Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 1 of 48
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`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF NEW YORK
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`
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`v.
`
`Amneal Pharmaceuticals, LLC,
`
`
`Defendants.
`
`
`Kowa Company, Ltd.,
`Kowa Pharmaceuticals America, Inc., and
`Nissan Chemical Industries, Ltd.,
`
`
`Plaintiffs,
`
`
`v.
`
`Apotex, Inc. and Apotex Corp.,
`
`Civil Action No. 14-CV-2758 (PAC)
`
`Civil Action No. 14-CV-7934 (PAC)
`
`Defendants.
`
`
`
`
`
`
`
`DEFENDANTS AMNEAL’S AND APOTEX’S POST-TRIAL BRIEF
`REGARDING ANTICIPATION AND OBVIOUSNESS OF THE ASSERTED
`“FORM A CLAIMS” OF U.S. PATENT NO. 8,557,993
`
`
`
`
`
`

`

`
`
`I.
`
`II.
`
`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 2 of 48
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`TABLE OF CONTENTS
`
`INTRODUCTION ........................................................................................................................... 1
`
`EXAMPLE 3 OF EP ’406 INERENTLY ANTICIPATES CLAIMS 1 AND 22-25 OF
`THE ’993 PATENT .......................................................................................................................... 8
`
`A.
`
`B.
`
`The Law of Inherent Anticipation ..................................................................................... 8
`
`Amneal and Apotex Presented Plaintiff Nissan’s Own Clear and Convincing
`Evidence of Inherent Anticipation, and Confirmed of its Scientific Accuracy. ......... 9
`
`1.
`
`2.
`
`Nissan’s Own Scientific Data and Conclusions Disclosed to the European
`Patent Office and Contained in Internal Lab Reports. ................................... 10
`
`Defendants’ Experts Confirmed the Scientific Accuracy of Nissan’s Work
`and Scientific Truthfulness of Nissan’s Submission to the European Patent
`Office. ..................................................................................................................... 14
`
`C.
`
`Dr. Byrn’s Theory Does Not Refute Nissan’s Own Confirmed Clear and
`Convincing Evidence of Anticipation. ............................................................................ 14
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`Dr. Byrn’s Theory is Trial-by-Ambush in Violation of Rule 26 and this
`Court’s Case Management Order. ...................................................................... 15
`
`Dr. Byrn Bases his Theory on Evidence That the Court Expressly
`Excluded, on Counsel’s Mischaracterization of Trial Testimony, and on an
`Anonymous, Unpublished and Unverified Report of an Alleged
`Experiment. ........................................................................................................... 16
`
`Dr. Byrn’s Opinion Testimony Fails With Respect to Virtually Every
`Reliability Factor Articulated by the Supreme Court in Daubert and Kumho
`Tire. ......................................................................................................................... 21
`
`Additional Evidence of the Unreliability of Dr. Byrn’s Drying Conditions
`Theory. ................................................................................................................... 24
`
`Dr. Byrn’s Evidence Regarding Forms “M” and “P” Is Unreliable and Not
`Probative. ............................................................................................................... 25
`
`D.
`
`E.
`
`F.
`
`There Is No Heightened Burden to Show Invalidity, and No Deference Due to the
`Examiner Because the Examiner Failed to Correctly Recognize the Closest Prior
`Art. ........................................................................................................................................ 26
`
`EP ’406 Also Inherently Anticipates Claim 22. ............................................................. 27
`
`Conclusion as to Anticipation .......................................................................................... 28
`
`
`
`ii
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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 3 of 48
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`
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`III.
`
`THE ASSERTED CLAIMS OF THE ’993 PATENT ARE INVALID AS OBVIOUS ... 28
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`A Person of Ordinary Skill in the Art Would Have Had a Reasonable Expectation
`of Success of Obtaining Form A of Pitavastatin Calcium from a Routine
`Polymorph Screen of Example 3 of EP ’406. ................................................................ 29
`
`Near Simultaneous Invention of Form A of Pitavastatin Calcium Further Supports
`the Obviousness of Claims 1 and 23-25 of the ’993 patent. ........................................ 33
`
`Plaintiffs’ Alleged Secondary Considerations of Non-Obviousness Do Not Rebut
`Defendants’ Strong Prima Facie Showing of Obviousness ......................................... 33
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`There is No Nexus Between Plaintiffs’ Alleged Secondary Considerations
`and The Asserted Claims of the ’993 Patent .................................................... 33
`
`Plaintiffs Have Failed to Demonstrate the Commercial Success of Livalo. 34
`
`Plaintiffs Have Failed to Demonstrate Any Long-Felt But Unmet Need for
`Livalo. ..................................................................................................................... 36
`
`Plaintiffs Have Failed to Demonstrate Any Unexpected Results. ................. 37
`
`Plaintiffs Have Failed to Demonstrate Licensing of Livalo as a Secondary
`Consideration Supporting Non-Obviousness. ................................................. 37
`
`Plaintiffs Have Failed to Demonstrate Any Industry Praise for Livalo. ...... 38
`
`Plaintiffs’ Reliance on Copying is Irrelevant. .................................................... 38
`
`Claim 22 of the ’993 Patent Is Obvious in Light of EP ’406 and the Prior Art. ...... 38
`
`Conclusion as to Obviousness ......................................................................................... 40
`
`
`
`
`
`iii
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`

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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 4 of 48
`
`TABLE OF AUTHORITIES
`
`
`
`Page(s)
`
`
`
`Cases
`
`In re ’639 Patent Litig.,
`154 F. Supp. 2d 157 (D. Mass. 2001) ..................................................................................................... 13
`
`AEP Energy Servs. Gas Holding Co. v. Bank of Am., N.A.,
`626 F.3d 699 (2d Cir. 2010) ..................................................................................................................... 24
`
`Am. Stock Exchange, LLC v. Mopex, Inc.,
`215 F.R.D. 87 (S.D.N.Y. 2002) ............................................................................................................... 15
`
`Anderson News, L.L.C. v. American Media, Inc.,
`No. 09 Civ. 2227 (PAC), 2015 WL 5003528 (S.D.N.Y. Aug. 20, 2015) (Crotty, J.) ....................... 22
`
`In re Antor Media Corp.,
`689 F.3d 1282 (Fed. Cir. 2012) ................................................................................................................ 38
`
`Astra Aktiebolag v. Andrx Pharm., Inc.,
`222 F. Supp. 2d 423 (S.D.N.Y. 2002)..................................................................................................... 12
`
`AstraZeneca AB v. Andrx Labs., LLC,
`Nos. 15-1057, 14-8030, 2017 WL 111928 (D.N.J. Jan. 11, 2017) ...................................................... 31
`
`Asyst Techs., Inc. v. Emtrak, Inc.,
`544 F.3d 1310 (Fed. Cir. 2008) ................................................................................................................ 34
`
`Bayer Healthcare Pharm., Inc. v. Watson Pharm., Inc.,
`713 F.3d 1369 (Fed. Cir. 2013) ................................................................................................................ 38
`
`Borsack v. Ford Motor Co.,
`No. 04 Civ. 3255 (PAC), 2007 WL 2142070 (S.D.N.Y. July 26, 2007) (Crotty, J.) ......................... 21
`
`Bristol-Myers Squibb Co. v. Teva Pharm. USA, Inc.,
`752 F.3d 967 (Fed. Cir. 2014) .................................................................................................................. 37
`
`Brown v. 3M,
`265 F.3d 1349 (Fed. Cir. 2001) .................................................................................................................. 8
`
`Caterpillar Tractor Co. v. Berco, S.p.A.,
`714 F.2d 1110 (Fed.Cir. 1983) ................................................................................................................. 12
`
`In re Cavanagh,
`436 F.2d 491 (C.C.P.A. 1971) .................................................................................................................. 36
`
`iv
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`

`

`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 5 of 48
`
`
`
`Cucuras v. Sec’y of Dep’t of Health & Human Servs.,
`993 F.2d 1525 (Fed. Cir. 1993) ................................................................................................................ 24
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litig.,
`676 F.3d 1063 (Fed. Cir. 2012) ................................................................................................................ 33
`
`Daubert v. Merrell Dow Pharm., Inc.,
`509 U.S. 579 (1993) ...................................................................................................................... 21, 22, 23
`
`Ecolochem, Inc. v. S. cal. Edison Co.,
`227 F.3d 1361 (Fed. Cir. 2000) ................................................................................................................ 33
`
`Eli Lilly & Co., Inc. Barr Labs., Inc.,
`251 F.3d 955 (Fed. Cir. 2001) .................................................................................................................... 9
`
`Eli Lilly & Co. v. Zenith Goldline Pharm., Inc.,
`471 F.3d 1369 (Fed. Cir. 2006) .................................................................................................................. 8
`
`Fresenius Kabi USA, LLC v. Dr. Reddy’s Labs., Ltd.,
`65 F. Supp. 3d 379 (D. Del. 2014) .......................................................................................................... 22
`
`In re Geisler,
`116 F.3d 1465 (Fed. Cir. 1997) ................................................................................................................ 37
`
`General Elec. Co. v. Joiner,
`522 U.S. 136 (1997) ............................................................................................................................ 22, 32
`
`Geo M Martin v. Alliance Mach.,
`618 F.3d 1294 (Fed. Cir. 2010) ................................................................................................................ 38
`
`In re Gershon,
`372 F.2d 535 (C.C.P.A. 1967) .................................................................................................................. 36
`
`In re GPAC, Inc.,
`57 F.3d 1573 (Fed. Cir. 1995) .................................................................................................................. 35
`
`In re Huang,
`100 F.3d 135 (Fed. Cir. 1996) ........................................................................................................... 34, 35
`
`J.T. Eaton & Co. v. Atl. Paste & Glue Co.,
`106 F.3d 1563 (Fed. Cir. 1997) ................................................................................................................ 35
`
`Joseph S. v. Hogan,
`No. 06 Civ. 1042, 2011 WL 2848330 (E.D.N.Y. July 15, 2011) ........................................................ 21
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ............................................................................................................................ 29, 39
`
`v
`
`

`

`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 6 of 48
`
`
`
`Kumho Tire Co., Ltd. v. Carmichael,
`526 U.S. 137 (1999) ............................................................................................................................ 21, 22
`
`Merck & Cie v. Watson Labs., Inc.,
`822 F.3d 1347 (Fed. Cir. 2016) ................................................................................................................ 23
`
`Microsoft Corp. v. i4i Ltd. P’ship,
`564 U.S. 91 (2011) ................................................................................................................................. 9, 26
`
`Minn. Mining & Mfg. Co. v. Johnson & Johnson Orthopaedics, Inc.,
`976 F.2d 1559 (Fed. Cir. 1992) .................................................................................................................. 9
`
`Newell Companies v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) .................................................................................................................. 36
`
`In re Omeprazole Patent Litig.,
`483 F.3d 1364 (Fed. Cir. 2007) ................................................................................................... 12, 13, 24
`
`Ormco Corp. v. Align Tech., Inc.,
`463 F.3d 1299 (Fed. Cir. 2006) ................................................................................................................ 35
`
`Orthopedic Equipment Co., Inc. v. All Orthopedic Appliances, Inc.,
`707 F.2d 1376 (Fed. Cir. 1983) ................................................................................................................ 36
`
`Par Pharm., Inc. v. TWI Pharm., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) ................................................................................................................ 33
`
`In re Paulsen,
`30 F.3d 1475 (Fed. Cir. 1994) .................................................................................................................. 34
`
`Perricone v. Medicis Pharm. Corp.,
`432 F.3d 1368 (Fed. Cir. 2005) .................................................................................................................. 9
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ................................................................................................... 29, 32, 39
`
`PowerOasis, Inc. v. T-Mobile USA, Inc.,
`522 F.3d 1299 (Fed. Cir. 2008) ................................................................................................................ 26
`
`Purdue Pharma Prods. L.P. v. Par Pharm., Inc.,
`377 Fed. App’x 978 (Fed. Cir. 2010) ...................................................................................................... 38
`
`In re Salem,
`465 F.3d 767 (7th Cir. 2006) .................................................................................................................... 21
`
`Sciele Pharma Inc. v. Andrx Corp.,
`684 F.3d 1253 (Fed. Cir. 2012) ................................................................................................................ 26
`
`vi
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`

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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 7 of 48
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`
`
`SmithKline Beecham Corp. v. Copley Pharm., Inc.,
`45 F. App’x 915 (Fed. Cir. 2002) ............................................................................................................ 13
`
`Sparton Corp. v. United States,
`89 Fed. Cl. 196 (Ct. Cl. 2009) .................................................................................................................. 35
`
`Tanabe Seiyaku Co., Ltd. v. U.S. Int’l Trade Comm’n,
`109 F.3d 726 (Fed. Cir. 1997) .................................................................................................................. 12
`
`Therasense, Inc. v. Becton, Dickinson & Co.,
`593 F.3d 1289 (Fed. Cir. 2010) ................................................................................................................ 34
`
`Titanium Metals Corp. of Am. v. Banner,
`778 F.2d 775 (Fed. Cir. 1985) .................................................................................................................... 8
`
`U.S. v. Philip Morris USA, Inc.,
`223 F.R.D. 1 (D.D.C. 2004) .................................................................................................................... 15
`
`UBS AG v. HealthSouth Corp.,
`645 F. Supp. 2d 135 (S.D.N.Y. 2008)..................................................................................................... 24
`
`Statutes
`
`21 U.S.C. §355(j)(5)(B)(iii) ................................................................................................................................ 1
`
`35 U.S.C. §102 (2006). ....................................................................................................................................... 8
`
`35 U.S.C. §103 (2012) .................................................................................................................................. 8, 28
`
`Other Authorities
`
`Rule 26 ............................................................................................................................................................... 15
`
`Rule 26(a)(2) ...................................................................................................................................................... 15
`
`Rule 702 ............................................................................................................................................................. 21
`
`
`
`vii
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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 8 of 48
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`
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`Defendants Amneal Pharmaceuticals, LLC (“Amneal”) and Apotex, Inc. and Apotex Corp.
`
`(“Apotex”) submit this Post-Trial Brief in support of their request for judgment that claims 1 and
`
`22-25 of U.S. Patent No. 8,557,993 (“the ’993 patent”) are invalid as anticipated or obvious, and for
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`judgment against Plaintiff-patentee Nissan Chemical Industries, Ltd. (“Nissan”) and Plaintiff-
`
`licensees Kowa Company, Ltd. and Kowa Pharmaceuticals America, Inc. (“Kowa”).
`
`I.
`
`INTRODUCTION
`
`Why did Nissan sue on patent claims that Nissan itself previously had admitted,
`
`demonstrated and even insisted are anticipated by prior art? And why was Nissan’s evidence at trial
`
`merely an untested theory, which Nissan’s expert did not form until after trial began?
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`The answer to both questions is the same: the 30-month automatic stay provision of the
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`Hatch Waxman Act. Under the Act, a brand company’s mere institution and maintenance of a
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`patent infringement suit automatically stays FDA approval of a challenger’s competing products –
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`regardless of the merits of the claims at the outset, and regardless of the ultimate outcome of the case. The stay lasts
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`until the earlier of 30 months or until there is a final judgment of non-infringement or invalidity. See
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`21 U.S.C. §355(j)(5)(B)(iii).
`
`Plaintiffs knew that merely filing and litigating this suit would be worth at hundreds of
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`millions of dollars in sales of Livalo® at patent-protected prices, regardless of whether the case had
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`any merit. Accordingly, despite Nissan’s prior insistence that the ’993 patent claims were invalid,
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`Nissan sued and litigated the case for as long as it possibly could, without risking a ruling on the
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`merits.
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`Amneal and Apotex presented the clear and convincing empirical evidence of Nissan’s own
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`replications, tests, data, and conclusions that Example 3 of European Patent Application 0 520 406
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`A1 (“EP ’406”) anticipates the asserted Form A claims of the ’993 patent. Amneal and Apotex even
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`presented confirmation of Nissan’s scientific accuracy by Dr. Kevin Roberts, an expert in
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`1
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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 9 of 48
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`crystallography, and Dr. Jonathan Sessler, an expert in synthetic process chemistry. They agreed that
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`Nissan was telling the truth when it told the European Patent Office (“EPO”) what the data
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`established:
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`Therefore, [EP ’406], Example 3 teaches inevitably directly and
`unambiguously the Form A pitavastatin hemicalcium salt of EP 04
`707 232.7. Therefore, original claims 1, 2 and 37 lack novelty.
`
`(DTX-1327 at MYLAN (Pitav) 060024.) It is undisputed that claims 1, 2 and 37 of European Patent
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`Application EP 04 707 232.7 (the “’232 Application”) were substantively identical to the Form A
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`claims of the ’993 patent subsequently asserted here against Amneal and Apotex.
`
`At the time of Nissan’s submission, Nissan’s competitor Ciba Specialty Chemicals (“Ciba”)
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`owned the ’232 Application, as well as the counterpart U.S. application which would eventually lead
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`to the ’993 patent. Nissan had filed EP ’406 ten years before Ciba had filed the ’232 Application.
`
`As the owner of EP ’406, Nissan had regarded itself as the inventor of crystalline pitavastatin
`
`calcium. In the words of Plaintiffs’ counsel, “it’s evident that Nissan’s discovery of Ciba’s claim to
`
`polymorphs of [Nissan’s] own invention, pitavastatin calcium, was not a happy discovery.” (Tr. at
`
`1850:6–8.)
`
`Accordingly, Nissan set about protecting its turf. Nissan scientists studied and replicated the
`
`process of EP ’406, Example 3 at least twice, under differing drying conditions. They found that the
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`replications of Example 3 always produced the Form A pitavastatin calcium claimed in the ’232
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`Application. Nissan submitted its conclusions, based on its own science, to the EPO in December
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`2006. What is more, the EPO subsequently considered and accepted Nissan’s scientific conclusions,
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`and expressly found claims 1, 2 and 37 of the ’232 Application to be anticipated by EP ’406,
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`Example 3.
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`In 2008, however, Nissan acquired from Ciba the ’232 Application and U.S. counterpart
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`application for the ’993 patent. Nissan’s view of scientific truth regarding EP ’406 changed with that
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`2
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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 10 of 48
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`change in ownership. Nissan attempted to do before the EPO the same thing Nissan attempted to
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`do here at trial – that is, to overcome its own empirical evidence of anticipation, without showing
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`that even one actual replication of EP ’406, Example 3 fails to produce Form A pitavastatin calcium.
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`The EPO would have none of it, and neither should this Court, in view of the trial record.
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`Defendants are not aware of any Federal Circuit decision to have upheld the validity of
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`patent claims that the patentee itself previously had insisted were invalid. Further, where a
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`challenger has produced empirical evidence that a prior art process produces a claimed composition,
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`Defendants are unaware of any Federal Circuit decision to have maintained the claim’s validity
`
`without empirical evidence from the patentee that the process actually failed to produce the
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`composition. A patentee’s mere say-so or hypothesis that the process could produce something else
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`is simply not enough to defeat empirical evidence – especially when the patentee is the source of
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`that empirical evidence.
`
`Against Nissan’s confirmed direct empirical evidence, Plaintiffs offered Dr. Stephen Byrn’s
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`untested and untestable theory that certain drying conditions could cause Example 3 to produce
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`Form E instead of Form A. First and foremost, Dr. Byrn admitted that he created this theory
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`during trial – and he had not disclosed it, or any of its bases, in his expert report. On that ground
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`alone, the Court should dismiss it. Nevertheless, the same dismissal is compelled by any one of (a)
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`Dr. Byrn’s failure to test the theory, (b) Dr. Byrn’s failure to provide specifics to allow anyone to test
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`his theory, (c) the illegitimacy and unreliability of his bases, or (d) the lack of scientific connection
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`between his bases and conclusion.
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`Dr. Byrn did not test his theory by applying any drying conditions to a replication of
`
`Example 3, and finding that it produced Form E. Dr. Byrn did not attempt even a single replication
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`of Example 3, or even rely on someone else’s purported replication of Example 3. Dr. Byrn
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`admitted that he could have done such an experiment, but he chose not to because he was “already
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`3
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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 11 of 48
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`convinced” that Form E would be the result of such an experiment. (Tr. at 1713:2–6.) Having
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`already convinced himself what the experiment would show, he saw no reason to produce empirical
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`evidence of his theory to the Court. This is unreliable, if not inadmissible, ipse dixit expert testimony.
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`Moreover, Dr. Byrn withheld information that might have allowed anyone else to test his
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`theory. Dr. Byrn did not identify what drying parameters he hypothesized would cause Example 3
`
`to produce Form E. He even admitted that he never even determined if such conditions actually
`
`exist. In this way, Dr. Byrn prevented any other scientist from testing the theory by replicating
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`Example 3, and applying drying conditions or parameters that Dr. Byrn says would produce Form
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`E. Such an untestable theory is just another form of ipse dixit.
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`Dr. Byrn’s purported bases for his theory are legally impermissible, the product of chicanery,
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`and not relied on by anyone in the field. His first basis is information contained in a document
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`which the Court expressly excluded and ruled that Dr. Byrn could not rely upon. His second is
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`Plaintiffs’ counsel’s own extraordinary mischaracterization of testimony from Dr. Roberts. The
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`third is an anonymous, unpublished, unverified purported humidity experiment, which Dr. Byrn
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`deemed to be “scientifically reliable” because the U.S. Patent Office seal appeared on a certification
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`that the document was an accurate excerpt from the ’993 patent prosecution history.
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`In addition, Dr. Byrn failed to offer evidence of the required rigorous analytical connection
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`between his bases and his ultimate conclusion. Even if the Court did not stand by its exclusion of
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`the untimely evidence Dr. Byrn relies on, that evidence does not reflect any purported replication of
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`Example 3 to produce any form of pitavastatin. Nor does it include any of the experimental data
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`from which its unknown author(s) drew their conclusions. The document on its face actually
`
`contradicts Dr. Byrn’s conclusion that Form E is produced by high humidity. It also simply does
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`not contain Dr. Byrn’s alleged “correlation” between 12% water content and greater than 50%
`
`humidity to make Form E. The ambiguity and contradiction of the document highlights the
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`4
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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 12 of 48
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`correctness of the Court’s ruling excluding the document based on untimely disclosure. The
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`document presents more questions than it even purports to answer, and Defendants’ expert should
`
`have had the opportunity to review, investigate, and opine on it.
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`Nor is there a rigorous, or even plausible, analytical connection between the anonymous
`
`humidity study and Dr. Bryn’s conclusion that certain drying parameters applied to Example 3 will
`
`produce form E. Dr. Byrn attempts to connect the humidity study to his ultimate conclusion by
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`means of an oxymoron: “If you dry such that you create high humidity, you end up with Form
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`E.” (Tr. at 1669:8–9 (emphasis added).) Not surprisingly, Dr. Byrn fails to provide any evidence
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`that anyone in his field has ever dried the precipitate from a crystallization process “such that you
`
`create high humidity.” “High humidity,” or any kind of “humidity,” does not appear in any
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`crystallization process in the case. It does not even appear on Dr. Byrn’s list of parameters that
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`“could” affect polymorphic form. It is plain to see why. Even a layman knows that drying a sample
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`removes water from its surface, which is precisely the opposite of adding water to the surface by
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`exposing it to high humidity.
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`Dr. Byrn’s untested, untestable, unreliable, and untimely theory fails to negate Nissan’s own
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`clear and convincing scientific evidence that the asserted ’993 patent claims are anticipated by
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`Example 3 of EP ’406. Plaintiffs’ reliance on the fact that EP ’406 was “considered” by the
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`Examiner does not change the analysis or conclusion. Experts for both sides agreed that the
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`Examiner erred as a matter of science in concluding that the crystalline pitavastatin calcium of EP
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`’406 was not the closest prior art. Accordingly, no deference is due to her analysis of the claimed
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`inventions compared with what she erroneously concluded was the closest prior art. Further, it is
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`undisputed that Nissan chose not to correct the record at the time. Nissan cannot benefit from
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`what all agree was a mistake, and that Nissan failed to disclose to the Examiner, in order to avoid
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`scrutiny of EP ‘406 and the Third Party Observation.
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`5
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`

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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 13 of 48
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`The remainder of Dr. Byrn’s evidence against Nissan’s own empirical data consist of two
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`unpublished, unreviewed and unverified Indian patent applications, purporting to have discovered
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`new forms M and P of pitavastatin calcium. Astonishingly, Dr. Byrn suggested that he regarded
`
`these applications to be as scientifically reliable as peer reviewed scientific articles, which he admitted
`
`others in his field would consider far more reliable. (Tr. at 1746:4–11.) In any event, the applications
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`are not probative even taken at face value. Dr. Byrn admitted that the processes used to make the
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`supposed new forms were different from Example 3, and that those differences could account for
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`the alleged production of the allegedly new forms.
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`Finally, even if the asserted claims were not anticipated by EP ’406, they would have been
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`obvious to the person of ordinary skill in the art in light of EP ’406 and the regulatory motivation to
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`identify all polymorphs of a potential drug, using what by February 2003 was routine polymorph
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`screens – either in-house at drug companies, or farmed out to numerous contract labs who provided
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`the service. Indeed, the evidence showed that the vast majority of the ’993 patent specification came
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`directly from a standard polymorph screen report by such a contract lab, to which Ciba had farmed
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`out the task of doing a routine polymorph screen on pitavastatin calcium.
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`Further, a different group of scientists came up with Form A of pitavastatin calcium at about
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`the same time as the inventors. Producing and characterizing the polymorphs of a known statin was
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`not cutting edge science. It was what was expected and routinely done throughout the drug
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`industry.
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`Dr. Byrn’s opinion on obviousness is as untested and untestable as his anticipation theory.
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`At bottom, Dr. Byrn and Dr. Roberts disagree about whether a person of ordinary skill in the art
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`would have had a reasonable expectation of obtaining the polymorphs of pitavastatin, including
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`Form A, by running a polymorph screen on the crystalline pitavastatin calcium disclosed on the face
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`of Example 3. They also disagree as to whether doing so was routine lab work. Dr. Roberts says
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`Case 1:14-cv-02758-PAC Document 139 Filed 02/21/17 Page 14 of 48
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`“yes,” and Dr. Byrn says “no.”
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`Dr. Roberts’s position finds more support in the objective evidence, including prior writings
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`by Dr. Byrn, describing the polymorph screening process to be followed, and identifying the
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`solvents to be used. Dr. Bryn’s writings cannot be reconciled with his trial testimony that a
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`polymorph screen required hundreds or thousands of experiments, and vast amounts of resources
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`and time – all without absolute certainty that polymorphs would be found. Dr. Byrn’s description is
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`contrary to the only actual polymorph screen reports in the record. The high through-put
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`processing and small number of solvents indicated in these reports are far more consistent with Dr.
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`Roberts’s testimony that polymorph screens were important but modest routine lab work. And at
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`least one other Court has rejected Dr. Byrn’s opinions, because they contradicted his prior writings.
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`Nor should the Court accept Dr. Byrn’s claim that a person of ordinary skill could not have
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`had a reasonable expectation that a polymorph screen would produce the polymorphs of pitavastatin
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`calcium. This is directly contrary to the literature and Dr. Byrn’s admission that at least two-thirds,
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`if not 85-90% of polymorph screens on potential drug molecules, were known to produce
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`polymorphs. Dr. Byrn conflates a reasonable expectation of getting the polymorphs of pitavastatin
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`calcium from a screen, on the one hand, with being able to predict in advance exactly how many
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`polymorphs will be produced and exactly what the structure of each polymorph will be, on the
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`other. The former is all that the law of obviousness requires.
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`Accordingly, Plaintiffs’ focused their trial presentation on evidence devoted to alleged
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`secondary considerations of non-obviousness, such as commercial success, meeting of a long-felt
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`need, unexpected results and industry praise relating to Livalo. Livalo’s failure to take more tha