matter jurisdiction over this action pursuant to 28 U.S.C. §§ 1331 and 1338(a). This action arises under the Patent Laws of the United States, 35 U.S.C. § 1, et seq.; Defendants' counterclaims arise under the Declaratory Judgment Act, 28 U.S.C. §§ 2201 and 2202, and the Patent Laws of the United States, 35 U.S.C. § 1, et seq. Because this action arises under the Patent Laws, the Court must apply the precedents of the United States Court of Appeals for the Federal Circuit, which has jurisdiction over any appeal of this judgment. See 28 U.S.C. § 1295(a). The Court has personal jurisdiction over Defendants; no Defendant has contested personal jurisdiction in these actions. Venue is proper in this district under 28 U.S.C. § 1391(b) and (c), and 28 U.S.C. § 1400(b).

II.BACKGROUND*fn1

Understanding the invention at issue requires a brief excursion into the history of the Doryx products.

A.THE DORYX® CAPSULE

Prior to the invention of the '161 Patent, Faulding developed a delayed release doxycycline hyclate capsule formulation, which was marketed under the brand name Doryx® Delayed Release Capsules ("Doryx Capsules" or the "Capsule"). Joint Appendix ("JA") 1470:2-5, ECF No. 288. Doxycycline hyclate is a broad-spectrum antibiotic that is used to treat bacterial infections such as severe acne. See JA 5469.

There are two issues associated with the rate at which doxycycline hyclate is released in the body (a drug's rate of release in the body is referred to as the drug's "dissolution profile"). If doxycycline hyclate is released immediately in the stomach, patients may experience gastric upset that could result in nausea and vomiting. JA 131:6-16; JA 1583 col. 2, ll. 55-64; JA 3289. If the drug is released too slowly, however, there will be an absorption (or "bioavailability") problem because less of the drug will be absorbed in the bloodstream. JA 1468:23-1470:1; JA 3299; JA 3385.

To address the competing problems of gastric upset and bioavailability, Faulding developed a modified release preparation*fn2 of doxycycline hyclate. JA 3289-90; JA 5653. Specifically, Faulding designed a drug formulation in which pellets containing doxycycline hyclate were coated in a special delayed release coating. JA 131:3-5. Multiple pellets would then be encased in a gelatin capsule. JA 1556:14-18; JA 5582. The special delayed release coating developed by Faulding maximized release of the active ingredient in the upper part of the small intestine. JA 3289-90. By creating a drug formulation that released the majority of the drug in the small intestine, Faulding solved the gastric upset problems associated with release in the stomach, and the bioavailability problems associated with release further down the gastrointestinal tract. JA 1470:2-10; JA 1471:23-1472:24; JA 3290.

An important aspect of the manufacture of pharmaceutical products is their stability over extended periods of time, which is commonly referred to as "shelf life." JA 1583. There are two general aspects to the stability or "shelf life" of a drug: (1) the chemical stability of the ingredients themselves ("chemical stability"), and (2) the maintenance over time of the drug's originally intended rate of release ("dissolution storage stability"). JA 1475-76; JA 1583; JA 3388.

The Doryx Capsule was marketed with a two year shelf life. JA 1311:13-14. The two-year shelf life in this case referred to the product's chemical stability: the active ingredient still functioned as an antibiotic after two years of storage. However, in 1990, scientists at Faulding observed that there was a problem with the drug's dissolution storage stability. JA 3286-91. They observed that the drug's rate of release would increase over time. JA 3290; JA 1470-72. Thus, if the drug were ingested immediately after being manufactured, the active ingredient would be released in the small intestine, as originally intended. But if the drug were ingested after sitting in storage for two years, more of the active ingredient would be released in the stomach, leading to an increase in the incidence of nausea. JA 3290; JA 1471:23-1472:20; JA 3386.

Faulding scientists were unable to determine the precise cause of the dissolution storage stability problem.*fn3 JA 3291; JA 1472:25-1473:7; JA 3387. In October 1993, the scientists compiled a long list of possible reasons for the dissolution instability. JA 3287-88; JA 1473:20-1475:3. The list contained 74 possible causes for the instability, and focused on factors related to the delayed release coating. See JA 3287-88. It was not until years later that Faulding unexpectedly discovered a solution to the dissolution storage stability problem. JA 1475:9-17; JA 1476:25-1477:15; JA 3389.

B.THE '161 PATENT AND THE DORYX® TABLET

The '161 Patent embodies Faulding's solution to the dissolution storage stability problem. Faulding scientists found that adding a "stabilizing coat"*fn4 between the doxycycline hyclate core and the delayed release coating of the pellets prolonged the shelf life of the Doryx Capsule's rate of release. JA 1583-89. The scientists postulated that this "stabilizing coat" improved dissolution stability by minimizing the interaction between the active ingredient and the delayed release coating. See JA 1585 col. 6, 1. 67 -- 1586 col. 7, 1. 2. The central issue for infringement is whether Mylan and Impax's ANDA products contain this "stabilizing coat." The '161 Patent also provides that the pellets can be contained in a tablet instead of a capsule. JA 1589. That is why products covered by the '161 Patent are sold under the brand name "Doryx Tablets."

Claims 1 and 21 of the '161 Patent describe the three-part structure for the pellets:

(1) a core element containing the active ingredient; (2) a modified release coating; and (3) a "stabilizing coat" between each core element and its modified release coating. See JA 1588 col. 12, ll. 36-47. The '161 Patent explains that the stabilizing coat "is intended to keep migration of core materials to a minimum such that their interaction with coating materials is reduced or prevented." JA 1585 col. 6, l. 67 - 1586 col. 7, l. 2. The '161 Patent states that the stabilizing coat can be comprised of "any suitable material." JA 1586 col. 7, ll. 4-5.

Claims 1, 2, 3, and 21 of the '161 Patent (among others) describe the Patent's dissolution storage stability limitations. Immediately after manufacturing, the pellets have their originally intended rate of release (a drug's originally intended rate of release is referred to as the drug's "pre-storage dissolution profile"*fn5 ). See JA 1583. After a certain amount of time in storage, the drug's rate of release can change (a drug's rate of release after storage is referred to as the drug's "post-storage dissolution profile"). Id. The dissolution storage stability limitations of the '161 Patent set forth the extent to which the drug's pre-storage rate of release can differ from its post-storage rate of release. For example, Claim 1 of the Patent states that "the amount of active ingredient released at any time on a post-storage dissolution profile [must be] within 40 percentage points of the amount of active ingredient released at any time on a pre-storage dissolution profile." JA 1588 col. 12, ll. 43-47. The '161 Patent provides that dissolution stability testing should be conducted according to FDA guidelines, which specify that the product should be tested "in its container and package" under "accelerated conditions." JA 1583 col. 2, ll. 29-37.

Claims 16 through 22 of the '161 Patent describe the Patent's tablet limitations. The claims provide that a plurality of pellets can be compressed to form a tablet. See JA 1589 col. 13, ll. 44-46. Several claims also set forth the percentage of the preparation that can be comprised of pellets. Claim 17, for example, describes a preparation "wherein the percentage of coated core elements in each tablet is in the range of 20 to 40 by weight of the total dosage weight." JA 1589 col. 14, ll. 1-3.

The patent application that led to the '161 Patent was filed April 12, 2002.*fn6 JA 1579. The '161 Patent was issued by the United States Patent and Trademark Office ("PTO") on October 25, 2005. Final Pretrial Order, Stipulation of Facts ("SF") ¶¶ 9-10, ECF No. 252; JA 1578. The '161 Patent is the sole patent-in-suit.

C.PROCEDURAL HISTORY

Mayne filed New Drug Application ("NDA") No. 50-795 with the FDA for 75 mg, 100 mg, and 150 mg Doryx Tablets. SF ¶ 14. On May 6, 2005, the FDA approved the use of 75 mg and 100 mg Doryx Tablets. SF ¶ 15. On June 20, 2008, the FDA approved the use of 150 mg Doryx Tablets. SF ¶ 26.

Mylan submitted to the FDA ANDA Nos. 90-431 and 91-052, seeking approval to market generic versions of 75 mg, 100 mg, and 150 mg Doryx Tablets. SF ¶¶ 19, 29. Mylan included with its ANDA filings certifications under 21 U.S.C. § 355(j)(2)(A)(vii)(IV) ("Paragraph IV Certifications") asserting that the '161 Patent is invalid, unenforceable, and/or will not be infringed by the manufacture, use, or sale of Mylan's proposed generic drugs. SF ¶¶ 20, 30. Mylan received final FDA approval of its 75 mg and 100 mg ANDA products in December 2010, and thereafter began selling its 75 mg and 100 mg ANDA products in the United States. SF ¶ 21. Mylan received tentative FDA approval for its 150 mg ANDA product on June 10, 2011. SF ¶ 31.

Impax submitted to the FDA ANDA Nos. 90-505 and 91-132, seeking approval to market generic versions of 75 mg, 100 mg, and 150 mg Doryx Tablets. SF ¶¶ 16, 27. Impax included with its ANDA filings Paragraph IV Certifications asserting that the '161 Patent is invalid, unenforceable, and/or will not be infringed by the manufacture, use, or sale of Impax's proposed generic drugs. SF ¶ 17, 28. Impax received final FDA approval of its 75 mg and 100 mg ANDA products in December 2010. SF ¶ 18.

In response to Defendants' ANDA filings, Plaintiffs filed these Hatch-Waxman actions, alleging that Mylan and Impax infringed the '161 Patent. These actions have been consolidated for purposes of discovery and trial.

On July 11, 2011, the parties participated in a hearing pursuant to Markman v. Westview Instruments, Inc., 52 F.3d 967 (Fed. Cir. 1995) (en banc). On July 20, 2011, this Court issued an opinion and order reflecting the Court's construction of the five disputed claim terms of the '161 Patent. The Court construed the phrase "stabilising coat is provided between each core element and its modified release coating" in Claims 1 and 21 to mean:

[A] layer of material(s) between each core element and its modified release coating, which keeps the migration of core materials to a minimum such that the interaction of core materials with coating materials is reduced or prevented.

Warner Chilcott Labs. Ireland v. Impax Labs., Inc., No. 08-6304, 2011 WL 2971155, at *7 (D.N.J. Jul. 20, 2011).

On August 24, 2011, Plaintiffs moved for a preliminary injunction to enjoin Mylan from selling its 150 mg ANDA product. See Mot. for Prelim. Inj., ECF No. 33 (No. 09-2073). On September 22, 2011, this Court granted Plaintiffs' motion, and Mylan subsequently appealed. See ECF Nos. 53, 56 (No. 09-2073). On December 12, 2011, the Federal Circuit vacated the preliminary injunction and remanded the action for further proceedings. See Warner Chilcott Labs. Ireland v. Impax Labs., Inc., No. 11-1611, 2011 WL 6144301 (Fed. Cir. Dec. 12, 2011). In remanding the action, the Federal Circuit noted that "the district court may consider entering a temporary restraining order after this court's mandate issues, then consolidating the preliminary injunction hearing with the bench trial on the merits." Id. at *5.

Consistent with the Federal Circuit's recommendation, this Court consolidated the preliminary injunction hearing with a bench trial on the merits, which the Court conducted between February 1, 2012 and February 9, 2012. At trial, Mylan's counsel indicated that Mylan received final FDA approval for its 150 mg ANDA product. JA 1334:11-15. On February 8, 2012, pursuant to the recommendation of the Federal Circuit, this Court entered a temporary restraining order enjoining Mylan from launching its generic version of 150 mg Doryx Tablets. TRO, ECF No. 133 (No. 09-2073); TRO, ECF No. 269 (No. 08-6304). The temporary restraining order was entered with the consent of the parties, "in order to permit this Court time to complete the pending trial of this matter, consider the evidence and render a decision." Id.

The Court will now address: (1) Plaintiffs' infringement cases against Mylan and Impax, (2) Defendants' invalidity defenses of anticipation and obviousness, and (3) Defendants' exceptional case claims.

III.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 the claim limitations of the patent-in-suit. See Adams Respiratory Therapeutics, Inc. v. Perrigo Co., 616 F.3d 1283, 1287 (Fed. Cir. 2010); Abbott Labs. v. TorPharm, Inc., 300 F.3d 1367, 1373 (Fed. Cir. 2002). Infringement must be proved by the patentee by a preponderance of the evidence. See SmithKline Diagnostics, Inc. v. Helena Labs. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988); Kegel Co., Inc. v. AMF Bowling, Inc., 127 F.3d 1420, 1425 (Fed. Cir. 1997).

A determination of infringement is a two-step analysis. Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448, 1466 (Fed. Cir. 1998). First, the Court construes the scope and meaning of the asserted patent claims as a matter of law. Id. In this case, the Court construed the claim terms at issue in its Opinion dated July 20, 2011. See Warner Chilcott Labs. Ireland v. Impax Labs., Inc., No. 08-6304, 2011 WL 2971155, at *7 (D.N.J. Jul. 20, 2011). Second, the construed claims are compared to the allegedly infringing product to determine whether each and every claim limitation is present. Cybor Corp., 138 F.3d at 1467. Literal infringement, a type of direct infringement, exists if any one of a patent's asserted claims covers the alleged infringer's product. See Markman v. Westview Instruments, Inc., 517 U.S. 370, 374 (1996). Literal infringement is shown where each limitation of at least one asserted claim of the patent-in-suit is found in the alleged infringer's product. See Panduit Corp. v. Dennison Mfg. Co., Inc., 836 F.2d 1329, 1330 n.1 (Fed. Cir. 1987).

Plaintiffs allege that Mylan and Impax's ANDA products both infringe the '161 Patent. The Court will first address Defendants' motions for judgment as a matter of law on the issue of infringement. The Court will then address Plaintiffs' infringement case against Mylan, followed by Plaintiffs' infringement case against Impax.

A.MOTIONS FOR JUDGMENT AS A MATTER OF LAW

During the bench trial, Defendants each made oral motions for judgment as a matter of law pursuant to Federal Rule of Civil Procedure 50. JA 184:1-1861. Because Rule 50 pertains only to jury trials, the Court will construe Defendants' motions as motions for judgment on partial findings under Federal Rule of Civil Procedure 52(c). Compare Fed. R. Civ. P. 50(a)(1) (Motion for judgment as a matter of law may be made after "a party has been fully heard on an issue during a jury trial"), with Fed. R. Civ. P. 52(c) (Motion for judgment on partial findings may be made after "a party has been fully heard on an issue during a non-jury trial").

Consistent with theterms of Rule 52(c), the Court exercised its discretion to reserve on the motions during the trial. JA 611:6-8; Fed. R. Civ. P. 52(c) ("The court may, however, decline to render any judgment until the close of the evidence."); see also Payne ex el Estate of Payne v. Equicredit Cor. of America, 71 F. App'x 131, 133 (3rd Cir. 2003) (The district court was "clearly within the strictures of Rule 52(c), and properly acted within its discretion to decline to render judgment until the close of all evidence."). The Court now concludes that the best course of action is to render a judgment based on due consideration of all of the evidence, testimony, and applicable law, and the parties' post-trial submissions. Accordingly, the Rule 52(c) motions are DENIED.

B.MYLAN'S ANDA PRODUCT DOES NOT INFRINGE THE '161 PATENT

Plaintiffs assert that Mylan's ANDA product infringes claims 1, 2, 5, 10, 16, 17, and 20-22 of the '161 Patent. SF ¶ 36.

Mylan's ANDA product, like the Doryx Tablet, is comprised of a series of beads that have been compressed into tablet. The parties agree that the beads have a doxycycline hyclate core and a delayed release coating. The only issue for infringement is whether Mylan's beads contain a "stabilizing coat." JA 145:11- 146:25. If the Court finds that Mylan's product contains a stabilizing coat, then Mylan's product infringes the '161 Patent. If the Court finds that Mylan's product does not contain a stabilizing coat, then Mylan's product does not infringe.

Consistent with this Court's claim construction, to prove that Mylan's ANDA product contains a "stabilizing coat," Plaintiffs must show that the product has:

[A] layer of material(s) between each core element and its modified release coating, which keeps the migration of core materials to a minimum such that the interaction of core materials with coating materials is reduced or prevented.

Warner Chilcott Labs. Ireland, 2011 WL 2971155, at *7.

For the reasons set forth below, the Court finds that Plaintiffs failed to prove, by a preponderance of the evidence, that Mylan's ANDA product infringes the '161 Patent. Specifically, the Court finds that Plaintiffs failed to prove that: (1) Mylan's ANDA product has "a layer of material(s) between each core element and its modified release coating"; and that (2) the alleged stabilizing coat "keeps the migration of core materials to a minimum such that the interaction of core materials with coating materials is reduced or prevented." Warner Chilcott Labs. Ireland, 2011 WL 2971155, at *7.

1.Plaintiffs Failed To Prove That Mylan's ANDA Products Has "A Layer Of Material(s) Between Each Core Element And Its Modified Release Coating"

Plaintiffs assert that Mylan's ANDA product has a "stabilizing coat." Specifically, Plaintiffs allege that each bead in Mylan's ANDA product has a 10 to 40 micron layer of povidone and crospovidone between its core elements and its delayed release coating. See JA 154:7-19; JA 201:23-202:2.

The Court finds that Plaintiffs failed to prove that Mylan's ANDA product has "a layer of material(s) between each core element and its modified release coating." Warner Chilcott Labs. Ireland, 2011 WL 2971155, at *7. The Court makes this finding for three reasons. First, it is undisputed that Mylan does not apply a stabilizing coat to its ANDA product. Second, five widely-accepted scientific testing methods did not show the presence of a stabilizing coat in Mylan's product. Finally, the one novel test that Plaintiffs rely on failed to show that there is a stabilizing coat in Mylan's product. Each of these findings is explained in greater detail below.

a.Mylan Does Not Apply a Stabilizing Coat to its ANDA Product

It is undisputed that Mylan does not apply a stabilizing coat to its ANDA product during the manufacturing process.

The manufacture of Mylan's ANDA product takes place in three stages. In the first stage, Mylan manufactures the uncoated active ingredient core beads by thoroughly mixing dry ingredients doxycycline hyclate, lactose, and crospovidone with purified water, sodium lauryl sulfate, povidone, and sodium chloride. JA 597:11-598:11. The resulting material is fed into an extruder machine, and the extruded material is then spheronized, dried, and screened. JA 598:18-599:12; JA 944:11-945:2. In the second stage, the uncoated core beads are fed into a specialized coating unit referred to as a Wurster coater, where a single, uniform delayed release coating containing hypromellose phthalate ("HPMCP") is sprayed onto the beads. JA 599:14-24. In the final stage, the delayed release coated beads are blended with inactive ingredients and fed into a tablet- compressing machine to produce 75 mg, 100 mg or 150 mg tablets. JA 600:3-12. Plaintiffs do not dispute that Mylan applies a single delayed release coating onto its beads and does not apply any other coating. JA 427:25-428:5.

b.Five Widely-Accepted Scientific Testing Methods Did Not Show the Presence of a Stabilizing Coat In Mylan's Product Five widely-accepted scientific testing methods did not show the presence of a stabilizing coat in Mylan's product. These five testing methods are: (1) Confocal Raman spectroscopy ("Raman"); (2) Time of Flight Ion Mass Spectroscopy ("ToF-SIMS"); (3) Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy ("ATR-FTIR"); (4) Atomic Force Microscopy ("AFM"); and (5) Scanning Electron Microscopy ("SEM").

The Court finds that each of these five testing methods is scientifically reliable and that the test results as a whole demonstrate that there is no stabilizing coat in Mylan's product. The Court specifically finds that Raman and ToF-SIMS data affirmatively show that there is no stabilizing coat in Mylan's product. The Court finds that the ATR-FTIR, AFM, and SEM tests conducted by Plaintiffs' expert, Dr. Martyn Davies, confirm that there is no stabilizing coat.

i.Raman Spectroscopy

For over twenty years, Raman has been used to determine the identity and location of materials in pharmaceutical products. JA 622:25-623:6. Raman has been subjected to extensive and rigorous peer review and is widely accepted and used by the pharmaceutical industry, academia, and contract labs. JA 630:16-631:1. Raman is the primary testing method relied on by Mylan, and was one of the first testing methods conducted by Plaintiffs' expert, Dr. Davies.

Dr. Neil Everall, Mylan's expert witness on Raman spectroscopy, is a world-renowned expert in Raman and infrared technology. JA 617:24-618:3. He was the first scientist to publish an article regarding the fundamentals of Raman spectroscopy, and the proper acquisition and interpretation of Raman data. JA 617:1-13; JA 3644-54. He is the editor of a definitive five volume encyclopedia set regarding Raman and infrared spectroscopy, and has analyzed hundreds of pharmaceutical samples using these techniques. JA 617:14-18; JA 3644-54. The Court qualified Dr. Everall as an expert regarding the application of Raman infrared spectroscopy and the interpretation of Raman and infrared data. JA 619:19-620:2.

The Court finds that Raman data provides the strongest evidence that there is no stabilizing coat in Mylan's product. The Court will address: (1) the methodology for using Raman and analyzing Raman data; (2) the Raman testing of Mylan's ANDA product and the results of that testing; and (3) the conclusions of the Court.

1) Methodology

Raman is a well-established method for determining the chemical composition and structure of pharmaceutical products. Raman does this by using chemical "fingerprints" to identify particular molecules.

Raman testing is conducted using a Raman machine, which has two parts: an optical microscope and a spectrometer. JA 623:14-22. The optical microscope is used to shine a laser beam onto a sample, which causes the material at the surface of the sample to scatter the laser light. JA 623:23-626:1. The Raman spectrometer measures wavelength patterns in the scattered light, and uses these wavelength patterns to generate Raman spectra. JA 624:14-626:1. The Raman spectra that are produced are referred to as "fingerprints" because each molecule produces a unique spectrum. JA 625:20-626:1.

Raman spectra are plotted on an X-Y graph. JA 625:12-19. The x-axis, called the "Raman Shift," shows the wavelengths of light that are being detected by the spectrometer. JA 625:15-17. The y-axis, called "intensity," shows the amount of light being detected at each wavelength. JA 625:12-19; JA 3908. An example of a Raman spectrum is shown in Figure 1.

Y-Axis

X-Axis Figure 1. Raman Spectrum. JA 3908.

Within each spectrum, scientists look for bands or peaks that are particularly distinctive, and they use these "characteristic peaks" or "characteristic bands" to help identify the molecule in the sample. JA 625:12-626:1. In Figure 1, for example, there is a characteristic band pattern at 1200-1400 wavelengths and at 1180 wavelengths.

Raman can be used to determine both the chemical composition of a product and the structure of a product. JA 625:20-JA 626:1. To determine the chemical composition of an unknown sample, scientists first obtain or develop a list of materials that they know or suspect are in the sample. They then obtain "fingerprints" for each individual material. These fingerprints are referred to as "reference spectra." JA 626:2-19. Next, scientists obtain a "fingerprint" from the unknown sample that they are testing ("sample spectrum"). Id. Finally, the scientists compare the sample spectrum to all the reference spectra that were collected. If the sample spectrum matches one of the reference spectra, then the material in the sample is identified. JA 626:2-19.

To determine the structure of a product, scientists can use various types of Raman analysis. Three types of structural Raman analyses were discussed at trial: (1) two-dimensional mapping, (2) one-dimensional line scanning, and (3) single point measurements. JA 638:18-24. To obtain two-dimensional maps, Raman data are taken from an area of a sample surface. JA 639:6-20. A computer analyzes the Raman data and then generates a two-dimensional, color-coded map that identifies each component on the surface and where it is located. JA 639:4-20; JA 641:10-16. To obtain Raman line scans, the laser beam in the optical microscope is moved along a single line, and the spectrometer acquires spectra at fixed intervals along that line. See JA 655:13-16. To obtain Raman single point measurements, the laser beam is positioned at a point of interest on the sample, and the spectrometer acquires the Raman spectrum for that point. JA 680:19-25.

2) Testing and Results

Dr. Everall performed a series of Raman analyses on Mylan's delayed release coated beads. JA 638:18-24. Dr. Everall received samples of Mylan's beads and samples of each of the ingredients used to manufacture the beads. JA 631:5-8. Using the ingredient samples, Dr. Everall generated reference spectra (or "fingerprints") for each material in the bead, including doxycycline (the active ingredient in the core), HPMCP (the primary ingredient in the delayed release coating), povidone/crospovidone*fn7 (the materials that allegedly comprise a stabilizing coat), lactose, and the other excipients. See JA 631:14-634:11; JA 3683. In a stack plot*fn8 containing the reference spectra generated by Dr. Everall, one can plainly see that the reference spectrum for each material is unique and readily distinguishable from the other spectra. See JA 3683. It is also easy to identify the characteristic peaks for each material. See id.

Next, Dr. Everall tested the delayed release coated beads themselves. Sample beads, chosen at random, were cross-sectioned using two different methodologies: (1) gluing beads onto an SEM stub and cross-sectioning them with a diamond ultramicrotome blade; and (2) embedding the beads in an epoxy resin and cross-sectioning them with a diamond ultramicrotome blade.*fn9 JA 634:20-635:4; JA 635:25-636:21. After Dr. Everall confirmed the quality of the cross-sections, he selected a microscope objective that was optimized for detecting a layer of povidone and crospovidone, optimized the laser focus just beneath the delayed release coating, and recorded Raman spectra from the face of the cross-sections. JA 637:11-638:17.

Dr. Everall performed three types of Raman analyses: (a) two-dimensional mapping, (b) one-dimensional line scanning, and (c) single point measurements. JA 638:18-24. Each type of analysis affirmatively showed that there is no stabilizing coat in Mylan's beads.

a) Dr. Everall's Two-Dimensional Maps

Dr. Everall's two-dimensional mapping clearly demonstrated the absence of a stabilizing coat in Mylan's product.

Dr. Everall acquired Raman spectra from two 90 by 90 micron areas of Mylan's cross-sectioned beads. JA 3695; JA 3696; JA 642:25-643:10. Dr. Everall used a computer to identify the materials that were present in these areas, and created color-coded maps to show how the components were distributed in each area. JA 641:11-16. Each color in the maps corresponded with a distinct chemical species that was identified in the cross-section. JA 641:19-20.

As noted above, both parties agree that the innermost part of Mylan's bead is a core comprised of the active ingredient (doxycycline) and various excipients. Both parties also agree that Mylan's bead is covered in a 10 to 12 micron delayed release coating containing HPMCP. See JA 643:10-11; JA 974:1-7. Plaintiffs allege that, between the delayed release coating and the core, there is a 10 to 40 micron stabilizing coat. JA 154:7-19; JA 201:23-202:2.

If there were a stabilizing coat in Mylan's product, one would expect to see the following in the Raman maps: (1) a 10 to 12 micron layer of color corresponding with HPMCP (the delayed release coat); next to (2) a 10 to 40 micron layer of color corresponding with povidone (the stabilizing coat); next to (3) various sections of different colors corresponding ...


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