Case 1:14—Cv—02758—PAC Document 168 Filed 09/19/17 Page 1 Of 98
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRTCT OF NEW YORK
`
`Kowa Company, Ltd., et al.,
`
`Plaintiffs,
`
`Amneal Pharmaceuticals, LLC
`
`Defendant.
`
`Kowa Company, Ltd., et al.,
`
`
`
`
`
`
`LED: 9/19/2017
`...M.,.W.W.-..mw~wmw”haw-CM...”
`
`
`
`Civil Action NO. 14~CV~2758 (PAC)
`
`Civil Action No. 14-CV-7934 (PAC)
`
`FINDINGS OF FACT AND
`
`CONCLUSIONS OF LAW
`
`
`
`v.
`
`Apotex, Inc., Ct 211.,
`’
`
`Plaintiffs,
`
`Defendants.
`
`
`
`TABLE OF ABBREVIATIONS
`
`TABLE OF CONTENTS
`
`INTRODUCTION AND LEGAL STANDARDS
`
`1.
`
`The Hatch—Waxman Act and ANDA Filings .......................................................................... 5
`
`H. The Parties .............................................................................................................................. 6
`
`HI.
`
`IV.
`
`Livalo® ................................................................................................................................. 7
`
`The ‘993 Patent .................................................................................................................... 8
`
`V. The Instant Dispute ............................................................................................................... '12
`
`VI.
`
`Legal Standards .................................................................................................................. 13
`
`a.
`
`Presumption Of Patent Validity .......................................................................................... 13
`
`b. Affirmative Defense of Patent Invalidity ........................................................................... l3
`
`Gilead 2009
`
`I-MAK v. Gilead
`
`|PR2018—00126
`
`

`

`Case 1:14—cv—02758—PAC Document 168 Filed 09/19/17 Page 2 of 98
`
`i. Anticipation (35 U.S.C. § 102) .................................................................. r ................... 14
`
`ii.
`
`Obviousness (35 [ISO § 103) ........................................................... 16
`
`c.
`
`Infringement............................................................................................................i............ 18
`i. Claim Construction ........................................................................................................ l9 '
`
`VII. Crystals and Polymorphs ................................................................................................... 20
`
`VIII.
`
`X—Ray Powder Diffraction and Characterization, .......................................................... 23
`
`IX.
`
`Jurisdiction..............L .......................................................................................................... 28
`
`X.
`
`Person of Ordinary Skill in the Art ....................................................................................... 28
`
`XI.
`
`Validity of the ‘993 Patent ................................................................................................. 29
`
`a. Anticipation (35 USC. § 102) ....................-..................................................V ....................... 2 9
`
`i.
`
`E]? ‘406 ........................................................._.................................................................. 3 1
`
`ii.
`
`iii.
`
`iv.
`
`The ‘993 Patent Prosecution History .............................................. ». ........................... 31
`
`Defendants’ Inherency Arguments ............................................................................. 37
`
`Conclusion Regarding Inherent Anticipation ............................................................. 40
`
`............................ 48
`b. Obviousness (35 use. § 1031;.....
`i. Levelof Ordinary Skill in
`6 Art.................................................................................. 50
`
`Scope and Content of the Prior Art and Differences Between Claimed Subject Matter
`ii.
`and the Prior Art.................................................................................................................... 50
`
`iii. Whether Obtaining Form A Would Have Been Obi/ions to a POSA in 2003............ 52
`
`iv.
`
`v.
`
`Objective Lndicia of Nonobviousness (Secondary Considerations) ........................... 59
`
`Conclusion Regarding Obviousness ................................. ; ......................................... 75
`
`0.
`
`Conclusion Regarding Validity............................................................................................. 75
`
`XII.
`
`Infringement of the ‘993 Patent ......................................................................................... 76
`
`a.
`
`Step One: Construing the Asserted Claims ........................................................................ 77
`
`i. Claims 1 and 24: “exhibits a characteristic x—ray diffraction pattern with characteristic
`
`peaks expressed in 29 at .
`
`. .” ............... -. ................................................................................ 77
`
`ii.
`
`Claims 23 and 25: “having an X—ray powder diffraction pattern substantially as
`
`depicted in Fig. 1 .
`
`.” ............................................................................ 80
`
`b.
`
`Step Two: Comparison ot‘Asserted Claims to Apotex’s Proposed ANDA Product ......... 81
`
`i. Apotex’s Proposed ANDA Product ............................................................................... 82
`ii.‘
`Dr. Kaduk’s Analysis and Conclusions....................................................................... 85
`
`iii.
`
`Dr. Sacchetti’s Analysis and Conclusions ...........'....................................................... 89
`
`2
`
`

`

`Case 1:14~cv—02758-PAC Document 168 Filed 09/19/17 Page 3 of 98
`
`iv;
`
`v.
`
`vi.
`
`Claims 1 and 24 ....................,...................................................................................... 91
`
`Claims 23 and25 ...................................................... 94
`
`Claim 22 .......>.............................................................................................................. 95
`
`0. Conclusion Regarding Infringement .................................................................................. 96
`
`CONCLUSION ~
`
`TABLE OF ABBREVIATIONS
`
`
`" ‘993 Patent
`us. Patent No. 8,557,993
`""
`
`FANDA
`Abbrevialed New Drug Application
`
`
`API
`Active pharmaceutical ingredient
`
`
`DMF
`Drug master file
`
`
`EPO
`European Patent Office
`
`
`EP ‘406
`European Patent Application No. EP 0 520 406Al
`
`
`FDA
`
`IDS
`
`US. Food and Drug Administration
`
`
`Information Disclosure Statement
`
`LAlZCL
`
`VVVVVVVV“liowa Company, Ltd.
`
`yyyyyyyyy-
`
`
`-AAAAAAAAAAAAAAAAAAAA
`
`
`
`a. US. Patent and Trademark Office
`U.S. Pharmacopeia
`
`
`Kowa Pharmaceuticals America, Inc.
`
`MSN Laboratories Pvt. Ltd.
`
`Nissan Chemical Industries, Ltd.
`4
`
`Third Party Observation
`
`USP
`
`XRPD or PXRDPPPPPPPPJ X—rayPOWder diffiaCfion
`
`

`

`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«W'axman patent infringement litigation initiated by Plaintiffs Kowa
`
`Company, Ltd, Kowa Pharmaceuticals Ainerica, 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”).1 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 contend that the ‘993
`
`patent is invalid as (l) anticipated based on prior art, under 35 U.S.C. § 102(b); and/or (2) obvious
`
`in view of prior art, under 35 U.S.C. § 103. Only Apotex asserts non~infringement; Amneal
`
`concedes infringement.
`
`The Court held a ten—day bench trial frorn January 17 through January 30, 2017, with
`
`closing arguments on February 3, 2017. Each of the parties submitted extensive post—trial ‘
`
`briefing on the ‘993 parent’s validity and infringement. Alter considering the documentary
`
`evidence and testimony, the Court makes the following findings of fact and conclusions of law
`
`pursuant to Fed. R. Civ. P. 52(a). As set forth below, the Court detennines that the ‘993 patent is
`
`valid; and that Apotex’s proposed ANDA product would infringe the ‘993 patent.
`
`1 Plaintiffs commenced this litigation against eight. generic drug manufacturer defendants. Defendants asserted
`defenses of invalidity and non—infringement. Four defendants settled before commencement of the ten-day bench
`trial. The fitth defendant settled mid-trial; and the sixth settled post~trial Only Amneal and Apotex remain. On
`April ll, 2017. the Court issued its Findings of Fact and Conclusions of Law regarding the other patent at issue at
`trial, US. Patent No, 5,856,336, finding it valid.
`(Kowa Co., Ltd. v. Amneal Phamz., LLC, No. l4—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
`
`1.
`
`The Hatch-Waxman Act and'ANDA Filings2
`1. The Hatch—Waxman Act, titled the Drug Price Competition and Patent Tenn Restoration
`
`Act of 1984, Pub. L. No. 98-417, permits pharmaceutical companies to seek United States Food
`
`and Drug Administration (FDA) approval for a generic drug based on an already-approved
`
`branded drug by filing an ANDA. (See 21 U.S.C. § 3SSQ)(Z)(A), (8)03». 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
`
`must file 3 “Paragraph IV” certification, establishing bioequivalence of the proposed generic
`
`version with the approved branded version of the drug. (See 21 U.S.C. § 355(jX2)(A)(vii)(IV);
`
`21 CPR. § 314.94(a)(9)). The certification must also state and explain either that the generic
`
`product will not infringe the branded manufacturer’s patent, or that the patent is invalid. (See 21
`
`U.S.C. § 3550)(2)(B)(iv)(11)).
`
`3. “An ANDA—IV certification itself constitutes an act of infringement, triggering the
`
`branded manufacturer’s right to sue.” (Ark. Carpenters Health & Welfare Fund v. Bayer A G,
`
`604 F.3d 98, 101 (2d Cir. 2010), cert. denied, 131 s. Ct. 1606 (2011) (citing 35 U.s.c. §
`
`271(c)(2)(A)).
`
`If, litigation is initiated, the generic’s entry to market is automatically stayed. (21
`
`U.S.C.. § 3550)(5)(B)(iii)). “[Tlhis structure allows the parties to try the dueling issues of patent
`
`infringement and patent invalidity simultaneously.” (In re: OxyContin Antitrust Litig, No. 13-
`
`CV—3372 (SHS), 2015 WL 1121-7239, at *5 (S.D.N.Y. Apr. 8, 2015)).
`
`2 For additional background on the policy goals of the HatchWaxman Act, see this Court’s April I l, 2017 Findings
`of Fact and Conclusions of Law regarding the other patent at issue at trial, US. Patent No. 5,856,336. (Kowa Co.,
`Ltd. v. Amneal Phann., LLC, No. 14-CV—2758 (PAC) (S.D.N.Y. Apr. 11, 2017) 319—40).
`
`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 oflinsiness in Aichi, Japan. (Compl. ‘ll 2). PlaintiffKowa
`Pharmaceuticals America, Inc. (“KPA”) is a wholly-oimed subsidiary ofKCL organized under
`
`the laws of Delaware, with its corporate headquarters and principal place of business in
`
`Montgomery, Alabama.
`
`([61). Plaintiff Nissan Chemical Industries, Ltd. (“NCY’ or “Nissan”) is
`
`a Japanese corporation with its corporate headquarters and principal place ofbusiness in Tokyo, /
`
`Japan. (Id. ‘fi 3). Plaintiffs are manufacturers, researchers, developers, and marketers of the
`
`cholesterol—lowering drug Livalo®. (Id. 1i 4).
`
`5. Defendant Amneal is incorporated in Delaware, with a place of business in Bridgewater,
`
`New Jersey. (Amneal Answer 11 5). Amneal filed ANDA No. 206961 seeking FDA approval to
`
`market 1 mg, 2 mg, and 4 mg pitavastatin calcium tablets. (Id. 1] 20).
`
`6. Defendant Apotex, Inc. is organized in and exists under the laws of Canada, with a
`
`principal place of business in Toronto, Ontario. (Apotex AnSWer 1} 5). Defendant Apotex Corp.
`
`is incorporated in and exists under the laws of Delaware, with a place of business in Weston,
`
`Florida. (Id. 1i 6). Apotex Corp. sells and markets Apotex,1nc.’s products in the United States.
`(Id) Apotex Corp. is Apotex inefs agent for purposes ofmaking regulatory submissions,
`
`including its ANDA No. 206068 filing, seeking FDA approval to market 1 mg, 2 mg, and 4 mg
`
`pitavastatin calcium tablets. (Id. 1H} 6, 20). Apotex’s ANDA filing contains a Paragraph IV .
`
`certification respecting the ‘993 patent. (Id. 11‘ 22).
`
`

`

`Case 1:14-CV-02758—PAC Document 168 Filed 09/19/17 Page 7 Of 98
`
`111.
`
`Livalo®
`
`7. At trial, Dr. Craig Sponseller, KPA’s Chief Medical Officer, provided an initial
`
`explanation of the history and workings of Livalo® pitavastatin. (See generally Tr. 67—136). A
`
`brief summary of relevant and uncentested facts is recited here.
`
`8. Statins are medications that address and control abnormal increases in blood cholesterol by
`
`inhibiting the Way in which the liver makes cholesterol, (Tr. 701841210). All 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. 7125—17).
`
`9. Patients have varying degrees of statin tolerance (or intolerance). (Tr. 713254413).
`
`Approximately 10~15% of patients 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 more specifically, as reflected on
`
`its label, hyperlipidemia or mixed dyslipidemia. (Tr. 7725—11; FIX-1098 (Lit/ale® Label
`(Revised: November 2016)) at KNbO3466196). It does so by reducing low density protein
`
`cholesterol (“LDL~C”), total cholesterol, triglycerides, and apolipoprotein B; and/or increasing
`
`(high density lipoprotein cholesterol (“BBL-C”). (Tr. Tr. 7715—1 1; PTX-1098 (Livalo® Label) at
`
`KN003466196).
`
`l 1. Approximately 75% of all metabolic drugs are metabolized through the “cytochrome
`P450” pathway (the “CYP450” or “CYP” pathway) in the liver. (Tr. 74: Ill-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
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`12. There. are currently seven available statins on the market; at the time Livalo® launched in
`
`the US. in mid—2010, there were six available statins with which Livalo® competed.3 (Tr.
`
`7021540).
`
`IV.
`
`The ‘993 Patent
`
`13. The ‘993 patent, “Crystalline Forms of Pitavastatin Calcium,” is assigned to NCI. (PTX-
`
`1063). KCL is NCI’s licensee for the ‘993 patent, and KPA holds a license from KCL for the
`
`‘993 patent. (Amneal Comp]. ll 15; Apotex Compl. l] 15). KPA sells the pitavastatin drug
`
`product under the trade name Livalo® in the United States; KCL manufactures the Livalo®
`
`products as sold by KPA. (Arrineal Compl. m 16—17; Apotex Compl. ‘lfil 16—17).
`
`14. The ‘993 patent issued on October 15, 2013, from US. Patent Application No.
`
`ifs/664,498 (the ““498 Application”), filed October 31, 2012. (FIX-1063 (“993 patent); PTX-
`
`0172 (‘498 Application (’993 patent file history)». The ‘498 Application is a continuation of
`
`US. Patent Application No. 10/544,752 (the “752 Application). (PTX-1337 and DIX—1359).4
`
`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 i993 patent states:
`
`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 by the
`chemical name: (3R,5S)m7—[2—cyclopropyl-4—(4-fluorophenyl)quinolinr3—yl]-3,5-
`dihydroxy—6(E)—heptenoic acid hemicalcium salt.
`
`(Id. at 1:17—46),
`
`3 Livalo® was approved by Japanese regulators and launched in 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 FIX—0480; PTX—0482).
`4 Both Plaintiffs and Defendants submitted the ‘752 Application and file history. (See PTX-1337; DTXv1359). Due
`to a copying error, DTX- 1359 was missing some pages; but the relevant testimony did not involve any such pages.
`(See Tr. 166129—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. (Id. at 1:43~50).
`
`18. Claims 1, 22, 23, 24, and 25 of the ‘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 amount of the form, and a phannaceutically
`acceptable carrier. (Id. at 10:50—»1 1 :37, 13:7941)’. Each claimed form includes a recitation of a'
`
`characteristic X—ray powder diffraction pattern having specific characteristic peaks (claims 1 and
`
`24) or a diffraction pattern substantially as depicted in specified Figures (claims‘23 and 25).
`
`(1d)
`
`19. Crystalline polymorph A of pitavastatin calcium (“Form A” or “Polymorph Form A”) is
`
`the subject of this action.5
`
`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% of water.” (Id.’at 6: 13—14).
`
`I
`
`21. Claims 1 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 intensities] .” The relevant parts of claims 1 and 24 are set forth below:
`
`I.
`
`A crystalline polymorph A, B, C, D, E, F, or the amorphous form,
`
`of [pitavastatin calcium] salt wherein
`A) polymorph A exhibits a characteristic X-ray powder
`diffraction pattern with characteristic peaks expressed in 29
`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
`
`5 The other polymorphic forms and the amorphous form of pitavastatin 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 (m), 29.6 (vw), 30.2
`(w), 34.0 (w);
`’
`.
`.
`. wherein, for each of said polymorphs, (vs) stands for very
`strong intensity; (3) stands for strong intensity; (In) stands for
`medium» intensity; (w) stands for weak intensity; (vw) stands
`for very weak-intensity.
`
`24. A crystalline polymorph A of [pitavastatin calcium] salt, which
`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 (in), 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 (in), 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 (In), 29.6 (vw), 30.2 (w), and
`34.0 (w), wherein (vs) stands for very strong intensity; (5) stands for
`strong intensity; (111) 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 powder diffraction
`
`pattern substantially as depicted in FIG. 1” of the ‘993 patent. Relevant parts of claims 23 and
`
`'25, and Figure 1, are set forth and reproduced below:
`
`. of [pitavastatin calcium] salt of ,
`A crystalline polymorph A. .
`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] salt, having
`25.
`an X—ray powder diffraction substantially as depicted in FIG. 1.
`
`10
`
`

`

`Case 1:14—Cv—02758-PAC Document 168 Filed 09/19/17 Page 11 of 98
`
`1500
`
`125a
`
`was
`mm
`come no
`
`~ — ~
`
`
`
`s:
`F”
`:5
`I:
`2
`
`8
`2;
`15‘;
`
`6:»imus
`
`za£65255?so
`
`23. Claim 22 states:
`
`A pharmaceutical composition comprising an effective amount
`22.
`of the crystalline polymorph or amorphous form aCCOrding to claim 1,
`and a phamiaceutically 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 (on) radiation (1.54060 A); 26 angles are recorded
`with an experimental error of-‘r/— 0.1—0.2". A discussion of the theory of X~
`ray powder dimaction patterns can be found in “X—ray diffraction
`procedures” by HP. Klug and LE. Alexander, I. Wiley, New York (1974).
`
`(Id, at 5:61—67 (citing PTX-lOll (Harold P. King & Leroy E. Alexander, X-ray Difii'actz‘on
`
`ProceduresfOr Polycrystalline and Amorphous Materials (2d ed, 19741))
`
`25. Example 1. of the ‘993 patent details preparation of Form A. It instructs:
`
`EXAMPLE 1
`
`Preparation of Form A
`
`4.15 gr of (3R,SS)~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 ml of a mixture‘of methyl tort-bury] 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 was stirred for 2.5
`
`ll
`
`

`

`Case 1:14—CV—02758—PAC Document 168 Filed 09/19/17 Page 12 Of 98
`
`hours at 50° C. The reaction mixture was cooled to room temperature
`
`followed by the 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
`
`CaClZ 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 powder diffraction pattern as shown in FIG. 1. Further
`characterization of the obtained Form A by thennogravimetry coupled
`
`with FToIR spectroscopy revealed a water content of about 10%.
`Differential scanning calorimetry revealed a melting point of 950 C.
`
`(Id. at 8:32~53).
`
`’ V.
`
`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. Animal stipulates that the active pharmaceutical ingredient (“API”) in its proposed
`
`ANDA product is Form A of the ‘993 patent, and would dikctly infringe the Assorted Claims.
`
`(FIX-1324 at l). Amneal also stipulates that it will not change the polymorphic form of its
`
`ANDA product fiom Form A.
`
`(Id. at 2)
`
`28. Apotex contends that the API in its proposed ANDA product does not meet the “993
`
`patent claim limitations and does not infringe the ‘993 patent.
`
`29. Defendants contend that the “993 patent is invalid for (_ l) inherent anticipation, under 35
`
`U.S.C. § 102(b); and/or (2) obviousness, under 35 U.S.C. § 103(a).
`
`12
`
`

`

`Case 1:14-cv-02758—PAC Document 168 Filed 09/19/17 Page 13 of 98
`
`VI.
`
`Legal Sttmdards6
`
`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
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`31. A defendant “in any action involving the validity .
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`.
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`. of a patent” may plead, as an
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`affirmative defense, that the asserted patent is invalid. (35 U.S.C. § 282). Because patent
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`validity is presumed, a defendant asserting this defense bears the burden of proving invalidity by
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`clear and convincing evidence.
`
`(See id; Microsoft Corp. v. 1'42" Ltd. Pj’shz'p, 564 US. 91, 95
`
`’ (2011)).
`
`32. Patent examiners are owed deference and are “presumed to have considered” prior art
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`references listed on the face of a patent. (Shire, LLC v. Amneal Pharm, LLC, 802 RM 1301,
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`1307 (Fed. Cir. 2015)). Infringement defendants thus “‘haVe the added burden of overcoming
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`the deference that is due to a qualified government agency presumed to have properly done its
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`job, which includes one or more examiners who are assumed to have some expertise in
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`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 PowerOasz's, Inc. v. T—Mobile USA,
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`Inc, 522 F.3d 1299, 1304 (Fed. Cir. 2008»).
`
`33. “(The issue of validity does not warrant findings of whether the examiner “really did
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`understand what he was ruling,” and “[i]ntrospection and speculation into the examiner’s
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`understanding of the prior art or the completeness or correctness of the examination process is
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`
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`6 The Leahy-Smith America invents Act (“MA”), 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.
`
`13
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`

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`Case 1:14—cv—02758-PAC Document 168 Filed 09/19/17 Page 14 of 98
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`not part ofthe objective review of patentability.” (Norian Corp. v. Stryker Corp.,'363 F.3d 1321,
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`1329 (Fed. Cir. 2004) (quoting Trial Tr. at 790)).
`
`i.
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`Anticipation (35»U.S.C. § 102)
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`34. To be patentable, the invention must be novel; invantions lacking novelty are invalid.
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`'
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`(35 U.S.C. § 102).
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`35. An invention is unpatentable as being anticipated ifit “was patented or described in a
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`printed publication in this or a foreign country or in public use or on sale in this country, more
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`than one year prior to the date of application for patent in the United States.” (Id. § 102(b)).
`36. “Invalidity based on lack ofnovelty (often called ‘anticipation’) requires that the same
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`invention, including each element and limitation of the 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 []
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`expressly or inherently disclose[s] each claim limitation.” (Finisar Corp. v. DirecTV 6177., Inc,
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`523 F.3d 1323, 1334 (Fed. Cir. 2008)).7 “[I]nvalidity by anticipation requires that the four
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`corners of a single, prior art document describe every element of the claimed invention, either
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`expressly or inherently, such that a person of ordinary skill in the art could practice the invention
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`Without undue experimentation.” (Advanced Display Syn, Inc. v. Kent State Univ., 212 F.3d
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`1272, 1282 (Fed. Cir. 2000)).
`
`38. “To show inherent anticipation, a defendant must demonstrate clearly and convincingly
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`that a claim limitation not disclosed in the anticipating reference will always be present when
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`the prior art is practiced as taught in that reference.” (In re: OxyContz'n, 2015 WL 11217239, at
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`7 Defendant do not assert express anticipation of the ‘993 patent.
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`l4
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`

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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). “[W}hen 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 persons ofordinary skill. It is not sufficient if a
`material element or limitation is ‘merely probably or possibly’ present in the prior art.” (In re
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`Omepraz-ole Patent Litig, 483 F.3d 1364, 1378 (Fed. Cir. 2007) (quotations and citations
`
`omitted». “Inherency {] may not be established by probabilities or possibilities. The mere fact
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`that a certain thing may result from a given set of circumstances is not sufficient.” (Com ’1 Can
`
`Co. USA v. Monsanto Ca, 948 F.2d 1264, 1269 (Fed. Cir. 1991) (quotations and citations
`
`omitted) (emphasis in original». Rather, the claimed invention must “necessarily and inevitably
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`formfl from” the alleged anticipatory reference. (Schering Corp. v. Geneva Phat-m, 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 Ling, No. 13—4507 (CCC-MF), 2016 WL 7163647, at *26 (DJNJ. 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 (1065 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, 104748 (Fed. Cir. 1995) (affirming district court’s rejection of
`
`anticipation defense where district court found that practice of prior art example “could yield
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`crystals of either [the claimed or a different] polymorph”)).
`
`40. The finding of anticipation is a question of fact. (Amkor T(ac/3L, Inc. V. 1m ’2 Trade
`
`Comm ’n, 692 F.3d 1250, 1254 (Fed. Cir. 2012)).
`
`15.
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`

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`Case 1:14-Cv-02758—PAC Document 168 Filed 09/19/17 Page 16 of 98
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`11.
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`Ohviousness (35 U.S.C. § 103)
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`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 invention was made to a person having ordinary skill in the art to which
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`said subject matter pertains.” (35 11.5.0 § 103(3)).
`
`42. in contrast to the anticipation inquiry, obviousness is determined by assessing “the
`
`combined teachings of the prior art, taken as a whole.” (In re Napier, 55 F.3d 610, 613 (Fed.
`
`‘
`
`Cir. 1995)). For purposes of obviousness, one skilled in the art is “presumed to know all of the .
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`teachings of the prior art in the field of the invention at the time of the patent’s priority date.”
`
`(In re: OxyContz'n, 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 of the prior art 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 deterniinations include: “(1) the scope and content of the prior
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`art, (2) the differences between the claimed invention and the prior art, (3) the leVel of ordinary
`
`skill in the art, and (4) objective indicia of nonobviousness,” that is, secondary considerations.
`
`(Pregz's Corp. v. Kappos, 700 F.3d 1348, 1354 (Fed. Cir. 2012); see Graham 12. John Deere. Co.
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`QfKansas City, 383 U.S. 1, 17~18 (1966)).
`
`45. The first three factors comprise the prima tacie case. (Winner Int ’2 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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`

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`Case 1:14—cv—02758-PAC Document 168 Filed 09/19/17 Page 17 of 98
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`a ‘rigid approach’ with respect to the prime face casein favor of ‘an expansive and flexible
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`approach,’ using common sense when asseSSing whether an invention would have been obvious
`to a person of ordinary skill in the art.” (Mitsubishi Chem. Corp. v. Barr Labs, Inc, 718 F.
`
`Supp. 2d 382, 425 (S.D.N.Y. 2010) (quoting KSR Int’l Co. v. Teleflex, Inn, 550 US. 398, 415—~
`
`16(2007) (providing extensive analysis of obviousness inquiry)); see OSRM 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
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`nonobviousness. (WMS Gaming Inc. v. Int ’1 Game Tech, 184 F.3d 1339, 1359 (Fed. Cir.
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`1999). “The party asserting invalidity, however, always retains the burden of persuasion on the
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`issue of obviousness until a final judgment is 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, unexpecte