IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_____________
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`ARGENTUM PHARMACEUTICALS LLC,
`
`Petitioner
`
`v.
`
`JANSSEN ONCOLOGY, INC.,
`
`
`
`
`
`
`
`
`
`
`
`Patent Owner
`
`
`U.S. Patent No. 8,822,438 to Auerbach et al. Issue Date: September 2, 2014
`Title: Methods and Compositions for Treating Cancer
`
`_____________
`
`Inter Partes Review No. IPR2016-01317
`
`_____________
`
`PETITION FOR INTER PARTES REVIEW
`
`35 U.S.C. §§ 311-319
`
`
`
`
`
`
`
`
`
`
`

`

`TABLE OF CONTENTS
`LISTING OF EXHIBITS PURSUANT TO 37 C.F.R. § 42.63(e) ........................ iii 
`TABLE OF ABBREVIATIONS .............................................................................. x 
`I. 
`INTRODUCTION ......................................................................................... 1 
`II.  MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)) .................................... 1 
`A.
`Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(1) .......................... 1 
` 
`Related Matters Under 37 C.F.R. § 42.8(b)(2) ..................................... 1 
`B.
` 
`Lead And Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3) ................. 2 
`C.
` 
`D.
`Service Information Under 37 C.F.R. § 42.8(b)(4) .............................. 3 
` 
`Service on Patent Owner Under 37 C.F.R. § 42.106(a) and 42.105(a) 3 
`E.
` 
`III.  GROUNDS FOR STANDING (37 C.F.R. §§ 42.101 and 42.104) ................ 3 
`IV.  PAYMENT OF FEES (37 C.F.R. § 42.103) .................................................. 3 
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`V. 
`REASONS THEREFOR (37 C.F.R. § 42.22(a)) ........................................... 3 
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b)) ................. 4 
`VI. 
`INTRODUCTION AND SUMMARY OF ARGUMENT ............................ 5 
`VII. 
`VIII.  LEVEL OF ORDINARY SKILL IN THE ART ............................................ 8 
`IX.  U.S. PATENT NO. 8,822,438 AND ITS FILE HISTORY ........................... 8 
`A.
`Specification of the ‘438 Patent ........................................................... 8 
` 
`File History of the ‘438 Patent ........................................................... 11 
`B.
` 
`CLAIM CONSTRUCTION (37 C.F.R. §§ 42.100(b), 42.104(b)(3)) .......... 18 
`X. 
`XI.  SCOPE AND CONTENT OF THE PRIOR ART ....................................... 19 
`  Overview ............................................................................................ 19 
`A.
`Background of Prostate Cancer and Its Treatment ............................. 23 
`B.
` 
`Prior Art References ........................................................................... 28 
`C.
` 
`1. 
`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 ......................... 28 
`In 1990, Gerber Disclosed the Use of Ketoconazole with Prednisone,
`a glucocorticoid, in Patients with Hormone Refractory Metastatic
`Prostate Cancer ................................................................................. 32 
`
`2. 
`
`
`
`i
`
`

`

`3. 
`
`In 1997, the ‘213 Patent Disclosed Abiraterone Acetate, and Its
`Superiority over Ketoconazole in the Treatment of Prostate Cancer34 
`XII.  XII. EXPLANATION OF GROUNDS FOR UNPATENTABILITY ........ 36 
`Claim 1 ............................................................................................... 36 
`A.
` 
`Claims 2 and 3 ................................................................................... 41 
`B.
` 
`Claim 4 ............................................................................................... 41 
`C.
` 
`D.
`Claim 5 ............................................................................................... 42 
` 
`Claims 6-9 .......................................................................................... 43 
`E.
` 
`Claim 10 ............................................................................................. 44 
`F.
` 
`G.
`Claim 11 ............................................................................................. 45 
` 
`Claims 12-16 ...................................................................................... 45 
`H.
` 
`Claim 17 ............................................................................................. 47 
`I.
` 
`J.
`Claim 18 ............................................................................................. 47 
` 
`K.
`Claim 19 ............................................................................................. 48 
` 
`Claim 20 ............................................................................................. 48 
`L.
` 
`XIII.  SECONDARY CONSIDERATIONS DO NOT INDICATE THAT THE
`CLAIMS OF THE ‘438 PATENT ARE NON-OBVIOUS ......................... 48 
`  Applicants Did Not Offer Relevant Evidence of Commercial Success
`A.
`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. ........................................................ 49 
`  One of Skill Would Not Anticipate Unexpected Benefits from the
`B.
`Claimed Invention and Applicants Did Not Offer Any Evidence of Relevant
`Unexpected Results ...................................................................................... 52 
`The ‘438 Patent Satisfied No Long-Felt But Unmet Need ................. 57 
`C.
` 
`D.
`The '213 is a Blocking Patent that Limits the Applicability of
` 
`Commercial Success ..................................................................................... 58 
`Copying By Generic Drug Makers Is Irrelevant ................................ 59 
`E.
` 
`XIII.  CONCLUSION ............................................................................................ 60 
`
`ii
`
`
`
`
`
`

`

`LISTING OF EXHIBITS PURSUANT TO 37 C.F.R. § 42.63(e)
`
`
`
`Exhibit
`
`Description
`
`1001
`
`U.S. Patent No. 8,822,438, Auerbach and Belldegrum, “Methods and
`Compositions for Treating Cancer” (“the ‘438 patent”)
`
`1002 Declaration of Dr. Scott Serels, MD (“Serels Decl.”)
`
`1003
`
`1004
`
`O’Donnell, A. et al., “Hormonal impact of the 17α-hydroxylase/C17-
`20-lyase inhibitor abiraterone acetate (CB7630) in patients with
`prostate cancer,” British Journal of 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,” The Journal of Urology, 144(5):1177-9 (1990)
`(“Gerber”)
`
`1005
`
`U.S. Patent No. 5,604,213, Barrie S.E. et al., “17-Substituted
`Steroids Useful In Cancer Treatment” ("the ‘213 patent")
`
`1006
`
`1007
`
`1008
`
`1009
`
`Tannock et al., “Chemotherapy with mitoxantrone plus prednisone or
`prednisone alone for symptomatic hormone-resistant prostate cancer: a
`Canadian randomized trial with palliative end points,” The Journal of
`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 et al., “Abiraterone in metastatic prostate cancer without
`previous chemotherapy,” The New England Journal of Medicine,
`368:138-148 (2012).
`
`
`
`iii
`
`

`

`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`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)
`
`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)
`
`1017 Declaration of Dr. DeForest McDuff, PhD (“McDuff Declaration”)
`
`1018
`
`1019
`
`1020
`
`2011 Zytiga® Approval Prescribing Information
`
`2015 Zytiga® Prescribing Information, Co-administration Brochure
`
`Harris et al., “Low dose Ketoconazole with replacement doses of
`hydrocortisone in patients with progressive androgen independent
`prostate cancer,” The Journal of Urology, volume 168:542-545
`(August 2002)
`
`1021
`
`William Oh, “Secondary hormonal therapies in the treatment of
`prostate cancer,” Urology, volume 60:87-93 (Supplement 3A)
`(September 2002)
`1022 Tannock, I. et al., “Docetaxel plus Prednisone or Mitoxantrone plus
`Prednisone for Advanced Prostate Cancer,” N. Eng. J. Med.,
`
`
`
`iv
`
`

`

`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 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), p. 549.
`
`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-
`
`Jubelirer, S.J., et al., “High dose ketoconazole for the treatment of
`hormone refractory metastatic prostate carcinoma,” J. Urol.,
`142(1):89-901 (1989)
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`U.S. Patent 5,688,977, Sisti, N.J. et al., “Method for Docetaxel
`Synthesis”
`
`1030
`
`1031
`
`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,” Journal of Clin. Oncology, 7:590-7 (1989)
`
`1032 Taxotere® Prescribing Information (2004)
`
`1033 Scher, H.I. et al., “Increased survival with Enzalutamide in Prostate
`
`
`
`v
`
`

`

`Cancer after Chemotherapy,” New Eng. J. Med., 367:1187-97 (2012)
`
`1034
`
`de Bono, J.S. et al., “Abiraterone and Increased Survival in
`Metastatic Prostate Cancer,” New Engl. J. Med., 364:1995-2005
`(2011)
`
`1035 Orange Book listing for Zytiga®
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`Initial Application (excerpt from prosecution history of ‘438 patent)
`
`November 25, 2011 Office Action (excerpt from prosecution history
`of ‘438 patent)
`
`December 21, 2011 Response (excerpt from prosecution history of
`‘438 patent)
`
`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-careand-
`treatment-recommendations-patients/treatment-metastatic-
`castrationresistant-prostate-cancer (accessed 7/24/2015).
`
`1041
`
`Cancer.org (ACS), “What are the key statistics about prostate
`cancer?” http://www.cancer.org/cancer/prostatecancer/detailed
`guide/prostatecancerkeystatistics (accessed 8/20/2015).
`
`1042 Cowen & Company, “Biotechnology Quarterly,” 7/2/2012.
`
`1043 Cowen & Company, “Quick Take – Johnson & Johnson,”
`
`1044
`
`Credit Suisse, “Prostate Cancer – Implications of Zytiga’s Pre-
`Chemo Approval,” 12/11/2012.
`1045 FDA News Release, “FDA expands Zytiga’s use for late-stage prostate
`cancer,” 12/10/2012,
`
`
`
`vi
`
`

`

`http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/u
`cm331492.htm.
`
`1046
`
`1047
`
`FDA Website, Drugs@FDA – Zytiga,
`http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fu
`seaction=Search.DrugDetails (accessed 7/23/2015).
`
`FDA Website, Orange Book, Zytiga (NDA 202379),
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm
`?Appl_No=202379&Product_No=001&table1=OB_Rx (accessed
`7/24/2015).
`
`1048
`
`Galderma Laboratories, L.P. et al. v. Tolmar, Inc., 737 F.3d 731, 740–
`41 (Fed. Cir. 2013).
`
`1049
`
`1050
`
`1051
`
`1052
`
`Jevtana Website, Dosing and Administration,
`http://www.jevtana.com/hcp/dosing/default.aspx (accessed
`8/20/2015).
`
`Kirby, M., C. Hirst, and E.D. Crawford (2011), “Characterising the
`Castration-Resistant Prostate Cancer Population: A Systematic
`Review,” International Journal of Clinical Practice 65(11): 1180-
`1192.
`
`Mayo Clinic Website, Prostate cancer,
`http://www.mayoclinic.org/diseasesconditions/prostate-
`cancer/basics/definition/con-20029597?p=1 (accessed 7/24/2015).
`
`Medivation Press Release, “U.S. FDA Approves New Indication for the
`Use of XTANDI® (Enzalutamide) Capsules for Patients With Metastatic
`Castration-Resistant Prostate Cancer,” 9/10/2014,
`http://investors.medivation.com/releasedetail.cfm?ReleaseID=870267.
`
`1053
`
`Merck & Co., Inc. v. Teva Pharmaceuticals USA, Inc., 395 F.3d 1364,
`1376–77 (Fed. Cir. 2005).
`
`1054 Murphy, William J., John L. Orcutt, and Paul C. Remus (2012),
`
`
`
`vii
`
`

`

`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_p
`roducts_by_global_sales (accessed 9/14/2015).
`
`RBC Capital Markets (via Barron’s Website), “Xtandi Beats
`Casodex, Set to Top Zytiga,” 4/3/2015,
`http://online.barrons.com/articles/xtandi-beats-casodexset-to-top-
`zytiga-1428075331 (accessed 7/24/2015).
`
`Syntex (U.S.A.) LLC and Allergan v. Apotex, Inc. et al., 407 F.3d
`1371, 1383 (Fed. Cir. 2005).
`
`UBS Investment Research, “Johnson & Johnson – Zytiga Label
`Extended,” 12/10/2012.
`
`UBS Research, “Medivation – A Look at the Growth and Share in
`Prostate Cancer,” 2/3/2014.
`
`Wedbush Securities, Inc., “Medivation: Zytiga Market Share Decline
`Accelerates From Last Quarter,” 7/14/2015.
`
`1055
`
`1056
`
`1057
`
`1058
`
`1059
`
`1060
`
`1061 Wells Fargo Securities, LLC., “Johnson & Johnson,” 6/29/2015.
`
`1062
`
`1063
`
`William Blair, “Biotechnology – Zytiga Fourth-Quarter Sales Imply
`Xtandi Strength,” 1/22/2013.
`
`William Blair, “Medivation, Inc. – Looking into Recent Weaknesses,”
`7/15/2015.
`
`1064 Zytiga Brochure, Putting Prednisone in Perspective, 3/2015.
`
`1065 Zytiga Label, 5/20/2015.
`
`1066 Zytiga Website, How Zytiga® (abiraterone acetate) Works,
`
`
`
`viii
`
`

`

`https://www.zytiga.com/print/about-zytiga/how-zytiga-works
`(accessed 7/23/2015).
`
`1067
`
`IMS Health Data 2012-2015 for Zytiga®, Xtandi® and Jevtana®
`
`1068 Reserved
`
`1069 Reserved
`
`1070 Reserved
`
`1071 Reserved
`
`1072 Reserved
`
`1073 Declaration of Devalingam Mahalingam, M.D., Ph.D.
`
`1074 Curriculum Vitae of Devalingam Mahalingam, M.D., Ph.D.
`
`
`
`ix
`
`

`

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

`

`CHALLENGED CLAIMS OF U.S. PATENT NO. 8,822,438
`
`
`1.
`
`A method for the treatment of a prostate cancer in a human
`
`comprising administering to said human a therapeutically effective amount of
`
`abiraterone acetate or a pharmaceutically acceptable salt
`
`thereof and a
`
`therapeutically effective amount of prednisone.
`
`
`2.
`
`The method of claim 1, wherein the therapeutically effective amount
`
`of abiraterone acetate or pharmaceutically acceptable salt thereof is from about 50
`
`mg/day to about 2000 mg/day.
`
`
`3.
`
`The method of claim 2, wherein the therapeutically effective amount
`
`of abiraterone acetate or pharmaceutically acceptable salt thereof is from about 500
`
`mg/day to about 1500 mg/day.
`
`
`4.
`
`The method of claim 3, wherein the therapeutically effective amount
`
`of abiraterone acetate or pharmaceutically acceptable salt thereof is about 1000
`
`mg/day.
`
`
`5.
`
`The method of claim 1, wherein the therapeutically effective amount
`
`of the abiraterone acetate or a pharmaceutically acceptable salt thereof is
`
`administered in at least one dosage form comprising about 250 mg of abiraterone
`
`acetate or a pharmaceutically acceptable salt thereof.
`
`
`6.
`
`The method of claim 1, wherein therapeutically effective amount of
`
`prednisone is from about 0.01 mg/day to about 500 mg/day.
`
`
`
`xi
`
`

`

`
`7.
`
`The method of claim 6, wherein therapeutically effective amount of
`
`prednisone is from about 10 mg/day to about 250 mg/day.
`
`
`8.
`
`The method of claim 7, wherein therapeutically effective amount of
`
`prednisone is about 10 mg/day.
`
`
`9.
`
`The method of claim 1, wherein the therapeutically effective amount
`
`of prednisone is administered in at least one dosage form comprising about 5 mg of
`
`prednisone.
`
` The method of claim 1, comprising administering to said human about
`10.
`
`500 mg/day to about 1500 mg/day of abiraterone acetate or a pharmaceutically
`
`acceptable salt thereof and about 0.01 mg/day to about 500 mg/day of prednisone.
`
` The method of claim 10, comprising administering to said human
`11.
`
`about 1000 mg/day of abiraterone acetate or a pharmaceutically acceptable salt
`
`thereof and about 10 mg/day of prednisone.
`
` The method of claim 1, wherein said prostate cancer is refractory
`12.
`
`prostate cancer.
`
` The method of claim 2, wherein refractory prostate cancer is not
`13.
`
`responding to at least one anti-cancer agent.
`
` The method of claim 13, wherein at least one anti-cancer agent
`14.
`
`comprises a hormonal ablation agent, an anti-androgen agent, or anti-neoplastic
`
`agent.
`
`
`
`xii
`
`

`

`
`
` The method of claim 14, wherein the hormonal ablation agent 15.
`
`comprises deslorelin, leuprolide, goserelin, or triptorelin.
`
` The method of claim 14, wherein the anti-androgen agent comprises
`16.
`
`bicalutamide, flutamide, or nilutamide.
`
` The method of claim 14, wherein the antineoplastic agent comprises
`17.
`
`docetaxel.
`
` The method of claim 12, comprising administering to said human
`18.
`
`about 500 mg/day
`
`to about 1500 mg/day of abiraterone acetate or a
`
`pharmaceutically acceptable salt thereof and about 0.01 mg/day to about 500
`
`mg/day of prednisone.
`
` The method of claim 18, comprising administering to said human
`19.
`
`about 1000 mg/day of abiraterone acetate or a pharmaceutically acceptable salt
`
`thereof and about 10 mg/day of prednisone.
`
` The method of claim 17, comprising administering to said human
`20.
`
`about 1000 mg/day of abiraterone acetate or a pharmaceutically acceptable salt
`
`thereof and about 10 mg/day of prednisone.
`
`
`
`
`
`
`
`
`
`
`
`xiii
`
`

`

`
`
`I.
`
`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
`
`INTRODUCTION
`Argentum Pharmaceuticals LLC ("Petitioner") requests that the Board
`
`institute inter partes review of and cancel 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”). Inter partes review of claims 1-20 of the ‘438
`
`patent was instituted in IPR2016-00286 on May 31, 2016, based on a petition filed
`
`by Amerigen Pharmaceuticals, Ltd (“Amerigen IPR”). Petitioner hereby files its
`
`own Petition on the same grounds as those instituted in the Amerigen IPR and
`
`concurrently seeks to join the instituted Amerigen IPR proceeding (IPR2016-
`
`00286). A motion for joinder with IPR2016-00286 is being filed concurrently with
`
`this Petition.
`
`II. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1))
`
`
`A.
`
` Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(1)
`The real parties in interest for this Petition are: Argentum Pharmaceuticals
`
`LLC; Intelligent Pharma Research LLC; APS GP LLC; and APS GP Investors
`
`LLC.
`
`B.
`
` Related Matters Under 37 C.F.R. § 42.8(b)(2)
`To the best of Petitioner’s knowledge, the following litigations or other
`
`related matters related to the ‘438 patent that would affect, or be affected by, a
`
`decision in this proceeding are pending:
`
`BTG International Limited et al. v. Glenmark Pharmaceuticals Inc., USA et
`
`
`
`-1-
`
`

`

`
`
`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
`
`al., 2-16-cv-03743 (District of New Jersey), filed June 24, 2016;
`
`BTG International Limited et al. v. Amerigen Pharmaceuticals, Inc. et al., 2-
`
`16-cv-02449 (District of New Jersey), filed May 2, 2016;
`
`Amerigen Pharmaceuticals Limited v. Janssen Oncology, Inc., IPR2016-
`
`00286, filed December 4, 2015, instituted on May 31, 2016;
`
`Janssen Biotech, Inc. et al. v. Mylan Pharmaceuticals Inc. et al., 1-15-cv-
`
`00130 (Northern District of West Virginia), filed August 4, 2015;
`
`Janssen Biotech, Inc. et al. v. Amneal Pharmaceuticals LLC et al., 1-15-cv-
`
`00679 (District of Delaware), filed August 3, 2015;
`
`BTG International Limited et al. v. Actavis Laboratories FL, Inc. et al., 9-
`
`15-cv-81076-DMM (Southern District of Florida), filed August 3, 2015; and
`
`BTG International Limited et al. v. Actavis Laboratories FL, Inc., et al., 2-
`
`15-cv-05909-KM-JBC (District of New Jersey), filed July 31, 2015.
`
`C.
`
` Lead And Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3)
`
`Lead Counsel
`
`Back-Up Counsel
`
`Teresa Stanek Rea (Reg. No. 30,427) 
`CROWELL & MORING LLP
`Intellectual Property Group
`1001 Pennsylvania Avenue, N.W.
`Washington, DC 20004-2595
`Telephone No.: (202) 624-2620
`Facsimile No.: (202) 628-5116
`TRea@Crowell.com
`
`Shannon M. Lentz (Reg. No. 65,382) 
`CROWELL & MORING LLP
`Intellectual Property Group
`1001 Pennsylvania Ave, N.W.
`Washington, DC 20004-2595
`Telephone No.: (202)624-2897
`Facsimile No.: (202) 628-5116
`SLentz@Crowell.com
`
`Filed concurrently herewith is a Power of Attorney pursuant to 37 C.F.R. §
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`42.10(b).
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`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
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`
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`D.
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`Service Information Under 37 C.F.R. § 42.8(b)(4)
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`Please direct all correspondence regarding this Petition to lead counsel at the
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`above address. Petitioner consents to service by email at: TRea@Crowell.com
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`and SLentz@crowell.com.
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`E.
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`Service on Patent Owner Under 37 C.F.R. § 42.106(a) and 42.105(a)
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`This petition is being served by FedEx® on Johnson & Johnson, owners of
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`the ‘438 Patent, at the address of record according to the USPTO PAIR database:
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`Johnson & Johnson, One Johnson & Johnson Plaza, New Brunswick, NJ 08933-
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`7003.
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`III. GROUNDS FOR STANDING (37 C.F.R. §§ 42.101 and 42.104)
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`Petitioner hereby certifies that the patent for which review is sought is
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`available for inter partes review, and that the petitioner is not barred or estopped
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`from requesting an inter partes review challenging the patent claims on the
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`Grounds identified in the petition.
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`IV. PAYMENT OF FEES (37 C.F.R. § 42.103)
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`The Office is authorized to charge the required fee, and any fee deficiencies
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`and credit overpayments to Deposit Acct. No. 05-1323, Customer ID No. 23911.
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`V.
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`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. § 42.22(a))
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`Petitioner requests inter partes review and cancellation of claims 1-20.
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`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
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`Petitioner’s full statement of the reasons for the relief requested is set forth in detail
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`in Sections XI-XIII below.
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`VI.
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`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b))
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`Petitioner respectfully requests inter partes review and cancellation of
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`claims 1-20 of the ‘438 Patent based on the grounds set forth in the table below:1
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`
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`Ground
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`1
`2
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`Challenged
`Claims
`1-20
`1-4 and 6-11
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`Statutory
`Basis
`§ 103
`§ 103
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`References
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`O’Donnell in view of Gerber
`‘213 patent in view of
`Gerber
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`Sections XI-XIII below explain how the ‘438 patent claims are unpatentable
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`on the grounds listed above. See Graham v. John Deere Co., 383 U.S. 1, 17-18
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`(1966) (obviousness analysis evaluates the level of ordinary skill in the art; the
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`scope and content of the prior art; whether any differences between the prior art
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`and the claims would have been obvious to the skilled artisan; and secondary
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`considerations).
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`In support of these grounds for unpatentability, Petitioner submits the expert
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`declaration of Dr. Scott Serels, M.D., (Ex. 1002 (“Serels Declaration”)), as well as
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`1 The grounds listed herein are consistent with those on which the Board instituted
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`IPR of the challenged claims. Amerigen Pharmaceuticals Ltd. v. Janssen
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`Oncology, Inc., IPR2016-00286, Institution Decision, Paper 14 at page 19.
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`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
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`the declaration of Dr. Devalingam Mahalingam (Ex. 1073 (“Mahalingam
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`Declaration”)) to discuss the relevant field and art in general, and the factual and
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`opinion bases underlying Petitioner’s Grounds 1 and 2 for the Graham factors
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`other than commercial success.2 Petitioner also submits the expert declaration of
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`economics expert Dr. DeForest McDuff, PhD (Ex. 1017 (“McDuff Declaration”))
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`on the secondary considerations of the Graham factors.
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`Petitioner also relies on the other Exhibits set forth in the concurrently filed
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`Listing of Exhibits.
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`VII. INTRODUCTION AND SUMMARY OF ARGUMENT
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`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 17 α-
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`hydroxylase/C17,20-lyase inhibitor (“CYP17 inhibitor”), in combination with
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`prednisone, a glucocorticoid. The prior art taught use of abiraterone acetate as an
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`effective anti-cancer agent which suppresses testosterone synthesis in prostate
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`2 Petitioner is willing to work with Amerigen and rely solely on Dr. Serels’
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`declaration and testimony and will withdraw the expert declaration of Dr.
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`Mahalingam upon agreement of Amerigen to jointly rely on Dr. Serels. However,
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`in the event that an agreement is not reached, Petitioner is prepared to rely on the
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`declaration and testimony of Dr. Mahalingam. This position is more explicitly
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`explained in the concurrently filed Motion for Joinder.
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`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
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`cancer patients. Ex. 1002, Serels Decl. ¶¶ 26, 45, 56, 58, Ex. 1073; Mahalingam
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`Decl. ¶¶ 26, 45, 56, 58. It was known that testosterone promoted prostate cancer
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`proliferation and progress so that to treat prostate cancer, testosterone synthesis
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`must be suppressed.
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`However, it was known that in using a CYP17 inhibitor to reduce
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`testosterone synthesis, the CYP17 inhibitor also undesirably suppressed the
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`production of cortisol, a glucocorticoid, which is necessary for other biochemical
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`cycles in the body and its reduced production caused adverse effects, including
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`hypertension, hypokalemia (decrease in circulating potassium levels), and fluid
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`retention. To address the suppressed synthesis of cortisol, the prior art also taught
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`that concomitant glucocorticoid replacement therapy might be necessary when
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`administering abiraterone to treat prostate cancer in a patient, and that this was
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`common practice in the treatment of prostate cancer with ketoconazole, another
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`CYP17 inhibitor. Ex. 1002, Serels Decl. ¶¶ 32, 34, 48, Ex. 1073; Mahalingam
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`Decl. ¶¶ 32, 34, 48.
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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. Ex. 1002, Serels Decl. ¶¶36, 45, Ex. 1073; Mahalingam Decl. ¶¶ 36,
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`45. The prior art also taught that the combination of ketoconazole and prednisone
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`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
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`was a safe and effective treatment for refractory metastatic prostate cancer. Ex.
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`1002, Serels Decl. ¶48, Ex. 1073; Mahalingam Decl. ¶ 48.
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`One of skill in the art would have combined abiraterone acetate and
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`prednisone based on 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 a
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`reasonable expectation of success because the prior art taught abiraterone acetate
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`as a more effective CYP17 inhibitor than ketoconazole and the combination of
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`ketoconazole and prednisone as safe and effective to treat patients with hormone
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`refractory metastatic prostate cancer. Ex. 1002, Serels Decl. ¶¶45-49; Ex. 1073,
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`Mahalingam Decl. ¶¶ 45-49.
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`There are no secondary considerations of commercial success that overcome
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`obviousness. The claims of the application resulting in the ‘438 patent were
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`repeatedly rejected for obviousness until the Examiner allowed the claims based on
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`the purported “unexpected commercial success” of Zytiga®, the brand name under
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`which abiraterone acetate is marketed in the United States by the Assignee. In
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`particular, the Examiner's allowance of the claims based on secondary
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`considerations of commercial success of Zytiga® was in error because Applicants
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`failed to show the necessary nexus between the claimed invention (which is
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`directed to method of treating prostate cancer by administering abiraterone acetate
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`and prednisone) and any commercial success of the drug Zytiga®.
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`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
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`VIII. LEVEL OF ORDINARY SKILL IN THE ART
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`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. Ex. 1002, Serels Decl. ¶8; Ex. 1073, Mahalingam Decl. ¶ 8. A person
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`of ordinary skill in the art would be a physician specializing in urology or
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`oncology, or holding a Ph.D. in pharmacology, biochemistry or a related
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`discipline. Ex. 1002, Serels Decl. ¶8; Ex. 1073, Mahalingam Decl. ¶ 8. Additional
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`experience could substitute for the advanced degree. Ex. 1002, Serels Decl. ¶8; Ex.
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`1073, Mahalingam Decl. ¶ 8. To the extent necessary, one of skill in the art may
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`collaborate with one or more other persons of skill in the art for one or more
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`aspects with which the other person may have expertise, experience and/or
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`knowledge that was obtained through his or her education, industrial or academic
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`experiences. Ex. 1002, Serels Decl. ¶9; Ex. 1073, Mahalingam Decl. ¶ 9. For
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`example, one of skill may consult with an enzymologist and/or molecular biologist
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`and thus may rely on the opinions of such specialists in evaluating the claims. Ex.
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`1002, Serels Decl. ¶10; Ex. 1073, Mahalingam Decl. ¶ 10.
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`IX. U.S. PATENT NO. 8,822,438 AND ITS FILE HISTORY
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`A.
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`The “Background” section describes prostatectomy and radiotherapy, a
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`Specification of the ‘438 Patent
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`Petition for Inter Partes Review of U.S. Patent No. 8,822,438
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`primary course of treatment for patients diagnosed with organ-confined prostate
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`cancer, as being highly invasive and ineffective on metastasized prostate cancer. In
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`addition, the specification states that these localized treatments are not effective on
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`prostate cancer after it has metastasized; and that, moreover, a large percent of
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`individuals who receive such localized treatments will suffer from “recurring
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`cancer.” The specification states that another treatment option for prostate cancer,
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`hormone therapy, is less invasive than surgery and has fewer side effects.
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`However, the specification notes that hormone therapy is not equally effective in
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`all patients thus treated; and some patients suffer from relapsing or recurring
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`cancer after hormone therapy. Ex. 1001, Col. 1, ll. 25-64.
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`The “Summary of the Invention” section describes various embodiments of
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`the invention being directed to methods and compositions of treating a refractory
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`cancer in a patient, involving administration of an effective amount of a CYP17
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`inhibitor and an effective amount of another anticancer agent such as
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`mitoxantrone, paclitaxel, docetaxel, leuprolide, goserelin, triptorelin, seocalcitol,
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`bicalutamide, flutamide, or a steroid including prednisone or dexamethasone. Ex.
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`1001, Col. 2, l. 9 – col. 3, l. 20.
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`The “Definitions” section defines “17α-hydroxylase/C17,20-lyase inhibitor” as
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`an inhibitor of the enzyme “17α-hydroxylase/C17,20-lyase” (an enzyme