Trials@uspto.gov
`571.272.7822
`
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`
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`Paper 18
`Entered: June 23, 2017
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`
`DR. REDDY’S LABORATORIES, LTD. and
`DR. REDDY’S LABORATORIES, INC.,
`Petitioners,
`
`v.
`
`INDIVIOR UK LIMITED,
`Patent Owner.
`____________
`
`Case IPR2016-01113
`Patent 8,475,832 B2
`____________
`
`
`
`Before JACQUELINE WRIGHT BONILLA, Vice Chief Administrative
`Patent Judge, TONI R. SCHEINER and ZHENYU YANG, Administrative
`Patent Judges.
`
`
`BONILLA, Vice Chief Administrative Patent Judge.
`
`
`
`DECISION
`Denying Petitioner’s Request for Rehearing
`37 C.F.R. § 42.71
`
`
`571.272.7822
`
`
`
`
`
`
`
`Paper 18
`Entered: June 23, 2017
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`
`DR. REDDY’S LABORATORIES, LTD. and
`DR. REDDY’S LABORATORIES, INC.,
`Petitioners,
`
`v.
`
`INDIVIOR UK LIMITED,
`Patent Owner.
`____________
`
`Case IPR2016-01113
`Patent 8,475,832 B2
`____________
`
`
`
`Before JACQUELINE WRIGHT BONILLA, Vice Chief Administrative
`Patent Judge, TONI R. SCHEINER and ZHENYU YANG, Administrative
`Patent Judges.
`
`
`BONILLA, Vice Chief Administrative Patent Judge.
`
`
`
`DECISION
`Denying Petitioner’s Request for Rehearing
`37 C.F.R. § 42.71
`
`
`
`IPR2016-01113
`Patent 8,475,832 B2
`
`I.
`
`INTRODUCTION
`
`Dr. Reddy’s Laboratories, Ltd. and Dr. Reddy’s Laboratories, Inc.
`
`(collectively “Petitioner”), filed a Request for Rehearing under 37 C.F.R.
`
`§ 42.71(d) of our Decision (Paper 16, “Decision” or “Dec.”) denying 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 17 (“Req. Reh’g”). In our Decision, we
`
`denied institution as to all of the grounds set forth in the Petition (Paper 1,
`
`“Pet.”). Dec. 2–4, 10–19. Petitioner’s Request for Rehearing seeks
`
`reconsideration of our denial to institute each of the grounds. Req. Reh’g 1.
`
`Under 37 C.F.R. § 42.71(c), “[w]hen rehearing a decision on petition,
`
`a panel will review the decision for an abuse of discretion.” An abuse of
`
`discretion occurs when a “decision was based on an erroneous conclusion of
`
`law or clearly erroneous factual findings, or . . . a clear error of judgment.”
`
`PPG Indus., Inc. v. Celanese Polymer Specialties Co., 840 F.2d 1565, 1567
`
`(Fed. Cir. 1988). The request for rehearing “must specifically identify all
`
`matters the party believes the Board misapprehended or overlooked, and the
`
`place where each matter was previously addressed in a motion, an
`
`opposition, or a reply.” 37 C.F.R. § 42.71(d). A party who requests
`
`rehearing bears the burden of showing that a decision should be modified.
`
`Id.
`
`II. ANALYSIS
`
`Petitioner argues that we “erred in applying a legally improper, overly
`
`restrictive obviousness analysis and ignoring the ample evidence provided
`
`by Petitioner and its expert.” Req. Reh’g 3. Specifically, Petitioner takes
`
`issue with our statement in the Decision that Petitioner did “not point to
`
`
`
`2
`
`
`
`IPR2016-01113
`Patent 8,475,832 B2
`
`where the SBOA,1 the Suboxone® 2002 Label,2 and/or LabTec3 suggest that
`
`anyone actually measured a local pH for the Suboxone tablets in an oral
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`cavity, much less determined that local pH should be from about 3 to about
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`3.5.” Id. at 4, 10 (quoting Dec. 13). Petitioner states that we “applied an
`
`overly restrictive standard in requiring the SBOA, the Suboxone® 2002
`
`Label, and/or LabTec to ‘actually measure a local pH for the Suboxone
`
`tablets in an oral cavity’ or to ‘[determine] that a local pH should be from
`
`about 3 to about 3.5,’” and that we “ignored the teachings in these references
`
`of the importance of pH, including specifically teaching that a pH range
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`exists, for dissolution and transmucosal absorption.” Id. at 10 (alteration in
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`original) (quoting Dec. 13).
`
`Petitioner alleges that our Decision took a teaching from LabTec out
`
`of context, namely that “[f]or a basic active ingredient,” one would lower the
`
`pH for the purpose of “retarding absorption of the active ingredient through
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`the oral mucosa.” Id. at 9 (alteration in original) (emphasis omitted)
`
`(quoting Dec. 17). Petitioner also repeats its argument that given the
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`teachings of the applied references, including “knowledge of the pH
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`dependence of the transmucosal absorption of buprenorphine and naloxone,”
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`it only would have required routine experimentation to obtain an optimal pH
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`range, and to arrive at the claimed pH range of about 3 to about 3.5. Id. at
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`13.
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`Petitioner further argues that it did not rely solely on the SBOA,
`
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`1 Suboxone® Tablet Summary Basis of Approval (“SBOA”) (Ex. 1009).
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`2 Suboxone® 2002 Label (Ex. 1008).
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`3 WO 2008/040534 A2, published Apr. 10, 2008 (“LabTec”) (Ex. 1007).
`
`
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`3
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`
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`IPR2016-01113
`Patent 8,475,832 B2
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`Suboxone® 2000 Label, and LabTec. Id. at 4. Specifically, the Request for
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`Rehearing summarizes the Petition’s description of LabTec, Oksche,4 Yang,5
`
`the Suboxone® 2002 Label, the SBOA, Dr. Çelik’s testimony (Ex. 1003),
`
`Birch,6 and the ’055 publication,7 and argues that as supported by Dr.
`
`Çelik’s testimony, LabTec and Oksche provided a motivation to develop the
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`film version of Suboxone® tablets, and Yang established a reasonable
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`likelihood of success in manufacturing a film product bioequivalent to
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`Suboxone® tablets. Req. Reh’g 4–8.
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`The Request for Rehearing also asserts that Birch taught
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`administration of buprenorphine-containing formulations to the nasal
`
`mucosa at a pH of about 3.5, which successfully resulted in transmucosal
`
`absorption of buprenorphine and the desired bioequivalence, such that as a
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`result, there was a motivation to use a pH of 3.4 for a film dosage form of
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`buprenorphine and naloxone with a reasonable likelihood of success of
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`achieving bioequivalence to the tablet form. Id. at 6, 11–12. Petitioner
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`relies on Dr. Çelik’s testimony in support of this assertion. Id. at 11–12.
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`Furthermore, Petitioner alleges that we erred in discounting Dr. Çelik’s
`
`testimony regarding similar anatomy of the oral and nasal mucosa as
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`conclusory. Id.
`
`We disagree with Petitioner that we applied an overly restrictive
`
`
`4 WO 2008/025791 A1, published Mar. 6, 2008 (“Oksche”) (Ex. 1005).
`
`5 Yang et al., U.S. Patent No. 7,357,891 B2, issued Apr. 15, 2008 (“Yang”)
`(Ex. 1006).
`
`6 Birch et al., U.S. Patent Application Publication No. 2005/0085440 A1,
`published Apr. 21, 2005 (“Birch”) (Ex. 1004).
`
`7 Yang et al., U.S. Patent Application Publication No. 2005/0037055 A1,
`published Feb. 17, 2005 (“the ’055 publication”) (Ex. 1010).
`
`
`
`4
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`
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`IPR2016-01113
`Patent 8,475,832 B2
`
`obviousness analysis. In stating that Petitioner did “not point to where the
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`SBOA, the Suboxone® 2002 Label, and/or LabTec suggest that anyone
`
`actually measured a local pH for the Suboxone tablets in an oral cavity,
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`much less determined that local pH should be from about 3 to about 3.5, as
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`recited in the challenged claims,” we addressed Petitioner’s reliance on those
`
`three references as collectively teaching or suggesting the claim limitations
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`“[a] buffer in an amount to provide a local pH” of “about 3 to about 3.5.”
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`Dec. 13 (citing Pet. 27–32). We concluded that those three references did
`
`not provide sufficient evidence to establish those claim limitations as known
`
`prior art elements. See id. at 13–14.
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`Petitioner is incorrect that we ignored teachings in those three
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`references concerning pH. Rather, we considered the Suboxone® Label’s
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`disclosure of a buffering system consisting of citric acid and sodium citrate
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`and Petitioner’s contention, relying on Dr. Çelik’s testimony, that a citric
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`acid and sodium citrate buffer operates within the range of 3.0 to 6.2. Id. at
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`12–13 (citing Pet. 31–32). We also considered the SBOA’s disclosure of in
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`vitro dissolution studies identifying redacted pH values, and Petitioner’s
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`conclusion based on the SBOA, “that in order for buprenorphine to dissolve,
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`the local pH of the saliva had to be below a certain value, and for naloxone
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`to dissolve, the pH had to be above a certain value because the solubility
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`profiles of these drugs are dependent on pH.” Id. at 11 (quoting Pet. 29); id.
`
`at 13 (citing Pet. 29–32). And we further considered LabTec’s disclosure of
`
`the relationship between pH and absorption. Id. at 11 (citing Pet. 27–28); id.
`
`at 17. We found, however, insufficient evidence to support a conclusion that
`
`a local pH value for Suboxone® in the oral cavity or a local pH range of
`
`about 3 to about 3.5 were known or obvious. Id. at 11–14.
`
`
`
`5
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`
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`IPR2016-01113
`Patent 8,475,832 B2
`
`
`We considered Petitioner’s argument that “‘it would have been
`
`nothing more than routine experimentation’ to identify ‘the claimed pH
`
`range of 3 to 3.5 as optimal.’” Id. at 16 (quoting Pet. 33). As we discussed
`
`in our Decision, however, the relationship between pH and absorption that
`
`LabTec discloses is that “[f]or a basic active ingredient, one would adjust the
`
`pH of the solution to below the pKa of the conjugate acid” as a “means for
`
`retarding absorption of the active ingredient through the oral mucosa.” Id. at
`
`17 (alteration in original) (emphasis omitted) (quoting Ex. 1007, at 15). In
`
`other words, for a basic active ingredient like buprenorphine, this teaching
`
`suggests to lower the pH where the goal is to retard oral absorption. See
`
`id.; see also Ex. 1009, at 28 (describing buprenorphine as a “weak base” and
`
`stating that “[a]bsorption of lipophilic weak bases should increase with
`
`salivary pH increases”). As such, as noted in our Decision, 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. Dec. 17. In contrast, the claims of the ’832 patent require
`
`adjusting the local pH to “optimize absorption of said buprenorphine,” and
`
`the specification further explains that “[i]n a dosage form that is to be placed
`
`in the oral cavity, it is desired to absorb the agonist [buprenorphine]
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`buccally, so as to provide rapid integration of the agonist into the body of the
`
`user.” Ex. 1001, 11:10–13, 23:65–67, 24:33–35.
`
`We disagree with Petitioner that our Decision takes LabTec’s teaching
`
`out of context. According to Petitioner,
`
`Naloxone, which is disclosed in LabTec at page 27, is precisely
`the active ingredient a POSA desires to be retarded from
`transmucosal absorption in the presence of buprenorphine.
`Moreover, while the pH of a basic active ingredient can be
`
`
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`6
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`
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`IPR2016-01113
`Patent 8,475,832 B2
`
`
`adjusted below the pKa of the conjugate acid, common sense
`dictates that the converse is equally true. That is, for a basic
`active ingredient, one would adjust the pH of the solution to
`above the pKa of the conjugate acid to enhance transmucosal
`absorption. This very application was discussed in Dr. Çelik’s
`testimony. Success by a POSA would be reasonably expected
`since enhanced buprenorphine transmucosal absorption was
`achieved along with retarded naloxone transmucosal absorption
`by the Suboxone® tablets.
`
`Req. Reh’g 9–10 (citations omitted). The problem with Petitioner’s
`
`conclusion, however, is that the evidence of record shows that both naloxone
`
`and buprenorphine are weak bases with similar pKas. See Prelim Resp. 3,
`
`14–17; Ex. 1001, 11:46–48; Ex. 1003 ¶¶ 46, 55 (stating that “[t]he pKa of
`
`naloxone is 7.94 and “[t]he pKa of buprenorphine is 8.42,” and quoting a
`
`statement made by the applicants in the prosecution history that both
`
`buprenorphine and naloxone “are conjugate acids with pKa’s at
`
`approximately 8”); Ex. 1009, at 28. Petitioner provides no explanation for
`
`why, when decreasing the pH to retard transmucosal absorption of the
`
`naloxone component as desired, one of ordinary skill in the art would have
`
`expected the opposite result (enhanced transmucosal absorption) to occur for
`
`the buprenorphine component, when both naloxone are buprenorphine are
`
`basic active ingredients having similar pKas.
`
`
`
`In addition, our Decision also was not limited to an analysis of the
`
`LabTec, Suboxone® 2002 Label, and SBOA references alone. We
`
`considered Petitioner’s arguments concerning Birch, including the argument
`
`that Birch taught that transmucosal absorption of buprenorphine was optimal
`
`within the pH range of about 3 to about 3.5, specifically, 3.4. Dec. 14 (citing
`
`Pet. 32–33). We were unpersuaded by Petitioner’s arguments, however,
`
`finding that Birch, which taught buprenorphine formulations (lacking
`
`
`
`7
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`
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`IPR2016-01113
`Patent 8,475,832 B2
`
`naloxone), exclusively applied to intranasal administration. Id. at 14–15.
`
`We found insufficient evidence to suggest that the pH values disclosed in
`
`Birch would have been applicable to optimal buprenorphine absorption in
`
`the context of oral administration. Id. Rather, we found that Birch indicated
`
`that buprenorphine pharmacokinetics (e.g., Cmax and bioavailability) differed
`
`when administered to oral versus nasal mucosa. Id. at 15 (citing Prelim.
`
`Resp. 27; Ex. 1004, at 16 tbl.11).
`
`
`
`We disagree with Petitioner that we erred in finding Dr. Çelik’s
`
`statement 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 ¶ 105) is merely conclusory.
`
`In the Request for Rehearing, Petitioner argues that Dr. Çelik’s testimony in
`
`the same paragraph as this statement provides support. Req. Reh’g 12
`
`(citing Ex. 1003 ¶ 105). We have reviewed this paragraph of Dr. Çelik’s
`
`declaration, however, and we find that with the exception of the paragraph’s
`
`final sentence (which is the statement at issue), the entirety of the paragraph
`
`is a summary of Birch’s disclosures and concerns delivery to the nasal
`
`mucosa. See Ex. 1003 ¶ 105. Before the final sentence of the paragraph, the
`
`testimony in this paragraph fails to mention oral mucosa, let alone provide
`
`reasoning or support for why Dr. Çelik concludes that “[t]he anatomy of the
`
`oral and nasal mucosa is quite similar” or why it would have been expected
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`“that the same principle of drug delivery will apply to both tissues.” See id.
`
`
`
`Finally, the Request for Rehearing reiterates the Petition’s discussion
`
`of various teachings of individual references, including LabTec, Oksche,
`
`Yang, the Suboxone® 2002 Label, the SBOA, and Birch. See Req. Reh’g 4–
`
`6. In our Decision, however, we considered and addressed Petitioner’s
`
`
`
`8
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`IPR2016-01113
`Patent 8,475,832 B2
`
`arguments regarding each of those references. See Dec. 10 (citing Pet. 24–
`
`27) (LabTec and Yang); id. at 11–13 (SBOA and Suboxone® 2002 Label);
`
`id. at 14–15 (Birch); id. at 18 (citing Pet. 40–50) (Oksche). Petitioner
`
`further asserts that the Petition discussed how it would have been obvious
`
`from LabTec and Oksche to develop a film version of Suboxone® and how
`
`Yang would have provided a reasonable expectation of success in
`
`manufacturing an oral film bioequivalent to Soboxone® tablets. Req. Reh’g
`
`6–8. The Petition, however, did not provide evidence accounting for the
`
`claim limitations pertaining to the local pH range discussed above.
`
`Likewise, the Request for Rehearing refers to Dr. Çelik’s testimony
`
`regarding the known absorption and nonabsorption characteristics of the
`
`buprenorphine and naloxone components, respectively, of the Suboxone®
`
`tablet (id. at 5–6 (citing Pet. 17; Ex. 1003 ¶¶ 75, 83)), and further refers to
`
`the Petition’s discussion of the ’055 publication (id. at 6). But again, neither
`
`the ’055 publication (which Petitioner only relied on in relation to dependent
`
`claims 3, 11, and 12 (see Pet. 11–12)), nor this testimony from Dr. Çelik,
`
`provides adequate evidence of the claimed local pH range.
`
`III. CONCLUSION
`
`
`
`The Request for Rehearing does not identify any matters that we
`
`misapprehended or overlooked, nor does it show that our Decision denying
`
`institution was based on an erroneous conclusion of law, clearly erroneous
`
`factual findings, or a clear error of judgment.
`
`IV. ORDER
`
`Accordingly, it is
`
`ORDERED that Petitioner’s Request for Rehearing is denied.
`
`
`
`
`
`9
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`
`
`IPR2016-01113
`Patent 8,475,832 B2
`
`PETITIONER:
`
`Jeffery B. Arnold
`Leslie-Anne Maxwell
`Peter R. Hagerty
`Andrew C. Ryan
`CANTOR COLBURN LLP
`jarnold@cantorcolburn.com
`phagerty@cantorcolburn.com
`amaxwell@cantorcolburn.com
`ryan@cantorcolburn.com
`
`
`
`PATENT OWNER:
`
`Andrea G. Reister
`Enrique D. Longton
`COVINGTON & BURLING LLP
`areister@cov.com
`rlongton@cov.com
`
`
`Dustin B. Weeks
`TROUTMAN SANDERS LLP
`dustin.weeks@troutmansanders.com
`
`
`
`
`10
`
`
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