Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 1 of 43 PageID #: 15553
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELA WARE
`
`RECKITT BENCKISER
`PHARMACEUTICALS INC., RB
`PHARMACEUTICALS LIMITED, and
`MONOSOL RX, LLC,
`
`Plaintiffs,
`
`v.
`
`DR. REDDY'S LABORATORIES S.A., and
`DR. REDD Y'S LABO RA TORIES, INC.,
`
`Defendants.
`
`RECKITT BENCKISER
`PHARMACEUTICALS INC., RB
`PHARMACEUTICALS LIMITED, and
`MONOSOL RX, LLC,
`
`Civil Action No. 14-1451-RGA
`
`Plaintiffs,
`
`v.
`
`Civil Action No. 14-1573-RGA
`
`PAR PHARMACEUTICAL, INC. and
`INTELGENX TECHNOLOGIES CORP.,
`
`Defendants.
`RECKITT BENCKISER
`PHARMACEUTICALS INC., RB
`PHARMACEUTICALS LIMITED, and
`MONOSOL RX, LLC,
`
`Plaintiffs,
`
`v.
`
`WATSON LABO RA TORIES, INC. and
`ACTAVIS LABORATORIES UT, INC.,
`
`Defendants.
`
`Civil Action No. 14-1574-RGA
`
`TRIAL OPINION
`
`Mary W. Bourke, Dana K. Severance, Daniel M. Attaway, WOMBLE CARLYLE
`SANDRIDGE & RICE, LLP, Wilmington, DE.
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 2 of 43 PageID #: 15554
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`Attorneys for Plaintiffs.
`
`Daniel A. Ladow, James M. Bollinger, Timothy P. Heaton, J. Magnus Essunger, TROUTMAN
`SANDERS LLP, New York, NY; Charanjit Brahma, TROUTMAN SANDERS LLP, San
`Francisco, CA; Robert E. Browne, Jr., TROUTMAN SANDERS LLP, Chicago, IL; Puja Patel
`Lea, TROUTMAN SANDERS LLP, Atlanta, GA; Jeffrey B. Elikan, Jeffrey Lerner, Erica N.
`Andersen, Ashley M. Kwon, COVINGTON & BURLING LLP, Washington, DC
`
`Attorneys for Plaintiffs Reckitt Benckiser Pharmaceuticals Inc. and RB Pharmaceuticals
`Limited
`
`James F. Hibey, Timothy C. Bickham, STEPTOE & JOHNSON LLP, Washington, DC; David
`L. Hecht, Cassandra A. Adams, STEPTOE & JOHNSON LLP, New York, NY
`
`Attorneys for Plaintiff Mono Sol Rx, LLC
`
`Richard D. Kirk, Stephen B. Brauerman, Sara E. Bussiere, BAYARD, P.A., Wilmington, DE;
`Elaine H. Blais, Robert Frederickson, III, Molly R. Grammel, Alexandra Lu, Kathryn, Kosinski,
`GOODWIN PROCTER LLP, Boston, MA; Ira J. Levy, Robert V. Cerwinsky, GOODWIN
`PROCTER LLP, New York, NY; John Coy Stull, GOODWIN PROCTOR LLP, Washington,
`DC
`
`Attorneys for Defendants Dr. Reddy's Laboratories S.A. and Dr. Reddy's Laboratories,
`Inc.
`
`Steven J. Fineman, Katharine L. Mowery, RICHARDS, LAYTON & FINGER, P.A.,
`Wilmington, DE; Daniel G. Brown, LA THAM & WATKINS LLP, New York, NY; Jennifer
`Koh, B. Thomas Watson, LATHAM & WATKINS LLP, San Diego, CA; Emily C. Melvin,
`Brenda L. Danek, LA THAM & WATKINS LLP, Chicago, IL; Terry Kearney, Michelle
`Woodhouse, Jie Wang, LATHAM & WATKINS LLP, Menlo Park, CA; B. Thomas Watson,
`LATHAM & WATKINS LLP, San Diego, CA.
`
`Attorneys for Defendants Par Pharmaceutical, Inc. and IntelGenx Technologies Corp.
`
`John C. Phillips, Jr., Megan C. Haney, PHILLIPS, GOLDMAN & SPENCE, P.A., Wilmington,
`DE; George C. Lombardi, Michael K. Nutter, WINSTON & STRAWN LLP, Chicago, IL;
`Stephen Smerek, David P. Dalke, Jason C. Hamilton, WINSTON & STRAWN LLP, Los
`Angeles, CA.
`
`Attorneys for Defendants Watson Laboratories, Inc. and Actavis Laboratories UT, Inc.
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`August J f, 2017
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 3 of 43 PageID #: 15555
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`Plaintiffs Reckitt Benckiser Pharmaceuticals, Inc., 1 RB Pharmaceuticals Limited,2 and
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`MonoSol Rx, LLC (collectively, "Plaintiffs") bring this suit against Defendants Dr. Reddy's
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`Laboratories S.A. and Dr. Reddy's Laboratories, Inc. (collectively, "DRL"),3 Defendant Watson
`
`Laboratories, Inc.4 ("Watson"), and Defendants Par Pharmaceutical, Inc. and IntelGenx
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`Technologies Corporation (collectively, "Par"). This opinion addresses allegations of
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`infringement and invalidity with respect to U.S. Patent Nos. 8,603,514 ('"the '514 patent") and
`
`8,900,497 ("the '497 patent").
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`The Court held a four-day bench trial relating to these patents. (D.I. 299; D.I. 300; D.I.
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`301; D.I. 302). 5 The parties filed proposed findings of fact (D.I. 275), post-trial briefing with
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`respect to infringement (D.I. 279; D.I. 285; C.A. No. 14-1574, D.I. 184; C.A. No. 14-1573, D.I.
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`203; D.I. 295), and post-trial briefing with respect to invalidity (D.I. 278; D.I. 288; D.I. 293). I
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`have also considered letters submitted regarding Medicines Co. v. Mylan, Inc., 853 F.3d 1296
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`(Fed. Cir. 2017). (D.I. 309; D.I. 310). Having considered the documentary evidence and
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`testimony, I make the following findings of fact and conclusions of law pursuant to Federal Rule
`
`of Civil Procedure 52(a).
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`1 Citations to "D.I.
`"are to the docket in C.A. No. 14-1451 unless otherwise noted. Plaintiff Reckitt Benckiser
`Pharmaceuticals, Inc. is now known as Indivior Inc. (D.I. 228-2, Admitted Fact No. 2).
`2 Plaintiff Reckitt Benckiser Pharmaceuticals Limited is now known as lndivior UK Limited. (D.1. 228-2, Admitted
`Fact No. 4).
`3 DRL was substituted as a party in place of Teva Pharmaceuticals USA, Inc. following Teva's transfer of ownership
`of ANDA Nos. 205299 and 205806 to DRL. (D.1. 228-2, Admitted Fact No. 12 at n.2).
`4 Defendant Watson Laboratories, Inc. is now known as Actavis Laboratories UT, Inc. (D.I. 228-2, Admitted Fact
`No. 6).
`5 Although the official transcript is filed in four parts (D.I. 299; D.I. 300; D.I. 301; D.I. 302), citations to the
`transcript herein are generally cited as "Tr."
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 4 of 43 PageID #: 15556
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`I.
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`BACKGROUND
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`Plaintiff Reckitt Benckiser Pharmaceuticals, Inc. is the holder of approved New Drug
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`Application No. 22-410 for Suboxone® sublingual film, which is indicated for maintenance
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`treatment of opioid dependence. (D.I. 228-2, Admitted Fact Nos. 13-14, 20). The active
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`ingredients of Suboxone® sublingual film are buprenorphine hydrochloride and naloxone
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`hydrochloride. (D.I. 228-2, Admitted Fact No. 15). Suboxone® sublingual film is available in
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`four dosage strengths (buprenorphine hydrochloride/naloxone hydrochloride): 2 mg/0.5 mg, 4
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`mg/1 mg, 8 mg/2 mg, and 12 mg/3 mg. (D.I. 228-2, Admitted Fact Nos. 16-18). Since the
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`approval ofNDA No. 22-410, Suboxone® sublingual film has been exclusively manufactured in
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`the United States by Plaintiff MonoSol and exclusively sold in the United States by Plaintiff
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`Reckitt Benckiser Pharmaceuticals, Inc. (D.I. 228-2, Admitted Fact No. 19).
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`The '514 patent, entitled "Uniform Films for Rapid Dissolve Dosage Form Incorporating
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`Taste-Masking Compositions," issued on December 10, 2013. (D.l. 228-2, Admitted Fact No.
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`21). The '514 patent is listed in the FDA's Approved Drug Products with Therapeutic
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`Equivalences Evaluations (the "Orange Book") as covering Suboxone® sublingual film. (D.I.
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`228-2, Admitted Fact No. 23).
`
`The '497 patent, entitled "Process for Making a Film Having a Substantially Uniform
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`Distribution of Components," issued on December 2, 2014. (D.I. 228-2, Admitted Fact No. 27).
`
`PlaintiffMonoSol owns the '514 and '497 patents and Plaintiff Reckitt Benckiser
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`Pharmaceuticals, Inc. is an exclusive licensee of the '514 and '497 patents. (D.I. 228-2,
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`Admitted Fact Nos. 22, 28).
`
`Plaintiffs are asserting claims 62-65, 69, 71, and 73 of the '514 patent against DRL.
`
`(D.I. 228-2, Admitted Fact No. 91; D.I. 279 at 1 n.l). Claim 62 of the '514 patent is an
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 5 of 43 PageID #: 15557
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`independent claim. Claims 63, 64, 65, 69, 71, and 73 all depend from claim 62. (D.I. 228-2,
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`Admitted Fact No. 92). The '514 patent was separately tried against Watson and Par. (C.A. No.
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`13-1674, D.I. 446).
`
`The asserted independent claim of the '514 patent reads as follows.
`
`62. A drug delivery composition comprising:
`
`(i) a cast film comprising a flowable water-soluble or water swellable film(cid:173)
`forming matrix comprising one or more substantially water soluble or water
`swellable polymers; and a desired amount of at least one active;
`
`wherein said matrix has a viscosity sufficient to aid in substantially maintaining
`non-self-aggregating uniformity of the active in the matrix;
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`(ii) a particulate active substantially uniformly stationed in the matrix; and
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`(iii) a taste-masking agent selected from the group consisting of flavors,
`sweeteners, flavor enhancers, and combinations thereof to provide taste-masking
`of the active;
`
`wherein the particulate active has a particle size of 200 microns or less and said
`flowable water-soluble or water swellable film-forming matrix is capable of being
`dried without loss of substantial uniformity in the stationing of said particulate
`active therein; and
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`wherein the uniformity subsequent to casting and drying of the matrix is measured
`by substantially equally sized individual unit doses which do not vary by more
`than 10% of said desired amount of said at least one active.
`
`(JTX-2, claim 62) (emphases added).
`
`Plaintiffs are asserting claim 24 of the '497 patent against all Defendants. (D.1. 228-2,
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`Admitted Fact Nos. 30, 64, 95). Claim 24 of the '497 patent depends from claim 1. (D.I. 228-2,
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`Admitted Fact No. 96). Claims 1 and 24 of the '497 patent reads as follows.
`
`I. A process for making a film having a substantially uniform distribution of
`components, comprising the steps of:
`
`(a) forming a flowable polymer matrix comprising an edible polymer, a solvent
`and a desired amount of at least one active, said matrix having a substantially
`uniform distribution of said at least one active;
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`(b) casting said flowable polymer matrix;
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`( c) rapidly evaporating at least a portion of said solvent upon initiation of drying
`to form a visco-elastic film within about the first 4.0 minutes to maintain said
`substantially uniform distribution of said at least one active by locking-in or
`substantially preventing migration of said at least one active within said visco(cid:173)
`elastic film;
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`( d) further drying said visco-elastic film to form a self-supporting edible film
`having a substantially uniform distribution of said at least one active component;
`and wherein said substantially uniform distribution of said at least one active
`component is measured by substantially equally sized individual unit doses which
`do not vary by more than 10% of said desired amount of said at least one active.
`
`(JTX-3, claim 1) (emphases added).
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`24. The process of claim 1, wherein said active is in the form of a particle.
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`(JTX-3, claim 24).
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`II.
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`LEGAL ST AND ARDS
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`A.
`
`Infringement
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`A patent is infringed when a person "without authority makes, uses, offers to sell, or sells
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`any patented invention, within the United States ... during the term of the patent .... " 35
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`U.S.C. § 271(a). A two-step analysis is employed in making an infringement determination. See
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`Markman v. Westview Instruments, Inc., 52 F.3d 967, 97 6 (Fed. Cir. 1995) (en bane), a.ff' d, 517
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`U.S. 370 (1996). First, the court must construe the asserted claims to ascertain their meaning and
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`scope. See id. The trier of fact must then compare the properly construed claims with the
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`accused infringing product. See id. This second step is a question of fact. Bai v. L & L Wings,
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`Inc., 160 F.3d 1350, 1353 (Fed. Cir. 1998).
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`"Literal infringement of a claim exists when every limitation recited in the claim is found
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`in the accused device." Kahn v. Gen. Motors Corp., 135 F.3d 1472, 1477 (Fed. Cir. 1998). "If
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`any claim limitation is absent from the accused device, there is no literal infringement as a matter
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`oflaw." Bayer AG v. Elan Pharm. Research Corp., 212 F.3d 1241, 1247 (Fed. Cir. 2000). If an
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`accused product does not infringe an independent claim, it also does not infringe any claim
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`depending thereon. See Wahpeton Canvas Co. v. Frontier, Inc., 870 F.2d 1546, 1553 (Fed. Cir.
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`1989). However, "[ o ]ne may infringe an independent claim and not infringe a claim dependent
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`on that claim." Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 1359 (Fed. Cir. 2007).
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`The patent owner has the burden of proving infringement by a preponderance of the evidence.
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`See SmithKline Diagnostics, Inc. v. Helena Labs. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988).
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`B.
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`Obviousness
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`The presumption that all patents are valid is the starting point for any obviousness
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`determination. 35 U.S.C. § 282. A patent claim is invalid as obvious under 35 U.S.C. § 103 "if
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`the differences between the claimed invention and the prior art are such that the claimed
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`invention as a whole would have been obvious before the effective filing date of the claimed
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`invention to a person having ordinary skill in the art to which the claimed invention pertains."
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`Id. § 103(a); see also KSR lnt'l Co. v. Teleflex Inc., 550 U.S. 398, 406-07 (2007). Obviousness
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`is a question oflaw that depends on the following factual inquiries: (1) the scope and content of
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`the prior art; (2) the differences between the claims and the prior art; (3) the level of ordinary
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`skill in the relevant art; and (4) any objective indicia of nonobviousness. See KSR, 550 U.S. at
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`406; see also Transocean Offehore Deepwater Drilling, Inc. v. Maersk Drilling USA, Inc., 699
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`F.3d 1340, 1347 (Fed. Cir. 2012). A court is required to consider secondary considerations, or
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`objective indicia of nonobviousness, before reaching an obviousness determination, as a "check
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`against hindsight bias." See In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
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`Patent Litig., 676 F.3d 1063, 1078-79 (Fed. Cir. 2012). Relevant secondary considerations
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`include commercial success, long felt but unsolved needs, failure of others, praise, unexpected
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 8 of 43 PageID #: 15560
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`results, and copying, among others. Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17-
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`18 (1966); Ruiz v. A.B. Chance Co., 234 F.3d 654, 662-63 (Fed. Cir. 2000); Tex. Instruments,
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`Inc. v. U.S. lnt'l Trade Comm 'n, 988 F.2d 1165, 1178 (Fed. Cir. 1993).
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`"Generally, a party seeking to invalidate a patent as obvious must demonstrate ... that a
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`skilled artisan would have had reason to combine the teaching of the prior art references to
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`achieve the claimed invention, and that the skilled artisan would have had a reasonable
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`expectation of success from doing so." In re Cyclobenzaprine Hydrochloride, 676 F .3d at 1068-
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`69. "The Supreme Court has warned, however, that, while an analysis of any teaching,
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`suggestion, or motivation to combine known elements is useful to an obviousness analysis, the
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`overall obviousness inquiry must be expansive and flexible." Id. at 1069. The improvement
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`over prior art must be "more than the predictable use of prior art elements according to their
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`established functions." KSR, 550 U.S. at 417. Evidence of obviousness, however, especially
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`when that evidence is proffered in support of an "obvious-to-try" theory, is insufficient unless it
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`indicates that the possible options skilled artisans would have encountered were "finite," "small,"
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`or "easily traversed," and "that skilled artisans would have had a reason to select the route that
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`produced the claimed invention." In re Cyclobenzaprine Hydrochloride, 676 F.3d at 1072.
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`Obviousness must be proven by clear and convincing evidence. Id. at 1078.
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`III. DISCUSSION
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`A.
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`Infringement
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`1.
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`DRL
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`a)
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`Findings of Fact
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`1. DRL uses the CL02 and CL03 dryers where the sole source of heat is hot air coming
`from air nozzles over the liner.
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`2. DRL's proposed ANDA manufacturing process (hereinafter, "ANDA process") is
`extensively controlled to achieve drug content uniformity.
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`3. DRL's ANDA process is designed to avoid the "rippling effect."
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`4. The extent of bottom drying employed by DRL is conventional.
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`5. General testimony that DRL's method is unconventional is conclusory and not credible.
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`6. There is insufficient evidence for me to conclude that DRL's ANDA process utilizes
`unconventional drying.
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`7. DRL does not infringe the "drying" limitation of the '497 patent or the "dried" limitation
`of the '514 patent.
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`8. About four minutes after "drying," the majority of the wet matrix is still water.
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`9. Dr. Prud'homme's testimony that a visco-elastic solid results after about four minutes of
`drying is given little to no weight.
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`10. DRL does not infringe the visco-elastic solid film limitation of the '497 patent.
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`11. DRL's ANDAs report drug content uniformity measurements across the 12 mg/3 mg, 8
`mg/2 mg, 4 mg/1 mg, and 2 mg/0.5 mg dosage strengths.
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`12. The '514 and the '497 patents do not require that Plaintiffs use the "three sigma rule"
`standard to establish infringement.
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`13. Plaintiffs establish that DRL infringes the drug content uniformity limitation of the
`asserted claims of both patents.
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`14. DRL's polymer matrix is specified to range between 5,000 to 20,000 centipoise for the 12
`mg/3 mg, 8 mg/2 mg, 4 mg/1 mg, and 2 mg/0.5 mg dosage strengths.
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`15. Dr. Davies offers credible testimony as to whether DRL's ANDA process is "sufficient to
`provide little to no aggregation of the active within the film."
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`16. Plaintiffs establish that DRL infringes the viscosity limitation of the asserted claims of
`the '514 patent
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`17. DRL does not infringe any asserted claim of the '497 and '514 patents.
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`b)
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`Conclusions of Law
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`(1)
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`Dried/Drying
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`DRL argues that it does not infringe the "dried" limitation of the asserted claims of the
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`'514 patent or the "drying" limitation of the asserted claim of the '497 patent. I construed
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`"dried" in the '514 patent to mean "dried without solely employing conventional convection air
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`drying from the top." (C.A. No. 15-1016, D.I. 87 at 5). I further clarified this construction as
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`follows:
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`"[D]ried without solely employing conventional convection air drying from the top" is
`meant to exclude drying techniques that are associated with the problem of the "rippling
`effect." This problem takes place when the initial drying of the upper surface of the film
`leads to the trapping of moisture inside the film, causing the top surface to be ripped open
`and reformed when the moisture trapped inside later evaporates. This does not
`necessarily exclude techniques where the only direct sources of air are from the top. This
`also should not be understood to require techniques to use direct sources of air from the
`bottom.
`
`(Id. at 5-6). "Drying" in the '497 patent is construed similarly. (Id. at 8-9). DRL argues that
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`their ANDA process is "conventional" because (1) the drying method used by DRL was ordinary
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`and commonplace in the web coating industry as of 2001, (2) DRL's ANDA products are dried
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`solely using top air, and (3) no bottom air or heat is used during the drying ofDRL's products.
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`In conventional coating and drying equipment, a POSA could control the temperature,
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`line speed, air velocity, and the direction of air nozzles. (See, e.g., Tr. 785:6-10, 784:17-24,
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`785:1-5, 799:18-21). It would be conventional to adjust these settings in order to produce a
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`desired product. (Tr. 1066: 19-22, 784: 17-785: 10). Dr. Gogolin opines that it was conventional
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`for an operator in 2001 to control a top air impingement dryer to prevent defects like rippling.
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`(Tr. 1344:1-14). I agree with Plaintiffs that merely employing a conventional oven does not
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`necessarily mean that a drying technique is conventional.
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`DRL uses the CL02 and CL03 dryers where the sole source of heat is hot air coming
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`from air nozzles over the liner. (Tr. 1353:20-1354:2, 1360:16-1361 :4). In both the CL02 and
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`CL03, there are no air nozzles below the liner. (D.I. 228-2, Admitted Fact No. 121). DRL's
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`ANDA process is extensively controlled. (See, e.g., Tr. 577:7-14). DRL's ANDAs state, "The
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`most critical aspect during coating and drying for this product is to achieve content uniformity in
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`the master roll." (JTX-59 at 32). To meet that objective, DRL's ANDA process regularly
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`monitors the oven temperature, fan speeds, supply dampers, and exhaust dampers in each zone.
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`(JTX-59 at 32).
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`Plaintiffs' evidence shows that DRL's ANDA process is designed to avoid the "rippling
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`effect." To avoid rippling, DRL's drying parameters are such that lower temperatures and air
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`velocities are employed at the beginning and higher temperatures and air velocities are used
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`toward the end of the drying process. (Tr. 982:1-983:3). DRL's ANDAs suggest that their films
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`did not have visual defects. (JTX-12 at 11). DRL's technique employs low airflow at the
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`surface of the web during the initial drying phase, such that the amount of heat transfer from the
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`bottom web approaches the amount of heat transfer from the top. 6 (Tr. 830:12-831:4). This is
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`consistent with a technique that is associated with minimizing the rippling effect. This is not
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`dispositive because my construction left open the possibility as to whether conventional
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`convection air drying techniques could also avoid the "rippling effect." Whether a technique
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`causes rippling is only a factor as to whether a technique constitutes conventional convection air
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`drying.
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`Plaintiffs argue that DRL's ANDA process is unconventional because it employs bottom
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`drying. I am not persuaded that the extent ofDRL's bottom drying is unconventional. No
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`6 In this opinion, "web" is synonymous with "liner."
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`measurements were taken of the temperature of the metal rollers. (Tr. 558:19-559:19). The
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`CL02 and CL03 dryers use a conventional exhaust system, which suggests that any bottom
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`drying is at most a conventional amount. (D.I. 228-2, Admitted Fact Nos. 122-124; Tr.
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`1410:18-1411 :2, 1352:2-19, 1356:8-21, 1358:9-1359:12, 1353:3-1354:13, 1360:3-15). I think
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`that DRL's use of "bottom drying" is essentially that the inside of the oven simply gets hot and
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`as a result, the bottom of film is incidentally heated. This is a conventional bottom drying
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`method. (See, e.g., JTX-24 at 4:37-42, Fig. 2; Tr. 1367:19-1368:19).
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`Taken as a whole, this evidence is not enough to persuade me that DRL's process is
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`unconventional. I am not persuaded that evidence of a controlled process that does not result in
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`rippling and that achieves drug content uniformity automatically amounts to an unconventional
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`process. Watson raises two good points that apply here. Watson argues that finding
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`unconventionality based on this kind of evidence would be using a "results-determinative"
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`approach. I agree. Finding infringement based on this evidence would put too much focus on
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`whether drug content uniformity is achieved, and would gloss over whether the parameters
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`employed are actually unconventional. This is similar to the "efficient mixing" issue that the
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`Federal Circuit addressed in Medicines Co. v. Mylan, Inc., 853 F.3d 1296 (Fed. Cir. 2017).
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`There, the court resisted the patentee's construction of "efficient mixing" which sought "to claim
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`all solutions to the identified 'impurities' problem, without describing the entire range of
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`solutions to that problem."' Medicines Co., 853 F.3d at 1307 (citingAriad Pharms., Inc. v. Eli
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`Lilly & Co., 598 F.3d 1336, 1352-53 (Fed. Cir. 2010)). Ifl were to find infringement, I would
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`effectively be construing the drying limitation to claim all drying techniques that solve the drug
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`content uniformity problem. This is not what the patents claim, however.
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 13 of 43 PageID #: 15565
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`Watson also argues that finding unconventionality based on this kind of evidence would
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`read out the uniformity limitation. I agree. If showing drug content uniformity was effectively
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`all that was required to meet the drying limitation, there would be no need for a separate
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`uniformity limitation. See Bicon, Inc. v. Straumann Co., 441 F.3d 945, 950 (Fed. Cir. 2006)
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`("[C]laims are interpreted with an eye toward giving effect to all terms in the claim."). Thus, on
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`these facts, Plaintiffs have not met their burden of showing that the "dried"/"drying" limitations
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`of the '497 and '514 patents are met. 7
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`(2)
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`Visco-Elastic
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`DRL argues that its drying process does not meet the visco-elastic solid film limitation of
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`the '497 patent. Claim 1 of the '497 patent requires "rapidly evaporating at least a portion of
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`said solvent upon initiation of drying to form a visco-elastic film within about the first 4.0
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`minutes to maintain said substantially uniform distribution of said at least one active by locking-
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`in or substantially preventing migration of said at least one active within said visco-elastic
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`film .... " (JTX-3, claim 1). I construed the phrase "to maintain said substantially uniform
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`distribution of said [pharmaceutical/at least one active] by locking-in or substantially preventing
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`migration of said [pharmaceutical/at least one active]" to mean "to maintain a distribution of [an
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`active/a pharmaceutical active] by drying to form a viscoelastic solid film, thereby limiting its
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`migration such that the individual dosage units do not vary by more than 10% from the intended
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`amount of the active for that dosage unit." (D.1. 175 at 8-9).
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`DRL's proposed product would lose about 20% of volatile solvent (water and alcohol) in
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`about four minutes. (Tr. 693:4-11). As a result, the majority of the wet matrix is still water.
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`7 DRL further argues that Dr. Davies is not qualified to offer an opinion concerning the phrase "conventional
`convection air drying from the top" in the context of the '514 patent. Having already found in DRL's favor, I do not
`reach this issue.
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 14 of 43 PageID #: 15566
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`(Tr. 1218:2-16). Rheological testing shows that the DRL's formulation is at best a visco-elastic
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`liquid after four minutes of drying. (Tr. 1224:3-22, 1227:17-1235:23, 773:14-774:1; JTX-488).
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`Plaintiffs' criticisms of this rheological testing make some points but are not persuasive.
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`Plaintiffs complain that the tested sample did not include buprenorphine, but it is unclear that the
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`inclusion of buprenorphine would be enough to change the results, that is, to render the sample a
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`visco-elastic solid. (Tr. 1232:18-1233:3). Plaintiffs complain that the wet mixture of material
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`was left out in open air to allow evaporation of solvent. This complaint neglects that after the
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`dehydrated sample was placed in a petri dish on a balance to monitor weight loss until it reached
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`the target 16% volatile weight loss, the sample was then transferred to a new vial, capped, and
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`sealed to prevent further loss. (Tr. 1199:4-21). Dr. Prud'homme concedes that the
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`measurements were well done on the solutions DRL used. (Tr. 772: 17-773 :7). Dr. Prud'homme
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`concedes that he had no criticisms of the methodology of the experiment for the ends that were
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`measured. (Tr. 773:3-7). I think the test was somewhat representative. Testing can be
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`probative without exactly duplicating the process being examined. Thus, I attribute some weight
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`to the rheological tests.
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`Plaintiffs argue that Dr. Prud'homme's testimony demonstrates that a visco-elastic solid
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`results because the solvent loss leads to a resulting increase in buprenorphine particle
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`concentration, which causes a particle network to form. Specifically, Plaintiffs argue that the
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`citric acid in DRL's casting dispersion interacts with PEO, causing the buprenorphine particles to
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`stick to each other to form large open aggregates of particles through micro-scale chaining and
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`aggregation. They argue that this finds support from Dr. Prud'homme's research conducted in
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`2010 regarding citric acid-PEO facilitated network formulation and literature showing micro(cid:173)
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`scale aggregation when particles are flowed in a visco-elastic fluid.
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 15 of 43 PageID #: 15567
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`I do not find this persuasive. First, Dr. Prud 'homme did not perform any actual testing to
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`see ifDRL's proposed ANDA products exhibited a yield stress before or after four minutes of
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`drying. (Tr. 781:19-782:7). Second, Dr. Prud'homme's work on the case had some sloppiness.
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`His original opinion relied on calculations performed of both "viscosity" and "yield stress." (Tr.
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`774:24-775:20). Those calculations were overstated due to mathematical errors. 8 (Tr. 776:20-
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`780: 19). Third, Dr. Prud 'homme fails to adequately explain when during the first four minutes
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`of drying and at what concentration of buprenorphine a visco-elastic solid forms. At the
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`beginning of the four minutes, the concentration of buprenorphine is 4.18%, and it is a visco-
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`elastic liquid. At the end, the concentration ofbuprenorphine is 4.87%, when he argues it is a
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`visco-elastic solid. (Tr. 762:14-22, 763.18-22, 764:14-19). His theoretical explanation does not
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`provide useful insight about when the change occurs and how one would recognize that the
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`change has occurred. In the end, what Dr. Prud'homme shows is that the concentration of
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`buprenorphine has increased, but it is not helpful in determining whether the film is then a visco-
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`elastic solid. Thus, Plaintiffs have failed to show that DRL infringes the visco-elastic solid film
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`limitation of the '497 patent.
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`(3)
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`Drug Content Uniformity
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`DRL argues that its ANDA products do not meet the drug content uniformity limitation
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`of the '514 or the '497 patent. I construed "without loss of substantial uniformity" to mean
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`"such that individual dosage units do not vary by more than 10% from the intended amount of
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`active for that dosage unit." (D.I. 175 at 23). I also construed "substantially uniformly
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`8 Dr. Prud'homme is a distinguished expert in his field. But when I have to choose which expert's testimony to
`accept, I am going to hesitate to rely on the expert whose report contained mistakes.
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 16 of 43 PageID #: 15568
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`stationed" to mean "[ s ]tationed in the matrix such that individual dosage units do not vary by
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`more than 10% from the intended amount of active for that dosage unit." (D.I. 156 at 15-16).
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`Plaintiffs successfully establish infringement of this limitation. DRL's ANDAs report
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`drug content uniformity measurements for individual dosage units. (JTX-57 at 18; JTX-274 at
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`36; Tr. 926: 16-20). The 8 mg/2 mg dose ranges from 96.9 percent to 102.2 percent
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`buprenorphine content uniformity. (Tr. 927:2-16; JTX-57 at 18). For the 12 mg/3 mg dose, it
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`ranges from 93.4 percent to 95.2 percent. (Tr. 927:24-928:11). For the 4 mg/1 mg dose, it
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`ranges from 94.8 percent to 106.2 percent. (Tr. 928:19-929:12). For naloxone, the 8 mg/2 mg
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`ranges from 97.2 percent to 101.8 percent. (Tr. 927:2-16). For the 12 mg/3 mg, it ranges from
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`95.3 percent to 96.1 percent. (Tr. 927:24-928:13). For the 4 mg/lmg dose, it ranges from 97.9
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`percent to 101.5 percent. (Tr. 928:19-929:12). As to the 2 mg/0.5 mg dose, information about
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`"acceptance values" and "assay requirements" indicate adequate content uniformity. (Tr. 932:7-
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`933:2). DRL does not substantively contest any of this.
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`DRL' s only argument is that Plaintiffs should be held to "three sigma rule" in their
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`infringement analysis and under such an approach, Plaintiffs have failed to adequate show
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`infringement. (D.I. 285 at pp. 19-20). The three sigma rule requires a showing that
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`approximately 99.8% of all samples fall within the claimed numeric ranges. (Tr. 1644:1-1645:1;
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`PTX-82 at 145). I disagree that Plaintiffs must be held to the three sigma rule in order to
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`establish infringement. There is no requirement in the claims for this to be necessary. The
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`evidence presented is sufficient to establish a case of infringement of this limitation.
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`(4)
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`Viscosity
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`DRL argues that its ANDA products do not meet the "viscosity" limitation of the '514
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`patent. I construed the phrase, "said matrix has a viscosity sufficient to aid in substantially
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`Case 1:14-cv-01451-RGA Document 312 Filed 08/31/17 Page 17 of 43 PageID