AstraZeneca Pharmaceuticals LP v. Anchen..., Not Reported in...
`2012 WL 1065458
`
`2012 WL 1065458
`Only the Westlaw citation is currently available.
`NOT FOR PUBLICATION
`United States District Court,
`D. New Jersey.
`
`ASTRAZENECA PHARMACEUTICALS LP
`and Astrazeneca UK Limited, Plaintiffs,
`v.
`ANCHEN PHARMACEUTICALS, INC.
`Osmotica Pharmaceutical Corporation,
`Torrent Pharmaceuticals Limited and
`Torrent Pharma Inc., Mylan Pharmaceuticals
`Inc. and Mylan Inc., Defendants.
`
`Civil Action Nos. 10–cv–1835 (JAP)(TJB), 10–cv–
`4203 (JAP)(TJB), 11–cv–2484 (JAP)(TJB), 10–
`cv–4205 (JAP)(TJB), 10–cv–4971 (JAP) (TJB),
`10–cv–5519 (JAP)(TJB), 11–cv–2483 (JAP)(TJB).
`|
`March 29, 2012.
`
`Attorneys and Law Firms
`
`Carissa L. Rodrigue, Elina Slavin, John Edmund Flaherty,
`Jonathan M.H. Short, Mark H. Anania, McCarter & English
`LLP, Newark, NJ, Robert John Czarnecki, Jr., Fitzpatrick
`Cella Harper & Scinto, New York, NY, for Plaintiffs.
`
`James S. Richter, Jeffrey P. Catenacci, Melissa Steedle
`Bogad, Winston & Strawn, LLP, Newark, NJ, for Defendants.
`
`OPINION
`
`PISANO, District Judge.
`
`I. INTRODUCTION
`*1 These are several Hatch–Waxman Act patent
`infringement actions brought by plaintiffs AstraZeneca
`Pharmaceuticals LP and AstraZeneca UK Limited
`against Anchen Pharmaceuticals,
`Inc.
`(“Anchen”);
`Osmotica Pharmaceutical Corporation (“Osmotica”); Torrent
`Pharmaceuticals Limited and Torrent Pharma Inc. (together,
`“Torrent”); and Mylan Pharmaceuticals Inc. (“Mylan
`Pharms”) and Mylan Inc. (together, “Mylan”). The patent-in-
`suit claims sustained release formulations of the antipsychotic
`compound quetiapine and a method for treating psychotic
`
`states by administering an effective amount of the claimed
`formulations.
`
`A 12–day bench trial was held in October 2011. Upon
`hearing the testimony on behalf of the parties and reviewing
`documentary evidence presented at trial, the Court herein sets
`forth its findings of fact and conclusions of law, and finds in
`favor of Plaintiffs.
`
`II. BACKGROUND
`
`A. Procedural Background
`Plaintiffs in all actions are AstraZeneca Pharmaceuticals
`LP (“AZLP”) and AstraZeneca UK Limited (“AZUK”)
`(collectively, “AstraZeneca” or “Plaintiffs”). Below is a
`summary of the instant civil actions: 1
`
`1
`
`Plaintiffs settled with certain defendants prior to the
`conclusion of trial. Those civil actions that were
`concluded prior to the end of trial are not listed here.
`
`Anchen
`
`•On April 10, 2010, AstraZeneca filed a complaint
`against Anchen (Civil Action No. 10–1835) alleging
`that Anchen's filing of its Abbreviated New Drug
`Application (“ANDA”) No. 90–757 infringed the ′437
`patent under 35 U.S.C. § 271(e)(2)(A).
`
`Osmotica
`
`• On August 16, 2010, AstraZeneca filed a complaint
`against Osmotica (Civil Action No. 10–4203) alleging
`that Osmotica's filing of its ANDA No. 201424 infringed
`the ′437 patent under 35 U.S.C. § 271(e)(2)(A).
`
`• On July 11, 2011, AstraZeneca filed a second
`complaint against Osmotica (Civil Action No. 11–
`2484) alleging that Osmotica's filing of its ANDA
`No. 202587 infringed the ′437 patent under 35
`U.S.C. § 271(e)(2)(A).
`
`Torrent
`
`• On August 16, 2010, AstraZeneca filed a complaint
`against Torrent (Civil Action No. 10–4205) alleging that
`Torrent's filing of its ANDA No. 201996 infringed the
`′437 patent under 35 U.S.C. § 271(e)(2)(A).
`
` © 2016 Thomson Reuters. No claim to original U.S. Government Works.
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`• On September 28, 2010, AstraZeneca filed a second
`complaint against Torrent (Civil Action No. 10–
`4971) alleging that Torrent's filing of its ANDA No.
`202000 infringed the ′437 patent under 35 U.S.C.
`§ 271(e)(2)(A).
`
`Mylan
`
`• On October 22, 2010, AstraZeneca filed a complaint
`against Mylan
`(Civil Action 10–5519) alleging
`infringement of the ′437 patent under 35 U.S.C. §
`271(e)(2)(A) based on Mylan Pharms's submission of an
`ANDA No. 202228.
`
`• On April 29, 2011, AstraZeneca filed a second
`complaint against Mylan (Civil Action No. 11–
`2483) alleging infringement of the ′437 patent
`under 35 U.S.C. § 271(e)(2)(A) based on Mylan
`Pharms's submission of an amendment to its ANDA
`No. 202228.
`Claims 1–13 of the ′437 patent are asserted against defendants
`Anchen and Mylan. Claims 1, 2, 10–13 are asserted against
`defendants Osmotica and Torrent. Anchen, Osmotica, and
`Mylan have conceded infringement but assert, along with
`Torrent, that the ′437 patent is invalid for obviousness. The
`trial of this matter proceeded in essentially two parts. The first
`part of the trial was directed to Plaintiffs' infringement claims
`against Torrent. The second part of the trial was directed to
`Defendants' defense of invalidity based upon obviousness.
`
`B. Witnesses at Trial
`*2 During the 12–day bench trial, all parties were
`provided the opportunity to present evidence. On the claim
`of infringement against Torrent, AstraZeneca called two
`witnesses, both expert witnesses: Dr. Martyn Davies (Bench
`Trial Transcript (“Tr.”) at 24–41), an expert in pharmaceutical
`delivery systems including sustained release formulations;
`and Dr. Robert Prud'homme (Tr. at 42–125), an expert in gels,
`pharmaceutical formulation and drug delivery. AstraZeneca
`also presented the video deposition testimony of William
`Blakemore, the 30(b)(6) witness for FMC Corporation, the
`manufacturer of the sustained release ingredient in Torrent's
`ANDA product.
`
`Torrent also presented testimony by video deposition of Mr.
`Blakemore.
`
`On the issue of obviousness, Defendants called two witnesses
`for their case-in-chief, Dr. Niham Park (Tr. at 375–570), an
`expert in the area of pharmaceutical formulation and drug
`delivery and, particularly, in formulating sustained release
`solid oral dosage form using hydroxypropyl methylcellulose;
`and Dr. Lee Kirsch (Tr. at 572–706), an expert in the field
`of formulation development and pharmaceutical delivery
`system including sustained release formulations.
`
`AstraZeneca responded to Defendants' obviousness case with
`the following seven witnesses, five of whom were expert
`witnesses and two of whom are fact witnesses: David
`DiCicco (Tr. at 746–787), President of Acumen Research
`and a specialist in marketing research for pharmaceuticals;
`Dr. Stuart Montgomery (Tr. at 787–898), an expert and
`practicing psychiatrist and a researcher in psychiatric
`illnesses; Dr. Philip Seeman (Tr. at 947–1044), an expert
`in neuropsychopharmacology with particular emphasis in
`antipsychotic drugs and how they affect the dopamine
`d2 receptor; Henry Grabowski (Tr. at 1045–1199), an
`expert in the economics of pharmaceutical industry; Dr.
`Joseph Calabrese (Tr. at 1201–1390), an expert in the
`clinical development of treatment options for psychotic
`diseases and in the use of quetiapine containing drug
`products in the treatment of those diseases; Dr. Prud'homme
`(Tr. at 1391–1500); and Sandford Sommer (Tr. at 1537–
`1610), Executive Director of Commercial Operations for
`AstraZeneca's Seroquel IR and XR business.
`
`In rebuttal, Defendants called three expert witnesses:
`Dr. Robert Mark Hamer (Tr. at 1614–1666), an expert
`in biostatistics, clinical trial methodology and research
`methodology; Dr. Christopher Reist (Tr. at 1697–1819), an
`expert in the area of the treatment of psychiatric patients,
`including patients that need antipsychotic medication; and
`Harry Boghigian (Tr. at 1848–1952), an expert in the areas of
`commercialization, 2 marketing and lifecycle management of
`pharmaceutical drug products.
`
`2
`
`In this context, “commercialization” is limited to
`marketing and sales.
`
`In response, Torrent proffered two fact witnesses on the
`issue of infringement: Kamesh Venugopal (Tr. at 176–198),
`president of Torrent's U.S. subsidiary, and Rajiv Shah (Tr.
`at 199–275), director of the patent department at Torrent.
`
`*3 The testimony of a number of witnesses was also
`submitted by both Plaintiffs and Defendants on the question
`of obviousness through deposition testimony. Defendants
`submitted deposition testimony of the following witnesses:
`
` © 2016 Thomson Reuters. No claim to original U.S. Government Works.
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`Dr. William Addicks, a former AstraZeneca employee, is one
`of the inventors of the ′437 patent. Dr. Addicks testified about
`AstraZeneca's development of a sustained release quetiapine
`formulation.
`
`Dr. Glenn Meyer is the Chief Scientific Officer of Osmotica.
`Dr. Meyer testified about Osmotica's work in developing a
`sustained release form of quetiapine.
`
`Mr. Daragh Bradley was an employee of Biovail
`Technologies (Ireland) Ltd., an affiliate of former defendants
`Biovail Laboratories International SRL, Biovail Corporation,
`and BTA Pharmaceuticals, Inc. (“Biovail”). 3 Mr. Bradley
`worked on Biovail's quetiapine fumarate sustained release
`formulation project. Mr. Bradley testified that quetiapine
`has pH-dependent solubility, and that this characteristic is
`a complicating factor in formulating a drug for sustained
`release.
`
`Dr. Jamie Mullen, a psychiatrist, is an AstraZeneca employee.
`Dr. Mullen testified about AstraZeneca's clinical trials
`relating to its sustained release quetiapine formulations.
`
`3
`
`Biovail is a defendant in a related civil action brought by
`AstraZeneca that was dismissed prior to the conclusion
`of trial.
`
`Dr. Svante Nyberg, a psychiatrist and AstraZeneca employee,
`has conducted extensive research on the effect of Seroquel IR
`and Seroquel XR at various receptors in the brain. Defendants
`rely on Dr. Nyberg's testimony about dosing regimens.
`
`Mr. James Dunne was also an employee of Biovail. He
`worked on Biovail's quetiapine fumarate sustained release
`formulation project and testified that “dose dumping” is a
`concern when formulating a sustained release dosage form.
`
`Dr. Bhavnish Parikh, a former AstraZeneca employee, is
`one of the inventors of the ′437 patent. Dr. Parikh testified
`about work at AstraZeneca on sustained release quetiapine
`formulations.
`
`Dr. Steven Potkin is a physician who participated in clinical
`trials of Seroquel IR and Seroquel XR.
`
`Dr. Robert Sepelyak is an AstraZeneca employee who
`testified as a Rule 30(b)(6) witness about AstraZeneca's
`research work on sustained release quetiapine formulations.
`
`Dr. Robert Timko, an AstraZeneca employee, is one of
`the inventors of the ′ 437 patent. Dr. Timko testified
`regarding AstraZeneca's work on sustained release quetiapine
`formulations.
`
`Dr. Martin Deberardinis is an AstraZeneca employee who
`testified about AstraZeneca's work on sustained release
`quetiapine.
`
`Mr. Marcelo Ricci is Vice President of Product Development
`of Osmotica Pharmaceutical Argentina. Mr. Ricci testified
`about Osmotica's work on sustained release quetiapine
`formulations.
`
`Plaintiffs presented deposition testimony of the following
`witnesses:
`
`Mr. Graham Jackson is an employee of Biovail. Mr. Jackson
`testified as a 30(b)(6) witness on behalf of Biovail and was
`the lead formulator in Biovail's quetiapine fumarate sustained
`release formulation project. Mr. Jackson testified regarding
`the challenge of formulating a sustained release drug with pH-
`dependent solubility.
`
`*4 Dr. Jonathan Embleton is an employee of Catalent
`Pharma Solutions LLC (“Catalent”), a collaborator of
`Handa Pharmaceuticals, LLC (“Handa”) 4 in developing its
`proposed sustained release quetiapine products. Dr. Embleton
`was designated by Catalent, and testified under Rule 30(b)(6),
`regarding the advantages to patients of Seroquel XR over the
`immediate release version.
`
`4
`
`Handa is a defendant in a related civil action brought by
`AstraZeneca that was dismissed prior to the conclusion
`of trial.
`
`Dr. Fang–Yi Liu testified as a 30(b)(6) witness on behalf of
`Handa, where he is president and CEO. Dr. Liu testified that
`formulation science is unpredictable, and he explained the
`need to perform experimentation before assessing whether
`something will work.
`
`Mr. Howard Martin testified as a 30(b)(6) witness on behalf
`of Mylan regarding the expected market performance of
`Seroquel XR and Mylan's proposed generic version. Mr.
`Martin testified that Mylan forecasted significant growth in
`the market for Seroquel XR.
`
` © 2016 Thomson Reuters. No claim to original U.S. Government Works.
`
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`Dr. Svante Nyberg, a psychiatrist and AstraZeneca employee,
`is discussed above.
`
`With respect to the witnesses testifying live at trial, having
`had had the opportunity to observe their demeanor and
`hear their testimony, the Court has made certain credibility
`determinations as well as determinations relating to the
`appropriate weight to accord various testimony. Such
`determinations are set forth infra where relevant.
`
`III. FINDINGS OF FACT AND CONCLUSIONS OF
`LAW
`
`A. Nature of Case 5
`5
`These facts recited in this section have been stipulated by
`the parties in the Stipulated Facts (“Stip.”) filed at Docket
`Entry No. 156 unless otherwise indicated by citation to
`a different source.
`
`The present actions are for patent infringement under 35
`U.S.C. § 271(e)(2)(A) and the Hatch–Waxman Act, codified
`in part at 21 U.S.C. § 355(j). AstraZeneca Pharmaceuticals
`LP sells quetiapine fumarate sustained-release tablets as
`described in New Drug Application (“NDA”) 22–047 under
`the trade name Seroquel XR. The U.S. Food and Drug
`Administration's publication, Approved Drug Products with
`Therapeutic Equivalence Evaluations (known as the “Orange
`Book”), identifies U.S. Patent No. 5,948,437 (the “#437
`patent”), which is entitled “Pharmaceutical Compositions
`Using Thiazepine”, in connection with NDA 22–047.
`
`The United States Patent Office (“USPTO”) issued the ′437
`patent on September 7, 1999. According to the Orange Book,
`the expiration date of the ′ 437 patent is May 28, 2017.
`The ′437 patent claims sustained release formulations of the
`antipsychotic compound quetiapine and a method for treating
`psychotic states or hyperactivity by administering an effective
`amount of the claimed formulations. The patent contains 15
`claims, and claims 1 through 13 are asserted in this action.
`
`AZLP is the holder of NDA No. 22–047, by which the FDA
`first granted approval for sustained release tablets containing
`the active ingredient 11–[4–[2–(2–hydroxyethoxy)ethyl]–1–
`piperazinyl] dibenzo [b, f] [1, 4] thiazepine (known as
`“quetiapine”) in the form of its pharmaceutically acceptable
`hemifumarate salt (“quetiapine fumarate”). AZUK is the
`owner by assignment of the ′437 patent.
`
`The FDA approved sustained release quetiapine fumarate
`tablets for the treatment of schizophrenia in May 2007.
`AstraZeneca began selling those tablets under the name
`Seroquel XR in or about August 2007. AstraZeneca sells its
`Seroquel XR extended release quetiapine fumarate product
`in five dosage strengths: 50 mg, 150 mg, 200 mg, 300
`mg and 400 mg. Each dosage strength is sold in the form
`of a tablet, which is a solid oral dosage form.Seroquel
`XR has been approved by the FDA for the treatment of
`a number of conditions, specifically, schizophrenia; the
`acute treatment of manic or mixed episodes associated
`with bipolar I disorder, both as monotherapy and as an
`adjunct to lithium or divalproex; the acute treatment of
`depressive episodes associated with bipolar disorder; the
`maintenance treatment of bipolar I disorder as an adjunct
`to lithium or divalproex; and the adjunctive treatment of
`major depressive disorder (“MDD”).Quetiapine fumarate is
`the active pharmaceutical ingredient (“API”), in Seroquel
`XR. Seroquel XR is formulated to be administered once-a-
`day.
`
`*5 Defendants Anchen, Torrent, Osmotica and Mylan
`each filed an ANDA with the FDA seeking approval
`to commercially sell quetiapine fumarate extended release
`tablets prior to the expiration of the ′437 patent. Each
`ANDA included a certification with respect to the ′437 patent
`pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV) (known as a
`“Paragraph IV Certification”) that, in the opinion of the
`defendant, the ′437 patent will not be infringed by the product
`that is the subject of the ANDA or is invalid.
`
`B. The #437 Patent 6
`6
`These facts recited in this section have been stipulated
`by the parties in the Stipulated Facts filed at Docket
`Entry No. 156 unless otherwise indicated by citation to
`a different source.
`The ′437 patent issued from an application (No. 08/864,306)
`filed with the USPTO on May 28, 1997, naming as inventors
`Bhavnish Vinod Parikh, Robert Joseph Timko and William
`Joseph Addicks (“the ′437 patent application”). The ′ 437
`patent application as filed in the USPTO contained 15 claims.
`Those claims issued unchanged as claims 1–15 of the ′437
`patent.
`
`Claim 1 of the ′437 patent reads as follows: “A sustained
`release formulation comprising a gelling agent and 11–[4–[2–
`(2–hydroxyethoxy)ethyl]–1–piperazinyl]dibenzo–[b, f] [1, 4]
`thiazepine or a pharmaceutically acceptable salt thereof,
`
` © 2016 Thomson Reuters. No claim to original U.S. Government Works.
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`together with one or more pharmaceutically acceptable
`excipients.”
`
`The term “a sustained release formulation” in claim 1 has
`been construed by the Court to mean “[a] solid oral dosage
`form that releases its active pharmaceutical ingredient over
`an extended period of time.”The term “gelling agent” in
`claim 1 has been construed by the Court to mean “any
`substance which forms a gel when in contact with water.”The
`parties agree that the term “excipient” in claim 1 means “any
`substance other than an active pharmaceutical ingredient.”
`
`Claim 2 of the ′437 patent reads as follows: “A sustained
`release formulation according to claim 1 wherein the gelling
`agent is hydroxypropyl methylcellulose.”Hydroxypropyl
`methylcellulose is commonly referred to as “HPMC.” As
`noted in the patent, HPMC is commercially available under
`several trademarks, e.g. Methocel E, F, J, and K from the Dow
`Chemical Company, U.S.A. and Metalose SH from Shin–
`Etsu, Ltd. Japan. JTX–1, col. 3, lines 3–5.
`
`Claim 3 of the ′437 patent reads as follows:
`
`formulation
`release
`sustained
`A
`according
`to claim 2 comprising
`about 5
`to 50% by weight
`of a hydroxypropyl methylcellulose
`selected from the group consisting of
`(a) a hydroxypropyl methylcellulose
`having a viscosity of about 40 to 60
`cps, a methoxy content of about 28 to
`30% by weight and a hydroxypropoxy
`content of from about 7 to less than
`9% by weight, (b) a hydroxypropyl
`methylcellulose having a viscosity
`of about 3,500
`to 5,600 cps, a
`methoxy content of about 28 to 30%
`by weight and a hydroxypropoxy
`content of about 7 to 12% by weight,
`(c) a hydroxypropyl methylcellulose
`having a viscosity of about 80 to 120
`cps, a methoxy content of about 19 to
`24% by weight and a hydroxypropoxy
`content of from about 7 to less than
`9% by weight and (d) a hydroxypropyl
`methylcellulose having a viscosity
`of about 3,500 to 5, 600 cps, a
`methoxy content of about 19 to 24%
`by weight and a hydroxypropoxy
`content of about 7
`to 12% by
`
`weight, or mixtures thereof; with the
`proviso that if the formulation contains
`a
`hydroxypropyl methylcellulose
`described under
`(d) above
`the
`total
`amount of hydroxypropyl
`methylcellulose
`present
`in
`the
`formulation must be greater than
`25.8% by weight.
`
`*6 Claim 4 of the ′437 patent reads as follows: “A sustained
`release formulation according to claim 3 comprising about
`5 to 40% by weight of a hydroxypropyl methylcellulose
`selected from the group consisting of (a)-(d) or mixtures
`thereof.”
`
`Claim 5 of the ′437 patent reads as follows: “A sustained
`release formulation according to claim 4 comprising about
`8 to 35% by weight of a hydroxypropyl methylcellulose
`selected from the group consisting of (a)-(d) or mixtures
`thereof.”
`
`Claim 6 of the ′437 patent reads as follows: “A formulation
`according to claim 5 comprising about 10 to 30% by weight
`of a hydroxypropyl methylcellulose selected from the groups
`(a)-(d) or mixtures thereof.”
`
`Claim 7 of the ′437 patent reads as follows: “A formulation
`according to claim 6 comprising about 15 to 30% by weight
`of a hydroxypropyl methylcellulose selected from the groups
`(a)-(d) or mixtures thereof.”
`
`′437 patent reads as follows: “A
`the
`Claim 8 of
`formulation according to claim 7 wherein the one or more
`pharmaceutically acceptable excipients are selected from
`the group consisting of microcrystalline cellulose, lactose,
`magnesium stearate, sodium citrate and povidone.”
`
`Claim 9 of the ′437 patent reads as follows:
`
`to
`according
`formulation
`A
`the one or
`claim 8 wherein
`more pharmaceutically acceptable
`excipients are selected from the group
`consisting of (a) about 4 to 20% by
`weight of microcrystalline cellulose,
`(b) about 5 to 20% by weight of
`lactose, (c) about 1 to 3% by weight
`of magnesium stearate, (d) about 10
`to 30% by weight of sodium citrate
`
` © 2016 Thomson Reuters. No claim to original U.S. Government Works.
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`and (e) about 1 to 15% by weight of
`povidone.
`
`Claim 10 of the ′437 patent reads as follows: “A formulation
`according to claim 1 wherein [quetiapine] is in the form of a
`hemifumarate salt.”
`
`Claim 11 of the ′437 patent reads as follows: “A formulation
`according to claim 1 wherein one of the one or more
`pharmaceutically acceptable excipients is a pH modifier.”The
`term “a pH modifier” in claim 11 has been construed by the
`Court to mean “one or more excipients capable of changing
`pH.”
`
`Claim 12 of the ′437 patent reads as follows: “A formulation
`according to claim 11 wherein the pH modifier is sodium
`citrate.”
`
`Claim 13 of the ′437 patent reads as follows: “A method of
`treating psychotic states or hyperactivity in a warmblooded
`animal which comprises administering to said warmblooded
`animal an effective amount of a formulation according to
`[any one] of claims 1–12.”The parties agree that the terms
`“treating,” “psychotic states,” and “an effective amount” in
`claim 13 have their plain and ordinary meaning.
`
`C. Prosecution History of #437 Patent
`In the ′437 patent application, the applicants informed the
`USPTO that, in the treatment of a number of diseases, it is
`desirable to provide the active pharmaceutical ingredient in
`a sustained release form, and that, desirably, the sustained
`release provides a generally uniform and constant rate of
`release over an extended period of time. According to the
`′437 patent application, this achieves a stable and desired
`blood plasma level of the active ingredient “without the
`need for frequent administration of the medicaments.”JTX–
`2 at 10. The applicants also informed the USPTO that there
`are “numerous” sustained release formulations known in the
`art that use gelling agents such as HPMC, but that “it has
`been found to be difficult to formulate sustained release
`formulations of soluble medicaments and gelling agents, such
`as [HPMC], for several reasons.”JTX–2 at 10.
`
`*7 In a paper filed in the USPTO on September 2, 1997, the
`applicants identified 47 prior art references for the USPTO
`Examiner. Those references were listed on a form called
`“Form PTO–1449.” Applicants also provided a copy of those
`prior art references for the USPTO Examiner. JTX–2 at 78–
`
`83. On March 9, 1998, the Examiner in charge of the ′437
`patent application placed his initials next to 46 of the 47
`prior art references cited by applicants, indicating that he
`considered those references. JTX–2 at 80–83. These prior art
`references considered by the USPTO Examiner during the
`prosecution of the ′ 437 patent application are listed on the
`face of the ′437 patent. JTX–1.
`
`issued an Office
`the USPTO
`On April 1, 1998,
`Action, rejecting all 15 claims of the application for
`′288 patent and acknowledging
`obviousness over the
`receipt of the applicant's Form PTO–1449. JTX–2 at 85–
`86. On October 5, 1998, the applicant responded to the
`Office Action. JTX–2 at 100–102. In its Response, the
`applicant acknowledged that the U.S. Patent No. 4,879,288,
`entitled “Novel Dibenzothiazepine Antipsychotic” (“the ′288
`patent”) 7 discloses pharmaceutical compositions containing
`quetiapine. But, the applicant argued that one skilled in the art
`would not have been motivated by the ′288 patent (referred
`to by the applicant as “Warawa”) to prepare the claimed
`sustained release formulations. In particular, the applicant
`argued as follows:
`
`7
`
`AZLP is the owner of the ′288 patent (JTX–423), which
`was issued by the U.S. Patent and Trademark Office
`on November 7, 1989. The ′ 288 patent expired on
`September 26, 2011. It claims, inter alia, quetiapine
`fumarate, the pharmaceutically active ingredient in
`Seroquel XR. The ′288 patent is no longer at issue in
`these actions. Stip. Fact 4, 5, 95.
`
`The Examiner has not identified any motivation in Warawa
`to modify the compositions disclosed therein and prepare
`the sustained release formulations recited by the instant
`claims. Warawa does not specifically disclose a sustained
`release formulation. Additionally, there is no suggestion
`in Warawa that it would be beneficial to administer
`the compounds disclosed therein in a sustained release
`formulation. In fact, Warawa does not disclose any
`pharmacokinetic data for the compounds disclosed therein.
`Thus, one skilled in the art would not be motivated by
`Warawa to prepare the instantly claimed sustained release
`formulation.
`JTX–2 at 101.
`The applicant also argued that there was nothing in the ′288
`patent that would have provided a POSA with a reasonable
`expectation that a sustained release formulation of quetiapine
`successfully could be prepared. In particular, the applicant
`argued as follows:
`
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`the Examiner has not
`Secondly,
`identified anything in Warawa that
`would have provided one skilled in
`the art with a reasonable expectation
`that the instantly claimed sustained
`release formulation could have been
`prepared. As disclosed in the instant
`specification at page 1, lines 13–28,
`it has generally been found to be
`difficult to formulate sustained release
`formulations of soluble medicaments
`and gelling agents. The Examiner
`has not identified any suggestion in
`Warawa that the instantly claimed
`sustained release formulations could
`successfully have been prepared.
`
`JTX–2 at 101.
`
`Following the October 5, 1998 Response, the Examiner
`allowed all 15 claims, and the ′437 patent issued on
`September 7, 1999. JTX–2 at 105–106; JTX–1 at 1.
`
`D. The Proposed ANDA Products 8
`8
`These facts recited in this section have been stipulated
`by the parties in the Stipulated Facts filed at Docket
`Entry No. 156 unless otherwise indicated by citation to
`a different source.
`
`*8 The proposed ANDA products of all of the defendants are
`tablets (i.e., solid oral dosage forms). All contain quetiapine
`as the pharmaceutically active ingredient, in the form of
`quetiapine hemifumarate, a pharmaceutically acceptable salt
`of quetiapine. All release quetiapine over an extended period
`of time. All contain pharmaceutically acceptable excipients.
`
`The proposed ANDA products of Anchen, Osmotica and
`Mylan Pharms contain HPMC, the preferred gelling agent
`of the ′437 patent. Anchen, Mylan and Osmotica have not
`contested that their proposed ANDA products would infringe
`various claims of the ′437 patent if those claims are not found
`to be invalid.
`
`Torrent seeks approval to commercially market generic
`quetiapine fumarate sustained release tablets in 50, 150, 200,
`300 and 400 mg dosage strengths. Torrent's proposed ANDA
`product does not contain HPMC as the sustained release
`agent, but rather contains an ingredient called “carageenan
`
`lambda.” Torrent obtains the carageenan lambda used in
`its proposed ANDA products from FMC Corporation, and
`the particular carageenan lambda in Torrent's product is
`FMC's Viscarin GP 209 NF (“Viscarin 209”). Torrent's
`proposed ANDA products contains about 25–30% by weight
`of Viscarin 209, JTX–88 at 3; PTX–1175; Tr. 90:9–17;
`Tr. 254:19–21, and contain divalent magnesium cations,
`Tr. 92:22–93:6, 94:3–11. It is undisputed that Torrent uses
`Viscarin 209 in its ANDA products to cause the sustained
`release of quetiapine. See Torrent Amended Proposed
`Findings at Finding 1.
`
`As discussed in more detail below, Torrent has argued that
`given its use of Viscarin 209 in its ANDA products as
`the sustained release agent, its products do not meet the
`limitations of and therefore do not infringe claim 1 or claim
`2 of ′437 patent. However, Torrent concedes that if the Court
`finds that Torrent infringes claim 1 or claim 2, then claims 10,
`11 and 13 are also infringed. Tr. 71:14–16.
`
`E. Infringement
`Plaintiffs contend that Torrent's ANDA products literally
`infringe claims 1, 10, and 11, infringe claim 2 under the
`doctrine of equivalents, and that Torrent would induce
`infringement of the method of claim 13 of the ′437 patent.
`
`1. Burden of Proof and Legal Standards
`Plaintiffs have the burden of proving Torrent's infringement
`of the ′437 patent by a preponderance of the evidence. Carroll
`Touch Inc. v. Electro Mechanical Systems, Inc., 15 F.3d
`1573, 1578 (Fed.Cir.1993). It is an act of infringement to
`submit an application under § 505(j) of the Federal Food,
`Drug, and Cosmetic Act (i.e.,21 U.S.C. § 355(j)) for a
`drug claimed in a patent or the use of which is claimed
`in a patent, if the purpose of such submission is to obtain
`approval to engage in the commercial manufacture, use, or
`sale of that same drug before the expiration of such patent.
`See35 U.S.C. § 271(e)(2)(A); see also Yamanouchi Pharm.
`Co., Ltd. v. Danbury Pharmacal, Inc., 231 F.3d 1339, 1346
`(Fed.Cir.2000) (“[M]ere act of filing an ANDA constitutes
`infringement.”). The question under 35 U.S.C. § 271(e) (2)
`(A) is whether the drug that is the subject of the ANDA
`will infringe the patent when approved and marketed. See
`Bristol–Myers Squibb Co. v. Royce Labs., Inc., 69 F.3d 1130,
`1135 (Fed.Cir.1995). Thus, to meet its preponderance of the
`evidence burden, 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
`
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`patent-in-suit. See Adams Respiratory Therapeutics, Inc. v.
`Perrigo Co., 616 F.3d 1283, 1287 (Fed.Cir.2010); Warner–
`Lambert Co. v. Teva Pharms. USA, Inc., 418 F.3d 1326, 1341
`n. 15 (Fed.Cir.2005).
`
`*9 The infringement analysis proceeds in two steps—the
`first is proper construction of the relevant claims, and the
`second is a comparison of those claims to the accused product
`or method. Abbott Labs. v. Sandoz, Inc., 566 F.3d 1282,
`1288 (Fed.Cir.2009). To prove infringement, the patentee
`must show that an accused product or method is within the
`claim limitations of the patent-in-suit either literally or under
`the doctrine of equivalents. See Amgen, 580 F.3d at 1374;
`Warner Jenkinson Co., Inc. v. Hilton Davis Chem. Co., 520
`U.S. 17, 21, 117 S.Ct. 1040, 137 L.Ed.2d 146 (1997).“A
`patent is infringed if any claim is infringed ... for each
`claim is a separate statement of the patented invention.”Pall
`Corp. v. Micron Separations, Inc., 66 F.3d 1211, 1220
`(Fed.Cir.1995). Infringement, whether literal or under the
`doctrine of equivalents, is a question of fact. Bai v. L & L
`Wings, Inc., 160 F.3d 1350, 1353 (Fed.Cir.1998).
`
`a. Literal Infringement
`Literal infringement exists if any one of a patent's asserted
`claims covers the alleged infringer's product or process. See
`Markman v. Westview Instr., 517 U.S. 370, 374, 116 S.Ct.
`1384, 134 L.Ed.2d 577 (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 or
`process. See Hormone Research Found., Inc. v. Genentech,
`Inc., 904 F.2d 1558, 1562 (Fed.Cir.1990); Panduit Corp.
`v. Dennison Mfg. Co., Inc., 836 F.2d 1329, 1330 n. 1
`(Fed.Cir.1987). Proof of literal infringement may be based
`on direct or circumstantial evidence. See Martek Biosciences
`Corp. v. Nutrinova, Inc., 579 F.3d 1363, 1372 (Fed.Cir.2009)
`(“A patentee may prove infringement by any method of
`analysis that is probative of the fact of infringement ... and