www.uspto.gov
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`PO. Box 1450
`Alexandria, Virginia 2231371450
`
`15/442,231
`
`02/24/2017
`
`Alexander OKSCHE
`
`18612700005
`
`8650
`
`STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
`1100 NEW YORK AVENUE NW
`WASHINGTON, DC 20005
`
`RICCI. CRAIG D
`
`PAPER NUMBER
`
`ART UNIT
`
`1611
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`03/20/2019
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above—indicated "Notification Date" to the
`
`following e—mail address(es):
`e-office @ sternekessler. com
`
`jcovert @ sternekessler.com
`
`PTOL-90A (Rev. 04/07)
`
`

`

`0,7709 A0170” Summary
`
`Application No.
`15/442,231
`Examiner
`CRAIG D RICCI
`
`Applicant(s)
`OKSCHE et al.
`Art Unit
`1611
`
`AIA (FITF) Status
`No
`
`- The MAILING DA TE of this communication appears on the cover sheet wit/7 the correspondence address -
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE g MONTHS FROM THE MAILING
`DATE OF THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed after SIX (6) MONTHS from the mailing
`date of this communication.
`|f NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`-
`- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any earned patent term
`adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1). Responsive to communication(s) filed on 8/10/2018.
`[:1 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
`
`2a)D This action is FINAL.
`
`2b)
`
`This action is non-final.
`
`3)[:] An election was made by the applicant in response to a restriction requirement set forth during the interview on
`; the restriction requirement and election have been incorporated into this action.
`
`4)[:] Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Expat/7e Quay/e, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims*
`
`5)
`
`Claim(s) fl is/are pending in the application.
`
`5a) Of the above claim(s)
`
`is/are withdrawn from consideration.
`
`E] Claim(s)
`
`is/are allowed.
`
`Claim(s) fl is/are rejected.
`
`[:1 Claim(s) _ is/are objected to.
`
`) ) ) )
`
`6 7
`
`8
`
`
`
`are subject to restriction and/or election requirement
`[j Claim(s)
`9
`* If any claims have been determined aflowabie. you may be eligible to benefit from the Patent Prosecution Highway program at a
`
`participating intellectual property office for the corresponding application. For more information, please see
`
`http://www.uspto.gov/patents/init events/pph/index.jsp or send an inquiry to PPeredback@uspto.gov.
`
`Application Papers
`10)[:] The specification is objected to by the Examiner.
`
`11)[:] The drawing(s) filed on
`
`is/are: a)D accepted or b)l:] objected to by the Examiner.
`
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`
`Priority under 35 U.S.C. § 119
`12):] Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
`
`a)D All
`
`b)I:I Some**
`
`c)CI None of the:
`
`1.[:] Certified copies of the priority documents have been received.
`
`2.[:] Certified copies of the priority documents have been received in Application No.
`
`3.[:] Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`
`** See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`
`1)
`
`Notice of References Cited (PTO-892)
`
`Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`2)
`Paper No(s)/Mai| Date 8/10/2018; 10/23/2018_
`U.S. Patent and Trademark Office
`
`3) C] Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`4) CI Other-
`
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20190314
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 2
`
`DETAILED ACTION
`
`Continued Examination Under37 CFR 1.114
`
`1.
`
`A request for continued examination under 37 CFR 1.114,
`
`including the fee set forth in 37
`
`CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for
`
`continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been
`
`timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR
`
`1.114. Applicant's submission filed on 8/10/2018 has been entered.
`
`Response to Arguments
`
`2.
`
`Applicant’s arguments, filed 8/10/2018, have been fully considered. Rejections and/or
`
`objections not reiterated from previous office actions are hereby withdrawn. The following
`
`rejections and/or objections are either reiterated or newly applied. They constitute the complete
`
`set presently being applied to the instant application. Arguments directed to withdrawn rejections
`
`have been rendered moot.
`
`Claim Rejections - 35 USC § 112
`
`3.
`
`The following is a quotation of the first paragraph of 35 U.S.C. 112:
`
`The specification shall contain a written description of the invention, and of the manner and process of
`making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art
`to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set
`forth the best mode contemplated by the inventor of carrying out his invention.
`
`4.
`
`The following is a quotation of the second paragraph of 35 U.S.C. 112:
`
`The specification shall conclude with one or more claims particularly pointing out and distinctly claiming
`the subject matter which the applicant regards as his invention.
`
`5.
`
`Claims 1-8 are rejected under35 U.S.C. 112, first paragraph, as failing to comply with
`
`the written description requirement. The claim(s) contains subject matter which was not
`
`described in the specification in such a way as to reasonably convey to one skilled in the
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 3
`
`relevant art that the inve ntor(s), at the time the application was file d, had possession of the
`
`claimed invention.
`
`6.
`
`The response filed 8/10/2018 has introduced NEW MATTER into the claims. Amended
`
`claim 1 is directed to a method which utilizes a mucoadhesive film dosage form which “does not
`
`include naloxone, naltrexone... or other opioid antagonists capable of inducing opioid
`
`withdrawal symptoms upon parenteral administration with bupre norphine ”.
`
`7.
`
`In the instant case, regarding opioid antagonists
`
`that are capable of inducing opioid
`
`withdrawal symptoms upon parenteral administration with buprenorphine,
`
`the Specification only
`
`discloses that “parenteral co—administration of buprenorphine and naloxone . .. will lead to serious
`
`withdrawal symptoms” (Page 3).
`
`8.
`
`As such, written description support
`
`is lacking for the broader genus of all “opioid
`
`antagonists capable of inducing opioid withdrawal symptoms upon parenteral administration with
`
`buprenorphine”, as is instantly claimed.
`
`9.
`
`Claims 1-8 are rejected under 35 U.S.C. 112, second paragraph, as being indefinite
`
`for failing to particularly point out and distinctly claim the subject matter which the
`
`applicant regards as the invention.
`
`10.
`
`Amended claim 1 is directed to a method which utilizes a mucoadhesive film dosage form
`
`which “does not include naloxone, naltrexone. .. or otheropioid antagonists capable of inducing
`
`opioid withdrawal symptoms upon parenteral administration with bupre norphine”.
`
`11.
`
`As discussed in MPEP 2173.05(g), “the use of functional language in a claim may fail ‘to
`
`provide a clear—cut indication of the scope of the subject matter embraced by the claim’ and thus
`
`be indefinite.
`
`In re Swinehart, 439 F.2d 210 (CCPA 1971). For example, when claims merely
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 4
`
`recite... a function or result achieved by the invention,
`
`the boundaries of the claim scope may be
`
`unclear. Halliburton Energy Servs., Inc. v. M-ILLC, 514 F.3d 1244, (Fed. Cir. 2008).”
`
`12.
`
`In the instant case, it is so unclear which opioid antagonists would be capable of inducing
`
`opioid withdrawal symptoms upon parenteral administration with buprenorphine that the claims
`
`are indefinite.
`
`Claim Rejections - 35 USC § 102
`
`13.
`
`The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the
`
`basis for the rejections under this section made in this Office action:
`
`A person shall be entitled to a patent unless —
`
`(b) the invention was patented or described in a printed publication in this or aforeign country or in public
`use or on sale in this country, more than one year prior to the date of application for patent in the United
`States.
`
`14.
`
`Claims 1 and 5 are rejected under 35 U.S.C. 102(b) as being anticipated by Cremer et
`
`al (AU 1998-56532 B2) as evidenced by McAleer et al (Drug and Alcohol Dependence 72:75-
`
`83, 2003).
`
`15.
`
`As amended, instant claim 1 is drawn to a method of treating pain in a subject in need
`
`thereof, comprising contacting an oral mucosal surface of the subject with a mucoadhesive film
`
`dosage form comprising:
`
`(a)
`
`buprenorphine in an amount sufficient to provide an average CmX of less than 2.5
`
`ng/ml and an average buprenorphine AUC0_4g of less than 15 (hrs*ng)/ml, which is
`
`dissolved or homogenously dispersed in (b):
`
`(b)
`
`at
`
`least
`
`one
`
`non—gelatin
`
`polymeric
`
`film—forming
`
`material
`
`(e. g.,
`
`carboxyme thylce llulos e );
`
`wherein:
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 5
`
`(i)
`
`within less than 5 minutes after contacting the subject’s oral mucosal surface with
`
`the mucoadhesive film dosage form, substantially all of the buprenorphine contacts
`
`the mucosal surface of the subject’s oral cavity; and
`
`(ii)
`
`the dosage form does not include naloxone, naltrexone, etc.
`
`16.
`
`Cremer et al teach the treatment of “acute conditions of pain” comprising administering a
`
`“buccal pharmaceutical preparation...
`
`comprising as [an] active substance buprenorphine
`
`[wherein, “the individual analgesic dose will be about 0.1 to 1 mg” (Page 8)]... characterized by
`
`a flat, film-like administration form, disintegratable in the aqueous medium of the oral cavity,
`
`which has a mucoadhesive, active substance—containing layer based on the water-soluble, film
`
`forming polymers of small thickness, for rapid active substance transfer” (Pages 4—4a), wherein
`
`“improved contact... with the oral mucosa can be achieved through selecting auxiliary
`
`substances... [such as] carboxymethylcellulose” — listed among 8 auxiliary substances — (Pages
`
`5—6), and further noting that the mucoadhesive film “administration form for buprenorphine...
`
`releases the active substance in the oral cavity while not having the disadvantages [such as “the
`
`not inconsiderable disintegration time...
`
`typically about 5 to 10 minutes” of sublingual
`
`tablets]
`
`described in the prior art” (Page 4).
`
`17.
`
`Significantly, Cremer et al further teach preparation of the film wherein “at least one water—
`
`soluble polymer capable of forming a film,
`
`the active substance(s) and a suitable, vaporizable
`
`liquid must be intimately mixed” wherein “it
`
`is possible to incorporate further auxiliary
`
`substances” (Pages 8—9).
`
`18.
`
`Based on Cremer et al, one of ordinary skill
`
`in the art would have immediately envisaged
`
`treating pain in a subject in need thereof comprising contacting the oral mucosal surface of the
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 6
`
`subject with a mucoadhesive film dosage form comprising buprenorphine which is dissolved or
`
`homogenously dispersed inthe auxiliary substance carboxymethycellulose.
`
`19.
`
`Cremer et al, however, do n_ot specifically indicate the Cmax, AUC and disintegration
`
`time.
`
`20.
`
`Yet, McAleer et al demonstrate that:
`
`*
`
`2 mg SubuteX [which is a sublingual buprenorphine tablet] provides an average
`
`CmX of 1.6 i 0.5 ng/ml and an AUC of 9.05 i 2.67 (hrs*ng)/ml (Page 81, Table 1);
`
`and
`
`*
`
`“[m]edian in viva times of sublingual disintegration were 6 (2— 17) min for
`
`Subutex® at 2... mg” (Page 80, Column 1).
`
`21.
`
`Based on the foregoing,
`
`it is asserted, absent evidence to the contrary, that administration
`
`of about 0.1 to 1 mg buprenorphine via a mucoadhesive film dosage form for the treatment of
`
`pain (as taught by Cremer et al) would necessarily provide an average CmX of less than 2.5 ng/ml
`
`and an average buprenorphine AUC0_48 of less than 15 (hrs*ng)/ml, as instantly claimed.
`
`22.
`
`And further considering that Cremer et al teach that the mucoadhesive film “administration
`
`form for buprenorphine...
`
`releases the active substance in the oral cavity while not having the
`
`disadvantages [such as “the not
`
`inconsiderable disintegration time...
`
`typically about 5 to 10
`
`minutes” of sublingual
`
`tablets] described in the prior art” (Page 4), it is further asserted, absent
`
`evidence to the contrary, that substantially all of the buprenorphine contacts the mucosal surface
`
`of the subject’s oral cavity within less than 5 minutes, as instantly claimed.
`
`23.
`
`Accordingly,
`
`instant claim 1 is anticipated.
`
`24.
`
`Instant claim 5 is drawn to the method of claim 1 wherein the mucoadhesive film dosage
`
`form achieves a buprenorphine tmX from approximately 45 to approximately 90 minutes.
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 7
`
`25.
`
`McAleer et al further demonstrate that 2 mg SubuteX provides an average tmX of 1.50 h
`
`(Page 81, Table l).
`
`26.
`
`As such,
`
`it
`
`is similarly asserted, absent evidence to the contrary, that administration of
`
`about 0.1 to 1 mg buprenorphine via a mucoadhesive film dosage form for the treatment of pain
`
`(as taught by Cremer etal) would necessarily provide tmax from approximately 45 to approximately
`
`90 minutes, as instantly claimed.
`
`27.
`
`Accordingly,
`
`instant claim 5 is also anticipated.
`
`Claim Rejections - 35 USC § 103
`
`28.
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousnes s
`
`rejections set forth in this Office action:
`
`(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth
`in section 102 of this title, if the differences between the subject matter sought to be patented and the
`prior art are such that the subject matter as a whole would have been obvious at the time the invention
`was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability
`shall not be negatived by the manner in which the invention was made.
`
`29.
`
`This application currently names joint inventors.
`
`In considering patentability of the claims
`
`under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was
`
`commonly owned at the time any inventions covered therein were made absent any evidence to
`
`the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor
`
`and invention dates of each claim that was not commonly owned at the time a later invention was
`
`made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35
`
`U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
`
`30.
`
`Claims 2-4 and 6-8 are rejected under 35 U.S.C. 103(a) as being unpatentable over
`
`Cremer et al (AU 1998-56532 B2) as evidenced by McAleer et al (Drug and Alcohol
`
`Dependence 72:75-83, 2003) as applied to claims 1 and 5 above, in further Viewof Zerbe et al
`
`(US 5,948,430).
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 8
`
`31.
`
`Instant claims 2-3 are directed to the method of claim 1 wherein the mucoadhesive film
`
`dosage form further comprises a pH modifier (claim 2), more specifically, citric acid (claim 3).
`
`32.
`
`Similarly,
`
`instant claim 4 is drawn to the method of claim 1 wherein the mucoadhesive
`
`film dosage form further comprises citric acid.
`
`33.
`
`And instant claims 7-8 are drawn to the method of claim 1 wherein the mucoadhesive film
`
`dosage form further comprises a flavoring agent (claim 7) such as, for example, mint, lemon,
`
`vanilla (claim 8).
`
`34.
`
`As taught by Cremer etal, the mucoadhesive film dosage form can further comprise “taste
`
`corrigents” (Page 9). However, Cremer et al do not specifically identify the inclusion of citric
`
`acid, mint, lemon and/or vanilla.
`
`35.
`
`Zerbe et al teach related rapidly dissolving films which can be adhered to the oral cavity
`
`thereby releasing a pharmaceutically. ..
`
`active agent” (Column 2, Lines 14—16) wherein “the
`
`mucoadhesive film include[s] polymers” (Column 2, Lines 36—39) which provides a “allow[s] for
`
`easy coating, converting, and packaging of a consumer—friendly product” (Column 2, Lines 10—
`
`11). Zerbe etal further teach ““using flavor enhancers like
`
`citric acid, vanillin” etc (Column
`
`3, Lines 36—37) and specifically identify formulations comprising “citric acid” and “lemon mint
`
`flavor” (Column 4, Lines 19—20; Example 1).
`
`36.
`
`Based further on Zerbe etal, it would have been obvious to utilize citric acid, lemon, mint
`
`and/or vanilla as the “taste corrigents” in the mucoadhesive film dosage form of Cremer et al.
`
`37.
`
`As such, instant claims 2-4 and 7-8 are rejected as primafacie obvious.
`
`38.
`
`Instant claim 6 is drawn to the method of claim 1 wherein the mucoadhesive film dosage
`
`form is administered once a day.
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 9
`
`39.
`
`As stated by MPEP 2144.05, “[g]enerally, differences in concentration or temperature will
`
`not support the patentability of subject matter encompassed by the prior art unless there is evidence
`
`
`indicating such concentration or temperature is critical” (see also In re Aller (220 F.2d 454
`
`(CCPA): “where the general conditions of a claim are disclosed in the prior art, it is not inventive
`
`to discover the optimum or workable ranges by routine experimentation...”
`
`Indeed, as further
`
`discussed by the court, “[s]uch experimentation is no more than the application of the expected
`
`skill of the [ordinarily skilled artisan] and failure to perform such experiments would,
`
`in our
`
`
`opinion, show a want of the expected skill”, see also In re Peterson, 315 F.3d at 1325 (Fed. Cir.
`
`2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally
`
`known provides the motivation to determine where in a disclosed set of percentage ranges is the
`
`optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are
`
`‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie
`
`(559 F.2d 618 (CCPA 1977))).
`
`40.
`
`In the instant case, it is similarly determined that the dosing regimen for the treatment of a
`
`condition is also a result—effective variable. Accordingly,
`
`it would have been customary for an
`
`artisan of ordinary skill
`
`in the art to determine the optimal dosing regimen for the treatment of
`
`pain.
`
`41.
`
`Accordingly,
`
`instant claim 6 is also rejected as prima facie obvious.
`
`42.
`
`Claims 1-8 are rejected under 35 U.S.C. 103(a) as being unpatentable over Malinoff
`
`et (Am J Therapeuts 12:379-384, 2005) in View of Zerbe et al (US 5,948,430) as further
`
`evidenced by McAleer et al (Drug and Alcohol Dependence 72:75 -83, 2003).
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 10
`
`43.
`
`As amended, instant claim 1 is drawn to a method of treating pain in a subject in need
`
`thereof, comprising contacting an oral mucosal surface of the subject with a mucoadhesive film
`
`dosage form comprising:
`
`(a)
`
`buprenorphine in an amount sufficient to provide an average CmX of less than 2.5
`
`ng/ml and an average buprenorphine AUC0_48 of less than 15 (hrs*ng)/ml, which is
`
`dissolved or homogenously dispersed in (b):
`
`(b)
`
`at least one non—gelatin polymeric
`
`film—forming material
`
`(e. g., hydroxye thyl
`
`cellulose);
`
`wherein:
`
`(i)
`
`within less than 5 minutes after contacting the subject’s oral mucosal surface with
`
`the mucoadhesive film dosage form, substantially all of the buprenorphine contacts
`
`the mucosal surface of the subject’s oral cavity; and
`
`(ii)
`
`the dosage form does not include naloxone, na1trexone, etc.
`
`44.
`
`As taught by Malinoffet al, “low doses [i.e., “4 to 16 mg (mean, 8 mg)”] of sub1ingua1
`
`(SL) buprenorphine
`
`[SubuteX] or buprenorphine/naloxone” provided “moderate to substantial
`
`relief of pain” in 86% of patients suffering from chronic pain (Abstract).
`
`45.
`
`As such, the method of Malinoff etal differs from the instantly claimed method in that:
`
`(1) Malinoff et al teaches administration via a subligual
`
`tablet as opposed to a
`
`mucoadhesive film; and
`
`(2) Malinoffetal does not teaches the instantly claimed Cmax, AUC and disintegration
`
`time.
`
`46.
`
`As to 11): Zerbe et al teach “a rapidly dissolving film which can be adhered to the oral
`
`cavity thereby releasing a pharmaceutically. .. active agent” (Column 2, Lines 14—16) wherein “the
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 11
`
`mucoadhesive film include[s] polymers” wherein “hydroxye thyl cellulose... [is] particularly
`
`preferred” (Column 2, Lines 36—39) which provides a “allow[s] for easy coating, converting, and
`
`packaging of aconsumer—friendly product” (Column 2, Lines 10—11).
`
`47.
`
`Based on Zerbe et al, it would have been primafacie obvious for a person of ordinary skill
`
`in the art to modify the method of Malinoff et al so as to administer the buprenorphine via a
`
`mucoadhesive film as opposed to a subligual tablet. It would have been obvious to do so in order
`
`to provide a consumer—friendly product with a reasonable expectation of success.
`
`48.
`
`And1 as to 12!: Considering that McAleer etal demonstrate that:
`
`*
`
`2 mg SubuteX provides an average CmX of 1.6 i 0.5 ng/ml and an AUC of 9.05 i
`
`2.67 (hrs*ng)/ml, while 8 mg SubuteX provides an average Cmax of 4.0 i 1.2 ng/ml
`
`and an AUC of 26.89 i 7.16 (hrs*ng)/ml (Page 81, Table 1); and
`
`*
`
`“[m]edian in viva times of sublingual disintegration were 6 (2—17) and 12 (6—32)
`
`min for Subutex® at 2 and 8 mg, respectively” (Page 80, Column 1),
`
`it is asserted that, absent evidence to the contrary, administration of 4 mg sublingual buprenorphine
`
`(Subutex) taught by Malinoff et al for the treatment of pain would necessarily provide an average
`
`CmX of less than 2.5 ng/ml and an average buprenorphine AUC0_48 of less than 15 (hrs*ng)/ml
`
`wherein substantially all of the buprenorphine contacts the mucosal surface of the subject’s oral
`
`cavity within less than 5 minutes, as instantly claimed. Moreover, it is further assertedthat, absent
`
`evidence to the contrary, administration of 4 mg buprenorphine as a mucoadhesive film dosage
`
`form based on Malinoffet al in view of Zerbe et al for the treatment of pain would also provide
`
`an average CmX of less than 2.5 ng/ml and an average buprenorphine AUC0_48 of less than 15
`
`(hrs*ng)/ml wherein substantially all of the buprenorphine contacts the mucosal surface of the
`
`subject’s oral cavity within less than 5 minutes, as instantly claimed.
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 12
`
`49.
`
`50.
`
`Based on all of the foregoing,
`
`instant claim 1 is rejected as prima facie obvious.
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`Instant claims 2-3 are directed to the method of claim 1 wherein the mucoadhesive film
`
`dosage form further comprises a pH modifier (claim 2), more specifically, citric acid (claim 3).
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`51.
`
`Similarly,
`
`instant claim 4 is drawn to the method of claim 1 wherein the mucoadhesive
`
`film dosage form further comprises citric acid.
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`52.
`
`Zerbe et al further teach “using... citric acid” (Column 3, Lines 36—37) and specifically
`
`identify formulations comprising “citric acid” (Column 4, Line 20; Example 1).
`
`53.
`
`As such, instant claims 2-4 are also rejected as primafacie obvious.
`
`54.
`
`Instant claim 5 is drawn to the method of claim 1 wherein the mucoadhesive film dosage
`
`form achieves a buprenorphine tmX from approximately 45 to approximately 90 minutes.
`
`55.
`
`Considering that McAleeretal further demonstrate that 2 mg Subutex provides an average
`
`tmax of 1.50 h, while 8 mg Subutex provides an average tmX of 1.02 h, it is asserted that, absent
`
`evidence to the contrary, administration of 4 mg sublingual buprenorphine (Subutex) taught by
`
`Malinoff et al for the treatment of pain would necessarily provide
`
`an average tmX from
`
`approximately 45 to approximately 90 minutes, as instantly claimed. Moreover, it
`
`is further
`
`asserted that, absent evidence to the contrary, administration of 4 mg buprenorphine
`
`as a
`
`mucoadhesive film dosage form based on Malinoff et al in view of Zerbe et al for the treatment
`
`of pain would also provide an average tmax from approximately 45 to approximately 90 minutes ,
`
`as instantly claimed.
`
`56.
`
`As such, instant claim 5 is also rejected as prima facie obvious.
`
`57.
`
`Instant claim 6 is drawn to the method of claim 1 wherein the mucoadhesive film dosage
`
`form is administered once a day
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 13
`
`58. Malinoffetalteaches “[d]aily doses ranged from 2 to 20 mg/d in divided doses” (Page 381,
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`Column 1).
`
`59.
`
`Based on the foregoing,
`
`it would have been obvious to administer the mucoadhesive film
`
`dosage form daily, wherein it would have been further obvious to do so in a single, once —a—day
`
`dosage.
`
`60.
`
`61.
`
`As such, instant claim 6 is also rejected as prima facie obvious.
`
`Instant claims 7-8 are drawn to the method of claim 1 wherein the mucoadhesive film
`
`dosage form further comprises a flavoring agent (claim 7) such as, for example, mint, lemon,
`
`vanilla (claim 8).
`
`62.
`
`Zerbe et al further teach “using flavor enhancers like... vanillin” (Column 3, Lines 36—
`
`37) and specifically identify formulations comprising “lemon mint flavor” (Column 4, Line 19;
`
`Example 1).
`
`63.
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`As such, instant claims 7-8 are also rejected as primafacie obvious.
`
`Conclusion
`
`Any inquiry concerning this communication or earlier communications from the examiner
`
`should be directed to CRAIG D RICCI whose telephone number is (571) 270—5864. The examiner
`
`can normally be reached on Monday through Thursday, and every other Friday, 7:30 am — 5:00 pm
`
`ET.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor,
`
`Bethany Barham can be reached on (571) 272—6175. The fax phone number for the organization
`
`where this application or proceeding is assigned is 571—273—8300.
`
`

`

`Application/Control Number: 15/442,231
`Art Unit: 1611
`
`Page 14
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`
`/CRAIG D RICCI/
`
`Primary Examiner, Art Unit 1611
`
`