Paper No. 12
`January 20, 2016
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`
`
`AGILA SPECIALTIES INC. and MYLAN LABORATORIES LIMITED,
`Petitioners,
`
`v.
`
`CEPHALON, INC.
`Patent Owner.
`
`_____________
`
`Case IPR2016-00026
`Patent No. 8,791,270 B2
`
`_____________________
`
`CEPHALON, INC.’S PRELIMINARY PATENT OWNER RESPONSE
`PURSUANT TO 37 C.F.R. § 42.107
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`IPR2016-00026
`Patent Owner’s Preliminary Response
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`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION ......................................................................................... 1
`
`II. BACKGROUND ............................................................................................ 3
`
`
`A.
`
`
`B.
`
`
`C.
`
`
`D.
`
`The Inventors Identified a Problem Not Recognized in the Art ........... 3
`
`The Inventions of the ’270 Patent ......................................................... 6
`
`FDA Approval and Market Response ................................................... 7
`
`Petitioners’ ANDA Filing ..................................................................... 8
`
`III. PETITIONERS FAILED TO IDENTIFY ALL OF THE REAL
`PARTIES-IN-INTEREST ............................................................................. 8
`
`
`A.
`
`
`B.
`
`The Legal Standard ............................................................................... 9
`
`Petitioners Should Have Identified Mylan Inc. and Mylan
`Pharmaceuticals Inc. as Real Parties-in-Interest .................................10
`
`IV. PETITIONERS’ PROPOSED CLAIM CONSTRUCTIONS AND
`DEFINITION OF AN ORDINARY ARTISAN .......................................16
`
`V.
`
`THE PETITION FAILS TO MAKE THE SHOWING
`REQUIRED UNDER 35 U.S.C. § 314(a) ...................................................17
`
` Ground 1: Petitioners Have Not Demonstrated a Reasonable
`A.
`Likelihood that They Will Prove that Claims 1, 2, 7-10, 13-16,
`19, and 20 Are Anticipated by Maas. ..................................................17
`1.
`Claims 1, 2, 10, 13 and 16 ........................................................19
`2.
`Claims 2, 10, 13 and 16 ............................................................22
`3.
`Claims 7-10, 13-15, 19 and 20 ..................................................23
`
` Ground 2: Petitioners Have Not Demonstrated a Reasonable
`B.
`Likelihood that They Will Prove that Claims 1-20 Are Obvious
`over Maas and Teagarden. ..................................................................25
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`IPR2016-00026
`Patent Owner’s Preliminary Response
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`1.
`
`2.
`
`3.
`
`Petitioners Fail to Establish Why an Ordinary Artisan
`Would Have Targeted the Claimed Degradant Profiles
`with a Reasonable Likelihood of Success. ................................26
`Petitioners Dramatically Overstate the Teaching of
`Teagarden ..................................................................................29
`Claim-by-Claim Analysis .........................................................35
`
` Ground 3: Petitioners Have Not Demonstrated a Reasonable
`C.
`Likelihood that They Will Prove that Claims 13 and 19 Are
`Obvious over Maas, Teagarden and Gust. ..........................................39
`
` Ground 4: Petitioners Have Not Demonstrated a Reasonable
`D.
`Likelihood that They Will Prove that Claims 20-23 Are Obvious
`over Maas, Teagarden and The Rote List. ..........................................41
`
`VI. PETITIONERS’ GROUNDS ARE REDUNDANT AND
`VIOLATE THE BOARD’S RULES ..........................................................42
`
`VII. CONCLUSION ............................................................................................44
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`IPR2016-00026
`Patent Owner’s Preliminary Response
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`
`
`Cases
`
`Agila Specialties Inc. v. Cephalon, Inc.,
`IPR2015-00503, Paper 4 (PTAB Dec. 24, 2014) ............................................... 11
`
`Agila Specialties Inc. v. Cephalon, Inc.,
`IPR2015-00503, Paper 10 (PTAB July 20, 2015) ........................................ 29, 36
`
`Agila Specialties Inc. v. Cephalon, Inc.,
`IPR2015-00503, Paper 16 (PTAB Oct. 7, 2015) ................................................ 11
`
`Agila Specialties Inc. v. Cubist Pharm., Inc.,
`IPR2015-00131, Paper 4, IPR2015-00132, Paper 4, IPR2015-
`00141, Paper 1, IPR2015-00142, Paper 1, IPR2015-00143,
`IPR2015-00144, Paper 1 (PTAB Oct. 23, 2014) .......................................... 11, 12
`
`Allergan, Inc. v. Apotex Inc.,
`754 F.3d 952 (Fed. Cir. 2014) ............................................................................ 21
`
`Aruze Gaming Macau, Ltd. v. MGT Gaming, Inc.,
`IPR2014-01288, Paper 13 (PTAB Feb. 20, 2015). ............................................. 10
`
`Atlanta Gas Light Co. v. Bennett Regulator Guards, Inc.,
`IPR2013-00453, Paper 88 (PTAB Jan. 6, 2015) ............................................ 9, 15
`
`Cadence Pharm. Inc. v. Exela PharmSci Inc.,
`780 F.3d 1364 (Fed. Cir. 2015) .......................................................................... 32
`
`Fresenius Kabi USA, LLC v. Cephalon, Inc.,
`IPR2016-00098, Paper 2 (PTAB Oct. 28, 2015) .......................................... 17, 22
`
`Galderma S.A. v. Allergan Industrie, SAS,
`IPR2014-01422, Paper 14 (PTAB Mar. 5, 2015) .................................... 9, 10, 14
`
`Gonzalez v. Banco Cent. Corp.,
`27 F.3d 751 (1st Cir. 1994) ................................................................................. 14
`
`63251651
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`IPR2016-00026
`Patent Owner’s Preliminary Response
`
`
`Illumina, Inc. v. Tr. of Columbia Univ.,
`IPR2012-0006, Paper 43 (PTAB May 10, 2013) ............................................... 43
`
`Liberty Mutual Ins. Co. v. Progressive Casualty Ins. Co.,
`CBM2012-0003 Paper 7 (PTAB Oct. 25, 2012). ............................................... 43
`
`Mylan Pharm. Inc. v. Baxter Int’l Inc.,
`IPR2016-00217, Paper 3 and IPR2016-00218, Paper 3
`(PTAB Nov. 19, 2015). ....................................................................................... 11
`
`Mylan Pharm. Inc. v. Nissan Chem. Indus. Ltd.,
`IPR2015-01069, Paper 12 (PTAB Aug. 28, 2015) ...................................... 14, 16
`
`Oracle Corp. v. Clouding IP, LLC,
`IPR2013-00075, Paper 15 (PTAB June 13, 2013) ............................................. 43
`
`Reflectix, Inc. v. Promethean Insulation Tech. LLC,
`IPR2015-00044, Paper 18 (PTAB Jan. 20, 2015) .............................................. 15
`
`Scaltech Inc. v. Retec/Tetra, LLC,
`178 F.3d 1378 (Fed. Cir. 2014) .......................................................................... 21
`
`Scripps Clinic & Research Found. v. Genentech, Inc.,
`927 F.2d 1565 (Fed. Cir. 1991) .......................................................................... 18
`
`TRW Auto. US L.L.C. v. Magna Elecs. Inc.,
`IPR2014-00257, Paper 16 (PTAB Apr. 8, 2013) ............................................... 35
`
`Zerto, Inc. v. EMC Corp.,
` IPR2014-01254, Paper 32 (PTAB Feb. 12, 2015) ......................................... 9, 10
`
`Zoll Lifecor Corp. v. Philips Elecs. N. Am. Corp.,
`IPR2013-00609, Paper 15 (PTAB Mar. 20, 2014) ......................................... 9, 15
`
`Statutes
`
`35 U.S.C. § 312(a) ............................................................................................... 9, 15
`
`35 U.S.C. § 315(b) ................................................................................................... 15
`
`35 U.S.C. § 325(d) ................................................................................................... 44
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`Patent Owner’s Preliminary Response
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`Other Authorities
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`37 C.F.R. § 42.1(b) .................................................................................................. 42
`
`37 C.F.R. § 42.108(b) .............................................................................................. 42
`
`Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,760
`(Aug. 14, 2014) ................................................................................................... 10
`
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`PATENT OWNER’S LIST OF EXHIBITS
`
`Paper No. 12
`January 20, 2016
`
`EXHIBIT
`
`DESCRIPTION
`
`2001
`
`2002
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`TREANDA® Prescribing Information
`
`“Treanda New Drug Application for the Treatment of
`Chronic Lymphocytic Leukemia Granted Priority
`Review Status by FDA,” Drugs.com (December 3,
`2007)
`Kanti R. Rai, et al., “Fludarabine Compared with
`Chlorambucil as Primary Therapy for Chronic
`Lymphocytic Leukemia,” 343(24) New Eng. J. Med.
`1752 (December 14, 2000)
`M. J. Keating, et al., “Long-Term Follow-up of
`Patients with Chronic Lymphocytic Leukemia (CLL)
`Receiving Fludarabine Regimens as Initial Therapy,”
`92 Blood 1165 (August 15, 1998)
`Guillaume Dighiero, et al., “Chlorambucil in Indolent
`Chronic Lymphocytic Leukemia,” 338 New Eng. J.
`Med. 1506 (May 21, 1998)
`The French Cooperative Group on Chronic
`Lymphocytic Leukemia, “Comparison of Fludarabine,
`Cyclophosphamide / Doxorubicin / Prednisone, and
`Cyclophosphamide / Doxorubicin / Vincristine /
`Prednisone in Advanced Forms of Chronic
`Lymphocytic Leukemia: Preliminary Results of a
`Controlled Clinical Trial,” 20 Seminarsin Oncology 21
`(October 1993)
`Suzanne Demko, et al., “FDA Drug Approval
`Summary: Alemtuzumab as Single-Agent Treatment
`for B-Cell Chronic Lymphocytic Leukemia,” 13 The
`Oncologist 167 (2008)
`A. J. Davies, et al., “Tositumomab and Iodine I 131
`Tositumomab for Recurrent Indolent and Transformed
`B-Cell Non-Hodgkin’s Lymphoma,” 22 J. Clin. Oncol.
`1469 (April 15, 2004)
`
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`IPR2016-00026
`Patent Owner’s Preliminary Response
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`EXHIBIT
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`DESCRIPTION
`
`2009
`
`2010
`
`2011
`
`2012
`
`2013
`
`2014
`
`2015
`
`2016
`
`Samuel A. Jacobs, et al., “Phase II Trial of Short-
`Course CHOP-R Followed by 90Y-ibritumomab
`Tiuexetan and Extended Rituximab in Previously
`Untreated Follicular Lymphoma,” 14(21) Clin. Cancer
`Res. 7088 (November, 1, 2008)
`Richard I. Fisher, et al., “Comparison of a Standard
`Regimen (CHOP) with Three Intensive Chemotherapy
`Regimens for Advanced Non-Hodgkin’s Lymphoma,”
`328(14) New Eng. J. Med. 1002 (April 8, 1993)
`Peter McLaughlin, et al., “Fludarabine, Mitoxantrone,
`and Dexamethasone: An Effective New Regimen for
`Indolent Lymphoma,” 14 J. Clin. Oncol. 1262 (April
`1996)
`“FDA Approves Treanda,” Drugs.com (March 20,
`2008)
`“Cephalon Receives FDA Approval for Treanda to
`Treat Patients with Relapsed Indolent Non-Hodgkin’s
`Lymphoma,” Drugs.com (October 31, 2008)
`Brad S. Kahl, et al., “Bendamustine Is Effective
`Therapy in Patients with Rituximab-Refractory,
`Indolent B-cell Non-Hodgkin Lymphoma: Results
`From a Multicenter Study,” Cancer 106 (January 1,
`2010)
`K. Sue Robinson, et al., “Phase II Multicenter Study of
`Bendamustine Plus Rituximab in Patients with
`Relapsed Indolent B-Cell and Mantle Cell Non-
`Hodgkin’s Lymphoma,” 26 J. Clin. Oncol. 4473
`(September 20, 2008)
`Wolfgang U. Knauf, et al., “Phase III Randomized
`Study of Bendamustine Compared with Chlorambucil
`in Previously Untreated Patients with Chronic
`Lymphocytic Leukemia,” 27 J. Clin. Oncol. 4278
`(September 10, 2009)
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`IPR2016-00026
`Patent Owner’s Preliminary Response
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`EXHIBIT
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`DESCRIPTION
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`2017
`
`2018
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`2019
`
`2020
`
`2021
`
`2022
`
`2023
`
`2024
`
`2025
`
`2026
`
`2027
`
`2028
`
`Wolfgang U. Knauf, et al., “Bendamustine Compared
`with Chlorambucil in Previously Untreated Patients
`with Chronic Lymphocytic Leukaemia: Updated
`Results of a Randomized Phase III Trial,” 159 Brit. J.
`Hematology 67 (August 4, 2012)
`Norbert Niederle, et al., “Bendamustine Compared to
`Fludarabine as Second-Line Treatment in Chronic
`Lymphocytic Leukemia,” 92 Ann. Hematology 653
`(January 23, 2013)
`Teva Pharmaceutical Industries Limited, Form 20-F,
`2014
`Teva Pharmaceutical Industries Limited, Form 20-F,
`2011
`Cephalon, Inc., Form 10-K, 2010
`
`Cephalon, Inc., Form 10-K, 2009
`
`Cephalon, Inc., Form 10-K, 2008
`
`Agila Specialties Inc. F/K/A Strides, Inc. and Onco
`Therapies Limited’s Corporate Disclosure Statement
`Pursuant To Fed. R. Civ. 7.1
`Agila Specialties Inc. F/K/A Strides, Inc. and Onco
`Therapies Limited’s Corporate Disclosure Statement
`Pursuant To Fed. R. Civ. 7.1
`February 12, 2015 Letter from Bradley L. Wideman,
`Vice President, Associate General Counsel, Securities
`and Assistant Secretary, Mylan, Inc. to Office of Chief
`Counsel, Securities and Exchange Commission
`“Leadership,” Mylan.com (last visited January 7,
`2016)
`Mylan Pharmaceuticals, Inc.’s Powers of Attorney
`submitted in IPR2016-00218, IPR2016-00217,
`IPR2015-01340, IPR2015-00830, IPR2015-00644,
`IPR2015-00643, and IPR2015-00682
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`EXHIBIT
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`DESCRIPTION
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`Patent Owner’s Preliminary Response
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`--- IPR2016-00026
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`2029
`
`2030
`
`2031
`
`March 4, 2015 Letter from Matt S. McNair, Special
`Counsel, United States Securities and Exchange
`Commission
`Email Chain between Assad Rajani, Kaye Scholer LLP
`and Steven W. Parmelee, Wilson Sonsini Goodrich &
`Rosati regarding Cephalon-IPR2016-00026
`Thissen Laboratories, Batch 02K27 Certificate of
`Analysis
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`IPR2016-00026
`Patent Owner’s Preliminary Response
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`I.
`
`INTRODUCTION
`
`Patent Owner Cephalon Inc.’s (“Cephalon’s”) U.S. Patent No. 8,791,270 B2
`
`(“the ’270 Patent”) claims life-saving pharmaceutical compositions of
`
`bendamustine used to treat cancers such as indolent B-cell non-Hodgkin’s
`
`lymphoma (“NHL”) and chronic lymphocytic leukemia (“CLL”). (Ex. 2001, 1).
`
`The inventors named on the ’270 Patent discovered that although
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`bendamustine had been sold for many years in Germany, the product suffered from
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`high impurity levels — owing to the recognized degradation of bendamustine in
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`water — which would have precluded FDA approval for sale in the United States.
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`The inventors devised new methods of manufacturing a bendamustine product that
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`increased its stability, reduced the degradants and allowed for FDA approval.
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`As discussed below, the Petition is predicated entirely on prior art that was
`
`before the Examiner during prosecution. All four of the Grounds of
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`unpatentability advanced by the Petitioners rely on B. Maas, C. Huber, I. Kramer,
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`Stability of Bendamustine Hydrochloride in Infusions, Pharmazie 49 (1994), 775-
`
`77 (“Maas”) (Ex. 1007),1 a prior art publication about Ribomustin, the
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`1 The title shown here is a translation. The article was published in German and is
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`entitled Stabilität von Bendamustinhydrochlorid in Infusionslösungen.
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`bendamustine product manufactured in Germany. Petitioners concede, however,
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`that the Maas reference lacks the specific degradant data that is key to the claims of
`
`the ’270 Patent. Petitioners propose two alternative approaches to remedy that
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`critical shortcoming. Neither has merit.
`
`In Ground 1, Petitioners argue that Maas anticipates certain claims of the
`
`’270 Patent, positing that the missing impurity data was inherent in Ribomustin, as
`
`reflected in Table 13 of the ’270 Patent. But the data in Table 13 of the ’270
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`Patent concerned the degradant content of lyophilized (freeze-dried) Ribomustin
`
`powder and does not reflect the degradant content of the reconstituted Ribomustin
`
`product that Maas tested. In fact, the Ribomustin described in Table 13 was from a
`
`different manufacturer than was Maas’s Ribomustin. In any event, Petitioners
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`cherry-pick the data from Table 13, ignoring those batches of Ribomustin that
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`undermine their theory. Hence, the data upon which Petitioners rely does not
`
`reflect degradant content that would need to be shown to be inherent — i.e.,
`
`“necessarily present” — in the reconstituted bendamustine formulation discussed
`
`in Maas in order for Petitioners’ argument to succeed
`
`In Ground 2, Petitioners argue that the degradant limitations of the claims of
`
`the ’270 Patent are obvious in light of Maas in combination with a second prior art
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`publication, D. Teagarden, D. Baker, Practical aspects of lyophilization using non-
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`aqueous co-solvent systems, 15 Eur. J. Phar. Sci. 115 (2002) (“Teagarden”) (Ex.
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`1006), which concerns lyophilizing compounds that are unstable in water. As
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`shown below, however, Teagarden makes no mention of bendamustine. Moreover,
`
`there is no merit to Petitioners’ conclusory assertion that unpublished findings
`
`reported by Teagarden about reducing the degradation of a single water-unstable
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`compound, trecetilide fumarate, are equally applicable to bendamustine, given that
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`the two compounds have entirely different structures and degrade via different
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`chemical pathways.
`
`In each of Grounds 3 and 4, Petitioners rely on Maas, Teagarden and a third
`
`reference. Yet, the additional cited art provides none of the information missing
`
`from the references cited in Grounds 1 and 2. Consequently, Grounds 3 and 4 fail
`
`as well.
`
`Accordingly, as detailed below, Petitioners do not establish a reasonable
`
`likelihood that they will prevail in invalidating any of the claims of the ’270 Patent,
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`and the Petition should be denied without institution.
`
`II. BACKGROUND
`
`
`
` The Inventors Identified a Problem Not Recognized in the Art A.
`
`Bendamustine was initially synthesized in 1963 in the East German
`
`Democratic Republic. (Ex. 1001, 2:1-2). The drug was available in East Germany
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`as Cytostasan® and later in re-unified Germany as Ribomustin®. (Id. at 2:2-5).
`
`Neither Cytostasan nor Ribomustin was ever approved by the U.S. Food and Drug
`
`Administration (“FDA”) and, before the invention of the ’270 Patent,
`
`bendamustine was unavailable to patients in the United States. (Ex. 2002, 1).
`
`Clinical studies performed both before and after the inventors’ 2005
`
`provisional patent application filing showed that treatments for NHL and CLL then
`
`available, though they elicited some response, did not improve survival and
`
`presented a risk of serious side effects in an already compromised patient
`
`population. (Ex. 2003, 1750; Ex. 2004, 1160; Ex. 2005, 1506; Ex. 2006, 21-23;
`
`Ex. 2007, 167; Ex. 2008, 1469; Ex. 2009, 7090; Ex. 2010, 1004; Ex. 2011, 1262).
`
`Thus, there was a recognized need for an effective pharmaceutical treatment.
`
`Based on the information publicly available at the time, Ribomustin, as
`
`formulated, appeared to be a viable candidate for FDA approval. Although
`
`bendamustine was known to degrade in the presence of water, the published
`
`product information indicated that the lyophilized Ribomustin product could be
`
`reconstituted in water relatively quickly such that the product would not degrade to
`
`the point that it was unusable. (See Ex. 1014, 9 (reconstitution “usually takes 5 to
`
`10 minutes”)). Researchers thus concluded that reconstituted Ribomustin was
`
`suitable for infusion into patients. (See Ex. 1007, 6 (“Likewise for the
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`recommended administration as a short infusion over 30 min, no stability problems
`
`are expected, since these bendamustine preparations have a stability of 9 h at room
`
`temperature.” (emphasis added))).
`
`In 2003, Salmedix, Inc. (“Salmedix”), a small pharmaceutical company
`
`(later acquired by Patent Owner), evaluated Ribomustin for purposes of seeking
`
`FDA approval to sell it in the United States. (Ex. 1001, 5:39-59). Salmedix
`
`licensed confidential information from Fujisawa Deutschland regarding the process
`
`for manufacturing Ribomustin and visited the German manufacturing facilities.
`
`Salmedix determined that the FDA would not approve Ribomustin as then
`
`formulated and that “an alternative to the Ribomustine® formulation of
`
`Bendamustine HCl” was needed. (Ex. 1019, 52).2 Salmedix was concerned that
`
`by modern FDA standards, the degradant levels in Ribomustin were too high. (Ex.
`
`1001, 20:47-61). In addition, in practice, reconstituting the lyophilized drug took
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`significantly longer (“may take 30-45 minutes”) than the publicly available product
`
`information indicated. (Id. at 33:20-24). The inventors realized that besides being
`
`burdensome for healthcare professionals tasked with reconstituting the Ribomustin
`
`for infusion, the exposure of bendamustine to water during the unexpectedly slow
`
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`2 The ’270 patent and Salmedix also referred to Ribomustin as “Ribomustine.”
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`reconstitution process increased the potential for loss of potency and for impurity
`
`formation due to the hydrolysis of bendamustine in water. (Id. at 2:40-49).
`
`The inventors of the ’270 Patent thus identified “a need for lyophilized
`
`formulations of bendamustine that are easier to reconstitute and which have a
`
`better impurity profile than the current lyophilate (lyophilized powder)
`
`formulations of bendamustine.” (Id. at 2:50-53).
`
`
`B.
`
`The Inventions of the ’270 Patent
`
`Salmedix undertook an extensive research and development program aimed
`
`at creating a bendamustine formulation that would satisfy FDA standards. (Ex.
`
`1019, 52-72). In an effort to develop a formulation that was easier to reconstitute
`
`and had “a better impurity profile than Ribomustin” (Ex. 1001, 2:50-53), the
`
`inventors conducted a multi-faceted inquiry, balancing interrelated factors such as
`
`chemical reactivity, solubility, physical properties, and compatibility with various
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`excipients, as well as the chosen formulation technique. (Id. at 2:26-35:67). The
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`inventors discovered that alcohols had a “unique” and “unexpected” effect on
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`bendamustine stability and were “useful in manufacturing bendamustine with
`
`fewer impurities since an aqueous solution can be used while maintaining the
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`stability of the bendamustine.” (Id. at 31:57-32:3). They found tertiary butanol
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`(“TBA”), “to be the best stabilizer of the six alcohols tested.” (Id. at 31:62-63,
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`FIGS. 2-4). Ultimately, the inventors succeeded in achieving unexpectedly
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`improved bendamustine-containing pharmaceutical compositions with
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`substantially lower degradant levels as compared to Ribomustin. (Id. at 20:43-
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`25:34; FIGS. 2-4).
`
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`C.
`
`FDA Approval and Market Response
`
`In 2007, the FDA granted “priority review” status to Cephalon’s New Drug
`
`Application for Treanda® for injection, a lyophilized bendamustine product which
`
`embodies the claimed inventions of the ’270 Patent, meaning that the drug would
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`potentially provide significant improvements in the safety or effectiveness of the
`
`treatment of serious conditions when compared to standard applications. (Ex.
`
`2004, 1). The FDA approved Treanda for injection in 2008. (Ex. 2012, 1; Ex.
`
`2013, 1).
`
`Researchers hailed Cephalon’s invention as a significant advance over prior
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`chemotherapy drugs and Treanda for injection quickly became a commercial
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`success. (Ex. 2014, 106; Ex. 2015, 4473; Ex. 2016, 4378; Ex. 2017, 67; Ex. 2018,
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`653). Since launch in 2008, Treanda for injection generated over $3 billion in
`
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`IPR2016-00026
`Patent Owner’s Preliminary Response
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`sales in the United States. (Ex. 2019, 61; Ex. 2020, 64; Ex. 2021, 47; Ex. 2022,
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`62; Ex. 2023, 65).3
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`D.
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`Petitioners’ ANDA Filing
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`Petitioners are seeking to sell a generic version of Treanda for injection in
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`the United States, using the same pharmaceutical formulation with the same
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`specific degradant profiles claimed in the ’270 Patent, prior to the expiration of the
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`patents covering Treanda. (Ex. 1020, ¶¶ 21-25).
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`III. PETITIONERS FAILED TO IDENTIFY ALL OF THE REAL
`PARTIES-IN-INTEREST
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`Petitioners Agila Specialties Inc. and Mylan Laboratories Limited filed the
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`instant Petition on the one year anniversary of Patent Owner having served them
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`with a complaint, filed in the United States District Court for the District of
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`Delaware, alleging infringement of the ’270 Patent. (Pet. 10). Petitioners identify
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`only Mylan N.V. as a real party-in-interest. (Id. at 9).
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`Petitioners describe Mylan Laboratories Limited as “a manufacturing
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`subsidiary of Mylan Inc.” and Mylan Inc. as “a wholly owned subsidiary of Mylan
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`N.V.” (Id.). Petitioner Agila Specialties Inc. is likewise a subsidiary of Mylan Inc.
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`3 Patent Owner reserves the right to address secondary indicia of non-obviousness
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`in detail in the event the Board decides to institute.
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`8
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`(Ex. 2024, 1; Ex. 2025, 1). As explained below, Petitioners should also have
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`identified at least Mylan Inc. and Mylan Pharmaceuticals Inc. as real parties-in-
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`interest.
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` The Legal Standard A.
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`A petition for inter partes review “may be considered only if . . . the petition
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`identifies all real parties in interest.” 35 U.S.C. § 312(a)(2) (emphasis added).
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`This statutory requirement is a “threshold issue” for substantive review of the
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`merits. Galderma S.A. v. Allergan Industrie, SAS, IPR2014-01422, Paper 14 at 5
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`(PTAB Mar. 5, 2015) (quoting Zoll Lifecor Corp. v. Philips Elec. N. Am. Corp.,
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`IPR2013-00609, Paper 15 at 11-12 (PTAB Mar. 20, 2014)); see also Zerto, Inc. v.
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`EMC Corp., IPR2014-01254, Paper 35 at 6 (PTAB Feb. 12, 2015); Atlanta Gas
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`Light Co. v. Bennett Regulator Guards, Inc., IPR2013-00453, Paper 88 at 7 (PTAB
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`Jan. 6, 2015). “[W]hen, as here, a patent owner provides sufficient rebuttal
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`evidence that reasonably brings into question the accuracy of a petitioner’s
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`identification of the real parties-in-interest, the burden remains with the petitioner
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`to establish that it has complied with the statutory requirement to identify all the
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`real parties-in-interest.” Galderma at 6-7; see also Zerto at 7; Atlanta at 8. “This
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`allocation of the burden . . . [to Petitioner] appropriately accounts for the fact that a
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`9
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`petitioner is far more likely to be in possession of, or have access to, evidence
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`relevant to the issue than is a patent owner.” Zerto at 7; see also Atlanta at 8.
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`The determination of whether a given party is a real party-in-interest turns
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`on the party’s relationship to the proceeding and the degree of control the party can
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`exert over that proceeding. See Aruze Gaming Macau, Ltd. v. MGT Gaming, Inc.,
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`IPR2014-01288, Paper 13 at 11 (PTAB Feb. 20, 2015). “[A] party that funds and
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`directs and controls an IPR or PGR petition or proceeding constitutes a ‘real party-
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`in-interest.’” (Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,760
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`(Aug. 14, 2014)). The concept of control generally means that “it should be
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`enough that the nonparty has the actual measure of control or opportunity to
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`control . . . .” (Id. at 48,759 (citing Wright & Miller § 4451)). “A common
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`consideration is whether the nonparty exercised or could have exercised control
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`over a party’s participation in a proceeding.” (Id. (emphasis added); see also id. at
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`48,617 (“Factors for determining actual control or the opportunity to control
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`include existence of a financially controlling interest in the petitioner.”)).
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`B.
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`Petitioners Should Have Identified Mylan Inc. and Mylan
`Pharmaceuticals Inc. as Real Parties-in-Interest
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`Petitioners have identified only their ultimate parent, Mylan N.V., as a real
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`party-in-interest, but have not identified Mylan Inc., their owner and direct parent,
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`10
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`as a real party-in-interest. (Pet. 9). Yet, in a related proceeding involving U.S.
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`Patent No. 8,436,190 (“’190 Patent”) — which the same Petitioners filed, the same
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`counsel of record prosecuted and also related to pharmaceutical compositions
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`containing bendamustine — Petitioners identified Mylan Inc., as a real party-in-
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`interest. Agila Specialties Inc. v. Cephalon, Inc., IPR2015-00503, Paper 4 at 13
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`(PTAB Dec. 24, 2014). Just two days before filing the instant Petition, Petitioners
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`in that related proceeding reaffirmed that Mylan Inc. was a real party-in-interest.
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`Agila Specialties Inc. v. Cephalon, Inc., IPR2015-00503, Paper 16 at 2 (PTAB Oct.
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`7, 2015). And in the district court litigation in which Patent Owner asserted the
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`’270 Patent, each Petitioner confirmed that it was a wholly owned subsidiary of
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`Mylan Inc. (Ex. 2026, 1; Ex. 2027, 1).
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`Furthermore, shortly after filing the instant Petition, Petitioner Mylan
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`Laboratories Limited filed petitions in IPR2016-00217 and IPR2016-00218,
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`through the same counsel of record. In those petitions, Mylan Laboratories
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`Limited identified Mylan Inc. as a real party-in-interest. Mylan Pharm. Inc. v.
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`Baxter Int’l Inc., IPR2016-00217, Paper 3 at 9 and IPR2016-00218, Paper 3 at 10
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`(PTAB Nov. 19, 2015). Petitioner Agila Specialties Inc. likewise has routinely
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`identified Mylan Inc. as a real party-in-interest when filing its own petitions for
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`inter partes review. Agila Specialties Inc. v. Cubist Pharm., Inc., IPR2015-00131,
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`11
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`Paper 4 at 4, IPR2015-00132, Paper 4 at 4, IPR2015-00141, Paper 1 at 3-4,
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`IPR2015-00142, Paper 1 at 3-4, IPR2015-00143, Paper 1 at 3-4, IPR2015-00144,
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`Paper 1 at 3 (PTAB Oct. 23, 2014).
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`Significantly, the executive officers and directors of Mylan N.V., which
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`Petitioners have named as a real party-in-interest (Pet. 9), are also the executive
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`officers and directors of Mylan Inc. (Ex. 2026, 16). They “carry out the day-to-day
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`conduct of Mylan N.V.’s worldwide business” at Mylan Inc.’s corporate
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`headquarters in Canonsburg, Pennsylvania. (Ex. 2027, 1). Mylan N.V.’s
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`president, Rajiv Malik, is responsible for “overseeing research and development
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`(R&D), business development regulatory affairs, manufacturing, quality, supply
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`chain, and medical affairs, as well as the sales and marketing of Mylan’s generics
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`business.” (Id. at 4). Notably, Mr. Malik was the Chief Executive Officer of
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`Matrix Laboratories (now Mylan Laboratories Limited) when Mylan Inc. acquired
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`a controlling stake in that company. (Id.). According to Mylan N.V.’s website,
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`Mr. Malik “played a significant role in leading the integration[] of Mylan and
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`Matrix . . . to leverage the benefits of global scale and vertical and horizontal
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`integration.” (Id.).
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`The overlapping control among Petitioners and various other Mylan entities
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`is borne out by the Power of Attorney that Petitioner Agila Specialties Inc.
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`submitted in this proceeding. The Power of Attorney was executed by Bradley L.
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`Wideman, as “Secretary.”4 Mr. Wideman has identified himself in numerous
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`PTAB proceedings (both before and after the filing of the instant Petition) as
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`Mylan Pharmaceuticals Inc.’s “Vice President and General Counsel Securities and
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`Secretary,” “Secretary,” or “Secretary, MPI.” (See, e.g., Ex. 2028 (IPR2016-
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`00218, executed Nov. 18, 2015; IPR2016-00217, executed Nov. 18, 2015;
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`IPR2015-01340, executed June 2, 2015; IPR2015-00830, executed Mar. 3, 2015;
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`IPR2015-00644, executed Feb. 6, 2015; IPR2015-00643, executed Feb. 6, 2015;
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`IPR2015-00682, executed Feb. 2, 2015) (consolidated as Ex. 2028 for the Board’s
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`convenience). Mr. Wideman has also been identified in SEC filings as the “Vice
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`President, Associate General Counsel and Assistant Secretary” of Mylan Inc. (Ex.
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`2029, 23-24).
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`4 Petitioner Mylan Laboratories Limited appears not to have filed a Power of
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`Attorney in this matter. To the extent that Mylan Laboratories Limited relies on
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`the Power of Attorney signed by Mr. Wideman for Petitioner Agila Specialties
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`Inc., this only highlights the blurred lines between the Mylan entities controlling
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`this proceeding.
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`Where there is an issue of “shared corporate leadership,” the Board
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`“consider[s] whether an unnamed party is a real party in-interest based on ‘the
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`availability of a significant degree of effective control in the prosecution or defense
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`of t