UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`Filed: June 30, 2016
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`MYLAN PHARMACEUTICALS INC.,
`
`Petitioner
`
`v.
`
`JANSSEN ONCOLOGY, INC.,
`
`Patent Owner
`
`
`
`U.S. Patent No. 8,822,438 to Auerbach et al.
`
`
`Inter Partes Review IPR2016-01332
`
`
`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
`
`
`
`

`
`TABLE OF CONTENTS
`
`Page
`
`INTRODUCTION .......................................................................................... 1
`I.
`II. MANDATORY NOTICES ............................................................................ 1
`A.
`Real Parties-In-Interest Under 37 C.F.R. § 42.8(b)(1) ......................... 1
`B.
`Related Matters Under 37 C.F.R. § 42.8(b)(2) .................................... 1
`C.
`Lead And Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3) ................ 2
`D.
`Service Information Under 37 C.F.R. § 42.8(b)(4) .............................. 2
`III. GROUNDS FOR STANDING (37 C.F.R. §§ 42.101 AND 42.104) ............ 3
`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)) ........................................................................................ 3
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW ............ 4
`V.
`VI. STATEMENT OF REASONS FOR THE RELIEF REQUESTED .............. 4
`A.
`Summary of the Argument ................................................................... 4
`B.
`Level of Ordinary Skill in the Art ........................................................ 6
`C. U.S. Patent No. 8,822,438 and Its File History .................................... 7
`1.
`Specification of the ’438 Patent ................................................. 7
`2.
`File History of the ’438 Patent ................................................. 10
`Claim Construction (37 C.F.R. §§ 42.100(b), 42.104(b)(3)) ............. 17
`Scope and Content of the Prior Art .................................................... 19
`1.
`Overview .................................................................................. 19
`2.
`Background of Prostate Cancer and Its Treatment .................. 24
`3.
`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
`
`D.
`E.
`
`i 
`
`

`
`b.
`
`c.
`
`b.
`
`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
`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.
`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
`10. Claim 18 was Obvious over O’Donnell in View of
`Gerber ....................................................................................... 50
`
`5.
`
`F.
`
`2.
`
`3.
`
`4.
`
`6.
`
`7.
`
`8.
`
`9.
`
`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
`Secondary Considerations do not Indicate that the Claims of the
`’438 Patent were Non-Obvious .......................................................... 51
`1.
`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 ...... 59
`The ’213 is a Blocking Patent that Limits the
`Applicability of Commercial Success ...................................... 59
`Copying by Generic Drug Makers is Irrelevant ...................... 61
`5.
`Conclusion .......................................................................................... 61
`
`
`3.
`4.
`
`2.
`
`G.
`
`H.
`
`
`
`iii 
`
`

`
`TABLE OF AUTHORITIES
`
`Page
`
`Cases
`Ashland Oil, Inc. v. Delta Resins & Refractories, Inc.,
`776 F.2d 281 (Fed. Cir. 1985) ....................................................................... 52
`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) ..................................................................... 18
`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
`
`
`Statutes
`35 U.S.C. § 102(b) ...................................................................................... 29, 33, 35
`35 U.S.C. § 103 ................................................................................................... 3, 16
`35 U.S.C. § 314(a) ..................................................................................................... 4
`35 U.S.C. §§ 311–319 ................................................................................................ 1
`
`Rules
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 1
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 1
`37 C.F.R. § 42.8(b)(3) ................................................................................................ 2
`
`iv 
`
`

`
`37 C.F.R. § 42.8(b)(4) ................................................................................................ 2
`37 C.F.R. § 42.10(b) .................................................................................................. 1
`37 C.F.R. § 42.15(a) ................................................................................................... 1
`37 C.F.R. § 42.22(a) ................................................................................................... 3
`37 C.F.R. § 42.63(e) ................................................................................................... 1
`37 C.F.R. § 42.100(b) .............................................................................................. 17
`37 C.F.R. § 42.101 ..................................................................................................... 3
`37 C.F.R. § 42.103 ..................................................................................................... 1
`37 C.F.R. § 42.104 ..................................................................................................... 3
`37 C.F.R. § 42.104(a) ................................................................................................. 3
`37 C.F.R. § 42.104(b) ................................................................................................ 3
`37 C.F.R. § 42.104(b)(3) .......................................................................................... 17
`37 C.F.R. § 42.106(a) ................................................................................................. 1
`
`Other Authorities
`MPEP § 716.03 ........................................................................................................ 52
`MPEP § 716.03(b) .................................................................................................... 52
`
`
`
`
`
`v 
`
`

`
`LISTING OF EXHIBITS
`
`Exhibit
`MYL 1001
`
`MYL 1004
`
`MYL 1005
`
`MYL 1006
`
`MYL 1002
`MYL 1003
`
`Description
`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)
`MYL 1011 March 4, 2013 Office Action (excerpt from prosecution history of
`’438 patent)
`June 4, 2013 Response (excerpt from prosecution history of ’438
`patent)
`
`MYL 1007
`
`MYL 1008
`
`MYL 1009
`
`MYL 1010
`
`MYL 1012
`
`vi 
`
`

`
`Exhibit
`MYL 1013
`
`MYL 1014
`
`MYL 1015
`
`MYL 1016
`
`MYL 1017
`MYL 1018
`MYL 1019
`
`MYL 1020
`
`MYL 1021
`
`MYL 1022
`
`MYL 1023
`
`MYL 1024
`
`MYL 1025
`
`Description
`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
`MYL 1026
`
`MYL 1027
`
`MYL 1028
`
`MYL 1029
`
`MYL 1030
`
`MYL 1031
`
`MYL 1032
`MYL 1033
`
`MYL 1034
`
`MYL 1035
`MYL 1036
`
`MYL 1037
`MYL 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
`MYL 1039
`
`MYL 1040
`
`MYL 1041
`
`MYL 1042
`MYL 1043
`MYL 1044
`MYL 1045
`
`MYL 1046
`
`MYL 1047
`
`MYL 1048
`
`MYL 1049
`
`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).
`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
`MYL 1050
`
`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).
`MYL 1051 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
`MYL 1052
`MYL 1053 Merck & Co. v. Teva Pharms. USA, Inc., 395 F.3d 1364 (Fed. Cir.
`2005).
`MYL 1054 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).
`
`MYL 1055
`
`MYL 1056
`MYL 1057
`
`MYL 1058-
`MYL 1063
`MYL 1064
`MYL 1065
`MYL 1066
`
`MYL 1067
`MYL 1068
`
`MYL 1069
`
`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
`MYL 1070
`
`Description
`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)
`MYL 1074 May 9, 2014 IDS (excerpt from prosecution history of ’438
`patent)
`MYL 1075 May 9, 2014 IDS (excerpt from prosecution history of ’438
`patent)
`MYL 1076 May 30, 2014 IDS (excerpt from prosecution history of ’438
`patent)
`MYL 1077 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)
`
`
`MYL 1078
`
`MYL 1079
`
`MYL 1080
`
`MYL 1071
`
`MYL 1072
`
`MYL 1073
`
`
`
`xi 
`
`

`
`Abbreviation
`ACTH
`AR
`CRPC
`mCRPC
`CYP17
`DHT
`IDS
`LH
`NDA
`POSA
`PSA
`RCE
`
`TABLE OF ABBREVIATIONS
`
`Definition
`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
`Mylan Pharmaceuticals Inc. (“Petitioner”) petitions for Inter Partes Review
`
`of claims 1-20 of U.S. Patent No. 8,822,438 to Auerbach et al. (“the ’438 patent”)
`
`(MYL 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 seeks 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
`Petitioner provides the following mandatory notices.
`
`A. Real Parties-In-Interest Under 37 C.F.R. § 42.8(b)(1)
`The real parties-in-interest for Petitioner are Mylan Pharmaceuticals Inc.,
`
`Mylan Inc., Mylan N.V., and Mylan LLC.
`
`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.);
`
`1 
`
`

`
` 
`
` 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.).
`
`C. Lead And Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3)
`
`Back-Up Counsel
`Lead Counsel
`Bryan D. Beel (pro hac vice to be filed)
`Brandon M. White (Reg. No. 52,354)
`Perkins Coie LLP
`Perkins Coie LLP
`1120 NW Couch Street
`700 Thirteenth Street, N.W.
`Tenth Floor
`Suite 600
`Portland, OR 97209
`Washington, D.C. 20005
`Telephone: (503) 727-2116
`Telephone: (202) 654-6206
`Facsimile: (503) 346-2116
`Facsimile: (202) 654-9681
`bbeel@perkinscoie.com
`bmwhite@perkinscoie.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. Petitioner consents to electronic service by e-mail at
`
`2 
`
`

`
` 
`
`the
`
`above
`
`listed
`
`email
`
`addresses
`
`of
`
`lead
`
`and
`
`back-up
`
`counsel
`
`(bmwhite@perkinscoie.com and bbeel@perkinscoie.com).
`
`III. GROUNDS FOR STANDING (37 C.F.R. §§ 42.101 and 42.104)
`As required by 37 C.F.R. § 42.104(a), Petitioner certifies that the ’438 patent
`
`is available for inter partes review and that the Petitioner is 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))
`Petitioner requests inter partes review and cancellation of claims 1–20.
`
`Petitioner’s full statement of the reasons for the relief requested is set forth below.
`
`Petitioner respectfully requests 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
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`U.S.C. § 103 over the ’213 patent in view of Gerber.
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`In support of these grounds for unpatentability, Petitioner submits the expert
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`declaration of Marc B. Garnick, M.D. (MYL Ex. 1002 (“Garnick Decl.”)) and the
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`1 Mylan’s asserted grounds of obviousness are the same as those instituted in
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`IPR2016-00286, filed by Amerigen Pharmaceuticals Limited.
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`declaration of economics expert Ivan T. Hofmann (MYL Ex. 1017 (“Hofmann
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`Decl.”)). Petitioner also relies on the other Exhibits set forth in the concurrently
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`filed Listing of Exhibits.
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`V. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`A petition for inter partes review must demonstrate “a reasonable likelihood
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`that the petitioner would prevail with respect to at least 1 of the claims challenged
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`in the petition.” 35 U.S.C. § 314(a). This Petition meets this threshold. As
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`explained below, there is a reasonable likelihood that Petitioner will prevail with
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`respect to at least one of the challenged claims.
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`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
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`administering therapeutically effective amounts of abiraterone acetate, a 17α-
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`hydroxylase/C17,20-lyase inhibitor (“CYP17 inhibitor”), in combination with
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`prednisone, a glucocorticoid. MYL Ex. 1002, Garnick Decl. ¶¶34–35. The prior
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`art taught the use of abiraterone acetate as an effective anti-cancer agent that
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`suppresses testosterone synthesis in prostate cancer patients. MYL Ex. 1002,
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`Garnick Decl. ¶¶36, 55, 66, 68. It was known as of the earliest priority date
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`claimed by the ’438 patent that testosterone promoted prostate cancer proliferation
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`and progress, so that testosterone synthesis must be suppressed to treat prostate
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`cancer.
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`However, it was also known that in using a CYP17 inhibitor to reduce
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`testosterone synthesis, the CYP17 inhibitor undesirably suppressed the production
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`of cortisol, a glucocorticoid, which is necessary for other biochemical cycles in the
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`body. In particular, reduced production of cortisol caused adverse effects,
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`including hypertension, hypokalemia (decrease in circulating potassium levels),
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`and fluid retention. To address the suppressed synthesis of cortisol, the prior art
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`taught that concomitant glucocorticoid replacement therapy might be necessary
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`when administering abiraterone to treat prostate cancer in a patient, and that this
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`was common practice in the treatment of prostate cancer with ketoconazole,
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`another CYP17 inhibitor. MYL Ex. 1002, Garnick Decl. ¶¶42, 44, 58.
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`The prior art also taught that abiraterone was a more effective CYP17
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`inhibitor than ketoconazole. For example, the prior art taught that abiraterone
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`acetate was more effective in decreasing testosterone levels in a mammal than
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`ketoconazole. MYL Ex. 1002, Garnick Decl. ¶¶46, 55. The prior art also taught
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`that the combination of ketoconazole and prednisone was a safe and effective
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`treatment for refractory metastatic prostate cancer. MYL Ex. 1002, Garnick Decl.
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`¶58.
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`One of skill in the art would have combined abiraterone acetate and
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`prednisone based on the teachings of O’Donnell in view of Gerber, and/or the ’213
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`patent in view of Gerber, for a safe and effective treatment of prostate cancer with
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`a reasonable expectation of success. The prior art taught that abiraterone acetate
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`was a more effective CYP17 inhibitor than ketoconazole and that the combination
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`of ketoconazole and prednisone was safe and effective to treat patients with
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`hormone refractory metastatic prostate cancer, which would have motivated the
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`combination. MYL Ex. 1002, Garnick Decl. ¶¶55–59. One of skill in the art may
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`also have been motivated by prednisone’s possible anti-cancer effects. Id. ¶ 89.
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`There are no secondary considerations of commercial success that overcome
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`this case of obviousness. The claims of the application that resulted in the ’438
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`patent were repeatedly rejected for obviousness until the Examiner allowed the
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`claims based on the purported “unexpected commercial success” of Zytiga, the
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`brand name under which abiraterone acetate is marketed in the United States by the
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`Assignee. In particular, the Examiner’s allowance of the claims based on
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`secondary considerations of commercial success of Zytiga was in error because
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`Applicants failed to show the necessary nexus between the claimed invention
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`(which is directed to a method of treating prostate cancer by administering
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`abiraterone acetate and prednisone) and any commercial success of the drug
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`Zytiga.
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`Level of Ordinary Skill in the Art
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`B.
`A person of ordinary skill in the art is presumed to be aware of all pertinent
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`art, thinks along conventional wisdom in the art, and is a person of ordinary
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`creativity. With respect to the ’438 patent, the scientific field relevant is oncology
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`or urology. MYL Ex. 1002, Garnick Decl. ¶18. A person of ordinary skill in the
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`art would be a physician specializing in urology, endocrinology, or oncology, or a
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`person holding a Ph.D. in pharmacology, biochemistry or a related discipline, such
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`as pharmaceutical science. MYL Ex. 1002, Garnick Decl. ¶18. Additional
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`experience could substitute for the advanced degree. MYL Ex. 1002, Garnick
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`Decl. ¶18. To the extent necessary, one of skill in the art may collaborate with one
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`or more other persons of skill in the art for one or more aspects with which the
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`other person may have expertise, experience and/or knowledge that was obtained
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`through his or her education, industrial or academic experiences. MYL Ex. 1002,
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`Garnick Decl. ¶19. For example, one of skill may consult with an endocrinologist,
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`oncologist, or medical biochemist and thus may rely on the opinions of such
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`specialists in evaluating the claims. MYL Ex. 1002, Garnick Decl. ¶20.
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`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
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`radiotherapy, a primary course of treatment for patients diagnosed with organ-
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`confined prostate cancer, as being highly invasive and ineffective on metastasized
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`prostate cancer. MYL Ex. 1001, col. 1, ll. 25–32. In addition, the specification
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`states that these localized treatments are not effective on prostate cancer after it has
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`metastasized and that, moreover, a large percent of individuals who receive such
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`localized treatments will suffer from “recurring cancer.” Id. at ll. 28–33. The
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`specification states that another treatment option for prostate cancer, hormone
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`therapy, is less invasive than surgery and has fewer side effects. Id. at ll. 43–44,
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`51–53. However, the specification notes that hormone therapy is not equally
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`effective in all patients thus treated, and some patients suffer from relapsing or
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`recurring cancer after hormone therapy. Id. at ll. 57-64.
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`The “Summary of the Invention” section of the ’438 patent describes various
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`embodiments of the invention as being directed to methods and compositions of
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`treating a refractory cancer in a patient, involving administering an effective
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`amount of a CYP17 inhibitor and an effective amount of another anticancer agent
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`such as mitoxantrone, paclitaxel, docetaxel, leuprolide, goserelin, triptorelin,
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`seocalcitol, bicalutamide, flutamide, or a steroid including prednisone or
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`dexamethasone. MYL Ex. 1001, col. 2, l. 9 – col. 3, l. 20.
`
`The “Definitions” section defines “17α-hydroxylase/C17,20-lyase inhibitor”
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`as an inhibitor of the enzyme “17α-hydroxylase/C17,20-lyase” (an enzyme
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`involved in testosterone synthesis). MYL Ex. 1001, col. 3, l. 66 – col. 4, l. 7. The
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`terms “treat,” “treating” and “treatment” are defined as “includ[ing] the
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`eradication, removal, modification, management or control of a tumor or primary,
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`regional, or metastatic cancer cells or tissue and the minimization or delay of the
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`spread of cancer.” MYL Ex. 1001, col. 3, ll. 46–50. The term “anti-cancer agent”
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`is defined as “any therapeutic agent that directly or indirectly kills cancer cells or
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`directly or indirectly prohibits stops or reduces the proliferation of cancer cells.”
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`MYL Ex. 1001, col. 4, ll. 8–16. The term “refractory cancer” is defined as “cancer
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`that is not responding to an anti-cancer treatment or cancer that is not responding
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`sufficiently to an anti-cancer treatment.” MYL Ex. 1001, col. 4, ll. 23–27.
`
`The “Detailed Description of the Invention” section refers to U.S. Patent No.
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`5,604,213 (MYL Ex. 1005) for its disclosure of CYP17 inhibitors being “shown to
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`be useful in the treatment of cancer, specifically hormone-dependent disorders
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`such as, androgen-dependent and estrogen-dependent disorders like prostate cancer
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`and breast cancer.” MYL Ex. 1001, col. 5, ll. 23–29. The specification provides a
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`list of various CYP17 inhibitors including abiraterone (17-(3-pyridyl)-androsta-
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`5,16-diene-3β-ol). MYL Ex. 1001, col. 5, ll. 30–40.
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`According to the specification, the CYP17 inhibitors may also be
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`administered or combined with steroids, such as corticosteroids or glucocorticoids
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`including hydrocortisone, prednisone, or dexamethasone, in the same or different
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`compositions. MYL Ex. 1001, col. 10, ll. 15–21. A single-unit solid oral dosage
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`form may contain about 50 mg to about 300 mg of abiraterone acetate and about
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`0.5 to 3 mg of a steroid, e.g., glucocorticoid, optionally with additional excipients.
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`MYL Ex. 1001, col. 10, ll. 42–50. Suitable daily dosages of CYP17 inhibitors
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`according to