Patent No. 8,475,832
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`Attorney Docket No. 117744-00041
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`Paper No._______
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
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` BIODELIVERY SCIENCES INTERNATIONAL, INC.
`Petitioner
`
`v.
`
`RB PHARMACEUTICALS LIMITED
`Patent Owner
`
`
`Patent 8,475,832
`
`_______________
`
`Mailed: January 15, 2014
`
`
`PETITION FOR INTER PARTES REVIEW
`UNDER 35 USC §§ 311-319 AND 37 CFR § 42.100 ET. SEQ.
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`Patent No. 8,475,832
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`Attorney Docket No. 117744-00041
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`TABLE OF CONTENTS
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`Page
`INTRODUCTION .............................................................................................. 1
`I.
`II. MANDATORY NOTICES AND CERTIFICATIONS ..................................... 2
`III. SUMMARY OF THE ‘832 PATENT AND PROSECUTION ......................... 4
`A. The invention described in the ‘832 patent is not new ....................... 4
`B. The invention disclosed in the ‘832 patent is not
`surprising ............................................................................................ 8
`C. The ‘832 patent was allowed in a haze of confusing
`definitions and incorrect arguments ................................................. 10
`D. The alleged novelty of the challenged claims is
`contradicted by the ‘832 patent specification ................................... 13
`IV. CONSTRUCTION OF THE CHALLENGED CLAIMS ................................ 14
`A. Construction of “film formulation.” ................................................. 15
`B. Construction of “provides an in vivo plasma profile.” ..................... 20
`V. STATEMENT OF PRECISE RELIEF REQUESTED AND
`CLAIM-BY-CLAIM EXPLANATION OF GROUNDS OF
`INVALIDITY................................................................................................... 22
`A. The only claim elements entitled to patentable weight in
`the challenged claims are found in the admitted prior art
`and additional art cited herein........................................................... 22
`B. The wherein clause, which recites a desired result, is not
`entitled to patentable weight ............................................................. 23
`C. Even if the desired result were entitled to patentable
`weight, it is still anticipated in the cited art ...................................... 26
`Ground 1. Claims 15-19 are anticipated by the
`Suboxone Tablet Label .................................................. 26
`Ground 2. Claims 15-19 are obvious over Suboxone
`Tablet Label ................................................................... 31
`Ground 3. Claims 15-19 are obvious over Suboxone
`Tablet Label in view of Yang ........................................ 33
`Ground 4. Claims 15-19 are obvious over Suboxone
`Tablet Label in view of Yang and Birch ....................... 35
`Ground 5. Claims 15-19 are anticipated by Labtec ........................ 38
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`Ground 6. Claims 15-19 are obvious in view of Labtec ................. 41
`Ground 7. Claims 15-19 are obvious over Labtec in
`view of Birch ................................................................. 43
`Ground 8. Claims 15-19 are obvious over Labtec in
`view of Birch and Yang ................................................. 44
`Ground 9. Claims 15-19 are anticipated by Euro-
`Celtique .......................................................................... 46
`Ground 10. Claims 15-19 are obvious in view of Euro-
`Celtique .......................................................................... 50
`Ground 11. Claims 15-19 are obvious over Euro-Celtique
`in view of Birch ............................................................. 53
`Ground 12. Claims 15-19 are obvious over Euro-Celtique
`in view of Birch and Yang ............................................. 54
`VI. CONCLUSION ................................................................................................ 56
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`Patent No. 8,475,832
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`Attorney Docket No. 117744-00041
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`Exhibit 1001:
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`US Patent 8,475,832
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`Exhibit List
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`Exhibit 1002:
`
`Reckitt Benckiser Pharmaceuticals, Inc., RB Pharmaceuticals
`Limited, and MonoSol, RX, LLC., WDNC Civil Action No.
`5:13-cv-760, Complaint filed October 29, 2013 (“Complaint”)
`
`Exhibit 1003:
`
`Reckitt Annual Report (“Annual Report”)
`
`Exhibit 1004:
`
`Declaration of Maureen Reitman, Sc.D. (“Reitman”)
`
`Exhibit 1005:
`
`Declaration of Phillip T. Lavin, Ph.D. (“Lavin”)
`
`Exhibit 1006:
`
`First Office Action mailed August 31, 2011 (“First OA”)
`
`Exhibit 1007:
`
`Response filed February 29, 2012 (“First Response”)
`
`Exhibit 1008:
`
`Second Office Action mailed May 2, 2012 (“Second OA”)
`
`Exhibit 1009:
`
`Response to filed October 22, 2012 (“Second Response”)
`
`Exhibit 1010:
`
`Third Office Action mailed November 6, 2012 (“Third OA”)
`
`Exhibit 1011:
`
`Response to filed April 30, 2013 (“Third Response”)
`
`Exhibit 1012:
`
`Notice of Allowance mailed May 24, 2013, including the
`attached Interview Summary (“NOA”)
`
`Exhibit 1013:
`
`Suboxone® tablet label, Revised September 2006 (“Suboxone
`Tablet Label”)
`
`Exhibit 1014: Merriam-Webster’s Collegiate Dictionary (10th ed. 2000)
`
`Exhibit 1015:
`
`European Medicines Agency (EMEA) Study Report on
`Suboxone® tablets, 2006 (“Suboxone Tablet Study Report”)
`
`Exhibit 1016:
`
`US Patent No. 7,357,891, published December 23, 2004, to
`Yang et al. (“Yang”)
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`
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`Exhibit 1017:
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`International Patent Publication No. WO 2008/040534,
`published April 10, 2008, to Applicant Labtec GmbH
`(“Labtec”)
`
`Exhibit 1018:
`
`International Patent Publication No. WO 2008/025791,
`published March 6, 2008, to Applicant Euro-Celtique S.A.
`(“Euro-Celtique”)
`
`Exhibit 1019:
`
`US Patent Publication No. 2005/0085440, published April 21,
`2005, to Birch et al. (“Birch”)
`
`Exhibit 1020:
`
`Power of Attorney
`
`Exhibit 1021:
`
`Assignment from Reckitt Benckiser Healthcare (UK) Limited
`to RB Pharmaceuticals Limited
`
`Exhibit 1022:
`
`Assignment from MonoSol Rx, LLC to Reckitt Benckiser
`Healthcare (UK) Limited
`
`Exhibit 1023:
`
`US Patent No. 7,425,292, published September 16, 2008, to
`Yang et al.
`
`Exhibit 1024: M.Voet, THE GENERIC CHALLENGE (Brown Walker Press 2d ed.
`2008)
`
`Certificate of Service
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`I.
`
`INTRODUCTION
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`Challenged claims 15-19 fail to recite any novel features that distinguish the
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`claimed formulation from prior art formulations. The only formulation limitations
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`recited in the challenged claims are an orally dissolving combination of two drugs,
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`buprenorphine and naloxone. The recited combination of buprenorphine and
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`naloxone is anticipated by Suboxone tablets, and that fact is acknowledged
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`throughout the ‘832 patent specification. The recitation of a “film formulation” is
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`also anticipated by Suboxone tablets because the components listed in the
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`Suboxone tablet label are described in the ‘832 patent as suitable for making films.
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`The recitation of Cmax ranges and other pharmacokinetic ranges—that are
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`broader than the acknowledged ranges resulting from prior art Suboxone tablets—
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`also fail to confer novelty. And even if these ranges were not anticipated, a
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`formulation claim must recite the formulation that it seeks to protect—e.g., specific
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`polymers or other components that are novel and non-obvious over the prior art—
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`and not desired properties that are the result of an unrecited, optional
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`administration step.
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`In short, the challenged claims 15-19 fail to recite even one novel feature.
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`The teaching in the prior art of every claim limitation—even those not entitled to
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`patentable weight—renders these claims invalid.
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`Patent No. 8,475,832
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`II. MANDATORY NOTICES AND CERTIFICATIONS
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`NOTICE OF LEAD AND BACKUP COUNSEL
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`Lead Counsel: Danielle L. Herritt (Reg. 43,670); Tel: 617.449.6513
`
`Backup Counsel: Kia L. Freeman (Reg. 47,577); Tel: 617.449.6549
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`Address: McCarter & English, LLP; 265 Franklin Street; Boston, MA 02110
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`617-549-6500 (reception); 617-607-9200 (fax)
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`NOTICE OF EACH REAL PARTY-IN-INTEREST
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`
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`The real-party-in-interest for this Petition is BioDelivery Sciences
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`International, Inc. (“Petitioner”); 801 Corporate Center Drive, Suite 210; Raleigh,
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`North Carolina 27607 USA.
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`NOTICE OF RELATED MATTERS
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`The subject of this petition is US Patent No. 8,475,832 (“the ‘832 patent”),
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`Ex. 1001. Reckitt Benckiser Pharmaceuticals, Inc. (“Reckitt”), RB
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`Pharmaceuticals Limited (“RB”), and MonoSol, RX, LLC (“MonoSol”) have
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`asserted the ‘832 patent against Petitioner to prevent Petitioner from launching a
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`product that would compete with its Suboxone films in a Complaint filed
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`October 29, 2013. See Reckitt Benckiser Pharmaceuticals, Inc., RB
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`Pharmaceuticals Limited, and MonoSol, RX, LLC. v. BioDelivery Sciences
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`International, Inc., WDNC Civil Action No. 5:13-cv-760, Complaint, Ex. 1002.
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`By way of background, Suboxone films are films sold by Reckitt that mimic
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`Reckitt’s predecessor Suboxone tablets. Reckitt voluntarily discontinued its
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`Suboxone tablets (a product that, until recently, enjoyed many years of FDA
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`exclusivity for sales) in order to convert its customers to Suboxone films (a product
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`that has recently begun to enjoy FDA exclusivity for sales). See Annual Report,
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`Ex. 1003. MonoSol is the developer and manufacturer of Suboxone films for
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`Reckitt. Shortly after filing, original assignee, MonoSol, assigned to Reckitt
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`Healthcare (UK) Limited (Ex. 1022), who then later assigned to RB (Ex. 1021).
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`For the avoidance of confusion, Reckitt Healthcare (UK) Limited, RB and
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`MonoSol, the successive owners of the ‘832 patent, who are plaintiffs in the above-
`
`captioned case, are collectively referred to as “Applicant.”
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`NOTICE OF SERVICE INFORMATION
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`
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`Please direct all correspondence regarding this proceeding to lead counsel at
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`the address shown above. Petitioner consents to electronic service by email at
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`IPR832@mccarter.com and dherritt@mccarter.com.
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`GROUNDS FOR STANDING
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`
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`Petitioner certifies that the patent for which review is sought is available for
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`inter partes review and that Petitioner is not barred or estopped from requesting an
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`inter partes review challenging the patent claims on the grounds identified in this
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`petition.
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`III. SUMMARY OF THE ‘832 PATENT AND PROSECUTION
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`A. The invention described in the ‘832 patent is not new.
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`In the ‘832 patent, Applicant summarizes its alleged invention as providing a
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`film dosage that is bioequivalent to its existing Suboxone tablet:
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`Currently, treatment of opioid dependence is aided by
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`administration of Suboxone® [tablet], which is an orally
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`dissolvable tablet. This tablet which provides a combination of
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`buprenorphine (an opioid agonist) and naloxone (an opioid
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`antagonist). [sic] Therefore, the present invention provides a
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`method of treating narcotic dependence by providing an orally
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`dissolvable film dosage, which provides a bioequivalent effect to
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`Suboxone® [tablets]. (‘832 patent at 4:52-60.)
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`In other words, the alleged invention features the same oral dissolvability,
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`same drug combination, same strength, same route of delivery, and the same or
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`similar pharmacokinetic parameters (such as bioequivalent Cmax and AUC) as the
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`Suboxone tablet. See also id. at Examples 1-8.
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`Even the film formulations described in the ‘832 patent are anticipated by
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`the Suboxone tablet—which is perhaps not surprising since Applicant was
`
`attempting to copy its own tablet. Compare e.g., Ex. 1013, Suboxone Tablet Label
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`at p. 1, col. 1, last two ¶s (“Each tablet also contains lactose, mannitol, cornstarch,
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`povidone K30 [polyvinyl pyrrolidone or PVP], citric acid, sodium citrate, FD&C
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`Yellow No. 6 color, magnesium stearate, and the tablets also contain Acesulfame
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`K Sweetener and a lemon lime flavor”) to Ex. 1001, ‘832 patent at 5:30-38
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`(“Specific examples of useful water-soluble polymers include…polyvinyl
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`pyrrolidone…starch”); at 9:67-10:4 (“The sweeteners may be chosen from
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`…mannitol…acesulfame-K…and natural intensive sweeteners”); and Example 5 at
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`Table 1 (“FD&C yellow #6”). Even the preferred buffer system used in all the
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`examples of the ‘832 patent (sodium citrate and citric acid) is disclosed in the
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`Suboxone Tablet Label. Compare e.g., Ex. 1013, Suboxone Tablet Label at p. 1,
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`last two ¶s (“Each tablet also contains …citric acid, sodium citrate”) to Ex. 1001,
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`‘832 patent at Examples 1 and 4-9 and at claim 7.
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`To the extent that films or methods of making films could be considered
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`new, the ‘832 patent admits that films could be formed by any process and
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`methods of making its allegedly inventive films were known. See Ex. 1001 at
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`15:29-30 (“The film compositions of the present invention may be formed via any
`
`desired process.”). Indeed, suitable processes are disclosed by incorporating prior
`
`art by reference, including US Patent No. 7,357,891. The ‘891 patent describes
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`methods of making films using the same polymers, e.g., polyvinyl pyrrolidone or
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`PVP (see Exhibit 1016 at 14:64 listing it as a suitable “Film Forming Polymer”),
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`and other ingredients the ‘832 patent disclosed as suitable, and which are listed in
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`the Suboxone Tablet Label.
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`The ‘832 patent discloses the process of copying the Suboxone tablet in its
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`examples. See Ex. 1001 at Examples 1-8. The examples purport to teach that, in
`
`order to provide a bioequivalent effect to Suboxone tablets, a pH of 3-3.5 is critical
`
`and surprising. But this pH is merely the pH of Suboxone tablets. Dr. Reitman has
`
`demonstrated that the pH of Suboxone tablets is about 3.5. See Ex. 1004, Reitman
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`Decl. at ¶ 5.
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`Example 1 provides a film component list that includes the same drugs at the
`
`same dosage strengths as Suboxone tablets. Ex. 1001 at Example 1. Example 1
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`uses the same buffer system (citric acid and sodium citrate) as that used in
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`Suboxone tablets. Example 2 verifies the pharmacokinetic parameters of the
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`existing Suboxone tablets. Example 3 calculates the values required “to be
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`considered bioequivalent to the Suboxone tablet” using the FDA’s standard 80-
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`125% rule.
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`Example 4 tests “various film products” at pH 3.5, having the same active
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`ratios and amounts as the Suboxone tablets (2 mg/0.5 mg and 16mg/mg of
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`buprenorphine/naloxone). In its first absorption study example, “[t]he inventive
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`films were . . . determined to have provided a bioequivalent absorption of
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`buprenorphine at a local pH of 3.5 as the commercially available Suboxone®
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`tablet.” Id. at 18:12-15. Indeed, as appears to be admitted in the foregoing
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`sentence, and verified by Dr. Reitman, the pH of Suboxone tablets is 3.5. Ex.
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`1004, Reitman Decl. at ¶ 5.
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`It was also found that “[t]he values for absorption of naloxone were very
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`close to the bioequivalent range of Suboxone®.” Ex. 1001 at 18:15-16. The ‘832
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`patent explains that the “slightly higher absorption of naloxone was not due to the
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`local pH but rather to the amount of buffer….” Id. at 18:17-22. Thus, on this first
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`try, Applicant had identified the appropriate pH of 3.5. Again, this is the pH of the
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`prior art Suboxone tablets. Indeed, Examples 5-8 test additional film products at a
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`buffered pH of 3.5 (the same pH already identified in Example 4, but now referred
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`to as pH 3-3.5) side-by-side against film products at other pHs. Test formulation 2,
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`with a pH of 3.5, is characterized as providing a “substantially bioequivalent”1
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`absorption of buprenorphine and naloxone as the commercially available Suboxone
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`tablet. Id. at patent at 23:1-10.
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`Examples 5-8 demonstrate that none of the buffered pHs provided
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`absorption values in the standard 80-125% bioequivalence range—as even the
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`
` It is not clear what Applicant means by “substantially bioequivalent” because Test
`
` 1
`
`formulation 2 does not fall within the 80-125% of the Suboxone tablet values
`
`presented in Tables 10, 11, or 2A. See Ex. 1005, Lavin Decl. at ¶ 5 (opining on
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`bioequivalence).
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`Examples admit. See also Ex. 1005, Lavin Decl. at ¶ 9 (opining that Tables 7, 9,
`
`and 11 do not show bioequivalence for Test Formulations 1, 2, or 3). And even if
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`the buffered pH of 3.5 did provide a bioequivalent absorption profile for both
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`actives—which it did not—neither the pH nor the allegedly resulting
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`pharmacokinetic profile is new. Again, the pH is merely the pH of Suboxone
`
`tablets (Ex. 1004, Reitman Decl. at ¶ 5), and the bioequivalent range is
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`characterized as merely 80-125% the prior art Suboxone tablets (Examples 2-3),
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`and therefore anticipated by the same.
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`In sum, the alleged invention disclosed in the ‘832 patent is not new.
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`B.
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`The invention disclosed in the ‘832 patent is not surprising.
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`In addition to lacking novelty, contrary to statements made by Applicant in
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`the specification (and later during prosecution), the invention disclosed in the ‘832
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`patent is not surprising. Specifically, the ‘832 patent states “it has been
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`surprisingly discovered by the Applicants that by buffering the dosage to a
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`particular pH level, the optimum levels of absorption of the agonist and antagonist
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`may be achieved.” Ex. 1001 at 11:50-53. But this statement and the
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`characterization of the results of Test formulation 2 (pH=3-3.5) is far from
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`“surprising” (id. at 23:1-6) as revealed by the Examples themselves.
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`First, contrary to the characterization of the results of Example 8 as
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`“surprising” (id. at 23:4), the results were consistent with the results of a prior
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`example of administering a film having the same pH, i.e., Example 4.2
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`Second, even the briefest examination of the data reported in Examples 6-8
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`reveals that the data was very likely obtained at the same time from the same in
`
`vivo study. Specifically, all three examples use the same Suboxone sublingual
`
`data. The Tmax, Cmax, AUClast, AUCinf and T1/2 values for Suboxone tablets—
`
`including the mean, standard deviation (SD) and CV%—for every single parameter
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`are identical. It is impossible that these are separate studies because these numbers
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`could never be exactly the same for three different studies. Ex. 1005, Lavin Decl.
`
`at ¶ 7 (“it is statistically impossible for new experiments to have been conducted
`
`
`
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`2 Indeed—from a side-by-side comparison of Test formulation 2 of Example
`
`5 and the “8/2” formulation of Example 1—it is clear that the very first
`
`formulations of Example 1 also had a pH of about 3.5 because the two compared
`
`formulations appear to be identical (except that Example 5 uses generic descriptors
`
`for some of the specific component names). The pH is reported to be 3-3.5 in
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`Example 5.
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`.
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`and yield identical results for Suboxone tablets three times in three different
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`comparisons. Contrary to the related description, the buprenorphine and naloxone
`
`absorption of all three Test Formulations could have been determined in a single in
`
`vivo study and the three Examples retrospectively constructed.”).
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`Third, there is nothing surprising or even novel about a formulation of the
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`recited actives with a pH of 3.5, because this is the pH of the prior art Suboxone
`
`tablets. See Ex. 1004, Reitman Decl. at ¶ 5. The pH of the prior art Suboxone
`
`tablets can be readily determined. The Applicant appears to have been in a
`
`particularly unique position to know the pH the Suboxone tablet, at least because it
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`had quantities of the tablets that it used as a control, and also because it has
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`manufactured and sold the Suboxone tablets for many years.
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`In short, there is nothing surprising about copying the pH of a tablet one is
`
`attempting to copy in film dosage form.
`
`C. The ‘832 patent was allowed in a haze of confusing definitions and
`incorrect arguments.
`
`Throughout prosecution, the examiner rejected challenged claims 15-19 as if
`
`they recited the pH range of claims 1-14. Ex. 1006, First OA at ¶ 12 on p. 4
`
`(“Furthermore, the cited reference does not teach the specific range of pH recited
`
`in the instant claims [all pending claims including issued claims 15-19]”); Ex.
`
`1008, Second OA at ¶ 14, pp. 5-6; and Ex. 1010, Third OA at ¶ 6 at p. 2
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`(“Applicants traversed the instant rejection on the grounds that [Euro-Celtique]
`
`does not disclose the pH range recited in the instant claims [claims that include
`
`issued claims 15-19]”). The Applicant repeatedly argued during prosecution that
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`the pH range was surprising because it “minimizes the absorption of naloxone but
`
`optimizes the absorption of buprenorphine”—suggesting that the absorption of
`
`naloxone was being decreased and the absorption of buprenorphine was being
`
`increased by lowering the pH. Ex. 1011, Third Response at 6:5-9; Ex. 1009,
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`Second Response at 10:10-14. But, in fact, the relevant definitions and examples
`
`reveal that there is nothing surprising because the Applicant was seeking to inhibit
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`the absorption of both naloxone and buprenorphine to copy Suboxone tablets.
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`Applicant appears to have been confused by its own confusing definitions
`
`and arguments. Applicant bases its “surprising” result on the premise that “[b]oth
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`compounds are conjugate organic acids with pKa’s at approximately 8, and yet as
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`the pH of the film for delivering the agents decreases, one compound undergoes a
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`optimum absorption, but the other compound surprisingly trends in the opposite
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`direction and is inhibited at the same lower pH levels.” Ex. 1011, Third Response
`
`at 7:2-5. Contrary to the Applicant’s suggestion, Examples 7 and 8 show that, as
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`the buffered pH is lowered from 5-5.5 to 3-3.5, both compounds trend in the same
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`direction and to a remarkably similar degree. In particular, the Cmax of
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`buprenorphine decreases from 3.47 to 2.68 ng/mL (i.e., a reduction to 77% of the
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`previous value) and the Cmax of naloxone decreases from 173 to 130 pg/mL (i.e.,
`
`a reduction to 75% of the previous value). The compounds did not “surprisingly”
`
`trend in the opposite direction, but rather both trended in the same direction.
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`Indeed, the facts in the ‘832 patent specification demonstrate that the compound
`
`trending from 5-5.5 to 3-3.5 is consistent in both direction and degree.
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`This line of argument—clearly incorrect, even according to the Applicant’s
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`own specification—seems to have confused and ultimately convinced the
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`examiner:
`
`Applicants explained that the prior art is silent regarding the use of
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`a buffer to provide a local pH which would achieve the optimized
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`absorption of buprenorphine and naloxone. The examiner agreed
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`that the prior art does not teach the claimed local pH.
`
`(Ex. 1012, NOA at p. 2.)
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`In short, the ‘832 patent was allowed in a haze of confusion and incorrect
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`arguments. Had the Office understood the full picture—not only that Applicant’s
`
`arguments were incorrect, but also that the prior art is not silent with respect to the
`
`use of buffers and pH to provide bioequivalent absorption of the actives—these
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`claims would not have been allowed.
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`D. The alleged novelty of the challenged claims is contradicted by the
`‘832 patent specification
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`It is not known why claims 15-19 were allowed, as they do not recite the pH
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`range that the Office relied upon in allowing the claims. Indeed, at the very end of
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`prosecution, Applicant explicitly took the position that challenged claims 15-19
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`were never examined. “These claims have not been addressed in any of the art
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`rejections, except by number. Thus, the limitations of these claims have never
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`been addressed by the Examiner.” See Ex. 1011, Third Response at p. 11:1-10.
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`Applicant then proceeds to identify its own reason why the claims were
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`allegedly patentable: that they recited a Cmax range for naloxone. Specifically,
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`Applicant argued that “while Oksche [Euro-Celtique] does discuss the Cmax for
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`buprenorphine, it is completely silent as to the Cmax for naloxone.” Id. At 11:9-
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`10.
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`But Euro-Celtique very clearly discloses that the absorption parameters of
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`Suboxone tablets (which include both buprenorphine and naloxone) are known and
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`expected in its inventive preparations. Ex. 1018, Euro-Celtique at 21:8-12. The
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`absorption parameters of Suboxone tablets, of course, explicitly anticipate a range
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`that is 80-125% of its absorption parameters. Applicant, once again, appears to
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`have been confused or have forgotten the basis of its claimed range.
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`As explained in the ‘832 patent, the Cmax and AUC ranges recited in the
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`challenged claims are by design 80-125% of Suboxone tablets (and therefore
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`anticipated by the Suboxone tablets). Ex. 1001 at 17:2-40 (Example 3). Whether
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`Euro-Celtique states the actual 80-125% ranges is irrelevant. The recited ranges
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`are still anticipated by those of the Suboxone tablets they were calculated to
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`encompass.
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`In short, the recited Cmax range—relied upon by Applicant during
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`prosecution as allegedly providing novelty—is, by design, anticipated by the prior
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`art Suboxone tablets and art disclosing films with absorption equivalent to the prior
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`art Suboxone tablets. There are no other recitations that could possibly confer
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`novelty, nor were any argued as such.
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`IV. CONSTRUCTION OF THE CHALLENGED CLAIMS
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`This Petition challenges claims 15-19 of the ‘832 patent. Claim 15 is the
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`only independent claim that is challenged. Claim 15 is directed to an orally
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`dissolving film formulation. The formulation of claim 15 includes buprenorphine
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`and naloxone. Claim 15 further recites that the formulation provides a desired in
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`vivo plasma profile for both buprenorphine and naloxone. Claim 15 is quoted
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`below:
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`15. An orally dissolving film formulation comprising
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`buprenorphine and
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`naloxone,
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`wherein said formulation provides
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`an in vivo plasma profile having a Cmax of between about
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`0.624 ng/ml and about 5.638 ng/ml for buprenorphine
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`and
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`an in vivo plasma profile having a Cmax of between about
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`41.04 pg/ml to about 323.75 pg/ml for naloxone.
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`In this proceeding, each claim must be given its broadest reasonable
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`construction in light of the specification of the ‘832 patent. See 37 CFR
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`§ 42.300(b).
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`A. Construction of “film formulation.”
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`While the specification does not expressly define the word “formulation” or
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`the phrase “film formulation” in the Definitions section, its usage defines this
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`phrase to include the combination of components capable of being used to prepare
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`a single film.
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`The ‘832 patent introduces, as the alleged problem to be solved, a single film
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`dosage that co-delivers an agonist and antagonist. In the Background section, the
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`‘832 patent states “[o]ral administration of two therapeutic actives in a single
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`dosage form can be complex.” Ex. 1001 at 1:19-20. The ‘832 patent refers to
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`“challenges in appropriately co-administering therapeutic agents.” Id. at 1:29-30.
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`The ‘832 patent concludes “t]here is currently a need for an orally dissolvable film
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`dosage form that provide the desired absorption levels of agonist and antagonist, . .
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`. thereby making abuse of the agonist difficult.” Id. at 1:65-2:2.
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`The specification discloses that “the invention relates to the treatment of
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`opioid dependence in an individual, while using a formulation and delivery that
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`hinders misuse of the narcotic.” Id. at 4:48-51. Applicant admitted that
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`“[d]elivery of compounds such as buprenorphine and naloxone was previously
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`known, however, the previously-accepted form of the delivery is in the form of a
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`tablet (e.g., a Suboxone® tablet).” Ex. 1007, First Response at 7:9-11. Applicant
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`explained: “The present invention is directed to formulation of a suitable film
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`product that provides a certain release profile.” Id. (emphasis added). Thus,
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`Applicant distinguished a film formulation from a resulting film product that
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`provides a release profile.
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`The specification incorporates US Patent Nos. 7,425,292 and 7,357,891 by
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`reference in their entirety. See Id. at 15:30-32. “Compositions P-Q [in the ‘292
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`patent] demonstrate the importance of proper formulation on the ability of the film
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`matrix to conform to a particular coating technique.” Ex. 1023, ‘292 patent at
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`24:4-6. “Each of the examples [in the ‘292 and ‘891 patents] shows the effect of
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`different ingredient formulations and processing techniques on the resultant film
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`products.” Id. at 23:49-51; see also Ex. 1016, ‘891 patent at 31:46-48. Thus, the
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`specification distinguishes a film formulation from a resulting film product.
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`The specification discloses that “[t]he formulations are set forth in Table 5.”
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`Ex. 1001, ‘832 patent at 18:41-42. Table 5 is entitled “Formulations of Test Films
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`. . . .” Id. at 18:44-67. Each of the three formulations consists of a combination of
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`components used in the preparation of a test film. Id. “Three film formulations . .
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`. were prepared.” Id. at 18:24-32. And the specification refers to the analysis of
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`the film formulations “as prepared in Example 5[: Preparation of Films for In Vivo
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`Study].” Id. at 19:7-9; 20:10-12; 21:45-47. In short, a “film formulation” in the
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`context of the ‘832 patent includes a combination of components capable of being
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`used to prepare a single film.
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`According to Applicant, “[t]he desired result [of the formulation] is a
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`product that provides a Cmax that is 80-120% the level provided by … the
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`Suboxone® tablet at the same dosage levels of the buprenorphine and the
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`naloxone.” Ex. 1007, First Response at 7:13-16. Moreover, “[t]he desired film
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`product includes the delivery of buprenorphine and naloxone together” at the same
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`time. Id. at 7:17-18. According to Applicant, “it was particularly surprising to
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`find that [both buprenorphine and naloxone] may be included in one film by
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`providing a buffer having a pH from about 2 to about 3.5.” Id. at 8 (emphasis
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`added). “The claims include both components to be together in a single film, with
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`a buffer capacity that is suitable for both.” Id. at 11 (emphasis added).
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`Accordingly, Applicant explained that the formulation is capable of being prepared
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`into a single film including both buprenorphine and naloxone. Thus, a “film
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`formulation” includes a “combination of components capable of being used to
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`prepare a single film.”
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`The foregoing construction is consistent with the common usage of the noun
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`formulation. A formulation generally refers to an act or product of formulating.
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`See e.g., Ex. 1014, Merriam-Webster’s Collegiate Dictionary (10th ed. 2000) at p.
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`458 (“formulation… n : an act or the product of formulating.”). In the context of
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`the challenged claims, which recite components but no steps, it does not make
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`sense to interpret the word formulation as an act. Accordingly, in the con