BioDelivery Sciences International, Inc.v.RB Pharmaceuticals Limited

Patent Trial and Appeal Board

Jun 30, 2015

12537571 (P.T.A.B. Jun. 30, 2015)

Trials@uspto.gov Paper 43
571-272-7822 Entered: June 30, 2015

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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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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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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Illustrative Claim
Among the challenged claims, claim 15 is the sole independent claim.
It reads:
15. An orally dissolving film formulation comprising
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)
15–19 § 102(b) Labtec1
15–19 § 103 Labtec, Birch,2 and Yang3

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:
When taken orally, buprenorphine undergoes first-pass
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

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
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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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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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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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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 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. If
it isn’t absorbed, it has to go somewhere.
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Ex. 1028, 237:9–17. In other words, after an orally dissolving film is
administered through the oral cavity, because a patient does not spit out the
drug, the amount of the drug that is swallowed and, thus, delivered to the GI
tract, is the amount not absorbed in the mouth. Thus, we are persuaded that,
when only 60% of the active ingredient reaches the GI tract, the rest (40%)
must have been absorbed through the oral mucosa. See Tr. 21:3–7.
Labtec discloses a film with 2.0 mg naloxone (Ex. 1017, 22), within
the “about 0.5 to about 4 mg of naloxone” range recited in claim 19. For a
film that delivers 60% of naloxone to the GI tract, 0.8 mg (2.0 mg x 40%)
naloxone is absorbed through the oral mucosa. Because plasma level
increases as the dose of naloxone increases (Ex. 2007, 2; Ex. 1028, 51:20–
52:4), the Cmax and AUC for 0.8 mg naloxone would necessarily fall within
the ranges recited in claims 15 and 17.9 See Ex. 1001, 17:20–48 (disclosing
the Cmax and mean AUC ranges for naloxone as between 80% of the Cmax
and AUC for 0.5 mg naloxone and 125% of those for 4 mg naloxone).
Patent Owner contends that “[d]ue to its much lower bioavailability,
peroral delivery of a given amount of buprenorphine or naloxone cannot
possibly give close to the same or substantially bioequivalent Cmax and
AUC values (80–125%) compared to oral-transmucosal delivery of the same
amounts of those active ingredients.” PO Resp. 34. As explained above, the
challenged claims are not limited to oral transmucosal absorption, and
Labtec is not limited to GI-tract absorption. Thus, the comparison argued by
Patent Owner is not meaningful in our analysis. Furthermore, the challenged

9 To illustrate our point in this analysis, we compare the pharmacokinetic
profile as if the claims were, as Patent Owner urges, limited to oral
transmucosal absorption.
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claims do not recite any dosage amount of either buprenorphine or naloxone.
Nor does the Specification include any dosage requirement when defining
what is considered bioequivalent. Ex. 1001, 17:42–48. During the oral
argument, the panel inquired whether orally administering 16 mg
buprenorphine to achieve a Cmax of 0.624 ng/ml would be considered
bioequivalent. Tr. 25:16–19, 27:12–19. Counsel for Patent Owner
responded affirmatively (id. at 25:20–22, 27:20–21), even though 16 mg is
the upper limit of the buprenorphine dosing range, whereas 0.624 ng/ml is
the lower limit of the Cmax range, calculated based on 80% of the Cmax of
sublingually administered buprenorphine (2 mg) Suboxone® tablets. See
Ex. 1001, 17:30–40. In other words, according to the ’832 patent, to be
considered the same or substantially bioequivalent does not require peroral
delivery of the same amount of buprenorphine or naloxone as in oral-
transmucosal delivery.
Patent Owner recognizes so, but qualifies its admission “with the
caveat that if [the active ingredient is administered] perorally, it would be
understood to be therapeutically unacceptable because of the variability
involved with the peroral dosing.” Tr. 27:20–24. We are not persuaded. As
Petitioner points out, the Data Sheet for Suboxone® tablets (again, an
official drug label from Patent Owner itself) acknowledges “a wide inter-
patient variability” in the absorption of buprenorphine and naloxone even
from sublingually administered Suboxone® tablets. Reply 10 (citing
Ex. 2007, 2). Further, naloxone has no detectable pharmacological activity
whether administered orally or sublingually. Ex. 2007, 1. We, therefore, are
not persuaded that Labtec is not enabled with respect to naloxone.
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For the foregoing reasons, Labtec, disclosing an oral film comprising
buprenorphine and naloxone with the pharmacokinetic profiles recited in the
challenged claims, anticipates claims 15–19.

Obviousness over Labtec, Birch, and Yang
Petitioner argues that the challenged claims would have been obvious
over the combination of Labtec, Birch,10 and Yang. Pet. 44–45. After
reviewing the complete record, we conclude Petitioner has shown by a
preponderance of the evidence that one of ordinary skill in the art would
have had reason to combine the teachings of Labtec and Yang to make an
orally dissolving film as recited in the challenged claims, and would have
had a reasonable expectation of success in doing so.
According to Petitioner, because “[t]he law provides three year market
exclusivity for new dosages of existing drug products” (id. at 45 (citing Ex.
102411,12)), a skilled artisan would have been motivated to create a film
formulation of Suboxone® to enjoy the market exclusivity. Id. Petitioner
argues that Labtec already discloses components suitable for making films.
Id. But, to the extent Labtec’s teaching on how to make a film is
insufficient, Yang teaches such methods. Id.
Patent Owner does not dispute that Yang teaches processes for
making a film but contends that the teaching of Yang “does not address the

10 See supra at 14 n.7.
11 M.A. VOET, THE GENERIC CHALLENGE: UNDERSTANDING PATENTS, FDA
& PHARMACEUTICAL LIFE-CYCLE MANAGEMENT 110 (Brown Walker Press
2d ed. 2008).
12 Petitioner mistakenly cites “Ex. 1025” but correctly describes Exhibit
1024. Pet. 45.
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deficiencies of Labtec.” PO Resp. 45. According to Patent Owner, one of
ordinary skill in the art would not look to Labtec to develop a buprenorphine
film, and would not have had a reasonable expectation of success in
combining the teachings of Labtec and Yang. Id. at 40–47. Patent Owner
rests these arguments on the premise that Labtec is limited to peroral
delivery of films formulated for GI-tract absorption only. See id. at 39–41,
45–47. As explained above, however, Labtec is not so limited. See supra at
18–20. Thus, we reject Patent Owner’s contentions on this basis.
In addition, even if we were to find that films according to Labtec’s
invention deliver active ingredients solely for absorption through the GI
tract, we still would be unpersuaded by Patent Owner’s arguments. Patent
Owner asserts that Labtec merely makes “an obviously mistaken and
unintentional suggestion to pursue” a buprenorphine film “that was
understood to be therapeutically ineffective and unacceptable.” PO Resp.
41. In addition, Patent Owner contends that a skilled artisan would not have
a reasonable expectation of success because combining the prior art to arrive
at the claimed invention would “transmogrify Labtec beyond recognition.”
Id. at 47. We are not persuaded.
“Under an obviousness analysis, a reference need not work to qualify
as prior art; it qualifies as prior art, regardless, for whatever is disclosed
therein.” Geo. M. Martin Co. v. Alliance Mach. Sys. Int’l LLC, 618 F.3d
1294, 1302 (Fed. Cir. 2010) (citations and internal quotation marks omitted).
As Patent Owner points out, Labtec recognizes that several manufacturers
proposed film formulations for the delivery of prescription drugs. PO Resp.
27 (citing Ex. 1017, 2). According to Labtec, “[t]he vast majority of these
formulations are ‘mucoadhesive’ formulations designed for adhesion of the
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dosage form to the mucosal tissue in the mouth, and transmission of the drug
from the dosage form through the mucosal tissue into the systemic
circulation.” Ex. 1017, 1. Labtec acknowledges that the “advantage of these
mucoadhesive films resides in their ability to bypass the gastrointestinal
tract, and barriers in the gastrointestinal tract to drug absorption such as first
pass metabolism and decomposition of the active ingredient in the stomach.”
Id. at 2.
Patent Owner emphasizes that these teachings appear in the
background section of Labtec. A person of ordinary skill, however, would
read a reference for all that it teaches, including uses beyond its primary
purpose. KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 418–21 (2007); see
also Beckman Instruments, Inc. v. LKB Produkter AB, 892 F.2d 1547, 1551
(Fed. Cir. 1989) (stating that a prior art reference is relevant “for all that it
teaches” to those of ordinary skill in the art). Here, regardless of which
section the teaching of “mucoadhesive film” appears in, Labtec suggests a
film formulated for oral mucosal absorption. Thus, a person of ordinary
skill in the art would have considered Labtec, and combining Labtec and
Yang would not be, as Patent Owner contends, “completely antithetical” to
Labtec’s teaching and a skilled artisan’s expectation. See PO Resp. 26.
Patent Owner further argues that even if the prior art references are
combined, it would require undue experimentation to arrive at the claimed
invention. Id. at 48–53. Undue experimentation is part of the enablement
inquiry. See Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d 1312, 1314
(Fed. Cir. 2008) (“[A] prior art reference must enable one of ordinary skill in
the art to make the invention without undue experimentation.”). A
reference, however, qualifies as prior art in determining obviousness,
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independent of enablement. In re Antor Media Corp., 689 F.3d 1282, 1292
(Fed. Cir. 2012); see also In re Morsa, 713 F.3d 104, 111–12 (Fed. Cir.
2013) (remanding for proper enablement analysis in anticipation rejection,
but affirming obviousness rejection based on the same prior art). Thus, we
do not engage in enablement analyses in our obviousness determination.13
Instead, we interpret Patent Owner’s undue-experimentation argument
as an assertion of no reasonable expectation of success. Here, Patent Owner
presents contentions based on the alleged different delivery and absorption
routes (see PO Resp. 50–53), which we have addressed above. We also note
Patent Owner’s emphasis on how recent and complex pharmaceutical film
technology is, and how extensive research and development was required to
develop Suboxone® film. PO Resp. 48–50. Obviousness, however, does
not require absolute predictability of success. In re O’Farrell, 853 F.2d 894,
903–04 (Fed. Cir. 1988). Instead, all that is required is a reasonable
expectation of success. Id. Based on evidence before us, we are persuaded
that the teachings of Labtec, as explained above, combined with the
information in Yang, which the ’832 patent itself relies on as teaching
suitable processes to make the claimed film (Ex. 1001, 15:29–32), provides
such a reasonable expectation of success.
Patent Owner asserts that objective indicia support a finding of
nonobviousness. PO Resp. 53–57. Specifically, Patent Owner argues that
“Suboxone® sublingual films, which are covered by the challenged claims
of the ’832 patent, have achieved significant commercial success and have

13 As explained above in the discussion of the anticipation ground, we are
not persuaded by Patent Owner’s enablement challenge of Labtec. See
supra at 17–22.
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received praise from others in the field, which provides objective indicia that
claims 15–19 are nonobvious.” Id. at 53. The evidence of record, however,
does not persuade us that the asserted commercial success and praise
overcome Petitioner’s showing of obviousness here.
For objective evidence of secondary considerations to be accorded
substantial weight, Patent Owner must establish a nexus between the
evidence and the merits of the claimed invention. Wyers v. Master Lock Co.,
616 F.3d 1231, 1246 (Fed. Cir. 2010). In this case, Suboxone® tablets, with
the combination of buprenorphine and naloxone as the pharmaceutical
ingredients, were already on the market when the application for the ’832
patent was filed. Ex. 1013. Thus, the alleged inventive aspect of the
challenged claims resides only in the film dosage form. According to Patent
Owner, evidence shows that in 2013, “sales of Suboxone sublingual film
increased to more than $1.3 billion in the U.S. while the total market grew to
more than $1.7 billion.” PO Resp. 55 (citing Ex. 2046, 2). But, Patent
Owner fails to account for the market share of, and revenue generated by,
Suboxone® tablets before the film dosage form was introduced. Here, the
lack of such information is critical for analyzing secondary considerations,
especially in view of the fact that on March 18, 2013, Patent Owner
voluntarily withdrew Suboxone® tablets from the US market. Pet. 3;
Ex. 1003, 3. With the tablets no longer on the market, it is unclear whether
the sales increase or the alleged patient preference was due to the film
dosage form, or because film was the only available form. As a result, we
find the evidence of secondary considerations in this case cannot overcome
the evidence of obviousness.

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Motion to Exclude
Petitioner filed a Motion to Exclude Exhibit 2043. Paper 35.
According to Petitioner, Exhibit 2043 is a paper filed by a subsidiary of
Petitioner in an unrelated IPR proceeding. Id. at 1. Patent Owner opposed
the Motion. Paper 37. Because we do not rely on Exhibit 2043 in rendering
our Decision, we dismiss the Motion as moot.

CONCLUSION
Petitioner has shown, by a preponderance of the evidence, that Labtec
anticipates claims 15–19, and that the combination of Labtec, Birch, and
Yang would have rendered claims 15–19 obvious.

ORDER
Accordingly, it is
ORDERED that claims 15–19 of the ’832 patent are determined to be
unpatentable;
FURTHER ORDERED that Petitioner’s Motion to Exclude is
dismissed as moot.

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For PETITIONER:

Danielle L. Herritt
dherritt@mccarter.com

Kia L. Freeman
kfreeman@mccarter.com

For PATENT OWNER:

James M. Bollinger
james.bollinger@troutmansanders.com

Daniel A. Ladow
daniel.ladow@troutmansanders.com