Paper No. ___
`Date Filed: July 20, 2015
`
`Filed on behalf of Janssen Sciences Ireland UC
`Irena Royzman
`By: Dianne B. Elderkin
`PATTERSON BELKMAP WEBB
`Barbara L. Mullin
`& TYLER LLP
`Ruben Munoz
`1133 Avenue of the Americas
`AKIN GUMP STRAUSS HAUER
`New York, NY 10036
`& FELD LLP
`Tel.: (212) 336-2081
`Two Commerce Square
`Fax: (212) 336-2222
`2001 Market Street, Suite 4100
`LupinIPR@pbwt.com
`Philadelphia, PA 19103
`Tel: (215) 965-1200
`Fax: (215) 965-1210
`JANS-LUPIN@akingump.com
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________________
`
`LUPIN LIMITED
`Petitioner
`
`v.
`
`JANSSEN SCIENCES IRELAND UC
`Patent Owner
`
`_______________________________
`
`CASE No. IPR2015-01030
`U.S. Patent No. 8,518,987 B2
`_______________________________
`
`
`
`JANSSEN’S PATENT OWNER PRELIMINARY RESPONSE
`UNDER 37 C.F.R. § 42.107
`
`
`
`

`
`Case IPR2015-01030
`Patent Owner’s Preliminary Response
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`
`
`TABLE OF CONTENTS
`
`Page
`
`I.
`INTRODUCTION .............................................................................................. 1
`II. THE PETITION FAILS TO IDENTIFY ALL REAL PARTIES-IN-
`INTEREST ......................................................................................................... 3
`A. The Real Party-in-Interest Standard ........................................................... 3
`B. Lupin Inc. and Lupin Atlantis are Real Parties-In-Interest ........................ 4
`C. The Petition Should be Dismissed .............................................................. 7
`III. BACKGROUND: THE ‘987 PATENT ............................................................ 7
`IV. CLAIM CONSTRUCTION ............................................................................... 9
`A. Determining the Broadest Reasonable Interpretation ................................ 9
`B. “Hydrate” (Claims 1-19) .......................................................................... 10
`1. The Ordinary Meaning of “Hydrate” .................................................. 11
`2. The Specification ................................................................................. 12
`3. Other Claims ........................................................................................ 14
`4. The Prosecution History ...................................................................... 15
`5. Lupin’s Position is at Odds with the Intrinsic Record ........................ 15
`C. The “Ratio” Limitations (Claims 1, 3-5, 9-18) ........................................ 17
`D. The Graphic Depiction in Claims 2 and 6 ................................................ 18
`E. The “Carrier” Limitations (Claims 3-8, 14-19) ........................................ 19
`V. THE CLAIMS ARE NOT ANTICIPATED .................................................... 20
`A. Lupin Mischaracterizes the Legal Test for Inherent Anticipation ........... 22
`B. Ghosh 1998 ............................................................................................... 23
`1. Lupin Failed To Prove Any Inherent Properties Of The Ghosh
`1998 Darunavir Because Its Expert Deviated From The Ghosh 1998
`Method ................................................................................................. 23
`2. The Ghosh 1998 Method Does Not Inevitably Yield a Crystalline
`Hydrate of Darunavir Under The Broadest Reasonable Interpretation
`of “Hydrate” ........................................................................................ 26
`
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`3. Lupin’s Testing Does Not Show That Ghosh 1998 Inherently
`Discloses A “Hydrate” of Darunavir Under Either Side’s
`Construction ........................................................................................ 26
`4. Lupin’s Testing Does Not Show That Ghosh 1998 Inherently
`Discloses the Claimed Ratios Under Either Side’s Construction ....... 28
`5. Lupin’s Arguments About the Prosecution History ............................ 32
`6. The Van Gyseghem Paper ................................................................... 33
`7. Ghosh 1998 Does Not Anticipate the ‘Pharmaceutically Acceptable
`Carrier’ or ‘Solid Carrier’ Limitations ................................................ 35
`C. The ‘775 Patent ......................................................................................... 36
`1. Under Either Side’s Construction, the ‘775 Patent Does Not
`Inherently Anticipate the Claimed Hydrates ....................................... 37
`2. Under Either Side’s Construction, the ‘775 Patent Does Not
`Inherently Anticipate the Claimed Ratios ........................................... 39
`VI. THE CLAIMED INVENTION WOULD NOT HAVE BEEN OBVIOUS TO
`A PERSON OF ORDINARY SKILL .............................................................. 40
`A. The Prior Art on Which Lupin Relies ...................................................... 41
`1. Byrn ..................................................................................................... 43
`2. Desiraju................................................................................................ 44
`B. No Reason to Choose Darunavir for Formulation ................................... 45
`C. There Is No Reasonable Expectation of Success in Making a Solvate of
`Darunavir .................................................................................................. 49
`D. There Was No Reason to Create a Hydrate of Darunavir, and No
`Reasonable Expectation of Success in Doing So ..................................... 51
`1. The Desiraju Paper Does Not Provide A Reasonable Expectation of
`Success in Making a Hydrate of Darunavir ........................................ 53
`2. Byrn Does Not Provide a Reasonable Expectation of Success in
`Making a Hydrate Of Darunavir ......................................................... 54
`3. Lupin’s Reliance on Van Gyseghem Is Misplaced ............................. 55
`4. The Prosecution History Does Not Support Lupin’s Obviousness
`Theory.................................................................................................. 55
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`E. No Reasonable Expectation of a Hydrate of Darunavir with the Claimed
`Ratios of Darunavir-to-Water ................................................................... 57
`F. No Reasonable Expectation that a Hydrate Would Be Useful as a
`Pharmaceutical Composition .................................................................... 58
`G. Lupin’s Unsuccessful Obviousness Challenge to a Related Patent ......... 59
`VII. CONCLUSION ................................................................................................ 60
`
`
`
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`iii
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`Case IPR2015-01030
`Patent Owner’s Preliminary Response
`TABLE OF AUTHORITIES
`
`Page(s)
`
`
`CASES
`
`Am. Calcar, Inc. v. Am. Honda Motor Co.,
`651 F.3d 1318 (Fed. Cir. 2011) .......................................................................... 22
`
`Atlanta Gas Light Co. v. Bennett Regulator Guards, Inc.,
`IPR2013-00453, Paper 88 (PTAB Jan. 6, 2015) .................................................. 6
`
`Crown Operations Int’l, Ltd. v. Solutia, Inc.,
`289 F.3d 1367 (Fed. Cir. 2002) .................................................................... 30, 40
`
`Daiichi Sankyo Co. v. Matrix Labs. Ltd.,
`619 F.3d 1346 (Fed. Cir. 2010) .............................................................. 45, 47, 48
`
`Eli Lilly & Co. v. Zenith Goldline Pharms., Inc.,
`471 F.3d 1369 (Fed. Cir. 2006) .......................................................................... 47
`
`Endo Pharms. Inc. v. v. Depomed, Inc.,
`Case IPR2014-00655, Paper 12 (PTAB Sept. 29, 2014) .................................... 25
`
`Ex Parte Peltz,
`Appeal 2012-011729, 2015 Pat. App. LEXIS 513 (PTAB Jan. 13, 2015) ......... 35
`
`Exergen Corp. v. Wal-Mart Stores, Inc.,
`575 F.3d 1312 (Fed. Cir. 2009) .................................................................... 23, 35
`
`Galderma S.A. v. Allergan Industrie, SAS,
`IPR2014-01422, Paper 14 (PTAB March 5, 2015) .................................. 3, 4, 5, 7
`
`Hoop v. Hoop,
`279 F.3d 1004 (Fed. Cir. 2002) .......................................................................... 56
`
`In re Am. Acad. of Science Tech. Center,
`367 F.3d 1359 (Fed. Cir. 2004) .................................................................... 10, 14
`
`In re Armodafinil Patent Litig.,
`939 F. Supp. 2d 456 (D. Del. 2013) .................................................................... 60
`
`In re Cyclobenzeprine Hydrochloride Capsule Patent Litig.,
`676 F.3d 1063 (Fed. Cir. 2012) .......................................................................... 56
`
`
`
`iv
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`Case IPR2015-01030
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`In re Gleave,
`560 F.3d 1331 (Fed. Cir. 2009) ............................................................. 30, 31, 40
`
`In re Montgomery,
`677 F.3d 1375 (Fed. Cir. 2012) .................................................................... 22, 35
`
`In re Morris,
`127 F.3d 1048 (Fed. Cir. 1997) .......................................................................... 10
`
`In re Paulsen,
`30 F.3d 1475 (Fed. Cir. 1994) ............................................................................ 10
`
`In re Rambus Inc.,
`694 F.3d 42 (Fed. Cir. 2012) ........................................................................ 14, 15
`
`In re Translogic Tech., Inc.,
`504 F.3d 1249 (Fed. Cir. 2007) .......................................................................... 10
`
`Janssen v. Lupin,
`2014 U.S. Dist. LEXIS 155110 (D.N.J. Aug. 14, 2014) .............................passim
`
`King Pharms., Inc. v Eon Labs., Inc.,
`616 F.3d 1267 (Fed Cir. 2010) ........................................................................... 22
`
`Merck Sharpe & Dohme Corp. v. Apotex, Inc.,
`2013 U.S. App. LEXIS 12102 (Fed. Cir. June 10, 2013) ................................... 60
`
`Microsoft Corp. v. Proxyconn, Inc.,
`___ F.3d ___, 2015 U.S. App. LEXIS 10081 (Fed. Cir. June 16, 2015) ............. 9
`
`Otsuka Pharm. Co. v. Sandoz, Inc.,
`678 F.3d 1280 (Fed. Cir. 2012) .................................................................... 45, 48
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .................................................................... 10, 14
`
`Purdue Pharma L.P. v. DepoMed, Inc.,
`Case IPR2014-00378, Paper No. 18 (PTAB Aug. 6, 2014) ............................... 25
`
`Roche Palo Alto LLC v. Ranbaxy Labs., Ltd.,
`No. 06-2003, 2009 U.S. Dist. LEXIS 90804 (D.N.J. Sept. 30, 2009) ................ 60
`
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`Sandoz Inc. v. EKR Therapeutics, LLC,
`Case IPR2015-00007, Paper 20 (PTAB Apr. 24, 2015) ........................ 30, 38, 40
`
`Sanofi-Synthelabo v. Apotex, Inc.,
`550 F.3d 1075 (Fed. Cir. 2008) .......................................................................... 60
`
`Schering Corp. v. Apotex, Inc.,
`No. 09-6373, 2012 U.S. Dist. LEXIS 83414 (D.N.J. June 15, 2012) ................ 60
`
`Smithkline Beecham Corp. v. Apotex Corp.,
`403 F.3d 1331 (Fed. Cir. 2005) .......................................................................... 22
`
`Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd.,
`492 F.3d 1350 (Fed. Cir. 2007) .......................................................................... 48
`
`Unigene Labs., Inc. v. Apotex, Inc.,
`655 F.3d 1352 (Fed. Cir. 2011) .......................................................................... 45
`
`Zoll Lifecor Corp. v. Philips Elecs. N. Am. Corp.,
`IPR2013-00606, Paper 13 (PTAB Mar. 20, 2014) ........................................... 5, 7
`
`STATUTES
`
`35 U.S.C. § 102 ........................................................................................................ 49
`
`35 U.S.C. § 312 .......................................................................................................... 3
`
`35 U.S.C. § 315 .......................................................................................................... 7
`
`OTHER AUTHORITIES
`
`37 C.F.R. § 42 ............................................................................................................ 9
`
`Bernstein, Polymorphism – A Perspective, CRYSTAL GROWTH & DESIGN
`PERSPECTIVE, 2011, Vol. 11 ............................................................................... 44
`
`Volume 77 Fed. Reg. 48756, 48759 (Aug. 14, 2012) ............................................... 3
`
`WEBSTER’S THIRD NEW INTERNATIONAL DICTIONARY (2002) ................................ 19
`
`vi
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`
`
`
`
`Janssen
`Exhibit No.
`
`2001
`
`2002
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`Case IPR2015-01030
`Patent Owner’s Preliminary Response
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`TABLE OF EXHIBITS
`
`Description
`
`Photographic image of outside of Lupin’s building in Baltimore,
`MD, accessed at http://articles.baltimoresun.com/2014-04-
`09/business/bal-lupin-name-marks-baltimore-expansion-
`20140408_1_lupin-pharmaceuticals-drug-company-drug-
`administration on July 17, 2015
`
`Lupin Annual Report 2015, accessed at
`http://lupinworld.com/pdf/15/Lupin_AR_2015-25-06-15.pdf
`
`2015 Annual Report – Lupin Pharmaceuticals, Inc., filed with the
`Commonwealth of Massachusetts on May 20, 2015
`
`“Application by Foreign Corporation for Authorization to
`Transact Business in Florida,” filed by Lupin Inc. with Florida
`Department of State, Division of Corporations on February 5,
`2014
`
`Florida Dept. of State Division of Corporations, “Detail by Entity
`Name” for Lupin Inc.
`
`LinkedIn Profile: Gary DePaolo, US Corporate Controller, Lupin
`Pharmaceuticals
`
`LinkedIn Profile: Bill Gileza, Finance Dept., Lupin
`Pharmaceuticals
`
`Lupin Pharmaceuticals, Inc., Pharmacy Times, July 14, 2014,
`accessed at http://www.pharmacytimes.com/publications/
`supplement/2014/Generic-Supplement-2014/Lupin-
`Pharmaceuticals-Inc on July 1, 2015
`
`Lupin Inc. to Expand Operations at Florida’s Coral Springs
`Corporate Park, Culrav.org, October 7, 2014, accessed at
`http://www.culrav.org/pr/lupin-inc-expand-operations-floridas-
`coral-springs-corporate-park.php on July 1, 2015
`
`8103872v.1
`
`vii
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`

`
`Janssen
`Exhibit No.
`
`2010
`
`2011
`
`2012
`
`2013
`
`2014
`
`2015
`
`2016
`
`2017
`
`2018
`
`Case IPR2015-01030
`Patent Owner’s Preliminary Response
`
`Description
`
`Research-Oriented Pharmaceutical Firm Lupin Expands Coral
`Springs, Fl. Research Hub, Area Development, Oct. 6, 2014,
`accessed at http://www.areadevelopment.com/newsItems/10-6-
`2014/lupin-operations-expansion-coral-springs-
`florida782378.shtml on July 1, 2015
`
`Business Tax Details for Lupin Inc. in 2016, Broward County,
`Flordia, accessed at https://www.broward.county-
`taxes.com/public/business_tax/accounts/120853 on July 8, 2015
`
`Kenneth A. Connors, The Karl Fischer Titration of Water, DRUG
`DEV. AND INDUSTRIAL PHARM., 14(14), 1891-1903(1988)
`
`Dario Braga & Fabrizia Grepioni, Making crystals from crystals:
`a green route to crystal engineering and polymorphism, CHEM.
`COMMUN., 3635-3645 (2005)
`
`Job Posting for Principal Scientist, Formulations at Lupin, RDD
`Online, accessed at http://www.rddonline.com/resources/jobs
`/job.php?id=267 on July 8, 2015
`
`License Information for Lupin Inc. in Coral Springs, Florida,
`accessed at https://govnow.coralsprings.org/wps/portal/!ut/p
`/c5/dY7LCoMwFES_pV9wL2o1XaYGacS on July 8, 2015
`
`Joel Bernstein, Polymorphism-A Perspective, CRYSTAL GROWTH
`& DESIGN PERSPECTIVE, Vol. 11, 632-650 (2011)
`
`Erik De Clercq, New Developments in Anti-HIV Chemotherapy,
`CURRENT MED. CHEM. Vol. 8, No. 13, 1543-1572 (2001)
`
`Erik De Clercq, Review New Developments in Anti-HIV
`Chemotherapy, BIOCHIMICA ET BIIOPHYSICA ACTA, Vol. 1587,
`258-275 (2002)
`
`2019
`
`U.S. Patent No. 7,470,506
`
`viii
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`Janssen
`Exhibit No.
`
`Case IPR2015-01030
`Patent Owner’s Preliminary Response
`
`Description
`
`2020
`
`2021
`
`2022
`
`2023
`
`2024
`
`2025
`
`2026
`
`2027
`
`2028
`
`2029
`
`2030
`
`2031
`
`Michael J. Jozwiakowski, Alteration of the Solid State of the
`Drug Substance: Polymorphs, Solvates, and Amorphous Forms,
`WATER-INSOLUBLE DRUG FORMULATION, 525-568, (2000)
`
`Sudha R. Vippagunta et al., Crystalline Solids, ADVANCE DRUG
`DELIVERY REVIEWS, Vol. 48, 3-26 (2001)
`
`Joel Bernstein, Crystal growth, polymorphism and structure-
`property relationships in organic crystals, J. PHYS. D: APPL.
`PHYS. Vol. 26, B66-B76 (1993)
`
`U.S. Patent No. 7,056,942
`
`U.S. Patent No. 6,861,426
`
`Matthew L. Peterson et al., Iterative High-Throughput
`Polymorphism studies on Acetaminophen and an Experimentally
`Derived Structure for Form III, J. AM. CHEM. SOC. Vol. 124,
`10958-10959 (2002)
`Sherry L. Morissette et al., High Throughput Crystallization:
`Polymorphs, Salts, Co-crystals and Solvates of Pharmaceutical
`Solids, ADVANCED DRUG DELIVERY REVIEWS, Vol. 56, 275-300
`(2004)
`Ning Shan and Michael J. Zaworotko, Polymorphic Crystal
`Foms and Cocrystals in Drug Delivery (Crystal Engineering),
`BURGER’S MED. CHEM., DRUG DISCOVERY, AND DEV. 7th ed.,
`187-218 (2010)
`Deposition of Michael J. Zaworotko, in Janssen Prods. v. Lupin
`Ltd., No. 10-5954 (D.N.J.), October 11, 2013 (excerpts)
`Trial Transcripts in Janssen Prods. v. Lupin Ltd., No. 10-5954
`(D.N.J.), for March 18, 2014-April 2, 2014 (excerpts)
`U.S. Patent No. 8,158,607
`Basics of Karl Fischer Titration, accessed at
`http://www.sigmaaldrich.com/analytical-chromatography/
`titration/hydranal/learning-center/theory.html on July 16, 2015
`
`ix
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`Janssen
`Exhibit No.
`
`Case IPR2015-01030
`Patent Owner’s Preliminary Response
`
`Description
`
`2032
`
`2033
`
`2034
`
`2035
`
`2036
`
`2037
`
`2038
`
`2039
`
`2040
`
`2041
`
`2042
`
`2043
`
`2044
`
`U.S. Patent No. 5,585,397
`“2013: Product Specification Sheet VX-478 (Amprenavir),”
`Cellagen Technology
`Otsuka Pharmaceutical v. Lupin et al., No. 14-cv-07105-JBS-
`KMW (D.N.J.), Lupin’s Answer to Amended Complaint for
`Patent Infringement, Mar. 9, 2015, ECF No. 37
`Orange Book: Approved Drug Products with Therapeutic
`Equivalence Evaluations, accessed at http://www.accessdata.
`fda.gov/scripts/cder/ob/default.cfm on July 15, 2015
`Sanofi et al. v. Lupin et al., No. 15-cv-00415-RGA (D. Del.),
`Complaint for Patent Infringement, May 21, 2015, ECF No. 1
`Warner Chilcott v. Lupin Atlantis et al., 14-cv-01827-RWT, (D.
`Md.), Complaint for Patent Infringement, June 6, 2014, ECF. No.
`1
`Lupin Atlantis Holdings SA Audited Accounts, 2014, accessed at
`http://www.lupinworld.com/pdf/14/subsidiaries/Lupin%20Atlant
`is%20(Standalone).pdf on July 16, 2015
`“The Lupin Story,” accessed at http://www.lupin.com/the-lupin-
`story.php on July 1, 2015
`WEBSTER’S THIRD NEW INTERNATIONAL DICTIONARY OF THE
`ENGLISH LANGUAGE UNABRIDGED (2002)
`AK Scientific, Inc., Fine & Specialty Chemicals in Catalog &
`Bulk, accessed at https://aksci.com/item_detail.php?cat=Z4214
`on July 15, 2015
`Hsien-Hsin Tung et al., Crystallization of Organic Compounds
`An Industrial Perspective (2009) (excerpts)
`Brian Moulton and Michael Zaworotko, From Molecules to
`Crystal Engineering: Supramolecular Isomerism and
`Polymorphism in Network Solids, CHEM. REVIEWS, Vol. 101, No.
`6, 1629-1658 (2001)
`Omathanu P. Perumal & Satheesh K. Podaralla, Role of
`Preformulation in Development of Solid Dosage Forms,
`PHARMACEUTICAL MANUFACTURING HANDBOOK: PRODUCTION
`AND PROCESSES 933-975 (Shayne Cox Gad ed., 2008), John
`Wiley & Sons, Inc.
`
`x
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`Description
`
`Deposition of Garland Marshall in Janssen Prods. v. Lupin Ltd.,
`No. 10-5954 (D.N.J.), October 22, 2013 (excerpts)
`Robert J. Ouellette and J. David Rawn, Organic Chemistry:
`Structure, Mechanism, and Synthesis (2014) (excerpts)
`Waiver of the Service of Summons, Janssen Prods., L.P. et al. v.
`Lupin Ltd. et al., C.A. No. 14-1370 (D.N.J.), Docs. 6-7.
`
`Janssen
`Exhibit No.
`
`2045
`
`2046
`
`2047
`
`
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`I.
`
`INTRODUCTION
`
`Patent Owner Janssen Science Ireland UC (“Janssen”) submits this
`
`Patent Owner Preliminary Response to the Petition by Lupin Limited (“Lupin”) for
`
`Inter Partes Review (“IPR”) of U.S. Patent No. 8,518,987. The ‘987 patent
`
`discloses and claims specific crystalline hydrates of darunavir with particular ratios
`
`of darunavir-to-water. The Petition should be denied because Lupin: (1) failed to
`
`identify all real parties-in-interest; and (2) has not shown a reasonable likelihood of
`
`prevailing on anticipation or obviousness with respect to any challenged claim.
`
`Failure to disclose real parties-in-interest: The Petition does not
`
`name two Lupin entities that should have been identified as real parties-in-interest,
`
`and it is too late for Lupin to correct the omission.
`
`As to anticipation: Lupin advances an inherent anticipation theory
`
`that is premised on an unreasonably broad interpretation of “hydrate” and ignores
`
`the darunavir-to-water ratio limitations in each of the challenged claims.
`
`The ‘987 patent specification defines a “solvate” as a “crystal form”
`
`that contains either stoichiometric or non-stoichiometric amounts of solvent and
`
`specifically identifies “hydrates” as an example of “solvates.” Col.4:64-67.1
`
`Lupin concedes that the “plain and ordinary meaning of ‘hydrate’” refers to a
`
`1 Citations in this form refer to the ‘987 patent (Ex. 1001), unless otherwise
`
`indicated.
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`“crystalline form” that contains water (Pet. 17). That is how the specification uses
`
`the term, and that is the broadest reasonable interpretation that the Examiner
`
`applied in the original examination.
`
`Lupin’s inherent anticipation theory depends on an unreasonably
`
`broad definition of “hydrate” that would encompass any darunavir form to which
`
`water is added, including that made in the presence of water or exposed to
`
`humidity. Lupin relies on this unreasonably broad construction because its expert
`
`obtained amorphous, not crystalline material when he made darunavir purportedly
`
`by following a prior art method. Lupin’s inherent anticipation theory inevitably
`
`fails when the correct and broadest reasonable interpretation of the term “hydrate”
`
`– a crystalline form of darunavir containing water – is applied.
`
`Lupin has no data indicating that the amorphous darunavir made by its
`
`expert actually had water or the specific darunavir-to-water ratios recited in the
`
`challenged claims. Lupin has not shown that the prior art methods would
`
`inevitably and necessarily result in a crystal form of darunavir, much less one with
`
`the claimed ratios of darunavir-to-water. Lupin has, therefore, failed to meet its
`
`burden of showing a reasonable likelihood of anticipation for any challenged
`
`claim.
`
`As to obviousness: Lupin’s obviousness arguments fail for the same
`
`reasons as its anticipation argument. Lupin argues that it would have been obvious
`
`2
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`to crystallize darunavir in the presence of water, but it cannot even say that its
`
`expert succeeded in doing so, much less that he succeeded in obtaining a hydrate
`
`with the claimed ratios of darunavir-to-water. Moreover, there was no reason to
`
`select darunavir for formulation out of the many compounds in the prior art; no
`
`reason to combine the references Lupin relies upon; no reason to try to make a
`
`hydrate of darunavir; and no reasonable expectation of success in doing so. The
`
`claimed invention would not have been obvious for persons of ordinary skill.
`
`II. THE PETITION FAILS TO IDENTIFY ALL REAL PARTIES-IN-
`INTEREST
`
`The Petition identifies two real parties-in-interest: Lupin Limited and
`
`Lupin Pharmaceuticals, Inc. (“Lupin Pharma”). (Pet. 5). Two related entities –
`
`Lupin Inc. and Lupin Atlantis Holdings SA (“Lupin Atlantis”) – should have been
`
`identified as real parties-in-interest, but are not identified.
`
`A. The Real Party-in-Interest Standard
`By statute, a petition for inter partes review “may be considered only
`
`if … the petition identifies all real parties in interest.” 35 U.S.C. § 312(a)(2).
`
`“That statutory requirement … defines a ‘threshold issue’ for substantive review”
`
`of a Petition. Galderma S.A. v. Allergan Industrie, SAS, IPR2014-01422, Paper 14
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`at 5 (PTAB March 5, 2015) (citation omitted). This statutory requirement “seeks
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`to protect patent owners from harassment via successive petitions by … related
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`parties ….” Vol. 77 Fed. Reg. 48756, 48759 (Aug. 14, 2012).
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`“In the context of an IPR, a real-party-in-interest is generally one that
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`‘desires review’ of the patent at issue ….” Galderma, at 6 (citation omitted). A
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`real party-in-interest “‘may be the party or parties at whose behest the petition has
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`been filed.’” Id. (citation omitted). It ultimately is the petitioner’s burden “to
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`establish that it has complied with the statutory requirement to identify all the real
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`parties-in-interest.” Id. at 7.
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`The real party-in-interest inquiry is “‘highly fact-dependent.’” Id.
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`(citation omitted). “[R]arely will one fact, standing alone, be determinative ….”
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`Id. A relevant question is whether an unnamed entity had “‘the power—whether
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`exercised or not—to call the shots [in the Petition].’” Id. at 8 (citation omitted)
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`(emphasis added in Galderma)). The ability to exercise such control “‘may be
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`overt or covert, and the evidence of it may be direct or circumstantial.’” Id. at 7
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`(citation omitted).
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`B.
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`Lupin Inc. and Lupin Atlantis are Real Parties-In-Interest
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`The IPR petition identifies Lupin Limited and Lupin Pharma as real
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`parties-in-interest. (Pet. 5). Two related entities – Lupin Inc. and Lupin Atlantis
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`Holdings SA (“Lupin Atlantis”) – should also have been identified as real parties-
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`in-interest but are not mentioned. As shown below, Lupin Inc. (an unnamed party)
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`is a wholly owned subsidiary of Lupin Atlantis (another unnamed party). Ex. 2002
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`at 43, 154. Lupin Inc. owns 97% of the stock of Lupin Pharma – an
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`identified party-in-interest. Lupin Inc. and Lupin
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`Pharma both have their principal place of business
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`at 111 South Calvert Street, 21st floor, Baltimore,
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`Maryland. Id. at 58, 60. Lupin Atlantis is based in
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`Switzerland. The ultimate parent, Lupin Limited, is based in India. Id. at 4.
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`“[S]hared corporate leadership” between a petitioner and an unnamed
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`party supports a finding that the latter is a real party-in-interest. Galderma, Paper
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`14 at 8. Here, Vinita Gupta is the President of Lupin Inc., and the CEO of both
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`Lupin Pharma and Lupin Limited. Ex. 2003 at 1; Ex. 2002 at 4; Ex. 2004 at 5; Ex.
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`2005 at 1. Her father is the founder and Chairman of Lupin Limited; her mother is
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`its Executive Director; her brother is its Managing Director. Ex. 2002 at 3, 75.
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`Other officers of Lupin Inc. – its Secretary, Gary DePaolo, and its Treasurer,
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`William Gileza – are also high-ranking officials of Lupin Pharma. Ex. 2004 at 5;
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`Ex. 2005 at 2; Exs. 2006 and 2007. The presence of the same people “at the helm
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`of both [Lupin Pharma] and its parent” “strongly implies ‘an involved and
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`controlling parent corporation representing the unified interests of [all of these
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`companies].’” Galderma, Paper 14 at 12 (quoting Zoll Lifecor Corp. v. Philips
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`Elecs. N. Am. Corp., IPR2013-00606, Paper 13 (PTAB Mar. 20, 2014) at 10).
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`The Lupin entities also have intertwined business relationships. Lupin
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`Inc. recently set up an R&D facility in Coral Springs, Florida to support Lupin
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`Pharma’s efforts to “offer products in new therapeutic areas,” Ex. 2008 at 2; Ex.
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`2009 at 1-2; Ex. 2010, and both companies have offices at the Coral Springs
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`address. Exs. 2011, 2014, and 2015. In addition, Lupin Atlantis holds New Drug
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`Applications (NDAs) and Abbreviated New Drug Applications (ANDAs) for drugs
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`that Lupin Pharma markets or seeks to market. Ex. 2034 ¶ 21; Ex. 2035; Ex. 2036
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`¶ 32; Ex. 2037 ¶ 17. There are extensive transactions between Lupin Atlantis and
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`Lupin Pharma, including sales of goods, services rendered, and reimbursement of
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`payments and expenses. Ex. 2038 at 21-23.
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`Moreover, the distinction between the Lupin entities is blurred in
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`presentations to the public. For example, the Lupin website describes “Lupin” as
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`“a fully integrated pharmaceutical company,” with operations in the U.S., India,
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`and elsewhere. Ex. 2039. In addition, the building where Lupin Inc. and Lupin
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`Pharma have their main offices prominently bears the
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`“Lupin” name. Ex. 2001. “Use of the umbrella term
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`[Lupin]” in referring to various Lupin entities “encourages
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`the perception that [the Lupin companies] … function as a
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`single entity.” Atlanta Gas Light Co. v. Bennett Regulator
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`Guards, Inc., IPR2013-00453, Paper 88 at 11 (PTAB Jan.
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`6, 2015). “[T]his factor weighs heavily in favor of finding
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`[Lupin Inc. and Lupin Atlantis] to be … real part[ies] in interest ….” Id.
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`On these facts, “the failure to identify the parent corporation[s],
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`[Lupin Inc. and Lupin Atlantis], violates the statutory and regulatory requirements
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`that the petition identify all real parties-in-interest.” Zoll, Paper 13 at 11; see also
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`Galderma, Paper 14 at 12-13 (finding that an intermediate entity in the corporate
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`hierarchy was a real party-in-interest).
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`C. The Petition Should be Dismissed
`Because the Petition fails to identify all real parties-in-interest, it is
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`“incomplete” and cannot be accorded a filing date. Id. at 13. Although this type of
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`omission ordinarily can be corrected, that would be “futile” here, id., because
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`Janssen brought suit on the ‘987 patent against Lupin Limited and Lupin Pharma
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`on March 4, 2014 and it is more than one year since April 11, 2014, when the
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`waiver of service was filed. Ex. 2047. Under 35 U.S.C. § 315(b), a corrected
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`petition would have to be “denied as untimely.” Galderma, Paper 14 at 13. The
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`Petition should accordingly be dismissed. Id.; see also Zoll, Paper 13 at 12.
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`III. BACKGROUND: THE ‘987 PATENT
`As explained in the ‘987 patent, protease inhibitors such as darunavir
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`are useful for treating the HIV virus. Col. 1:25-34. But more is required for a
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`pharmaceutical product. As the specification explains, pharmaceutical products
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`must have “good stability … [to] ensure that the[ir] desired chemical integrity … is
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`maintained,” col. 2:20-22, and good bioavailability to ensure that “a therapeutically
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`effective concentration is achieved,” col. 2:40-41. Finding a formulation that
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`meets these objectives is “a complex technical discipline.” Col. 2:5-7.
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`It is “not obvious to foresee which pharmaceutical formulations will
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`be acceptable.” Col. 2:51-53. The inventors of the ‘987 patent “unexpectedly
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`found that certain modifications of the solid state of [darunavir] positively
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`influenced its applicability in pharmaceutical formulations.” Col. 2:53-56. More
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`specifically, they found that pseudopolymorphic forms of darunavir had good
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`stability and bioavailability. Col. 2:6-64. The ‘987 patent explains that such
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`pseudopolymorphic forms had “high purity … for pharmaceutical use,” and are
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`useful in medicines that inhibit HIV protease activity. Col. 2:64-67.
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`The ‘987 patent is entitled “Pseudopolymorphic Forms of a[n] HIV
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`Protease Inhibitor.” The technical field of the invention relates to
`“pseudopolymorphic forms” of darunavir. Col. 1:17-20.
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`The specification states that “[t]he term pseudopolymorph is applied
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`to crystalline forms that have solvent molecules incorporated in their lattice
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`structures.” Col. 4:67-5:2 (emphasis added). The specification notes that “[t]he
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`term pseudopolymorphism is used frequently to designate solvates.” Col. 5:2-5.
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`The term “solvate” is expressly defined as a “crystal form that contains either
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`stoichiometric or non-stoichiometric amounts of solvent.” Col. 4:64-66 (emphasis
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`added). “Since water is a solvent, solvates also include hydrates.” Col. 4:66-67.
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`The ‘987 patent has nineteen claims. Each claim requires a hydrate of
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`darunavir that has a specified ratio of darunavir-to-water. The