Filed on behalf of: Celgene Corporation
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________________
`
`ALVOGEN PINE BROOK LLC,
`Petitioner
`
`v.
`
`CELGENE CORPORATION,
`Patent Owner
`_______________________
`
`Case IPR2018-01714
`U.S. Patent No. 7,968,569
`_______________________
`
`PATENT OWNER PRELIMINARY RESPONSE
`
`

`

`Contents
`
`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`Page
`
`I.
`
`II.
`
`III.
`
`INTRODUCTION ...........................................................................................1
`
`THE BOARD SHOULD DENY THE PETITION UNDER 35 U.S.C.
`§ 314(A) BECAUSE INSTITUTION WOULD RESULT IN AN
`INEFFICIENT USE OF RESOURCES ..........................................................5
`
`A.
`
`B.
`
`The Timing of the Petition and the Advanced Nature of the
`District Court Litigation Render Institution Inefficient........................5
`
`Institution Should Be Denied Because it Would Upset the
`Careful Balance Struck by the Hatch-Waxman Act .............................8
`
`THE BOARD SHOULD DENY INSTITUTION BECAUSE
`PETITIONER DOES NOT DEMONSTRATE A REASONABLE
`LIKELIHOOD THAT ANY CHALLENGED CLAIM WOULD
`HAVE BEEN OBVIOUS IN VIEW OF THE TWO ASSERTED
`GROUNDS ....................................................................................................11
`
`A.
`
`The State of the Art & The ʼ569 Patent ..............................................12
`
`1.
`
`2.
`
`MM Is a Unique and Difficult-to-Treat Cancer........................12
`
`The Inventions of the ʼ569 Patent Unexpectedly Treat
`MM............................................................................................13
`
`B.
`
`Scope and Content of the Asserted References ..................................16
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`Palumbo ....................................................................................16
`
`The May Press Release .............................................................17
`
`The August Press Release.........................................................18
`
`Hideshima .................................................................................19
`
`The ʼ230 Patent .........................................................................19
`
`C.
`
`Level of Ordinary Skill in the Art.......................................................20
`
`- i -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`D.
`
`E.
`
`Claim Construction..............................................................................20
`
`Petitioner Does Not Demonstrate a Reasonable Likelihood that
`Claims 1–15 Would Have Been Obvious in View of its Two
`Asserted Grounds ................................................................................20
`
`1.
`
`2.
`
`3.
`
`Neither Ground 1 nor Ground 2 Teaches or Suggests the
`Specific Amounts of Lenalidomide in the Specific
`Dosing Cycles of the Claimed Inventions ................................21
`
`Petitioner Cannot Rely on Dr. Tricot’s Conclusory and
`Contradictory Declaration to Supply a Limitation that Is
`Missing from the Prior Art........................................................25
`
`The Additional References that Petitioner Relies Upon
`Do Not Fill the Gaps of Grounds 1 and 2.................................28
`
`(a)
`
`(b)
`
`The Board Should Disregard Petitioner’s
`Additional References ....................................................29
`
`Petitioner Has Not Established a Motivation to
`Arrive at the Claimed Cyclic-Dosing Limitation,
`or any Reasonable Expectation of Successfully
`Doing So .........................................................................31
`
`(i)
`
`(ii)
`
`REVIMID Was Known to Cause Profound
`Cytopenias and Significant
`Myelosuppression.................................................32
`
`Petitioner Does Not Explain Why a POSA
`Would Have Been Motivated to Dose
`REVIMID in Accordance with the Claims..........34
`
`IV. CONCLUSION..............................................................................................47
`
`- ii -
`
`

`

`Authorities
`
`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`Page(s)
`
`Cases
`AIDS Healthcare Found., Inc. v. Gilead Scis., Inc.,
`890 F.3d 986 (Fed. Cir. 2018) ..............................................................................9
`
`Applications in Internet Time, LLC v. RPX Corp.,
`897 F.3d 1336 (Fed. Cir. 2018) ................................................................... 10, 11
`
`Avanir Pharm. v. Actavis S. Atl.,
`36 F. Supp. 3d 475 (D. Del. 2014) .....................................................................40
`
`Celgene Corp. v. Cipla Ltd.,
`No. 17-cv-06163 (D.N.J.) .....................................................................................6
`
`Celgene Corp. v. Dr. Reddy’s Labs., Inc. et al.,
`No. 16-cv-07704 (D.N.J.) .....................................................................................7
`
`Celgene Corp. v. Sun Pharma Global FZE et al.,
`No. 18-cv-11630 (D.N.J.) .....................................................................................6
`
`Celgene Corp. v. Zydus Pharmaceuticals (USA) Inc. et al.,
`No. 17-cv-02528 (D.N.J.) ................................................................................. 6-7
`
`Coalition for Affordable Drugs VIII, LLC v. The Trustees of the University
`of Pennsylvania,
`IPR2015-01835 (PTAB March 6, 2017)...................................................... 37, 46
`
`Depomed, Inc. v. Actavis Elizabeth LLC,
`2014 WL 4215435 (D.N.J. Aug. 25, 2014) ................................................. 37, 46
`
`Hospira, Inc. v, Genentech, Inc.,
`IPR2017-00804 (PTAB Oct. 03, 2018) ..............................................................47
`
`Initiative for Medicines, Access & Knowledge (I-Mak), Inc. v. Gilead
`Pharmasset LLC,
`IPR2018-00119 (PTAB May 4, 2018)................................................................26
`
`- iii -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`Initiative for Meds., Access & Knowledge (I-Mak), Inc. v. Gilead
`Pharmasset LLC,
`IPR2018-00103 (PTAB June 13, 2018)..............................................................26
`
`Janssen Prod., L.P. v. Lupin Ltd.,
`109 F. Supp. 3d 650 (D.N.J. 2014).....................................................................35
`
`K/S Himpp v. Hear-Wear Techs., LLC,
`751 F.3d 1362 (Fed. Cir. 2014) .................................................................... 25-26
`
`Mylan Pharmaceuticals, Inc. v. Bayer Intellectual Property,
`IPR2018-01143 (PTAB December 3, 2018).....................................................7, 8
`
`NHK Spring Co. v. Intri-Plex Techs., Inc.,
`IPR2018-00752 (PTAB Sept. 12, 2018)...............................................................5
`
`Oil States Energy Servs., LLC v. Greene’s Energy Grp., LLC,
`138 S. Ct. 1365 (2018)..........................................................................................5
`
`Orexo AB v. Actavis Elizabeth LLC,
`903 F.3d 1265 (Fed. Cir. 2018) ..........................................................................21
`
`Panduit Corp. v. Corning Optical Communications LLC,
`IPR2017-00528 (PTAB May 30, 2017)..............................................................22
`
`Proctor & Gamble Co. v. Teva Pharm. USA,
`566 F.3d 989 (Fed. Cir. 2009) ............................................................................21
`
`QuantifiCare, Inc. v. Proctor & Gamble Co.,
`IPR2017-02113 (PTAB Mar. 16, 2018) .............................................................30
`
`Ex Parte Solomon Bekele,
`No. 2011-003027, 2012 WL 2573051 (BPAI June 12, 2012)............................22
`
`Unified Patents v. Custom Media,
`No. IPR2015-00516 (PTAB June 25, 2015).......................................................26
`
`Zetec, Inc. v. Westinghouse Elec. Co.,
`Case IPR2014-00384 (PTAB July 23, 2014) .....................................................30
`
`- iv -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`Rules / Statutes
`
`35 U.S.C. § 311(b) ...................................................................................................26
`
`35 U.S.C. § 312(a) ...................................................................................................10
`
`35 U.S.C. § 312(a)(3)...............................................................................................29
`
`35 U.S.C. § 313..........................................................................................................1
`
`35 U.S.C. § 314(a) ................................................................................ 5, 7, 8, 11, 30
`
`35 U.S.C. § 315(b) .....................................................................................................6
`
`37 C.F.R. § 42.65(a).................................................................................................25
`
`37 C.F.R. § 42.104(b)(4)..........................................................................................29
`
`37 C.F.R. § 42.107(a).................................................................................................1
`
`37 C.F.R. § 42.108(b) ..............................................................................................30
`
`- v -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`Abbreviations
`
`IPR
`MM
`DRL
`MDS
`
`inter partes review
`multiple myeloma
`Dr. Reddy’s Laboratories
`myelodysplastic syndromes
`
`- vi -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`Exhibits
`
`EX
`2001
`
`2008
`2009
`
`Description
`T. Hideshima, et al., A review of lenalidomide in combination with
`dexamethasone for the treatment of multiple myeloma, Ther. Clin. Risk
`Management, 4(1):129-36 (2008)
`2002 August 2018 Update to the Office Patent Trial Practice Guide, 83 Fed.
`Reg. 39,989 (Aug. 13, 2018)
`2003 Hatch-Waxman Integrity Act of 2018
`The Merck Manual (17th ed. 1999)
`2004
`2005 H.F. Barker, et al., Multiple myeloma: The biology of malignant plasma
`cells, Blood Reviews, 7(1):19-23 (1993)
`2006 H.T. Lynch, et al., Familial Multiple Myeloma: a Family Study and
`Review of the Literature, J. Nat’l Cancer Ins., 93(19):1479-1483 (2001)
`2007 M.N. Fishman, et al., Considerations in the management of myeloma,
`Oncology, 14(11A):72-81 (2000)
`Excerpt from Certified File History of US Patent No. 7968569
`J.B. Marriott, et al., Thalidomide and its analogues have distinct and
`opposing effects on TNF-α and TNFR2 during co-stimulation of both
`CD4+ and CD8+ T cells, Clin. Exp. Immunol., 130:75-84 (2002)
`2010 M. Zangari, et al., Abstract #3226, Results of Phase I Study of CC-5013 for
`the Treatment of Multiple Myeloma (MM) Patients Who Relapse after
`High Dose Chemotherapy (HDCT), Blood, 98(11):775a (2001)
`2011 M. Zangari, et al., Abstract #1642, Revimid 25 mg (REV 25) x 20 Versus
`50 mg (REV 50) x 10 q 28 Days with Bridging of 5 mg x 10 Versus 10 mg x
`5 as Post-Transplant Salvage Therapy for Multiple Myeloma (MM),
`Blood, 102(11):450a (2003)
`2012 M.S. Gordon, Myelosuppression, Current Cancer Therapeutics (4th ed.
`2001)
`2013 K. Remes, et al., Priming Therapy with Alpha-Interferon Chemotherapy-
`Resistant Multiple Myeloma, Leukemia & Lymphoma, 6:239-43 (1992)
`2014 B. Barlogie, Toward a Cure for Multiple Myeloma?, New Eng. J. Med.,
`325(18):1304-06 (1991)
`J.L. Harousseau, et al., Double-Intensive Therapy in High-Risk Multiple
`Myeloma, Blood, 79(11):2827-33 (1992)
`2016 H.M. Lokhorst, et al., High-Risk Multiple Myeloma Treated With High-
`Dose Melphalan, J. Clin. Oncol., 10(1):47-51 (1992)
`
`2015
`
`- vii -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`2017 X. Troussard, et al., Human recombinant granulocyte-macrophage colony
`stimulating factor (hrGM-CSF) improves double hemibody irradiation
`(DHBI) tolerance in patients with stage III multiple myeloma: a pilot
`study, Br. J. Haemat., 89:191-95 (1995)
`J.K. Weick, et al., The Evaluation of Gemcitabine in Resistant or
`Relapsing Multiple Myeloma, Phase II: a Southwest Oncology Group
`Study, Investigational New Drugs, 20(1):117-21 (2002)
`2019 K. Goudarzipour, et al., Epstein-Barr Virus-Induced Hemophagocytic
`Lymphohistiocytosis, Int’l. J. Hemat., 7(1):42-45 (2013)
`
`2018
`
`- viii -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`I.
`
`INTRODUCTION
`
`Pursuant to 35 U.S.C. § 313 and 37 C.F.R. § 42.107(a), Patent Owner Celgene
`
`Corporation (“Celgene”) submits this Preliminary Response to Petitioner Alvogen
`
`Pine Brook LLC’s Petition seeking inter partes review (“IPR”) of claims 1-15 of
`
`Celgene’s U.S. Patent No. 7,968,569 (“the ʼ569 Patent”). Petitioner’s two alleged
`
`grounds of unpatentability should be denied institution for any of the following
`
`independent reasons.
`
`As an initial matter, the Board should deny institution because it would be an
`
`inefficient use of the Board’s resources. The validity of the ʼ569 Patent—including
`
`the same alleged prior art and arguments that Petitioner presents here—have been
`
`pending before the same district court judge for several years in five Hatch-Waxman
`
`litigations, one of which names Petitioner as a defendant. These cases are
`
`substantially advanced, with the first scheduled to complete expert discovery in two
`
`months (February 2019), and likely to progress to trial shortly thereafter. Given the
`
`advanced nature of the pending district court litigations and the fact that the same
`
`references and arguments presented in the Petition will be tried to a judge that is
`
`intimately familiar with the subject matter of the ’569 Patent before a trial in this
`
`IPR occurs, institution of trial here would be inefficient, and would disrupt the
`
`careful balance Congress created when it enacted the Hatch-Waxman Act.
`
`- 1 -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`Moreover, Petitioner’s two alleged grounds of unpatentability—both of which
`
`are based on obviousness—should be denied institution because neither ground is
`
`supported by references that teach or suggest all elements of the challenged claims.
`
`Those claims recite novel methods of treating multiple myeloma (“MM”) with
`
`specific amounts of
`
`the
`
`immunomodulatory compound
`
`lenalidomide for
`
`21 consecutive days, followed by 7 days of rest, in a 28-day treatment cycle, in
`
`combination with dexamethasone on certain days. MM is a rare and difficult-to-
`
`treat blood cancer that, prior to the inventions of the ’569 Patent, had one of the
`
`worst prognoses of all cancers. The inventor of the ’569 Patent added a key weapon
`
`to the arsenal in the battle against MM when he discovered the claimed methods of
`
`treating MM using lenalidomide. In multiple studies (e.g., Ex. 1037; Ex. 1040), the
`
`claimed methods treated over 60% of patients with MM, which are “among the
`
`highest values that have been reported in the treatment of relapsed or refractory
`
`[MM].” (Ex. 1037 at 9.) The claimed methods were also hailed as “one of the most
`
`promising MM novel treatment options.” (Ex. 2001 at 3.)
`
`Fatal to the Petition, neither of Petitioner’s two alleged obviousness grounds
`
`teaches or suggests treating MM with specific doses of lenalidomide in specific
`
`dosing cycles, as required by claims 1-15. Indeed, none of the five references that
`
`form the basis of Petitioner’s alleged Grounds teaches or suggests cyclic dosing of
`
`any agent—let alone the compound that was later known as lenalidomide—for
`
`- 2 -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`21 consecutive days followed by a 7-day rest period.1 Petitioner and its declarant do
`
`not contend otherwise. For this reason alone, the Petition should be denied.
`
`Perhaps recognizing the void in its asserted grounds, Petitioner relies upon a
`
`conclusory expert declaration to assert that a person of ordinary skill in the art
`
`(“POSA”) “would have been motivated to incorporate a 7-day rest period into the
`
`28-day lenalidomide treatment cycle because [the] introduction of rest periods into
`
`cancer treatments was routine.” (Pet. at 34 (citing Ex. 1003 at ¶ 99).) But neither
`
`Petitioner nor its declarant provide any evidence that a 7-day rest period was
`
`“routine.” To the contrary, references authored by Petitioner’s declarant—including
`
`a reference that Petitioner’s declarant omitted from the lengthy curriculum vitae he
`
`submitted to the Board—demonstrate that he dosed the compound that Petitioner
`
`contends is lenalidomide without teaching or suggesting any rest period at all.
`
`Petitioner’s declarant ignores his own prior work and instead relies on hindsight
`
`when asserting that dosing lenalidomide with a 7-day rest period would have been
`
`“routine.” This, too, is fatal to the Petition.
`
`Petitioner also points to a host of additional “background” references (not set
`
`forth in the grounds) to argue that it was “obvious to vary drug dosages and
`
`
`1 As explained below, the ’569 Patent issued after Patent Owner amended its claims
`
`to add the 21+7 cyclic dosing regimen.
`
`- 3 -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`frequencies” in accordance with the claims. (Pet. at 34.) But those references—
`
`none of which concern the compound that was later known as lenalidomide—do not
`
`cure the fatal flaws in Petitioner’s stated Grounds. Instead, they teach away from
`
`the claimed inventions.
`
`Specifically, Petitioner’s additional references disclose that when dosing
`
`cancer therapies, to the extent that a POSA wanted to use a rest period of any
`
`duration, a “familiar 2-week interval between cycles” should be used. (Ex. 1017 at
`
`16.) Absent hindsight, neither Petitioner nor its declarant provide any reason why a
`
`POSA would deviate from this “familiar” convention to arrive at the 7-day rest
`
`period of the claimed inventions. To the contrary, Petitioner’s references, to the
`
`extent that they teach a rest period of any duration, teach the use of longer rest
`
`periods of three weeks or greater for MM. In other words, Petitioner’s cited
`
`references taught away from, or at the very least would not have led a POSA to arrive
`
`at, the claimed dosing regimens and 7-day rest period. On this independent basis,
`
`the Petition should be denied.
`
`For any of the above reasons, Petitioner does not demonstrate a reasonable
`
`likelihood that any of the challenged claims is unpatentable. The Board should deny
`
`institution.
`
`- 4 -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`II.
`
`THE BOARD SHOULD DENY THE PETITION UNDER
`35 U.S.C. § 314(a) BECAUSE INSTITUTION WOULD
`RESULT IN AN INEFFICIENT USE OF RESOURCES
`
`“The decision whether to institute inter partes review is committed to the
`
`Director’s discretion.” Oil States Energy Servs., LLC v. Greene’s Energy Grp., LLC,
`
`138 S. Ct. 1365, 1371 (2018). The August 2018 Update to the Office Patent Trial
`
`Practice Guide (Ex. 2002) “invites parties to address additional factors that may bear
`
`on the Board’s discretionary decision to institute or not institute under
`
`§§ 314(a) . . . .” See NHK Spring Co. v. Intri-Plex Techs., Inc., IPR2018-00752,
`
`Paper 8, at 20 n.4 (PTAB Sept. 12, 2018). Here, two such factors counsel against
`
`institution: (1) inefficiency; and (2) contradiction of the Hatch-Waxman Act.
`
`A.
`
`The Timing of the Petition and the Advanced Nature of the
`District Court Litigation Render Institution Inefficient
`
`The ’569 Patent is the subject of five ongoing Hatch-Waxman cases, all of
`
`which are pending before the same judge in the District of New Jersey. Those
`
`litigations are substantially advanced, rendering institution of trial here inefficient,
`
`and an unnecessary and undue burden on both the Board and Patent Owner.
`
`The litigation against Petitioner—Case No. 17-cv-06842 (the “Alvogen
`
`Litigation”)—was filed by Patent Owner on September 6, 2017 in response to a
`
`Paragraph IV notice that Petitioner sent to Patent Owner under the Hatch-Waxman
`
`Act on July 24, 2017 (the “Notice Letter”). Petitioner served invalidity contentions
`
`- 5 -
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`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`in the Alvogen Litigation regarding the ’569 Patent—which include the same
`
`references cited by Petitioner in the instant proceeding—on January 19, 2018. Fact
`
`discovery in that case has been open for nearly a year and closes in May 2019, claim
`
`construction exchanges have occurred, and the case is progressing toward a
`
`Markman hearing in March/April 2019.
`
`Nonetheless, Petitioner chose to wait nearly nine months after serving its
`
`invalidity contentions in the Alvogen Litigation to file its Petition. The timing of
`
`that filing—less than one week before the expiration of Petitioner’s 1-year statutory
`
`bar under 35 U.S.C. § 315(b)—appears calculated to exploit the system to
`
`Petitioner’s advantage. Petitioner knew its invalidity theories at least as early as its
`
`January 2018 invalidity contentions (and in the months leading up to serving those
`
`contentions, as evidenced by its July 2017 Notice Letter), but chose to wait for the
`
`Alvogen Litigation to further develop before filing the Petition at the last possible
`
`minute.
`
`Celgene submits that there is a reason for Petitioner’s calculated delay. The
`
`ʼ569 Patent is subject to four additional cases filed by Patent Owner, and it appears
`
`that Petitioner waited until the eleventh hour to file the Petition in order to evaluate
`
`Patent Owner’s and other parties’ litigation positions in an attempt to address them
`
`in the Petition. See Celgene Corp. v. Sun Pharma Global FZE et al., No. 18-cv-
`
`11630 (D.N.J.); Celgene Corp. v. Cipla Ltd., No. 17-cv-06163 (D.N.J.); Celgene
`
`- 6 -
`
`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`Corp. v. Zydus Pharmaceuticals (USA) Inc. et al., No. 17-cv-02528 (D.N.J.);
`
`Celgene Corp. v. Dr. Reddy’s Labs., Inc. et al., No. 16-cv-07704 (D.N.J.). The
`
`earliest-filed of these actions—Case No. 16-cv-07704 (the “DRL Litigation”)—was
`
`filed by Patent Owner more than two years ago. Dr. Reddy’s Laboratories (“DRL”),
`
`the defendant in the DRL Litigation, is relying on each of the five references asserted
`
`in Petitioner’s two alleged Grounds, and is asserting the same arguments presented
`
`in the Petition. The DRL Litigation is in the midst of expert discovery, and the
`
`parties expect to proceed to trial on the ʼ569 Patent in the summer of 2019—months
`
`before the Board would hear oral arguments and many months before the Board
`
`would issue a Final Written Decision if it were to institute trial here.
`
`In view of the progression of the district court litigations involving the
`
`ʼ569 Patent, institution of IPR would be an inefficient use of the Board’s resources.
`
`The Board has exercised its discretion to deny institution in such instances. For
`
`instance, in Mylan Pharmaceuticals, Inc. v. Bayer Intellectual Property, the Board
`
`denied institution under § 314(a) where, “[g]iven the advanced stage of [a]
`
`copending district court case and the extensive overlap of the asserted prior art,
`
`expert testimony, and claim construction . . . it would be an inefficient use of Board
`
`resources to proceed with this inter partes review in parallel with the district court
`
`case.” IPR2018-01143, Paper 13 at 13 (PTAB December 3, 2018).
`
`- 7 -
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`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`Likewise here, Petitioner is relying on the same alleged prior art, arguments,
`
`and expert declarant in the Alvogen Litigation. Moreover, the defendants in the
`
`DRL Litigation rely on the same references, and their expert has made the same
`
`arguments that Petitioner makes here. A proceeding before the Board on the current
`
`Petition would not conclude until March 2020. Meanwhile, in the Alvogen
`
`Litigation, fact discovery closes nearly a year earlier in May 2019, expert discovery
`
`will likely be closed, and the case will likely be close to, if not on the eve of trial. In
`
`the DRL Litigation, it is likely that trial will have been over for months and that the
`
`district court judge will have issued a ruling. Thus, institution here, as in Mylan,
`
`“would be an inefficient use of Board resources.” Id. The Petition should be denied
`
`on this basis alone.
`
`B.
`
`Institution Should Be Denied Because it Would Upset the
`Careful Balance Struck by the Hatch-Waxman Act
`
`Institution also should be denied under § 314(a) because IPR of the
`
`’569 Patent—an Orange Book-listed patent—would disrupt the careful balance
`
`between innovation and competition reflected in the Hatch-Waxman Act. It has long
`
`been recognized that the Hatch-Waxman Act—and in particular, its procedure for
`
`litigating patent disputes between innovator and generic manufacturers—was the
`
`product of compromise
`
`intended
`
`to balance
`
`the objectives of
`
`inducing
`
`pharmaceutical companies to invest in the research and development necessary to
`
`- 8 -
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`

`

`IPR2018-01714
`U.S. Patent No. 7,968,569
`
`make new products, while promoting competitors to bring generic copies of those
`
`products to market. See AIDS Healthcare Found., Inc. v. Gilead Scis., Inc., 890 F.3d
`
`986, 995 (Fed. Cir. 2018). That balance is disrupted by allowing generic companies
`
`to take advantage of the benefits of the Hatch-Waxman Act (i.e., to file an
`
`Abbreviated New Drug Application relying on the innovator’s data) and thereafter
`
`challenge the innovator company’s patents through the entirely separate IPR
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`proceeding, with its different burdens, standards, and procedures than in Hatch-
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`Waxman litigation.
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`Senator Orrin Hatch, one of the framers of the Hatch-Waxman Act,
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`recognized this disruption to the carefully-crafted balance and introduced the
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`“Hatch-Waxman Integrity Act of 2018” earlier this year. Senator Hatch’s proposal
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`would require a generic company to choose between two options: (i) availing itself
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`of the benefits of the Act, including by resolving patent disputes in district court
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`pursuant to the framework established under the Act or (ii) petitioning for IPR. But
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`not both. (See Ex. 2003.) The proposal seeks to restore the Act’s balance by
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`prohibiting parties from taking advantage of favorable provisions of the Act while
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`making an end-run around others.
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`The instant case is particularly instructive as to the potential for inefficiency
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`and disruption of the carefully-crafted statutory framework. Both Petitioner and
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`DRL are seeking to market generic versions of Celgene’s Revlimid® drug product
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`IPR2018-01714
`U.S. Patent No. 7,968,569
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`with an indication for MM, and both are also seeking approval for an indication for
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`myelodysplastic syndromes (“MDS”). Although Petitioner filed this Petition on the
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`ʼ569 Patent, which covers methods of treating MM, DRL did not. DRL, meanwhile,
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`filed petitions seeking IPR for each of Celgene’s Orange Book-listed patents
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`covering methods of treating MDS, but Petitioner did not.
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`By employing such a divide-and-conquer strategy, Petitioner and DRL are
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`seeking two bites at the invalidity apple despite the AIA’s stated goal of efficiency.
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`Specifically, even if their respective IPR challenges ultimately fail, DRL will still
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`likely seek to challenge the validity of the ʼ569 Patent in district court, and Petitioner
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`will likely seek to do so for the challenged MDS patents, despite the fact that they
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`have repeatedly demonstrated that they are working together in the underlying
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`District Court cases. This runs counter to the objectives of the Hatch-Waxman Act
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`and the AIA, and would result in an inefficient use of the Board’s resources.
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`Moreover, the selective petitioning strategy employed by Petitioner and
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`DRL—the only two generic companies against whom both the MM and MDS
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`patents have been asserted—raises questions as to whether DRL is a real party-in-
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`interest in the present Petition under 35 U.S.C. § 312(a), particularly in view of the
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`Federal Circuit’s recent edict that “Congress intended that the term ‘real party in
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`interest’ have its expansive common-law meaning.” Applications in Internet Time,
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`LLC v. RPX Corp., 897 F.3d 1336, 1351 (Fed. Cir. 2018). As the Federal Circuit
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`U.S. Patent No. 7,968,569
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`noted, “the common law seeks to ascertain who, from a ‘practical and equitable’
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`standpoint, will benefit from the redress that the chosen tribunal might provide.” Id.
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`(citing the Office Patent Trial Practice Guide, 77 Fed. Reg. 48,759 (Aug. 14, 2012)).
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`Here, DRL will indisputably “benefit” from Petitioner’s Petition (and Petitioner will
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`likewise benefit from DRL’s petitions). Notably, however, DRL is time-barred from
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`petitioning for IPR of the ʼ569 Patent.2 As such, institution would allow DRL and
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`Petitioner to make an end-run around the statutory framework.
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`Under these circumstances, the Board should exercise its discretion under
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`35 U.S.C. § 314(a) and deny institution.
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`III. THE BOARD SHOULD DENY INSTITUTION BECAUSE
`PETITIONER DOES NOT DEMONSTRATE A REASONABLE
`LIKELIHOOD THAT ANY CHALLENGED CLAIM WOULD HAVE
`BEEN OBVIOUS IN VIEW OF THE TWO ASSERTED GROUNDS
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`The Petition also fails on the merits. As discussed below, neither of the two
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`alleged Grounds of obviousness demonstrates a reasonable likelihood that any
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`challenged claim would have been obvious.
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`
`2 The one-year bar date for DRL to file an IPR challenging the ’569 Patent passed
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`13 months ago on November 18, 2017.
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`IPR2018-01714
`U.S. Patent No. 7,968,569
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`A.
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`The State of the Art & The ʼ569 Patent
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`1. MM Is a Unique and Difficult-to-Treat Cancer
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`“Cancer” is a generic name for a collection of diseases wherein some of the
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`body’s cells divide abnormally and spread into surrounding tissues. Normally, cells
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`grow and divide to form new cells as needed. When normal cells are old or damaged,
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`they die and are replaced by new cells. Cancer disrupts this orderly process, causing
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`old or damaged cells to survive when they should die, and new cells to form when
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`they are not needed. These extra cells can divide without stopping and may form
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`growths called tumors. Malignant tumors can spread into and invade nearby tissues.
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`Through a process called metastasis, tumors can travel through the blood or lymph
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`system to form new tumors throughout the body.
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`The medical literature describes an enormous variety of cancers. MM is one
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`type of blood cancer characterized by plasma cell tumors and overproduction of
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`monoclonal immunoglobulin. (See Ex. 2004 at 4.) Prior to the claimed inventions,
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`it was known that MM was “a difficult disorder to treat and cures [were] virtually
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`unknown.” (Ex. 2005 at 1.) It was also known that the etiology of MM “remain[ed]
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`obscure” (ex. 2006 at 1), and the condition was viewed as an “incurable cancer” (Ex.
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`2007 at 2). Despite these predictions of failure, the inventor of the ʼ569 Patent
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`invented a novel and extremely beneficial treatment for patients suffering from this
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`enigmatic and deadly condition.
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`IPR2018-01714
`U.S. Patent No. 7,968,569
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`2.
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`The Inventions of the ʼ569 Patent Unexpectedly Treat MM
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`The ʼ569 Patent is directed to novel methods of treating MM with specific
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`doses of lenalidomide and dexamethasone in specific dosing cycles, and covers an
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`FDA-approved use of Celgene’s Revlimid® drug product. The patent claims priority
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`to two provisional applications: Provisional Application No. 60/380,842 (“the ’842
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`Application”) (filed May 17, 2002) and Provisional Application No. 60/424,600
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`(filed November 6, 2002).3 The ’569 Patent issued on June 28, 2011 and contains
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`fifteen claims. The two independent claims, claims 1 and 13, are illustrative and
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`recite as follows:
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`1.
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`A method of treating multiple myeloma, which comprises
`cyclically administering to a patient having multiple myeloma
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`3 Petitioner argues that the claims of the ʼ569 Patent are not entitled to claim priority
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`to the ʼ842 Application. Because the alleged prior art references cited in the Petition,
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`either alone or in combination with other references, do not render obvious the
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`inventions claimed in the ʼ569 Patent, Celgene does not address herein Petitioner’s
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`argument that the ʼ569 Patent is not entitled to a priority date of May 17, 2002.
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`Celgene reserves the right to contest Petitioner’s argument should the Board decide
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`to institute IPR. For the purposes of this Preliminary Response only, Celgene
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`assumes the time of the claimed inventions is November 2002.
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`IPR2018-01714
`U.S. Patent No. 7,968,569
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`about 5 to about 25 mg per day of [lenalidomide] or a
`pharmaceutically acceptable salt thereof, for 21 consecutive days
`followed by seven consecutive days of rest from administration
`of said compound during a 28 day cycle in combination with
`40 mg per day of dexamethasone.4
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`13. A method of treating multiple myeloma, which comprises
`administering, on a 28 day cycle, to a patient having multiple
`myeloma: (a) about 25 mg per day of [lenalidomide] or a
`pharmaceutical