Trials@uspto.gov
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` Paper 43
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`Entered: June 30, 2015
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`BIODELIVERY SCIENCES INTERNATIONAL, INC.,
`Petitioner,
`
`v.
`
`RB PHARMACEUTICALS LIMITED,
`Patent Owner.
`____________
`
`Case IPR2014-00325
`Patent 8,475,832 B2
`____________
`
`
`Before TONI R. SCHEINER, JACQUELINE WRIGHT BONILLA, and
`ZHENYU YANG, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
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`571-272-7822
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` Paper 43
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`Entered: June 30, 2015
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`BIODELIVERY SCIENCES INTERNATIONAL, INC.,
`Petitioner,
`
`v.
`
`RB PHARMACEUTICALS LIMITED,
`Patent Owner.
`____________
`
`Case IPR2014-00325
`Patent 8,475,832 B2
`____________
`
`
`Before TONI R. SCHEINER, JACQUELINE WRIGHT BONILLA, and
`ZHENYU YANG, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
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`IPR2014-00325
`Patent 8,475,832 B2
`
`
`INTRODUCTION
`BioDelivery Sciences International, Inc. (“Petitioner”) filed a Petition
`for an inter partes review of claims 15–19 of U.S. Patent No. 8,475,832 B2
`(Ex. 1001, “the ’832 patent”). Paper 8 (“Pet.”). On July 29, 2014, the Board
`instituted trial to review patentability of the challenged claims. Paper 17
`(“Dec.”). Thereafter, RB Pharmaceuticals Limited (“Patent Owner”) filed a
`Corrected Response (Paper 25 (“PO Resp.”)), and Petitioner filed a Reply
`(Paper 31). Petitioner also filed a Motion to Exclude Exhibit 2043. Paper
`35. Patent Owner filed an Opposition to the Motion (Paper 37), and
`Petitioner filed a Reply in support of the Motion (Paper 38).
`In support of their respective positions, Petitioner relies on the
`Declarations of Drs. Maureen Reitman (Ex. 1004), Philip T. Lavin
`(Ex. 1005), David W. Feigal (Ex. 1029), and Christine S. Meyer (Ex. 1031),
`and the deposition testimony of Dr. Thomas P. Johnston (Ex. 1028); Patent
`Owner relies on the Declaration of Dr. Johnston (Ex. 2003).
`Oral hearing was held on March 20, 2015. See Paper 42 (“Tr.”).
`The Board has jurisdiction under 35 U.S.C. § 6(c) and issues this final
`written decision pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73.
`Petitioner has established by a preponderance of the evidence that
`claims 15–19 of the ’832 patent are unpatentable. In rendering this
`Decision, we do not rely on Exhibit 2043, the subject of Petitioner’s Motion
`to Exclude. Thus, we dismiss the Motion as moot.
`
`
`The ’832 Patent
`The ’832 patent relates to compositions and methods for treating
`narcotic dependence using an orally dissolvable film comprising
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`Patent 8,475,832 B2
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`buprenorphine and naloxone, wherein the film provides a bioequivalent
`effect to Suboxone®. Ex. 1001, 4:53–58. 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
`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.
`The ’832 patent relates to film dosage compositions comprising
`buprenorphine and naloxone. Id. at 2:6–3:2. Such compositions are
`particularly useful for treating narcotic dependence. Id. at 1:13–14.
`
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`Patent 8,475,832 B2
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`
`Illustrative Claim
`Among the challenged claims, claim 15 is the sole independent claim.
`It reads:
`formulation comprising
`film
`15. An orally dissolving
`buprenorphine and naloxone, wherein said formulation provides
`an in vivo plasma profile having a Cmax of between about
`0.624 ng/ml and about 5.638 ng/ml for buprenorphine and an in
`vivo plasma profile having a Cmax of between about 41.04
`pg/ml to about 323.75 pg/ml for naloxone.
`
`
`Reviewed Grounds of Unpatentability
`The Board instituted trial on the following grounds of unpatentability:
`Claims Challenged
`Basis
`Reference(s)
`Labtec1
`15–19
`§ 102(b)
`Labtec, Birch,2 and Yang3
`15–19
`§ 103
`
`
`
`ANALYSIS
`Claim Construction
`In an inter partes review, the Board interprets a claim term in an
`unexpired patent according to its broadest reasonable construction in light of
`the specification of the patent in which it appears. 37 C.F.R. § 42.100(b); In
`re Cuozzo Speed Techs., LLC, 778 F.3d 1271, 1280–81 (Fed. Cir. 2015).
`Under that standard, absent any special definitions, we assign claim terms
`
`
`1 Leichs et al., Int’l Pub. No. WO 2008/040534 A2, published on April 10,
`2008 (Ex. 1017, “Labtec”).
`2 Birch et al., U.S. Patent Publication No. 2005/0085440 A1, published on
`April 21, 2005 (Ex. 1019, “Birch”).
`3 Yang et al., U.S. Patent No. 7,357,891 B2, issued on April 15, 2008
`(Ex. 1016, “Yang”).
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`their ordinary and customary meaning, as understood by a person of
`ordinary skill in the art, in the context of the entire patent disclosure. In re
`Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007).
`In the Decision to Institute, we concluded that “film formulation”
`encompasses film dosage, film composition, or film, but not a formulation
`that is not in the form of a film. Dec. 11. We also determined that the term
`“provides an in vivo plasma profile” needs no construction beyond its
`ordinary meaning. Id. at 12. During trial, the parties did not dispute these
`constructions. Having considered the complete record developed at trial, we
`see no reason to change our interpretation of those terms.
`In its Response, however, Patent Owner presents arguments with
`respect to two additional terms. PO Resp. 18–26. First, Patent Owner
`challenges Petitioner’s position that the wherein clause of claim 15 is not
`entitled to patentable weight. Id. at 18–20. Second, Patent Owner contends
`that “the challenged claims should be construed as requiring a film
`formulation that provides, and as reciting pharmacokinetic ranges resulting
`from, oral transmucosal absorption.” Id. at 20–26. We address each issue in
`turn.
`
`The “Wherein” Clause
`Claim 15 recites an orally dissolving film formation, “wherein said
`formulation provides” specific pharmacokinetic profiles. Ex. 1001, 24:56–
`61. Petitioner argues that the wherein clause merely recites a desired result,
`and is not entitled to patentable weight. Pet. 23–26. Patent Owner counters
`that the pharmacokinetic ranges recited in the wherein clause “give crucial
`meaning to, and provide defining characteristics provided by the film
`formulation at issue.” PO Resp. 19–20. We agree with Patent Owner.
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`A wherein clause is not given patentable weight if it merely expresses
`the intended result of a process. Hoffer v. Microsoft Corp., 405 F.3d 1326,
`1329 (Fed. Cir. 2005). But, when the wherein clause states a condition that
`is material to patentability, it cannot be ignored. Id.
`Here, a film formulation that meets the requirements of claim 15 must
`be capable of producing the pharmacokinetic profile recited in the wherein
`clause of the claim. Petitioner does not contend that all orally dissolving
`films comprising buprenorphine and naloxone would provide the in vivo
`plasma profile recited in the wherein clause. As a necessary property of the
`claimed formulation, the pharmacokinetic profile gives meaning and purpose
`to the claim. See Griffin v. Bertina, 285 F.3d 1029, 1033–34 (Fed. Cir.
`2002).
`After reviewing the entirety of the patent, we conclude that the
`wherein clause of claim 15 (as well as claims 16 and 17) is a meaningful
`limitation and, thus, is entitled to patentable weight.
`
`
`Oral Transmucosal Absorption
`Patent Owner asserts that “the challenged claims should be construed
`as requiring a film formulation that provides, and as reciting
`pharmacokinetic ranges resulting from, oral transmucosal absorption.” PO
`Resp. 20. We disagree.
`First, it is a bedrock principle of patent law that the words of the
`claims themselves define the scope of the patented invention. In re Baxter
`Int'l, Inc., 678 F.3d 1357, 1362 (Fed. Cir. 2012). None of the challenged
`claims includes any language to the effect of requiring oral transmucosal
`absorption. Instead, the claims recite an “orally dissolving film
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`formulation.” Dissolution and absorption are two distinct properties. Thus,
`“orally dissolving” does not translate into oral transmucosal absorption.
`Second, the specification “is always highly relevant to the claim
`construction analysis. Usually, it is dispositive; it is the single best guide to
`the meaning of a disputed term.” In re Abbott Diabetes Care Inc., 696 F.3d
`1142, 1149 (Fed. Cir. 2012). Here, contrary to Patent Owner’s assertion, the
`Specification does not “make[] clear that . . . the claimed film delivers
`buprenorphine through the oral mucosa.” See PO Resp. 21. The ’832 patent
`describes its invention as an “orally dissolvable film” that is “preferably
`administered to a patient through the oral cavity of the patient, but may be
`administered in any desired means.” Ex. 1001, 15:12–15; see also id. at
`15:1–3 (stating administering the film “most desirably into the oral cavity”).
`These disclosures suggest that the film of the ’832 patent can be
`administered through routes other than the oral cavity, albeit not preferred or
`most desired.
`Patent Owner relies on various portions of the Specification. PO
`Resp. 21–23. None of the cited language, however, supports Patent Owner’s
`position. For example, Patent Owner points out that the title of the ’832
`patent reads “Sublingual and Buccal Film Composition.” Id. at 21. But, “if
`we do not read limitations into the claims from the specification that are not
`found in the claims themselves, then we certainly will not read limitations
`into the claims from the patent title.” Pitney Bowes, Inc. v. Hewlett–
`Packard Co., 182 F.3d 1298, 1312 (Fed. Cir. 1999).
`Patent Owner refers to the Specification for disclosing “a method of
`treating narcotic dependence by providing an orally dissolvable film dosage,
`which provides a bioequivalent effect to Suboxone®.” PO Resp. 22
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`(quoting Ex. 1001, 4:51–58). According to Patent Owner, a skilled artisan
`would have understood that Suboxone® delivers buprenorphine through the
`oral mucosa and that the claimed film formulation is “intended to work the
`same way.” Id. As support, Patent Owner cites the Specification for
`disclosing: “In a dosage form that is to be placed in the oral cavity, it is
`desired to absorb the agonist [buprenorphine] bu[c]cally so as to provide
`rapid integration of the agonist into the body of the user.” Id. (quoting
`Ex. 1001, 11:10–13). This sentence, however, states that the buccal
`absorption (i.e., oral transmucosal absorption) is merely “desired,” and not
`required.
`Patent Owner also contends “the specification notes that a key
`criterion in polymer selection is ‘the time period for which it is desired to
`maintain the film in contact with the mucosal tissue,’” because different
`actives may require different lengths of time “for delivery through the
`mucosal tissue.” PO Resp. 23 (quoting Ex. 1001, 6:42–47). According to
`Patent Owner, this “[f]urther confirm[s] the oral transmucosal nature of the
`claimed film.” Id. Patent Owner, however, neglects to note the sentence
`immediately preceding the ones quoted, which reads: “Although a variety of
`different polymers may be used, it is desired to select polymers that provide
`mucoadhesive properties to the film, as well as a desired dissolution and/or
`disintegration rate.” Ex. 1001, 6:39–42 (emphasis added). This disclosure
`provides the context for the language Patent Owner emphasizes. Because
`mucoadhesiveness is only a desired property, we again, decline to read it, or
`oral transmucosal absorption, into the challenged claims.
`
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`Patent Owner further asserts that the Specification “repeatedly
`emphasizes the important role” of “local pH.” PO Resp. 23. According to
`Patent Owner,
`The skilled person would appreciate that the specification’s
`strong emphasis on the use of a buffer to provide a local pH (in
`the presence of saliva as the matrix dissolves adjacent to the
`oral mucosa) is solely applicable to oral transmucosal
`absorption.
`Id. at 24. The challenged claims, however, do not recite a local pH. This is
`in sharp contrast to the unchallenged claims, all of which, either directly or
`through their dependency, require a local pH of about 3 to about 3.5. As a
`result, Patent Owner’s reliance on the importance of a local pH does not
`support its argument on oral transmucosal absorption in relation to the
`challenged claims.
`In addition, Patent Owner argues that a person of ordinary skill
`“would understand that all of the pharmacokinetic data provided about the
`test film formulations was intended to and did result from oral transmucosal
`absorption.” Id. at 25. This, according to Patent Owner, is because “all of
`the pharmacokinetic data and ranges in the specification relating to
`Suboxone® sublingual tablets . . . result or would be expected to result from
`oral transmucosal absorption, the known route employed by that commercial
`product.” Id. We are not persuaded.
`First, the ’832 patent does not mention that the pharmacokinetic data
`for Suboxone® tablets result from oral transmucosal absorption. In fact,
`when characterizing Suboxone®, the Specification only describes it as “an
`orally ingestible” (Ex. 1001, 1:54) or “an orally dissolvable” tablet (id. at
`4:53). Neither can be reasonably equated with oral transmucosal absorption.
`
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`
`Second, during his deposition, Dr. Johnston explained:
`[I]f you give an orally dissolving film, and if the drug is not
`absorbed across the oral mucosa, sublingual, buccal, whatever,
`then it has to be swallowed, because the patient -- where else
`would it go? The patient doesn’t expectorate that saliva drug
`solution. So to answer your question, it has to be swallowed.
`Ex. 1028, 237:9–17, see also id. at 125:8–12 (testifying that Suboxone®
`tablets “dissolve[] in saliva, the majority of which is absorbed sublingually,
`then that saliva of buprenorphine solution is swallowed”). As a result, we
`find the evidence of record does not support Patent Owner’s position that
`“all of the pharmacokinetic data” of Suboxone® tablets result from oral
`transmucosal absorption.
`Third, Dr. Johnston opines that “[o]ne of ordinary skill in the art
`would understand that Suboxone® sublingual tablets deliver buprenorphine
`through the oral mucosa.” Ex. 2003 ¶ 66. Patent Owner argues the same.
`PO Resp. 22–23. As support, they both rely on the March 2006 version of
`the Data Sheet for Suboxone® tablets, which states:
`first-pass
`When
`taken orally, buprenorphine undergoes
`metabolism with N-dealkylation and glucuroconjugation in the
`small intestine and the liver. The use of SUBOXONE by the
`oral route is therefore inappropriate. SUBOXONE tablets are
`for sublingual administration.
`PO Resp. 16 (quoting Ex. 2007, 2); Ex. 2003 ¶ 43 (quoting Ex. 2007, 2).
`Petitioner, however, pointing to the same document—indeed, the same page
`of the same Data Sheet—argues that the bioavailability of orally
`administered buprenorphine overlaps with that of sublingually administered
`Suboxone® tablets. Reply 9–10 (citing Ex. 2007, 2). We find that the
`evidence of record supports Petitioner’s position.
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`
`During his deposition, Dr. Johnston testified that the mean absolute
`bioavailability of buprenorphine from oral administration is “anywhere from
`5 percent to 14 percent.” Ex. 1028, 76:8–14. The Data Sheet for
`Suboxone® tablets states that the mean absolute bioavailability of
`buprenorphine from sublingual administration is 13.6% (range 5.1–24.9%).
`Ex. 2007, 2. When questioned about this statement during a deposition,
`Dr. Johnston stated that he disagreed with the data. Ex. 1028, 77:4–23,
`80:14–19. At the hearing, counsel for Patent Owner downplayed the data as
`“numbers in that one study that’s in the label.” Tr. 23:23–24, see also id. at
`24:19–21 (stating that “yes . . . the 13.6 is in the Suboxone tablet label, but
`that was one study”). According to Dr. Johnston, “the upper range thereof,
`essentially 25 percent, the upper range falls more in line with reported
`values.” Ex. 1028, 78:19–23. Specifically, Patent Owner directs our
`attention to some “lengthy” and “extensive” review articles, including page
`663 of Exhibit 20164 and page 302 of Exhibit 2029,5 as “deal[ing]
`specifically with this issue about absorption.” Tr. 24:7–11.
`According to Exhibit 2016, “[s]tudies utilizing specific assays have
`reported buprenorphine sublingual solution’s mean bioavailability of 28–
`51%. The plasma bioavailability of the sublingual tablet has been estimated
`as 49–63% that of the sublingual solution.” Ex. 2016, 663 (internal citations
`omitted). Thus, the bioavailability of buprenorphine sublingual tablet could
`
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`4 Elkader and Sproule, Buprenorphine Clinical Pharmacokinetics in the
`Treatment of Opioid Dependence, 44 CLIN. PHARMACOKINET. 661–80
`(2005).
`5 Johnson et al., Buprenorphine: Considerations for Pain Management,
`3 J. PAIN AND SYMPTOM MANAGEMENT 297–326 (2005).
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`be 13.72% (28% x 49%), in line with the 13.6% average reported in the Data
`Sheet for Suboxone® tablets.
`Exhibit 2029 notes, for buprenorphine sublingual tablets, an average
`systemic bioavailability of 55%. Ex. 2029, 302. This number, however, is
`not without qualification. Indeed, it is reported “with large intersubject
`variability.” Id. Moreover, it appears to be based on the administration of
`0.4 or 0.8 mg doses for postoperative pain management (id.),6 significantly
`lower than the 2, 4, 8, or 16 mg doses of Suboxone® tablets for treating
`narcotic dependency (Ex. 1001, 16:40–17:13).
`Considering the data in Exhibit 2007 relied on by Petitioner against
`the data in Exhibits 2016 and 2029 relied on by Patent Owner, we assign the
`former more weight. We do so because a party may not selectively point to
`one portion of an exhibit to buttress its argument, and, meanwhile, ask us to
`disregard another part of the same document that undermines its contention.
`Here, Patent Owner relies on Exhibit 2007 to support its position. See
`Prelim. Resp. 16 (quoting Ex. 2007, 2); Ex. 2003 ¶ 43 (quoting Ex. 2007, 2).
`We accord Exhibit 2007 more weight also because it is the Data Sheet for
`Suboxone® tablets, an official document from Patent Owner itself,
`informing both regulatory agencies and the public of its own Suboxone®
`tablet data. As a result, we decline to discount the 13.6% bioavailability of
`
`
`6 Exhibit 2029 cites two references (endnotes 76 and 77) in support of this
`portion of the discussion. Ex. 2029, 302. They are entitled “Sublingual
`buprenorphine used postoperatively: Clinical observations and preliminary
`pharmacokinetic analysis,” and “Sublingual buprenorphine used
`postoperatively: Ten-hour plasma drug concentration analysis,”
`respectively. Id. at 319–20.
`
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`sublingual Suboxone® tablets, shown on the same page of the same
`document, as a single-study abnormality.
`Given that the undisputed bioavailability of buprenorphine from oral
`administration is “anywhere from 5 percent to 14 percent,” we find that the
`evidence of record supports Petitioner’s position that the bioavailability of
`orally administered buprenorphine overlaps with that of sublingually
`administered Suboxone® tablets.
`In sum, we decline to construe the challenged claims as requiring oral
`transmucosal absorption, because the challenged claims do not explicitly
`recite such a limitation, and because neither the ’832 patent nor any other
`evidence Patent Owner relies on sufficiently demonstrates otherwise.
`
`
`Patentability Analysis
`Prior Art Disclosures7
`Labtec describes “non-mucoadhesive orally disintegrating film dosage
`forms that mimic the pharmacokinetic profile of orally administered drug
`products such as tablets.” Ex. 1017, 2. It lists Suboxone® as such a tablet.
`Id. at 22.
`Specifically, Table A of Labtec lists “[e]xamples of doses for specific
`pharmaceutically active agents that can be delivered per one strip of rapidly
`dissolving oral film . . . along with preferred dosing schedules and
`
`
`7 Petitioner relies on Birch for its discussion of a pH range. Pet. 43. As
`explained in our Decision to Institute, because the challenged claims do not
`recite any pH levels, “we do not rely on Birch in our obviousness
`determination.” Dec. 17–18. We, therefore, do not discuss the teachings of
`Birch.
`
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`pharmacokinetic parameters.” Id. at 20. One such example is a film that
`mimics the pharmacokinetic profile of Suboxone®. Id. at 22. The example
`discloses the combination of buprenorphine HCl/naloxone HCl dehydrate as
`the pharmaceutically active agents. Id. It also describes the Cmax for
`buprenorphine and naloxone and AUC for buprenorphine. Id.
`Yang “relates to rapidly dissolving films and methods of their
`preparation.” Ex. 1016, 1:27–28. It teaches a process for making a film
`from a polymer component, polar solvent, and an active component. Id. at
`4:23–35. Yang is one of the two U.S. patents incorporated by reference into
`the ’832 patent for disclosing suitable processes to form the claimed film.
`Ex. 1001, 15:29–31.
`
`
`Anticipation by Labtec
`Petitioner asserts that Labtec anticipates claims 15–19. Pet. 38–41.
`After reviewing the entire record, we conclude Petitioner has shown by a
`preponderance of the evidence that Labtec discloses each and every
`limitation of the challenged claims.
`According to Petitioner, Labtec discloses a film comprising
`pharmaceutical active agents, a film-forming agent, and other ingredients.
`Id. at 39 (citing Ex. 1017, 13–14). Specifically, Labtec discloses an orally
`disintegrating film comprising buprenorphine and naloxone, as recited in
`claim 15. Id. at 38 (citing Ex. 1017, 20, 22). In addition, Labtec discloses
`formulating a film to ensure bioequivalence between the film and an existing
`product, such as the Suboxone® tablets. Id. at 40 (citing Ex. 1017, 2, 22). It
`discloses formulating the film to mimic the known pharmacokinetics of
`Suboxone®, including Cmax and mean AUC of buprenorphine and
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`naloxone, as recited in claims 15–17. Id. (citing Ex. 1017, 2, 12, 22).
`Labtec further discloses preferred doses for buprenorphine and naloxone, as
`recited in claims 18 and 19. Id. at 41 (citing Ex. 1017, 22).
`Patent Owner contends that Labtec does not anticipate the challenged
`claims because it only discloses films designed to provide absorption
`through the gastrointestinal (“GI”) tract, while the claimed film requires oral
`transmucosal absorption. PO Resp. 27–30. Patent Owner also argues that
`Labtec merely discloses a wish or a goal, and not the claimed film itself. Id.
`at 30–32. Further, Patent Owner asserts that, because Labtec fails the
`enablement requirement, it is not an anticipatory reference. Id. at 32–38.
`We address each argument in turn.
`First, as explained above in the Claim Construction section, we reject
`Patent Owner’s proposal to read oral transmucosal absorption into the
`challenged claims. As a result, Patent Owner’s attempt to distinguish the
`claimed invention over Labtec based on the route of absorption is
`unpersuasive.
`Second, Patent Owner is correct that Labtec does not disclose any
`specific embodiment of a buprenorphine-containing film. PO Resp. 30–31.
`As we explained in our Decision to Institute, however, “anticipation does not
`require actual performance of suggestions in a disclosure.” Dec. 16 (quoting
`Novo Nordisk Pharm., Inc. v. Bio-Tech. Gen. Corp., 424 F.3d 1347, 1355
`(Fed. Cir. 2005)). In other words, a reference may anticipate a claim “even
`if the author or inventor did not actually make or reduce to practice that
`subject matter.” Id. (quoting Schering Corp. v. Geneva Pharm., Inc.,
`339 F.3d 1373, 1380 (Fed. Cir. 2003)). We stated our position in the context
`of enablement. See id. Patent Owner, however, appears to argue Labtec’s
`15
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`IPR2014-00325
`Patent 8,475,832 B2
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`lack of an example of a buprenorphine-containing film in its disclosure in
`the context of insufficient written description. PO Resp. 31.
`Nevertheless, the written description requirement does not demand
`examples or an actual reduction to practice either. Ariad Pharm., Inc. v. Eli
`Lilly & Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010) (en banc). Instead, “a
`constructive reduction to practice that in a definite way identifies the
`claimed invention can satisfy the written description requirement.” Id. In
`this case, Labtec lists Suboxone® in Table A as a drug of interest, and
`describes an oral film that mimics the pharmacokinetics of Suboxone®.
`Ex. 1017, 22. Labtec describes that the film formulation comprises
`buprenorphine and naloxone, as recited in claim 15. Id. It states that
`buprenorphine is to be dosed at 4–16 mg/day. Id. Cmax is 1.84 and 3.0
`ng/ml and AUC0-48 is 12.52 and 20.22 hr.ng/ml, for 4 mg and 8 mg
`buprenorphine, respectively. Id. Labtec further states that “[m]ean peak
`naloxone levels range from 0.11 to 0.28 ng/ml in dose range of 1–4 mg.” Id.
`This description amounts to a constructive reduction to practice that
`describes an oral film with the specified composition and pharmacokinetic
`profile. Nothing more is needed. Thus, Labtec does not fail as anticipatory
`prior art merely because it does not disclose any specific embodiment of the
`recited film.
`Third, Patent Owner asserts that Labtec fails to enable a skilled artisan
`to practice the claimed invention. PO Resp. 32. According to Patent Owner,
`a skilled artisan would have recognized that, as Labtec is devoted to films
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`IPR2014-00325
`Patent 8,475,832 B2
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`with peroral delivery8 of the active ingredients, listing Suboxone®, a
`sublingual tablet absorbed through oral mucosa, “must simply be a mistake.”
`Id. at 32–33. In addition, regardless of whether the challenged claims are
`limited to oral transmucosal films, Patent Owner contends, Labtec is
`inoperable if applied to Suboxone® (id. at 33–35), and a buprenorphine film
`formulated for GI-tract absorption would not be therapeutically acceptable
`(id. at 35–36). We are not persuaded.
`Patent Owner’s arguments center on the alleged “large differences in
`bioavailability” of buprenorphine and naloxone when absorbed through oral
`mucosal membrane compared to when absorbed through the GI tract. Id. at
`34. But, as explained above, the evidence of record supports Petitioner’s
`position that the bioavailability of orally administered buprenorphine
`overlaps with that of sublingually administered Suboxone® tablets. See
`supra at 11–13. Thus, regardless of whether Labtec is limited to providing
`GI-tract absorption only, we are not persuaded that Labtec is not enabled
`with respect to buprenorphine.
`We similarly are not persuaded that Labtec is not enabled with respect
`to naloxone. We conclude so although we disagree with Petitioner’s
`argument that orally and sublingually administered naloxone have “similar
`bioavailability” (Reply 10), and Petitioner’s characterization of
`Dr. Johnston’s deposition testimony as “reluctantly admitt[ing] that the
`mean absolute bioavailability of oral naloxone is ‘one-third’ that of a
`Suboxone tablet” (id. at 12 (citing Ex. 1028, 45:7–20)). We conclude so
`
`8 According to Dr. Johnston, peroral delivery “means a dosage form is
`swallowed for subsequent absorption in the gastrointestinal tract.” Ex. 1028,
`3:23–25.
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`IPR2014-00325
`Patent 8,475,832 B2
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`also despite our recognition of Patent Owner’s evidence showing that oral
`administration of naloxone, even at 4 mg or 5 mg, cannot achieve the Cmax
`range recited in claim 15. See PO Resp. 37–38 (citing Ex. 2003 ¶¶ 90–92).
`We conclude so because we agree with Petitioner that “Labtec is not
`limited to ‘peroral GI-absorbed dosages.’” See Reply 5. We note Patent
`Owner’s argument that Labtec summarizes its invention as providing “film
`dosage forms that are formulated or administered for gastrointestinal
`absorption of the active pharmaceutical agent, and that are bioequivalent to
`and interchangeable with existing orally administered drug products.” PO
`Resp. 32 (citing Ex. 1017, 2). We further note Patent Owner’s argument that
`Labtec describes its film as “non-mucoadhesive,” and defines the term to
`mean that “the dosage form is not designed for administration of the active
`pharmaceutical agent through the oral mucosa.” Id. at 27 (citing Ex. 1017,
`8).
`
`Petitioner, on the other hand, points to Labtec for disclosing an
`invention that “provides an orally disintegrating film comprising: (a) an
`active pharmaceutical agent that is absorbable through the oral mucosa when
`dissolved; and (b) means for retarding absorption of said active
`pharmaceutical ingredient through the oral mucosa.” Reply 5 (citing
`Ex. 1017, 14). Labtec also discloses various means, for example, using pH
`adjusting agents, for retarding absorption of the active ingredient through the
`oral mucosa. Id. (citing Ex. 1017, 14–15).
`The evidence of record supports a finding that the active ingredients
`in Labtec’s films are absorbed through not only the GI tract, but also the oral
`mucosa. Despite its stated object to formulate the film to promote GI-tract
`absorption, Labtec explains in its Summary of the Invention that the active
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`IPR2014-00325
`Patent 8,475,832 B2
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`ingredients from its non-mucoadhesive film dosages are absorbed
`“predominantly” through the GI tract. Ex. 1017, 3; see also id. at 14 (“The
`active ingredient from the dosage form is preferably absorbed predominantly
`through the gastrointestinal tract.”). The question, then, is whether the rest
`of the active ingredient is absorbed through the oral mucosa, or not absorbed
`at all. Evidence supports a finding that the answer is the former.
`According to Petitioner, “Labtec discloses that, in some embodiments,
`as little as about 60% of the active ingredient is delivered to the GI tract.”
`Reply 6 (citing Ex. 1017, 14). In those cases, Petitioner argues, “as much as
`about 40%” is absorbed through the oral mucosa. Id. Patent Owner disputes
`this conclusion, arguing that “the point [is] not just delivery. It’s absorption,
`gastrointestinal absorption.” Tr. 34:11–12. Patent Owner correctly notes
`that delivery is not the same as absorption. In fact, Labtec makes clear this
`distinction:
`[O]f the active ingredient absorbed, the predominant amount
`(greater than 60, 70, 80, 90, 95 and up to 100 wt.%) is
`preferably absorbed through the GI tract. Therefore, the means
`should be able to deliver greater than 60, 70, 80, 90 or 95 and
`up to 100 wt.% of the active ingredient to the gastrointestinal
`tract.
`Ex. 1017, 14 (emphases added). For this analysis, we focus our attention on
`the delivery of the drug.
`During his deposition, Dr. Johnston testified:
`[I]f you give an orally dissolving film, and if the drug is not
`absorbed
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