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`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`APOTEX INC.
`Petitioners
`
`v.
`
`ALKERMES PHARMA IRELAND LIMITED
`Patent Owner
`__________________
`
`Case No. IPR2025-00514
`Patent 7,919,499
`__________________
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 7,919,499
`
`
`
`

`

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`Page
`INTRODUCTION ........................................................................................... 1
` MANDATORY NOTICES PURSUANT TO 37 C.F.R. §42.8(a)(1) ............. 3
`Real Parties-In-Interest .......................................................................... 3
`Identification of Related Matters Under 37 C.F.R. §42.8(b)(2) ........... 3
`Lead and Backup Counsel ..................................................................... 5
`Service Information Under 37 C.F.R. §42.8(b)(4) ................................ 6
`
`FEES ................................................................................................................ 6
`
` REQUIREMENTS UNDER 37 C.F.R. §42.104 ............................................. 6
` Grounds for Standing ............................................................................ 6
`Identification of Challenges and Precise Relief Requested .................. 6
`Prior Art Qualification of Asserted References .................................... 7
`
`BACKGROUND ............................................................................................. 8
`The ’499 Patent ..................................................................................... 8
`The ’499 Patent Examination History ................................................. 10
`The Terminated ’943 IPR .................................................................... 12
`Summary of the Applied Prior Art ...................................................... 14
`1.
`Comer (EX1004) ....................................................................... 14
`2.
`Nuwayser (EX1005) ................................................................. 17
`3.
`Rubio (EX1006) ........................................................................ 18
`4. Wright (EX1007) ...................................................................... 19
`Person of Ordinary Skill in the Art (“POSITA”) ................................ 20
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`TABLE OF CONTENTS
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`i
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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` CLAIM CONSTRUCTION .......................................................................... 20
`“the step of parenterally administering a long acting
`formulation comprising about 310 mg to about 480 mg of
`naltrexone” .......................................................................................... 21
`“the serum AUC of naltrexone … than that achieved by 50
`mg/day oral administration” ................................................................ 23
`“about three” ........................................................................................ 25
`“five or more days” ............................................................................. 26
`“initial oral dose” ................................................................................. 26
`“about 35% by weight” ....................................................................... 27
`
` PETITIONER HAS A REASONABLE LIKELIHOOD OF
`PREVAILING ............................................................................................... 27
` Ground 1: Claims 1, 3-5, and 12 Are Anticipated by Comer as
`evidenced by Nuwayser ...................................................................... 28
`1.
`Claim 1 (Preamble): A method for treating an individual
`in need of naltrexone comprising the step of ............................ 28
`a.
`[1.1]: parenterally administering a long acting
`formulation comprising .................................................. 29
`[1.2]: about 310 mg to about 480 mg of naltrexone ....... 32
`[1.3]: and a biocompatible polymer to the
`individual ........................................................................ 33
`[1.4]: wherein the serum AUC of naltrexone is
`about three times greater than that achieved by 50
`mg/day oral administration ............................................. 33
`[1.5]: and wherein the biocompatible polymer is a
`polylactide-co-glycolide polymer. .................................. 36
`Claim 3: The method of claim 1 wherein the long acting
`formulation releases naltrexone for a period of at least
`two weeks. ................................................................................. 36
`ii
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`b.
`c.
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`d.
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`e.
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`2.
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`3.
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`4.
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`Claim 4: The method of claim 1 wherein the long acting
`formulation releases naltrexone for a period of about four
`weeks. ........................................................................................ 37
`Claim 5: The method of claim 1 wherein the long acting
`formulation is administered in a dose of about 380 mg of
`naltrexone wherein the serum AUC is about 3.3 times
`greater than that achieved by 50 mg/day oral
`administration. ........................................................................... 37
`Claim 12: The method of claim 1 wherein naltrexone is
`administered by injection. ......................................................... 38
`Ground 2: Claims 1-13 Would Have Been Obvious Over
`Comer in view of Nuwayser, Rubio, and Wright ............................... 38
`1.
`Claim 1 ...................................................................................... 38
`2.
`Claim 2 ...................................................................................... 48
`3.
`Claim 3 ...................................................................................... 49
`4.
`Claim 4 ...................................................................................... 49
`5.
`Claim 5 ...................................................................................... 49
`6.
`Claim 6 ...................................................................................... 49
`7.
`Claims 7-9 ................................................................................. 50
`8.
`Claim 10 .................................................................................... 51
`9.
`Claim 11 .................................................................................... 51
`10. Claim 12 .................................................................................... 52
`11. Claim 13 .................................................................................... 52
`Ground 3: Claims 1-13 Would Have Been Obvious Over
`Nuwayser in View of Comer, Rubio, and Wright ............................... 53
`1.
`Claim 1 (Preamble) ................................................................... 53
`a.
`Element [1.1] .................................................................. 54
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`5.
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`b.
`Element [1.2] .................................................................. 54
`Element [1.3] .................................................................. 57
`c.
`Element [1.4] .................................................................. 57
`d.
`Element [1.5] .................................................................. 58
`e.
`Claim 2 ...................................................................................... 58
`2.
`Claim 3 ...................................................................................... 58
`3.
`Claim 4 ...................................................................................... 59
`4.
`Claim 5 ...................................................................................... 59
`5.
`Claim 6 ...................................................................................... 59
`6.
`Claims 7-9 ................................................................................. 60
`7.
`Claim 10 .................................................................................... 60
`8.
`Claim 11 .................................................................................... 60
`9.
`10. Claim 12 .................................................................................... 60
`11. Claim 13 .................................................................................... 61
` OTHER CONSIDERATIONS ...................................................................... 61
` Any Purported Secondary Considerations Evidence Does Not
`Overcome the Strong Evidence of the Obviousness of the
`Claims .................................................................................................. 61
`The Amneal IPR Does Not Warrant Discretionary Denial Under
`General Plastic .................................................................................... 62
` CONCLUSION .............................................................................................. 68
`APPENDIX A - Naltrexone AUC calculations based on 384 mg IM dose
`APPENDIX B - LIST OF EXHIBITS
`CERTIFICATE OF COMPLIANCE WITH 37 C.F.R. §42.24
`
`CERTIFICATE OF SERVICE
`
`
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`iv
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`TABLE OF AUTHORITIES
`
`Page(s)
`
`Cases
`Amneal Pharmaceuticals LLC v. Alkermes Pharma Ireland Limited,
`IPR2018-00943 ............................................................................................passim
`Apple Inc. v. Fintiv, Inc.,
`IPR2020-00019, Paper 11 (PTAB Mar. 20, 2020) ....................................... 65, 66
`Baldwin Graphic Sys., Inc. v. Siebert, Inc.,
`512 F.3d 1338 (Fed. Cir. 2008) .......................................................................... 21
`In re Baxter Travenol Labs.,
`952 F.2d 388 (Fed. Cir. 1991) ............................................................................ 30
`Comcast Cable Commn’s, LLC v. Rovi Guides, Inc.,
`IPR2019-00231, Paper 14 (PTAB May 20, 2019) ............................................. 66
`DISH Network LLC v. Sound View Innovations, LLC,
`IPR2020-01041, Paper 13 (PTAB Jan 19, 2021) ............................................... 67
`General Plastic Indus. Co., Ltd. v. Canon Kabushiki Kaisha,
`IPR2016-01357, Paper 19 (PTAB Sept. 6, 2017) ............................. 62, 63, 64, 65
`Google LLC v. Multimodal Media LLC,
`IPR2024-00053, Paper 10 (PTAB Jun. 5, 2024) ................................................ 65
`Inergy Tech., Inc. v. Force Mos Tech., Co., Ltd.,
`IPR2024-00094, Paper 9 (PTAB May 21, 2024) ............................................... 66
`Puma N. Am., Inc. v. Nike, Inc.,
`IPR2019-01058, Paper 10 (PTAB Oct. 31, 2019) .............................................. 68
`Roku, Inc. v. Universal Electronics, Inc.,
`IPR2019-01615 (PTAB April 17, 2020) ............................................................ 67
`Santarus, Inc. v. Par Pharm., Inc.,
`694 F.3d 1344 (Fed. Cir. 2012) ............................................................................ 2
`Trans Ova Genetics, LC v. XY, LLC,
`IPR2018-00250, Paper 9 (PTAB June 27, 2018) ............................................... 67
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`Valve Corp. v. Electronic Scripting Prods., Inc.,
`IPR2019-00062, Paper 11 (PTAB Apr. 2, 2019) ......................................... 63, 64
`Videndum Prod. Solutions, Inc. v. Rotolight Ltd.,
`IPR2023-01218, Paper 12 (PTAB Apr. 19, 2024) ............................................. 64
`
`
`Statutes
`35 U.S.C. §102(b) .................................................................................................. 7, 8
`35 U.S.C. §102(e) ...................................................................................................... 8
`35 U.S.C. §103(a) ...................................................................................................... 7
`35 U.S.C. §112 ................................................................................................... 22, 25
`35 U.S.C. §§311-319.................................................................................................. 1
`35 U.S.C. §314(a) .................................................................................................... 65
`35 U.S.C. §325(d) .................................................................................................... 67
`
`Rules
`37 C.F.R. §1.75(c) .................................................................................................... 22
`37 C.F.R. §1.102(e) .................................................................................................. 10
`37 C.F.R. §1.132 ................................................................................................ 11, 24
`37 C.F.R. §42.8(a)(1) ................................................................................................. 3
`37 C.F.R. §42.8(b)(1) ................................................................................................. 3
`37 C.F.R. §42.8(b)(2) ................................................................................................. 3
`37 C.F.R. §42.8(b)(3) ................................................................................................. 5
`37 C.F.R. §42.8(b)(4) ................................................................................................. 6
`37 C.F.R. § 42.10(a) ................................................................................................... 5
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`vi
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`37 C.F.R. §42.10(b) ................................................................................................... 6
`37 C.F.R. §42.15(a) .................................................................................................... 6
`37 C.F.R. §42.100 et seq. ........................................................................................... 1
`37 C.F.R. §42.102(a)(2) ............................................................................................. 6
`37 C.F.R. §42.104 ...................................................................................................... 6
`37 C.F.R. §42.104(a) .................................................................................................. 6
`37 C.F.R. §42.104(b) ................................................................................................. 7
`MPEP §2131.01 [I], [II] ........................................................................................... 30
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`INTRODUCTION
`Apotex Inc. (“Petitioner”) respectfully request inter partes review for Claims
`
`1-13 (“the Challenged Claims”) of U.S. Patent No. 7,919,499 (“the ’499 Patent”)
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`(EX1001) in accordance with 35 U.S.C. §§311-319 and 37 C.F.R. §42.100 et seq.
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`The ’499 Patent discloses methods of using formulations of naltrexone, a
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`well-known drug for treating alcoholics and heroin-dependent individuals. The ’499
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`Patent proposes use of a long acting formulation of naltrexone to address problems
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`with patient compliance. EX1001, 1:25-33; EX1046, ¶63; EX1048, ¶38. Yet, it was
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`already known that “[s]ustained-release forms of naltrexone could increase
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`compliance and ultimately improve treatment effectiveness.” EX1004, 352.
`
`The purported invention of the ’499 Patent calls for a known drug (naltrexone)
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`at a known dose (about 310-480 mg) used with a known sustained release excipient
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`(polylactide-co-glycolide, “PLGA”), to address the known problem of patient
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`compliance. The claimed serum AUC is merely a predictable and expected result of
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`such combination of known elements, and is also expressly disclosed in the prior art.
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`EX1046, ¶¶64-67; EX1010; EX1011; EX1012; EX1013; EX1014; EX1016;
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`EX1017; EX1018; EX1019; EX1020; EX1025; EX1029; EX1042; EX1056;
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`EX1048, ¶¶39-42; EX1031.
`
`Thus, the Examiner erred in allowing the Challenged Claims. Comparisons
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`made to oral naltrexone treatments, and even those made during prosecution to the
`
`1
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`

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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`depot injection formulation of Tice (EX1015), are not comparisons to the closest
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`prior art cited here. The closest prior art actually includes identical PLGA
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`formulations containing about 380 mg of naltrexone, administered in monthly depot
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`injections.
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`Patent Owner acknowledges that pharmacokinetic results are dose dependent
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`in this system. The claimed dose (about 380 mg), delivered from a PLGA depot
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`injection, over the same time period, was known. The resulting AUC, a
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`pharmacokinetic property, must therefore be the same as, or sufficiently similar to
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`the AUC of the claimed formulation so as to render it unpatentable. The same is true
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`for any AUC differential between depot injection and oral dosing. As the Federal
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`Circuit has previously held in similar circumstances, “an obvious formulation cannot
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`become nonobvious simply by administering it to a patient and claiming the resulting
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`serum concentrations.” Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed.
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`Cir. 2012). The same should be true of the otherwise known method claimed here.
`
`The Challenged Claims were previously challenged by a different, unrelated
`
`petitioner in IPR2018-00943. The Board instituted trial, finding it reasonably likely
`
`that the Challenged Claims would be found unpatentable over the same art cited in
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`this Petition. EX1058. The parties subsequently settled and jointly moved to
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`terminate the ’943 IPR, and the Board granted the motion. EX1059. Given that the
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`Board did not have the opportunity to reach final written decision in the ’943 IPR,
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`2
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`serious unresolved questions remain concerning the validity of the Challenged
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`Claims. Petitioner requests the Board to institute trial to resolve these questions.
`
` MANDATORY NOTICES PURSUANT TO 37 C.F.R. §42.8(a)(1)
` Real Parties-In-Interest
`Pursuant to 37 C.F.R. §42.8(b)(1), Petitioner certifies that Apotex Inc. is the
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`real party-in-interest. Additional real parties-in-interest are Artemis Parent, Inc.,
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`Artemis Intermediate Holdings, Inc., Apotex Holdco Inc., Apotex Corp., and
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`Aposherm Delaware Holdings Corporation.
`
`
`Identification of Related Matters Under 37 C.F.R. §42.8(b)(2)
`The following is a list of any judicial or administrative matters that would
`
`affect, or be affected by, a decision in this proceeding:
`
`Related District Court and PTAB Proceedings
`
`Alkermes, Inc. et al. v. Teva Pharmaceutical Industries Ltd. et al., Civ. Action
`
`No. 2:20-cv-12470 (D.N.J.) (“Related Litigation”) (Terminated); and
`
`Amneal Pharmaceuticals LLC v. Alkermes Pharma Ireland Limited,
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`IPR2018-00943 (PTAB) (“the ’943 IPR”) (Terminated).
`
`Related Applications
`
`The ’499 Patent issued from U.S. Patent Application No. 11/083,167, filed on
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`March 17, 2005 and claims priority to U.S. Provisional Application No. 60/564,542,
`
`filed on April 22, 2004.
`
`The following applications are listed in the ’499 Patent’s continuity child data:
`3
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`U.S. Patent Application No. 18/243,832, filed on September 8, 2023
`
`(abandoned);
`
`U.S. Patent Application No. 18/099,645 (abandoned);
`
`U.S. Patent Application No. 17/861,575, filed on July 11, 2022 (abandoned);
`
`U.S. Patent Application No. 17/540,490, filed on December 2, 2021
`
`(abandoned);
`
`U.S. Patent Application No. 17/244,110, filed on April 29, 2021 (abandoned);
`
`U.S. Patent Application No. 17/070,173, filed on October 14, 2020
`
`(abandoned);
`
`U.S. Patent Application No. 16/844,020, filed on April 9, 2020 (abandoned);
`
`U.S. Patent Application No. 16/656,022, filed on October 17, 2019
`
`(abandoned);
`
`U.S. Patent Application No. 16/565,907, filed on September 10, 2019
`
`(abandoned);
`
`U.S. Patent Application No. 16/251,542, filed on January 18, 2019
`
`(abandoned);
`
`U.S. Patent Application No. 16/107,218, filed on August 21, 2018
`
`(abandoned);
`
`U.S. Patent Application No. 15/486,869, filed on April 13, 2017 (abandoned);
`
`4
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`U.S. Patent Application No. 15/254,580, filed on September 1, 2016
`
`(abandoned);
`
`U.S. Patent Application No. 13/871,534, filed on April 26, 2013 (abandoned);
`
`U.S. Patent Application No. 13/037,713, filed on March 1, 2011 (abandoned);
`
`and
`
`PCT International Application No. PCT/US05/09133, filed on March 18,
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`2005 (published).
`
` Lead and Backup Counsel
`Pursuant to 37 C.F.R. §§42.8(b)(3) and 42.10(a), Petitioner hereby identifies
`
`its lead and backup counsel as follows:
`
`Lead Counsel:
`Matthew L. Fedowitz, Esq.
`Registration No. 61,386
`BUCHANAN INGERSOLL & ROONEY PC
`1700 K Street, NW, Suite 300
`Washington, DC 20006
`Direct Telephone (202) 452-7306
`Main Facsimile (202) 452-7989
`matthew.fedowitz@bipc.com
`Backup Counsel:
`Mythili Markowski, Ph.D., Esq.
`Registration No. 67,063
`BUCHANAN INGERSOLL & ROONEY PC
`1700 K Street, N.W., Suite 300
`Washington, DC 20006
`Direct Telephone (202) 452-7314
`Main Facsimile (202) 452-7989
`mythili.markowski@bipc.com
`
`
`
`Backup Counsel:
`Roger H. Lee, Esq.
`Registration No. 46,317
`BUCHANAN INGERSOLL & ROONEY PC
`1737 King Street, Suite 500
`Alexandria, VA 22314
`Direct Telephone (703) 838-6545
`Main Facsimile (703) 836-2021
`roger.lee@bipc.com
`Backup Counsel:
`James T. Moore, Esq.
`Registration No. 35,619
`BUCHANAN INGERSOLL & ROONEY PC
`500 Delaware Avenue, Suite 720
`Wilmington, DE 19801
`Direct Telephone (302) 552-4212
`Main Facsimile (302) 552-4295
`james.moore@bipc.com
`
`5
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`A Power of Attorney is being filed concurrently herewith in accordance with
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`37 C.F.R. §42.10(b).
`
`
`Service Information Under 37 C.F.R. §42.8(b)(4)
`Petitioners consent to e-mail service at the addresses listed above.
`
` FEES
`The undersigned authorizes the Office to charge Deposit Account 02-4800 for
`
`fees required by 37 C.F.R. §42.15(a).
`
` REQUIREMENTS UNDER 37 C.F.R. §42.104
` Grounds for Standing
`Pursuant to 37 C.F.R. §42.104(a), Petitioner hereby certifies that the ’499
`
`Patent is available for inter partes review in accordance with 37 C.F.R.
`
`§42.102(a)(2). Petitioner is not barred or estopped from requesting inter partes
`
`review of the challenged claims of the ’499 Patent on the grounds identified herein.
`
`
`Identification of Challenges and Precise Relief Requested
`Pursuant to 37 C.F.R. §42.104(b), Petitioner challenges Claims 1-13 of the
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`’499 Patent, and request that these claims be found unpatentable over the prior art
`
`for the reasons given below. Petitioner’s Grounds for challenging the validity of the
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`Challenged Claims are as follows:
`
`Ground
`
`1
`
`References
`Comer (EX1004) as evidenced by
`Nuwayser (EX1005)
`
`Basis
`
`Claims Challenged
`
`§102(b)
`
`1, 3-5, 12
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`6
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`Ground
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`2
`
`3
`
`References
`Comer in view of Nuwayser,
`Rubio (EX1006), and Wright
`(EX1007)
`Nuwayser in view of Comer,
`Rubio, and Wright
`
`Basis
`
`Claims Challenged
`
`§103(a)
`
`§103(a)
`
`1-13
`
`1-13
`
`In addition to the above prior art, Petitioner relies upon evidence listed in the
`
`Exhibit List, including the Declaration and Curriculum Vitae of Dr. Thomas
`
`Dowling (EXs1046-1047), the Declaration and Curriculum Vitae of Dr. Jason
`
`Schiffman (EXs1048-1049), and the Declaration and Curriculum Vitae of June Ann
`
`Munford (EXs1050-1051), in their entirety.
`
`
`Prior Art Qualification of Asserted References
`The ’499 Patent (EX1001) was filed on March 17, 2005 as U.S. Patent
`
`Application No. 11/083,167 (“the ’167 Application”). The ’167 Application claims
`
`priority to U.S. Provisional Application No. 60/564,542, filed on April 22, 2004
`
`(EX1003).
`
`Even if the ’499 Patent is deemed entitled to its earliest priority date, all of the
`
`cited references in this Petition are prior art.
`
`Comer (EX1004) published in 2002. EX1050, ¶¶8-14. Comer is 35 U.S.C.
`
`§102(b) prior art.
`
`U.S. Patent No. 7,157,102 (“Nuwayser”) (EX1005), was filed on May 31,
`
`2002, with a nonpublication request. Nuwayser is prior art under 35 U.S.C. §102(e).
`
`7
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`Rubio (EX1006) published in 2001. EX1050, ¶¶15-21. Rubio is 35 U.S.C.
`
`§102(b) prior art.
`
`U.S. Patent No. 6,264,987 (“Wright”) (EX1007), issued on July 24, 2001.
`
`Wright is prior art under 35 U.S.C. §102(b) and/or §102(e).
`
`Kranzler (EX1008) published in August 1998. EX1050, ¶¶22-25. Kranzler is
`
`35 U.S.C. §102(b) prior art.
`
` BACKGROUND
` The ’499 Patent
`The ’499 Patent describes a method of treating an individual in need of
`
`naltrexone by parenterally administering a long acting formulation that includes 310-
`
`480 mg of naltrexone and PLGA to the individual, where the serum AUC of
`
`naltrexone is about three times greater than what is achieved by administration of 50
`
`mg/day oral administration. EX1001, 1:30-46; EX1046, ¶39.
`
`The ’499 Patent alleges that the “inventions described herein arose from
`
`unexpected discoveries made during clinical trials with a long acting formulation of
`
`naltrexone.” EX1001 Abstract, 1:31-33; EX1046, ¶40; EX1048, ¶11. However, the
`
`’499 Patent provides no direct data for the AUC of any claimed formulation or the
`
`comparator—50 mg/day oral dosing. EX1001, 18:10-12. During prosecution,
`
`comparisons were made using data from an Alkermes’ study referenced in the ’499
`
`8
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`Patent and from Tice. EX1002, at 300-304; EX1055. But none of this data could be
`
`determined from the ’499 Patent itself.
`
`The specification discusses a purported need for improving naltrexone
`
`therapies, based on patient compliance. EX1001, 1:13-26, 17:24-29; EX1046, ¶41.
`
`In some embodiments, the naltrexone is combined with well-known polymers, such
`
`as PLGA, to “entrap or encapsulate” the naltrexone and provide a long-acting
`
`formulation. EX1001, 3:14-15; EX1046, ¶42; EX1048, ¶¶12-13.
`
`The specification describes its long-acting formulations as releasing
`
`naltrexone over a period of at least one week. EX1001, 3:59-64, 4:42-44. It then
`
`describes “Vivitrex” as a monthly administration that releases naltrexone for four
`
`weeks, and that the therapy can be maintained for 24 weeks or more. Id. 4:54-64;
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`EX1046, ¶42; EX1048, ¶12.
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`Five examples are included, three of which (Examples 3-5) were not present
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`in the provisional application. Compare EX1001 and EX1003. Example 1 describes
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`how to manufacture Vivitrex formulations. The microparticles portion of this
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`example is virtually identical to the preparation described in Example 3 of Wright.
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`Compare EX1001, 3:3-33, 5:35-8:2 and EX1007, 7:50-8:60. The remaining
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`examples describe various aspects of a clinical trial and meta-analysis. Example 2
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`describes screening, eligibility, and adverse events. EX1001, 8:5-18:2. Example 3
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`compares the “efficacy” of oral versus injectable naltrexone but clearly states that “a
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`direct head-to-head comparison of efficacy has not been studied” and thus “a
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`definitive comparison of efficacy between Vivitrex and oral naltrexone cannot be
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`made.” EX1001, 18:10-12 (emphases added). Instead, the specification admits to
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`using data from three nonrelated studies for a “semi-quantitative” comparison that
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`resulted in efficacy “compares favorably with oral naltrexone.” “Favorably” in this
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`context would be understood by a POSITA to mean comparable or equivalent to, as
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`the ’499 Patent’s data would not establish improved efficacy to a POSITA. EX1001,
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`18:12-29, 19:30-33. Finally, Examples 4 and 5 are directed to “quality of life” and
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`“durability of effect and tolerability” of long acting naltrexone formulations.
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`EX1046, ¶¶43-45; EX1048, ¶¶14-16.
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`
`The ’499 Patent Examination History
`The ’499 Patent was filed under 37 C.F.R. §1.102(e) on March 17, 2005, as
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`the ’167 Application. On September 5, 2007, Alkermes filed a preliminary
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`amendment, which merely canceled original claims 24 and 25. A restriction
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`requirement was mailed on February 20, 2009, and Alkermes responded on March
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`20, 2009, electing Group 1, i.e., claims 1, 2, and 6-23, with traverse. See also
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`EX1046, ¶¶38, 46-47; EX1048, ¶¶10, 17-18.
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`A non-final rejection was mailed on May 5, 2009 (EX1002, at 333-342),
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`which rejected the claims as allegedly being anticipated by Tice and, in the
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`alternative, as being obvious over the combination of Tice and Chandrashekar.
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`Alkermes responded on October 5, 2009 (EX1002, at 291-299), with claim
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`amendments and a declaration under 37 C.F.R. §1.132 by Elliot Ehrich (the “Ehrich
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`Declaration” (EX1002, at 300-304; EX1055)), the sole inventor of the ’499 Patent.
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`The Ehrich Declaration argued that Tice used polylactic acid (“PLA”), not PLGA,
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`and that the AUC of Tice’s formulation was about the same as that of 50 mg/day
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`oral dosing. In contrast, the claimed invention allegedly resulted in 3.3 times the oral
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`AUC. Alkermes also argued the existence of this AUC differential using its own oral
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`data from a clinical trial. EX1046, ¶47; EX1048, ¶18.
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`The Examiner issued a second office action on January 6, 2010, which
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`withdrew the anticipation and obviousness rejections over Tice in view of the Ehrich
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`Declaration but nevertheless rejected the claims for lack of enablement. EX1002, at
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`276-286. Alkermes responded in an Amendment dated April 5, 2010, by amending
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`the claims to require a biocompatible polymer. EX1002, at 177-188. A final rejection
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`was mailed on July 20, 2010, maintaining the enablement rejection. EX1002, at 130-
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`143. Alkermes filed a response after final on October 20, 2010, amending the claims
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`further to require that the biocompatible polymer be PLGA. EX1002, at 121-126;
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`EX1046, ¶48; EX1048, ¶19.
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`A Notice of Allowance was mailed on December 1, 2010, which
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`acknowledged a telephone interview of November 19, 2010, where Alkermes agreed
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`to an Examiner’s Amendment to insert certain language into the claims, e.g., “about
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`310 mg to about 480 mg” into claim 1. EX1002, at 106-114. The Examiner also
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`included reasons for allowance, concluding that “[t]here is no prior art disclosing the
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`applicant’s composition and effect, particularly an AUC about three times greater
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`than that achieved by 50 mg/day oral administration”. EX1002, at 111-112.
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`According to the Examiner, Tice (EX1009) was the closest prior art and reported
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`that its injectable formulation was comparable to taking 50 mg tablets orally. (Id.)
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`But, as discussed below, Tice is not the closest prior art. The prior art cited in this
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`Petition discloses administering the same amount of naltrexone (about 310 mg to
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`about 480 mg) with the same biocompatible polymer (PLGA), resulting in the same
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`serum AUC (about three times greater than that achieved by 50 mg/day oral
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`administration) as claimed. EX1046, ¶49; EX1048, ¶20.
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` The Terminated ’943 IPR
`The ’499 Patent was previously challenged in IPR2018-00943 (“the Amneal
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`IPR”) filed by a different petitioner, Amneal Pharmaceuticals LLC (“Amneal”). The
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`Board instituted trial of the ’943 IPR. EX1058. Parties subsequently settled and
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`jointly moved to terminate the IPR, and the Board granted the motion. EX1059.
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`Given that the Amneal IPR was terminated after institution but prior to issuance of
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`a final written decision, serious unresolved questions remain concerning the validity
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`of the Challenged Claims of the ’499 Patent.
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`Petition for Inter Partes Review of U.S. Patent No. 7,919,499
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`In the ’943 IPR, the Board determined that the petitioner met its burden for
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`purposes of institution concerning the anticipation ground based on Comer as
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`evidenced by Nuwayser with respect to claims 1, 3-5 and 12. EX1058, 21 (“we are
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`satisfied on this record that Comer teaches, either explicitly or inherently, each and
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`every limitation of claim 1.”), 25 (“We have reviewed Petitioner’s contentions and
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`supporting evidence … and find them sufficient based on the current record for
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`claims 3–5 and 12.”). Ground 1 of this Petition applies the same references a