UNITED STATES PATENT AND TRADEMARK OFFICE
`
`______________
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`______________
`
`Sawai USA Inc., and Sawai Pharmaceutical Co., Ltd,
`Petitioners,
`
`v.
`
`Nissan Chemical Industries, Ltd.,
`Patent Owner
`________________
`
`
`
`U.S. Patent No. 5,856,336
`
`Issue Date: January 5, 1999
`
`Title: Quinoline Type Mevalonolactones
`
`________________
`
`Inter Partes Review No. IPR2015-01648
`
`
`
`NISSAN CHEMICAL INDUSTRIES, LTD.’S
`PRELIMINARY RESPONSE
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`

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`TABLE OF CONTENTS
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`PAGE
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`I.
`
`INTRODUCTION ........................................................................................... 1
`
`II.
`
`SAWAI’S OBVIOUSNESS ARGUMENTS FAIL ......................................... 6
`
`A.
`
`
`RELEVANT ASPECTS OF THE PROSECUTION HISTORY
`AND INTERFERENCE PROCEEDINGS ........................................... 6
`
`B.
`
`SUMMARY OF THE ‘336 PATENT .................................................. 10
`
`C.
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`PERSON OF ORDINARY SKILL IN THE ART ............................... 11
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`D.
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`E.
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`F.
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`LEGAL STANDARD FOR INSTITUTION OF INTER PARTES
`REVIEW ............................................................................................. 12
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`LEGAL PRINCIPLES REGARDING CHEMICAL
`OBVIOUSNESS ................................................................................. 12
`
`SAWAI HAS FAILED TO DEMONSTRATE A REASONABLE
`LIKELIHOOD THAT THE CHALLENGED CLAIMS WOULD
`HAVE BEEN OBVIOUS OVER KESSELER IN VIEW
`OF PICARD ........................................................................................ 14
`
`1.
`
`
`
`Sawai fails to supply a coherent reason for why a POSA
`would have selected Compound IIac of Kesseler as a
`“lead compound” for an HMG-CoA reductase inhibitor .......... 15
`
`
`
`
`
`
`
`
`(a) Kesseler discloses hundreds of compounds with
` “interesting possibilities” for further research .................... 16
`
`(b) Sawai supplies no reason, other than hindsight,
` for selection of Compound IIac in Kesseler as a lead
` compound ............................................................................ 18
`
`2.
`
`
`Even if Kesseler Compound IIac were a proper selection of
`a lead compound for an HMG-CoA reductase inhibitor, it
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`3.
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`4.
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`would not have been obvious to make a “ring-fused analog”
`of that compound. ...................................................................... 24
`
`(a) Kesseler Compound IIac is not “structurally similar”
` to the compound depicted in Claim 1 of the ‘336
` Patent ................................................................................... 25
`
`(b) Sawai fails to identify a reason to modify the core of
` Kesseler Compound IIac from pyridine to quinoline ........ 28
`
`Sawai fails to identify any reason to change the final form of
`the quinoline compound to a calcium salt ................................. 32
`
`Secondary considerations of record demonstrate non-
`obviousness ............................................................................... 34
`
`G.
`
`
`
`
`SAWAI HAS FAILED TO DEMONSTRATE A REASONABLE
`LIKELIHOOD THAT CLAIM 2 OF THE ‘336 PATENT WOULD
`HAVE BEEN OBVIOUS OVER KESSELER IN VIEW OF
`PICARD .............................................................................................. 37
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`III. SAWAI’S PETITION SHOULD BE REJECTED AS
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`DUPLICATIVE UNDER 35 U.S.C. §325(d) ................................................ 38
`
`IV. SAWAI’S “INTERFERENCE ESTOPPEL” ARGUMENTS ARE NOT
`
`PROPERLY POSED IN AN IPR PROCEEDING, AND LACK
`
`MERIT ........................................................................................................... 39
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`V.
`
`CONCLUSION .............................................................................................. 44
`
`ii
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`

`
`TABLE OF AUTHORITIES
`
`
`
`PAGE
`
`Cases
`
`Bayer AG v. Carlsbad Tech., Inc.,
`No. 01-CV-0867-B, 2002 U.S. Dist. LEXIS 27830
`(S. D. Cal. Aug. 6, 2002) .................................................................................... 27
`
`
`
`Bristol-Myers Squibb Co. v. Teva Pharm USA., Inc.,
`
`752 F.3d 967 (Fed. Cir. 2014) ............................................................................ 28
`
`Daiichi Sankyo Co, Ltd.. v. Matrix Labs, Ltd.,
`619 F.3d 1346 (Fed. Cir. 2010) .............................................................. 14, 20, 23
`
`Daiichi Sankyo Co., Ltd. v. Mylan Pharm., Inc.,
`670 F. Supp. 2d 359 (D.N.J. 2009) ..................................................................... 23
`
`
`Depuy Spine, Inc. v. Medtronic Sofamor Danek, Inc.,
`
`567 F.3d 1314 (Fed. Cir. 2009) .......................................................................... 14
`
`Eli Lilly & Co. v. Zenith Goldline Pharm. Inc.,
`471 F.3d 1369 (Fed. Cir. 2006) .......................................................................... 14
`
`
`Ex Parte Cullis,
`11 U.S.P.Q. 2d 1876 (BPAI 1989) ................................................................. 5, 40
`
`Exxon Corp. v. Phillips Petroleum Co.,
`265 F.3d 1249 (Fed. Cir. 2001) ................................................................ 5, 40, 41
`
`Fujikawa v. Wattanasin
`
`93 F.3d 1559 (Fed. Cir. 1996) ........................................................................ 9, 10
`
`Grain Processing Corp. v. Am. Maize-Prods. Co.,
`
`840 F.2d 902 (Fed. Cir. 1988) ............................................................................ 13
`
`In re Deckler,
`977 F.2d 1449 (Fed. Cir. 1992) .................................................................... 41, 42
`
`In re Hedges,
`
`783 F.2d 1038 (Fed. Cir. 1986) .......................................................................... 13
`
`iii
`
`

`
`
`
`In re Kahn,
`441 F.3d 977 (Fed. Cir. 2006) ............................................................................ 23
`
`
`In re Kroekel,
`803 F.2d 705 (Fed. Cir. 1986) ...................................................................... 41, 42
`
`In re NTP, Inc.,
`654 F.3d 1279 (Fed. Cir. 2011) .......................................................................... 20
`
`In re Ogiue,
`517 F.2d 1382 (CCPA 1975) .............................................................................. 40
`
`In re Risse,
`378 F.2d 948 (CCPA 1967) ................................................................................ 40
`
`In re Rosuvastatin Calcium Patent Litig.,
`703 F.3d 511 (Fed. Cir. 2012) ...................................................................... 28, 29
`
`KSR Int’l Co. v. Teleflex, Inc.,
`550 U.S. 398 (2007) ................................................................................ 23, 26, 32
`
`Kowa Company, Ltd., et al. v. Apotex Inc., et al.,
` C.A. No. 14-cv-7934 (S.D.N.Y.) ........................................................................ 37
`
`Kowa Company, Ltd., et al. v. Lupin Limited, et al.,
` C.A. No. 15-cv-3935 (S.D.N.Y.) ........................................................................ 37
`
`Orthopedic Equip. Co. v. United States,
`
`702 F.2d 1005 (Fed. Cir. 1983) .......................................................................... 13
`
`Otsuka Pharm. Co. v. Sandoz, Inc.,
`678 F.3d 1280 (Fed. Cir. 2012), ..................................................................passim
`
`
`Pfizer Inc. v. Mylan Pharm. Inc.,
`C.A. No. 10-528, 2014 U.S. Dist. LEXIS 150283
`(D.Del. Oct. 22, 2014) ........................................................................................ 23
`
`Pfizer Inc. v. Teva Pharm. U.S.A., Inc.,
`555 F. App’x 961 (Fed. Cir. 2014) ..................................................................... 18
`
`Procter & Gamble Co. v. Teva Pharm. USA, Inc.,
`566 F.3d 989 (Fed. Cir. 2009) ............................................................................ 31
`
`
`iv
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`

`
`
`
`
`Shire LLC v. Amneal Pharm.,
`2015 U.S. App. LEXIS 16908 (Fed. Cir. Sept. 24, 2015) .................................. 20
`
`Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd.,
`492 F.3d 1350 (Fed. Cir. 2007) ........................................................ 13, 19, 20, 24
`
`PTAB
`
`Apotex Inc. v. Merck Sharp & Dohme Corp.,
`IPR2015-00419, Paper No. 14 ............................................................................ 14
`
`
`Apotex Inc. v. Wyeth LLC,
`IPR2014-00115, Paper No. 94 (PTAB Apr. 20, 2015) ................................ 25, 26
`
`Athena Automation Ltd. v. Husky Injection Molding Systems Ltd.,
`IPR2013-00290, Paper No. 45 (PTAB Oct. 23, 2014) ....................................... 35
`
`Conopco, Inc. DBA Unilever v. The Procter & Gamble Co.,
`
`IPR2014-00506, Paper No. 17 (PTAB Jul. 7, 2014) .......................................... 38
`
`Kinetic Techs., Inc. v. Skyworks Solutions, Inc.,
`
`IPR2014-00529, Paper No. 8 (PTAB Sept. 23, 2014) ........................................ 22
`
`LG Electronics, Inc. v. ATI Technologies, ULC,
`
`IPR2015-00327, Paper No. 15 (PTAB Sep. 2, 2015) ......................................... 38
`
`Mylan Pharm. Inc. v. Gilead Sciences, Inc.,
`
`IPR2014-00885, Paper No. 15 (PTAB Dec. 9, 2014) ........................................ 12
`
`Mylan Pharm. Inc. v. Gilead Sciences, Inc.,
`IPR2014-00887, Paper No. 16 (PTAB Dec. 9, 2014) ........................................ 24
`
`Mylan Pharm. Inc. v. Nissan Chem. Ind.,
`
`IPR2015-01069 Paper No. 24 (PTAB Oct. 20, 2015) .................................passim
`
`Synopsys, Inc. v. Mentor Graphics Corp.,
`
`IPR2012-00041, Paper No. 16 (PTAB Feb. 22, 2013) ................................. 22, 26
`
`Tate & Lyle Americas LLC v. Cargill, Inc.,
`IPR2014-00084, Paper No. 12 (PTAB Apr. 1, 2014)......................................... 22
`
`
`v
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`

`
`
`
`Torrent Pharm., Ltd. v. Merck Frosst Canada & Co.,
`IPR2014-00559, Paper No. 8 (PTAB Oct. 1, 2014) ..................................... 12, 24
`
`Unified Patents Inc. v. PersonalWeb Technologies, LLC
`
`IPR2014-00702, Paper No. 13 (PTAB Jul. 24, 2014) ........................................ 39
`
`WL Gore & Associates, Inc. v. Lifeport Science LLC,
`IPR2014-01319, Paper No. 7 (PTAB Feb. 23, 2015) ..................................... 5, 42
`
`
`
`Rules
`
`37 C.F.R. § 42.65 ..................................................................................................... 35
`
`
`
`Statutes
`
`35 U.S.C. § 102 ........................................................................................................ 42
`
`35 U.S.C. § 103 .................................................................................................. 13, 42
`
`35 U.S.C. § 112 .......................................................................................................... 2
`
`35 U.S.C. § 311 ........................................................................................................ 42
`
`35 U.S.C. § 314 ........................................................................................................ 12
`
`35 U.S.C. § 316 .................................................................................................. 39, 43
`
`35 U.S.C. § 325 ........................................................................................................ 38
`
`
`
`
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`vi
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`PATENT OWNER’S EXHIBIT LIST
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`
`
`
`Exhibit No.
`
`2002
`
`Livalo® Package Insert
`
`Description
`
`
`
`vii
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`

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`
`
`I.
`
`INTRODUCTION
`
`Sawai USA Inc. and Sawai Pharmaceutical Co., Ltd’s (“Sawai,” or
`
`“Petitioners”) Petition (“Pet.”) seeking inter partes review of U.S. Patent No.
`
`5,856,336 (the “’336 Patent”) should be denied.
`
`The claims of the ‘336 Patent are directed to a novel compound, pitavastatin
`
`calcium, and to a method for reducing hyperlipidemia, hyperlipoproteinemia, or
`
`atherosclerosis by administering that compound. Pitavastatin calcium is sold under
`
`the trademark Livalo® and has enjoyed substantial commercial success. Prior to
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`the invention claimed in the ‘336 Patent, no one had disclosed a compound with
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`pitavastatin calcium’s unique structure. The two claims of the ‘336 Patent issued
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`after a years-long interference proceeding in which both the Board of Patent
`
`Appeals and Interferences and the Federal Circuit expressly found the
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`incorporation of a cyclopropyl substituent on the quinoline core of the molecule to
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`be non-obvious. Livalo® remains the only statin product ever approved by the
`
`FDA with a quinoline core, as well as the only statin ever approved by the FDA
`
`with a cyclopropyl substituent:
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`
`
`1
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`

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`
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`[Ex. 2002 (Livalo® Package Insert, Oct. 2013).]
`
`In its petition, Sawai relies primarily upon two references – Kesseler [Ex.
`
`1010] and Picard [Ex. 1009]. Sawai relies on one of the many compounds
`
`identified in Kesseler as a supposed “lead” compound, and argues that it would
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`have been obvious to modify it based on Picard.1 Sawai’s attempts to build a case
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`for invalidity based on Kesseler and Picard are contrary to law, reason, and sound
`
`chemistry.
`
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`1 In order to make Kesseler and Picard available as prior art to the ‘336 Patent,
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`Sawai relies on extensive expert testimony to try to support an argument that the
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`‘336 Patent is not entitled to claim priority from earlier filed Japanese patent
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`applications. In making this argument, Sawai misapplies the law of priority under
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`35 U.S.C. § 112, ignores specific disclosures found in the foreign Japanese priority
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`applications that support the effective filing date of the ‘336 Patent, treats those
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`priority applications as broad genus applications, and generally mis-frames the
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`issue surrounding whether or not the foreign applications adequately support the
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`‘336 Patent claims. The Board, however, need not address priority at this time,
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`because Sawai’s obviousness arguments are so clearly without merit. In the event
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`the Board were to decide to institute review, Patent Owner reserves its right to
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`submit evidence and argument in order to establish the entitlement of the ‘336
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`Patent to the August 20, 1987 priority date.
`
`2
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`

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`
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`First, Sawai’s “lead compound” selection is unconvincing. Out of hundreds
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`of potentially active statin compounds disclosed in Kesseler, Sawai conveniently
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`argues that a person of ordinary skill in the art (POSA) would have selected the
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`one with a cyclopropyl substituent. There is little basis for this selection over the
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`dozens of other compounds with non-cyclic substituents, other than sheer
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`hindsight. Sawai simply appears to have scoured the patent literature for any
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`compounds that might remotely resemble the unique, cyclopropyl-containing
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`structure of pitavastatin. This is in contrast to Sawai’s selection of a structurally
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`different “lead” compound in another IPR petition that Sawai filed on the same day
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`as this petition. It is a reflection of the novelty of the pitavastatin compound that
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`even Sawai cannot decide on a single lead compound and must instead come at it
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`from two diverging angles in two separate IPR petitions. Add to this a third
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`structurally distinct “lead” compound proposed by a different generic company
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`(which had previously filed its own IPR petition against the same ‘336 Patent
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`claims), and it is clear that even today, with the benefit of hindsight, there is no
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`direction in the prior art on where even to begin. [Compare this Petition, IPR2015-
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`01648 (proposing pyridine lead compound) with Sawai’s other Petition, IPR2015-
`
`01467 (proposing quinoline lead compound) and with Mylan’s Petition, IPR2015-
`
`010692 (proposing indole lead compound).]
`
`
`2 The Board denied Mylan’s petition for institution of inter partes review on
`
`3
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`

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`
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`Second, even if a POSA would have selected Kesseler Compound IIac as a
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`lead compound, Sawai has completely failed to provide a reason for why a POSA
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`would then have changed the pyridine core of Compound IIac to what was by all
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`accounts a less active quinoline core. The Board has already rejected, in the
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`related Mylan proceeding, an argument similar to Sawai’s “core change” argument.
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`See Mylan Pharm. Inc., IPR2015-01069, Paper No. 24 at 7 (PTAB Oct. 20, 2015)
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`(holding that the steps needed to go from fluvastatin [indole core] to pitavastatin
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`[quinoline core] did not constitute “routine optimization,” but instead “would have
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`required a number of chemical alterations, each having a number of possible
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`combinations”). Sawai also has not explained how a POSA would have had a
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`reasonable expectation of success that the change from a pyridine to a quinoline
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`core – via a process that Sawai terms “benzofusion” – would have resulted in a
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`compound with improved properties. The data disclosed in Picard for quinoline
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`based statin compounds, rather than supporting Sawai’s obviousness arguments in
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`view of Kesseler, actually taught away.
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`Third, even if Sawai’s wholly unsupported “benzofusion” theory were to be
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`accepted, Sawai fails to show why a POSA would have taken the additional step to
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`create the calcium salt of pitavastatin. For this argument, Sawai tries to rely on
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`
`October 20, 2015 (Paper 24).
`
`4
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`

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`
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`alleged statements made by NCI during the prior interference proceedings, and yet
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`Sawai’s characterization of those statements is both false and misleading.
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`Grasping at straws, Sawai tries to manufacture an interference estoppel
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`invalidity argument based on the interference proceedings involving the
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`grandparent application of the ‘336 Patent. This argument isfundamentally flawed:
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`the doctrine of interference estoppel simply does not exist as a mechanism by
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`which a third party can challenge the validity of an issued patent. See Exxon Corp.
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`v. Phillips Petroleum Co., 265 F.3d 1249, 1254 (Fed. Cir. 2001). Rather,
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`interference estoppel applies only to patent applicants challenging decisions of the
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`Patent Office. Even if interference estoppel were available to Sawai as a defense –
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`and it is not – it would not apply here, because the subject matter that Sawai
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`alleges was disclaimed was not described in the application of the party that won
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`the interference proceeding. See Ex Parte Cullis, 11 U.S.P.Q. 2d 1876 (BPAI
`
`1989). Even if interference estoppel were applicable here, Sawai could not raise it
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`as a proposed basis of invalidity in this IPR proceeding because it is not a
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`“patented or printed publication” on which inter partes review can be based. See
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`WL Gore & Associates, Inc. v. Lifeport Science LLC, IPR2014-01319, Paper No. 7
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`at 15 (PTAB Feb. 23, 2015).
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`Worse than the legal missteps Sawai makes in trying to manufacture a new
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`invalidity defense of interference estoppel is Sawai’s attempt to take factual
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`5
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`
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`arguments made in connection with the interference that were rejected by the
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`Board of Patent Appeals and Interferences and the Federal Circuit and, without
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`explanation or qualification, hold them forth as “unquestionably correct” or
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`“undoubtedly correct.” [See Pet. at 4, 40, 43.] While Sawai discusses the
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`interference at length, devoting nineteen (19) pages of its Petition to interference
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`related arguments, the Petition is devoid of any meaningful discussion of the
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`Federal Circuit’s decision or the Board’s rulings with respect to the interference.
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`Sawai’s silence is telling. Clearly, arguments already rejected by the Federal
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`Circuit do not form a sound foundation for an invalidity challenge.
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`II.
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`SAWAI’S OBVIOUSNESS ARGUMENTS FAIL
`
`Sawai’s attempts to build a case for invalidity based on Kesseler and Picard
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`cannot form a reasonable basis for invalidity of compound claim 1 or method claim
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`2 of the ‘336 Patent, because those hindsight efforts are so contrary to law, reason,
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`and sound chemistry.
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`A. RELEVANT ASPECTS OF THE PROSECUTION HISTORY
`AND INTERFERENCE PROCEEDINGS
`
`Throughout its petition, Sawai repeatedly states that NCI lost the
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`interference proceedings involving U.S. Patent Application No. 08,233,752
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`(“Fujikawa ‘752 Application”), the grandparent application of the ‘336 Patent.
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`The interference proceedings, however, did not involve the claims of the ‘336
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`Patent. While NCI tried repeatedly to add a count corresponding to the claims of
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`6
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`

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`
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`the ‘336 Patent, the Board rejected NCI’s efforts because the disclosure of the
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`other party to the interference, Wattanasin, did not support the proposed additional
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`count.
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`The Fujikawa ‘752 Application was filed on August 19, 1988. [Ex. 1004 at
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`1.] After the Fujikawa ‘752 Application was filed, NCI requested that an
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`interference be declared between its application and Picard. [Id. at 130-33.] In an
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`August 27, 1990 interview, the Examiner indicated that an interference “will be
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`declared in the near future.” [Id. at 419.] On December 19, 1990, long before any
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`interference was declared, the patentee filed an amendment cancelling claim 10, a
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`claim that corresponds to, but is slightly broader than current claim 1 of the ‘336
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`Patent. [Id. at 422-23.] Patentee explained:
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`Applicants have discovered that the subject matter of Claim 10, and
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`related subject matter, exhibits unobvious and distinguishing
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`properties, with respect to the genus circumscribed by the remaining
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`claims, as well as the claims of the patent with which an Interference
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`is to be declared. Accordingly, that claim will be pursued in a
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`separate application.
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`[Id. at 423.] On the same day, the patentee filed a continuation application in
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`which it pursued claims corresponding to the cancelled claim 10. [Ex. 1003 at 3-
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`4.]
`
`7
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`

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`
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`On March 11, 1992, interference No. 102,648 was declared between the
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`Fujikawa ‘752 Application, Picard, and U.S. Patent App. No. 07/498,301
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`(“Wattanasin”). [Ex. 1004 at 429.] The interference included two counts: the first
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`directed to a broad genus of compounds encompassing, inter alia, the species of
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`claim 1 of the ‘336 Patent, and the second directed to a method of inhibiting
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`cholesterol biosynthesis by administering a compound from the genus of count 1.3
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`Shortly thereafter, Picard requested an adverse judgment, effectively conceding
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`that it could not establish an invention date before Fujikawa’s priority date. [Ex.
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`1005 at 27.]
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`As noted above, the interference did not include a count corresponding to the
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`claims of the ‘336 Patent. In its initial motions, NCI moved to redefine the
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`interference by adding Counts 3 and 4, directed to compounds of Count 1 where R5
`
`was cyclopropyl, and to a method of inhibiting cholesterol biosynthesis by
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`administering a compound of proposed Count 3. [Ex. 1005 at 35-45.] In support
`
`of its motion to redefine the interference, the patentee included the declaration of
`
`Masaki Kitahara, Ph.D., who explained that compounds having a cyclopropyl
`
`substituent at R5 showed unexpected and enhanced inhibitory activity even as
`
`
`3 The interference was ultimately combined with interference No. 102,975. [Ex.
`
`1005 at 1948-49.]
`
`8
`
`

`
`
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`compared to otherwise identical compounds where R5 was isopropyl or n-propyl.
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`[Id. at 46-54.]
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`The Board declined to add Counts 3 and 4, finding that the subgenus of
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`Count 3 was not disclosed in Wattanasin. Importantly, in finding that Wattanasin
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`(not Fujikawa) did not support a count corresponding to the claims of the ‘336
`
`Patent, the Board had to decide whether a disclosure of cycloalkyl for R5 in
`
`Wattanasin would have led a POSA to the cyclopropyl compounds of proposed
`
`additional count. The Board found unequivocally that it would not. [See Ex. 1005
`
`at 4149 (Final Decision in Interference No. 102,648) at 10 (finding no “motivation
`
`to guide one skilled in the art to select the cyclopropyl compounds of proposed
`
`claims . . . .”)); see also Ex. 1005 at 4192-3 (Decision on Request for
`
`Reconsideration) at 3-4 (maintaining this finding).] On appeal, the Federal Circuit
`
`reached the same conclusion, explaining:
`
`Although, in hindsight, the substitution of cyclopropyl for isopropyl
`
`might seem simple and foreseeable, Wattanasin’s disclosure provides
`
`no indication that position R would be a better candidate for
`
`substitution than any other.
`
`Fujikawa v. Wattanasin, 93 F.3d 1559, 1571 (Fed. Cir. 1996).
`
`While the interference was pending, prosecution of the patent application
`
`that resulted in the ‘336 Patent (U.S. Patent Application No. 883,398, “the ‘398
`
`Application”) was suspended. After the Board found, and the Federal Circuit
`
`9
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`

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`
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`affirmed, that Wattanasin had proved an earlier invention date than Fujikawa
`
`(NCI) for the genus claim of Count 1, prosecution of the ‘398 Application
`
`resumed. The Examiner was undoubtedly aware of the interference proceedings,
`
`as is clear from the office communications referencing the interference. In fact,
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`Examiner Richter, who was the primary Examiner in the ‘398 Application, had
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`taken over as Examiner in the Fujikawa ‘752 Application, the application involved
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`in the interference. [See Ex. 1004 at 1, 425-26.] The Examiner, correctly, did not
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`view the interference as affecting the patentability of the claims of the ‘398
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`Application, and allowed those claims. [Ex. 1002 at 144.]
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`With the ‘336 Patent in place, NCI and its licensee Kowa Company Ltd.
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`spent the large amounts of both money and time necessary to conduct clinical trials
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`of the compound claimed in claim 1 for the uses claimed in claim 2, and obtained
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`FDA approval to market that compound for those uses on August 3, 2009. [See
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`Ex. 1002 at 161-176 (describing IND and NDA timeline for Livalo®).]
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`B.
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`SUMMARY OF THE ‘336 PATENT
`
`The ‘336 Patent has two claims. Claim 1 provides:
`
`10
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`

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`
`
`
`
`[Ex. 1001 at Col. 32:22-36.] Claim 2 is directed to a “method for reducing
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`hyperlipidemia, hyperlipoproteinemia or atherosclerosis which comprises
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`administering an effective amount of the compound of the formula A as defined in
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`claim 1.” [Id. at Col. 32:36-40.]
`
`C.
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`PERSON OF ORDINARY SKILL IN THE ART
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`Patent Owner disagrees with Sawai’s definition of the person of ordinary
`
`skill in the art (“POSA”) to the extent that Sawai contends such a person would
`
`need to have what appears to be an expert level of familiarity with
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`mevalonolactones. However, although Patent Owner disagrees with Sawai’s
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`definition of the POSA, Sawai’s Petition does not warrant institution even under its
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`own definition. NCI reserves the right to offer evidence and argument on the
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`proper definition of a POSA for this proceeding in the event the Board were to
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`institute review.
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`11
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`

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`
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`D. LEGAL STANDARD FOR INSTITUTION OF INTER PARTES
`REVIEW
`
`
`The Board may not institute review unless it determines that there is “a
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`reasonable likelihood that the petitioner would prevail with respect to at least one
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`of the claims challenged in the petition.” 35 U.S.C. § 314(a). The Board has, on
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`multiple occasions, found that this standard was not met in validity challenges
`
`based on chemical obviousness, for reasons which have direct applicability in this
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`case. See, e.g., Mylan Pharm. Inc., IPR2015-01069, Paper No. 24 at 7 (PTAB Oct.
`
`20, 2015) (no reasonable likelihood of invalidity for obviousness where the process
`
`of modifying the proposed lead compound “would have required a number of
`
`chemical alterations, each having a number of possible combinations”); Mylan
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`Pharm. Inc. v. Gilead Sciences, Inc., IPR2014-00885, Paper No. 15 at 9-11 (PTAB
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`Dec. 9, 2014) (denying institution of IPR for failure to identify teachings which
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`would have “prompted an ordinary artisan to modify [a lead compound] so as to
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`arrive at a compound encompassed by the challenged claims”); see also Torrent
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`Pharm., Ltd. v. Merck Frosst Canada & Co., IPR2014-00559, Paper No. 8 at 7, 9
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`(PTAB Oct. 1, 2014).
`
`E.
`
`LEGAL PRINCIPLES REGARDING CHEMICAL
`OBVIOUSNESS
`
`Patent challengers may not prove obviousness through “hindsight
`
`reconstruction by using ‘the patent in suit as a guide through the maze of prior art
`
`12
`
`

`
`
`
`references, combining the right references in the right way so as to achieve the
`
`result of the claims in suit.’” Grain Processing Corp. v. Am. Maize-Prods. Co.,
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`840 F.2d 902, 907 (Fed. Cir. 1988) (citing Orthopedic Equip. Co. v. United States,
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`702 F.2d 1005, 1012 (Fed. Cir. 1983)); see also Mylan Pharm. Inc., IPR2014-
`
`00885, Paper No. 15 at 9 (“[I]t is impermissible within the framework of section
`
`103 to pick and choose from any one reference only so much of it as will support a
`
`given position, to the exclusion of other parts necessary to the full appreciation of
`
`what such reference fairly suggests to one of ordinary skill in the art.”) (citing In re
`
`Hedges, 783 F.2d 1038, 1041 (Fed. Cir. 1986)).
`
`“[W]hether a new chemical compound would have been prima facie obvious
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`over particular prior art compounds ordinarily follows a two-part inquiry.” Otsuka
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`Pharm. Co. v. Sandoz, Inc., 678 F.3d 1280, 1291 (Fed. Cir. 2012), cert. denied, 133
`
`S. Ct. 940 (2013). The first part asks whether a POSA at the time of the invention
`
`would have selected the asserted prior art compound as a lead compound. Id.
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`(noting that a lead compound is “a compound in the prior art that would be most
`
`promising to modify in order to improve upon its . . . activity and obtain a
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`compound with better activity”) (citation omitted)); see also Takeda Chem. Indus.,
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`Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007). The second
`
`part asks whether the prior art would have provided the POSA with a reason or
`
`motivation to modify the lead compound and make the claimed compound with a
`
`13
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`

`
`
`
`reasonable expectation of success. Otsuka Pharm. Co., 678 F.3d at 1292; see also
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`Daiichi Sankyo Co., Ltd. v. Matrix Labs, Ltd., 619 F.3d 1346, 1352 (Fed. Cir.
`
`2010), cert. denied, 131 S. Ct. 1678 (2011); Apotex Inc. v. Merck Sharp & Dohme
`
`Corp., IPR2015-00419, Paper No. 14 at 7-8 (PTAB June 25, 2015). “[P]roving a
`
`reason to select a compound as a lead compound depends on more than just
`
`structural similarity, but also knowledge in the art of the functional properties and
`
`limitations of the prior art compounds.” Daiichi Sankyo Co., Ltd., 619 F.3d at
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`1354; see also Eli Lilly & Co. v. Zenith Goldline Pharm. Inc., 471 F.3d 1369, 1377-
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`79 (Fed. Cir. 2006). Moreover, references teach away from a claimed invention
`
`where a POSA would be discouraged from following the path set out in the
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`reference, or would be led in a different direction than the applicant. Depuy Spine,
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`Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009).
`
`F.
`
`SAWAI HAS FAILED TO DEMONSTRATE A REASONABLE
`LIKELIHOOD THAT THE CHALLENGED CLAIMS WOULD
`HAVE BEEN OBVIOUS OVER KESSELER IN VIEW OF
`PICARD.
`
`
`
`Sawai’s Petition fails to mention that both Kesseler and Picard were raised
`
`during NCI’s lengthy, prior interference proceedings before the Patent Office.
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`[See, e.g., Ex. 1005 at 27, 203.] Indeed, Picard requested adverse judgment in the
`
`interference, effectively conceding that it could not establish priority to NCI. [Id.
`
`at 27.] Sawai’s obviousness arguments fail on the merits, even assuming Kesseler
`
`and Picard were deemed to be prior art to the ‘336 Patent.
`
`14
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`

`
`
`
`1.
`
`Sawai fails to supply a coherent reason for why a POSA
`would have selected Compound IIac of Kesseler as a “lead
`compound” for an HMG-CoA reductase inhibitor.
`
`
`Sawai concedes that “[b]y 1988 there were a number of pharmaceutical
`
`companies researching HMG-CoA reductase inhibitors directed to use as
`
`cholesterol-lowering agents.” [Pet. at 15.] Sawai also concedes that some of the
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`HMG-CoA reductase inhibitors being investigated at that time were “based on
`
`natural products,” some were “synthetic,” and some were “semisynthetic.” [Id. at
`
`17.] Sawai further concedes that among the “synthetic” inhibitors, multiple
`
`different molecular cores were being investigated. [Id. at 18.] Still further,
`
`Sawai’s expert admits that any distinction between these “natural product,”
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`“synthetic,” and “semisynthetic” inhibitors of HMG-CoA reductase is entirely
`
`“arbitrary.” [Ex. 1012 (Brown Decl.) at ¶ 25 n.1.] This is a concession that at the
`
`time of the ‘336 Paten