`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria1 Virginia 22313- 1450
`wwwusptogov
`
`APPLICATION NO.
`
`
`
`
`
` F ING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`
`
`
`
`CONF {MATION NO.
`
`13/964,975
`
`08/12/2013
`
`Garry L. Myers
`
`2333—2 CON II
`
`8904
`
`EXAMINER
`Hoffmannmamm —
`03/07/2014 —
`7590
`23869
`6900 Jericho Turnpike
`EPPS -SMITH, JANET L
`ART UNIT
`PAPER NUMBER
`Syosset, NY 11791
`
`1633
`
`MAIL DATE
`
`03/07/2014
`
`DELIVERY MODE
`
`PAPER
`
`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.
`
`Page 1
`PTOL—90A (Rev. 04/07)
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`BDSI EXHIBIT 1029
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`Page 1
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`

`

`
`
`Applicant(s)
`Application No.
` 13/964,975 MYERS ET AL.
`
`Examiner
`Art Unit
`AIA (First Inventorto File)
`Office Action Summary
`
`1633Janet Epps-Smith a?”
`
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTH(S) OR THIRTY (30) DAYS,
`WHICHEVER IS LONGER, 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 () MONTHS from the mailing date of this communication.
`If 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)IXI Responsive to communication(s) filed on 01/02/2014.
`[I A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
`
`2b)|:| This action is non-final.
`a)IXl This action is FINAL.
`3)I:I 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)|:I 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 EX parte Quay/e, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims
`5)|XI CIaim(s)1-_28is/are pending in the application.
`5a) Of the above claim(s)
`is/are withdrawn from consideration.
`6)|:l Claim(s) _ is/are allowed.
`7)IZ| Claim(s)_1 -28 is/are rejected.
`8)I:I Claim(s) _ is/are objected to.
`
`9)|:l Claim((s)
`are subject to restriction and/or election requirement.
`* If any claims have been determined allowable, 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
`htt
`://www.usoto. ov/ atents/init events"
`
`
`
`h/indax.‘s , or send an inquiry to PF"I-Ifeedback{<‘buspto.qov.
`
`Application Papers
`
`10)I:I The specification is objected to by the Examiner.
`11)|:I The drawing(s) filed on _ is/are: a)I:I accepted or b)I:I 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)I:I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. §119(a)-(d) or (f).
`Certified copies:
`
`b)I:I Some * c)I:I None of the:
`a)I:I All
`1.I:I Certified copies of the priority documents have been received.
`2.I:I Certified copies of the priority documents have been received in Application No.
`3.|:I 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) E Notice of References Cited (PTO-892)
`
`3) I] Interview Summary (PTO-413)
`
`Paper NOISIIMa” Date —
`PTO/SB/08
`t
`St t
`I
`D'
`t'
`f
`2 I:l I
`)
`4) I:I Other:
`a emen (s)(
`Isc osure
`n orma Ion
`)
`Paper No(s )/Mai| Date
`
`U..S Patent andfiarg 09:8
`PTOL-326
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20140225
`
`Page 2
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`

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`Application/Control Number: 13/964,975
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`Page 2
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`Art Unit: 1633
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`1.
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`The present application is being examined under the pre-AIA first
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`to invent
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`provisions.
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`2.
`
`Claims 1-28 are presently pending for examination.
`
`DETAILED ACTION
`
`Response to Amendment
`
`Claim Rejections - 35 USC § 1 12
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`3.
`
`The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
`
`IN GENERAL—The specification shall contain a written description of the
`(a)
`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 orjoint inventor of carrying out the invention.
`
`The following is a quotation of the first paragraph of pre-AIA 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.
`
`Claims 1-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), 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
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`reasonably convey to one skilled in the relevant art that the inventor or a joint inventor,
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`or for pre-AIA the inventor(s), at the time the application was filed, had possession of
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`the claimed invention.
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`(New Matter).
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`5.
`
`Instant claim 1 was amended as follows:
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`Page 3
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`Page 3
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`

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`Application/Control Number: 13/964,975
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`Page 3
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`Art Unit: 1633
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`S. t'fiiT'LtswnEijv: s‘iq‘smztd-fdiii‘: :3ch «$3113 dissolving; mm {Ensintdsjssiioa whinging KR iii-isms 13m
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`animus ~'§ {rig at he"
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`
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`6.
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`The specification as filed does not provide any express support for the phrase
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`"free base equivalent amount of said buprenorphine.” Additionally, the specification as
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`filed does not provide any support for the range of 1:06 to about 1:25 by weight of free
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`base equivalent amount of buprenorphine to polymer.
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`7.
`
`Applicants have made reference to paragraphs [0066] and [0067] as support for
`
`this amendment. However, paragraph [0066] makes reference only to "self-supporting
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`film forming polymers...” The instant claims broadly refer to any form of polymer.
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`8.
`
`Moreover, Table 1 and Table 5 are referenced as support for the newly added
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`limitations. Table 1 recites specific polymers in combination with buprenorphine and
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`naloxone. However, the instant claims are generically drawn to any form of polymer
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`and are not
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`limited to the specific polymers recited in Table 1. Table 5 describes
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`formulations of buprenorphine/naloxone with and without buffer and at specific pH
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`levels. Again,
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`the instant claims make no reference to pH or the presence and/or
`
`
`absence of buffer. Therefore, the broad range of buprenorphine to polymer of “from
`
`
`about 1 :.06 to about 1 :25 by weight,” as recited in the instant claims is not supported
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`by the specification as filed.
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`Page 4
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`Page 4
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`

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`Application/Control Number: 13/964,975
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`Page 4
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`Art Unit: 1633
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`9.
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`35 U.S.C. 132(a) states that no amendment shall introduce new matter into the
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`disclosure of the invention. Applicant is required to cancel the new matter in the reply to
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`this Office Action.
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`Claim Rejections - 35 USC § 103
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`10.
`
`The following is a quotation of pre-AlA 35 U.S.C. 103(a) which forms the basis
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`for all obviousness 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.
`
`11.
`
`Claims 1-28 stand rejected under pre-AlA 35 U.S.C. 103(a) as being
`
`unpatentable over Oksche et al. (US2010/0087470A1 or WO 2008025791 A1 ; citations
`
`given from the PGPUB) in view of US Patent No. 7,357,891, and Merriam Webster
`
`definition of “bioequivalence.”
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`12.
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`Applicant's arguments filed 01/02/2014 have been fully considered but they are
`
`not persuasive. Applicants traversed the instant rejection on the grounds that the
`
`Oksche et al. reference “does not teach or suggest how to achieve the claimed Cmax
`
`values for buprenorphine and naloxone alone or in combination in a film composition.
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`In
`
`addition Oksche does not provide any direction as to how to achieve a non-divertible
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`film that produces optimized buprenorphine release while simultaneously producing a
`
`Cmax for naloxone that is within the claimed invention.”
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`13.
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`Contrary to Applicant’s assertions, Oksche et al. clearly describe Suboxone
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`preparations, see 11[001 2]:
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`Page 5
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`Page 5
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`Application/Control Number: 13/964,975
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`Page 5
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`Art Unit: 1633
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`14.
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`“Another buprenorphine preparation aimed at preventing this potential possibility
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`of abuse has recently gained administrative approval in the United States (Suboxone®).
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`The Suboxone® preparation comprises buprenorphine hydrochloride and the opioid
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`antagonist naloxone hydrochloride dihydrate. The presence of naloxone is intended to
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`prevent parenteral abuse of buprenorphine as parenteral
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`co-administration of
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`buprenorphine and naloxone in e.g. an opioid-dependent addict will
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`lead to serious
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`withdrawal symptoms.”
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`15.
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`The specification as filed clearly teaches that the compositions of the instant
`
`invention are intended to produce a “bioequivalent” of Suboxone. 1i[0073] of the issued
`
`patent Application recites:
`
`to a
`result
`the film dosage composition provides a bioequivalent
`“As explained,
`commercially available SuboxoneRTM. product. As will be explained more in the
`Examples below, commercially available SuboxoneRTM. provides different absorption
`levels depending on the amount of buprenorphine and naloxone administered. The
`present invention desirably provides a film product providing bioequivalent release as
`that of
`the SuboxoneRTM. product. As with the SuboxoneRTM. product,
`the
`buprenorphine may be present in an amount of from about 2 mg to about 16 mg per
`dosage, or, if desired about 4 mg to about 12 mg per dosage. Additionally, the naloxone
`may be present
`in any desired amount, preferably at about 25% the level of
`buprenorphine. For example, an inventive film product may have 2 mg buprenorphine
`and 0.5 mg naloxone, 4 mg buprenorphine and 1 mg naloxone, 8 mg buprenorphine
`and 2 mg naloxone, 12 mg buprenorphine and 3 mg naloxone, 16 mg buprenorphine
`and 4 mg naloxone, or any similar amounts.”
`
`16.
`
`Thus,
`
`it can reasonably be argued that whatever Cmax of buprenorphine or
`
`naloxone that can be achieved with the prior art Suboxone product would be expected
`
`to be equivalent to the Cmax values achieved by the instantly claimed formulations.
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`Page 6
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`Page 6
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`Application/Control Number: 13/964,975
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`Page 6
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`Art Unit: 1633
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`17. Moreover,
`
`in regards to the specific Cmax of naloxone as recited in the instant
`
`claims, Oksche et al. describes the Cmax of buprenorphine in these oral formulations as
`
`follows:
`
`[0040] The oral pharmaceutical dosage forms in accordance with the invention may
`have the further characteristic of providing a Cmax of approximately 1.5 to 2.5 ng/ml in
`the case of a dose of 4 mg buprenorphine hydrochloride being administered. A
`preferred Cmax in the case of a dose of 4 mg of buprenorphine hydrochloride being
`administered may be approximately between 1.7 ng/ml to 2 ng/ml.
`
`[0041] In the case of a dose of 8 mg buprenorphine hydrochloride being administered,
`the Cmax may be approximately between 2.5 and 3.5 ng/ml.
`In a preferred embodiment
`the Cmax may be approximately between 2.75 ng/ml and 3.25 ng/ml
`in the case of a
`dose of 8 mg buprenorphine hydrochloride being administered.
`
`[0042] In case of a dose of 16 mg buprenorphine hydrochloride being administered, the
`Cmax may preferably be in the range of approximately 5 to 7 ng/ml.
`In a preferred
`embodiment the Cmax may be between 5.5 and 6.5 ng/ml
`if 16 mg of buprenorphine
`hydrochloride are administered.
`
`18. Moreover, in regards to the newly added limitations of polymer to buprenorphine
`
`ratio recited in the instant claims. Oksche et al. teaches that:
`
`to which
`the extent
`[0083] “[T]he person skilled in the art will appreciate that
`buprenorphine and optionally an opioid antagonist such as naloxone are instantly
`released depends in part on the type of matrix-forming polymer chosen. For example, a
`dosage form using polyvinylalcohol as matrix-forming polymer may disintegrate faster
`than a dosage form using HPMC as matrix-forming polymer. The disintegration time
`may be adjusted by mixing a combination of different polymers in suitable amounts.”
`
`[0084] The person skilled in the art also knows disintegrating agents, which can "pull"
`water
`into the matrix which then pushes the dosage forms apart.
`Thus, such
`disintegrating agents may also be used for adjustment of the disintegration time.”
`
`19.
`
`Oksche et al. clearly discloses the Suboxone® oral formulation comprising both
`
`buprenorphine and naloxone, and further teaches the use of a film forming polymer in
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`the design of an oral formulation.
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`Page 7
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`Page 7
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`Application/Control Number: 13/964,975
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`Page 7
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`Art Unit: 1633
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`20.
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`Absent evidence of unexpected properties associated with the full scope of the
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`claimed invention, it would have been obvious to the ordinary skilled artisan at the time
`
`of
`
`the
`
`instant
`
`invention,
`
`seeking alternative formulations
`
`for
`
`treating narcotic
`
`dependence to modify the prior art by routine experimentation to as to identify optimal
`
`dosage of buprenorphine, naloxone and polymer to achieve the appropriate level of
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`absorption of both agonist and antagonist so that optimal results are achieved, namely
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`treatment of narcotic dependence. As per MPEP 2144.05 [R-5], since the general
`
`conditions of the instantly claimed invention are disclosed in the prior art, identification
`
`of the optimal dosage of naloxone to achieve the optimal absorption of the active drug,
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`using a film formulation appears to be a matter of routine experimentation. Suitable
`
`processes for producing film formulations are disclosed by incorporating prior art by
`
`reference into the specification as filed (see 11 [0080] of the published US Application),
`
`including US Patent No. 7,357,891. This reference provides for the incorporation of an
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`agonist and antagonist in a film formulation.
`
`21.
`
`As stated above, Applicants admit that their formulations are designed to provide
`
`a bioequivalent effect to the prior art compound disclosed in Oksche et al., specifically
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`Suboxone®.
`
`In other words, the claimed invention would be expected to have the same
`
`bioavailability and produce the same effect at the site of physiological activity as the
`
`prior art Suboxone.
`
`(See Merriam Webster definition of “bioequivalence”). Thus,
`
`applicant’s claimed compounds are obvious variants of the prior art compound.
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`22.
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`Regarding the rationale for combining prior art elements according to known
`
`methods to yield predictable results, all of the claimed elements were known in the prior
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`Page 8
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`Page 8
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`Application/Control Number: 13/964,975
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`Page 8
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`Art Unit: 1633
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`art and one skilled in the art could have combined the element as claimed by known
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`methods with no change in their respective functions, and the combination would have
`
`yielded predictable results to one of ordinary skill in the art at the time of the invention.
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`23.
`
`Applicant's amendment necessitated the new ground(s) of rejection presented in
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`this Office action.
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`Accordingly, THIS ACTION IS MADE FINAL.
`
`See MPEP
`
`§ 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37
`
`CFR1.136(a).
`
`A shortened statutory period for reply to this final action is set to expire THREE
`
`MONTHS from the mailing date of this action.
`
`In the event a first reply is filed within
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`TWO MONTHS of the mailing date of this final action and the advisory action is not
`
`mailed until after the end of the THREE-MONTH shortened statutory period, then the
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`shortened statutory period will expire on the date the advisory action is mailed, and any
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`extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of
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`the advisory action.
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`In no event, however, will the statutory period for reply expire later
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`than SIX MONTHS from the date of this final action.
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`Page 9
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`Page 9
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`Application/Control Number: 13/964,975
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`Page 9
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`Art Unit: 1633
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`24.
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Janet Epps-Smith whose telephone number is (571 )272—
`
`0757. The examiner can normally be reached on M-F, 1OAM-6:3OPM.
`
`25.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
`
`supervisor, Joseph Woitach can be reached on (571)-272—O739. The fax phone number
`
`for the organization where this application or proceeding is assigned is 571 -273-8300.
`
`1.
`
`Information regarding the status of an application may be obtained from the
`
`Patent Application Information Retrieval
`
`(PAIR)
`
`system.
`
`Status information for
`
`published applications may be obtained from either Private PAIR or Public PAIR.
`
`Status information for unpublished applications is available through Private PAIR only.
`
`For more information about the PAIR system, see http://pair-direct.uspto.gov. Should
`
`you have questions on access to the Private PAIR system, contact the Electronic
`
`Business Center (EBC) at 866-217-9197 (toll-free).
`
`If you would like assistance from a
`
`USPTO Customer Service Representative or access to the automated information
`
`system, call 800-786-9199 (IN USA OR CANADA) or 571-272—1000.
`
`/JANET L. EPPS -SMITH/
`
`Primary Examiner, Art Unit 1633
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`Page 10
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`Page 10
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