Positive
`As of: October 10, 2018 2:11 PM Z
`
`AstraZeneca Pharms. LP v. Anchen Pharms., Inc.
`
`United States District Court for the District of New Jersey
`
`March 28, 2012, Decided; March 29, 2012, Filed
`
`Civil Action No. 10-cv-1835 (JAP)(TJB); Civil Action No. 10-cv-4203 (JAP)(TJB); Civil Action No. 11-cv-
`2484 (JAP)(TJB); Civil Action No. 10-cv-4205 (JAP)(TJB); Civil Action No. 10-cv-4971 (JAP)(TJB); Civil
`Action No. 10-cv-5519 (JAP)(TJB); Civil Action No. 11-cv-2483 (JAP)(TJB)
`
`Reporter
`2012 U.S. Dist. LEXIS 43989 *; 2012 WL 1065458
`
`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.
`
`Notice: NOT FOR PUBLICATION
`
`Subsequent History: Affirmed without opinion by
`Astrazeneca Pharms. Lp v. Anchen Pharms., Inc.,
`2013 U.S. App. LEXIS 3070 (Fed. Cir., Feb. 14,
`2013)
`
`Prior History: Astrazeneca Pharms. LP v. Handa
`Pharms., LLC, 2010 U.S. Dist. LEXIS 126078
`(D.N.J., Nov. 30, 2010)
`
`Core Terms
`
`quetiapine, patent, Seroquel, patients, dose,
`antipsychotic, formulations, pharmaceutical, drugs,
`side effect, prior art, occupancy, gel, infringement,
`receptor, schizophrenia, references, combine,
`depression, effective, invention, teachings, release
`form, bipolar, discloses, products, dosage,
`psychotic, efficacy, reasonable expectation
`
`Counsel: [*1] For TORRENT
`PHARMACEUTICALS LIMITED, TORRENT
`PHARMA INC. (3:10-cv-01835), Movants:
`THOMAS R. CURTIN, LEAD ATTORNEY,
`GRAHAM CURTIN, PA, MORRISTOWN, NJ.
`
`For ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:10-cv-01835),
`
`Plaintiffs: 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 ANCHEN PHARMACEUTICALS, INC. (3:10-
`cv-01835), Defendant: JAMES S. RICHTER,
`JEFFREY P. CATENACCI, MELISSA STEEDLE
`BOGAD, WINSTON & STRAWN, LLP, NEWARK,
`NJ.
`
`For ANCHEN, INC. (3:10-cv-01835), Counter
`Claimant: JAMES S. RICHTER, WINSTON &
`STRAWN, LLP, NEWARK, NJ.
`
`For ANCHEN PHARMACEUTICALS, INC. (3:10-
`cv-01835), Counter Claimant: JAMES S.
`RICHTER, JEFFREY P. CATENACCI, WINSTON
`& STRAWN, LLP, NEWARK, NJ.
`
`For ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:10-cv-01835),
`Counter Defendants: 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 TORRENT PHARMACEUTICALS LIMITED,
`TORRENT PHARMA INC. (3:10-cv-04203),
`Movants: THOMAS [*2] R. CURTIN, LEAD
`ATTORNEY, GRAHAM CURTIN, PA,
`MORRISTOWN, NJ.
`
`For ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:10-cv-04203),
`Plaintiff: CARISSA L. RODRIGUE, ELINA SLAVIN,
`
`Page 1
`
`SHIRE EX. 2078
`KVK v. SHIRE
`IPR2018-00293
`
`

`

`2012 U.S. Dist. LEXIS 43989, *2
`
`Page 2 of 48
`
`JOHN EDMUND FLAHERTY, JONATHAN M.H.
`SHORT, MCCARTER & ENGLISH LLP, NEWARK,
`NJ; HENRY J. RENK; ROBERT JOHN
`CZARNECKI, JR., FITZPATRICK CELLA HARPER
`& SCINTO, NEW YORK, NY.
`
`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 OSMOTICA PHARMACEUTICAL
`CORPORATION (3:10-cv-04203), Defendant:
`KEITH J. MILLER, LEAD ATTORNEY, DONALD A.
`ROBINSON, MICHAEL JAMES GESUALDO,
`LEDA DUNN WETTRE, ROBINSON, WETTRE &
`MILLER LLC, NEWARK, NJ.
`
`For TORRENT PHARMACEUTICALS LIMITED,
`TORRENT PHARMA INC. (3:10-cv-04205),
`Defendants, Counter Claimants: THOMAS R.
`CURTIN, LEAD ATTORNEY, GEORGE C.
`JONES, GRAHAM CURTIN, PA, MORRISTOWN,
`NJ.
`
`For OSMOTICA PHARMACEUTICAL
`CORPORATION (3:10-cv-04203), Counter
`Claimant: LEDA DUNN WETTRE, ROBINSON,
`WETTRE & MILLER LLC, NEWARK, NJ.
`
`For ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:10-cv-04203),
`Counter Defendants: HENRY J. RENK; JOHN
`EDMUND FLAHERTY, JONATHAN M.H. SHORT,
`MCCARTER & ENGLISH LLP, NEWARK, NJ;
`ROBERT JOHN CZARNECKI, JR., FITZPATRICK
`CELLA HARPER & SCINTO, NEW YORK, NY.
`
`For ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:11-cv-02484),
`Plaintiffs, Counter Defendants: CARISSA L.
`RODRIGUE, ELINA SLAVIN, JOHN EDMUND
`FLAHERTY, JONATHAN M.H. SHORT, MARK H.
`ANANIA, MCCARTER & ENGLISH LLP,
`NEWARK, NJ; ROBERT [*3] JOHN CZARNECKI,
`JR., FITZPATRICK CELLA HARPER & SCINTO,
`NEW YORK, NY.
`
`For OSMOTICA PHARMACEUTICAL
`CORPORATION (3:11-cv-02484), Defendant:
`KEITH J. MILLER, LEDA DUNN WETTRE, LEAD
`ATTORNEYS, MICHAEL JAMES GESUALDO,
`ROBINSON, WETTRE & MILLER LLC, NEWARK,
`NJ.
`
`For OSMOTICA PHARMACEUTICAL
`CORPORATION (3:11-cv-02484), Counter
`Claimant: LEDA DUNN WETTRE, LEAD
`ATTORNEY, MICHAEL JAMES GESUALDO,
`ROBINSON, WETTRE & MILLER LLC, NEWARK,
`NJ.
`
`For ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:10-cv-04205),
`Plaintiffs: CARISSA L. RODRIGUE, ELINA
`
`For ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:10-cv-04205),
`Counter Defendants: 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 ASTRAZENECA PHARMACEUTICALS
` [*4] LP, ASTRAZENECA UK LIMITED (3:10-cv-
`04971), Plaintiffs: 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 TORRENT PHARMACEUTICALS LIMITED,
`TORRENT PHARMA INC. (3:10-cv-04971),
`Defendants, Counter Claimants: THOMAS R.
`CURTIN, LEAD ATTORNEY, GEORGE C.
`JONES, GRAHAM CURTIN, PA, MORRISTOWN,
`NJ.
`
`For ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:10-cv-04971),
`Counter Defendants: 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 ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:10-cv-05519),
`Plaintiffs: 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
`
`Page 2
`
`

`

`2012 U.S. Dist. LEXIS 43989, *4
`
`Page 3 of 48
`
`CELLA HARPER & SCINTO, NEW YORK, NY.
`
`For MYLAN PHARMACEUTICALS INC., MYLAN
`INC. (3:10-cv-05519), Defendants, Counter
`Claimants: ARNOLD B. CALMANN, GERI L.
`ALBIN, SAIBER LLC, NEWARK, NJ.
`
`For ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA [*5] UK LIMITED (3:10-cv-
`05519), Counter Defendants: CARISSA L.
`RODRIGUE, 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 ASTRAZENECA PHARMACEUTICALS LP,
`ASTRAZENECA UK LIMITED (3:11-cv-02483),
`Plaintiffs, Counter Defendants: 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 MYLAN PHARMACEUTICALS INC., MYLAN
`INC. (3:11-cv-02483), Defendants, Counter
`Claimants: ARNOLD B. CALMANN, SAIBER LLC,
`NEWARK, NJ.
`
`Judges: Joel A. Pisano, United States District
`Judge.
`
`Opinion by: Joel A. Pisano
`
`Opinion
`
`PISANO, District Judge.
`
`I. INTRODUCTION
`
`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- [*6] 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
`
`in all actions are AstraZeneca
`Plaintiffs
`Pharmaceuticals LP ("AZLP") and AstraZeneca UK
`Limited ("AZUK") (collectively, "AstraZeneca" or
`"Plaintiffs"). Below is a summary of the instant civil
`actions: 1
`
`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
` [*7] complaint against Osmotica (Civil Action
`No. 11-2484) alleging that Osmotica's filing of
`
`the
`to
`1 Plaintiffs settled with certain defendants prior
`conclusion of trial. Those civil actions that were concluded
`prior to the end [*8] of trial are not listed here.
`
`Page 3
`
`

`

`2012 U.S. Dist. LEXIS 43989, *8
`
`Page 4 of 48
`
`its AND A 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).
`• 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
`
`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
`
`(Bench Trial
`witnesses: Dr. Martyn Davies
`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 [*9] release ingredient in Torrent's
`ANDA product.
`
`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.
`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.
`
`Defendants'
`to
`responded
`AstraZeneca
`following seven
`obviousness case with
`the
`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 [*10] 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;
`
`Page 4
`
`

`

`2012 U.S. Dist. LEXIS 43989, *10
`
`Page 5 of 48
`
`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.
`
`three expert
`rebuttal, Defendants called
`In
`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.
`
`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:
`
`former AstraZeneca
`Dr. William Addicks, a
`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.
`
`Dr. Jamie Mullen, a psychiatrist, is an AstraZeneca
`employee. Dr. Mullen testified about AstraZeneca's
`clinical trials relating to its sustained release
`quetiapine formulations.
`
`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.
`
`former AstraZeneca
`Dr. Bhavnish Parikh, a
`employee, is one of the inventors of the '437
`
`testified about work at
`patent. Dr. Parikh
`AstraZeneca on sustained release quetiapine
`formulations.
`
` [*12] is a physician who
`Dr. Steven Potkin
`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.
`
`is an AstraZeneca
`Dr. Martin Deberardinis
`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. 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
` [*13] is a complicating factor in formulating a drug
`for sustained release.
`
`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.
`
`Mr. Graham Jackson is an employee of Biovail. Mr.
`
`2 In this context, "commercialization" is limited to marketing
` [*11] and sales.
`
`3 Biovail is a defendant in a related civil action brought by
`AstraZeneca that was dismissed prior to the conclusion of trial.
`
`Page 5
`
`

`

`2012 U.S. Dist. LEXIS 43989, *13
`
`Page 6 of 48
`
`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.
`
`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.
`
`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.
`
`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 Case5
`
`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
` [*16] 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,
`
`4 Handa is a defendant in a related civil action brought by
`AstraZeneca that was dismissed [*14] prior to the conclusion
`of trial.
`
`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 [*15] to a
`different source.
`
`Page 6
`
`

`

`2012 U.S. Dist. LEXIS 43989, *15
`
`Page 7 of 48
`
`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
` [*17] disorder ("MDD"). Quetiapine fumarate is the
`active pharmaceutical
`ingredient
`("API"),
`in
`Seroquel XR. Seroquel XR is formulated to be
`administered once-a-day.
`
`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 Patent6
`
`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 [*18] 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, together
`
`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.
`
`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.
` [*19] JTX-1, col. 3, lines 3-5.
`
`Claim 3 of the '437 patent reads as follows:
`
`A sustained release formulation 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
`
`Page 7
`
`

`

`2012 U.S. Dist. LEXIS 43989, *19
`
`Page 8 of 48
`
`hydroxypropyl methylcellulose described under
`(d) above the total amount of hydroxypropyl
`methylcellulose
`present
`in
`the
` [*20] formulation must be greater than 25.8%
`by weight.
`
`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."
`
`Claim 8 of the '437 patent reads as follows: "A
`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 [*21] and povidone."
`
`Claim 9 of the '437 patent reads as follows:
`A formulation according to claim 8 wherein the
`one or 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 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 [*22] 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.
`
`In a paper filed in the USPTO on September 2,
`1997, the applicants identified 47 prior [*23] art
`references
`for
`the USPTO Examiner. Those
`references were listed on a form called "Form
`PTO-1449." Applicants also provided a copy of
`
`Page 8
`
`

`

`2012 U.S. Dist. LEXIS 43989, *23
`
`Page 9 of 48
`
`the USPTO
`for
`references
`those prior art
`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.
`
`On April 1, 1998, the USPTO issued an Office
`Action, rejecting all 15 claims of the application for
`obviousness
`over
`the
`'288
`patent
`and
`acknowledging 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 [*24] to by the applicant as "Warawa") to
`prepare
`the
`claimed
`sustained
`release
`formulations. In particular, the applicant argued as
`follows:
`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 [*25] 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:
`Secondly, the Examiner has not 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 Products8
`
`the
`The proposed ANDA products of all of
`defendants are tablets