Trials@uspto.gov
`571-272-7822
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`
`
`
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`Paper 23
`Date: June 10, 2016
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`
`TEVA PHARMACEUTICALS USA, INC.,
`Petitioner,
`
`v.
`
`INDIVIOR UK LIMITED,
`Patent Owner.
`____________
`
`Case IPR2016-00280
`Patent 8,475,832 B2
`____________
`
`
`
`Before TONI R. SCHEINER, JACQUELINE WRIGHT BONILLA, and
`ZHENYU YANG, Administrative Patent Judges.
`
`BONILLA, Administrative Patent Judge.
`
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`

`

`IPR2016-00280
`Patent 8,475,832 B2
`
`I.
`
`INTRODUCTION
`Teva Pharmaceuticals USA, Inc., (“Petitioner”) filed a Petition
`requesting an inter partes review of claims 1–7 and 9–12 of U.S. Patent No.
`8,475,832 B2 (Ex. 1001, “the ’832 patent”). Paper 1 (“Pet.”). Indivior UK
`Limited (“Patent Owner”) filed a Preliminary Response. Paper 16 (“Prelim.
`Resp.”). Under 35 U.S.C. § 314(a), an inter partes review may not be
`instituted unless it is determined that there is “a reasonable likelihood that
`the petitioner would prevail with respect to at least 1 of the claims
`challenged in the petition.”
`We determine that Petitioner has not established a reasonable
`likelihood that it would prevail in showing the unpatentability of any claim
`challenged in the Petition. Accordingly, we decline to institute an inter
`partes review.
`A. Related Proceedings
`The parties identify multiple lawsuits where Patent Owner has filed
`suit against Petitioner and other defendants asserting infringement of the
`’832 patent in several U.S. district courts. Pet. 7–8; Paper 7, 3–4. In
`addition, the parties discuss IPR2014-00998, where a panel previously
`denied an inter partes review based on a petition filed by a different
`petitioner, challenging claims 15–19 of the same patent at issue here. Pet.
`8–9; Paper 7, 2; BioDelivery Scis. Int’l., Inc. v. RB Pharm. Ltd., Case No.
`IPR2014-00998 (PTAB Dec. 19, 2014) (Paper 12). The parties also refer to
`IPR2014-00325, where a panel determined in a Final Written Decision that
`the petitioner in IPR2014-00998 had established by a preponderance of the
`evidence that claims 15–19 of the ’832 patent were unpatentable. Pet. 8–9;
`Paper 7, 2; BioDelivery Scis. Int’l., Inc. v. RB Pharm. Ltd., Case No.
`
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`IPR2016-00280
`Patent 8,475,832 B2
`
`IPR2014-00325 (PTAB June 30, 2015) (Paper 43). Patent Owner indicates
`that the Final Written Decision “is currently on appeal to the Court of
`Appeals for the Federal Circuit, Docket No. 16-1044.” Paper 7 at 2–3; Pet.
`9.
`
`B. Proposed Grounds of Unpatentability
`Petitioner advances four grounds of unpatentability under 35 U.S.C.
`§ 103(a) in relation to claims 1–7 and 9–12 of the ’832 patent (Pet. 12–13):
`
` References
`
`LabTec1 in view of Yang,2 the
`Suboxone® 2002 Label,3 SBOA4 and
`Birch5
`
`LabTec in view of Yang, the
`Suboxone® 2002 Label, SBOA, Birch,
`and the ’055 publication6
`
`Statutory
`Basis
`§ 103(a)
`
`Challenged Claims
`
`1, 2, 4–7, 9, and 10
`
`§ 103(a)
`
`3, 11, and 12
`
`
`1 WO 2008/040534 A2, published Apr. 10, 2008 (“LabTec”) (Ex. 1007)
`2 Yang et al., U.S. Patent No. 7,357,891 B2, issued Apr. 15, 2008 (“Yang”)
`(Ex. 1006).
`3 Suboxone® 2002 Label (Ex. 1008).
`4 Suboxone® Tablet Summary Basis of Approval (“SBOA”) (Ex. 1009).
`5 Birch et al., U.S. Pat. Appl. Publ. No. 2005/0085440 A1, published Apr.
`21, 2005 (“Birch”) (Ex. 1004).
`6 Yang et al., U.S. Pat. Appl. Publ. No. 2005/0037055 A1, published Feb.
`17, 2005 (“the ’055 publication”) (Ex. 1010).
`3
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`IPR2016-00280
`Patent 8,475,832 B2
`
` References
`
`Oksche7 in view of Yang, the
`Suboxone® 2002 Label, SBOA, and
`Birch
`
`Oksche in view of Yang, the
`Suboxone® 2002 Label, SBOA, Birch,
`and the ’055 publication
`
`Statutory
`Basis
`§ 103(a)
`
`Challenged Claims
`
`1, 2, 4–7, 9, and 10
`
`§ 103(a)
`
`3, 11, and 12
`
`In addition, Petitioner supports its challenges in the Petition with a
`Declaration by Nandita Das, Ph.D. (“Das Decl.”) (Ex. 1003). Pet. 13.
`C. The ’832 Patent
`The ’832 patent relates to compositions and methods for treating
`narcotic dependence using an orally dissolvable film comprising
`buprenorphine and naloxone, wherein the film provides a bioequivalent
`release profile and drug absorption as compared to that of a Suboxone®
`tablet. Ex. 1001, 4:53–58, 2:55–62, 3:19–21. The ’832 patent defines
`bioequivalent as “obtaining 80% to 125% of the Cmax and AUC values for a
`given active in a different product.” Id. at 3:48–50. According to the ’832
`patent, “Cmax refers to the mean maximum plasma concentration after
`administration of the composition to a human subject,” and “AUC refers to
`the mean area under the plasma concentration-time curve value after
`administration of the compositions.” Id. at 3:9–14.
`At the time of the ’832 patent invention, Suboxone®, an orally
`dissolvable tablet of buprenorphine and naloxone, was on the market for
`treating opioid dependency. Id. at 4:51–55. Buprenorphine, an opioid
`
`
`7 WO 2008/025791, published March 6, 2008 (“Oksche”) (Ex. 1005).
`4
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`IPR2016-00280
`Patent 8,475,832 B2
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`agonist, provides an effect of satisfying the body’s urge for the narcotics, but
`not the “high” associated with misuse. Id. at 1:36–40. Naloxone, an opioid
`antagonist, reduces the effect of buprenorphine, and, thus, decreases the
`likelihood of diversion and abuse of buprenorphine. Id. at 1:46–52.
`The tablet form, however, still has the potential for abuse because it
`can be removed easily from the mouth for later extraction and injection of
`buprenorphine. Id. at 1:55–62. According to the ’832 patent,
`There [was] a need for an orally dissolvable film dosage form
`that provides the desired absorption levels of the agonist and
`antagonist, while providing an adhesive effect in the mouth,
`rendering it difficult to remove once placed in the mouth, thereby
`making abuse of the agonist difficult.
`Id. at 1:65–2:2.
`In relation to a “self-supporting film composition,” the ’832 patent
`describes that “local pH of the dosage is preferably controlled to provide the
`desired release and/or absorption” of the drugs. Id. at 11:8–10, 44–46,
`11:62–12:3. As described in the patent:
`Buprenorphine is known to have a pKa of about 8.42, while
`naloxone has a pKa of about 7.94. According to pH partition
`theory, one would expect that saliva (which has a pH of about
`6.5) would maximize the absorption of both actives. However,
`it has been surprisingly discovered by the Applicants that by
`buffering the dosage to a particular pH level, the optimum
`levels of absorption of the agonist and antagonist may be
`achieved. Desirably, the local pH of a composition including
`an agonist and an antagonist is between about 2 to about 4, and
`most desirably is from 3 to 4. At this local pH level, the
`optimum absorption of the agonist and the antagonist is
`achieved.
`
`Id. at 11:46–57. Thus, the inventors achieved optimum absorption of both
`buprenorphine (agonist) and naloxone (antagonist) at a “local pH” of “about
`
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`IPR2016-00280
`Patent 8,475,832 B2
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`2 to about 4, and most desirably [] from 3 to 4.” Id. The ’832 patent defines
`“local pH” as “the pH of the region of the carrier matrix immediately
`surrounding the active agent as the matrix hydrates and/or dissolves, for
`example, in the mouth of the user.” Id. at 3:35–38.
`The ’832 patent describes in an example that “a film having a
`combination of buprenorphine and naloxone and a local pH of 6.5 did not
`provide a bioequivalent effect as the Suboxone® tablet for both
`buprenorphine and naloxone.” Id. at 19:61–67. By contrast, as stated in
`another example, “in vivo data indicated that the absorption of
`buprenorphine was substantially bioequivalent to that of the one dose tablet
`when the film composition local pH was lowered to about 3–3.5.” Id. at
`23:1–4. The ’832 patent states that this “result was surprising as it did not
`appear to follow the pH partition theory,” and “[f]urther, at a local pH of
`about 3–3.5, it was seen that the absorption of naloxone was substantially
`bioequivalent to that of the one dose tablet.” Id. at 23:4–11.
`D. Claims
`Among the challenged claims, claims 1 and 9 are independent. Claim
`1 is representative, and is reproduced below.
`1. A film dosage composition comprising:
`a. A polymeric carrier matrix;
`b. A therapeutically effective amount of buprenorphine or a
`pharmaceutically acceptable salt thereof;
`c. A therapeutically effective amount of naloxone or a
`pharmaceutically 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.
`
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`IPR2016-00280
`Patent 8,475,832 B2
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`Claims 2–7 depend from claim 1. Independent claim 9 recites a method of
`treating narcotic dependence of a user comprising providing a composition
`similar to that recited in claim 1 and administering that composition to an
`oral cavity. Claims 10–12 depend from claim 9.
`
`II. ANALYSIS
`A. Claim Construction
`For inter partes review, claim terms in an unexpired patent are given
`their broadest reasonable interpretation in light of the patent specification.
`37 C.F.R. § 42.100(b); In re Cuozzo Speed Techs., LLC, 793 F.3d 1268,
`1278–79 (Fed. Cir. 2015), cert. granted sub nom. Cuozzo Speed Techs. LLC
`v. Lee, 136 S.Ct. 890 (mem.) (2016). Claim terms are given their ordinary
`and customary meaning, as would be understood by one of ordinary skill in
`the art in the context of the entire disclosure. In re Translogic Tech., Inc.,
`504 F.3d 1249, 1257 (Fed. Cir. 2007). Any special definition for a claim
`term must be set forth in the specification with reasonable clarity,
`deliberateness, and precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir.
`1994).
`As noted above, the ’832 patent defines “local pH” as “the pH of the
`region of the carrier matrix immediately surrounding the active agent as the
`matrix hydrates and/or dissolves, for example, in the mouth of the user.” Ex.
`1001, 3:35–38. We adopt that definition. In relation to other claim
`constructions proposed by Patent Owner (Prelim. Resp. 15–17), we
`determine that construction of other terms is not necessary to our analysis on
`whether to institute. Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d
`795, 803 (Fed. Cir. 1999) (only claim terms in controversy need to be
`construed, and only to the extent necessary to resolve the controversy).
`
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`
`B. The Suboxone® 2002 Label and SBOA as “Printed Publication”
`Prior Art Under 35 U.S.C. §102
`35 U.S.C. § 311(b) states that a “petitioner in an inter partes review
`may request to cancel . . . claims of a patent only on a ground that could be
`raised under section 102 or 103 and only on the basis of prior art consisting
`of patents or printed publications.” All four grounds in the Petition rely on
`the Suboxone® 2002 Label (Ex. 1008) and SBOA (Ex. 1009). Pet. 12–13,
`20, 25–29, 33–37, 40–46. Thus, before considering the grounds before us,
`we must address whether Petitioner has provided a sufficient threshold
`showing that the Suboxone® 2002 Label and SBOA constitute prior art
`under 35 U.S.C. § 102—a legal question based on underlying factual
`determinations. Panduit Corp. v. Dennison Mfg. Co., 810 F.2d 1561, 1568
`(Fed. Cir. 1987); Kyocera Wireless Corp. v. Int’l Trade Comm’n, 545 F.3d
`1340, 1350 (Fed. Cir. 2008).
`The Federal Circuit has held that “public accessibility” is the
`touchstone in determining whether a reference is a “printed publication”
`under § 102. In re Hall, 781 F.2d 897, 898–99 (Fed. Cir. 1986). “A
`reference is publicly accessible ‘upon a satisfactory showing that such
`document has been disseminated or otherwise made available to the extent
`that persons interested and ordinarily skilled in the subject matter or art
`exercising reasonable diligence, can locate it . . . .”’ Kyocera, 545 F.3d at
`1350 (quoting SRI Int’l, Inc. v. Internet Sec. Sys. Inc., 511 F.3d 1186, 1194
`(Fed. Cir. 2008)); In re Lister, 583 F.3d 1307, 1315 (Fed. Cir. 2009).
`A party seeking to introduce a reference “should produce sufficient
`proof of its dissemination or that it has otherwise been available and
`accessible to persons concerned with the art to which the document relates
`and thus most likely to avail themselves of its contents.” In re Wyer, 655
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`F.2d 221, 227 (CCPA 1981) (quoting Philips Elec. & Pharm. Indus. Corp. v.
`Thermal & Elecs. Indus., Inc., 450 F.2d 1164, 1171 (3d Cir. 1971)). As
`explained by the Federal Circuit, a “determination of whether a reference is
`a ‘printed publication’ under 35 U.S.C. § 102(b) involves a case-by-case
`inquiry into the facts and circumstances surrounding the reference’s
`disclosure to members of the public.” In re Klopfenstein, 380 F.3d 1345,
`1350 (Fed. Cir. 2004).
`In relation to the Suboxone® 2002 Label (Ex. 1008) and SBOA (Ex.
`1009), Petitioner contends that “Patent Owner stipulated in a co-pending
`litigation that the Suboxone® 2002 Label and SBOA are prior art to the ’832
`patent,” relying on a citation in footnote 12 of the Petition. Pet. 18–19.
`Footnote 12 in the Petition reads in full:
`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 qualify as 102(b)
`prior art as both were publicly available printed publications at
`least as early as 2002.
`Id. at 18–19 n.12.
`Patent Owner responds that Petitioner fails to show that either the
`Suboxone® Label or SBOA constitutes a “printed publication” or qualifies
`as prior art under 35 U.S.C. § 102. Prelim. Resp. 17–24. For example,
`Patent Owner points out that the above-quoted contentions and footnote 12
`in the Petition constitute Petitioner’s entire argument that Exhibits 1008 and
`1009 qualify as prior art. Id. at 20.
`We agree with Patent Owner that Petitioner fails to provide a
`threshold showing that either the Suboxone® Label or SBOA is a “printed
`publication” under 35 U.S.C. §§ 102 and 311(b). See Apple Inc. v. DSS
`Tech. Mgmt., Inc., Case IPR2015-00369, slip op. at 5 (PTAB Aug. 12, 2015)
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`(Paper 14) (noting that Petitioner has the burden to make a threshold
`showing that a reference is “printed publication” prior art under 35 U.S.C.
`§§ 102 and 311(b)); Hughes Network Systems, LLC v. California Institute of
`Technology, IPR2015-00059, slip op. at 4 (PTAB Dec. 30, 2015) (Paper 34).
`In its Petition, Petitioner’s attorney argument and reference to an
`exhibit in a district court case is insufficient. As Patent Owner notes,
`Petitioner filed no exhibits with its Petition, such as a court document, in
`relation to Patent Owner’s alleged stipulation in a district court case. Prelim.
`Resp. 20–21. When considering the record before us, we cannot tell whether
`any documents allegedly at issue in the district court case correspond to
`Exhibits 1008 and 1009 in this case.
` Moreover, even assuming Patent Owner stipulated regarding the
`prior art status of the Suboxone® 2002 Label and SBOA in a co-pending
`district court litigation, that fact, by itself, also would be insufficient to
`provide a threshold showing. During the district court litigation, Patent
`Owner might have agreed to stipulate to certain facts to streamline matters at
`trial there, for example, or had other reasons to stipulate on the issue in a
`case involving different parties in a different forum, regardless of whether
`the Suboxone® 2002 Label and SBOA were, in fact, publicly accessible or
`not. Prelim. Resp. 21.
`The Petition does not include or cite to information directly related to
`whether the Suboxone® 2002 Label and SBOA themselves were actually
`publicly accessible in the relevant time frame, how one might have obtained
`a copy of those documents, or whether they were reasonably accessible
`through generally available means. Without more here, contentions by
`Petitioner do not rise to the level of “threshold evidence” that justifies going
`
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`IPR2016-00280
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`forward with a trial on a ground that relies on the Suboxone® 2002 Label
`and SBOA as “printed publication” prior art.
`C. Asserted Obviousness of Claims 1, 2, 4–7, 9, and 10 by LabTec,
`Yang, Suboxone® 2002 Label, SBOA, and Birch
`Petitioner contends that claims 1, 2, 4–7, 9, and 10 would have been
`obvious over LabTec in view of Yang, the Suboxone® 2002 Label, SBOA,
`and Birch. Pet. 20–35. Petitioner relies on LabTec as teaching film dosage
`forms for delivering active agents, including buprenorphine and naloxone,
`where the dosage forms mimic pharmacokinetic profiles of tablet products,
`such as Suboxone®. Id. at 20–23 (citing Ex. 1007, 2–3, 20, 22). Petitioner
`argues that such teachings would have motivated an ordinary artisan to make
`a film dosage composition comprising buprenorphine and naloxone as
`disclosed in Table A in LabTec and recited in the challenged claims. Id.
`(citing Ex. 1007, 22). Petitioner also contends LabTec identifies a “need” to
`“replicat[e] the ‘optimum’ absorption of the Suboxone® tablet with a
`bioequivalent film dosage form.” Id. at 23 (citing Ex. 1007, 2).
`Petitioner further contends that “Yang would have supplied the person
`of ordinary skill with all the knowledge she needed in order to have a
`reasonable expectation of success regarding the manufacture of oral film
`products that are bioequivalent to Suboxone® tablets.” Id. Specifically,
`according to Petitioner, Yang would have taught an ordinary artisan “how to
`create a ‘film dosage composition’ comprising a ‘polymeric carrier matrix’”
`(id. at 24 (citing Ex. 1003 ¶ 91)), as also recited in independent claims 1 and
`9.
`
`Both independent claims 1 and 9 further require a film comprising 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
`11
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`IPR2016-00280
`Patent 8,475,832 B2
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`pH is from about 3 to about 3.5 in the presence of saliva.” Ex. 1001, cols.
`23–24. Petitioner relies on LabTec as identifying an effect of pH on
`absorption, stating that the reference “provides the methods and materials for
`exploiting this pH effect to optimize absorption,” and “teaches that pH can
`be adjusted to decrease or increase absorption of the active.” Pet. 24–25
`(citing Ex. 1007, 15–16).
`Petitioner then argues that “[b]ecause LabTec discloses a film
`designed to mimic Suboxone® tablets,” an ordinary artisan “would have
`naturally looked to any publicly available information about the Suboxone®
`tablets for information about additional film dosage composition
`components, including a specific buffer system to adjust the pH.” Id. at 25.
`Notably, Petitioner relies on SBOA and the Suboxone® 2002 Label as
`teaching such information and, particularly, as suggesting the use of a
`“buffer in an amount to provide a local pH,” as recited in claims 1 and 9.
`Pet. 25–29 (citing Ex. 1008, 8, 10; Ex. 1009, 28, 29).
`For example, according to Petitioner, “[b]ased on the SBOA, the
`person of ordinary skill would have concluded that (1) pH is important to
`achieving the Cmax and AUC values necessary for bioequivalence and (2)
`that an optimum range of pH values had been achieved by the Suboxone®
`tablet formulation.” Id. at 28. Again relying on SBOA and the Suboxone®
`2002 Label, Petitioner argues that “[b]ecause Suboxone® tablets were
`readily available at the time, it would have been routine for a person of
`ordinary skill to test the pH produced by the tablets in saliva and other
`dissolution media,” and that “[c]reating a film formulation that used the
`same buffers as the tablets, to produce the same pH produced by the tablets,
`would have been trivial.” Id.
`
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`
`In relation to the specific pH recited in claims 1 and 9, Petitioner
`relies on Birch as motivating an ordinary artisan “to target a value between
`about 3 to about 3.5, since Birch taught that transmucosal absorption of
`buprenorphine was optimal within that range.” Id. at 29 (citing Ex. 1004,
`Figs. 1 and 3, Ex. 8; Ex. 1003 ¶¶ 80, 102–03). Petitioner also argues an
`ordinary artisan “would not have expected that the claimed pH would cause
`problematic transmucosal absorption of [naloxone] because the prior art
`disclosed that such absorption was not seen with Suboxone® tablets or the
`citric acid buffer system used therein.” Id. at 30. Petitioner relies on the
`Suboxone® 2002 Label as teaching the citric acid buffer system in this
`regard. Id. at 28–29.
`In other words, Petitioner necessarily relies on a combination of
`disclosures in SBOA, the Suboxone® 2002 Label, and Birch as teaching or
`suggesting a “buffer in an amount to provide a local pH . . . sufficient to
`optimize absorption of said buprenorphine, wherein said local pH is from
`about 3 to about 3.5 in the presence of saliva,” as required in all challenged
`claims.
`As discussed above, we are not persuaded that Petitioner has made a
`threshold showing that SBOA and the Suboxone® 2002 Label were
`sufficiently publicly accessible to qualify as a “printed publication” under
`§ 102(b). Thus, Petitioner may not rely on teachings in those references to
`make its case here.8
`
`8 In addition, as Patent Owner points out, neither the Suboxone® tablet
`itself, nor alleged prior use of that tablet, for example, qualify as “patents or
`printed publications” under 35 U.S.C. § 311(b) (presenting the scope and
`basis of a ground a petitioner may raise in an inter partes review). Prelim.
`Resp. 21, 28.
`
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`
`In any case, as Patent Owner notes, Petitioner relies on Birch where it
`provides information about the pharmacokinetic profiles of buprenorphine
`formulations administered intranasally, i.e., Birch “teaches that a pH range
`of 3.4 can be used for nasal absorption,” not oral transmucosal absorption
`relevant to a film dosage. Prelim. Resp. 33. All figures and examples in
`Birch cited in the Petition, and by Petitioner’s expert, Dr. Das, relate to
`formulations administered intranasally. Ex. 1004, Figs. 1–4, ¶¶ 38–39,
`Examples 1, 3, 5, ¶¶ 139–154, Example 8, ¶¶ 206–211; Ex. 1003 ¶¶ 80, 102–
`03. Petitioner does not indicate sufficiently if or where Birch discusses oral
`transmucosal absorption, or how pH information in relation to nasal
`absorption might be relevant to oral transmucosal absorption or local pH in
`saliva as generated by a buffer in a film. Pet. 29–30 (citing Ex. 1004, Figs. 1
`and 3, Ex. 8; Ex. 1003 ¶¶ 80, 102–03).
`Thus, Petitioner does not explain adequately how Birch’s pH
`information in relation to buprenorphine formulations administered
`intranasally teaches or suggests a buffer providing a specific “local pH . . . in
`the presence of saliva” as it pertains to a film composition comprising both
`buprenorphine and another drug, naloxone, as required in the challenged
`claims.
`At most, Petitioner cites a paragraph in Dr. Das’s Declaration that
`states, without itself citing evidence in support, that the “anatomy of the oral
`and nasal mucosa is quite similar, thus, one of ordinary skill would expect
`that the same principle of drug delivery will apply to both tissues.” Ex. 1003
`¶ 80; Pet. 29–30. We agree with Patent Owner that this conclusory
`statement by Dr. Das, without more, is insufficient to make the leap
`Petitioner asks us to make. Prelim. Resp. 33 (citing 37 C.F.R. § 42.65(a)
`
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`(stating that “[e]xpert testimony that does not disclose the underlying facts
`or data on which the opinion is based is entitled to little or no weight”)).
`Moreover, Patent Owner points us to evidence in Birch itself indicating that
`buprenorphine pharmacokinetics differ when administered to oral versus
`nasal mucosa. Id. at 33–34 (citing Ex. 1004, 16, Table 11).
`Petitioner also argues that “[e]ven without these explicit teachings,”
`an ordinary artisan would have “had (i) the ability to prepare buffered films;
`(ii) a starting point for testing; (iii) the published target Cmax and AUC
`values, and (iv) knowledge of the pH dependence of the transmucosal
`absorption of buprenorphine and naloxone.” Pet. 30. Petitioner further
`contends that “it would have been nothing more than routine
`experimentation” to identify “the claimed pH range of 3 to 3.5 as optimal”
`upon testing a “number of films that produced a range of pH values in the
`saliva.” Id. at 30–31 (citing Ex. 1003 ¶¶ 108, 109, 116, 117).
`Neither Petitioner nor Dr. Das explains adequately, however, why an
`ordinary artisan would have wanted to try to make a film that produced a
`local pH of 3 to 3.5 in saliva in the first place, based on LabTec’s teachings
`regarding the Suboxone® tablet and/or Yang’s teachings regarding general
`methods for making films. See, e.g., Ex. 1003 ¶¶ 108, 109, 116, 117
`(asserting that arriving at a pH of 3–3.5 would have been “routine
`experimentation,” and “[t]here would not have been anything surprising”
`about identifying a pH of 3–3.5, without disclosing underlying facts or data
`in support, other than to refer to Cmax and AUC values for buprenorphine);
`Pet. 30–31.9
`
`
`9 In a footnote, Petitioner discusses Dr. Das’ assertion that a “person of
`ordinary skill would have known that she had to consider the solubility of
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`Moreover, as Patent Owner points out (Prelim. Resp. 8), LabTec
`teaches that “formulations can rely on various means for retarding
`absorption of the active ingredient through the oral mucosa,” including by
`using “pH adjusting agents that adjust the pH of the environment
`surrounding the dosage form to a pH that renders the active agent less
`permeable.” Ex. 1007, 15. In this context, LabTec states that “[s]uitable pH
`adjusting agents function by ionizing the active agent to a less permeable
`state,” and “for a basic active ingredient, one would adjust the pH of the
`solution to below the pKa of the conjugate acid.” Id.; Prelim. Resp. 2, 9–10
`(discussing the effect of pH on buprenorphine, a “weakly basic compound”).
`In view of such teachings, Patent Owner persuades us that LabTec does not
`suggest preparing a film that lowers a local pH to 3–3.5 in the saliva for the
`purpose of increasing absorption of an active ingredient such as
`buprenorphine.
`Upon consideration of information presented in the Petition and the
`Preliminary Response, we are not persuaded that Petitioner has
`
`both drugs, because a drug must be dissolved before it can be absorbed into
`the body.” Pet. 27 n.14. Petitioner and Dr. Das rely on Cassidy as teaching
`that “solubility of buprenorphine increases as pH decreases,” and that
`“buprenorphine is more soluble at or below a pH of 4.2 than at any pH
`above 4.2.” Id. (citing Cassidy, Controlled Buccal Delivery of
`Buprenorphine, 25 J. CONTROLLED RELEASE 24, 27–28, Fig. 1 (1993) (Ex.
`1012)). Petitioner does not explain adequately, however, how solubility of
`buprenorphine relates to absorption of the drug when administered in a film
`or how teachings in Cassidy relate to a film comprising buprenorphine,
`naloxone, and a buffer producing a local pH. Id. In addition, consistent
`with Patent Owner’s position (Prelim. Resp. 30–31), Cassidy discusses a
`delivery system using a non-woven or hydrogel disk, not a film, where the
`disk comprises a solution of buprenorphine (without naloxone) at a pH of 4,
`not a pH 3–3.5. Ex. 1012, 21, 23, 25–26, Fig. 4.
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`demonstrated that there is a reasonable likelihood that it would prevail in
`showing that challenged claims 1, 2, 4–7, 9, and 10 of the ’832 patent are
`unpatentable over LabTec in view of Yang, the Suboxone® 2002 Label,
`SBOA, and Birch.10
`D. Other Obviousness Grounds Relying on the Suboxone® 2002
`Label, SBOA, and Birch
`The other three grounds raised in the Petition also rely on the
`Suboxone® 2002 Label, SBOA, and Birch in the essentially same way as
`discussed above. Pet. 39–41. Grounds 2 and 4 discuss the ’055 publication
`as it relates to certain limitations in challenged dependent claims, without
`indicating that the publication provides any teachings or suggestion in
`relation to a buffer providing a local pH of about 3–3.5, as recited in
`independent claims 1 and 9. Pet. 35–36, 45–46.
`In grounds 3 and 4, Petitioner relies on Oksche (Ex. 1005) for
`disclosures similar to those in LabTec, i.e., an oral film comprising
`buprenorphine and naloxone that is “just as effective as,” i.e., bioequivalent
`to, Suboxone® tablets. Pet. 37–39. Petitioner also points to where Oksche
`discloses “the target Cmax and AUC0–48 values for buprenorphine.” Id. at 41
`(citing Ex. 1005, 9). Petitioner again relies on SBOA, the Suboxone® 2002
`
`
`10 On June 7, 2016, Petitioner filed “Second Updated Mandatory Notices” in
`this case. Paper 22. The Notices state that “the District Court for the
`District of Delaware in Reckitt Benckiser Pharmaceuticals Inc., et al v. Par
`Pharmaceutical, Inc., et al, 1-14- cv-00422, and Reckitt Benckiser
`Pharmaceuticals Inc. et al v. Watson Laboratories Inc., et al., 1-13-01674,
`found that claims 1, 3, 6, and 15–19 of the ’832 patent are invalid as obvious
`over the prior art.” Paper 22, 3–4 (also referring to “case 13-cv-01674”).
`We address a different record than the one before the district court, including
`different cited art and witness testimony.
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`Label, and Birch in relation to a buffer providing a local pH from about 3–
`3.5. Id. at 39–41.
`As discussed above, on the record before us, Petitioner fails to provide
`a sufficient threshold showing that SBOA and the Suboxone® 2002 Label
`qualify as prior art. In addition, Petitioner does not persuade us sufficiently
`that an ordinary artisan would have understood that that the pH information
`in Birch regarding a nasal formulation comprising buprenorphine would be
`applicable to an oral film comprising buprenorphine and another drug,
`naloxone, as well as a buffer providing a local pH in saliva, i.e., in the
`mouth.
`Beyond that, Petitioner refers to the Cmax and AUC0–48 values for
`buprenorphine as disclosed in Oksche when asserting it “would have been
`nothing more than routine experimentation for a person of ordinary skill to
`arrive at the claimed pH of 3 to 3.5.” Id. at 41 (citing Ex. 1003 ¶¶ 116, 117).
`Once again, neither Petitioner nor Dr. Das explains adequately why an
`ordinary artisan would have wanted to try to make a film that produced a
`local pH of 3 to 3.5 in saliva in the first place, based on teachings in Oksche
`and/or Yang. See Ex. 1003 ¶¶ 116, 117 (asserting that arriving at a pH of 3–
`3.5 would have been “routine experimentation,” and “there would not have
`been anything surprising” about identifying a pH of 3–3.5, without
`disclosing underlying facts or data in support, other than to refer to Cmax and
`AUC values for buprenorphine); Pet. 41.
`Upon consideration of the information presented in the Petition and
`the Preliminary Response, for the reasons discussed above, we are not
`persuaded that Petitioner has demonstrated that there is a reasonable
`likelihood that it would prevail in showing that challenged claims are
`
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`unpatentable over any cited art, including LabTec, Oksche, Yang, and the
`’055 publication, in view of the Suboxone® 2002 Label, SBOA, and Birch.
`E. Patent Owner’s Motion to Change the Petition’s Filing Date
`As authorized by the panel in an Order dated February 18, 2016
`(Paper 8), Patent Owner filed a Motion to change the filing date of the
`Petition from December 3, 2015, to December 4, 2015. Paper 10 (Patent
`Owner’s Motion to Change the December 3, 2015 Filing Date to December
`4, 2015, “Motion”). As also authorized (Paper 8), Petitioner filed an
`Opposition to that Motion. Paper 12