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CHALLENGED CLAIMS OF U.S. PATENT NO. 8,822,4381.A method for the treatment of a prostate cancer in a humancomprising administering to said human a therapeutically effective amount ofabiraterone acetate or a pharmaceutically acceptable salt thereof and atherapeutically effective amount of prednisone.2.The method of claim 1, wherein the therapeutically effective amountof abiraterone acetate or pharmaceutically acceptable salt thereof is from about 50mg/day to about 2000 mg/day.3.The method of claim 2, wherein the therapeutically effective amountof abiraterone acetate or pharmaceutically acceptable salt thereof is from about 500mg/day to about 1500 mg/day.4.The method of claim 3, wherein the therapeutically effective amountof abiraterone acetate or pharmaceutically acceptable salt thereof is about 1000mg/day.5.The method of claim 1, wherein the therapeutically effective amountof the abiraterone acetate or a pharmaceutically acceptable salt thereof isadministered in at least one dosage form comprising about 250 mg of abirateroneacetate or a pharmaceutically acceptable salt thereof.6.The method of claim 1, wherein therapeutically effective amount ofprednisone is from about 0.01 mg/day to about 500 mg/day.xi

7.The method of claim 6, wherein therapeutically effective amount ofprednisone is from about 10 mg/day to about 250 mg/day.8.The method of claim 7, wherein therapeutically effective amount ofprednisone is about 10 mg/day.9.The method of claim 1, wherein the therapeutically effective amountof prednisone is administered in at least one dosage form comprising about 5 mg ofprednisone.10.The method of claim 1, comprising administering to said human about500 mg/day to about 1500 mg/day of abiraterone acetate or a pharmaceuticallyacceptable salt thereof and about 0.01 mg/day to about 500 mg/day of prednisone.11.The method of claim 10, comprising administering to said humanabout 1000 mg/day of abiraterone acetate or a pharmaceutically acceptable saltthereof and about 10 mg/day of prednisone.12.The method of claim 1, wherein said prostate cancer is refractoryprostate cancer.13.The method of claim 2, wherein refractory prostate cancer is notresponding to at least one anti-cancer agent.14.The method of claim 13, wherein at least one anti-cancer agentcomprises a hormonal ablation agent, an anti-androgen agent, or anti-neoplasticagent.xii

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

Petition for Inter Partes Review of U.S. Patent No. 8,822,438I.INTRODUCTIONArgentum Pharmaceuticals LLC ("Petitioner") requests that the Boardinstitute 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 toJanssen Oncology, Inc. (“Janssen”). Inter partes review of claims 1-20 of the ‘438patent was instituted in IPR2016-00286 on May 31, 2016, based on a petition filedby Amerigen Pharmaceuticals, Ltd (“Amerigen IPR”). Petitioner hereby files itsown Petition on the same grounds as those instituted in the Amerigen IPR andconcurrently seeks to join the instituted Amerigen IPR proceeding (IPR201600286). A motion for joinder with IPR2016-00286 is being filed concurrently withthis 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 PharmaceuticalsLLC; Intelligent Pharma Research LLC; APS GP LLC; and APS GP InvestorsLLC.B.Related Matters Under 37 C.F.R. § 42.8(b)(2)To the best of Petitioner’s knowledge, the following litigations or otherrelated matters related to the ‘438 patent that would affect, or be affected by, adecision 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. 8,822,438al., 2-16-cv-03743 (District of New Jersey), filed June 24, 2016;BTG International Limited et al. v. Amerigen Pharmaceuticals, Inc. et al., 216-cv-02449 (District of New Jersey), filed May 2, 2016;Amerigen Pharmaceuticals Limited v. Janssen Oncology, Inc., IPR201600286, filed December 4, 2015, instituted on May 31, 2016;Janssen Biotech, Inc. et al. v. Mylan Pharmaceuticals Inc. et al., 1-15-cv00130 (Northern District of West Virginia), filed August 4, 2015;Janssen Biotech, Inc. et al. v. Amneal Pharmaceuticals LLC et al., 1-15-cv00679 (District of Delaware), filed August 3, 2015;BTG International Limited et al. v. Actavis Laboratories FL, Inc. et al., 915-cv-81076-DMM (Southern District of Florida), filed August 3, 2015; andBTG International Limited et al. v. Actavis Laboratories FL, Inc., et al., 215-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 CounselBack-Up CounselTeresa Stanek Rea (Reg. No. 30,427)CROWELL & MORING LLPIntellectual Property Group1001 Pennsylvania Avenue, N.W.Washington, DC 20004-2595Telephone No.: (202) 624-2620Facsimile No.: (202) 628-5116TRea@Crowell.comShannon M. Lentz (Reg. No. 65,382)CROWELL & MORING LLPIntellectual Property Group1001 Pennsylvania Ave, N.W.Washington, DC 20004-2595Telephone No.: (202)624-2897Facsimile No.: (202) 628-5116SLentz@Crowell.comFiled concurrently herewith is a Power of Attorney pursuant to 37 C.F.R. §-2-

Petition for Inter Partes Review of U.S. Patent No. 8,822,43842.10(b).D.Service Information Under 37 C.F.R. § 42.8(b)(4)Please direct all correspondence regarding this Petition to lead counsel at theabove address. Petitioner consents to service by email at: TRea@Crowell.comand SLentz@crowell.com.E.Service on Patent Owner Under 37 C.F.R. § 42.106(a) and 42.105(a)This petition is being served by FedEx on Johnson & Johnson, owners ofthe ‘438 Patent, at the address of record according to the USPTO PAIR database:Johnson & Johnson, One Johnson & Johnson Plaza, New Brunswick, NJ 089337003.III.GROUNDS FOR STANDING (37 C.F.R. §§ 42.101 and 42.104)Petitioner hereby certifies that the patent for which review is sought isavailable for inter partes review, and that the petitioner is not barred or estoppedfrom requesting an inter partes review challenging the patent claims on theGrounds identified in the petition.IV.PAYMENT OF FEES (37 C.F.R. § 42.103)The Office is authorized to charge the required fee, and any fee deficienciesand credit overpayments to Deposit Acct. No. 05-1323, Customer ID No. 23911.V.STATEMENT OF THE PRECISE RELIEF REQUESTED AND THEREASONS THEREFOR (37 C.F.R. § 42.22(a))Petitioner requests inter partes review and cancellation of claims 1-20.-3-

Petition for Inter Partes Review of U.S. Patent No. 8,822,438Petitioner’s full statement of the reasons for the relief requested is set forth in detailin Sections XI-XIII below.VI.IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b))Petitioner respectfully requests inter partes review and cancellation ofclaims 1-20 of the ‘438 Patent based on the grounds set forth in the table below:1Ground1ChallengedClaims1-20StatutoryBasis§ 10321-4 and 6-11§ 103ReferencesO’Donnell in view of Gerber‘213 patent in view ofGerberSections XI-XIII below explain how the ‘438 patent claims are unpatentableon the grounds listed above. See Graham v. John Deere Co., 383 U.S. 1, 17-18(1966) (obviousness analysis evaluates the level of ordinary skill in the art; thescope and content of the prior art; whether any differences between the prior artand the claims would have been obvious to the skilled artisan; and secondaryconsiderations).In support of these grounds for unpatentability, Petitioner submits the expertdeclaration of Dr. Scott Serels, M.D., (Ex. 1002 (“Serels Declaration”)), as well as1The grounds listed herein are consistent with those on which the Board institutedIPR of the challenged claims. Amerigen Pharmaceuticals Ltd. v. JanssenOncology, Inc., IPR2016-00286, Institution Decision, Paper 14 at page 19.-4-

Petition for Inter Partes Review of U.S. Patent No. 8,822,438the declaration of Dr. Devalingam Mahalingam (Ex. 1073 (“MahalingamDeclaration”)) to discuss the relevant field and art in general, and the factual andopinion bases underlying Petitioner’s Grounds 1 and 2 for the Graham factorsother than commercial success.2 Petitioner also submits the expert declaration ofeconomics expert Dr. DeForest McDuff, PhD (Ex. 1017 (“McDuff Declaration”))on the secondary considerations of the Graham factors.Petitioner also relies on the other Exhibits set forth in the concurrently filedListing of Exhibits.VII. INTRODUCTION AND SUMMARY OF ARGUMENTThe claims of the ‘438 patent are directed to treating prostate cancer byadministering therapeutically effective amounts of abiraterone acetate, a 17 αhydroxylase/C17,20-lyase inhibitor (“CYP17 inhibitor”), in combination withprednisone, a glucocorticoid. The prior art taught use of abiraterone acetate as aneffective anti-cancer agent which suppresses testosterone synthesis in prostate2Petitioner is willing to work with Amerigen and rely solely on Dr. Serels’declaration and testimony and will withdraw the expert declaration of Dr.Mahalingam upon agreement of Amerigen to jointly rely on Dr. Serels. However,in the event that an agreement is not reached, Petitioner is prepared to rely on thedeclaration and testimony of Dr. Mahalingam. This position is more explicitlyexplained in the concurrently filed Motion for Joinder.-5-

Petition for Inter Partes Review of U.S. Patent No. 8,822,438cancer patients. Ex. 1002, Serels Decl. ¶¶ 26, 45, 56, 58, Ex. 1073; MahalingamDecl. ¶¶ 26, 45, 56, 58. It was known that testosterone promoted prostate cancerproliferation and progress so that to treat prostate cancer, testosterone synthesismust be suppressed.However, it was known that in using a CYP17 inhibitor to reducetestosterone synthesis, the CYP17 inhibitor also undesirably suppressed theproduction of cortisol, a glucocorticoid, which is necessary for other biochemicalcycles in the body and its reduced production caused adverse effects, includinghypertension, hypokalemia (decrease in circulating potassium levels), and fluidretention. To address the suppressed synthesis of cortisol, the prior art also taughtthat concomitant glucocorticoid replacement therapy might be necessary whenadministering abiraterone to treat prostate cancer in a patient, and that this wascommon practice in the treatment of prostate cancer with ketoconazole, anotherCYP17 inhibitor. Ex. 1002, Serels Decl. ¶¶ 32, 34, 48, Ex. 1073; MahalingamDecl. ¶¶ 32, 34, 48.The prior art also taught that abiraterone was a more effective CYP17inhibitor than ketoconazole. For example, the prior art taught that abirateroneacetate was more effective in decreasing testosterone levels in a mammal thanketoconazole. Ex. 1002, Serels Decl. ¶¶36, 45, Ex. 1073; Mahalingam Decl. ¶¶ 36,45. The prior art also taught that the combination of ketoconazole and prednisone-6-

Petition for Inter Partes Review of U.S. Patent No. 8,822,438was a safe and effective treatment for refractory metastatic prostate cancer. Ex.1002, Serels Decl. ¶48, Ex. 1073; Mahalingam Decl. ¶ 48.One of skill in the art would have combined abiraterone acetate andprednisone based on teachings of O’Donnell in view of Gerber and/or the ‘213patent in view of Gerber for a safe and effective treatment of prostate cancer with areasonable expectation of success because the prior art taught abiraterone acetateas a more effective CYP17 inhibitor than ketoconazole and the combination ofketoconazole and prednisone as safe and effective to treat patients with hormonerefractory metastatic prostate cancer. Ex. 1002, Serels Decl. ¶¶45-49; Ex. 1073,Mahalingam Decl. ¶¶ 45-49.There are no secondary considerations of commercial success that overcomeobviousness. The claims of the application resulting in the ‘438 patent wererepeatedly rejected for obviousness until the Examiner allowed the claims based onthe purported “unexpected commercial success” of Zytiga , the brand name underwhich abiraterone acetate is marketed in the United States by the Assignee. Inparticular, the Examiner's allowance of the claims based on secondaryconsiderations of commercial success of Zytiga was in error because Applicantsfailed to show the necessary nexus between the claimed invention (which isdirected to method of treating prostate cancer by administering abiraterone acetateand prednisone) and any commercial success of the drug Zytiga .-7-

Petition for Inter Partes Review of U.S. Patent No. 8,822,438VIII. LEVEL OF ORDINARY SKILL IN THE ARTA person of ordinary skill in the art is presumed to be aware of all pertinentart, thinks along conventional wisdom in the art, and is a person of ordinarycreativity. With respect to the ‘438 patent, the scientific field relevant is oncologyor urology. Ex. 1002, Serels Decl. ¶8; Ex. 1073, Mahalingam Decl. ¶ 8. A personof ordinary skill in the art would be a physician specializing in urology oroncology, or holding a Ph.D. in pharmacology, biochemistry or a relateddiscipline. Ex. 1002, Serels Decl. ¶8; Ex. 1073, Mahalingam Decl. ¶ 8. Additionalexperience could substitute for the advanced degree. Ex. 1002, Serels Decl. ¶8; Ex.1073, Mahalingam Decl. ¶ 8. To the extent necessary, one of skill in the art maycollaborate with one or more other persons of skill in the art for one or moreaspects with which the other person may have expertise, experience and/orknowledge that was obtained through his or her education, industrial or academicexperiences. Ex. 1002, Serels Decl. ¶9; Ex. 1073, Mahalingam Decl. ¶ 9. Forexample, one of skill may consult with an enzymologist and/or molecular biologistand thus may rely on the opinions of such specialists in evaluating the claims. Ex.1002, Serels Decl. ¶10; Ex. 1073, Mahalingam Decl. ¶ 10.IX.U.S. PATENT NO. 8,822,438 AND ITS FILE HISTORYA.Specification of the ‘438 PatentThe “Background” section describes prostatectomy and radiotherapy, a-8-

Petition for Inter Partes Review of U.S. Patent No. 8,822,438primary course of treatment for patients diagnosed with organ-confined prostatecancer, as being highly invasive and ineffective on metastasized prostate cancer. Inaddition, the specification states that these localized treatments are not effective onprostate cancer after it has metastasized; and that, moreover, a large percent ofindividuals who receive such localized treatments will suffer from “recurringcancer.” The specification states that another treatment option for prostate cancer,hormone therapy, is less invasive than surgery and has fewer side effects.However, the specification notes that hormone therapy is not equally effective inall patients thus treated; and some patients suffer from relapsing or recurringcancer after hormone therapy. Ex. 1001, Col. 1, ll. 25-64.The “Summary of the Invention” section describes various embodiments ofthe invention being directed to methods an

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 .