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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_________________________________
`
`
`
`TEVA PHARMACEUTICALS USA, INC.
`
`Petitioner
`
`v.
`
`RB PHARMACEUTICALS LTD.
`
`Patent Owner
`
`
`
`U.S. Patent No. 8,475,832
`
`_______________
`
`Case IPR2016: Unassigned
`
`_______________
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 8,475,832
`
`
`
`

`

`
`
`Exhibit No.
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`PETITIONER EXHIBIT LIST
`
`
`Reference
`
`U.S. Patent No. 8,475,832 (filed August 7, 2009)
`
`File History, U.S. Patent No. 8,475,832
`
`Expert Declaration of Nandita Das, Ph.D., Relating to U.S. Patent
`No. 8,475,832
`
`U.S. Patent Application Publication 2005/0085440 (published April
`21, 2005) (“Birch”)
`
`WO 2008/025791 (published March 6, 2008) (“Oksche”)
`
`U.S. Patent No. 7,357,891 (published December 23, 2004) (issued
`April 15, 2008) (“Yang”)
`
`WO 2008/040534 (published April 10, 2008) (“LabTec”)
`
`Suboxone® Label
`
`Suboxone® Tablet Summary Basis of Approval (“SBOA”)
`
`U.S. Patent Application Publication No. 2005/0037055 (“the ’055
`publication”)
`
`European Medicines Agency Initial Marketing-Authorisation
`Document, Scientific Discussion, Oct. 19, 2006 for Suboxone
`sublingual tablets (“EMEA”)
`
`J.P. Cassidy et al., Controlled Buccal Delivery of Buprenorphine, 25
`J. Controlled Release 21 (1993)
`
`Rex M. C. Dawson et al., Data for Biochemical Research (3d ed.
`1986)
`
`Domenic A. Ciraulo et al., Pharmacokinetics and
`Pharmacodynamics of Multiple Sublingual Buprenorphine Tablets
`in Dose-Escelation Trials, 46 J. Clinical Pharmacology 179 (2006)
`
`
`
`i
`
`

`

`
`
`Exhibit No.
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`
`
`
`
`Reference
`
`C. Nora Chiang & Richard L. Hawks, Pharmacokinetics of the
`Combination Tablet of Buprenorphine and Naloxone, 70 Drug &
`Alcohol Dependence S39 (2003)
`
`Campbell et al., The History of the Development of Buprenorphine
`as an Addiction Therapeutic, 1248 Ann. N.Y. Acad. Sc. (Issue:
`Addiction Reviews), 124 (2012) (“Campbell”)
`
`Bullingham et al., Sublingual Buprenorphine Used Postoperatively:
`Clinical Observations and Preliminary Pharmacokinetic Analysis,
`12 Br. J. Clinical Pharmacology 117 (1981)
`
`U.S. Patent App. No. US 2010/0087470
`
`U.S. Patent No. 4,582,835
`
`Center for Drug Evaluation and Research, Approval Package for
`App. No. 22-410/S006/S007 (approval date 8/10/12) (“Film
`Approval Package”)
`Encyclopedia of Pharmaceutical Technology, 2nd ed., Vol. I, Drug
`Delivery—Buccal Route (McElnay et al.) (“McElnay”)
`
`U.S. Patent No. 5,288,497 (“Stanley”)
`
`Declaration by Maureen Reitman, SC.D. (“Reitman Decl.”)
`
`Parkhurst A. Shore et al., The Gastric Secretion of Drugs: A pH
`Partition Hypothesis, 119 J. Pharmacology Exp. Ther. 361 (1957)
`
`Curriculum Vitae of Nandita Das, Ph.D.
`
`List of Materials Considered by Nandita Das, Ph.D.
`
`ii
`
`

`

`
`
`TABLE OF CONTENTS
`
`Page
`
`V.
`
`I.
`II.
`
`INTRODUCTION ........................................................................................... 1
`BACKGROUND ............................................................................................. 1
`A.
`Brief Overview of the ’832 Patent ........................................................ 1
`B.
`Brief Overview of the Prosecution History ........................................... 4
`III. GROUNDS FOR STANDING (§ 42.104(a)) ................................................. 6
`IV. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8 ................................... 7
`A.
`Real Party in Interest (§ 42.8(b)(1)) ...................................................... 7
`B.
`Related Proceedings (§ 42.8(b)(2)) ....................................................... 7
`C.
`Lead and Backup Counsel (§ 42.8(b)(3)) ............................................ 10
`D.
`Service Information (§ 42.8(b)(4)) ...................................................... 11
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND
`IDENTIFICATION OF THE CHALLENGE (§ 42.104(b)) ......................... 12
`VI. LEVEL OF ORDINARY SKILL IN THE ART ........................................... 14
`VII. THE CHALLENGED CLAIMS OF THE ’832 PATENT ............................ 14
`VIII. CLAIM CONSTRUCTION .......................................................................... 15
`IX. SCOPE AND CONTENT OF THE PRIOR ART ......................................... 16
`A. WO2008/040534 (“LabTec”) (Ex. 1007) ........................................... 16
`B. WO 2008/025791 (“Oksche”) (Ex. 1005) ........................................... 17
`C. U.S. Patent No. 7,357,891 (“Yang”) (Ex. 1006) ................................. 17
`D.
`Suboxone® Sublingual Tablets (Label and SBOA, Exs. 1008 and
`1009) .................................................................................................... 18
`U.S. Patent Publication 2005/0085440 (“Birch”) (Ex. 1004) ............. 19
`E.
`The ’055 Publication (Ex. 1010) ......................................................... 20
`F.
`X. DETAILED EXPLANATION OF THE GROUNDS FOR
`UNPATENTABILITY .................................................................................. 20
`A. Ground 1: Claims 1-2, 4-7, and 9-10 are Obvious Over LabTec in
`View of Yang, the Suboxone® 2002 Label, SBOA, and Birch .......... 20
`i.
`The film dosage limitations. ..................................................... 20
`ii.
`The buffer and pH range limitations. ........................................ 24
`
`
`
`iii
`
`

`

`
`
`B. Ground 2: Claims 3 and 11-12 are Obvious Over LabTec in View
`of Yang, the Suboxone® 2002 Label, SBOA, Birch, and the ’055
`Publication ........................................................................................... 35
`C. Ground 3: Claims 1-2, 4-7, and 9-10 are Obvious Over Oksche in
`View of Yang, Birch, the Suboxone® 2002 Label, and SBOA .......... 37
`i.
`The film dosage limitations. ..................................................... 37
`ii.
`The buffer and pH range limitations. ........................................ 39
`D. Ground 4: Claims 3 and 11-12 are Obvious Over Oksche in View
`of Yang, Birch, the Suboxone® 2002 Label, SBOA, and the ’055
`Publication ........................................................................................... 45
`XI. CONCLUSION .............................................................................................. 46
`
`
`
`
`
`iv
`
`

`

`
`
`Cases
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Reckitt Benckiser Pharmaceuticals, Inc. et al. v. Watson Laboratories,
`Inc. et al.,
`Civil Action No. 13- 0167 (D. Del.) ................................................................... 19
`
`Reckitt Benckiser Pharmaceuticals, Inc., RB Pharmaceuticals
`Limited, et al v. Teva Pharmaceuticals USA, Inc.,
`Civil Action No. 14-1451 (D. Del.) ...................................................................... 5
`
`In re Translogic Tech., Inc.,
`504 F.3d 1249 (Fed. Cir. 2007) .......................................................................... 16
`
`Statutes
`
`35 U.S.C. § 311 .................................................................................................... 1, 11
`
`35 U.S.C. § 325(d) ..................................................................................................... 9
`
`Regulations
`
`37 C.F.R. Part 42 ........................................................................................................ 1
`
`37 C.F.R. § 42.8 ......................................................................................................... 6
`
`37 C.F.R. § 42.100(b) .............................................................................................. 16
`
`37 C.F.R. § 42.104(a) ................................................................................................. 5
`
`
`
`v
`
`

`

`
`
`I.
`
`INTRODUCTION
`
`Under 35 U.S.C. § 311, § 6 of the Leahy-Smith America Invents Act
`
`(“AIA”), and 37 C.F.R. Part 42, Teva Pharmaceuticals USA, Inc., (“Petitioner”)
`
`respectfully requests inter partes review of claims 1-7 and 9-12 of U.S. Patent No.
`
`8,475,832 (“the ’832 patent”; Ex. 1001), which is currently assigned to RB
`
`Pharmaceuticals, Ltd. (“Patent Owner”). This petition and supporting exhibits
`
`demonstrate that there is a reasonable likelihood that claims 1-7 and 9-12 of the
`
`’832 patent are unpatentable over the prior art and should be canceled.
`
`II. BACKGROUND
`
`A. Brief Overview of the ’832 Patent
`
`The ’832 patent relates to compositions and methods for treating narcotic
`
`dependence. In general, the patent claims concern an orally-dissolvable film
`
`composition containing buprenorphine and naloxone that produces “optimal”
`
`absorption of buprenorphine, which includes, according to the patent, absorption
`
`that is bioequivalent to Suboxone® tablets. (Ex. 1001, 4:55-58.)
`
`Suboxone® tablets were in the prior art. Like the claimed film, they are
`
`orally-dissolvable formulations containing buprenorphine and naloxone. (Id. at
`
`4:51-55.) Buprenorphine is an opioid that can satisfy an opioid addict’s urge for
`
`narcotics, but does not provide the “high” associated with misuse of opioids. (Id. at
`
`1:36-40.) Naloxone blocks the effect of buprenorphine. Unlike buprenorphine, it is
`
`
`
`1
`
`

`

`
`
`not absorbed orally and thus does not exert an effect when the tablet is used as
`
`intended. Should an abuser attempt to extract and inject buprenorphine from the
`
`tablets, however, the naloxone will also be extracted and will prevent the
`
`buprenorphine from having a narcotic effect. The naloxone thus decreases the
`
`likelihood of diversion and abuse of buprenorphine. (Id. at 1:46-52.) Nevertheless,
`
`according to the inventors of the ’832 patent, the tablet is more susceptible to abuse
`
`than the claimed film because it can purportedly be removed more easily from the
`
`mouth for later extraction of buprenorphine. (Id. at 1:55-62.)
`
`More particularly, the challenged claims concern, inter alia, a composition
`
`comprising a polymeric carrier, buprenorphine, naloxone, and a buffer to “provide
`
`for a local pH” from about 3 to about 3.5 in the presence of saliva. (See infra
`
`Section VII.) The ’832 patent states that controlling the local pH with a buffer in
`
`this manner will maximize the absorption of the buprenorphine while
`
`simultaneously minimizing the absorption of the naloxone, i.e., will produce
`
`absorption that is bioequivalent to Subxone® tablets. (Ex. 1001, ’832 patent, at
`
`11:26-30.) According to the patent, “it has been surprisingly discovered” that, at a
`
`local pH level from about 2 to about 4, and most desirably from 3 to 4, the film
`
`
`
`2
`
`

`

`
`
`composition of the invention achieves bioequivalence1 to the Suboxone® tablet.
`
`(Id. at 11:50–61.)
`
`Patent Owner relied upon this buffer and pH range during prosecution as the
`
`alleged novel features of the invention. (See infra Section II.B.) But this buffer is
`
`the same as that used in the Suboxone® tablet to maximize absorption of the
`
`buprenorphine and minimize the absorption of naloxone. Moreover, the buffer was
`
`well-known in the prior art, as was the pH range at which the absorption of
`
`buprenorphine across mucosal membranes would be optimal. (Compare, e.g., Ex.
`
`1008, Suboxone® 2002 Label at 8 (“Each tablet also contains … citric acid,
`
`sodium citrate”), with Ex. 1001, ’832 patent, at 15:55-16:32, Example 1, 17:49-
`
`23:55, Examples 4-9, 24:19-21, Claim 7.) It would have been well-within the skill
`
`of the ordinary artisan to create a film that uses the same buffer as in the tablets, to
`
`provide the same local pH as the tablets, and to produce the same absorption of
`
`buprenorphine as the tablets. Thus, these claimed features cannot confer
`
`patentability.
`
`
`
`1 In other words, the alleged invention features the same oral dissolvability, same
`
`drug combination, same strength, same route of delivery, and the same or similar
`
`pharmacokinetic parameters (such as bioequivalent Cmax and AUC) as the
`
`Suboxone® tablets. (See id. at 15:55-23:11, Examples 1-8.)
`
`
`
`3
`
`

`

`
`
`B.
`
`Brief Overview of the Prosecution History
`
`The application leading to the ’832 patent (U.S. Patent Application No.
`
`12/537,571, hereinafter “’571 application”) was filed on August 7, 2009 and lists
`
`Garry L. Myers, Samuel D. Hilbert, Bill J. Boone, B. Arlie Bogue, Pradeep
`
`Sanghvi, and Madhusudan Hariharan as inventors. (’832 patent, Ex. 1001.) The
`
`’571 application initially included 31 claims. (’571 application, Ex. 1002, at 33-
`
`36.) Claims 1, 11, 15, 17, 24, 26, and 27 were independent claims. (Id.) None of
`
`these independent claims recited any pH ranges. (Id.)
`
`Responding to a rejection of claims 1, 4, 5, 7-10, 15, 17, and 20-24, the
`
`applicants amended the claims “to recite a particular local pH value and/or to recite
`
`that the buffer optimizes absorption of buprenorphine while also inhibiting
`
`absorption of the naloxone.” (Ex. 1002, 2/29/12 Amendment and Response, at 7.)
`
`In particular, claim 1 was amended to include a “local pH” of from about 2 to
`
`about 3.5 in the presence of saliva. (Ex. 1002, 2/29/12 Amendment and Response,
`
`at 2.) Claim 17 (which issued as independent claim 9) was also amended to include
`
`a “local pH of about 2 to about 3.5.” (Ex. 1002, 2/29/12 Amendment and
`
`Response, at 4 (emphasis in original).)
`
`The alleged invention was intended to provide a maximum blood
`
`concentration (Cmax) that is 80 to 125% of the level provided by a Suboxone®
`
`tablet at the same dosage levels of buprenorphine and naloxone. (Ex. 1002, 2/29/12
`
`
`
`4
`
`

`

`
`
`Amendment and Response, at 7.) In order to achieve this, applicants “discovered
`
`that the film product should include a buffer that provides a specific buffer
`
`capacity to the film in order to achieve the desired result.” (Ex. 1002, 2/29/12
`
`Amendment and Response, at 7.) Applicants failed to mention to the examiner that
`
`the claimed film used the identical buffer (citric acid/sodium citrate) as had been
`
`used in Suboxone® tablets, to produce the same local pH as the tablets.
`
`To distinguish the prior art, the applicants focused on pH, and argued that it
`
`“discovered that at a pH of about 2-3.5, the relative absorptions [of buprenorphine
`
`and naloxone] can be controlled effectively.” (Ex. 1002, 2/29/12 Amendment and
`
`Response, at 12.) Nevertheless, the examiner again rejected the claims.
`
`In an advisory action, the examiner noted that Example 8—on which
`
`applicants relied to show “unexpected” results—only “tested products at a pH of
`
`from 3.0-3.5.” (Ex. 1002, 11/6/12 Advisory Action, at 3(emphasis in original).)
`
`According to the examiner, this was “not sufficient to provide evidence of
`
`unexpected or significant benefits associated with the full scope of the claimed
`
`invention, which recites a ‘local pH of about 2 to about 3.5 in the presence of
`
`saliva.’” (Id. at 3-4 (emphasis in original).) Thus, the examiner determined that
`
`“Applicant’s showing is not commensurate in scope with the claimed invention.”
`
`(Id. at 4.) Eventually, the claims were amended to recite the local pH range of
`
`about 3 to about 3.5 to provide a scope that “is fully and expressly supported by the
`
`
`
`5
`
`

`

`
`
`experimental results.” (Ex. 1002, 4/30/13 Amendment and Response with Request
`
`for Continued Examination, at 6.)
`
`On May 24, 2013, the examiner issued a Notice of Allowability. (Ex. 1002,
`
`5/24/13 Notice of Allowability.) The examiner cited the results of an interview as
`
`the basis on which the claims were allowed. (Id.) At the May 20, 2013 interview,
`
`the examiner “agreed that the prior art does not teach the claimed local pH” based
`
`on applicants’ representation that “the prior art is silent regarding the use of a
`
`buffer to provide a local pH which would achieve optimized absorption of
`
`buprenorphine and naloxone.” (Ex. 1002, 5/20/13 Examiner-Initiated Interview
`
`Summary.)
`
`III. GROUNDS FOR STANDING (§ 42.104(A))
`
`Petitioner certifies under 37 C.F.R. § 42.104(a) that the ’832 patent is
`
`available for Inter Partes Review and that Petitioner is not barred or estopped from
`
`requesting Inter Partes Review on the grounds identified in this Petition. Petitioner
`
`was served with a complaint asserting the ’832 patent on December 3, 2014 in
`
`Reckitt Benckiser Pharmaceuticals, Inc. v. Teva Pharmaceuticals USA, Inc., No.
`
`1:14-cv-01451-RGA (D. Del. Nov. 17, 2015). This Petition was timely filed on
`
`December 3, 2015.
`
`
`
`
`
`
`
`6
`
`

`

`
`
`IV. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
`
`A. Real Party in Interest (§ 42.8(b)(1))
`
`The real party-in-interest is Teva Pharmaceuticals USA, Inc. (“Teva” or
`
`“Petitioner”).2
`
`B. Related Proceedings (§ 42.8(b)(2))
`
`The following proceedings may affect or be affected by a decision in this
`
`proceeding:
`
`Name
`
`Number
`
`District
`
`Indivior Inc. v. Sandoz Inc.
`
`1-15-cv-01051
`
`DED
`
`Indivior Inc. v. Mylan Technologies Inc.
`
`1-15-cv-00209 WVND
`
`Indivior Inc. v. Mylan Technologies Inc.
`
`1-15-cv-01016
`
`DED
`
`Reckitt Benckiser Pharmaceuticals Inc. v.
`
`Alvogen Pine Brook, Inc.
`
`Reckitt Benckiser Pharmaceuticals Inc. v.
`
`Teva Pharmaceuticals USA, Inc.
`
`1-15-cv-00477
`
`DED
`
`1-14-cv-01451
`
`DED
`
`
`2 Teva is owned directly or indirectly by: Teva Pharmaceutical Industries Ltd.,
`
`Orvet UK, Teva Pharmaceuticals Europe B.V., Teva Pharmaceutical Holdings
`
`Coöperatieve U.A., and IVAX LLC.
`
`
`
`7
`
`

`

`
`
`Reckitt Benckiser Pharmaceuticals Inc. v. Par
`
`Pharmaceutical, Inc.
`
`1-14-cv-00422
`
`DED
`
`Reckitt Benckiser Pharmaceuticals Inc. v.
`
`Alvogen Pine Brook, Inc.
`
`Reckitt Benckiser Pharmaceuticals Inc. v.
`
`Watson Laboratories Inc.
`
`Reckitt Benckiser Pharmaceuticals, Inc. v.
`
`Par Pharmaceutical, Inc.
`
`1-13-cv-02003
`
`DED
`
`1-13-cv-01674
`
`DED
`
`1-13-cv-01461
`
`DED
`
`
`The following administrative proceedings may affect or be affected by a
`
`decision in this proceeding:
`
`The ’832 patent is part of a family of applications. Petitioner is aware of at
`
`least one currently pending U.S. patent application that claims the benefit of the
`
`’832 patent: U.S. Patent Application Serial No. 14/715,462, filed on May 18, 2015,
`
`which is pending.
`
`The ’832 patent was also the subject of two Inter Partes Reviews: IPR2014-
`
`00325 (“the BDSI IPR”) and IPR2014-00998, both initiated by petitioner
`
`Biodelivery Sciences International, Inc. In the BDSI IPR, the Board instituted
`
`
`
`8
`
`

`

`
`
`review of claims 15-19 as unpatentable over LabTec3 alone, and LabTec in view of
`
`Yang4 and Birch. (IPR2014-00325, Paper 17 at 17, 20.) The Board ultimately
`
`found that petitioner established by a preponderance of the evidence that claims
`
`15-19 are unpatentable on both instituted grounds. (IPR2014-00325, Paper 43 at
`
`27.) That decision is currently on appeal.
`
`In the IPR2014-00998 proceeding, the petitioner challenged claims 15-19 as
`
`unpatentable over Oksche5 (referred to in that case as “Euro-Celtique”); Oksche in
`
`view of the European Medicines Agency (EMEA) Study Report on Suboxone®
`
`tablets, 2006 (“EMEA Study Report”)6; Oksche in view of the EMEA Study
`
`Report and WO 2003/030883; and Oksche in view of the EMEA Study Report and
`
`Yang. (IPR2014-00998, Paper 12 at 5.) In view of the earlier BDSI IPR, the Board
`
`
`3 Ex. 1007, WO 2008/040534, published April 10, 2008, to Applicant LabTec
`
`GmbH (“LabTec”).
`
`4 Ex. 1006, U.S. Patent No. 7,357,891, published December 23, 2004 and
`
`issued April 15, 2008, to Yang et al. (“Yang”).
`
`5 Ex. 1005, WO 2008/025791, published March 6, 2008, to Applicant Euro-
`
`Celtique S.A. (“Oksche”).
`
`6 Ex. 1011, European Medicines Agency Initial Marketing-Authorisation
`
`Document, Scientific Discussion, Oct. 19, 2006 for Suboxone sublingual tablets.
`
`
`
`9
`
`

`

`
`
`exercised its discretion under 35 U.S.C. § 325(d) to deny the Petition without
`
`reaching the merits. (Id. at 2)
`
`C. Lead and Backup Counsel (§ 42.8(b)(3))
`
`Lead Counsel
`
`Backup Counsel
`
`Elizabeth Holland
`
`(Reg. No. 47,657)
`
`Eleanor M. Yost
`
`(Reg. No. 58,013)
`
`GOODWIN PROCTER LLP
`
`J. Coy Stull
`
`The New York Times Building
`
`(Reg. No. 62,599)
`
`620 Eighth Avenue
`
`GOODWIN PROCTER LLP
`
`New York, NY 10018
`
`901 New York Avenue NW
`
`(212) 813-8800 (telephone)
`
`Washington, DC 20001
`
`(212) 355-3333 (facsimile)
`
`(202) 346-4000 (telephone)
`
`eholland@goodwinprocter.com
`
`(202) 346-4000 (facsimile)
`
`eyost@goodwinprocter.com
`
`jstull@goodwinprocter.com
`
`
`
`Elaine H. Blais
`
`Robert Frederickson III
`
`(both to seek pro hac vice admission)
`
`GOODWIN PROCTER LLP
`
`
`
`10
`
`

`

`
`
`
`
`Exchange Place
`
`53 State Street
`
`Boston, Massachusetts 02109
`
`(617) 570-1000 (telephone)
`
`(617) 523-1231 (facsimile)
`
`eblais@goodwinprocter.com
`
`rfrederickson@goodwinprocter.com
`
`
`
`Robert V. Cerwinski
`
`(to seek pro hac vice admission)
`
`GOODWIN PROCTER LLP
`
`The New York Times Building
`
`620 Eighth Avenue
`
`New York, NY 10018
`
`(212) 813-8800 (telephone)
`
`(212) 355-3333 (facsimile)
`
`rcerwinski@goodwinprocter.com
`
`D.
`
`Service Information (§ 42.8(b)(4))
`
`Please direct all correspondence to counsel at the contact information above.
`
`Petitioner consents to service by electronic mail.
`11
`
`
`
`

`

`
`
`V.
`
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND
`IDENTIFICATION OF THE CHALLENGE (§ 42.104(B))
`
`Petitioner challenges claims 1-7 and 9-12 of the ’832 patent and requests
`
`review of those claims under 35 U.S.C. § 311 and AIA § 6. Petitioner’s grounds of
`
`challenge are as follows:
`
`Ground Claims
`
`Description
`
`1
`
`2
`
`3
`
`4
`
`1-2, 4-7, and
`
`Obvious under § 103 over LabTec in view of Yang,
`
`9-10
`
`3, and
`
`11-12
`
`the Suboxone® 2002 Label,7 SBOA,8 and Birch9
`
`Obvious under § 103 over LabTec in view of Yang,
`
`the Suboxone® 2002 Label, SBOA, Birch, and the
`
`’055 publication10
`
`1-2, 4-7, and
`
`Obvious under § 103 over Oksche in view of Yang,
`
`9-10
`
`3, and
`
`the Suboxone® 2002 Label, SBOA, and Birch
`
`Obvious under § 103 over Oksche in view of Yang,
`
`
`7 Ex. 1008, Suboxone® 2002 Label.
`
`8 Ex. 1009, Suboxone® Tablet Summary Basis of Approval (“SBOA”).
`
`9 Ex. 1004, U.S. Patent Publication No. 2005/0085440, published April 21,
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`2005 (“Birch”).
`
`10 Ex. 1010, U.S. Patent Application Publication No. 2005/0037055 (“the ’055
`
`publication”).
`
`
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`12
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`

`
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`11-12
`
`the Suboxone® 2002 Label, SBOA, Birch, and the
`
`’055 publication
`
`
`In support of these grounds of unpatentability, this Petition is accompanied by the
`
`declaration of Dr. Nandita Das (“Das Decl.,” Ex. 1003).
`
`
`
`The Grounds raised in this Petition are meaningfully distinct. Ground 1
`
`presents obviousness of claims 1-2, 4-7, and 9-10 based upon a combination of
`
`LabTec in view of Yang, the Suboxone® 2002 Label, SBOA, and Birch. Ground 3
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`differs from Ground 1 in asserting obviousness of claims 1-2, 4-7, and 9-10 based
`
`upon the combination of Oksche in View of Yang, the Suboxone® 2002 Label,
`
`SBOA, and Birch. This ground is not cumulative of Ground 1. LabTec explicitly
`
`identifies and explains the criticality of pH on the absorption of buprenorphine and
`
`naloxone through mucosal membranes, a teaching applicants claimed was lacking
`
`in Oksche. Oksche teaches a mucoadhesive film, which Patent Owner asserted was
`
`not disclosed in LabTec.11 Thus, LabTec and Oksche each recite distinct and non-
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`cumulative teachings relevant to the ’832 patent claims.
`
`11 In the BDSI IPR, Patent Owner incorrectly urged that the ’832 patent claims are
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`limited to mucoadhesive films and mucosal absorption of active ingredients, and
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`that LabTec purportedly failed to teach a mucoadhesive film. The Board ultimately
`
`found that the petitioner established that LabTec’s teachings nevertheless
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`
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`13
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`Nor are Grounds 2 and 4 cumulative of Grounds 1 and 3. Both assert
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`obviousness of dependent claims 3, 11-12 in further view of the ’055 publication.
`
`VI. LEVEL OF ORDINARY SKILL IN THE ART
`
`A person of ordinary skill in the art would include a person who possesses a
`
`Master’s or Ph.D. in pharmaceutical sciences, formulation chemistry, or a related
`
`filed, plus a number of years of relevant experience in developing drug
`
`formulations.. (See Das Decl., Ex. 1003 at ¶ 26.) Alternatively, a person of
`
`ordinary skill could have a master’s degree or Ph.D. and less practical experience.
`
`(Id.)
`
`VII. THE CHALLENGED CLAIMS OF THE ’832 PATENT
`
`Petitioner challenges claims 1-7 and 9-12. Independent claims 1 and 9
`
`provide:
`
`1.
`
`A film dosage composition comprising:
`a.
`A polymeric carrier matrix;
`b.
`A
`therapeutically effective amount of buprenorphine or a
`pharmaceutically acceptable salt thereof;
`
`anticipated the challenged claims. (See, e.g., BDSI IPR, Paper 17 at 20.) The
`
`challenged claims here, like the challenged claims in the BDSI IPR, are not limited
`
`to mucoadhesive films or mucosal absorption of active ingredients. To the extent
`
`that the Board finds otherwise, Oksche teaches a mucoadhesive film, and the
`
`Patent Owner has not asserted otherwise.
`
`
`
`14
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`

`
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`A therapeutically effective amount of naloxone or a pharmaceutically
`c.
`acceptable salt thereof; and
`d.
`A buffer in an amount to provide a local pH for said composition of a
`value sufficient to optimize absorption of said buprenorphine, wherein said
`local pH is from about 3 to about 3.5 in the presence of saliva.
`
`9. A method of treating narcotic dependence of a user, comprising the steps
`of:
`
`a.
`
`b.
`
`providing a composition comprising:
`i.
`A polymeric carrier matrix;
`ii.
`A therapeutically effective amount of buprenorphine or a
`pharmaceutically acceptable salt thereof;
`iii. A
`therapeutically effective amount of naloxone or a
`pharmaceutically acceptable salt thereof; and
`iv. A buffer in an amount to provide a local pH of about 3 to about
`3.5 for said composition of a value sufficient to optimize absorption
`of said buprenorphine and also sufficient to inhibit absorption of said
`naloxone; and
`administering said composition to the oral cavity of a user.
`
`(Ex. 1001 at 23:58-67; 24:25-39.) The dependent claims are directed to
`
`pharmacokinetic parameters, specific compositions of polymers, buffers, dosage
`
`strengths, etc.
`
`VIII. CLAIM CONSTRUCTION
`
`A claim subject to Inter Partes Review receives the broadest reasonable
`
`construction or interpretation in light of the specification of the patent in which it
`15
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`
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`appears because, among other reasons, the patent owner has an opportunity to
`
`amend the claims. 37 C.F.R. § 42.100(b); In re Cuozzo Speed Techs., LLC, 793
`
`F.3d 1268, 1275-79 (Fed. Cir. 2015). For purposes of this proceeding only, no
`
`claim term warrants a specific construction.
`
`IX. SCOPE AND CONTENT OF THE PRIOR ART
`
`A. WO2008/040534 (“LabTec”) (Ex. 1007)
`
`LabTec qualifies as prior art because it published on April 10, 2008, over
`
`one year prior to the earliest priority date claimed in the ’832 patent. LabTec was
`
`not considered by the Office during prosecution of the ’832 patent.
`
`LabTec discloses the use of an orally-disintegrating film dosage form for
`
`delivering buprenorphine and naloxone that is bioequivalent to Suboxone® tablets.
`
`(Ex. 1007, LabTec, at 2-3, 22; see also BDSI IPR, Paper 43 at 13.) Labtec’s film
`
`can be formulated to include pharmaceutical active agents, a film-forming agent,
`
`and other ingredients. (Ex. 1007, LabTec, at 13-14.) LabTec also discloses the
`
`necessary pharmacokinetic profile to achieve bioequivalence between the film and
`
`an existing product, such as the Suboxone® tablet. (Id. at 4-5, 13, 22; BDSI IPR,
`
`Paper 43 at 14.) LabTec teaches that to make a film bioequivalent to a tablet, the
`
`film product should “follow[] the same metabolic and bioabsorption pathways as
`
`the innovator’s [tablet] product, to ensure that the dosage form achieves the proven
`
`clinical efficacy of the innovator [tablet] product.” (Ex. 1007, LabTec, at 2.)
`
`
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`16
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`

`

`
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`B. WO 2008/025791 (“Oksche”) (Ex. 1005)
`
`Oksche was filed on August 29, 2007 and is prior art to the ’832 patent.
`
`Oksche discloses that one can make an orally-disintegrating film dosage form
`
`containing buprenorphine and naloxone. (Ex. 1005, Oksche at 17.) Oksche
`
`expressly referenced Suboxone® tablets, (id. at 3, 6, 21), and disclosed the target
`
`Cmax and AUC0-48 for buprenorphine that would be necessary to make a film
`
`bioequivalent to those tablets, as well as methods for making that film. (Id. at 9.)
`
`The disclosed dosage forms contain at least one matrix-forming polymer. (Id. at
`
`17.) Oksche reports that the disclosed film dosage forms can be made to release
`
`buprenorphine rapidly—in less than 3 minutes—upon sublingual administration.
`
`(Id. at 4, 17-18.) The films may also contain pH modifiers. (Id. at 15.)
`
`C. U.S. Patent No. 7,357,891 (“Yang”) (Ex. 1006)
`
`Yang was published on August 15, 2008, and is prior art to the ’832 patent.
`
`Yang “relates to rapidly dissolving films and methods of their preparation.” (Ex.
`
`1006, Yang at 1:27-28.)
`
`Yang teaches methods for making ingestible films using the same polymers
`
`and ingredients disclosed in the ’832 patent. (Id. at 14:56-15:5.) In fact, the ’832
`
`patent admits that the processes set forth in Yang are suitable for creating an
`
`embodiment of the ’832 patent. (Ex. 1001 at 15:29-37.)
`
`
`
`
`
`17
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`

`
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`D.
`
`Suboxone® Sublingual Tablets (Label and SBOA, Exs. 1008 and
`1009)
`
`The Suboxone® tablet 2002 label (“Suboxone® 2002 Label”) identifies
`
`Suboxone® as a tablet containing buprenorphine hydrochloride and naloxone
`
`hydrochloride and, inter alia, excipients such as a citric acid/sodium citrate buffer
`
`system. (Ex. 1008, at 8.) The drug was approved by FDA on October 8, 2002 and
`
`indicated to treat opioid dependence. (Id. at 7.) The tablets have been available on
`
`the market in the United States since approval.
`
`The pharmacokinetic profile of Suboxone® sublingual tablets was published
`
`in the prior art. (See, e.g., Ex. 1011, EMEA Study Report; Ex. 1009, Tablet
`
`Summary Basis of Approval (“SBOA”).) It was also known that under the
`
`conditions provided by the tablets at the site of administration in the mouth,
`
`buprenorphine absorbed transmucosally, avoiding the first-pass effect, while
`
`naloxone was not significantly absorbed, either transmucosally or through the GI
`
`tract. (Ex. 1003, Das Decl. at ¶ 50, 58.)
`
`Patent Owner stipulated in a co-pending litigation that the Suboxone® 2002
`
`Label and SBOA are prior art to the ’832 patent.12
`
`
`12 Reckitt Benckiser Pharmaceuticals, Inc. v. Watson Laboratories, Inc., No. 13-
`
`cv-0167-RGA P.I. 347, Ex. 1, at ¶¶ 123-24. The Suboxone® Label and SBOA
`
`
`
`18
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`

`
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`E. U.S. Patent Publication 2005/0085440 (“Birch”) (Ex. 1004)
`
`Birch was published on April 21, 2005 and is prior art to the ’832 patent.
`
`Birch describes pharmaceutical formulations that contain buprenorphine. (Ex.
`
`1004, Birch, at [0001], [0010].) Like the ’832 patent, Birch’s formulations are
`
`designed to provide transmucosal absorption of the buprenorphine into the plasma.
`
`(Id. at [0010].) Also like the ’832 patent, Birch’s formulations include polymers,
`
`sugars, buffers, and other additives. (See id. at [0064] (disclosing HPMC, the
`
`polymer preferred in the ’832 patent), [0050] (disclosing sugars such as mannitol),
`
`[0071] (disclosing buffers).)
`
`Birch also discloses administering buprenorphine-containing formulations
`
`(aqueous solutions) to the nasal mucosa at a pH of about 3.5—within the ’832
`
`patent’s claimed pH range. (Id. at Figures 1-4, [0139-41] Example 1, [0145-47]
`
`Example 3, [0152-54] Example 5, [0206-11] Example 8.) At claim 1, Birch also
`
`discloses administering a buprenorphine solution at a pH range of 3 to 4.2. (Id. at
`
`16 Claim 1.)
`
`As the anatomy of the oral and nasal mucosa is quite similar, a person of
`
`ordinary skill would have understood that the same principle of drug delivery will
`
`apply to both tissues. (Ex. 1003, Das Decl. at ¶ 80.)
`
`qualify as 102(b) prior art as both were publicly available printed publications at
`
`least as early as 2002.
`
`
`
`19
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`

`
`
`F.
`
`The ’055 Publication (E