Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 1 of 73
`
`Kowa Company, Ltd. et al. v. Aurobindo Pharma Limited et al.,
`Civil Action No. 14-CV-2497 (PAC) (and related cases)
`
`
`
`
`
`Exhibit 8 to Supplemental Declaration of
`Thomas R. Burns, dated June 10, 2015, in
`support of Defendants’ Joint Responsive
`Claim Construction Brief
`
`
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 2 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`Mylan Pharmaceuticals Inc., Petitioner
`
`v.
`
`Nissan Chemical Industries Ltd.
`Patent Owner
`
`U.S. Patent No. 5,856,336 to Fujikawa et al.
`Issue Date: January 5, 1999
`Title: Quinoline Type Mevalonolactones
`
`_____________________
`
`Inter Partes Review No.: IPR2015-01069
`
`Petition for Inter Partes Review of U.S. Patent No. 5,856,336
`Under 35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42.1-.80, 42.100-.123
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 3 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION ..............................................................................................1
`
`II. MANDATORY NOTICES (37 C.F.R. § 42.8(A)(1))......................................1
`A.
`Each Real Party-in-Interest (37 C.F.R. § 42.8(b)(1)) ............................1
`B.
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2)) ..............................1
`1.
`Judicial Matters Involving the ’336 patent ..................................1
`2.
`Administrative Matters .................................................................2
`Designation of Lead and Back-Up Counsel (37 C.F.R. §
`42.8(b)(3)) ................................................................................................2
`Notice of Service Information (37 C.F.R. § 42.8(b)(4)) .......................2
`
`D.
`
`C.
`
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.104(A)) AND
`PROCEDURAL STATEMENTS......................................................................2
`
`IV.
`
`V.
`
`VI.
`
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(B)) AND
`STATEMENT OF THE PRECISE RELIEF REQUESTED (37 C.F.R.
`§ 42.22(A))..........................................................................................................3
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW .............5
`
`STATEMENT OF REASONS FOR THE RELIEF REQUESTED (37
`C.F.R. § 42.22(A))..............................................................................................5
`A.
`Summary of the Argument......................................................................5
`B.
`The Claims of the ’336 Patent.................................................................6
`C.
`The Priority Date of the ’336 Patent.....................................................10
`1.
`The Earliest Effective Date for the Challenged Claims of
`the ’336 Patent Is August 3, 1988 ..............................................10
`
`VII. THE ’336 PATENT AND CLAIM CONSTRUCTION................................15
`A.
`POSA......................................................................................................15
`B.
`Ground 1: Claims 1 and 2 of the ’336 Patent Are Unpatentable
`Under 35 U.S.C. § 103 ..........................................................................16
`1.
`The Scope and Content of the Prior Art ....................................16
`2.
`Legal Principles Regarding Structural Obviousness.................16
`3.
`Claim 1 Would Have Been Obvious under 35 U.S.C. §
`103................................................................................................17
`Claim 2 Would Have Been Obvious Under 35 U.S.C. §
`103................................................................................................47
`
`4.
`
`i
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 4 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`5.
`
`Fluvastatin Would Have Been Selected as the Lead
`Compound for at Least the Following Additional
`Reasons ........................................................................................50
`Any Secondary Considerations Fail to Overcome the
`Showing of Obviousness ............................................................57
`Ground 2: Claims 1 and 2 of the ’336 Patent are Unpatentable
`Under 35 U.S.C. § 102 in View of the Picard ’419 Patent..................58
`
`6.
`
`C.
`
`VIII. CONCLUSION.................................................................................................60
`
`ii
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 5 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`CASES
`
`Abbvie Inc. v. Mathilda & Terence Kennedy Inst. of Rheumatology Trust,
`764 F.3d 1366 (Fed. Cir. 2014).............................................................................59
`
`Aventis Pharma Deutschland GmbH v. Lupin, Ltd.,
`499 F.3d 1293 (Fed. Cir. 2007).......................................................................42, 43
`
`Bristol-Myers Squibb Co. v. Teva Pharm. USA, Inc.,
`752 F.3d 967 (Fed. Cir. 2014)........................................................................passim
`
`Daiichi Sankyo Co. v. Matrix Labs., Ltd.,
`619 F.3d 1346 (Fed. Cir. 2010).............................................................................36
`
`Eisai Co. v. Dr. Reddy’s Labs., Ltd.,
`533 F.3d 1353 (Fed. Cir. 2008).............................................................................54
`
`Eli Lilly and Co. v. Zenith Goldline Pharma, Inc.,
`471 F.3d 1369 (2006) ............................................................................................17
`
`In re Aller,
`220 F.2d 454 (C.C.P.A. 1955) ..............................................................................49
`
`In re Dillon,
`919 F.2d 688 (Fed. Cir. 1990)...............................................................................39
`
`In re Gosteli,
`872 F.2d 1008 (Fed. Cir. 1989) .............................................................................13
`
`In re Ruschig,
`379 F.2d 990 (C.C.P.A. 1967) ..............................................................................13
`
`In re Wilder,
`563 F.2d 457 (C.C.P.A. 1977) ..............................................................................39
`
`KSR Int’l Co. v. Teleflex, Inc.,
`550 U.S. 398 (2007)...........................................................................................5, 15
`
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988)...............................................................................57
`
`iii
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 6 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`Otsuka Pharm. Co., Ltd. v. Sandoz, Inc.,
`678 F.3d 1280 (Fed. Cir. 2012).................................................................17, 28, 45
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2008)......................................................................passim
`
`PowerOasis, Inc. v. T-Mobile USA, Inc.,
`522 F.3d 1299 (Fed. Cir. 2008) .............................................................................13
`
`Schering Corp. v. Geneva Pharm., Inc.,
`339 F.3d 1373 (Fed. Cir. 2003).......................................................................58, 59
`
`SkinMedica, Inc. v. Histogen, Inc.,
`727 F.3d 1187 (Fed. Cir. 2013).............................................................................48
`
`Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd.,
`492 F.3d 1350 (Fed. Cir. 2007).............................................................................17
`
`OTHER CASES
`
`Amneal Pharm., LLC v. Supernus Pharm., Inc.
`IPR2013-00368 ......................................................................................................57
`
`Kowa Company, Ltd. et al v. Amneal Pharmaceuticals, LLC,
`1:14-cv-02758 (S.D.N.Y., Apr. 17, 2014)..............................................................1
`
`Kowa Company, Ltd. et al v. Aurobindo Pharma Limited et al.,
`1:14-cv-02497 (S.D.N.Y., Apr. 9, 2014)................................................................2
`
`Kowa Company, Ltd. et al v. Mylan, Inc. et al.,
`1:14-cv-02647 (S.D.N.Y., Apr. 14, 2014)..............................................................1
`
`Kowa Company, Ltd. et al v. Orient Pharma Co., Ltd.,
`1:14-cv-02759 (S.D.N.Y., Apr. 17, 2014)..............................................................1
`
`Kowa Company, Ltd. et al v. Sawai USA, Inc. et al.,
`1:14-cv-05575 (S.D.N.Y., July 23, 2014) ..............................................................1
`
`Kowa Company, Ltd. et al v. Zydus Pharmaceuticals (USA) Inc. et al.,
`1:14-cv-02760 (S.D.N.Y., Apr. 17, 2014)..............................................................1
`
`Metrics, Inc. v. Senju Pharm. Co.,
`IPR 2014-01041.....................................................................................................49
`
`iv
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 7 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`FEDERAL STATUTES
`
`35 U.S.C. § 102 .....................................................................................................58, 60
`
`35 U.S.C. § 103 ....................................................................................................passim
`
`35 U.S.C. § 112 ..........................................................................................................13
`
`35 U.S.C. § 119 ...........................................................................................................11
`
`REGULATIONS
`37 C.F.R. § 42.6(d)........................................................................................................3
`
`37 C.F.R. § 42.8(a)(1) ...................................................................................................1
`
`37 C.F.R. § 42.8(b)(1)...................................................................................................1
`
`37 C.F.R. § 42.8(b)(3)...................................................................................................2
`
`37 C.F.R. § 42.10(b)......................................................................................................3
`
`37 C.F.R. § 42.63(e)......................................................................................................3
`
`37 C.F.R. § 42.22(a)......................................................................................................3
`
`37 C.F.R. § 42.100(b) .................................................................................................15
`
`37 C.F.R. § 42.104(a)....................................................................................................2
`
`37 C.F.R. § 42.106(a)................................................................................................2, 3
`
`v
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 8 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`Exhibit
`#
`
`Petitioner’s Exhibit List
`
`Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`U.S. Patent No. 5,856,336 (“the ’336 patent”)
`
`U.S. Patent No. 5,872,130
`
`U.S. Application Ser. No. 233,752
`
`Japanese Patent Application No. JP 62-207224 with English
`translation provided by the ’336 patentee from U.S. Application Ser.
`07/233,752,
`related family member of
`the ’336 patent, with
`accompanying sworn declaration provided by the patentee to the
`USPTO attesting to the accuracy of the translation.
`
`JP 63-15585 with English
`Japanese Patent Application No.
`translation provided by the ’336 patentee from U.S. Application Ser.
`07/233,752,
`related family member of
`the ’336 patent, with
`accompanying sworn declaration provided by the patentee to the
`USPTO attesting to the accuracy of the translation.
`
`Japanese Patent Application No. JP 63-193606 with English
`translation provided by the ’336 patentee from U.S. Application Ser.
`07/233,752,
`related family member of
`the ’336 patent, with
`accompanying sworn declaration provided by the patentee to the
`USPTO attesting to the accuracy of the translation.
`
`Curriculum Vitae of Roger Frank Newton, Ph.D.
`
`Declaration of Roger Frank Newton, Ph.D.
`
`Faizulla G. Kathawala, et al., XU 62-320, An HMG-CoA Reductase
`Inhibitor, More Potent Than Compactin, Abstract for American
`Chemical Society library stamp July 29, 1987
`
`1010
`
`U.S. Patent No. 4,739,073
`
`vi
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 9 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`Exhibit
`#
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`Description
`
`R. G. Engstrom et al., Hypolipoproteinemic Effects of a Potent
`HMG-CoA Reductase Inhibitor, IX International Symposium on
`Drugs Affecting Lipid Metabolism, Florence (Italy), Oct. 22-25,
`1986
`
`Jonathan A. Tobert, New Developments in Lipid-Lowering Therapy:
`The Role of
`Inhibitors of Hydroxymethylglutaryl-Coenzyme A
`Reductase, 76 CIRCULATION 534 (1987)
`
`Ta-Jyh Lee, Synthesis, SARs and Therapeutic Potential of HMG-
`CoA Reductase Inhibitors, 8 TRENDS PHARMACOL. SCI. 442 (1987)
`
`Akira Endo et al., ML-236A, ML-236B, and ML-236C, New
`Inhibitors of Cholesterogenesis Produced by Penicillium Citrinium,
`29 J. ANTIBIOTICS 1346 (1976)
`
`Declaration of David Gortler, Pharm.D.
`
`U.S. Patent No. 4,647,576
`
`Approved Drug Products with Therapeutic Equivalence Evaluations
`(“Orange Book”), FOOD AND DRUG ADMINISTRATION,
`available
`at
`listing
`for
`active
`ingredient
`“lovastatin,”
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?A
`ppl No=019643&TABLE1= OB Disc (last visited April 13, 2015)
`
`U.S. Patent No. 4,613,610
`
`U.S. Patent No. 4,681,893
`
`U.S. Patent No. 4,751,235
`
`U.S. Patent No. 4,761,419
`
`Alfred W. Alberts, Mevinolin: A Highly Potent Competitive
`Inhibitor of Hydroxymethylglutaryl-Coenzyme a Reductase and a
`Cholesterol-Lowering Agent, 77 PROC. NAT’L. ACAD. SCI. U.S.A.
`3957 (1980)
`
`vii
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 10 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`Exhibit
`#
`
`Description
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`J.B. Taylor & P.D. Kennewell, Introductory Medicinal Chemistry
`94 (1981)
`
`Corwin Hansch et al., “Aromatic” Substituent Constants for
`Structure-Activity Correlations, 16 J. MED. CHEM. 1207 (1973)
`(“Hansch II”)
`
`European Patent No. 0114027
`
`U.S. Patent No. 4,537,859
`
`Stephen M. Berge, Pharmaceutical Salts, 66 J. PHARM. SCI. 1
`(1977)
`
`Philip L. Gould, Salt Selection for Basic Drugs, 33 INT. J. PHARM.
`201 (1986)
`
`John T. Suh et al., Angiotensin-Converting Enzyme Inhibitors New
`Orally
`Active
`Antihypertensive
`(Mercaptoalkanoyl)-
`and
`[(Acylthio)alkanoyl]glycine Derivatives, 28 J. MED. CHEM. 57
`(1985)
`
`Michael S. Brown, M.D. et al., Lowering Plasma Cholesterol by
`Raising LDL Receptors, 305 NEW ENG. J. MED. 515 (1981)
`
`Fujikawa Reply to the Opposition to Fujikawa et al.’s Motion to
`Add Counts 3 and 4, received July 21, 1992. U.S. Interference No.
`102,608 (“Paper No. 32”)
`
`Declaration of Masaki Kitahara, submitted in the ’336 patent, dated
`May 25, 1992
`
`O. E. Schultz et al., Schätzung des Verteilungfkoeffizienten mit Hilfe
`Quantenchemischer Molekülgroen,
`25
`ZEITSCHRIFT
`FÜR
`NATURFORSCHUNG B 1024 (1970), certified English translation
`included
`
`viii
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 11 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`Exhibit
`#
`
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`Description
`
`Corwin Hansch et al., The Effect of Intramolecular Hydrophobic
`Bonding on Partition Coefficients, 32 J. ORG. CHEM. 2583 (1967)
`(“Hansch I”)
`
`European Patent Publication 179,559
`
`I. T. Scoular et al., Human Studies on the Bioavailability of a
`Quaternary Ammonium Compound, Tiemonium Iodide
`and
`Tiemonium Methosulphate, 4 CURR. MED. RES. OPIN. 732 (1977)
`
`Curriculum Vitae of David Gortler, Pharm.D.
`
`David J. Shapiro & Victor W. Rodwell, Regulation of Hepatic 3-
`Hydroxy-3-Methylglutaryl Coenzyme A Reductase and Cholesterol
`Synthesis, 246 J. BIOL. CHEM. 3210 (1971)
`
`Yoshio Tsujita et al., CS-514, A Competitive Inhibitor of 3-Hydroxy-
`3-Methylglutaryl Coenzyme
`A
`Reductase:
`Tissue-Selective
`Inhibition of Sterol Synthesis and Hypolipidemic Effect on Various
`Animal Species, 877 BIOCHIMICA ET BIOPHYSICA ACTA 50 (1986)
`
`al., 3-Hydroxy-3-Methylglutaryl-Coenzyme A
`G.E. Stokker et
`Reductase Inhibitors. 1. Structural Modification of 5-Substituted
`3,5-Dihydroxypentanoic Acids and Their Lactone Derivatives, 28 J.
`MED. CHEM. 347 (1985) (“Stokker I”)
`
`al., 3-Hydroxy-3-Methylglutaryl-Coenzyme A
`G.E. Stokker et
`Reductase Inhibitors 3. 7-(3,5-Disubstituted [1,1’-biphenyl]-2-yl)-
`3,5-Dihydroxy-6-Heptenoic Acids and Their Lactone Derivatives,
`29 J. MED. CHEM. 170, 175 (1986) (“Stokker II”)
`
`1042
`
`Final Hearing, November 22, 1994. U.S. Interference No. 102,608
`(“Paper No. 122”)
`
`ix
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 12 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`I.
`
`INTRODUCTION
`
`Mylan Pharmaceuticals Inc. (“Petitioner”) respectfully petitions for Inter
`
`Partes Review (“IPR”) of Claims 1 and 2 (the “challenged claims”) of U.S. Patent
`
`No. 5,856,336 to Fujikawa et al. entitled, “Quinoline Type Mevalonolactones”
`
`(“the ’336 patent”) (EX1001). Based on the records of the U.S. Patent and
`
`Trademark Office (“USPTO”), the ’336 patent is assigned to Nissan Chemical
`
`Industries Ltd.
`
`II. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1))
`
`A.
`
`Each Real Party-in-Interest (37 C.F.R. § 42.8(b)(1))
`
`The real parties-in-interest are Mylan Pharmaceuticals Inc. and Mylan Inc.
`
`B.
`
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2))
`
`1.
`
`Judicial Matters Involving the ’336 patent
`
`Petitioner is a defendant to the following litigation involving the ’336 patent:
`
`Kowa Company, Ltd. et al v. Mylan, Inc. et al., 1:14-cv-02647 (S.D.N.Y., Apr. 14,
`
`2014). Petitioner is aware of at least the following pending judicial matters
`
`involving the ’336 patent: Kowa Company, Ltd. et al v. Sawai USA, Inc. et al.,
`
`1:14-cv-05575 (S.D.N.Y., July 23, 2014); Kowa Company, Ltd. et al v. Zydus
`
`Pharmaceuticals (USA) Inc. et al., 1:14-cv-02760 (S.D.N.Y., Apr. 17, 2014);
`
`Kowa Company, Ltd. et al v. Orient Pharma Co., Ltd., 1:14-cv-02759 (S.D.N.Y.,
`
`Apr. 17, 2014); Kowa Company, Ltd. et al v. Amneal Pharmaceuticals, LLC, 1:14-
`
`1
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 13 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`cv-02758 (S.D.N.Y., Apr. 17, 2014); and Kowa Company, Ltd. et al v. Aurobindo
`
`Pharma Limited et al., 1:14-cv-02497 (S.D.N.Y., Apr. 9, 2014).
`
`2.
`
`Administrative Matters
`
`The ’336 patent is a division of U.S. Patent Number 5,872,130, which issued
`
`on December 16, 1999. The ’130 patent is a continuation of U.S. Application No.
`
`07/233,752,
`
`filed August 19, 1988, which is abandoned. U.S. Patent No.
`
`5,854,259, a division of the ’336 patent, issued on December 29, 1998.
`
`C.
`
`Designation of Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3))
`
`Lead Counsel
`Jitendra Malik
`Reg. No. 55823
`ALSTON & BIRD LLP
`4721 Emperor Blvd., Suite 400
`Durham, North Carolina 27703
`
`Back-Up Counsel
`Deanne M. Mazzochi
`Reg. No. 50158
`RAKOCZY MOLINO MAZZOCHI SIWIK LLP
`6 West Hubbard St., Suite 500
`Chicago, Illinois 60654
`
`D.
`
`Notice of Service Information (37 C.F.R. § 42.8(b)(4))
`
`Please direct all correspondence to lead and back-up counsel at the above
`
`address. Petitioner consents to email service at:
`
`thomas.parker@alston.com,
`
`jitty.malik@alston.com, bryan.skelton@alston.com, dmazzochi@rmmslegal.com,
`
`wrakoczy@rmmslegal.com, abrody@rmmslegal.com and tburns@rmmslegal.com.
`
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)) AND
`PROCEDURAL STATEMENTS
`
`Petitioner certifies that (1) the ’336 patent is available for IPR; and (2)
`
`Petitioner is not barred or estopped from requesting IPR of any claim of the ’336
`
`2
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 14 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`patent on the grounds identified herein. This Petition is filed in accordance with 37
`
`C.F.R. § 42.106(a). Concurrently filed herewith are a Power of Attorney and an
`
`Exhibit List pursuant to § 42.10(b) and § 42.63(e), respectively. The required fee
`
`is paid when filing the Petition, and the Office is authorized to charge any fee
`
`deficiencies and credit overpayments, to Deposit Acct. No. 160605 (Customer ID
`
`No. 00826).
`
`IV.
`
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b)) AND
`STATEMENT OF THE PRECISE RELIEF REQUESTED (37 C.F.R. §
`42.22(a))
`
`Petitioner requests inter partes review and cancellation of Claims 1 and 2 of
`
`the ’336 patent under 35 U.S.C. §§ 102 and 103. The ’336 patent is to be reviewed
`
`under pre-AIA §§ 102 and 103. Petitioner’s detailed statement of the reasons for
`
`relief requested is set forth below in the section titled, “Statement of Reasons for
`
`Relief Requested.” Pursuant to 37 C.F.R. § 42.6(d), copies of the exhibits are filed
`
`herewith.
`
`In support of the proposed grounds for unpatentability, this Petition is
`
`accompanied by a Declaration of Roger Frank Newton, Ph.D. (EX1008), and a
`
`Declaration of Dr. David Gortler (EX1015).
`
`The challenged claims of the ’336 patent are generally directed to the
`
`calcium salt of compounds having the formula, Z = —CH(OH)—CH2—CH(OH)
`
`—CH2—COO.1/2Ca,
`
`including the compound “pitavastatin” and methods of
`
`reducing
`
`hyperlipidemia,
`
`hyperlipoproteinemia,
`
`or
`
`atherosclerosis
`
`by
`
`3
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 15 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`administering an effective amount of the compound of Claim 1. Claims 1 and 2 of
`
`the ’336 patent are unpatentable based on the following grounds:
`
`Ground
`11
`
`12
`
`2
`
`References
`and
`’073
`patent
`Kathawala
`in
`Abstract,
`Kathawala
`’576,
`combination with Hoefle
`’235,
`Roth
`’893,
`Anderson
`Wareing ’610, Hansch II, Suh,
`Berge, and Gould in view of the
`knowledge of a POSA.
`and
`Kathawala
`’073
`patent
`in
`Kathawala
`Abstract,
`’576,
`combination with Hoefle
`’235,
`Roth
`’893,
`Anderson
`Wareing ’610, Hansch II, Suh,
`Berge, Gould, Engstrom Abstract,
`Tobert, Lee, and Picard ’419 patent
`in view of the knowledge of a
`POSA.
`Picard ’419 patent
`
`Basis Claims Challenged
`
`103
`
`1 and 2
`
`103
`
`1 and 2
`
`102
`
`1 and 2
`
`In addition to the primary references listed above, additional prior art
`
`references will provide further background in the art and motivation to combine
`
`the teachings of these references and/or further support why a person of ordinary
`
`1 In the event the Board determines that JP 62-207224 (EX1004), filed August 20,
`
`1987, supports the priority claim of the ’336 patent.
`
`2 In the event the Board determines that JP 62-207224 (EX1004), filed August 20,
`
`1987, does not support the priority claim of the ’336 patent, but that the priority
`
`claim is supported by JP 63-15585 (EX1005), filed January 26, 1988.
`
`4
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 16 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`skill in the art (“POSA”) would have had a reasonable expectation of success in
`
`combining the teachings of the references to arrive at the methods recited in the
`
`challenged claims.
`
`V.
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`
`A petition for IPR must demonstrate “a reasonable likelihood that
`
`the
`
`petitioner would prevail with respect to at least one of the claims challenged in the
`
`petition.” 35 U.S.C. § 314(a). This Petition meets this threshold. As explained
`
`below, there is a reasonable likelihood that Petitioner will prevail with respect to at
`
`least one of the challenged claims.
`
`VI.
`
`STATEMENT OF REASONS FOR THE RELIEF REQUESTED (37
`C.F.R. § 42.22(a))
`
`A.
`
`Summary of the Argument
`
`The claims of the ’336 patent (1 and 2) are unpatentable for failing to satisfy
`
`the nonobviousness requirements of 35 U.S.C. § 103, based on a combination of
`
`the relevant prior art in view of the knowledge of a person of ordinary skill in the
`
`art (“POSA”) and/or as obvious to try, as well as unpatentable for being anticipated
`
`by the prior art under 35 U.S.C. § 102. To this end, the alleged “inventions”
`
`involved no more than selecting an obvious prior art lead compound (fluvastatin),
`
`and routinely modifying it, leading to a predictable result. The claims are not
`
`inventive in any way and are invalid as a matter of law as obvious. KSR Int’l Co.
`
`5
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 17 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`v. Teleflex, Inc., 550 U.S. 398, 417 (2007). Claims 1 and 2 of the ’336 patent also
`
`are invalid as being anticipated under 35 U.S.C. § 102 by the ’419 Picard patent.
`
`B.
`
`The Claims of the ’336 Patent
`
`The challenged claims of the ’336 patent are reproduced below:
`
`1.
`
`A compound of the formula,
`
`Z = —CH(OH)—CH2—CH(OH) —CH2—COO.1/2Ca.3
`
`hyperlipidemia,
`reducing
`for
`A method
`2.
`hyperlipoproteinemia or atherosclerosis, which comprises
`administering an effective amount of the compound of
`Formula A as defined in Claim 1.
`
`Claim 1 is purportedly directed to the structure of the calcium salt of a chemical
`
`formula that includes the drug compound “pitavastatin.” Claim 2 is purportedly
`
`3 Petitioner understands that the Patent Owner contends that the “Δ” in Claim 1
`
`represents a cyclopropyl group found in pitavastatin. Although Petitioner disputes
`
`this construction, solely for the purposes of this IPR, Petitioner will accept the
`
`Patent Owner’s construction in evaluating the prior art.
`
`6
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 18 of 73
`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 18 of 73
`
`Petition for Inter Partes Review of USPN 5,856,336
`
`directed to a method of reducing hyperlipidemia, hyperlipoproteinemia or
`
`atherosclerosis by administering an effective amount of the compound of Claim 1.
`
`For at least the reasons discussed below, the POSA would have selected the
`
`following prior art compound, also known as fluvastatin, as the lead compound:
`
`
`
`(Newton Dec. 1] 7 (EX1008))- The prior art, such as US. patent No. 4,739,073
`
`(“Kathawala ’073 patent”) ((EXIOIO), filed Mar. 4, 1985, and published Apr. 19,
`
`1988 (102(e) prior art», at the relevant time showed that fluvastatin possessed
`
`excellent in vitro activity and demonstrated relatively high activity for in vivo
`
`cholesterol biosynthesis inhibition.
`
`(Newton Dec. 1] 8; Kathawala ’073 patent at
`
`col. 33).
`
`The prior art disclosed that this compound lowered several
`
`lipid
`
`parameters in animals and was used in human clinical trials by at least 1987.
`
`(Newton Dec. 1] 8; Kathawala Abstract, EX1009 page 5, library stamp July 29,
`
`1987 (102(a) prior art); Engstrom Abstract, EX1011, library stamp Dec. 22, 1987
`
`(102(3) prior art)).
`
`In fact, POSAs recognized fluvastatin as one of only five
`
`HMG-CoA reductase inhibitors in clinical trials as of 1987, and as a “particularly
`
`interesting” compound.
`
`(Newton Dec. 11 9; Tobert, EX1012, library stamp Sept-
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 19 of 73
`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 19 of 73
`
`Petition for Inter Partes Review of USPN 5,856,336
`
`11, 1987 (102(a) prior art), pages 534-35; Lee, EX1013, available at the National
`
`Library Dec. 2, 1987 (102(3) prior art), page 444). It was also known by 1987 that
`
`HMG-CoA reductase inhibitors were useful in lowering cholesterol. (Gortler Dec.
`
`1H] 27, 28 (EX1015)).
`
`Indeed,
`
`it was public knowledge that several major
`
`pharmaceutical groups were actively researching these compounds by that time.
`
`Thus,
`
`the POSA would have been motivated to select fluvastatin as a lead
`
`compound for modification. (Newton Dec. 1] 10).
`
`In considering further modifications, the POSA would have considered the
`
`logical structural avenues available to fiirther optimize the compound. Within
`
`fluvastatin, both the 4-fluorophenyl group (boxed in green) and isomeric side chain
`
`(boxed in blue) reflected prior efforts to optimize structural groups in comparison
`
`to the early-generation statin molecules (i.e-, compactin and mevinolin):
`
` R2\\\\\
`Mevinol In (R2 - CH3)
`
`Compactin (R2 .-: H)
`
`Fluvastatin.
`
`(Newton Dec. 1] 11)-
`
`The prior art also taught advantages to incorporating
`
`nitrogen-containing ring systems in the molecule’s core. The POSA would have
`
`been motivated to filrther optimize the ring system with structural analogs of
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 20 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`fluvastatin’s 6,5 indole ring system. A 6,6 quinoline ring would have been an
`
`obvious structural modification the POSA would have reasonably expected to
`
`work (such rings were in fact proposed for use in the relevant time frame in statin
`
`compounds). (Id. ¶ 12). Likewise, the prior art taught interchangeable options for
`
`the isopropyl group, including cyclopropyl. The art further taught a finite number
`
`of salt structures suitable for use with statins, e.g., a calcium salt. Based on these
`
`known strategies, the POSA would have reasonably expected to modify fluvastatin
`
`and arrive at the pitavastatin compound of the ’336 patent. (Id. ¶ 13).
`
`The indole-quinoline modification is a simple structural modification
`
`involving the addition of a single carbon atom that would have been obvious in
`
`light of the prior art. It was also known during the relevant time that cyclopropyl
`
`and isopropyl groups are very similar.
`
`(Newton Dec. ¶ 14). This selection of
`
`cyclopropyl was so obvious that even the Patent Owner admitted that doing so
`
`would have been “the next logical, and analogous compound.” Fujikawa Reply to
`
`the Opposition to Fujikawa et al.’s Motion, received July 21, 1992 at 5 (Paper No.
`
`32 (hereinafter “Paper No. 32”)) (EX1031).
`
`With these two structural modifications, the POSA would have had a finite
`
`number of salt options, particularly since the salt had to be a positive cation, and
`
`there were limited cations that were approved by the U.S. Food and Drug
`
`Administration (“FDA”) at the time of the invention. (Newton Dec. ¶ 16).
`
`9
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 21 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`Given that each of the above modifications would have been routine, the
`
`POSA would have arrived at
`
`the compound of Claim 1 with a reasonable
`
`expectation of success. Moreover, given the prior art disclosures concerning
`
`biological activity, the POSA would have reasonably expected that such compound
`
`would have been effective in reducing hyperlipidemia and hyperlipoproteinemia as
`
`recited in Claim 2. (Newton Dec. ¶¶ 17, 18).
`
`No evidence of “secondary considerations” would change this conclusion.
`
`The patentee alleged during prosecution that
`
`the compounds of the alleged
`
`invention, which contain a cyclopropyl substituent, had unexpected potency over
`
`the isopropyl substituent. However, this difference was within the range the POSA
`
`would have expected when replacing isopropyl with its close analog cyclopropyl,
`
`and would not have been clinically relevant. (Newton Dec. ¶ 15).
`
`The claims of the ’336 patent are further invalid as anticipated by the
`
`teachings of U.S. Patent No. 4,761,419 (“Picard ’419 patent”) ((EX1021), filed
`
`Dec. 7, 1987, and published Aug. 2, 1988 (102(e) prior art)).
`
`C.
`
`The Priority Date of the ’336 Patent
`
`1.
`
`The Earliest Effective Date for the Challenged Claims of the
`’336 Patent Is August 3, 1988
`
`Before addressing invalidity, Petitioner addresses the effective filing date of
`
`the ’336 patent for purposes of evaluating the prior art. As explained further
`
`below, the challenged claims are not entitled to the benefit of priority of either JP
`
`10
`
`

`

`Case 1:14-cv-02758-PAC Document 69-3 Filed 06/10/15 Page 22 of 73
`Petition for Inter Partes Review of USPN 5,856,336
`
`62-207224 (Aug. 20, 1987) or JP 63-15585 (Jan. 26, 1988) under 35 U.S.C. § 119.
`
`Rather, the earliest effective priority date is that of JP 63-193606, which the face of
`
`the ’336 patent identifies as August 3, 1988.
`
`The ’336 patent issued from U.S. Application Serial Number 883,398 (“the
`
`’398 application”), filed May 15, 1992, which was a division of U.S. Application
`
`Serial Number 631,092 (“the ’092 application”), filed December 19, 1990, now
`
`U.S. Patent Number 5,872,130 (“the ’130 patent”) (EX1002), which was a
`
`continuation of U.S. Application Serial Number 233,752 (“the ’752 application”)
`
`(EX1003), now abandoned. The ’336 patent,
`
`the ’130 patent and the ’752
`
`application claim priority to three foreign priority documents:
`
`
`
`
`
`