`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Filed: February 8, 2017
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`ACTAVIS LABORATORIES FL, INC., AMNEAL PHARMACEUTICALS LLC,
`AMNEAL PHARMACEUTICALS OF NEW YORK, LLC, DR. REDDY’S
`LABORATORIES, INC., DR. REDDY’S LABORATORIES, LTD., SUN
`PHARMACEUTICALS INDUSTRIES, LTD., SUN PHARMACEUTICALS
`INDUSTRIES, INC., TEVA PHARMACEUTICALS USA, INC., WEST-WARD
`PHARMACEUTICAL CORP., and HIKMA PHARMACEUTICALS, LLC
`
`Petitioners
`
`v.
`
`JANSSEN ONCOLOGY, INC.,
`
`Patent Owner
`
`
`
`U.S. Patent No. 8,822,438 to Auerbach et al.
`
`
`
`Inter Partes Review IPR2017-00853
`
`
`
`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
`
`
`
`

`

`TABLE OF CONTENTS
`
`Page
`
`I.
`
`INTRODUCTION .......................................................................................... 1
`
`II. MANDATORY NOTICES ............................................................................ 1
`
`A.
`
`B.
`
`C.
`
`D.
`
`Real Parties-In-Interest Under 37 C.F.R. § 42.8(b)(1) ......................... 1
`
`Related Matters Under 37 C.F.R. § 42.8(b)(2) .................................... 2
`
`Lead And Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3) ................ 3
`
`Service Information Under 37 C.F.R. § 42.8(b)(4) .............................. 3
`
`III. GROUNDS FOR STANDING (37 C.F.R. §§ 42.101 AND 42.104) ............ 4
`
`IV.
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED (37 C.F.R. § 42.22(A) AND 37
`C.F.R. § 42.104(B)) ........................................................................................ 4
`
`V.
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW ............ 5
`
`VI. STATEMENT OF REASONS FOR THE RELIEF REQUESTED .............. 5
`
`A.
`
`B.
`
`Summary of the Argument ................................................................... 5
`
`Level of Ordinary Skill in the Art ........................................................ 7
`
`C. U.S. Patent No. 8,822,438 and Its File History .................................... 8
`
`1.
`
`2.
`
`Specification of the ’438 Patent ................................................. 8
`
`File History of the ’438 Patent ................................................. 11
`
`D.
`
`E.
`
`Claim Construction (37 C.F.R. §§ 42.100(b), 42.104(b)(3)) ............. 18
`
`Scope and Content of the Prior Art .................................................... 20
`
`1.
`
`2.
`
`3.
`
`Overview .................................................................................. 20
`
`Background of Prostate Cancer and Its Treatment .................. 24
`
`Prior Art References................................................................. 29
`
`a.
`
`In 2004, O’Donnell Described the Administration
`of Abiraterone Acetate as More Effective for
`Treating Metastatic Refractory Prostate Cancer
`than Ketoconazole, and Possibly Requiring
`Concomitant Glucocorticoid Replacement Therapy ..... 29
`
`i
`
`

`

`b.
`
`c.
`
`In 1990, Gerber Disclosed the Use of
`Ketoconazole with Prednisone, a Glucocorticoid,
`in Patients with Hormone Refractory Metastatic
`Prostate Cancer .............................................................. 33
`
`In 1997, the ’213 Patent Disclosed Abiraterone
`Acetate and Its Superiority over Ketoconazole in
`Treating Prostate Cancer ............................................... 35
`
`F.
`
`Explanation of Grounds for Unpatentability ...................................... 38
`
`1.
`
`The Method of Claim 1 was Obvious over Either
`O’Donnell in view of Gerber (Ground 1) or the ’213
`Patent in View of Gerber (Ground 2) ...................................... 38
`
`a.
`
`b.
`
`O’Donnell and the ’213 Patent Disclosed the Use
`of Abiraterone Acetate to Treat Prostate Cancer ........... 38
`
`Gerber Disclosed Co-Administering Prednisone
`with a CYP17 Inhibitor, like Abiraterone Acetate ........ 39
`
`O’Donnell and the ’213 Disclosed the Dosing
`Limitations Recited in Claims 2 and 3 ..................................... 42
`
`The Dose Recited in Claim 4 was Disclosed to One of
`Skill in the Art by either O’Donnell or the ’213 Patent ........... 43
`
`The Dose Recited in Claim 5 was Disclosed to One of
`Skill in the Art by O’Donnell................................................... 44
`
`Claims 6–9 were Obvious over O’Donnell or the ’213
`Patent in View of Gerber ......................................................... 45
`
`Claim 10 was Obvious over O’Donnell or the ’213 Patent
`in View of Gerber .................................................................... 46
`
`Claim 11 was Obvious over O’Donnell or the ’213 Patent
`in View of Gerber .................................................................... 47
`
`Claims 12–16 were Obvious over O’Donnell in View of
`Gerber ....................................................................................... 47
`
`The Docetaxel Treatment in Claim 17 was Part of the
`Background Knowledge of One of Skill in the Art ................. 49
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`10. Claim 18 was Obvious over O’Donnell in View of
`Gerber ....................................................................................... 50
`
`ii
`
`

`

`11. Claim 19 was Obvious over O’Donnell in View of
`Gerber ....................................................................................... 50
`
`12. Claim 20 was Obvious over O’Donnell in View of
`Gerber ....................................................................................... 50
`
`G.
`
`Secondary Considerations do not Indicate that the Claims of the
`’438 Patent were Non-Obvious .......................................................... 50
`
`1.
`
`2.
`
`3.
`
`4.
`
`Applicants did not Offer Relevant Evidence of
`Commercial Success and the Examiner Issued the ’438
`Patent Based on the Erroneous Conclusion that the
`Asserted Commercial Success of Zytiga Overcame the
`Obviousness of the Claimed Invention. ................................... 51
`
`One of Skill in the Art would not Anticipate Unexpected
`Benefits from the Claimed Invention and Applicants did
`not Offer Any Evidence of Relevant Unexpected Results ...... 54
`
`The ’438 Patent Satisfied No Long-Felt but Unmet Need ...... 58
`
`The ’213 is a Blocking Patent that Limits the
`Applicability of Commercial Success ...................................... 59
`
`5.
`
`Copying by Generic Drug Makers is Irrelevant ...................... 60
`
`H.
`
`Conclusion .......................................................................................... 61
`
`
`
`
`
`iii
`
`

`

`TABLE OF AUTHORITIES
`
`Page
`
`Federal Cases
`Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281 (Fed. Cir.
`1985) .....................................................................................................................51
`
`
`Bayer Healthcare Pharms., Inc. v. Watson Pharms., Inc., 713 F.3d 1369 (Fed. Cir.
`2013) .....................................................................................................................61
`
`
`BTG Int’l Ltd. v. Actavis Labs. FL, Inc., No. 15-cv-5909-KM-JBC (D.N.J.) .........19
`
`Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d 731 (Fed. Cir. 2013) ....................60
`
`In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359 (Fed. Cir. 2004) ........................19
`
`Merck & Co., Inc. v. Teva Pharms. USA, Inc., 395 F.3d 1364 (Fed. Cir. 2005) .....59
`
`Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007) ....................................51
`
`Smith & Nephew, Inc. v. ConvaTec Techs., Inc., Case No. IPR2013-00097 (PTAB
`May 29, 2014) .......................................................................................................52
`
`
`Smith & Nephew, Inc. v. ConvaTec Techs., Inc., Case No. IPR2013-00102 (PTAB
`May 29, 2014) .......................................................................................................52
`
`
`
`Federal Statutes
`35 U.S.C. § 102(b) ...................................................................................... 29, 33, 35
`
`35 U.S.C. § 103 ....................................................................................................4, 17
`
`35 U.S.C. § 314(a) ..................................................................................................... 5
`
`35 U.S.C. §§ 311–319 ................................................................................................ 1
`
`
`
`Federal Regulations
`37 C.F.R. § 42.10(b) .................................................................................................. 1
`
`37 C.F.R. § 42.100(b) ..............................................................................................18
`
`37 C.F.R. § 42.101 ..................................................................................................... 4
`
`iv
`
`

`

`
`37 C.F.R. § 42.103 ..................................................................................................... 1
`37 C.F.R. § 42.103 ................................................................................................... ..1
`
`37 C.F.R. § 42.104 ..................................................................................................... 4
`37 C.F.R. § 42.104 ................................................................................................... ..4
`
`37 C.F.R. § 42.104(a) ................................................................................................. 4
`37 C.F.R. § 42.104(a) ............................................................................................... ..4
`
`37 C.F.R. § 42.104(b) ................................................................................................ 4
`37 C.F.R. § 42.104(b) .............................................................................................. ..4
`
`37 C.F.R. § 42.104(b)(3) ..........................................................................................18
`37 C.F.R. § 42.104(b)(3) ........................................................................................ ..18
`
`37 C.F.R. § 42.106(a) ................................................................................................. 1
`37 C.F.R. § 42.106(a) ............................................................................................... ..1
`
`37 C.F.R. § 42.15(a) ................................................................................................... 1
`37 C.F.R. § 42.15(a) ................................................................................................. ..1
`
`37 C.F.R. § 42.22(a) ................................................................................................... 4
`37 C.F.R. § 42.22(a) ................................................................................................. ..4
`
`37 C.F.R. § 42.63(e) ................................................................................................... 1
`37 C.F.R. § 42.63(e) ................................................................................................. ..1
`
`37 C.F.R. § 42.8(b)(1) ............................................................................................... 1
`37 C.F.R. § 42.8(b)(1) ............................................................................................. ..1
`
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 2
`37 C.F.R. § 42.8(b)(2) .............................................................................................. ..2
`
`37 C.F.R. § 42.8(b)(3) ............................................................................................... 3
`37 C.F.R. § 42.8(b)(3) ............................................................................................. ..3
`
`37 C.F.R. § 42.8(b)(4) ................................................................................................ 3
`37 C.F.R. § 42.8(b)(4) .............................................................................................. ..3
`
`
`
`Other
`Other
`
`MPEP § 716.03 ........................................................................................................53
`MPEP § 716.03 ...................................................................................................... ..53
`
`MPEP § 716.03(b) ....................................................................................................53
`MPEP § 716.03(b) .................................................................................................. ..53
`
`
`
`
`
`
`
`v
`
`

`

`LISTING OF EXHIBITS
`
`Exhibit #
`
`Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`U.S. Patent No. 8,822,438, Auerbach and Belldegrun, “Methods
`and Compositions for Treating Cancer” (“the ’438 patent”)
`
`Declaration of Marc B. Garnick, MD (“Garnick Decl.”)
`
`O’Donnell, A. et al., “Hormonal impact of the 17α-
`hydroxylase/C17,20-lyase inhibitor abiraterone acetate (CB7630)
`in patients with prostate cancer,” Br. J. Cancer, (90):2317–2325
`(2004) (“O’Donnell”)
`
`Gerber, G.S. et al., “Prostate specific antigen for assessing
`response to ketoconazole and prednisone in patients with hormone
`refractory metastatic cancer,” J. Urology, 144(5):1177–9 (1990)
`(“Gerber”)
`
`U.S. Patent No. 5,604,213, Barrie S.E. et al., “17-Substituted
`Steroids Useful In Cancer Treatment” (“the ’213 patent”)
`
`Tannock, I. et al., “Chemotherapy with mitoxantrone plus
`prednisone or prednisone alone for symptomatic hormone-
`resistant prostate cancer: a Canadian randomized trial with
`palliative end points,” J. Clinical Oncology, 14:1756–1764 (1996)
`(“Tannock”)
`
`February 3, 2012 Office Action (excerpt from prosecution history
`of ’438 patent)
`
`July 3, 2012 Response (excerpt from prosecution history of ’438
`patent)
`
`Ryan, C.J. et al., “Abiraterone in metastatic prostate cancer
`without previous chemotherapy,” New Eng. J. Med., 368:138–148
`(2013).
`
`January 11, 2013 Response (excerpt from prosecution history of
`’438 patent)
`
`March 4, 2013 Office Action (excerpt from prosecution history of
`’438 patent)
`
`June 4, 2013 Response (excerpt from prosecution history of ’438
`patent)
`
`vi
`
`

`

`Exhibit #
`
`Description
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`July 3, 2013 Notice of Allowance (excerpt from prosecution
`history of ’438 patent)
`
`October 25, 2013 Notice of Allowance (excerpt from prosecution
`history of ’438 patent)
`
`February 11, 2014 Notice of Allowance (excerpt from prosecution
`history of ’438 patent)
`
`June 2, 2014 Notice of Allowance (excerpt from prosecution
`history of ’438 patent)
`
`Declaration of Ivan T. Hofmann (“Hofmann Declaration”)
`
`2011 Zytiga® Approval Prescribing Information
`
`2015 Zytiga® Prescribing Information, Co-administration
`Brochure
`
`Harris, K.A. et al., “Low dose ketoconazole with replacement
`doses of hydrocortisone in patients with progressive androgen
`independent prostate cancer,” J. Urology, 168:542–545 (August
`2002)
`
`Oh, W.K. “Secondary hormonal therapies in the treatment of
`prostate cancer,” Urology, 60(Supp. 3A):87–93 (2002)
`
`Tannock, I. et al., “Docetaxel plus prednisone or mitoxantrone
`plus prednisone for advanced prostate cancer,” N. Eng. J. Med.,
`351:1502–12 (2004)
`
`Attard, G. et al., “Selective blockade of androgenic steroid
`synthesis by novel lyase inhibitors as a therapeutic strategy for
`treating metastatic prostate cancer,” Br. J. Urol. 96(9): 1241–1246
`(2005)
`
`Hellerstedt, B.A. et al., “The current state of hormonal therapy for
`prostate cancer,” CA Cancer J. Clin., 52:154–179 (2002).
`
`Kasper, D.L. et al. (Eds.), Harrison’s Principles of Internal
`Medicine, 16th Edition (2005), 549.
`
`vii
`
`

`

`Exhibit #
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`Description
`
`Auchus, R.J. “The genetics, pathophysiology, and management of
`human deficiencies of P450c17,” Endocrinol. Metab. Clin. North
`Am. 30(1):101–119 (2001)
`
`Costa-Santos, M. et al., “Two prevalent CYP17 mutations and
`genotype-phenotype correlations in 24 Brazilian patients with 17-
`hydroxylase deficiency,” J. Clin. Endocrin. & Metabol. 89(1):49–
`60 (2004)
`
`Jubelirer, S.J., et al., “High dose ketoconazole for the treatment of
`hormone refractory metastatic prostate carcinoma,” J. Urol.,
`142(1):89–91 (1989)
`
`U.S. Patent 5,688,977, Sisti, N.J. et al., “Method for Docetaxel
`Synthesis”
`
`U.S. Food and Drug Administration (“FDA”) FDA News Release
`dated May 19, 2004, “FDA Approves New Indication for
`Taxotere-Prostate Cancer”
`
`Tannock, I. et al., “Treatment of metastatic prostatic cancer with
`low-dose prednisone: evaluation of pain and quality of life as
`pragmatic indices of response,” J. Clin. Oncology, 7:590–7 (1989)
`
`Intentionally left blank
`
`Scher, H.I. et al., “Increased survival with enzalutamide in
`prostate cancer after chemotherapy,” New Eng. J. Med.,
`367:1187–97 (2012)
`
`de Bono, J.S. et al., “Abiraterone and increased survival in
`metastatic prostate cancer,” New Engl. J. Med., 364:1995–2005
`(2011)
`
`Orange Book listing for Zytiga®
`
`Initial Application (excerpt from prosecution history of ’438
`patent)
`
`Intentionally left blank
`
`Intentionally left blank
`
`viii
`
`

`

`Exhibit #
`
`1039
`
`1040
`
`Description
`
`September 11, 2012 Office Action (excerpt from prosecution
`history of ’438 patent)
`
`Cancer.net (ASCO Patient Website), Treatment of Metastatic
`Castration-Resistant Prostate Cancer,
`http://www.cancer.net/research-and-advocacy/asco-care-and-
`treatment-recommendations-patients/treatment-metastatic-
`castration-resistant-prostate-cancer (accessed 6/28/2016).
`
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`1048
`
`1049
`
`Cancer.org (ACS), “What are the key statistics about prostate
`cancer?”
`http://www.cancer.org/cancer/prostatecancer/detailedguide/prostat
`e-cancer-key-statistics (accessed 6/28/2016).
`
`Intentionally left blank
`
`Intentionally left blank
`
`Intentionally left blank
`
`FDA News Release, “FDA expands Zytiga’s use for late-stage
`prostate cancer,” 12/10/2012
`http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements
`/ucm331492.htm (access 6/30/2016).
`
`FDA Website, Drugs@FDA – Zytiga,
`http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?
`fuseaction=Search.DrugDetails (accessed 6/28/2016).
`
`FDA Website, Orange Book, Zytiga (NDA 202379),
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cf
`m?Appl_No=202379&Product_No=001&table1=OB_Rx
`(accessed 6/30/2016).
`
`Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d 731, 740–41 (Fed.
`Cir. 2013).
`
`Jevtana Website, Dosing and Administration,
`http://www.jevtana.com/hcp/dosing/default.aspx (accessed
`6/28/2016).
`
`ix
`
`

`

`Exhibit #
`
`1050
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`1057
`
`1058-
`1063
`
`1064
`
`1065
`
`1066
`
`1067
`
`1068
`
`1069
`
`Description
`
`Kirby, M. et al., “Characterising the castration-resistant prostate
`cancer population: A systematic review,” Int’l J. Clinical Practice
`65(11):1180–1192 (2011).
`
`Mayo Clinic Website, Prostate cancer,
`http://www.mayoclinic.org/diseasesconditions/prostate-
`cancer/basics/definition/con-20029597?p=1 (accessed 6/28/2016).
`
`Intentionally left blank
`
`Merck & Co. v. Teva Pharms. USA, Inc., 395 F.3d 1364 (Fed. Cir.
`2005).
`
`Murphy, W.J., J.L. Orcutt & P.C. Remus (2012), Patent
`Valuation: Improving Decision Making through Analysis,
`Hoboken, NJ: Wiley.
`
`PMLiVe Website, “Top 50 Pharmaceutical Products by Global
`Sales,”
`http://www.pmlive.com/top_pharma_list/Top_50_pharmaceutical
`_products_by_global_sales (accessed 6/30/2016).
`
`Intentionally left blank
`
`Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371 (Fed. Cir.
`2005).
`
`Intentionally left blank
`
`Zytiga Brochure, Putting Prednisone in Perspective, 3/2015.
`
`Zytiga Label, 5/20/2015.
`
`Zytiga Website, How Zytiga® (abiraterone acetate) Works,
`https://www.zytiga.com/print/about-zytiga/how-zytiga-works
`(accessed 6/28/2016).
`
`Intentionally left blank
`
`November 25, 2011 Office Action (excerpt from prosecution
`history of ’438 patent)
`
`December 21, 2011 Response (excerpt from prosecution history
`of ’438 patent)
`
`x
`
`

`

`Exhibit #
`
`Description
`
`1070
`
`1071
`
`1072
`
`1073
`
`1074
`
`1075
`
`1076
`
`1077
`
`1078
`
`1079
`
`1080
`
`September 11, 2012 Office Action (excerpt from prosecution
`history of ’438 patent)
`
`October 3, 2013 IDS (excerpt from prosecution history of ’438
`patent)
`
`October 3, 2013 IDS (excerpt from prosecution history of ’438
`patent)
`
`January 10, 2014 IDS (excerpt from prosecution history of ’438
`patent)
`
`May 9, 2014 IDS (excerpt from prosecution history of ’438
`patent)
`
`May 9, 2014 IDS (excerpt from prosecution history of ’438
`patent)
`
`May 30, 2014 IDS (excerpt from prosecution history of ’438
`patent)
`
`May 30, 2014 IDS (excerpt from prosecution history of ’438
`patent)
`
`Barrie et al., “Pharmacology of novel steroidal inhibitors of
`Cytochrome P45017α (17α-hydroxylase/C17,20 lyase),”
`J. Steroid Biochem. Molec. Biol. 50:267-73 (1994)
`
`Fakih, M. et al., “Glucocorticoids and treatment of prostate
`cancer: A preclinical and clinical review,” Urology 60:553-561
`(2002)
`
`Lam, J.S. et al., “Secondary hormonal therapy for advanced
`prostate cancer,” J. Urology 175:28-34 (2006)
`
`
`
`
`
`xi
`
`

`

`TABLE OF ABBREVIATIONS
`
`Abbreviation
`
`Definition
`
`ACTH
`
`AR
`
`CRPC
`
`mCRPC
`
`CYP17
`
`DHT
`
`IDS
`
`LH
`
`NDA
`
`POSA
`
`PSA
`
`RCE
`
`Adrenocorticotropic hormone
`
`Androgen receptor
`
`Castration-resistant prostate cancer
`
`Metastatic castration-resistant prostate cancer
`
`17α-hydroxylase/C17,20-lyase
`
`Dihydrotestosterone
`
`Information Disclosure Statement
`
`Luteinizing hormone
`
`New Drug Application
`
`Person of Ordinary Skill in the Art
`
`Prostate-specific antigen
`
`Request for Continued Examination
`
`xii
`
`

`

`
`
`I.
`
`INTRODUCTION
`
`Actavis Laboratories FL, Inc., Amneal Pharmaceuticals LLC, Amneal
`
`Pharmaceuticals Of New York, LLC, Dr. Reddy’s Laboratories, Inc., Dr. Reddy’s
`
`Laboratories, Ltd., Sun Pharmaceuticals Industries, Ltd., Sun Pharmaceuticals
`
`Industries, Inc., Teva Pharmaceuticals USA, Inc., West-Ward Pharmaceutical Corp.,
`
`and Hikma Pharmaceuticals, LLC (“Petitioners”) petition for Inter Partes Review
`
`of claims 1-20 of U.S. Patent No. 8,822,438 to Auerbach et al. (“the ’438 patent”)
`
`(Ex. 1001), which is assigned to Janssen Oncology, Inc. (“Janssen”), under 35
`
`U.S.C. §§ 311–319 and 37 C.F.R. Part 42 and seek a determination that all claims
`
`(1-20) of the ’438 patent be canceled as unpatentable.
`
`This Petition is filed in accordance with 37 C.F.R. § 42.106(a). Concurrently
`
`filed herewith is a power of attorney and an exhibit list per § 42.10(b) and § 42.63(e),
`
`respectively. Pursuant to 37 C.F.R. § 42.103, the fee set forth in § 42.15(a)
`
`accompanies this Petition.
`
`II. MANDATORY NOTICES
`
`Petitioners provide the following mandatory notices.
`
`A. Real Parties-In-Interest Under 37 C.F.R. § 42.8(b)(1)
`
`The real parties-in-interest for Petitioners are Amneal Pharmaceuticals, LLC;
`
`Amneal Pharmaceuticals of New York, LLC; Sun Pharma FZE; Sun Pharmaceutical
`
`Industries, Ltd.; Sun Pharmaceutical Industries, Inc.; Dr. Reddy’s Laboratories, Ltd.;
`
`Dr. Reddy’s Laboratories,
`
`Inc.; Hikma Pharmaceuticals PLC; Hikma
`
`1
`
`

`

`
`
`Pharmaceuticals, LLC; West-Ward Pharmaceutical Corp.; Actavis Laboratories FL,
`
`Inc.; Actavis Pharma, Inc.; Teva Pharmaceuticals Industries Ltd.; and Teva
`
`Pharmaceuticals USA, Inc. And, in an abundance of caution, Petitioners also
`
`identify Amneal Holdings, LLC and Amneal Pharmaceutical Holdings Company,
`
`LLC real parties-in-interest.
`
`B. Related Matters Under 37 C.F.R. § 42.8(b)(2)
`
`The following litigations or instituted inter partes reviews related to the ’438
`
`patent are pending:
`
` Amerigen Pharms. Ltd. v. Janssen Oncology, Inc., IPR2016-00286
`
`(P.T.A.B.);
`
` Argentum Pharms. LLC v. Janssen Oncology, Inc., IPR2016-01317
`
`(P.T.A.B.).
`
` BTG Int’l Ltd. v. Actavis Labs. FL, Inc., No. 15-cv-5909-KM-JBC
`
`(D.N.J.);
`
`
`
`BTG Int’l Ltd. v. Amerigen Pharms., Inc., No. 16-cv-02449-KM-JBC
`
`(D.N.J.);
`
`
`
`BTG Int’l Ltd. v. Glenmark Pharms. Inc., USA, No. 16-cv-03743-KM-
`
`JBC (D.N.J.); and
`
`
`
`Janssen Biotech, Inc. v. Mylan Pharms. Inc., No. 15-cv-00130-IMK
`
`(N.D.W. Va.).
`
`2
`
`

`

`
`
`
`
`Mylan Pharmaceuticals Inc. v. Janssen Oncology, Inc., IPR2016-
`
`01332 (P.T.A.B.).
`
`
`
`Wockhardt Bio AG v. Janssen Oncology, Inc., IPR2016-01582
`
`(P.T.A.B.).
`
`C. Lead And Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3)
`
`Back-Up Counsel
`Jovial Wong (Reg. No. 60,115)
`Winston & Strawn, LLP
`1700 K St. NW
`Washington, DC 20006
`Telephone: (202) 282-5867
`Facsimile: (202) 282-5100
`jwong@winston.com
`
`Lead Counsel
`Samuel S. Park (Reg. No. 59,656)
`Winston & Strawn, LLP
`35 W. Wacker Dr.
`Chicago, IL 60601
`Telephone: (312) 558-7931
`Facsimile: (312) 558-5700
`spark@winston.com
`Back-Up Counsel
`Ryan B. Hauer (Reg. No. 73,646)
`Winston & Strawn, LLP
`35 W. Wacker Dr.
`Chicago, IL 60601
`Telephone: (312) 558-8116
`Facsimile: (312) 558-5700
`rhauer@winston.com
`
`D.
`
`Service Information Under 37 C.F.R. § 42.8(b)(4)
`
`Please direct all correspondence to lead counsel and back-up counsel at the
`
`contact information above. Petitioners consent to electronic service by e-mail at the
`
`above listed email addresses of lead and back-up counsel.
`
`3
`
`

`

`
`
`III. GROUNDS FOR STANDING (37 C.F.R. §§ 42.101 and 42.104)
`
`As required by 37 C.F.R. § 42.104(a), Petitioners certify that the ’438 patent
`
`is available for inter partes review and that the Petitioners are not barred or estopped
`
`from requesting inter partes review on the grounds identified herein.
`
`IV.
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED (37 C.F.R. § 42.22(a) and 37 C.F.R.
`§ 42.104(b))
`
`Petitioners request inter partes review and cancellation of claims 1–20.
`
`Petitioners’ full statement of the reasons for the relief requested is set forth below.
`
`Petitioners respectfully request inter partes review and cancellation of claims
`
`1–20 of the ’438 Patent based on the grounds set forth below:1
`
`Ground 1: Claims 1-20 are unpatentable as obvious under 35 U.S.C. § 103
`
`over O’Donnell in view of Gerber
`
`Ground 2: Claims 1-4 and 5-11 are unpatentable as obvious under 35 U.S.C.
`
`§ 103 over the ’213 patent in view of Gerber.
`
`In support of these grounds for unpatentability, Petitioners submit the expert
`
`declaration of Marc B. Garnick, M.D. (Ex. 1002 (“Garnick Decl.”)) and the
`
`
`1 Petitioners’ asserted grounds of obviousness are the same as those instituted in
`
`IPR2016-00286, filed by Amerigen Pharmaceuticals Limited and IPR2016-01332,
`
`filed by Mylan Pharmaceuticals, Inc.
`
`4
`
`

`

`
`
`declaration of economics expert Ivan T. Hofmann (Ex. 1017 (“Hofmann Decl.”)).
`
`Petitioners also rely on the other Exhibits set forth in the concurrently filed Listing
`
`of Exhibits.
`
`V. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`
`A petition for inter partes review must demonstrate “a reasonable likelihood
`
`that the petitioner would prevail with respect to at least 1 of the claims challenged
`
`in the petition.” 35 U.S.C. § 314(a). This Petition meets this threshold. As
`
`explained below, there is a reasonable likelihood that Petitioners will prevail with
`
`respect to at least one of the challenged claims.
`
`VI. STATEMENT OF REASONS FOR THE RELIEF REQUESTED
`
`A.
`
`Summary of the Argument
`
`The claims of the ’438 patent are directed to treating prostate cancer by
`
`administering therapeutically effective amounts of abiraterone acetate, a 17α-
`
`hydroxylase/C17,20-lyase inhibitor (“CYP17 inhibitor”), in combination with
`
`prednisone, a glucocorticoid. Ex. 1002, Garnick Decl. ¶¶34–35. The prior art taught
`
`the use of abiraterone acetate as an effective anti-cancer agent that suppresses
`
`testosterone synthesis in prostate cancer patients. Ex. 1002, Garnick Decl. ¶¶36, 55,
`
`66, 68. It was known as of the earliest priority date claimed by the ’438 patent that
`
`testosterone promoted prostate cancer proliferation and progress, so that testosterone
`
`synthesis must be suppressed to treat prostate cancer.
`
`5
`
`

`

`
`
`However, it was also known that in using a CYP17 inhibitor to reduce
`
`testosterone synthesis, the CYP17 inhibitor undesirably suppressed the production
`
`of cortisol, a glucocorticoid, which is necessary for other biochemical cycles in the
`
`body. In particular, reduced production of cortisol caused adverse effects, including
`
`hypertension, hypokalemia (decrease in circulating potassium levels), and fluid
`
`retention. To address the suppressed synthesis of cortisol, the prior art taught that
`
`concomitant glucocorticoid replacement therapy might be necessary when
`
`administering abiraterone to treat prostate cancer in a patient, and that this was
`
`common practice in the treatment of prostate cancer with ketoconazole, another
`
`CYP17 inhibitor. Ex. 1002, Garnick Decl. ¶¶42, 44, 58.
`
`The prior art also taught that abiraterone was a more effective CYP17 inhibitor
`
`than ketoconazole. For example, the prior art taught that abiraterone acetate was
`
`more effective in decreasing testosterone levels in a mammal than ketoconazole. Ex.
`
`1002, Garnick Decl. ¶¶46, 55. The prior art also taught that the combination of
`
`ketoconazole and prednisone was a safe and effective treatment for refractory
`
`metastatic prostate cancer. Ex. 1002, Garnick Decl. ¶58.
`
`One of skill in the art would have combined abiraterone acetate and
`
`prednisone based on the teachings of O’Donnell in view of Gerber, and/or the ’213
`
`patent in view of Gerber, for a safe and effective treatment of prostate cancer with a
`
`reasonable expectation of success. The prior art taught that abiraterone acetate was
`
`6
`
`

`

`
`
`a more effective CYP17 inhibitor than ketoconazole and that the combination of
`
`ketoconazole and prednisone was safe and effective to treat patients with hormone
`
`refractory metastatic prostate cancer, which would have motivated the combination.
`
`Ex. 1002, Garnick Decl. ¶¶55–59. One of skill in the art may also have been
`
`motivated by prednisone’s possible anti-cancer effects. Id. ¶ 89.
`
`There are no secondary considerations of commercial success that overcome
`
`this case of obviousness. The claims of the application that resulted in the ’438
`
`patent were repeatedly rejected for obviousness until the Examiner allowed the
`
`claims based on the purported “unexpected commercial success” of Zytiga, the brand
`
`name under which abiraterone acetate is marketed in the United States by the
`
`Assignee. In particular, the Examiner’s allowance of the claims based on secondary
`
`considerations of commercial success of Zytiga was in error because Applicants
`
`failed to show the necessary nexus between the claimed invention (which is directed
`
`to a method of treating prostate cancer by administering abiraterone acetate and
`
`prednisone) and any commercial success of the drug Zytiga.
`
`B.
`
`Level of Ordinary Skill in the Art
`
`A person of ordinary skill in the art is presumed to be aware of all pertinent
`
`art, thinks along conventional wisdom in the art, and is a person of ordinary
`
`creativity. With respect to the ’438 patent, the scientific field relevant is oncology
`
`or urology. Ex. 1002, Garnick Decl. ¶18. A person of ordinary skill in the art would
`
`7
`
`

`

`
`
`be a physician specializing in urology, endocrinology, or oncology, or a person
`
`holding a Ph.D. in pharmacology, biochemistry or a related discipline, such as
`
`pharmaceutical science. Ex. 1002, Garnick Decl. ¶18. Additional experience could
`
`substitute for the advanced degree. Ex. 1002, Garnick Decl. ¶18. To the extent
`
`necessary, one of skill in the art may collaborate with one or more other persons of
`
`skill in the art for one or more aspects with which the other person may have
`
`expertise, experience and/or knowledge that was obtained through his or her
`
`education, industrial or academic experiences. Ex. 1002, Garnick Decl. ¶19. For
`
`example, one of skill may consult with an endocrinologist, oncologist, or medical
`
`biochemist and thus may rely on the opinions of such specialists in evaluating the
`
`claims. Ex. 1002, Garnick Decl. ¶20.
`
`C. U.S. Patent No. 8,822,438 and Its File History
`
`1.
`
`Specification of the ’438 Patent
`
`The “Background” section of the ’438 patent describes prostatectomy and
`
`radiotherapy, a primary course of treatment for patients diagnosed with organ-
`
`confined prostate cancer, as being highly invasive and ineffective on metastasized
`
`prostate cancer. Ex. 1001, col. 1, ll. 25–32. In addition, the specification states that
`
`these localized treatments are not effective on prostate cancer after it has
`
`metastasized and that, moreover, a large percent of individ