`Filed on behalf of: Celgene Corporation
`
`
`Filed: November 14, 2018
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________________
`
`DR. REDDY’S LABORATORIES, INC.,
`Petitioner
`
`v.
`
`CELGENE CORPORATION,
`Patent Owner
`_______________________
`
`Case IPR2018-01504
`U.S. Patent No. 9,056,120
`_______________________
`
`
`PATENT OWNER PRELIMINARY RESPONSE
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`
`TABLE OF CONTENTS
`
`B. 
`
`
`TABLE OF CONTENTS ........................................................................................ i 
`TABLE OF AUTHORITIES ................................................................................ iv 
`TABLE OF ABBREVIATIONS ........................................................................ viii 
`LIST OF EXHIBITS .............................................................................................. ix 
`I. 
`INTRODUCTION ........................................................................................ 1 
`II. 
`THE BOARD SHOULD DENY THE PETITION UNDER 35
`U.S.C. § 314(a) BECAUSE INSTITUTION WOULD RESULT IN
`AN INEFFICIENT USE OF BOARD RESOURCES ............................... 7 
`A. 
`The Timing of the Petition and the Advanced Nature of the
`Corresponding District Court Litigation Render Institution
`Inefficient ............................................................................................. 8 
`Institution Would Upset the Careful Balance Struck by the
`Hatch-Waxman Act ............................................................................ 10 
`III.  THE BOARD SHOULD DENY THE PETITION UNDER 35
`U.S.C. § 314(a) BECAUSE IT LACKS THE REQUIRED
`SPECIFICITY ............................................................................................. 12 
`IV.  THE BOARD SHOULD DENY THE PETITION UNDER 35
`U.S.C. § 325(d) BECAUSE IT PRESENTS SUBSTANTIALLY
`THE SAME ART AND ARGUMENTS PREVIOUSLY
`CONSIDERED BY THE OFFICE ........................................................... 15 
`A. 
`The ’740 Patent Prosecution History ................................................. 18 
`B. 
`The ’717 Patent Prosecution History ................................................. 19 
`C. 
`The ’120 Patent Prosecution History ................................................. 21 
`D. 
`Petitioner Relies on Cumulative Art and Repeats the Same
`Arguments Already Overcome During Prosecution .......................... 22 
`SCOPE AND CONTENT OF THE ASSERTED REFERENCES ........ 25 
`A. 
`List 2001 ............................................................................................. 25 
`B. 
`Thomas 2000a .................................................................................... 27 
`C. 
`The ’230 Patent .................................................................................. 29 
`
`V. 
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`D. 
`
`2. 
`
`3. 
`
`IPR2018-01504
`U.S. Patent No. 9,056,120
`Celgene Press Release 5/8/2001 and Celgene Press Release
`8/28/2001 ............................................................................................ 29 
`VI.  LEVEL OF ORDINARY SKILL IN THE ART ..................................... 31 
`VII.  CLAIM CONSTRUCTION ....................................................................... 32 
`VIII.  STATE OF THE ART ................................................................................ 32 
`A. 
`TNF-α Was Not a Known or Effective Target for Treating
`MDS ................................................................................................... 33 
`1. 
`The Art Shows Significant Uncertainty Regarding the
`Pathology of MDS and the Appropriate Target for
`Treatment ................................................................................. 34 
`TNF-α Inhibitors Did Not Work in Treating MDS ................. 37 
`2. 
`Lenalidomide Was Not Known as the “Next Generation”
`Thalidomide ........................................................................................ 38 
`1. 
`Thalidomide and Lenalidomide are Distinct Compounds
`with Different Structures .......................................................... 39 
`The Art Disclosed Different Categories of Thalidomide
`Analogs, Including IMiDs and SelCIDs, and, if
`Anything, Would Have Led a POSA to Use a SelCID to
`Treat MDS ................................................................................ 42 
`The Compound Now Known as Lenalidomide Was One
`of the Least Potent TNF-α Inhibitors ....................................... 43 
`Even Accepting Petitioner’s Arguments as True, the Art Taught
`Away From the Claimed Inventions Because What Petitioner
`Contends Were Known to Be IMiDs Caused Cytopenias, the
`Primary Symptoms that Manifest in MDS Patients ........................... 45 
`1. 
`Thalidomide Did Not Cause Cytopenias ................................. 46 
`2. 
`CC-5013 Was Known to Cause Cytopenias ............................ 47 
`IX.  PETITIONER DOES NOT DEMONSTRATE A REASONABLE
`LIKELIHOOD THAT CLAIMS 1–8, 12–34, AND 38–53 WOULD
`HAVE BEEN OBVIOUS IN VIEW OF PETITIONER’S TWO
`ASSERTED GROUNDS ............................................................................ 48 
`A. 
`Petitioner’s Hindsight-Driven Approach Does Not Fill in the
`Missing Gaps in the Prior Art and Ignores the State of the Art ......... 49 
`
`B. 
`
`C. 
`
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`ii
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`

`B. 
`
`C. 
`
`2. 
`
`3. 
`
`IPR2018-01504
`U.S. Patent No. 9,056,120
`Neither List 2001 Nor Thomas 2000a Teaches or Suggests the
`Treatment of MDS or TDA with Lenalidomide ................................ 50 
`Neither the ’230 Patent Nor the Alleged Press Releases Cure
`the Shortfalls of List 2001 or Thomas 2000a ..................................... 51 
`D.  A POSA Would Not Have Had Any Motivation to Treat MDS
`or TDA with the Compound Now Known as Lenalidomide, or
`Any Reasonable Expectation of Success ........................................... 52 
`1. 
`A POSA Would Not Have Had Any Motivation to
`Combine List 2001 or Thomas 2000a with the Cited
`Secondary References .............................................................. 53 
`A POSA Would Have Had No Expectation of Success in
`Treating MDS or TDA with What is Now Known as
`Lenalidomide ........................................................................... 54 
`The Art Taught Away From the Use of Thalidomide
`Analogs for Treating MDS or TDA Because They
`Caused the Main Symptoms of MDS ...................................... 55 
`The Dependent Claims are Patentable Over Grounds 1 and 2 for
`the Same Reasons as Claims 1 and 28 ............................................... 56 
`SECONDARY CONSIDERATIONS SUPPORT
`NONOBVIOUSNESS ................................................................................. 56 
`A.  Unexpected Results ............................................................................ 57 
`B. 
`Long-Felt But Unresolved Need ........................................................ 58 
`XI.  CONCLUSION ........................................................................................... 59 
`
`
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`E. 
`
`X. 
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`iii
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`
`TABLE OF AUTHORITIES
`
`Page
`
`
`
`CASES
`
`Abbott Labs. v. Young,
`920 F.2d 984 (D.C. Cir. 1990) ............................................................................ 10
`
`Apotex Inc. v. Celgene Corp.,
`IPR2018-00685, Paper 8 (PTAB Sept. 27, 2018) ............................................... 30
`
`Applications in Internet Time, LLC v. RPX Corp.,
`897 F.3d 1336 (Fed. Cir. 2018) .......................................................................... 12
`
`Ariosa Diagnostics v. Verinata Health, Inc.,
`IPR2013-00276, Paper 43 (PTAB Oct. 23, 2014) .............................................. 14
`
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Paper 8 (PTAB Dec. 15, 2017) ................................... 15, 16, 17
`
`Belden Inc. v. Berk-Tek LLC,
`805 F.3d 1064 (Fed. Cir. 2015) .......................................................................... 52
`
`Boston Sci. Corp. v. Johnson & Johnson,
`647 F.3d 1353 (Fed. Cir. 2011) .................................................................... 40, 53
`
`Coal. for Affordable Drugs VI LLC v. Celgene Corp.,
`IPR2015-01169, Paper 22 (PTAB Nov. 16, 2015) ....................................... 41, 53
`
`Comcast Cable Commc’ns, LLC v. Veveo, Inc.,
`IPR2017-00932, Paper 10 (PTAB Sept. 7, 2017) ............................................... 31
`
`DeSilva v. DiLeonardi,
`181 F.3d 865 (Fed. Cir. 1999) ............................................................................ 14
`
`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc.,
`800 F.3d 1375 (Fed. Cir. 2015) .......................................................................... 29
`
`
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`iv
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`

`IPR2018-01504
`U.S. Patent No. 9,056,120
`
`Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd.,
`533 F.3d 1353 (Fed. Cir. 2008) .............................................................. 39, 41, 53
`
`Ford Motor Co. v. Versata Dev. Grp.,
`IPR2016-01019, Paper 9 (PTAB Oct. 4, 2016) .................................................. 30
`
`Gen. Plastic Indus. Co. v. Canon Kabushiki Kaisha,
`IPR2016-01357, Paper 19 (PTAB Sept. 6, 2017) ................................................. 9
`
`Glastetter v. Novartis Pharm. Corp.,
`252 F.3d 986 (8th Cir. 2001) .............................................................................. 40
`
`Heckler v. Chaney,
`470 U.S. 821 (1985) ............................................................................................ 14
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig.,
`676 F.3d 1063 (Fed. Cir. 2012) .......................................................................... 52
`
`In re Magnum Oil Tools Int’l, Ltd.,
`829 F.3d 1364 (Fed. Cir. 2016) .......................................................................... 31
`
`In re Soni,
`54 F.3d 746 (Fed. Cir. 1995) .............................................................................. 57
`
`Kayak Software Corp. v. Int’l Bus. Machs. Corp.,
`CBM2016-00075, Paper 16 (PTAB Dec. 15, 2016) ........................................... 16
`
`Leo Pham. Prods., Ltd. v. Rea,
`726 F.3d 1346 (Fed. Cir. 2013) .................................................................... 57, 58
`
`Moses Lake Indus., Inc. v. Enthone, Inc.,
`IPR2014-00243, Paper 6 (PTAB June 18, 2014) ............................................... 41
`
`NHK Spring Co. v. Intri-Plex Techs., Inc.,
`IPR2018-00752, Paper 8 (PTAB Sept. 12, 2018) ............................................. 8, 9
`
`
`
`v
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`

`

`IPR2018-01504
`U.S. Patent No. 9,056,120
`Oil States Energy Servs., LLC v. Greene’s Energy Grp., LLC,
`138 S. Ct. 1365 (2018) .......................................................................................... 7
`
`Par Pharm., Inc. v. Novartis AG,
`IPR2016-00084, Paper 73 (PTAB Jan. 11, 2018) .............................................. 40
`
`Pfizer Inc. v. Teva Pharm. U.S.A., Inc.,
`882 F. Supp. 2d 643 (D. Del. 2012) .............................................................. 40, 53
`
`Schumer v. Lab. Comput. Sys., Inc.,
`308 F.3d 1304 (Fed. Cir. 2002) .......................................................................... 15
`
`Shire LLC v. Amneal Pharm., LLC,
`802 F.3d 1301 (Fed. Cir. 2015) .................................................................... 50, 52
`
`Stampa v. Jackson,
`78 USPQ2d 1567 (BPAI 2005) .......................................................................... 15
`
`Zetec, Inc. v. Westinghouse Elec. Co., LLC,
`IPR2014-00384, Paper 10 (PTAB July 23, 2014) ........................................ 14, 15
`
`STATUTES
`
`35 U.S.C. § 312(a) ................................................................................................... 12
`
`35 U.S.C. § 312(a)(3) ............................................................................................... 13
`
`35 U.S.C. § 314(a) ......................................................................................... 7, 12, 14
`
`35 U.S.C. § 315(b) ..................................................................................................... 9
`
`35 U.S.C. § 325(d) ....................................................................................... 15, 17, 25
`
`REGULATIONS AND OTHER AUTHORITIES
`
`37 C.F.R. § 42.65(a) ........................................................................................... 24, 31
`
`37 C.F.R. § 42.104(b)(4) .......................................................................................... 13
`
`37 C.F.R. § 42.108(b) .............................................................................................. 14
`vi
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,759 (Aug.
`14, 2012) (to be codified at 37 C.F.R. pt. 42) ..................................................... 12
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`
`
`
`TABLE OF ABBREVIATIONS
`
`Myelodysplastic Syndrome
`MDS
`Multiple Myeloma
`MM
`Patent Owner or Celgene Celgene Corporation
`Petition or Pet.
`IPR2018-01504 Petition for Inter Partes Review
`Petitioner
`Dr. Reddy’s Laboratories, Inc.
`POSA
`Person of Ordinary Skill in the Art
`TDA
`Transfusion Dependent Anemia
`TGF-β
`Transforming Growth Factor-Beta
`TNF-α
`Tumor Necrosis Factor-Alpha
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`viii
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`
`LIST OF EXHIBITS
`
`Description
`EX
`2001 Hematology 2001: American Society of Hematology Education Program
`Book, December 7–11, 2001, containing List 2001.
`2002 Excerpt from File History of U.S. Patent No. 7,189,740 (Declaration by
`Jerome B. Zeldis, M.D., Ph.D., Under 37 C.F.R. § 1.131 dated June 22,
`2006).
`2003 Excerpt from File History of U.S. Patent No. 9,056,120 (IDS showing the
`’230 patent disclosed and considered).
`2004 Excerpt from File History of U.S. Patent No. 7,189,740 (Office Action dated
`11/3/2005).
`2005 WO 01/87307 (“Zeldis”).
`2006 U.S. Patent Application Publication No. 2003/0235909 (“Hariri”).
`2007 Excerpt from File History of U.S. Patent No. 8,404,717 (Preliminary
`Amendment dated 3/24/2011, including listing of claims).
`2008 Pellegrino Musto et al., “Thalidomide Abolishes Transfusion-Dependence
`in Selected Patients with Myelodysplastic Syndromes,” Haematologica
`(2002) 87(8):884–886 (“Pellegrino”).
`2009 Excerpt from File History of U.S. Patent No. 8,404,717 (Office Action dated
`5/9/2012).
`2010 Excerpt from File History of U.S. Patent No. 8,404,717 (Patent Owner’s
`Response to Office Action dated 9/10/2012).
`2011 Excerpt from File History of U.S. Patent No. 8,404,717 (Notice of
`Allowance dated 1/17/2013).
`2012 Excerpt from File History of U.S. Patent No. 9,056,120 (Office Action dated
`4/29/2014).
`2013 Excerpt from File History of U.S. Patent No. 9,056,120 (Response to Office
`Action dated 10/28/2014).
`2014 Raza, A., “Anti-TNF Therapies in Rheumatoid Arthritis, Crohn’s Diseases,
`Sepsis, and Myelodysplastic Syndromes,” Microscopy Research and
`Technique (2002) 50:229–235.
`
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`
`Description
`EX
`2015 Gupta, P. et al., “Fas Ligand Expression in the Bone Marrow in
`Myelodysplastic Syndromes Correlates with FAB Subtype and Anemia, and
`Predicts Survival,” Leukemia (1999) 13:44–53.
`2016 Bincoletto, C. et al., “Autonomous Proliferation and bcl-2 Expression
`Involving Hematopoietic Cells
`in Patients with Myelodysplastic
`Syndrome,” British Journal of Cancer (1998) 78(5):621–624.
`2017 Cortelezzi, A. et al., “Non-Transferrin-Bound Iron in Myelodysplastic
`Syndromes: A Marker of Ineffective Erythropoiesis?,” Hematology Journal
`(2000) 1:153–158.
`2018 Zang, D.Y. et al., “Expression of Tumor Necrosis Factor-Related
`Apoptosis-Inducing Ligand, Apo2L, and its Receptors in Myelodysplastic
`Syndrome: Effects on In Vitro Hemopoiesis,” Blood (2001) 98(10):3058–
`3065.
`2019 Rosenfeld, C. & List, A., “A Hypothesis for the Pathogenesis of
`Myelodysplastic Syndromes: Implications for New Therapies,” Leukemia
`(2000) 14:2–8.
`2020 Excerpt from File History of U.S. Patent No. 7,189,740 (Office Action dated
`3/30/2006).
`2021 Zorat, F. et al., “The Clinical and Biological Effects of Thalidomide in
`Patients with Myelodysplastic Syndromes,” British Journal of Haematology
`(2001) 115:881–894 (“Zorat”).
`2022 Excerpt from File History of U.S. Patent No. 7,189,740 (Response to Office
`Action dated 6/23/2006).
`2023 Singhal, S. et al., “Antitumor Activity of Thalidomide in Refractory
`Multiple Myeloma,” The New England Journal of Medicine (1999)
`341(21):1565–1571.
`2024 Dimopoulos, M.A. et al., “Thalidomide and Dexamethasone Combination
`for Refractory Multiple Myeloma,” Annals of Oncology (2001) 12:991–995.
`2025 Rosenfeld, C.S. et al., “Pilot Study of Recombinant Human Soluble Tumor
`Necrosis Factor Receptor (TNFR:Fc)
`in Patients with Low Risk
`Myelodysplastic Syndrome,” Leukemia Research (2002) 26:721–724.
`2026 U.S. Patent No. 5,635,517 (“the ’517 patent”).
`2027 Merriam-Webster’s Medical Desk Dictionary 459 (1993).
`
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`
`Description
`EX
`2028 List, A. et al., “Erythropoietic Remitting Activity of the Immunomodulatory
`Thalidomide Analog CC5013 (Revimid™) in Patients with Myelodysplastic
`Syndrome (MDS): Results of a Phase I/II Trial,” Cancer Investigation:
`Chemotherapy Foundation Symposium XXI (2004) 22(Supp.1):15–16,
`Abstract #9.
`2029 List, A. et al., “Efficacy of Lenalidomide in Myelodysplastic Syndromes,”
`The New England Journal of Medicine (2005) 352(6): 549–557.
`2030 S. 974, 115th Cong. (2018) (“The Hatch-Waxman Integrity Act of 2018”).
`2031 Stedman’s Medical Dictionary 73–74, 455, 1215, 1831 (27th ed. 2000).
`2032 Barlogie, B. et al., “Thalidomide in the Management of Multiple Myeloma,”
`Seminars in Hematology (2001) 38(3):250–259.
`2033 Oxford Dictionary of Biochemistry and Molecular Biology (Revised ed.
`2000) (definition of IC50).
`
`
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`
`I.
`
`INTRODUCTION
`The Petition submitted by Petitioner1 seeking inter partes review (“IPR”) of
`
`claims 1–8, 12–34, and 38–53 of Celgene’s U.S. Patent No. 9,056,120 (“the ’120
`
`patent”) should be denied. Petitioner engages in a tortured, hindsight-driven attempt
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`to cobble together a multitude of references to form an obviousness challenge using
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`the ’120 patent claims as a roadmap. For that reason alone, institution should be
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`denied. The Petition, however, also presents multiple procedural and threshold flaws,
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`each of which independently warrants denial, and collectively all the more so.
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`First, the Petition should be denied because institution would be an inefficient
`
`use of Board resources. Petitioner waited to file its petition until the eve of its one-
`
`year statutory deadline. Although the America Invents Act (“AIA”) permits parties
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`to petition for IPR challenging the validity of patent claims up to one year after being
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`served with a civil action, where, as here, the civil action has substantially
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`progressed, the Board is within its discretion in denying the Petition. Because the
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`civil action is likely to proceed to trial by the time this proceeding would conclude
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`
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`1 The petition identifies both Dr. Reddy’s Laboratories, Inc. and Dr. Reddy’s
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`Laboratories, Ltd. as real parties-in-interest. (Pet. at 55.)
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`U.S. Patent No. 9,056,120
`if instituted, instituting trial here does not foster efficiency, a principal consideration
`
`in IPRs.
`
`Moreover, Petitioner’s dual efforts to challenge the ’120 patent claims here
`
`and in district court are contrary to another aspect of the patent system, the Hatch-
`
`Waxman Act. That Act, with its carefully crafted provisions for civil actions that
`
`balance innovation and competition, does not contemplate proceedings such as IPR.
`
`Having taken advantage of the Hatch-Waxman Act, Petitioner should not be heard
`
`to invoke this separate proceeding, too. That reason for denial is all the more
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`appropriate given Petitioner’s apparent coordination with another Hatch-Waxman
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`defendant, with whom Petitioner has divided its challenges (on otherwise time-
`
`barred petitions)—another aspect that is contrary to congressional intent.
`
`Second, the Petition should be denied because it does not provide the required
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`specificity, under both the AIA and the Board’s Rules, for its alleged invalidity
`
`grounds. Instead of providing an element-by-element (or even claim-by-claim)
`
`mapping of the alleged prior art to the challenged claims, Petitioner takes a shotgun,
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`scattershot approach that leaves it up to Patent Owner and the Board to guess which
`
`references Petitioner is relying upon for which elements. That is plainly contrary to
`
`the rules.
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`Third, institution should be denied because the Petition merely retreads
`
`grounds that have already been examined and rejected by the Patent Office.
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`Petitioner relies on art that is cumulative of art already considered by the Examiner
`
`during the prosecution of the ’120 patent family. Petitioner likewise relies on the
`
`same (rejected) arguments and (rejected) alleged motivations to combine. Petitioner
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`does not (and cannot) offer any explanation as to why the Examiner erred in allowing
`
`the claims or how the arguments in the Petition differ from those already asserted
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`and then withdrawn by the Examiner.
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`Fourth, the Petition should be denied because several of the references
`
`(List 2001, Celgene Press Release 5/8/2001, and Celgene Press Release 8/28/2001)
`
`in the only two asserted grounds are not prior art. Notably, List 2001 is a primary
`
`reference in Petitioner’s first ground, and the other two references (Celgene Press
`
`Release 5/8/2001 and Celgene Press Release 8/28/2001 (together, “Alleged Press
`
`Releases”)) are asserted in both grounds. Despite Petitioner’s allegation, List 2001
`
`is not prior art. As discussed below, List 2001 was not published on January 1, 2001
`
`as Petitioner contends, and the claimed inventions pre-date List 2001. As for the
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`Alleged Press Releases, Petitioner has not offered any evidence whatsoever to
`
`establish that they were publicly available.
`
`Finally, the Petition’s lack of merit is further reason to deny institution.
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`Petitioner’s alleged grounds of invalidity result from classic hindsight bias and
`
`ignorance of teachings away.
`
`The ’120 patent claims a method of treating MDS and TDA due to low to
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`intermediate-1-risk MDS through the administration of a compound now known as
`
`lenalidomide.2 MDS is a diverse group of hematopoietic stem cell disorders that
`
`
`
`2 The ’120 patent has two independent claims, claims 1 and 28. (Ex. 1001 at 21–
`
`22.) The text of those two claims is as follows:
`
`1. A method of treating myelodysplastic syndrome, which comprises
`
`administering to a patient in need thereof about 1 mg to about 25 mg
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`per day of a compound having the formula:
`
`
`
`or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.
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`28. A method of treating transfusion dependent anemia due to low to
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`intermediate-1-risk myelodysplastic syndrome, which comprises
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`administering to a patient in need thereof about 1 mg to about 25 mg
`
`per day of a compound having the formula:
`
`
`
`or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`manifest in various cytopenias (a condition in which a patient has a reduced level of
`
`blood cells).3
`
`Prior to the inventions claimed in the ’120 patent, little was known about MDS,
`
`its etiology, or effective targets for treatment. Celgene had previously invented (and
`
`later patented) lenalidomide as part of an innovative medicinal chemistry program it
`
`launched in the mid-1990s to develop and study compounds for possible therapeutic
`
`effects. Celgene later discovered that, despite teachings in the art directing a POSA
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`away from the use of the compound now known as lenalidomide to treat MDS, it
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`was unexpectedly successful. This presented new hope for MDS patients.
`
`In disputing this, Petitioner relies heavily on the premise that a POSA would
`
`have known of a link between tumor necrosis factor-alpha (“TNF-”) inhibition and
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`MDS. Not so. The etiology of MDS was unknown as of the relevant date, and there
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`was no link between TNF- inhibition and MDS or TDA in the claimed MDS
`
`
`
`3 Several types of cytopenias exist, with each type determined by what type of blood
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`cells is low or decreased. Anemia occurs when red blood cells are low; leukopenia
`
`or neutropenia is a low level of white blood cells; and thrombocytopenia is a
`
`deficiency of platelets. (Ex. 2031 at 3–4, 7–9 (dictionary definitions of anemia,
`
`cytopenia, neutropenia, and thrombocytopenia).)
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`subpopulation (and, in fact, there was evidence suggesting there was no such link).
`
`Moreover, Petitioner’s obviousness allegations rest on the premise that the art taught
`
`a POSA that the compound later known as lenalidomide “demonstrat[ed] the most
`
`potent anti-TNF activity.” (Pet. at 15.) Again, not so. The art taught that the
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`compound now known as lenalidomide was one of the least potent of several other
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`compounds at inhibiting TNF- production.
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`Petitioner’s contention to the contrary is based upon its (and its expert’s)
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`misunderstanding of published data. Specifically, Petitioner (and its expert)
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`contends that the compound now known as lenalidomide was the “most potent”
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`compound because its TNF- IC50 value was higher than that of other compounds.
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`But the opposite is true: the higher the TNF- IC50 value, the less potent the
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`compound at inhibiting TNF- production. Petitioner’s (and its expert’s)
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`fundamental misunderstanding of this data undermines its entire argument.
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`That said, even accepting all of Petitioner’s arguments as true, Petitioner
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`ignores that the art taught away from using the compound now known as
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`lenalidomide for the treatment of MDS.4 It was known at the time of the inventions
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`
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`4 As noted herein, the compound now known as “lenalidomide” was not known by
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`that name until many years after the issuance of U.S. Patent No. 5,635,517
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`that cytopenias are the main symptoms that manifest in MDS patients. The art,
`
`however, taught that the compound that Petitioner contends would have been known
`
`to be lenalidomide caused cytopenias. A POSA would not have been motivated to
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`treat a patient with a compound that would cause and exacerbate the very symptoms
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`being treated.
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`Because Petitioner cannot demonstrate a reasonable likelihood that any of the
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`challenged claims is unpatentable, and because additional procedural and threshold
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`grounds support denial, the Board should decline to institute trial.
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`II. THE BOARD SHOULD DENY THE PETITION UNDER 35 U.S.C.
`§ 314(a) BECAUSE INSTITUTION WOULD RESULT IN AN
`INEFFICIENT USE OF BOARD RESOURCES
`“The decision whether to institute inter partes review is committed to the
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`Director’s discretion.” Oil States Energy Servs., LLC v. Greene’s Energy Grp., LLC,
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`138 S. Ct. 1365, 1371 (2018). The August 2018 Update to the Office Patent Trial
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`Practice Guide “invites parties to address additional factors that may bear on the
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`Board’s discretionary decision to institute or not institute under §§ 314(a) and
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`
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`(“the ’517 patent”) to Patent Owner. Petitioner relies on different codenames in the
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`prior art without establishing that a POSA would have known that they referred to
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`the compound later known as lenalidomide.
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`325(d).” NHK Spring Co. v. Intri-Plex Techs., Inc., IPR2018-00752, Paper 8, at 20
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`n.4 (PTAB Sept. 12, 2018). Here, two such factors counsel against institution.
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`A. The Timing of the Petition and the Advanced Nature of the
`Corresponding District Court Litigation Render Institution
`Inefficient
`The ’120 patent is the subject of a currently-pending Hatch-Waxman litigation
`
`between Patent Owner and Petitioner. That litigation has substantially advanced,
`
`rendering institution of trial here inefficient.5
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`The litigation against Petitioner—Case No. 17-5314, D.N.J. (“DRL
`
`Litigation”)—was filed by Patent Owner on July 20, 2017. Petitioner served
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`invalidity contentions in the DRL Litigation regarding the ’120 patent—which
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`included the same art cited by Petitioner in the instant proceeding—on January 19,
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`2018. Further, fact discovery has been open for nearly a year and closes in May 2019,
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`claim construction exchanges have occurred, and the case is progressing toward a
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`Markman hearing in March/April 2019.
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`
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`5 The ’120 patent is also the subject of a separate case filed by Patent Owner against
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`Lotus Pharmaceutical Co., Ltd. and Alvogen Pine Brook, LLC (collectively
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`“Lotus”), Case No. 17-6842, D.N.J. That case has also substantially advanced at
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`this time.
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`Yet Petitioner chose to wait nearly seven months after serving its invalidity
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`contentions to file its Petition. The timing of that filing—on the eve of the expiration
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`of Petitioner’s one-year statutory bar under 35 U.S.C. § 315(b)—appears calculated
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`to exploit the system to Petitioner’s advantage. Petitioner knew its invalidity
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`theories at least as early as January 2018, but chose to wait for the district court case
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`to further develop before filing the Petition at the last possible minute.
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`In view of the progression of the district court litigation, institution of IPR
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`would be inefficient. The Board has exercised its discretion to deny institution
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`where the advanced state of a corresponding district court litigation would render
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`IPR an inefficient use of Board resources. NHK Spring, IPR2018-00752, Paper 8,
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`at 19–21. Here, a proceeding before the Board on the current Petition would not
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`conclude until February 2020. Meanwhile, in the DRL Litigation, fact discovery
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`will have been closed for nine months, expert discovery will likely be closed, and
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`the case will likely be close to, if not on the eve of, trial. Thus, institution, like in
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`NHK Spring, “would not be consistent with ‘an objective of the AIA . . . to provide
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`an effective and efficient alternative to district court litigation’” and, therefore,
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`should be denied. Id. at 20 (quoting Gen. Plastic Indus. Co. v. Canon Kabushiki
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`Kaisha, IPR2016-01357, Paper 19, at 16–17 (PTAB Sept. 6, 2017)).
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`IPR2018-01504
`U.S. Patent No. 9,056,120
`Institution Would Upset the Careful Balance Struck by the
`Hatch-Waxman Act
`Institution should also be denied because instituting IPR on an Orange Book-
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`B.
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`listed patent, such as the ’120 patent, would disrupt the careful balance between
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`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
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`product of compromise
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`intended
`
`to balance
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`the objectives of
`
`inducing
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`pharmaceutical companies to invest in the research and development necessary to
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`make new products while promoting competitors to bring cheaper, generic copies of
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`those products to market. Abbott Labs. v. Young, 920 F.2d 984, 991 (D.C. Cir. 1990)
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`(Edwards, J., dissenting). That balance is disrupted by allowing generic companies
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`to take advantage of the benefits of the Hatch-Waxman Act (i.e., to file an
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`Abbreviated New Drug Application relying on the in