Case 1:14-cv-02758-PAC Document 179-1 Filed 02/11/19 Page 1 of 99
`Case 1:14-cv-02758—PAC Document 179-1 Filed 02/11/19 Page 1 of 99
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`EXHIBIT 1
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`EXHIBIT 1
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`Case 1:14-cv-02758-PAC Document 168 Filed 09/19/17 Page 1 of 98Case 1:14-cv-02758-PAC Document 179-1 Filed 02/11/19 Page 2 of 99
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`USDC SDNY
`DOCUMENT
`ELECTRONICALLY FILED
`DOC #:
`DATE FILED:
`
`9/19/2017
`
`Civil Action No. 14-CV-2758 (PAC)
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF NEW YORK
`
`Kowa Company, Ltd., et al.,
`
`Plaintiffs,
`
`v.
`
`Amneal Pharmaceuticals, LLC
`
`Defendant.
`
`Kowa Company, Ltd., et al.,
`
`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
`
`II. The Parties
`
`III.
`
`Livalo®
`
`IV. The '993 Patent
`
`V. The Instant Dispute
`
`VI.
`
`Legal Standards
`
`a. Presumption of Patent Validity
`
`b. Affirmative Defense of Patent Invalidity
`
`1
`
` 5
`
` 6
`
`7
`
`8
`
` 12
` 13
` 13
`
` 13
`
`

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`Case 1:14-cv-02758-PAC Document 179-1 Filed 02/11/19 Page 3 of 99
`
`2
`
`iii. Dr. Sacchetti's Analysis and Conclusions .................................................................. 89
` 14
`. Anticipation (35 U.S.C. § 102)
`Dr. Kaduk's Analysis and Conclusions ...................................................................... 85
`u.
` 16
`Obviousness (35 U.S.C. § 103)
`ii.
`I. Apotex's Proposed ANDA Product ............................................................................... 82
`18
`Infringement
`c.
`b. Step Two: Comparison of Asserted Claims to Apotex's Proposed ANDA Product.. ....... 81
`19
`i. Claim Construction
`depicted in Fig. 1 ... " ........................................................................................................... 80
`20
`VII. Crystals and Polymorphs
`Claims 23 and 25: "having an x-ray powder diffraction pattern substantially as
`ii.
`VIII. X-Ray Powder Diffraction and Characterization.
`23
`peaks expressed in 29 at ... " ................................................................................................ 77
`i. Claims 1 and 24: "exhibits a characteristic x-ray diffraction pattern with characteristic
`Jurisdiction
`28
`IX.
`
`28
`a. Step One: Construing the Asserted Claims ........................................................................ 77
`X. Person of Ordinary Skill in the Art
`
`Infringement of the '993 Patent ......................................................................................... 76
`XI. Validity of the '993 Patent
`
`XII.
`29
`
`c. Conclusion Regarding Validity ............................................................................................. 75
`a. Anticipation (35 U.S.C. § 102)
`29
`
`Conclusion Regarding Obviousness ................................. ; ......................................... 75
`i. EP '406
`
`v.
`31
`
`Objective Indicia ofNonobviousness (Secondary Considerations) ........................... 59
`The '993 Patent Prosecution History
`ii.
`
`1v.
`31
`
`iii. Defendants' Inherency Arguments
`m. Whether Obtaining Form A Would Have Been Obvious to a POSA in 2003 ............ 52
`37
`
`and the Prior Art .................................................................................................................... 50
`iv. Conclusion Regarding Inherent Anticipation
`40
`Scope and Content of the Prior Art and Differences Between Claimed Subject Matter
`ii.
`48
`b. Obviousness (35 U.S.C. § 103)
`i. Level of Ordinary Skill in fhe Art .................................................................................. 50
`Level of Ordinary Skill in e Art
`50
`b. Obviousness (35 U.S.C. § 103)1 ............................................................................................. 48
`ii.
`Scope and Content of the Prior Art and Differences Between Claimed Subject Matter
`Conclusion Regarding Inherent Anticipation ............................................................. 40
`iv.
`and the Prior Art
`50
`
`UL Defendants' Inherency Arguments ............................................................................. 37
`52
`iii. Whether Obtaining Form A Would Have Been Obvious to a POSA in 2003
`
`The '993 Patent Prosecution History .............................................. , ........................... 31
`iv. Objective Indicia of Nonobviousness (Secondary Considerations)
`
`ii.
`59
`
`75
`I. EP'406 ........................................................................................................................... 31
`Conclusion Regarding Obviousness
`v.
`
`a. Anticipation (35 U.S.C. § 102) ............................................................................................. 29
`75
`c. Conclusion Regarding Validity
`
`XI. Validity of the '993 Patent.. ............................................................................................... 29
`Infringement of the '993 Patent
`XII.
`76
`
`X. Person of Ordinary Skill in the Art ....................................................................................... 28
`77
`a. Step One: Construing the Asserted Claims
`
`IX.
`Jurisdiction ......................................................................................................................... 28
`i. Claims 1 and 24: "exhibits a characteristic x-ray diffraction pattern with characteristic
`77
`"
`peaks expressed in 20 at
`X-Ray Powder Diffraction and Characterization ........................................................... 23
`VIII.
`Claims 23 and 25: "having an x-ray powder diffraction pattern substantially as
`ii.
`VII. Crystals and Polymorphs ................................................................................................... 20
`80
`depicted in Fig, 1
`"
`i. Claim Construction ........................................................................................................ 19
`b. Step Two: Comparison of Asserted Claims to Apotex's Proposed ANDA Product
`81
`Infringement ....................................................................................................................... 18
`c.
`Apotex's Proposed ANDA Product
`82
`Obviousness (35 U.S.C. § 103) .................................................................................. 16
`11.
`ii. Dr. Kaduk's Analysis and Conclusions
`85
`1. Anticipation (35 U.S.C. § 102) ...................................................................................... 14
`89
`iii. Dr. Sacchetti's Analysis and Conclusions
`
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`2
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`Case 1:14-cv-02758-PAC Document 179-1 Filed 02/11/19 Page 4 of 99
`3
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`iv. Claims 1 and 24
`
`v,
`
`Claims 23 and 25
`
`vi. Claim 22
`
`c. Conclusion Regarding Infringement
`
`CONCLUSION
`
`91
`
`94
`
`95
`
`96
`
`X-ray powder diffraction
`
`XRPDorPXRD
`
`U.S. Pharmacopeia
`TABLE OF ABBREVIATIONS
`Third Party Observation
`
`U.S. Patent No. 8,557,993
`U.S. Patent and Trademark Office
`Abbreviated New Drug Application
`Nissan Chemical Industries, Ltd.
`Active pharmaceutical ingredient
`MSN Laboratories Pvt. Ltd.
`
`Drug master file
`Kowa Pharmaceuticals America, Inc.
`European Patent Office
`
`Kowa Company, Ltd.
`European Patent Application No. EP 0 520 406A1
`Information Disclosure Statement
`U.S. Food and Drug Administration
`U.S. Food and Drug Administration
`Information Disclosure Statement
`European Patent Application No. EP 0 520 406Al
`Kowa Company, Ltd.
`
`European Patent Office
`Kowa Pharmaceuticals America, Inc.
`Drug master file
`
`MSN Laboratories Pvt. Ltd.
`Active pharmaceutical ingredient
`Nissan Chemical Industries, Ltd.
`Abbreviated New Drug Application
`U.S. Patent and Trademark Office
`U.S. Patent No. 8,557,993
`
`Third Party Observation
`TABLE OF ABBREVIATIONS
`U.S. Pharmacopeia
`
``993 Patent
`
`ANDA
`
`API
`
`DMF
`
`EPO
`
`EP '406
`
`FDA
`
`IDS
`
`KCL
`
`KPA
`
`MSN
`
`NCI
`
`PTO
`
`TPO
`
`USP
`
`USP
`
`TPO
`
`PTO
`
`NCI
`
`MSN
`
`KPA
`
`KCL
`
`IDS
`
`FDA
`
`EP '406
`
`EPO
`
`DMF
`
`API
`
`ANDA
`
`'993 Patent
`
`XRPD or PXRD
`
`X-ray powder diffraction
`
`CONCLUSION -
`
`c. Conclusion Regarding Infringement .................................................................................. 96
`
`Claim 22 ..................................................................................................................... 95
`
`Claims 23 and 25 ................................................. : ...................................................... 94
`
`Claims 1 and 24 .......................................................................................................... 91
`
`vi.
`
`v.
`
`1v.
`
`3
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`4
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`(S.D.N.Y. Apr. 11, 2017)).
`HONORABLE PAUL A. CROTTY, United States District Judge:
`trial, U.S. Patent No. 5,856,336, finding it valid. (Kowa Co., Ltd. v. Amneal Phann., LLC., No. 14-CV-2758 (PAC)
`April 11, 2017, the Court issued its Findings of Fact and Conclusions of Law regarding the other patent at issue at
`trial The fifth defendant settled mid-trial; and the sixth settled post-trial. Only Amneal and Apotex remain. On
`This is a Hatch-Waxman patent infringement litigation initiated by Plaintiffs Kowa
`defenses of invalidity and non-infringement. Four defendants settled before commencement of the ten-day bench
`1 Plaintiffs commenced this litigation against eight generic drug manufacturer defendants. Defendants asserted
`Company, Ltd., Kowa Pharmaceuticals America, Inc., and Nissan Chemical Industries, Ltd.
`
`(collectively, "Plaintiffs"), manufacturers of the cholesterol-lowering drug Livalo , against
`
`defendants Anneal 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
`valid; and that Apotex's proposed ANDA product would infringe the '993 patent.
`U.S. Patent No. 8,557,993 (the '993 patent"). Both Amneal and Apotex contend that the '993
`pursuant to Fed. R. Civ. P. 52(a). As set forth below, the Court determines that the '993 patent is
`patent is invalid as (1) anticipated based on prior art, under 35 U.S.C. § 102(b); and/or (2) obvious
`evidence and testimony, the Court makes the following findings of fact and conclusions oflaw
`in view of prior art, under 35 U.S.C. § 103. Only Apotex asserts non-infringement; Amneal
`briefing on the '993 patent's validity and infringement. After considering the documentary
`concedes infringement.
`
`closing arguments on February 3, 2017. Each of the parties submitted extensive post-trial
`The Court held a ten-day bench trial from January 17 through January 30, 2017, with
`The Court held a ten-day bench trial from January 17 through January 30, 2017, with
`closing arguments on February 3, 2017. Each of the parties submitted extensive post-trial
`concedes infringement.
`briefing on the '993 patent's validity and infringement. After considering the documentary
`in view of prior art, under 35 U.S.C. § 103. Only Apotex asserts non-infringement; Amneal
`evidence and testimony, the Court makes the following findings of fact and conclusions of law
`patent is invalid as (1) anticipated based on prior art, under 35 U.S.C. § 102(b); and/or (2) obvious
`pursuant to Fed. R. Civ. P. 52(a). As set forth below, the Court determines that the '993 patent is
`U.S. Patent No. 8,557,993 (the '"993 patent"). Both Amneal and Apotex contend that the '993
`valid; and that Apotex's proposed ANDA product would infringe the '993 patent.
`Defendants' proposed Abbreviated New Drug Application ("ANDA") products would infringe
`
`("Apotex"), generic drug manufacturers (together, "Defendants").1 Plaintiffs allege that
`
`defendants Amneal Pharmaceuticals, LLC ("Amneal"), and Apotex, Inc. and Apotex Corp.
`
`(collectively, "Plaintiffs"), manufacturers of the cholesterol-lowering drug Livalo®, against
`
`Company, Ltd., Kowa Pharmaceuticals America, Inc., and Nissan Chemical Industries, Ltd.
`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
`This is a Hatch-Waxman patent infringement litigation initiated by Plaintiffs Kowa
`trial. The fifth defendant settled mid-trial; and the sixth settled post-trial. Only Anneal and Apotex remain. On
`April 11, 2017, the Court issued its Findings of Fact and Conclusions of Law regarding the other patent at issue at
`HONORABLE PAUL A. CROTTY, United States District Judge:
`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)).
`
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`5
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`Ltd. v. Amneal Phann., LLC, No. 14-CV-2758 (PAC) (S.D.N.Y. Apr. 11, 2017) at 9-10).
`of Fact and Conclusions of Law regarding the other patent at issue at trial, U.S. Patent No. 5,856,336. (Kawa Co.,
`INTRODUCTION AND LEGAL STANDARDS
`2 For additional background on the policy goals of the Hatch-Waxman Act, see this Court's April 11, 2017 Findings
`
`I.
`
`The Hatch-Waxman Act and ANDA Filings2
`
`1. The Hatch-Waxman Act, titled the Drug Price Competition and Patent Term Restoration
`CV-3372 (SHS), 2015 WL 11217239, at *5 (S.D.N.Y. Apr. 8, 2015)).
`Act of 1984, Pub. L. No. 98-417, permits pharmaceutical companies to seek United States Food
`infringement and patent invalidity simultaneously." (In re: OxyContin Antitrust Litig., No. 13-
`and Drug Administration (FDA) approval for a generic drug based on an already-approved
`U.S.C. § 355(j)(5)(B)(iii)). "[T]his structure allows the parties to trythe dueling issues of patent
`branded drug by filing an ANDA. (See 21 U.S.C. § 355(j)(2)(A), (8)(B)). In so doing, the
`27l(e)(2)(A)). Iflitigation is initiated, the generic's entry to market is automatically stayed. (21
`generic manufacturer may rely on the branded drug's safety and efficacy data submitted to the
`604 F.3d 98, 101 (2d Cir. 2010), cert. denied, 131 S. Ct. 1606 (2011) (citing 35 U.S.C. §
`FDA. (See id.).
`branded manufacturer's right to sue." (.Ark. Carpenters Health & Welfare Fund v. Bayer AG,
`2. If the branded drug manufacturer's patent has not yet expired, the generic manufacturer
`3. "An ANDA-IV certification itself constitutes an act of infringement, triggering the
`must file a "Paragraph IV" certification, establishing bioequivalence of the proposed generic
`U .S.C. § 355(j)(2)(B)(iv)(ll)).
`version with the approved branded version of the drug. (See 21 U.S.C. § 355(j)(2)(A)(vii)(IV);
`product will not infringe the branded manufacturer's patent, or that the patent is invalid. (See 21
`21 C.F.R. § 314.94(a)(9)). The certification must also state and explain either that the generic
`21 C.F.R. § 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
`version with the approved branded version of the drug. (See 21 U.S.C. § 355(j)(2)(A)(vii)(N);
`U.S.C. § 355(j)(2)(B)(iv)(II)).
`must file a "Paragraph IV" certification, establishing bioequivalence of the proposed generic
`3. "An ANDA-IV certification itself constitutes an act of infringement, triggering the
`2. If the branded drug manufacturer's patent has not yet expired, the generic manufacturer
`branded manufacturer's right to sue." (Ark. Carpenters Health & Welfare Fund v. Bayer AG,
`FDA. (See id.).
`604 F.3d 98, 101 (2d Cir. 2010), cert. denied, 131 S. Ct. 1606 (2011) (citing 35 U.S.C. §
`generic manufacturer may rely on the branded drug's safety and efficacy data submitted to the
`271(e)(2)(A)). If litigation is initiated, the generic's entry to market is automatically stayed. (21
`branded drug by filing an ANDA. (See 21 U.S.C. § 355(j)(2)(A), (8)(B)). In so doing, the
`U.S.C. § 355(j)(5)(B)(iii)). "[T]his structure allows the parties to try the dueling issues of patent
`and Drug Administration (FDA) approval for a generic drug based on an already-approved
`infringement and patent invalidity simultaneously." (In re: OxyContin Antitrust Litig., No. 13-
`Act of 1984, Pub. L. No. 98-417, permits pharmaceutical companies to seek United States Food
`CV-3372 (SHS), 2015 WL 11217239, at *5 (S.D.N.Y. Apr. 8, 2015)).
`1. The Hatch-Waxman Act, titled the Drug Price Competition and Patent Term Restoration
`
`2 For additional background on the policy goals of the Hatch-Waxman Act, see this Court's April 11, 2017 Findings
`INTRODUCTION AND LEGAL STANDARDS
`of Fact and Conclusions of Law regarding the other patent at issue at trial, U.S. Patent No. 5,856,336. (Kowa Co.,
`Ltd. V. Amneal Pharm., LLC, No. 14-CV-2758 (PAC) (S.D.N.Y. Apr. 11, 2017) at 9-10).
`
`The Hatch-Waxman Act and ANDA Filings2
`
`I.
`
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`6
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`IL
`
`The Parties
`
`4. Plaintiff Kowa Company, Ltd. ("KCL") is a Japanese corporation with its corporate
`
`headquarters and principal place of business in Aichi, Japan. (Compl. ¶ 2). Plaintiff Kowa
`
`Pharmaceuticals America, Inc. ("KPA") is a wholly-owned subsidiary of KCL organized under
`certification respecting the '993 patent. (Id. 'i[ 22).
`the laws of Delaware, with its corporate headquarters and principal place of business in
`pitavastatin calcium tablets. (Id. 'il'il 6, 20). Apotex's ANDA filing contains a Paragraph IV
`Montgomery, Alabama. (Id.). Plaintiff Nissan Chemical Industries, Ltd. ("NCI" or "Nissan") is
`including its ANDA No. 20-6068 filing, seeking FDA approval to market 1 mg, 2 mg, and 4 mg
`a Japanese corporation with its corporate headquarters and principal place of business in Tokyo,
`(Id.). Apotex Corp. is Apotex Inc. 's agent for purposes of making regulatory submissions,
`Japan. (Id ¶ 3). Plaintiffs are manufacturers, researchers, developers, and marketers of the
`Florida. (Id. 'i[ 6). Apotex Corp. sells and markets Apotex, Inc.'s products in the United States.
`cholesterol-lowering drug Livaloa'. (Id. ¶ 4).
`is incorporated in and exists under the laws of Delaware, with a place of business in Weston,
`5. Defendant Amneal is incorporated in Delaware, with a place of business in Bridgewater,
`principal place of business in Toronto, Ontario. (Apotex Answer 'i[ 5). Defendant Apotex Corp.
`New Jersey. (Amneal Answer ¶ 5). Amneal filed ANDA No. 20-5961 seeking FDA approval to
`6. Defendant Apotex, Inc. is organized in and exists under the laws of Canada, with a
`market 1 mg, 2 mg, and 4 mg pitavastatin calcium tablets. (Id. ¶ 20).
`market 1 mg, 2 mg, and 4 mg pitavastatin calcium tablets. (Id. 'i[ 20).
`6. Defendant Apotex, Inc. is organized in and exists under the laws of Canada, with a
`New Jersey. (Amneal Answer 'i[ 5). Amneal filed ANDA No. 20-5961 seeking FDA approval to
`principal place of business in Toronto, Ontario. (Apotex Answer ¶ 5). Defendant Apotex Corp.
`5. Defendant Amneal is incorporated in Delaware, with a place of business in Bridgewater,
`is incorporated in and exists under the laws of Delaware, with a place of business in Weston,
`cholesterol-lowering drug Livalo®. (Id. 'i[ 4).
`Florida. (Id. ¶ 6). Apotex Corp. sells and markets Apotex, Inc.'s products in the United States.
`Japan. (Id. 'i[ 3). Plaintiffs are manufacturers, researchers, developers, and marketers of the
`(Id.). Apotex Corp. is Apotex Inc.'s agent for purposes of making regulatory submissions,
`a Japanese corporation with its corporate headquarters and principal place of business in Tokyo,
`including its ANDA No. 20-6068 filing, seeking FDA approval to market 1 mg, 2 mg, and 4 mg
`Montgomery, Alabama. (Id.). Plaintiff Nissan Chemical Industries, Ltd. ("NCI" or "Nissan") is
`pitavastatin calcium tablets. (Id. Tif 6, 20). Apotex's ANDA filing contains a Paragraph IV
`the laws of Delaware, with its corporate headquarters and principal place of business in
`certification respecting the '993 patent. (Id. ¶ 22).
`Pharmaceuticals America, Inc. ("KP A") is a wholly-owned subsidiary ofKCL organized under
`
`headquarters and principal place ofbusiness in Aichi, Japan. (Compl. 'i[ 2). PlaintiffKowa
`
`4. PlaintiffKowa Company, Ltd. ("KCL") is a Japanese corporation with its corporate
`
`The Parties
`
`II.
`
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`7
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`III. 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
`76:1, 85:6-21).
`
`brief summary of relevant and uncontested facts is recited here.
`Livalo® mostly avoids, and is only minimally metabolized by, the CYP450 pathway. (Tr. 75:10-
`
`8. Statins are medications that address and control abnormal increases in blood cholesterol by
`P450" pathway (the "CYP450" or "CYP" pathway) in the liver. (Tr. 74:14-75:9). By contrast,
`
`inhibiting the way in which the liver makes cholesterol. (Tr. 70:8-71:10). All statins generally
`11. Approximately 75% of all metabolic drugs are metabolized through the "cytochrome
`
`work in the same way, but differ in the manner in which they bind to enzymes and dissolve in
`KN003466196).
`
`solvents; and how they are processed and metabolized by the body. (Tr. 71:5-17).
`high density lipoprotein cholesterol ("HDL-C"). (Tr. Tr. 77:5-11; PTX-1098 (Livalo® Label) at
`9. Patients have varying degrees of statin tolerance (or intolerance). (Tr. 71:25-74:13).
`cholesterol ("LDL-C"), total cholesterol, triglycerides, and apolipoprotein B; and/or increasing
`Approximately 10-15% of patients with elevated cholesterol are statin intolerant, which amounts
`(Revised: November 2016)) at KN003466196). It does so by reducing low density protein
`to approximately 4 to 6 million statin-intolerant patients in the United States. (Tr. 73:22-74:7).
`its label, hyperlipidemia or mixed dyslipidemia. (Tr. 77 :5-11; PTX-1098 (Livalo ® Label
`10. Livalo® is a statin used to treat elevated cholesterol; or more specifically, as reflected on
`10. Livalo® is a statin used to treat elevated cholesterol; or more specifically, as reflected on
`its label, hyperlipidemia or mixed dyslipidernia. (Tr. 77:5-11; PTX-1098 (Livalo® Label
`to approximately 4 to 6 million statin-intolerant patients in the United States. (Tr. 73:22-74:7).
`(Revised: November 2016)) at KN003466196). It does so by reducing low density protein
`Approximately 10-15% of patients with elevated cholesterol are statin intolerant, which amounts
`cholesterol ("LDL-C"), total cholesterol, triglycerides, and apolipoprotein B; and/or increasing
`9. Patients have varying degrees of statin tolerance (or intolerance). (Tr. 71:25-74:13).
`high density lipoprotein cholesterol ("HDL-C"). (Tr. Tr. 77:5-11; PTX-1098 (Livalo® Label) at
`solvents; and how they are processed and metabolized by the body. (Tr. 71 :5-17).
`
`KNO03466196).
`work in the same way, but differ in the manner in which they bind to enzymes and dissolve in
`
`11. Approximately 75% of all metabolic drugs are metabolized through the "cytochrome
`inhibiting the way in which the liver makes cholesterol. (Tr. 70:8-71: 10). All statins generally
`
`P450" pathway (the "CYP450" or "CYP" pathway) in the liver. (Tr. 74:14-75:9). By contrast,
`8. Statins are medications that address and control abnormal increases in blood cholesterol by
`
`Livalo® mostly avoids, and is only minimally metabolized by, the CYP450 pathway. (Tr. 75:10-
`brief summary of relevant and uncontested facts is recited here.
`
`76:1, 85:6-21).
`explanation of the history and workings ofLivalo® pitavastatin. (See generally Tr. 67-136). A
`
`7. At trial, Dr. Craig Sponseller, KP A's Chief Medical Officer, provided an initial
`
`Livalo®
`
`III.
`
`7
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`8
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`corresponding trial testimony.
`(See Tr. 1661:9-21). For ease of reference, the Court cites both exhibits and Bates pages used and referenced in the
`12. There are currently seven available statins on the market; at the time Livalo® launched in
`to a copying error, DTX-1359 was missing some pages; but the relevant testimony did not involve any such pages.
`4 Both Plaintiffs and Defendants submitted the '752 Application and file history. (See PTX-1337; DTX-1359). Due
`2009; and launched in the United States in Juue 2010. (Tr. 1534:17-20, 103:8-9; see PTX-0480; PTX-0482).
`the U.S. in mid-2010, there were six available statins with which Livalo® competed.3 (Tr.
`3 Livalo® was approved by Japanese regulators and launched in Japan in 2003; was approved by the FDA in August
`
`70:15-20).
`
`IV.
`
`The '993 Patent
`
`(Id. at 1:17-26).
`
`13. The '993 patent, "Crystalline Forms of Pitavastatin Calcium," is assigned to NCI. (PTX-
`dihydroxy-6(E)-heptenoic acid hemicalcium salt.
`chemical name: (3R,5S)-7-[2-cyclopropyl-4-( 4-fluorophenyl)quinolin-3-yl]-3,5-
`1063). KCL is NCI's licensee for the '993 patent, and KPA holds a license from KCL for the
`compositions comprising these forms ... Pitavastatin calcium is known by the
`Pitavastatin calcium, processes for the preparation thereof and pharmaceutical
``993 patent. (Amneal Compl. ¶ 15; Apotex Compl. ¶ 15). KPA sells the pitavastatin drug
`The present invention is directed to new crystalline forms and the amorphous form of
`product under the trade name Livalo® in the United States; KCL manufactures the Livalo®
`16. The '993 patent states:
`16-17; Apotex Compl. TT 16-17).
`products as sold by KPA. (Amneal Compl.
`2003. (PTX-1063 (claiming entitlement to European Application No. 03405080) ).
`14. The '993 patent issued on October 15, 2013, from U.S. Patent Application No.
`15. The earliest priority date to which the '993 patent claims entitlement is February 12,
`13/664,498 (the '498 Application"), filed October 31, 2012. (PTX-1063 (`993 patent); PTX-
`U.S. Patent Application No. 10/544,752 (the '"752 Application). (PTX-1337 and DTX-1359).4
`0172 (`498 Application ('993 patent file history))). The '498 Application is a continuation of
`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).4
`13/664,498 (the "'498 Application"), filed October 31, 2012. (PTX-1063 ('993 patent); PTX-
`15. The earliest priority date to which the '993 patent claims entitlement is February 12,
`14. The '993 patent issued on October 15, 2013, from U.S. Patent Application No.
`2003. (PTX-1063 (claiming entitlement to Europeans Application No. 03405080)).
`products as sold by KPA. (Amneal Comp\. m 16--17; Apotex Comp\. 'if'if 16--17).
`16. The '993 patent states:
`product under the trade name Livalo® in the United States; KCL manufactures the Livalo®
`The present invention is directed to new crystalline forms and the amorphous form of
`'993 patent. (Amneal Comp\. 'if 15; Apotex Compl. 'if 15). KP A sells the pitavastatin drug
`Pitavastatin calcium, processes for the preparation thereof and pharmaceutical
`compositions comprising these forms . . Pitavastatin calcium is known by the
`1063). KCL is NCI's licensee for the '993 patent, and KPA holds a license from KCL for the
`chemical name: (3R,5S)-742-cyclopropy1-4-(4-fluorophenyl)quinolin-3-y1]-3,5-
`dihydroxy-6(E)-heptenoic acid hemicalcium salt.
`13. The '993 patent, "Crystalline Forms of Pitavastatin Calcium," is assigned to NCI. (PTX-
`
`(Id. at 1:17 —26).
`
`The '993 Patent
`
`IV.
`
`70:15-20).
`
`3 Livalo® was approved by Japanese regulators and launched in Japan in 2003; was approved by the FDA in August
`the U.S. in mid-2010, there were six available statins with which Livalo® competed.3 (Tr.
`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 and file 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.
`12. There are currently seven available statins on i:he market; at the time Livalo® launched in
`(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 8 of 98
`
`8
`
`

`

`Case 1:14-cv-02758-PAC Document 179-1 Filed 02/11/19 Page 10 of 99
`9
`
`irrelevant to this action, and are not discussed further.
`17. The '993 patent explains that Plaintiffs recently developed pitavastatin calcium "as a new
`5 The other polymorphic forms and the amorphous form ofpitavastatin calcium claimed in the '993 patent are
`
`chemically synthesized and powerful statin . . [that] is safe and well tolerated in the treatment of
`(vw), 13.7 (s), 14.0 (w), 14.7 (w), 15.9 (vw), 16.9 (w), 17.1
`patients with hypercholesterolemia;" and that the statin has "extremely low" interactions with
`at 5.0 (s), 6.8 (s), 9.1 (s), 10.0 (w), 10.5 (m), 11.0 (m), 13.3
`diffraction pattern with characteristic peaks expressed in 20
`other commonly-used drugs. (Id. at 1:43-50).
`A) polymorph A exhibits a characteristic X-ray powder
`of [pitavastatin calcium] salt wherein
`18. Claims 1, 22, 23, 24, and 25 of the '993 patent claim six different polymorphs of
`A crystalline polymorph A, B, C, D, E, F, or the amorphous form,
`1.
`pitavastatin calcium, polymorphic forms A, B, C, D, E, and F, and the amorphous form; and a
`and relative intensities]." The relevant parts of claims 1and24 are set forth below:
`pharmaceutical composition comprising an effective amount of the form, and a pharmaceutically
`powder diffraction pattern with characteristic peaks expressed in 20 at [recited peak positions
`acceptable carrier. (Id. at 10:50-11:37, 13:7-41). Each claimed form includes a recitation of a
`21. Claims 1 and 24 are directed to, inter alia, Form A exhibiting "a characteristic X-ray
`characteristic X-ray powder diffraction pattern having specific characteristic peaks (claims 1 and
`preferably about 3 to 12%, more preferably 9 to 11% of water." (Id. at 6:13-14).
`24) or a diffraction pattern substantially as depicted in specified Figures (claims 23 and 25).
`20. The '993 patent specification discloses that "Form A may contain up to 15% water,
`
`(Id.).
`
`the subject of this action. 5
`19. Crystalline polymorph A of pitavastatin calcium ("Form A" or "Polymorph Form A") is
`19. Crystalline polymorph A ofpitavastatin calcium ("Form A" or "Polymorph Form A") is
`the subject of this action.5
`
`(Id.).
`
`20. The '993 patent specification discloses that "Form A may contain up to 15% water,
`24) or a diffraction pattern substantially as depicted in specified Figures (claims 23 and 25).
`preferably about 3 to 12%, more preferably 9 to 11% of water." (Id. at 6:13-14).
`characteristic X-ray powder diffraction pattern having specific characteristic peaks (claims 1 and
`21. Claims 1 and 24 are directed to, inter alia, Form A exhibiting "a characteristic X-ray
`acceptable carrier. (Id. at 10:50-11 :37, 13:7--41 ). Each claimed form includes a recitation of a
`powder diffraction pattern with characteristic peaks expressed in 20 at [recited peak positions
`pharmaceutical composition comprising an effective amount of the form, and a pharmaceutically
`and relative intensities]." The relevant parts of claims 1 and 24 are set forth below:
`pitavastatin calcium, polymorphic forms A, B, C, D, E, and F, and the amorphous form; and a
`A crystalline polymorph A, B, C, D, E, F, or the amorphous form,
`1.
`18. Claims 1, 22, 23, 24, and 25 of the '993 patent claim six different polymorphs of
`of [pitavastatin calcium] salt wherein
`A) polymorph A exhibits a characteristic X-ray powder
`other commonly-used drugs. (Id. at 1 :43-50).
`diffraction pattern with characteristic peaks expressed in 28
`at 5.0 (s), 6.8 (s), 9.1 (s), 10.0 (w), 10.5 (m), 11.0 (m), 13.3
`patients with hypercholesterolemia;" and that the statin has "extremely low" interactions with
`(vw), 13.7 (s), 14.0 (w), 14.7 (w), 15.9 (vw), 16.9 (w), 17.1
`chemically synthesized and powerful statin ... [that] is safe and well tolerated in the treatment of
`
`5 The other polymorphic forms and the amorphous form of pitavastatin calcium claimed in the '993 patent are
`17. The '993 patent explains that Plai