Purdue Pharma L.P.
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`Appl. No. 14/500,409
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`Remarks
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`Upon entry of the present amendment, claims 1-9, 21, and 24 will be pending. Claims
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`10-20 and 22 are withdrawn. Claims 1 and 24 are currently amended. Claim 23 is canceled.
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`No claims are new.
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`Reconsideration is respectfully requested in view of the noted
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`amendments and following remarks.
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`Discussion of Claim Amendments
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`Claims
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`1 and 24 have been amended to reflect
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`that
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`the buprenorphine or
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`the
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`pharmaceutically acceptable salt thereof and the naloxone or the pharmaceutically acceptable salt
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`thereof are dissolved or homogeneously dispersed in the film. Support for this amendment can
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`be found in at least former claim 23 and the first filll paragraph on page 17 of the application as
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`filed.
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`Claims 1 and 24 have been further amended to note that the dosage form releases
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`substantially all of the buprenorphine or the pharmaceutically acceptable salt thereof and the
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`naloxone or the pharmaceutically acceptable salt thereof in less than 5 minutes upon sublingual
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`administration such that the buprenorphine and naloxone or the pharmaceutically acceptable salts
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`thereof are available for absorption by the sublingual mucosa.
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`Support for the release of naloxone as set forth in the amended claims can be found
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`throughout the application as filed and at least in the last full paragraph of page 21 of the
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`application as filed. Support for the claim element "such that the buprenorphine and naloxone or
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`the pharmaceutically acceptable salts thereof are available for absorption by the sublingual
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`mucosa" can be found in at least the third filll paragraph on page 16 of the application as filed.
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`Support for addition of the claim element "average" in claim 1 can be found in at least the
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`first full paragraph on page 5 of the application as filed.
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`Applicant filrther notes that the phrase "the sublingual dosage form is a film" has been
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`moved up in claims 1 and 24. This amendment was made for purposes of clarity.
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`

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`Purdue Pharma L.P.
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`Appl. No. 14/500,409
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`Interview Summary
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`On April 21, 2015, Applicant's representatives Matthew S. Bodenstein, John Covert,
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`Richard Inz, and Philip Strassburger conducted a telephonic interview with the Examiner.
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`Applicant's expert, Sudip Das, PhD. was also present on the call.
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`During the call,
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`the parties discussed the differences between the cited art and the
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`presently claimed dosage form.
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`In particular, Applicant's representatives and expert described
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`how the secondary reference, Firm, is limited to dosage forms wherein the antagonist (naloxone)
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`is not available for transmucosal absorption because it is associated with an abuse-resistant
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`matrix. No formal agreement regarding patentability was reached.
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`Applicant's representatives again thank the Examiner for his availability and time.
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`Reply to 35 U.S.C. §103(a) Rejection
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`Claims 1-9, 21, and 23-24 stand rejected under 35 U.S.C. 103(a) as being unpatentable
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`over the Suboxone ® Tablet Package Insert ("Suboxone® PI") and US. 2007/0148097 to Finn,
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`et a] ("Firm"). According to the Examiner, a skilled artisan would have found it obvious to
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`modify the Suboxone ® Tablets in view of Firm to arrive at a mucoadhesive film having the
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`presently claimed properties with a reasonable expectation of success. The Examiner asserts that
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`a skilled artisan would have been motivated to modify the Suboxone ® Tablets because it is well
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`known in the art that some patients have difficulty swallowing tablets and capsules. Applicant
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`disagrees and traverses.
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`Foremost, Applicant does not agree that a skilled artisan would have been motivated to
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`modify the Suboxone ® Tablet because some patients have "difficulty swallowing tablets and
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`capsules." The Suboxone ® Tablet is a sublingual dosage form and is not administered orally.
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`As such, the Examiner's rationale for combination would not have been considered reasonable by
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`a person of ordinary skill in the art.
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`Purdue Pharma L.P.
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`Appl. No. 14/500,409
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`But even if a skilled artisan would have been motivated to modify the Suboxone ® Tablet
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`in view of Finn for some other reason, which Applicant does not concede, a skilled artisan would
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`not have arrived at the dosage forms of claims 1 or 24 wherein both buprenorphine and naloxone
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`are available for transmucosal absorption.
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`Instead, a skilled artisan would have arrived at a
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`dosage form wherein the antagonist (naloxone) is substantially transmucosally unavailable.
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`Specifically, while Finn teaches a mucoadhesive dosage form, Finn associates its
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`antagonist, naloxone, with an "abuse-resistant matrix." See paragraphs 8-9 of the attached 37
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`C.F.R. §1.132 declaration of Sudip Das ("Das"). Finn's abuse-resistant matrix is a layer or
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`coating, such as a water-erodable coating or layer at least partially disposed about the antagonist.
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`Alternatively, it can be a water-hydrolyzable, water erodible, or water soluble matrix, such as an
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`ion exchange polymer. Das, 1113.
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`When used as directed, Finn's abuse-resistant matrix ensures that the antagonist
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`is
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`substantially transmucosally unavailable, with the abuse-resistant matrix ensuring that
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`substantially all of the antagonist is delivered to the GI tract.
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`See, Finn, 1126 ("In some
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`embodiments, the antagonist is substantially transmucosally unavailable when used in a non-
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`abusive manner.") Once present in the GI tract, the antagonist is absorbed and subsequently
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`metabolized in the liver during so-called "first pass metabolism." First-pass metabolism renders
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`the antagonist therapeutically ineffective such that it does not interfere with the effects of the
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`abusable drug present in Finn's formulation. Das, 1110. Moreover, Finn teaches that separating
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`the antagonist and the abusable drug is necessary in order to ensure the efficacy of the abusable
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`drug in view of the effects of the antagonist. Das, 1111. See also, Finn, 1110.
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`Although Finn's abuse-resistant matrix does not effectively release the antagonist when
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`the device is used in a non-abusive manner, it releases the antagonist when the dosage form is
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`used in an abusive manner (i.e. dissolved in a solvent, opened, chewed, and/or cut apart).
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`In
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`contrast, the antagonist in the instant application is released along with the buprenorphine such
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`that both are available for transmucosal absorption. Das, 1112. See also, claims 1 and 24.
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`Finn describes various permutations of his device, with the abuse-resistant matrix
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`potentially present in one of various layers referred to as a "mucoadhesive layer," a "backing
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`Purdue Pharma L.P.
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`Appl. No. 14/500,409
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`layer," and a "third layer," wherein the third layer is disposed in between the mucoadhesive layer
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`and the backing layer. Das, 1114.
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`But in each of the embodiments supported as of Finn's provisional filing datesl, the
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`antagonist
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`is associated with the abuse-resistant matrix such that
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`it
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`is
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`substantially
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`transmucosally unavailable.
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`Instead, the antagonist is only delivered to the GI tract, where it is
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`safely metabolized. Das, 111115-16.
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`In summary, even if a skilled artisan would have been motivated to modify the
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`Suboxone ® Tablet in view of Finn, which is not admitted, at best, a skilled artisan would have
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`developed a film having its antagonist associated with an abuse-resistant matrix.
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`In such an
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`system, and as discussed at length in Finn and Das, the antagonist is substantially transmucosally
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`unavailable. But that is not the system that is presently claimed. Thus, the Examiner has not
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`established a primafacie case of obviousness.
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`In view of the foregoing, Applicants respectfully submit that the combination proposed
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`by the Examiner does not render claims 1-9, 21, and 24 obvious. The Examiner is therefore
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`requested to withdraw the pending rejection and allow all claims.
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`Reply to Double Patenting Rejection
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`The Examiner has provisionally rejected claims 1-9, 21, and 23-24 of the pending
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`application over claims 21-37 of co-pending application 12/439,410 for non-statutory
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`obviousness-type double patenting. Applicant has included a terminal disclaimer over U.S.
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`12/439,410 with this reply rendering this rejection moot. The Examiner is therefore requested to
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`withdraw this rejection.
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`1Although Finn's paragraph 51 states that the "antagonist may be commingled with the [abusable] drug in the
`mucoadhesive layer," Applicant respectfully submits that this embodiment implicitly associates the antagonist with
`the abuse-resistant matrix in view of the totality of Finn's disclosure. To the extent the Examiner disagrees and
`believes the disclosure in Finn's 1151 supports an embodiment wherein the antagonist and the abusable drug are
`commingled in the absence of an abuse-resistant matrix, the noted gassage is not grior art against the gending
`claims. The disclosure in Finn's 1151 was not present in either Finn provisional and thus is only art under pre-AIA 35
`U.S.C. §102(e) as of Dec. 13, 2006 (Finn's non-provisional filing date) or under pre-AIA 35 U.S.C. §102(a) as of
`June 28, 2007 (Finn's U.S. Publication Date). Because Applicant has perfected priority under 35 U.S.C. ll9(a)-(d)
`to EP 061198396 (filed August 30, 2006), the noted passage is not art under any pre-AIA 35 U.S.C. §102 provision.
`See MPEP E9, 706.02(b)(2).
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`Purdue Pharma L.P.
`
`Appl. No. 14/500,409
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`Conclusion
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`All claims are believed to be in condition for allowance. An early action to that end is
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`earnestly solicited. To the extent the Examiner believes it would be useful or would expedite
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`examination, the Examiner is invited to telephone Applicant's undersigned representative.
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`Respectfully submitted,
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`STERNE, KESSLER, GOLDSTEIN & Fox P.L.L.C.
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`/Matthew S. Bodenstein/
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`Matthew S. Bodenstein
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`Registration No. 58,885
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`Date:
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`May 26, 2015
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`1100 New York Avenue, NW.
`Washington, DC. 20005-3934
`(202) 371-2600
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`199467073
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`-10-
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