Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 1 of 98
`
`UNITED STATES DISTRICT COURT
`
`SOUTHERN DISTRICT OF NEW YORK Kowa Company,Ltd., et al.,
`
`Plaintiffs,
`
`v.
`
`Anineal Pharmaceuticals, LLC
`
`Defendant.
`
`
`
`Kowa Company, Ltd., et al.,
`
`|
`
`Civil Action No. 14-CV-2758 (PAC)
`
`
`
`Plaintiffs,
`
`Civil Action No. 14-CV-7934 (PAC)
`
`v.
`
`Apotex, Inc., et al.,
`,
`
`Defendants.
`
`FINDINGS OF FACT AND
`
`CONCLUSIONS OF LAW
`
`TABLE OF CONTENTS
`
`TABLE OF ABBREVIATIONS
`
`INTRODUCTION AND LEGAL STANDARDS
`
`I.
`
`The Hatch-Waxman Act and ANDA Filings... ccccccccccscsscsesscsesersesesecsesscsescsssecessecesesscees 5
`
`TT. The Parties 0. eesccccsessesescsessescsesvsssesssccavazscssvasscevsssusessvavacacsevavasasssatsavavsvevevsvesecevevacevees 6
`TIL,
`Livalo® cess cecccseescsssseesssecsssensessnssecessnnnsecqusmneessstssesssssusessssessssssseessessnnesssusnuesersennaneesessnses 7
`
`TV.
`
`The £993 Patent 0... ecccccccccsesessssesescsssesssecssstssnsvssscsesssssesauavssecsavavassssssevavessssvavavavavecenessesees 8
`
`V. The Instant Dispute... ccc ceeeceeeessseescsssseesesressseacsesvsuessssevsssssssnsavaveusazstasasateausssssanssesevaess 12
`
`VI.
`
`Legal Standards... ccccessssssssssssesessessssescsesesvacevsssvevsvsssssvsvsvareususscsssessnsseassvevaveveseceveees 13
`
`a.
`
`Presumption of Patent Validity... cc cceeeessseessssesesescssscscscsesesssvevacscacsestasesseaeanavaceves 13
`
`b. Affirmative Defense of Patent Invalidity... cceecccscessssescscesesstssececasstscecsuscstsesesessses 13
`
`|
`
`Gilead 2009
`I-MAKv. Gilead
`IPR2018-00126
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 2 of 98
`
`i. Anticipation (35 U.S.C. § 102)... eecssessssnerseenereesnenseessserenereseastearsvaneeseysecareegenenenenetes 14
`ii.—Obviousness (35 U.S.C. § 103) cscscsessnecssacesneessenseessneeansecstsessssnsecanessasecnssnesseanseenanies 16
`©.
`Infringement...cce-scccssessccseccsseesssarecsssecsssesesnecesssesssnsesssecesveecesusessiseenssasessseeststennngseenesseseessennee 18
`Claism Construction ssssssssssssecesssesesssesecsessesscuevsscnsseseeeussusssensereseeeuueseensssensessesetuaeeseesen 19
`
`i,
`
`VIL. Crystals and Polymorph.....cceccssesenestssesesscssersesnscsarerseassanpersceaasereecauensrssatacatravreasaeeeettens 20
`
`Vill.
`
`X-Ray Powder Diffraction and Characterization 0... cscs csssceesectecnenercesecnenerseeereneeeaes 23
`
`TX.
`
`Jurisdiction... ees cceceessseseseeeeeteneceeateenecseseseecsecaevesuceusessaessaeastacssaessaesevesseqesassteseseseteasasees 28
`
`X.
`
`Person of Ordinary Skill in the Art... lee sssseseesccesseseeeasseeeseeasessnesesarsesaeacadensseeeeensonsete 28
`
`XI.-Validity ofthe ‘993 Patent... ccccecsssesecseseeserscnssseeneeeseeesessetseenesacsesessneensersnsapasuenseenses 29
`
`a. Anticipation 35 US.C, § 102) occeaseeseaceacessssateaneedeseveccsaneaesaesnenstatsevatteeeeeeaeesecetnee 29
`
`1, EP 406Le cee ccesceceesseneseeasssteeeessneneeeatceecetseuseaneesceanaevepeetsecensesstasaraanseseeneesaeaeapert 31
`
`il.
`
`iii.
`
`iv.
`
`The ‘993 Patent Prosecution HistOry.....cccccccsecssscsssssesessstscensseseesas euseaeaeeucerearearsenenes 31
`
`Defendants’ Inherency Arguments ......... cc cescscseseeeeseceeeeeeonevseetaaseaseeeeversaessansesseserse 37
`
`Conclusion Regarding Inherent Anticipation... cc ceceeeecessssscnsensceneeneeseeueesensnsavecs 40
`
`b. Obviousness (35 U.S.C. § 5sesssssseusasenensunanngcetuanageetsnnensseaaseasenvesanseagauenseestsasarssen 48
`i.
`LevelofOrdinary Skill in
`the Artscccscsssscsssssessssssssstusssinssienesiesssisesientsnesesneese 50
`ii.
`Scope and Contentof the Prior Art and Differences Between Claimed Subject Matter
`and the Prior Art....cccccccscsscesesssensensesssevessseseaeenecssecsessscnsseeeusneasesenesceastenucsseataceceassuenseeseneenees 50
`
`ili. Whether Obtaining Form A Would Have Been Obvious to a POSA in 2003........... 52
`iv.
`Objective Indicia of Nonobviousness (Secondary Considerations) ...........cccceeeee 59
`
`Conclusion Regarding Obviousness.........-.ceeneeeeeeees veveseansneenecssennvsseasseuceaetatencees 75
`v.
`Conclusion Regarding Validity... cscs eeeseeescsseeseseacseneecetsesnenescenscaareseecnecneaeeaeenseates 75
`Infringementof the (993 Patent ........cccesssesesstssesssesseesneanecseessecsessssssesusssesesesuesneeseceeye 76
`
`c.
`XIL
`
`a.
`
`Step One: Construing the Asserted Claims... cc sss sesstsenerscceseeeesseasesnesenteercnetsateees 77
`
`i. Claims 1 and 24: “exhibits a characteristic x-ray diffraction pattern with characteristic
`peaks expressed in 20 at...” boseeeevesasececsenstseassenssenseesssneasseaesaneeseeesnavscasiseneessnetetiracs 77
`
`Claims 23 and 25: “having an x-ray powder diffraction pattern substantially as
`ii,
`depicted tn Fig. Lo. ceeceeecsensesenecsansesesenennessecseessecsesatacsenstesanevaventessuseeeaeseeseeseeasegeeseateens 80
`
`b.
`
`Step Two: Comparison of Asserted Claims to Apotex’s Proposed ANDA Product......... 81
`
`i, Apotex’s Proposed ANDA Product oo...cccece ssstsetsceevecsnenerscnseaueeeesstearsesessersterstvees 82
`ii,
`Dr. Kaduk’s Analysis and Conclusions .cccceccsssseceeenenseesetaaeeneseeseaeseuessenneeseteasertenss 85
`iti.
`Dr. Sacchetti’s Analysis and Conclusions...........eneecsasetasevesssausavesesaceseaeetasneseseseateeses 89
`
`2
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 3 of 98
`
`
`
`iiv.
`
`
`
`ClaimsAIMS 1 and
`
`d2
`
`
`
`:24 oo eeccecccesccoscecscccecccsssssevevcscesennscuscssesnssecsctescuscencsveseeeessosenassenseceuseauenaca 91
`
`
`
`V.—-Claims 23 ard 25 wo. cecsssescesseseneeesenenessseseetetsescessnsnssassatanassassuseesnsnseseseeaseetscseasseeasenss 94
`
`VA CaM 22 eee ececescceseeesenssseensernevencaneussenscesscanesaanspesseepaesaerstsonaneaescssaaensenseasneevessoenenes 95
`
`c. Conclusion Regarding Infringement... i.e csesseeraseccnrsnvssssssesseseesasecencressevseseensoserase 96
`
`CONCLUSION ~
`
`TABLE OF ABBREVIATIONS
`
`| *993 Patent
`U.S. Patent No. 8,557,993
`
`-ANDA
`Abbreviated New Drug Application
`
`API
`Active pharmaceutical ingredient
`
`DMF
`Drug master file
`
`EPO
`European Patent Office
`
`EP ‘406
`European Patent Application No. EP 0 520 406A1
`
`FDA.
`U.S. Food and Drug Administration
`
`
`IDS
`Information Disclosure Statement
`
`KCL
`~~|Kowa Company, Ltd.
`st”:
`
`
`Kowa Pharmaceuticals America, Inc.
`
`
`
`
`“XRPDorPXRD©7 X-raypowderdiffraction
` | Third Party Observation -
`
`MSNLaboratories Pvt. Ltd.
`
`
`Nissan Chemical Industries, Ltd.
`
`
`U.S. Patent and Trademark Office
`
`USP
`
`U.S. Pharmacopeia
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 4 of 98
`
`HONORABLE PAUL A. CROTTY, United States District Judge:
`
`_ This is a Hatch-Waxman patentinfringementlitigationinitiated by Plaintiffs Kowa
`
`Company, Lid., Kowa Pharmaceuticals America, Inc., and NissanChemical Industries, Ltd.
`(collectively, “Plaintiffs”), manufacturers ofthe cholesterol-lowering drug Livalo®, against
`defendants Amneal Pharmaceuticals, LLC (“Amneal”), and Apotex, Inc. and Apotex Corp.
`(“Apotex”), generic drug manufacturers (together, “Defendants”).! Plaintiffs allege that
`Defendants’ proposed Abbreviated New Drug Application (“ANDA”) products would infringe
`US. Patent No.8,557,993 (the “993 patent”). Both Amneal and Apotex contendthat the “993
`patent is invalid as (1) anticipated basedon priorart, under 35 U.S.C. § 102(b); and/or (2) obvious
`
`in view ofpriorart, under 35 U.S.C. § 103. Only Apotex asserts non-infringement; Amneal
`
`concedes infringement.
`
`The Court held a ten-day benchtrial from January 17 through January 30, 2017, with
`closing arguments on February 3, 2017. Each ofthe parties submitted extensive post-trial
`
`briefing on the ‘993 patent’s validity and infringement. After considering the documentary
`
`evidence and testimony, the Court makes the following findings offact and conclusions of law
`
`pursuant to Fed. R. Civ. P. 52(a). As set forth below, the Court determines that the ‘993 patent is
`
`valid; and that Apotex’s proposed ANDAproduct would infringe the ‘993 patent.
`
`1 Plaintiffs commencedthis litigation against eight generic drug manufacturer defendants. Defendants asserted
`defenses of invalidity and non-infringement. Four defendants settled before commencementof the ten-day bench
`trial. The fifth defendantsettled mid-trial; and the sixth settied post-trial. Only Ammeal and Apotex remain. On
`April 11, 2017, the Court issued its Findings of Fact and Conclusions of Law regarding the other patentatissue at
`trial, U.S. Patent No. 5,856,336, finding it valid.
`(Kowa Co., Ltd. v. Amneal Pharm., LLC., No, 14-CV-2758 (PAC)
`(S.D.N.Y. Apr. 11, 2017)).
`
`4
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 5 of 98
`
`INTRODUCTION AND LEGAL STANDARDS
`
`L
`
`The Hatch-WaxmanAct and ANDAFilings?
`1. The Hatch-Waxman Act, titled the Drug Price Competition and Patent Term Restoration
`‘Act of 1984, Pub. L. No. 98-417, permits pharmaceutical companies to seek United States Food
`and Drug Administration (FDA) approvalfor a generic drug based on an already-approved
`
`branded drug by filing an ANDA. (See 21 U.S.C. § 355G)(2)(A), (8)(B)). In so doing, the
`
`generic manufacturer may rely on the branded drug’s safety and efficacy data submitted to the
`FDA. (See id.).
`|
`
`2. If the branded drug manufacturer’s patent has not yet expired, the generic manufacturer
`
`mustfile a “Paragraph IV”certification, establishing bioequivalence of the proposed generic
`
`version with the approved branded version of the drug. (See 21 U.S.C. § 355Q@)2)(A)WiDCY);
`21 CFR. § 314.94(a)(9)). The certification must also state and explain cither that the generic
`
`productwill not infringe the branded manufacturer’s patent, or that the patentis invalid. (See 21
`
`ULS.C. § 355Q)(2)(B) Gv}CD).
`
`3. “An ANDA-IV certification itself constitutes an act of infringement, triggering the
`
`branded manufacturer’s right to sue.” (Ark. Carpenters Heaith & Welfare Fund v, Bayer AG,
`
`604 F.3d 98, 101 (2d Cir. 2010), cert. denied, 131 S. Ct. 1606 (2011) (citing 35 U.S.C. §
`271 (e)(2)(A)). If litigation is initiated, the generic’s entry to market is automatically stayed. (21
`U.S.C. § 355@)(5)(B)Gii)). “[T]his structure allowsthe parties to try the dueling issues ofpatent
`
`infringement and patent invalidity simultaneously.” (Jn re: OxyContin Antitrust Litig., No. 13-
`
`CV-3372 (SHS), 2015 WL 11217239,at *5 (S.D.N.Y. Apr. 8, 2015)).
`
`2 For additional background on the policy goals of the Hatch-Waxman Act, see this Court’s April 11, 2017 Findings
`of Fact and Conclusions of Law regarding the other patentat issueattrial, U.S. Patent No. 5,856,336. (Kowa Co.,
`Lid. y. Amneal Pharm., LLC, No. 14-CV-2758 (PAC) (S.D.N-Y. Apr. 11, 2017) at 9-10).
`
`5
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 6 of 98
`
`II.
`
`The Parties
`
`4, Plaintiff Kowa Company, Ltd. (“KCL”) is a Japanese corporation with its corporate
`headquarters and principal place ofbusiness in Aichi, Japan. (Compl. § 2). PlaintiffKowa
`Pharmaceuticals America, Inc. (“KPA”) is a wholly-owned subsidiary ofKCL organized under
`
`the laws of Delaware, with its corporate headquarters and principal place ofbusiness in
`
`Montgomery, Alabama. (/d.). Plaintiff Nissan ChemicalIndustries, Ltd. “NCI”or “Nissan”)is
`a Japanese corporation with its corporate headquarters and principal place ofbusiness in Tokyo,
`Japan. (id. $3). Plaintiffs are manufacturers, researchers, developers, and marketers of the
`
`cholestero}-lowering drug Livalo®. (Id. 4 4).
`
`5. Defendant Amnealis incorporated in Delaware, with a place ofbusiness in Bridgewater,
`
`New Jersey. (Amneal Answer 5). Amneal filed ANDA No. 20-5961 seeking FDA approvalto
`market 1 mg, 2 mg, and 4 mg pitavastatin calcium tablets. Ud. § 20).
`|
`6. Defendant Apotex, Ine. is organized in and exists under the laws of Canada, with a
`
`principal place of business in Toronto, Ontario, (Apotex Answer ¥ 5). Defendant Apotex Corp.
`
`is incorporated in and exists under the Jaws of Delaware, with a place ofbusiness in Weston,
`
`Florida.
`(7d. 6). Apotex Corp. sells and markets Apotex, Inc.’s products in the United States.
`(7d.). Apotex Corp. is Apotex Inc.’s agent for purposes ofmaking regulatory submissions,
`
`including its ANDA No. 20-6068filing, secking FDA approval to market | mg, 2 mg, and 4 mg
`
`pitavastatin calcium tablets. (Jd. J] 6, 20). Apotex’s ANDAfiling contains a Paragraph IV.
`
`certification respecting the ‘993 patent. (/d. { 22).
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 7 of 98
`
`Ill.—Livalo®
`
`7, At trial, Dr. Craig Sponseller, KPA’s Chief Medical Officer, provided an initial
`
`explanation ofthe history and workings of Livalo® pitavastatin. (See generally Tr. 67-136). A
`
`brief summary ofrelevant and uncontested facts is recited here.
`
`8. Statins are medications that address and control abnormal increases in blood cholesterol by
`
`inhibiting the wayin which the liver makes cholesterol, (Tr. 70:8~71:10). Ali statins generally
`
`work in the same way, but differ in the manner in which theybind to enzymes and dissolve in
`solvents; and how they are processed and metabolized by the body. (Tr. 71:5-17).
`
`9. Patients have varying degreesofstatin tolerance (or intolerance), (Tr. 71 :25-74:13).
`
`Approximately 10-15% ofpatients with elevated cholesterol are statin intolerant, which amounts
`
`to approximately 4 to 6 million statin-intolerant patients in the United States. (Tr. 73:22~74:7).
`
`10. Livalo® is a statin used to treat elevated cholesterol; or morespecifically, as reflected on
`
`its label, hyperlipidemia or mixed dyslipidemia. (Tr. 77:5~11; PTX-1098 (Livalo® Label
`(Revised: November 2016)) at KN003466196). It does so by reducing low density protein
`
`cholesterol (“LDL-C”), total cholesterol, triglycerides, and apolipoprotein B; and/or increasing
`
`high density lipoprotein cholesterol (“HDL-C”). (Tr. Tr. 77:5—11; PTX-1098 (Livalo® Label) at
`
`KN003466196).
`
`11. Approximately 75% of all metabolic drugs are metabolized through the “cytochrome
`P450” pathway (the “CYP450”or “CYP”pathway)in the liver. (Tr. 74:14-75:9). By contrast,
`
`Livalo® mostly avoids, and is only minimally metabolized by, the CYP450 pathway. (Tr. 75:10—
`
`76:1, 85:6-21).
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 8 of 98
`
`12. Thereare currently seven available statins on the market: at the time Livalo® launched in
`
`the U.S. in mid-2010, there weresix available statins with which Livalo® competed? (Tr.
`
`70:15~20).
`
`IV.
`
`The ‘993 Patent
`
`13. The ‘993 patent, “Crystalline Forms ofPitavastatin Calcium,”is assigned to NCI. (PTX-
`
`1063). KCL is NCI’s licensee for the ‘993 patent, and KPA holds a license from KCLforthe
`
`‘993 patent. (Amneal Compl. 7 15; Apotex Compl. { 15). KPAsells the pitavastatin drug
`
`product under the trade name Livalo® in the United States; KCL manufactures the Livalo®
`products as sold by KPA. (Amneal Compl. fff] 16-17; Apotex Compl. {f] 16-17).
`
`14. The ‘993 patent issued on October 15, 2013, from U.S. Patent Application No.
`
`13/664,498 (the ““498 Application”),filed October 31, 2012. (PTX-1063 (‘993 patent); PTX-
`
`0172 (*498 Application (°993 patent file history))). The ‘498 Application is a continuation of
`
`U.S. Patent Application No. 10/544,752 (the “*752 Application). (PTX-1337 and DTX-1359).*
`
`15. The earliest priority date to which the ‘993 patent claims entitlement is February 12,
`
`2003. (PTX-1063 (claiming entitlement to European Application No. 03405080).
`16. The ‘993 patentstates:
`
`The present invention is directed to new crystalline forms and the amorphous form of
`Pitavastatin calcium, processes for the preparation thereof and pharmaceutical
`compositions comprising these forms .
`.
`. Pitavastatin calcium is known bythe
`chemical name: (3R,58)-7-(2-cyclopropy!-4-(4-fluorophenyl)quinolin-3-yl}-3,5-
`dihydroxy-6(E)-heptenoic acid hemicalcium salt.
`
`(Id. at 1:17--26).
`
`3 Livalo® was approved by Japanese regulators and launchedin Japan in 2003; was approved by the FDA in August
`2009; and launched in the United States in June 2010, (Tr. 1534:17-20, 103:8-9; see PTX-0480; PTX-0482),
`4 Both Plaintiffs and Defendants submitted the ‘752 Application andfile history. (See PTX-1337; DTX-1359). Due
`to a copying error, DTX-1359 was missing some pages; but the relevant testimony did not involve any such pages.
`(See Tr, 1661:9-21). For ease of reference, the Court cites both exhibits and Bates pages used and referenced in the
`corresponding trial testimony.
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 9 of 98
`
`17. The ‘993 patent explains that Plaintiffs recently developed pitavastatin calcium “as a new
`
`chemically synthesized and powerful statin .. . [that] is safe and well tolerated in the treatment of
`
`patients with hypercholesterolemia;” and that the statin has “extremely low”interactions with
`
`other commonly-used drugs. (/d. at 1:43-50).
`
`18. Claims 1, 22, 23, 24, and 25 ofthe ‘993 patent claim six different polymorphs of
`pitavastatin calcium, polymorphic forms A, B, C, D, E, and F, and the amorphous form; and a
`pharmaceutical composition comprising an effective amountofthe form, and a pharmaceutically
`acceptable carrier. Ud. at 10:50-11:37, 13:7-41), Each claimed form includes a recitation ofa
`characteristic X-ray powderdiffraction pattern having specific characteristic peaks (claims | and
`
`24) or a diffraction pattern substantially as depicted in specified Figures (claims23 and 25).
`
`(id.).
`19. Crystalline polymorph A ofpitavastatin calcium (“Form A” or “Polymorph Form A”) is
`
`the subject ofthis action.°
`
`20. The ‘993 patent specification discloses that “Form A may contain up to 15% water,
`
`.
`preferably about 3 to 12%, more preferably 9 to 11% ofwater.” (dd. at 6:13-14).
`21. Claims J and 24 are directed to, inter alia, Form A exhibiting “a characteristic X-ray
`
`powder diffraction pattern with characteristic peaks expressed in 28 at [recited peak positions
`
`and relative mtensities].” The relevant parts of claims 1 and 24 are set forth below:
`
`Accrystalline polymorphA,B,C, D, E, F, or the amorphous form,
`1.
`of {[pitavastatin calctum] salt wherein
`A) polymorph A exhibits a characteristic X-ray powder
`diffraction pattern with characteristic peaks expressed in 20
`at 5.0 (s), 6.8 (s), 9.1 (s), 10.0 (w), 10.5 (m), 11.0 (m), 13.3
`(vw), 13.7 (s), 14.0 (w), 14.7 Gw), 15.9 (ww), 16.9 (w), 17.1
`
`5 The other polymorphic forms and the amorphous form ofpitavastatin calcium claimed in the ‘993 patent are
`irrelevant to this action, and are not discussed further.
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 10 of 98
`
`(vw), 18.4 (m), 19.1 (w), 20.8 (vs), 21.1 (m), 21.6 (m), 22.9
`(m), 23.7 (m), 24.2 (s), 25.2 (w), 27.1 (mn), 29.6 (vw), 30.2
`(w), 34.0 (w);
`.
`... wherein, for each of said polymorphs, (vs) stands for very
`strong intensity; (s) stands for strong intensity; (m) stands for
`medium.intensity; (w) stands for weak intensity; (vw) stands
`for very weakintensity.
`
`24. Acrystalline polymorph A of [pitavastatin calciuin] salt, which
`exhibits a characteristic X-ray powderdiffraction pattern with
`characteristic peaks expressed in 26 at 5.0 (s), 6.8 (s), 9.1 (s), 10.0 (w),
`10.5 (m), 11.0 (m), 13.3 (vw), 13.7 (s), 14.0 (w), 14.7 (w), 15.9 (vw),
`16.9 (w), 17.1 (vw), 18.4 (m), 19.1 (w), 20.8 (vs), 21.1 (im), 21.6 (m),
`22.9 (m), 23.7 (m), 24.2 (s), 25.2 (w), 27.1 (m), 29.6 (vw), 30.2 (w), and
`34.0 (w), wherein (vs) stands for very strong intensity; (s) stands for
`strong intensity; (m) stands for medium intensity; (w) stands for weak
`intensity; and (vw) stands for very weak intensity.
`
`22. Claims 23 and 25 are directed to, inter alia, Form A having “an X-ray powderdiffraction
`
`pattern substantially as depicted in FIG. 1”ofthe ‘993 patent. Relevant parts of claims 23 and
`
`25, and Figure 1, are set forth and reproduced below:
`
`Acerystalline polymorph A... of [pitavastatin calcium] salt of.
`23.
`claim 1, wherein polymorph A has an X-ray powder diffraction pattern
`substantially as depicted in FIG. 1...
`
`A crystalline polymorph A of[pitavastatin calcium] sait, having
`25.
`an X-ray powderdiffraction substantially as depicted in FIG.1.
`
`10
`
`

`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 11 of 98
`
` 78£66'4S9'9SA
`
`yusyeT“S'1
`
`e102‘S147G
`Gyobas
`
`23. Claim 22 states:
`22.
`A pharmaceutical composition comprising an effective amount
`ofthe crystalline polymorph or amorphous form according |to claim 1,
`and a pharmaceutically acceptable carrier.
`
`24, The specification of the ‘993 patent provides:
`
`Powder X-ray diffraction is performed on a Philips 1710 powder X-ray
`diffractometer using CuK (a1) radiation (1.54060 A); 26 angles are recorded
`with an experimental error of+/- 0.1-0.2°. A discussion ofthe theory of X~
`ray powder diffraction patterns can be found in “X-ray diffraction
`procedures” by H.P. Klug and L-E. Alexander, J. Wiley, New York (1974).
`
`(id. at 5:61-67 (citing PTX-1011 (Harold P. Klug & Leroy E. Alexander, X-ray Diffraction
`
`Proceduresfor Polycrystalline and Amorphous Materials (2d ed. 1974))).
`
`25. Example |. of the ‘993 patent details preparation of Form A. It instructs:
`
`EXAMPLE1
`
`Preparation of Form A
`
`4.15 gr of 3R,58)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-
`dihydroxy-6(E)-heptenoic acid tert-butyl ester (Pitavastatin tert-butyl
`ester) was suspended in 52 mi of a mixtureof methyltert-butyl ether and
`methanol (10:3). To this mixture were added 2.17 ml of a 4M aqueous
`solution of NaOH,and the resulting yellowish solution wasstirred for 2.5
`
`1]
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`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 12 of 98
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`hours at 50° C. The reaction mixture was cooled to room temperature
`followed bythe addition of 50 ml water and stirring for an additional hour.
`The aqueous phase was separated and once extracted with 20 ml ofmethyl -
`tert-butyl ether. To this aqueous solution were added a solution of 0.58 gr
`CaCl2 in 80 ml of water over a period of 1 hour. The resulting suspension
`was stirred for about 16 hours at room temperature. The suspension was
`filtered and the obtained solid was dried at 40°C and 50 mbar for about 16
`hours. The obtained product is crystal Form A which is characterized by
`an X-ray powderdiffraction pattern as shown in FIG. 1, Further
`characterization of the obtained Form A by thermogravimetry coupled
`with FT-IR spectroscopy revealed a water content of about 10%.
`Differential scanning calorimetry revealed a melting point of 95° C.
`
`(id. at 8:32~53).
`
`Nz
`
`The Instant Dispute
`26. Plaintiffs assert that Defendants* proposed ANDA products contain Form A, as claimed
`
`by the ‘993 patent; and would infringe claims 1, 22, 23, 24, and 25 of the ‘993 patent (together,
`
`the “Asserted Claims”).
`
`27. Amneal stipulates that the active pharmaceutical ingredient (“API”) in its proposed
`ANDAproductis Form A ofthe ‘993 patent, and would directly infringe the Asserted Claims.
`
`(PTX-1324 at ]). Amneal also stipulates thatit will not change the polymorphic form ofits
`
`ANDAproduct from Form A.
`
`(Id. at 2)
`
`28. Apotex contends that the APIin its proposed ANDA product does not meet the ‘993
`
`patent claim limitations and does notinfringe the ‘993 patent.
`
`29. Defendants contend that the ‘993 patent is invalid for (1) inherentanticipation, under 35
`
`U.S.C. § 102(b); and/or (2) obviousness, under 35 U.S.C. § 103(a).
`
`12
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`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 13 of 98
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`VI.
`
`Legal Standards®
`
`a. Presumption of Patent Validity
`30. Patents are presumed valid, and each patent claim is “presumed valid independently of
`the validity of other claims.” (35 U.S.C. § 282).
`|
`
`b. Affirmative Defense of Patent Invalidity
`
`31. A defendant “in any action involving the validity.. . of a patent” may plead, as an
`
`affirmative defense, that the asserted patent is invalid. (35 U.S.C. § 282). Because patent
`
`validity is presumed, a defendant asserting this defense bears the burden of proving invalidity by
`
`clear and convincing evidence.
`
`(See id.; Microsoft Corp. v. i4i Lid. P’ship, 564 U.S. 91, 95
`
`(2011).
`32. Patent examiners are owed deference and are “presumed to have considered”prior art
`
`referenceslisted on the face of a patent. (Shire, LDC v. Amneal Pharm., LLC, 302 F.3d 1301,
`
`1307 (Fed. Cir. 2015)). Infringement defendantsthus ““have the added burden of overcoming
`
`the deferencethat is due to a qualified government agency presumed to have properly doneits
`
`job, which includes one or more examiners who are assumed to have some expertise in
`
`interpreting the references and to be familiar from their work with the level of skill in the art and
`whose duty it isto issue only valid patents.’ (id. (quoting PowerOasis, Inc. v. T-Mobile USA,
`
`Inc., 522 F.3d 1299, 1304 (Fed. Cir. 2008))).
`33. “(T]he issue of validity does not warrantfindings of whether the examiner‘really did
`understand what he wasruling,’” and “[i]nteospection and speculation into the examiner’s
`understanding of the prior art or the completeness or correctness of the examination process is
`
`
`
`6 The Leahy-Smith America Invents Act (“AIA”), Pub L. No, 112-29, 125 Stat. 284, was signed into law on
`September 16, 2011. Because the earliest priority date to which the ‘993 patent claims entitlement is February 12,
`2003, the ‘993 patent is subject to pre-AIA statutes,
`
`43
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`

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`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 14 of 98
`
`not part ofthe objective review ofpatentability.” (Norian Corp. v. Stryker Corp.,363 F.3d 1321,
`
`1329 (Fed. Cir. 2004) (quoting Trial Tr. at 790).
`
`i.
`Anticipation G5 U.S.C. § 102)
`34. To be patentable, the invention must be novel; inventions lacking novelty are invalid.
`
`(35 U.S.C. § 102).
`
`35. An invention is unpatentable as being anticipated ifit “was patented or described in a
`
`printed publication inthis or a foreign country or in public use or on sale in this country, more
`
`than one year prior to the date of application for patent in the United States.” (Ud. § 102(b)).
`36. “Invalidity based on lack ofnovelty (often called ‘anticipation’) requires that the same
`invention, including each element andlimitation ofthe claims, was known or used by others
`before it was invented by the patentee.” (Hoover Grp., Inc, v. Custom Metalcrafi, Inc., 66 F.3d
`299, 302 (Fed. Cir. 1995)).
`
`37. Accordingly, patents are invalid as anticipated when “a single prior art reference []
`
`expressly or inherently disclose[s] each claim limitation.” (Finisar Corp. v. DirecTV Grp., Inc.,
`
`523 F.3d 1323, 1334 (Fed. Cir. 2008)).’ “{I]nvalidity by anticipation requires that the four
`
`corners of a single, prior art document describe every elementofthe claimed invention,either
`
`expresslyor inherently, such that a person of ordinaryskill in the art could practice the invention
`
`without undue experimentation.” (Advanced DisplaySys., Inc, v. Kent State Univ., 212 F.3d
`
`1272, 1282 (Fed. Cir. 2000)).
`
`38. “To show inherent anticipation, a defendant must demonstrate clearly and convincingly
`
`that a claimlimitation not disclosed in the anticipating reference will always be present when
`
`the priorart is practiced as taught in that reference.” (In re: OxyContin, 2015 WL 11217239,at
`
`Defendantdo not assert express anticipation of the “993 patent.
`
`14
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`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 15 of 98
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`*6). “[When a claim limitation is not explicitly set forth in a reference, evidence must make
`clear that the missing descriptive matter is necessarily present in the thing described in the
`reference, and that it would be so recognized by personsofordinary skill. It is not sufficient ifa
`material element or limitation is ‘merely probably or possibly’ present in the prior art.” (dn re
`Omeprazole PatentLitig., 483 F.3d 1364, 1378 (Fed. Cir. 2007) (quotations and citations:
`
`omitted)). “Inherency {] maynot be established by probabilities or possibilities. The mere fact
`
`that a certain thing may result from a given set of circumstancesis not sufficient.” (Cont 1 Can
`
`Co. USA v. Monsanto Co., 948 F.2d 1264, 1269 (Fed. Cir. 1991) (quotations and citations
`
`omitted) (emphasis in original)). Rather, the claimed invention must “necessarily and inevitably
`
`form{] from”the alleged anticipatory reference. (Schering Corp. v. Geneva Pharm., 339 F.3d
`
`1373, 1378 (Fed. Cir. 2003)).
`
`39. Thus, “if the teachings of the prior art can be practiced in a way that yields a product
`
`lacking the allegedly inherent property, the prior art in question does not inherently anticipate.”
`
`(in re Depomed Patent Litig., No. 13-4507 (CCC-MF), 2016 WL 7163647, at *26 (D.N.J. Sept.
`30, 2016)). Specifically, even where practice of an example taught by a prior art reference
`
`sometimes results in a patented polymorphic form, the prior art does not inherently anticipate if
`its teachings can also be practiced in a way that produces a different form. (Glaxco Inc.v.
`|
`
`Novopharm Ltd., 52 F.3d 1043, 1047-48 (Fed. Cir. 1995) (affirming district court’s rejection of
`
`anticipation defense where district court found that practice of prior art example “could yield
`
`crystals of either [the clatmed or a different] polymorph”)).
`
`40. The finding of anticipation is a question of fact. (Amkor Tech., Inc. v. Int'l Trade
`
`Comm ’n, 692 F.3d 1250, 1254 (Fed. Cir. 2012)).
`
`15
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`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 16 of 98
`
`ii,
`Obviousness (35 U.S.C. § 103)
`41. An invention is invalid as obvious “if the differences between the subject matter sought
`to be patented and the prior art are such that the subject matter as a whole would have been
`obvious at the time the mvention was madeto a person having ordinary skill in the art to which
`
`said subject matter pertains.” (35 U.S.C. § 103¢a)).
`
`42. In contrast to the anticipation inquiry, obviousness is determined by assessing “the
`
`.
`combined teachings of the prior art, taken as a whole.” (dn re Napier, 55 F.3d 610, 613 (Fed.
`Cir. 1995)). For purposes of obviousness, one skilled in the art is “presumed to know allofthe .
`
`teachings of the prior art in the field of the invention at the time of the patent’s priority date.”
`(In re: OxyContin, 2015 WL 11217239, at *7).
`43. A party asserting obviousness “must demonstrate by clear and convincing evidence that
`
`a skilled artisan would have been motivated to combine the teaching ofthe priorart references
`to achieve the claimed invention,and that the skilled artisan would have had a reasonable
`expectation of success in doing so.” (OSRAM Sylvania, Inc. v, Am. Induction Techs., inc., 701
`
`F.3d 698, 706 (Fed. Cir. 2012) (quotations and citation omitted)).
`
`44, “Obviousness is a question of law based on underlying factual determinations.” (Amkor,
`692 F.3d at 1254). These factual determinations include: “(1) the scope and contentofthe prior
`
`art, (2) the differences between the claimed invention andthe priorart, (3) thelevel of ordinary
`
`skill in the art, and (4) objective indicia of nonobviousness,” that is, secondary considerations.
`
`(Pregis Corp. v. Kappos, 700 F.3d 1348, 1354 (Fed. Cir. 2012); see Graham v. John Deere Co.
`
`ofKansas City, 383 U.S. 1, 17-18 (1966)).
`
`45, The first three factors comprise the prima facie case. (Winner Int'l Royalty Corp.v.
`
`Wang, 202 F.3d 1340, 1350 (Fed. Cir. 2000)). “The Supreme Court has directed courts to reject
`
`16
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`

`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 17 of 98
`
`a ‘rigid approach’ with respect to the prima face case in favor of ‘an expansiveand flexible
`
`approach,’ using common sense when assessing whether an invention would have been obvious
`to a person ofordinary skill in the art.” (Mitsubishi Chem. Corp. v. BarrLabs., Inc.,'718 F.
`
`Supp. 2d 382, 425 (S.D.N.Y. 2010) (quoting KSR Int 1 Co. v. Teleflex, inc., 550 U.S. 398, 415-
`16(2007) (providing extensive analysis ofobviousness inquiry)); see OSRAM, 701 F.3d at 707).
`
`46. Once a patent challenger establishes a prima facie case of obviousness by clear and
`convincing evidence, the burden shifts to the patentee to provide rebuttal evidence of
`
`nonobviousness. (WMS Gaming Inc. v. Int'l Game Tech., 184 F.3d 1339, 1359 (Fed. Cir.
`
`1999). “The party asserting invalidity, however, always retains the burden of persuasion on the
`
`issue of obviousness untif a final judgmentis rendered.” (Afitsubishi, 718 F. Supp. 2d at 427—
`
`28).
`
`47. Secondary considerations of nonobviousness may include “copying, long felt but
`
`unsolved need, failure of others, commercial success, unexpected results created by the claimed
`
`invention, unexpected properties of the claimed invention, licenses showing industry respect for
`
`the invention, and skepticism of skilled artisans before the invention.” (Power Integrations,
`
`Ine. v. Fairchild Semiconductor Int’l, Inc., 711 F.3d 1348, 1368 (Fed. Cir. 2013)).
`48. These secondary considerations help courts guard against impermissible hindsight bias,
`
`“which often overlooks that the genius of invention is often a combination of known elements
`
`whichin hindsight seems preordained.” (Power Jntegrations, 711 F.3d at 1368 (quotations and
`
`citations omitted); see also Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc.,