IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`Biocon Pharma Limited
`Petitioner,
`
`v .
`
`Novartis Pharmaceuticals Corporation
`Patent Owner.
`
`U.S. Patent No. 8,101,659 to Ksander et al.
`Issue Date: January 24, 2012
`Title: Methods of Treatment and Pharmaceutical Composition
`
`Inter Partes Review No.: IPR2020-01263
`
`Petition for Inter Partes Review of U.S. Patent No. 8,101,659 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
`
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`

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`TABLE OF CONTENTS
`
`C.
`
`V.
`
`I.
`II.
`III.
`
`Page
`INTRODUCTION ........................................................................................... 1
`OVERVIEW .................................................................................................... 1
`STANDING (37 C.F.R. § 42.104(A); PROCEDURAL
`STATEMENTS) .............................................................................................. 6
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)) ...................................... 7
`A.
`Each Real Party in Interest (37 C.F.R. § 42.8(b)(1)) ............................ 7
`B.
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2)) .............................. 7
`1.
`Judicial Matters: .......................................................................... 7
`2.
`Administrative Matters: .............................................................. 9
`Designation of Lead and Back-Up Counsel (37 C.F.R. §
`42.8(b)(3)): ............................................................................................ 9
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. § 42.22(A)) .........................................10
`VI. OVERVIEW OF THE ’659 PATENT ..........................................................10
`A.
`The Claims ..........................................................................................10
`B.
`The Specification .................................................................................11
`C.
`Prosecution History .............................................................................11
`VII. CLAIM CONSTRUCTION (37 C.F.R. §§ 42.100(B), 42.104(B)(3)) .........12
`VIII. PERSON OF ORDINARY SKILL IN THE ART (“POSA”) .......................12
`IX.
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b)) .................14
`X.
`INVALIDITY ANALYSIS ...........................................................................14
`A.
`The Law of Obviousness .....................................................................14
`i
`
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`The Level of Ordinary Skill in the Pertinent Art ................................15
`The Scope and Content of the Prior Art ..............................................15
`1.
`Angiotensin II and NEP Inhibition ...........................................15
`2.
`EP’072 .......................................................................................18
`3.
`Shetty.........................................................................................20
`4.
`Gomez-Monterrey .....................................................................22
`5.
`Ksander .....................................................................................23
`6.
`The ’996 Patent .........................................................................25
`7.
`PDR ...........................................................................................26
`Ground 1: Claims 1-4 Would Have Been Obvious over EP’072,
`Shetty, Gomez-Monterrey, and Ksander .............................................26
`1.
`Claim 1 ......................................................................................26
`a.
`EP’072 Teaches Pharmaceutical Compositions
`Comprising the Combination of an AT 1-
`Antagonist and a NEP Inhibitor in about a 1:1
`Ratio ................................................................................26
`A POSA Would Have Substituted Valsartan for
`Irbesartan ........................................................................29
`Gomez-Monterrey and Ksander teach replacement
`of SQ28603 .....................................................................31
`“About a 1:1 Ratio” ........................................................36
`d.
`Reasonable Expectation of Success ................................39
`e.
`Representative Claim Chart ............................................42
`f.
`Dependent Claims 2-4 ...............................................................43
`a.
`Claim 2 ............................................................................43
`b.
`Claim 3 ............................................................................45
`c.
`Claim 4 ............................................................................45
`Ground 2: Claims 1-4 Would Have Been Obvious over the
`PDR in View of the ’996 Patent, Gomez-Monterrey and EP’072 ......46
`
`b.
`
`c.
`
`B.
`C.
`
`D.
`
`E.
`
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`2.
`
`ii
`
`

`

`b.
`
`F.
`
`XI.
`
`1.
`
`2.
`
`2.
`
`Claim 1 ......................................................................................46
`a.
`Pharmaceutical Compositions Comprising
`Valsartan for the Treatment of Hypertension Were
`Known .............................................................................46
`Pharmaceutical Compositions Comprising
`Sacubitril for the Treatment of Hypertension Were
`Known .............................................................................47
`Combination of Valsartan and an NEP Inhibitor ...........50
`c.
`“About a 1:1 Ratio” ........................................................53
`d.
`Reasonable Expectation of Success ................................54
`e.
`Representative Claim Chart ............................................54
`f.
`Dependent Claims 2-4 ...............................................................56
`a.
`Claim 2 ............................................................................56
`b.
`Claim 3 ............................................................................58
`c.
`Claim 4 ............................................................................58
`No Secondary Considerations of Nonobviousness .............................59
`1.
`No Unexpected Results .............................................................60
`2.
`No Commercial Success ...........................................................63
`THE BOARD SHOULD INSTITUTE TRIAL BASED ON
`BIOCON’S PETITION; 35 U.S.C. § 325(D) AND § 314(A) ......................64
`A.
`No Denial Should Be Based on §325(d) .............................................64
`1.
`Petitioner’s Asserted Grounds Are Not Cumulative of Art
`Considered during Prosecution (Becton Factors (a-d)). ...........64
`Petitioner Has Pointed Out Sufficiently How the
`Examiner Erred in Its Evaluation of the Asserted Prior
`Art (Becton Factor (e))/Additional Evidence and Facts
`Presented in the Petition Warrant Reconsideration
`(Becton Factor (f)) ....................................................................65
`§ 314(a)/ The Apple Factors Favor Institution ....................................67
`B.
`XII. CONCLUSION ..............................................................................................70
`
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`

`

`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Acorda Therapeutics, Inc. v. Roxane Labs., Inc.,
`903 F.3d 1310 (Fed. Cir. 2018) .................................................................... 15, 63
`Actavis LLC v. Abraxis Bioscience, LLC,
`IPR2017-01103 Paper 7 (October 10, 2017) ...................................................... 66
`Advanced Bionics, LLC v. MED-EL Elektromedizinische Geräte
`GmbH,
`IPR2019-01469, Paper 6 (Feb. 13, 2020) ............................................... 64, 65, 66
`Amgen Inc. v. Alexion Pharmaceuticals Inc.,
`IPR2019-00740 ................................................................................................... 65
`Amgen Inc. v. F. Hoffman-La Roche, Ltd.,
`580 F.3d 1340 (Fed. Cir. 2009) .......................................................................... 39
`Amneal Pharmaceuticals, LLC v. Supernus Pharmaceuticals, Inc.,
`IPR2013-00368, Paper 8 (PTAB Dec. 2013) ..................................................... 59
`Apotex, Inc. v. UCB Biopharma, SPRL,
`IPR2019-00400, Paper 17 (July 15, 2019) ......................................................... 64
`Apple Inc. v. Fintiv, Inc.,
`IPR2020-00019, Paper 11 (PTAB Mar. 20, 2020) ............................................. 67
`Apple Inc. v. Fintiv, Inc.,
`IPR2020-00019, Paper 15 (May 13, 2020) ......................................................... 67
`Apple Inc. v. Seven Networks LLC,
`IPR2020-00156, Paper 10 (PTAB Jun. 15, 2020) .............................................. 67
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Paper 8 (Dec. 15, 2017) .......................................................... 64
`
`Biomarin Pharmaceutical Inc. v. Genzyme Therapeutic Products Ltd.
`Partnership,
`IPR2013-00534, Paper 81 (P.T.A.B. Feb. 23, 2015) .......................................... 38
`iv
`
`145240266v6
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`

`

`Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc.,
`752 F.3d 967 (Fed. Cir. 2014) ............................................................................ 62
`Constant v. Advanced Micro-Devices, Inc.,
`848 F.2d 1560 (Fed. Cir. 1988) .................................................................... 11, 27
`Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc.,
`807 F.2d 955 (Fed. Cir. 1986) ............................................................................ 12
`Duramed Pharm., Inc. v. Watson Labs., Inc.,
`413 F. App’x 289 (Fed. Cir. 2011) ..................................................................... 15
`Dystar Textilfarben GmbH v. C.H. Patrick Co.,
`464 F.3d 1356 (Fed. Cir. 2006) .......................................................................... 28
`Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd.,
`533 F.3d 1353 (Fed. Cir. 2008) .................................................................... 28, 35
`Galderma Labs. v. Tolmar Inc.,
`737 F.3d 731, 740 (Fed. Cir. 2013) .................................................................... 63
`Google LLC v. Uniloc 2017 LLC,
`IPR2020-00441, Paper 13 (PTAB July 17, 2020) .................................. 67, 68, 69
`Graham v. John Deere Co. of Kansas City,
`383 U.S. 1 (1966) ................................................................................................ 14
`Grüenthal GmbH v. Antecip Bioventures II LLC,
`PGR2018-00062, Paper 32 (PTAB Oct. 29, 2019) ............................................ 62
`Grunenthal GMBH v. Antecip Bioventures II LLC,
`PGR2019-00027, Paper 24 (PTAB July 28, 2020) ............................................ 45
`Hospira, Inc. v. Genentech, Inc.,
`IPR2017-00804, Paper 13 (PTAB July 27, 2017) .............................................. 66
`Hyperbranched Medical Technology, Inc., v. Confluent Surgical, Inc.,
`IPR2018-01097, Paper 14 (PTAB Nov. 14, 2018) ............................................. 65
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) .......................................................................... 29
`
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`
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`
`

`

`In re Baxter-Travenol Labs.,
`952 F.2d 388 (Fed. Cir. 1991) ............................................................................ 62
`In re Crockett,
`279 F.2d 274 (CCPA 1960) .......................................................................... 50, 51
`In re Cyclobenzaprine Hydrochloride,
`676 F.3d 1063 (Fed. Cir. 2012) .......................................................................... 51
`In re Diamond,
`360 F.2d 214 (C.C.P.A. 1966) ............................................................................ 52
`In re Fout,
`675 F.2d 297 (CCPA 1982) .......................................................................... 35, 52
`In re Harris,
`409 F.3d 1339 (Fed. Cir. 2005) .......................................................................... 62
`In re Huellmantal,
`324 F.2d 998 (CCPA 1963) ................................................................ 5, 41, 54, 61
`In re Kerkhoven,
`626 F.2d 846 (CCPA 1980) ................................................................................ 51
`In re Omeprazole,
`483 F.3d 1364 (Fed. Cir. 2007) .......................................................................... 35
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) ................................................................ 6, 38, 54
`Iron Grip Barbell Co., Inc. v. USA Sports, Inc.,
`392 F.3d 1317 (Fed. Cir. 2004) .......................................................................... 62
`Koios Pharms. LLC v. medac Gesellschaft für klinische
`Spezialpräparate mbH,
`IPR2016-01370, Paper 13 at 35 (P.T.A.B. Feb. 8, 2017) ................................... 59
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) .............................................................................................. 6
`Medichem, S.A. v. Rolabo, S.L.,
`437 F.3d 1157 (Fed. Cir. 2006) .......................................................................... 15
`
`145240266v6
`
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`
`

`

`Mylan v. Merck Sharpe & Dohme Corp.,
`IPR2020-00040, Paper 21 (PTAB May 11, 2020) ............................................. 67
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) ............................................................................ 59
`Pfizer, Inc. v. Apotex, Inc.,
`480 F. 3d 1348 (Fed. Cir. 2007) ......................................................................... 30
`Oticon Med. AB v. Cochlear Ltd.,
`IPR2019-00975, Paper 15 (PTAB Oct. 16, 2019) .............................................. 68
`PharmaStem Therapeutics, Inc. v. ViaCell, Inc.,
`491 F.3d 1342 (Fed. Cir. 2007) .......................................................................... 11
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc) .......................................................... 12
`Purdue Pharma Prods. L.P. v. Par Pharm., Inc.,
`377 F. App’x 978 (Fed. Cir. 2010) ..................................................................... 60
`Quanergy Systems, Inc. v. Velodyne Lidar, Inc.,
`IPR2018-00256, Paper 14 (PTAB May 25, 2018) ............................................. 59
`Sand Revolution II, LLC v. Continental Intermodal Group – Trucking
`LLC,
`IPR2019-01393, Paper 24 (June 16, 2020) ......................................................... 67
`Schering Pharma AG v. Barr Laboratories,
`575 F.3d 1341 (Fed. Cir. 2008) .......................................................................... 50
`Vandenberg v. Dairy Equip. Co.,
`740 F.2d 1560 (Fed. Cir. 1984) .......................................................................... 63
`Statutes
`35 U.S.C. § 100 et. seq. ............................................................................................ 14
`35 U.S.C. § 102(b) ............................................................................................passim
`35 U.S.C. § 325(D) .................................................................................................. 64
`
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`

`

`Regulations
`37 C.F.R. § 42.6(d) .................................................................................................. 14
`37 C.F.R. § 42.100(b) .............................................................................................. 12
`37 C.F.R. § 42.106(a) ................................................................................................. 6
`
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`

`

`Petitioner’s Exhibit List
`
`Exhibit #
`
`Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`1008
`
`1009
`
`1010
`
`U.S. Patent No. 8,101,659 (“the ’659 patent”)
`
`EP Patent Application No. 0726072A2 (“EP’072”)
`
`Trippodo et al., “REPRESSION OF ANGIOTENSIN II AND
`POTENTIATION OF BRADYKININ CONTRIBUTE TO THE
`SYNERGISTIC EFFECTS OF DUAL METALLOPROTEASE
`INHIBITION IN HEART FAILURE”, Journal of Pharmacology
`and Experimental Therapeutics, Vol. 272, No. 2, February 01, 1995,
`619-627 (“Trippodo”)
`Shetty et al., “DIFFERENTIAL INHIBITION OF THE
`PREJUNCTIONAL ACTIONS OF ANGIOTENSIN II IN RAT
`ATRIA BY VALSARTAN, IRBESARTAN, EPROSARTAN,
`AND LOSARTAN”, Journal of Pharmacology and Experimental
`Therapeutics, Vol. 294, No. 1, July 01, 2000, 179-186 (“Shetty”)
`Gomez-Monterrey et al., “NEW THIOL INHIBITORS OF
`NEUTRAL ENDOPEPTIDASE EC 3.4.24.11: SYNTHESIS AND
`ENZYME ACTIVE-SITE RECOGNITION”, Journal of Medicinal
`Chemistry, Vol. 37, Issue 12, June 01, 1994, 1865–1873. (“Gomez-
`Monterrey”)
`Ksander et al., “DICARBOXYLIC ACID DIPEPTIDE NEUTRAL
`ENDOPEPTIDASE INHIBITORS”, Journal of Medicinal
`Chemistry, Vol. 38, Issue 10, May 01, 1995, 1689–1700
`(“Ksander”)
`Reserved
`U.S. Patent No. 5,399,578 (“the ’578 patent”)
`
`U.S. Patent No. 5,217,996 (“the ’996 patent”)
`
`The prosecution history for U.S. Patent No. 8,101,659 (“the ’659
`prosecution history”)
`
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`

`

`Exhibit #
`
`1011
`
`1012
`1013
`
`1014
`1015
`
`1016
`
`1017
`
`1018
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`Description
`
`Thurmann, “VALSARTAN: A NOVEL ANGIOTENSIN TYPE 1
`RECEPTOR ANTAGONIST,” Expert Opinion on
`Pharmacotherapy, Vol. 1, Issue 2, January 2000, 337-350
`(“Thurmann”)
`Physician’s Desk Reference (2000), DIOVAN® (“PDR”)
`Roques, et al., “NEUTRAL ENDOPEPTIDASE 24.11:
`STRUCTURE, INHIBITION, AND EXPERIMENTAL AND
`CLINICAL PHARMACOLOGY,” Pharmacological Reviews, Vol.
`45, Issue 1, March 01 1993, 87-146.
`U.S. Patent No. 7,468,390 (“the ’390 patent”)
`The prosecution history for U.S. Patent No. 7,468,390 (“the ’390
`prosecution history”)
`
`Ferrario, et al., “COUNTERREGULATORY ACTIONS OF
`ANGIOTENSIN,” Hypertension, Vol. 30, Issue 3, September 1997,
`535-541 (“Ferrario”)
`Orange Book Entry for ENTRESTO® (“Orange Book listing for
`ENTRESTO”)
`Curriculum Vitae of Prof. Y.W. Francis Lam
`Physician’s Desk Reference (2000), NORVASC® (“PDR-
`NORVASC”)
`Physician’s Desk Reference (2000), TENORMIN® (“PDR-
`TENORMIN”)
`Physician’s Desk Reference (2000), TAGAMET® (“PDR-
`TAGAMET”)
`Physician’s Desk Reference (2000), LANOXIN® (“PDR-
`LANOXIN”)
`Physician’s Desk Reference (2000), Furosemide (“PDR-
`Furosemide”)
`Physician’s Desk Reference (2000), MICRONASE® (“PDR-
`MICRONASE”)
`
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`

`

`Exhibit #
`
`1025
`
`1026
`
`Description
`
`Physician’s Desk Reference (2000), HydroDIURIL® (“PDR-
`HydroDIURIL”)
`Physician’s Desk Reference (2000), INDOCIN® (“PDR-
`INDOCIN”)
`
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`

`I.
`
`INTRODUCTION
`Biocon Pharma Limited (“Petitioner”) petitions for Inter Partes Review,
`
`seeking cancellation of Claims 1-4 (“challenged claims”) of U.S. Patent
`
`No. 8,101,659 (“the ’659 patent”) (EX1001). The ’659 patent is assigned to
`
`Novartis Pharmaceuticals Corporation (“Patent Owner”).
`
`II. OVERVIEW
`The challenged claims of the ’659 patent, at a high level, are directed to
`
`pharmaceutical compositions comprising an AT 1-antagonist, a NEP inhibitor, and
`
`a pharmaceutically acceptable carrier, where the AT 1-antagonist and NEP
`
`inhibitor are administered in combination in about a 1:1 ratio. EX1018, ¶57. As
`
`shown below, this Petition demonstrates that all challenged claims of the ’659
`
`patent are unpatentable as obvious under at least two separate and independent
`
`grounds:
`
`Ground 1. The challenged claims are unpatentable over EP’072 in view of
`
`Shetty, Gomez-Monterrey, and Ksander. Id., ¶¶112-185. Before the priority date
`
`for the ’659 patent, pharmaceutical compositions comprising a combination of AT
`
`1-antagonists and NEP inhibitors were known in the art. EP’072 discloses the
`
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`combination of an AT 1-antagonist (i.e., irbesartan) and a NEP inhibitor (i.e., SQ
`
`28603) in a 1:1 ratio and that this combination provides a synergistic
`
`antihypertensive effect.1
`
`Id., ¶¶112-118. In view of Shetty, a POSA would have
`
`found it obvious to substitute irbesartan with valsartan. Id., ¶¶124-126. The
`
`structure of valsartan is reproduced below:
`
`1 While in the text of EP’072 and elsewhere this molecule is referred to as an
`
`“angiotensin II antagonist”, as explained by Dr. Lam, in the terms of the
`
`challenged patent, a POSA would recognize this that compounds that bind to the
`
`AT 1 receptor (i.e., antagonists) are often termed Ang (angiotensin) II antagonists.
`
`EX1018, ⁋112. This is admitted by the ’659 patent in the background section.
`
`EX1001, 1:46-49 (“In recent times great efforts have been made to identify
`
`substances that bind to the AT 1-receptor. Such active ingredients are often termed
`
`Ang II antagonists.”). For the sake of clarity, the claimed term “AT-1 antagonist”
`
`used in this Petition includes “angiotensin II antagonist,” as would be understood
`
`by a POSA.
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`EX1012, “Description,” EX1018, ¶43.
`
`Substitution of SQ 28603 with sacubitril would have been obvious to a
`
`POSA in view of Gomez-Monterrey and Ksander. EX1018, ¶¶127-139. The
`
`structure of sacubitril or N-(3-carboxy-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-
`
`4-amino-(2R)-methylbutanoic acid ethyl ester, i.e., Compound 19a of Ksander, is
`
`reproduced below:
`
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`EX1006, 1691; EX1018, ¶131.
`
`Ground 2. The challenged claims also would have been obvious over the
`
`PDR in view of the ’996 patent and EP’072. EX1018, ¶¶186-229. The PDR
`
`discloses that valsartan is an angiotensin II receptor antagonist marketed as
`
`DIOVAN® and approved by the FDA for the treatment of hypertension. EX1012,
`
`“Description”, “Indications and Usage”; EX1018, ¶186. As Petitioner’s expert
`
`shows, sacubitril, i.e., N-(3-carboxy-1-oxopropyl)-4-(p-phenylphenylmethyl)-4-
`
`amino 2-methylbutanoic acid ethyl ester, is the most prominent compound taught
`
`by the ’996 patent for the treatment of hypertension. Id., ¶¶195-201. It would
`
`have been obvious to a POSA to combine the compounds from the PDR and ’996
`
`patent because each was known for treating hypertension. Id., ¶¶202-209. As
`
`further motivation for this combination, EP’072 discloses the combination of an
`
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`

`AT 1-antagonist and a NEP inhibitor in a 1:1 ratio provides a synergistic
`
`antihypertensive effect. Id., ¶213.
`
`In rebuttal to both Grounds, Patent Owner will no doubt point to the
`
`Examiner’s “Notice of Allowance” (EX1010, page 240) where the Examiner noted
`
`that in the parent patent application Patent Owner had shown that the claimed
`
`subject matter exhibited an alleged synergistic effect. Id., 156 (“During
`
`prosecution of the ’390 patent, Applicants presented experimental data showing
`
`that the combination of valsartan and specific NEP inhibitor (AHU377) had a
`
`synergistic, unexpected and surprising antihypertensive effect.”); EX1015 (the
`
`’390 patent prosecution history), at 885 (Webb Declaration (5/11/2006)) at ¶¶5, 6,
`
`23, 24; id. at 948 (Webb Declaration (11/16/2006)) at ¶3; id. at 1046; id. 1094
`
`(Notice of Allowance); EX1018, ¶¶230-231.
`
` “[W]e attribute no magic status to synergism per se since it may be
`
`expected or unexpected. On the record before us, we see nothing “unexpected” in
`
`appellant’s synergism . . . . [N]othing in the record shows that similar synergism is
`
`not attained by [the prior art].” In re Huellmantal, 324 F.2d 998, 1003 (CCPA
`
`1963. First, the synergistic effect was not unexpected to a POSA because the prior
`
`art (i.e., EP’072) expressly taught the same synergistic effect when combining an
`
`AT 1-antagonist with a NEP inhibitor. EX1002, 2:29-31 (“The combination of this
`
`angiotensin II antagonist and the selective or dual acting neutral endopeptidase
`
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`

`inhibitor produced significant reductions in left ventricular end diastolic pressure
`
`(LVEDP) and left ventricular systolic pressure (LVSP) that were greater than
`
`those produced by either treatment alone.”) (emphasis added); id., 9:22-23;
`
`EX1018, ¶¶232.
`
`Put simply, this is a textbook case of obviousness: “the combination of
`
`familiar elements according to known methods is likely to be obvious when it does
`
`no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S.
`
`398, 416 (2007); In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003) (explaining
`
`that the normal desire of artisans to improve upon what is already generally known
`
`provides the motivation to determine optimum amounts).
`
`III.
`
`STANDING (37 C.F.R. § 42.104(A); PROCEDURAL STATEMENTS)
`Petitioner certifies that (1) the ’659 patent is available for IPR and
`
`(2) Petitioner is not barred or estopped from requesting IPR of any claim of the
`
`’659 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 through, and the Office is authorized to charge any fee
`
`deficiencies and credit overpayments to, Deposit Acct. No. DA501290 (Customer
`
`ID No. 27160).
`
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`

`IV. 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 for this petition are Biocon Limited, Biocon
`
`Pharma Limited, and Biocon Pharma, Inc.
`
`B.
`
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2))
`1.
`Judicial Matters:
`Petitioner is aware of the at least following district court actions involving
`
`the ’659 patent:
`
`1. Novartis Pharmaceuticals Corporation v. Alkem Laboratories, Ltd.;
`
`2. Novartis Pharmaceuticals Corporation v. Aurobindo Pharma USA
`
`Inc., Aurobindo Pharma Ltd.;
`
`3. Novartis Pharmaceuticals Corporation v. Biocon Pharma Limited,
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`Biocon Limited, Biocon Pharma, Inc.;
`
`4. Novartis Pharmaceuticals Corporation v. Crystal Pharmaceutical
`
`(Suzhou) Co., Ltd.;
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`5. Novartis Pharmaceuticals Corporation v. Laurus Labs Limited,
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`Laurus Generics Inc.;
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`6. Novartis Pharmaceuticals Corporation v. Lupin Atlantis Holdings,
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`S.A., Lupin Limited, Lupin Inc., Lupin Pharmaceuticals, Inc.;
`
`7. Novartis Pharmaceuticals Corporation v. Nanjing Noratech
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`Pharmaceutical Co., Limited,;
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`8. Novartis Pharmaceuticals Corporation v. Teva Pharmaceuticals
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`USA, Inc.;
`
`9. Novartis Pharmaceuticals Corporation v. Torrent Pharma Inc.,
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`Torrent Pharmaceuticals Ltd.;
`
`10. Novartis Pharmaceuticals Corporation v. Alembic Pharmaceuticals
`
`Limited, Alembic Pharmaceuticals, Inc.;
`
`11. Novartis Pharmaceuticals Corporation v. Macleods
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`Pharmaceuticals Ltd., and Macleods Pharma USA, Inc.;
`
`12. Novartis Pharmaceuticals Corporation v. Dr. Reddy’s Laboratories,
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`Inc., Dr. Reddy’s Laboratories, Ltd.;
`
`13. Novartis Pharmaceuticals Corporation v. Hetero USA Inc., Hetero
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`Labs Limited, Hetero Labs Limited Unit III,;
`
`14. Novartis Pharmaceuticals Corporation v. MSN Pharmaceuticals
`
`Inc., MSN Laboratories Private Limited, MSN Life Sciences Private
`
`Limited,;
`
`15. Novartis Pharmaceuticals Corporation v. Novugen Pharma
`
`(Malaysia) SDN. BHD.;
`
`16. Novartis Pharmaceuticals Corporation v. Zydus Pharmaceuticals
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`Inc., Cadila Healthcare Ltd.; and
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`17. Novartis Pharmaceuticals Corporation v. Mylan Pharmaceuticals,
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`Inc.
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`Administrative Matters:
`2.
`The Public Patent Application Information Retrieval (PAIR) website
`
`indicates that the ’659 patent is a Divisional Application of Application
`
`No. 10/341,868, filed on January 14, 2003 (now issued as U.S. Patent
`
`No. 7,468,390), and claims priority to Provisional Application Nos. 60/386,792,
`
`filed on June 7, 2002, and 60/349,660, filed on January 17, 2002. PAIR also
`
`indicates that U.S. Patent Nos. 8,404,744 and 8,796,331 claim priority to the ’659
`
`patent. There are no pending applications claiming priority to the ’659 patent
`
`according to PAIR.
`
`C.
`
`Designation of Lead and Back-Up Counsel (37 C.F.R. §
`42.8(b)(3)):
`Lead Counsel
`Christopher Ferenc
`Reg. No. 59,365
`Katten Muchin Rosenman LLP
`2900 K Street NW, Suite 200
`Washington, DC 20007
`christopher.ferenc@katten.com
`
`Back-Up Counsel
`Brian Sodikoff
`Reg. No. 54,697
`Katten Muchin Rosenman LLP
`525 West Monroe Street, Suite 1900
`Chicago, IL 60661
`brian.sodikoff@katten.com
`
`Petitioner consents to email service as indicated above.
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`V.
`
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. § 42.22(A))
`Petitioner requests IPR and cancellation of Claims 1-4 of the ’659 patent.
`
`Petitioner’s full statement of the reasons for the relief requested is set forth in
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`detail below.
`
`VI. OVERVIEW OF THE ’659 PATENT
`The
`’659 patent claims priority
`to U.S. Provisional Application
`
`Nos. 60/386,792, filed June 7, 2002 (“’792 provisional”), and 60/349,660, filed
`
`January 17, 2002 (“’660 provisional”). EX1001, Cover; EX1018, ¶¶54.
`
`The Claims
`A.
`The ’659 patent issued with 4 claims. The sole independent claim (Claim 1)
`
`at a high level is directed to a pharmaceutical composition comprising an AT 1-
`
`antagonist, a NEP inhibitor, and a pharmaceutically acceptable carrier, where the
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`AT 1-antagonist and NEP inhibitor “are administered in combination in about a 1:1
`
`ratio.” EX1018, ¶57. More specifically, the AT 1-antagonist is “valsartan or a
`
`pharmaceutically acceptable salt thereof,” and the NEP inhibitor is “N-(3-carboxy-
`
`1-oxopropy1)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methylbutanoic
`
`acid
`
`ethyl ester or (2R,4S)-5-bipheny1-4-y1-4(3-carboxy-propionyl amino)-2-methyl-
`
`pentanoic acid or a pharmaceutically acceptable salt thereof.” Id. The recited NEP
`
`inhibitor “N-(3-carboxy-1-oxopropy1)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-
`
`methylbutanoic acid ethyl ester” is also known as sacubitril. Id.
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`The Specification
`B.
`The ’659 patent acknowledges that AT 1-antagonists were well known when
`
`stating “[i]nhibitors of the renin angiotensin system are well-known drugs that
`
`lower blood pressure and exert beneficial actions in hypertension and in congestive
`
`heart failure.” EX1001, 1:55-57; EX1018, ¶59. The ’659 patent also admits that it
`
`was known that “NEP inhibitors lower blood pressure and exert ANF-like effects.”
`
`EX1001, 2:39-40; EX1018, ¶59. Importantly, the ’659 patent concedes that the
`
`prior art taught that combinations of AT 1-antagonists and NEP inhibitors were
`
`known. EX1001, 2:50-56; EX1018, ¶59; PharmaStem Therapeutics, Inc. v.
`
`ViaCell, Inc., 491 F.3d 1342, 1362 (Fed. Cir. 2007) (“Admissions in the
`
`specification regarding the prior art are binding on the patentee.”); Constant v.
`
`Advanced Micro-Devices, Inc., 848 F.2d 1560, 1570 (Fed. Cir. 1988).
`
`Prosecution History
`C.
`At a high level, the Examiner rejected the pending claims as obvious over
`
`the ’578 patent, or the ’578 patent in view of the ’996 patent. EX1010, 82-85, 170-
`
`172, 195-197; EX1018 ¶60. The claims were allowed only after arguments that the
`
`currently claimed subject matter allegedly showed a certain “synergistic,
`
`unexpected and surprising antihypertensive effect,” pointing to events that
`
`occurred during the prosecution of the parent ’390 patent. EX1010, 240; EX1018;
`
`¶60. Petitioner addresses the allegations of unexpected results below. For the
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`reasons explained in § X(F)(1) and throughout this Petition, the alleged unexpected
`
`results evidence presented to the Examiner is legally insufficient.
`
`VII. CLAIM CONSTRUCTION (37 C.F.R. §§ 42.100(B), 42.104(B)(3))
`Under applicable guidance, the claims must be given “the meaning that the
`
`term would have to a person of ordinary skill in the art in question at the time of
`
`the invention.” See 37 C.F.R. § 42.100(b); Phillips v. AWH Corp., 415 F.3d 1303,
`
`1313 (Fed. Cir. 2005) (en banc). Petitioner is unaware of any prior claim
`
`construction determination concerning the ’659 patent. EX1018, ¶62. For all
`
`terms, Petitioner submits that no construction is necessary and the challenged
`
`claims should be afforded a meaning “in accordance with the ordinary and
`
`customary meaning of such claim as understood by one of ordinary skill in the art
`
`and the prosecution history pertaining to the patent.” 37 C.F.R. § 42.100(b).
`
`VIII. PERSON OF ORDINARY SKILL IN THE ART (“POSA”)
`A POSA is a hypothetical person who is presumed to be aware of all
`
`pertinent art, thinks along conventional wisdom in the art, and is a person of
`
`ordinary creativity. KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 420 (2007);
`
`Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962 (Fed. Cir.
`
`1986). With respect to the ’659 patent, a POSA would have had experience in the
`
`fields of cardiology and pharmacology, including an understanding of drug-drug
`
`interactions, rationales