w’l AND1%
`
` If?
`
`
`
`
`
`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
`
`7590
`23869
`Hoffmann & Baron LLP
`
`6900 Jericho Turnpike
`Syosset, NY 11791
`
`11/07/2013
`
`EXAMINER
`
`EPPS -SMITH, JANET L
`
`ART UNIT
`
`1633
`
`MAIL DATE
`
`11/07/2013
`
`PAPER NUMBER
`
`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.
`
`BDSI, Inc. vs. RB Pharmaceuticals Limited
`PTOL—90A (Rev. 04/07)
`Page 1
`
`|PR2014-OO325
`
`BDSI EXHIBIT 1037
`
`Page 1
`
`

`

`
`
`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 9-27-2013.
`[I A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
`
`2b)lX| This action is non-final.
`a)I:| 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 Claim(s) it is/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 2—4 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
`US. Patent and Trademark Office
`PTOL-326 (Rev. 08-13)
`
`Part of Paper No./Mai| Date 20131105
`
`Office Action Summary
`
`Page 2
`
`Page 2
`
`

`

`Application/Control Number: 13/964,975
`
`Page 2
`
`Art Unit: 1633
`
`DETAILED ACTION
`
`1.
`
`The prior Office Action mailed 10/29/2013 is now vacated. The previous Office
`
`Action improper/z indicated that
`
`the instant application was Under Accelerated
`
`Examination, and limited Applicants to a 1-month response time with no extensions of
`
`time available. The instant Office Action grants Applicants a 3-month response time
`
`with extensions of time available.
`
`2.
`
`The present application is being examined under the pre-AlA first
`
`to invent
`
`provisions.
`
`DETAILED ACTION
`
`Claim Rejections - 35 USC § 103
`
`3.
`
`The following is a quotation of pre-AlA 35 U.S.C. 103(a) which forms the basis
`
`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.
`
`4.
`
`Claims 1-24 are 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).
`
`5.
`
`Independent claims 1 and 7 recite the following:
`
`1. An orally dissolving film formulation comprising from about 2 to about 16 mg of
`buprenorphine and from about 0.5 to about 4 mg of naloxone, wherein said formulation
`provides an in vivo plasma profile having a mean Cmax of between about 0.6 ng/ml and
`about 5.7 ng/ml for buprenorphine and an in vivo plasma profile having a mean Cmax of
`between about 41 pg/ml to about 324 pg/ml for naloxone.
`
`Page 3
`
`Page 3
`
`

`

`Application/Control Number: 13/964,975
`
`Page 3
`
`Art Unit: 1633
`
`7. An orally dissolving film formulation comprising from about 2 to about 16 mg of
`buprenorphine and from about 0.5 to about 4 mg of naloxone, wherein said formulation
`provides an in vivo plasma profile having a mean Cmax of between about 0.7 ng/ml and
`about 6.9 ng/ml for buprenorphine and an in vivo plasma profile having a mean Cmax of
`between about 40 pg/ml to about 405 pg/ml for naloxone.
`
`6.
`
`Oksche et al. discloses the following embodiments, see the following paragraphs:
`
`[0039] As regards the dosage amount, the pharmaceutical compositions in accordance
`
`with the present invention will
`
`typically comprise between approximately 0.1 mg and
`
`approximately 16 mg of buprenorphine or a pharmaceutically acceptable salt thereof
`
`such as buprenorphine hydrochloride. Preferred dosage amounts will be in the range of
`
`between approximately 0.4 mg and approximately 12 mg or between approximately 2
`
`mg and approximately 8 mg buprenorphine or a pharmaceutically acceptable salt
`
`thereof.
`
`[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.
`
`Page 4
`
`Page 4
`
`

`

`Application/Control Number: 13/964,975
`
`Page 4
`
`Art Unit: 1633
`
`[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.
`
`[0043] The AUCo-48 (i.e. the Area under the Curve for 48 hours after administration) may
`
`in the case of administration of 4 mg of buprenorphine hydrochloride be in the range of
`
`approximately 10 to 15 hours.times.ng/ml.
`
`In a preferred embodiment the AUCo-48 may
`
`be approximately 12 to 13 hours.times.ng/ml.
`
`In the case of 8 mg buprenorphine
`
`hydrochloride being administered the AUCo.48 may be approximately in the range of 15
`
`to 25 hours X ng/ml.
`
`In a preferred embodiment the AUCo.48 in this case may be
`
`between approximately 20 to 22 hours.times.ng/ml.
`
`In the case of 16 mg
`
`buprenorphine hydrochloride being administered, the AUCo-48 may be in the range of 25
`
`to 40 hours X ng/ml.
`
`In a preferred embodiment the AUCo.48 in this case may be in the
`
`range of approximately 30 to 35 hours X ng/ml.
`
`[0050] A particularly preferred antagonist is naloxone. Of the naloxone salts, naloxone
`
`hydrochloride
`
`dihydrate may
`
`be
`
`particularly
`
`preferable
`
`in
`
`combination with
`
`buprenorphine hydrochloride.
`
`Page 5
`
`Page 5
`
`

`

`Application/Control Number: 13/964,975
`
`Page 5
`
`Art Unit: 1633
`
`[0051] The pharmaceutical dosage forms in accordance with the invention will comprise
`
`buprenorphine and the antagonist, which preferably is naloxone,
`
`in a weight ratio of
`
`from 1:1 to 10:1. A weight ratio of from 2:1 to 8:1 may be preferred, with a weight ratio
`
`of 4:1 being particularly preferred.
`
`[0052] Thus,
`
`if an oral dosage form in accordance with the present
`
`invention for
`
`example comprises 2 mg buprenorphine hydrochloride it will comprise approximately
`
`0.5 mg naloxone.
`
`If the dosage form comprises 0.4 mg buprenorphine hydrochloride, it
`
`will comprise 0.1 mg naloxone and if the dosage form comprises 8 mg buprenorphine
`
`hydrochloride it will comprise e.g. 2 mg naloxone hydrochloride.
`
`[0053] A particularly preferred embodiment
`
`thus relates to an oral dosage form
`
`comprising buprenorphine, preferably buprenorphine hydrochloride, and naloxone,
`
`preferably naloxone hydrochloride, wherein the dosage form releases said active agents
`
`within less than one minute, preferably within less than thirty seconds and more
`
`preferably within less than ten seconds after sublingual application of the dosage form.
`
`In addition, the dosage forms may provide the preferred values of the aforementioned
`
`pharmacokinetic parameters Cmax, and AUCo-48.
`
`[0054] Thus, the person skilled in the art will have to ensure that indeed an oral dosage
`
`form is used which is able to allow for
`
`incorporation of
`
`sufficient amounts of
`
`Page 6
`
`Page 6
`
`

`

`Application/Control Number: 13/964,975
`
`Page 6
`
`Art Unit: 1633
`
`buprenorphine and preferably also of naloxone and which at
`
`the same time
`
`disintegrates rapidly enough to release the active agents instantly.
`
`[0055] In one embodiment one may use non-gelatin film materials, e.g. films of modified
`
`cellulose materials as dosage forms.
`
`In this case, buprenorphine and optionally opioid
`
`antagonists such as naloxone are incorporated into the film matrix and films thus
`
`prepared may be administered orally.
`
`The following embodiments of Oksche et al. are also disclosed: [0012] Another
`
`buprenorphine preparation aimed at preventing this potential possibility of abuse has
`
`recently gained administrative approval
`
`in the United States (Suboxone®).
`
`The
`
`Suboxone® preparation comprises buprenorphine hydrochloride and the opioid
`
`antagonist naloxone hydrochloride dihydrate. The presence of naloxone is intended to
`
`prevent parenteral abuse of buprenorphine as parenteral
`
`co-administration of
`
`buprenorphine and naloxone in e.g. an opioid-dependent addict will
`
`lead to serious
`
`withdrawal symptoms.
`
`Oksche et al. does not precisely recite the specific Cmax of naloxone as recited
`
`in the instant claims. However, Oksche et al. does describe 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
`
`Page 7
`
`Page 7
`
`

`

`Application/Control Number: 13/964,975
`
`Page 7
`
`Art Unit: 1633
`
`the Cmax may be approximately between 2.75 ng/ml and 3.25 ng/ml
`dose of 8 mg buprenorphine hydrochloride being administered.
`
`in the case of a
`
`[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.
`
`7.
`
`Additionally, Oksche et al. discloses the Suboxone® oral formulation comprising
`
`both buprenorphine and naloxone. According to the specification as filed (see page 8, 11
`
`[0023]),
`
`the claimed compositions of the instant application are described as orally
`
`dissolvable film dosage, which provides a bioequivalent effect to Suboxone®.
`
`8.
`
`Absent evidence of unexpected properties,
`
`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 both buprenorphine and naloxone to
`
`achieve the appropriate level of absorption of both agonist and antagonist so that
`
`optimal results are achieved, namely 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, appears to be a matter of routine experimentation.
`
`9.
`
`Moreover, Applicants admit that their formulations are designed to provide a
`
`bioequivalent effect to the prior art compound disclosed in Oksche et al., specifically
`
`Suboxone®. Thus, applicant’s claimed compounds are obvious variants of the prior art
`
`compound.
`
`Page 8
`
`Page 8
`
`

`

`Application/Control Number: 13/964,975
`
`Page 8
`
`Art Unit: 1633
`
`10.
`
`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
`
`art and one skilled in the art could have combined the element as claimed by known
`
`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.
`
`11.
`
`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.
`
`12.
`
`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.
`
`13.
`
`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.
`
`Page 9
`
`Page 9
`
`

`

`Application/Control Number: 13/964,975
`
`Page 9
`
`Art Unit: 1633
`
`/JANET L. EPPS -SM|TH/
`
`Primary Examiner, Art Unit 1633
`
`Page 10
`
`Page 10
`
`