WO 95/31217
`
`PCT/EP95/01835
`
`PHARMACOLOGY :
`
`C
`
`i
`
`bbi
`
`;
`
`Preparations containing CNS active and muscle relaxing
`drugs such as diazepam and midazolam were tested ina
`
`pharmacodynamic model in rabbits.
`
`The model consists of the following tests:
`
`Test1:
`
`-
`
`Hind legs to one side and the rabbit must stay in
`this position even after a firm tip with a finger
`on the hip.
`The test is immediately repeated with
`both legs placed on the other side.
`
`Test2:
`
`-
`
`Hind legs stretched out backwards and the rabbit
`must stay in this position even after a firm tip
`with a finger on the hip.
`
`Test3:
`
`-
`
`The rabbit must stay in a supine position, when
`placed in such a position.
`
`After administration of the formulations (i.n., oral or
`i.v.) the rabbits were exposed to the three tests
`approximately once per minute until positive
`pharmacodynamic response, and thereafter every 2
`minutes.
`The total test period was 20 minutes after
`
`i.n. and i.v. administration and 30 minutes after
`
`peroral administration.
`
`The time elapsed from administration until the first
`positive response in test 1 was used to compare the
`
`AQUESTIVE EXHIBIT 1004
`
`AQUESTIVE EXHIBIT 1004 page 2101
`
`page 2101
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`- 27 -
`
`onset of action of the different formulations.
`
`STUDY1
`
`This pharmacodynamic study compared the nasal
`formulation of Example 8
`(C) containing 5% of diazepam
`to a commercially available diazepam formulation,
`Stesolid® 2mg tablet, Dumex (D). The study was run in 8
`rabbits in a randomized cross-over study. The rabbits
`were tested for pharmacodynamic response as described
`previously, but the test period was 30 minutes after
`peroral administration to be sure to obtain a
`
`pharmacodynamic effect.
`
`Formulation C was given intranasally (i.n.) with a
`laboratory pipette. Each rabbit was held in a supine
`position during and one minute after i.n. dosing in one
`nostril.
`The rabbits received a volume
`equivalent to
`2.5 mg diazepam. After each administration the actual
`dose received is calculated by subtraction of the weight
`of the pipette before and after administration. Only
`applications determined to 80% (2 mg diazepam) were
`accepted.
`
`Formulation D was given as an oral administration using
`a stomach pump. The tablet was dissolved in 5 ml water
`immediately before administration. The tube was rinsed
`with 10 ml water.
`
`The time to onset of pharmacodynamic response in test 1
`is 4.5minutes (median, n=7 ) using formulation C
`and 19,4minutes (median, n=8) using formulation D.
`
`STUDY2
`
`This pharmacokinetic study compared the nasal
`formulation of Example 8
`(C) containing 5% of diazepam
`
`AQUESTIVE EXHIBIT 1004=page 2102
`
`AQUESTIVE EXHIBIT 1004 page 2102
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`- 28 -
`
`to a commercially available diazepam formulation,
`Stesolid® 2mg tablet, Dumex (D). The study was run in 8
`rabbits in a randomized cross-over study.
`
`’
`
`Formulation C was given intranasally (i.n.) as described
`in study 1.
`
`Formulation D was given by oral administration as
`described in study 1 using a stomach pump.
`
`Blood samples from the ear-vein were taken before
`administration (time = 0) and at 2, 5, 10, 15, 30, 45,
`60, 75, 90, 120, 180 and 240 minutes.
`
`Serum was analyzed for diazepam and the metabolite,
`desmethyldiazepam using Gas Chromatografy (GC).
`The limit of detection was 5ng/ml for both substances.
`
`The pharmacokinetic parameters found for diazepam were
`tmax = 23 minutes (median, n=6), C,. = 68.2 ng/ml
`(median, n=6) after administration of formulation C and
`Cmax = 45 Minutes (median, n=6), C,,, = 9.7 ng/ml
`(median, n=6) after administration of formulation D.
`
`illustrate the mean serum
`Figures 1 and 2
`concentrations of diazepam and desmethyldiazepam after
`administration of formulations C and D.
`
`STUDY3
`
`This pharmacodynamic study compared Example 8 (C)
`containing 5% of diazepam with Example 19 (E) containing
`2.5% of midazolam. The study was using 6 rabbits.
`
`Formulations C and E were given intranasally (i-.n.) with
`a laboratory pipette. Each rabbit was held ina supine
`position during and one minute after i.n. dosing in one
`
`AQUESTIVE EXHIBIT 1004=page 2103
`
`AQUESTIVE EXHIBIT 1004 page 2103
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`- 29 -
`
`nostril.
`
`The rabbits received a volume equivalent to
`
`2.5 mg diazepam or 1.25 mg midazolam, respectively.
`
`After each administration the actual dose received was
`
`calculated by subtraction of the weight of the pipette
`before and after administration. Only doses equivalent
`
`to 80% were accepted.
`
`The time to onset of pharmacodynamic response in test 1
`
`was 3,1minutes (median, n=6) using formulation C
`containing diazepam and 2.5minutes (median, n=6) using
`formulation E containing midazolam.
`
`Example23
`
`1
`
`ixrit
`
`in}
`
`.
`
`The investigation was carried out in order to estimate
`
`irritation after nasal application of 10 mg of diazepam;
`100 mg of the preparation from Example 8 in each
`
`nostril.
`
`6 volunteers,
`
`3 male and 3 female participated in the
`
`trial.
`
`The investigator inspected both nostrils macroscopically
`for local irritation at the following times:
`Immediately
`
`after medication, at 30 minutes, and 1, 2, 4, and 6
`
`hours.
`
`In one volunteer the macroscopic inspection showed light
`blush of both nostrils immediately after medication.
`
`None of the six volunteers had local irritation of the
`nostrils 30 minutes after application, see table 2.
`
`AQUESTIVE EXHIBIT 1004
`
`AQUESTIVE EXHIBIT 1004 page 2104
`
`page 2104
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`CONCLUSION
`
`The total results of the trial have shown that
`preparation of Example 8 does not cause unacceptable
`irritation of the nostrils.
`
`.
`
`1
`
`AQUESTIVE EXHIBIT 1004=page 2105
`
`AQUESTIVE EXHIBIT 1004 page 2105
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`Table 2.
`
`- 31 -
`
`Individual local irritation of the nostrils after intranasal
`administration of 10 mg diazepam,
`(Example 8)
`
`
`
`Local irritation
` Imme -
`
` diately
`
`medication
`
` after
`
`
`
`
`
`Light|Light
`blush |-blush
`
`
`
`
`R: right nestril
`L: left nostril
`
`AQUESTIVE EXHIBIT 1004=page 2106
`
`AQUESTIVE EXHIBIT 1004 page 2106
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`Claims
`
`Use of a tocopherol or a derivative thereof as a
`1.
`solvent and/or emulsifier for substantially insoluble
`or sparingly soluble biologically active agents.
`
`2.
`
`Use as claimed in claim 1 in the manufacture of
`
`pharmaceutical compositions.
`
`A composition for delivery of a substantially
`3.
`insoluble or sparingly soluble biologically active
`agent, comprising said agent dissolved in a tocopherol
`or a derivative thereof.
`
`4.
`A composition as claimed in claim 3 wherein the
`tocopherol is a-tocopherol or an ester thereof.
`
`A composition as claimed in claim 3 or claim 4 in
`5.
`a form suitable for transmucosal,
`topical, enteral or
`parenteral application.
`
`in a form
`A composition as claimed in claim 5,
`6.
`suitable for intranasal, vaginal or rectal application
`or for administration via the oral cavity.
`
`A composition as claimed in any one of claims 1 to
`7.
`6 in the form of an emulsion.
`
`A composition as claimed in claim 7, additionally
`8.
`comprising an emulsifying agent.
`
`9.
`
`A composition as claimed in claim 8, wherein the
`
`emulsifying agent is a tocopherol derivative.
`
`10. A composition as claimed in claim 9, wherein the
`
`emulsifying agent is a tocopherol ester.
`
`AQUESTIVE EXHIBIT 1004=page 2107
`
`AQUESTIVE EXHIBIT 1004 page 2107
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`- 33 -
`
`A composition as claimed in claim 10, wherein the
`11.
`emulsifying agent is Vitamin E TPGS.
`
`12. A composition suitable for delivery of
`substantially insoluble or sparingly soluble
`biologically active agents, comprising a tocopherol or
`a derivative thereof, and an emulsifier.
`
`13. A composition as claimed in claim 12, wherein the
`emulsifier is Vitamin E TPGS.
`
`14. A composition as claimed in any of claims 3 to 13,
`further comprising one or more additional components
`selected from solvents, surfactants, stabilizers,
`bicadhesive polymers, preservatives, and odour- or
`taste-masking agents.
`,
`
`15. A composition as claimed in any one of claims 3 to
`14, wherein the biologically active agent is a
`benzodiazepine or an anti-mycotic.
`
`16. A composition as claimed in claim 15, wherein the
`biologically active agent is diazepam, midazolam or
`miconazole.
`
`A composition as claimed in any one of claims 3 to
`17.
`16, wherein the content of the tocopherol or derivative
`thereof is from 1 to 99.99% (w/w).
`
`18. A composition as claimed in claim 17, wherein the
`content of the tocopherol or derivative thereof is from
`20 to 99.99% (w/w).
`
`19. A composition as claimed in claim 17, wherein the
`content of the tocopherol or derivative thereof is from
`40 to 99.99% (w/w).
`
`AQUESTIVE EXHIBIT 1004=page 2108
`
`AQUESTIVE EXHIBIT 1004 page 2108
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`_ 34 -
`
`20. A method of preparing a composition for delivery
`of a substantially insoluble or sparingly soluble
`biologically active agent, said method comprising
`dissolving said agent in an amount of a tocopherol or a
`derivative thereof, sufficient to dissolve said agent.
`
`aq
`
`21. A method as claimed in claim 20, further
`
`comprising forming an emulsion of said
`tocopherol/biologically active agent solution, by
`mixing with an aqueous phase.
`
`22.
`
`2A method as claimed in claim 21, wherein the
`
`emulsification step is performed in the presence of an
`emulsifying agent.
`
`23. A method as claimed in claim 22, wherein the
`
`emulsifying agent is Vitamin E TPGS.
`
`24. Use of a tocopherol or a derivative thereof for
`the preparation of a composition as claimed in any one
`of claims 3 to 18.
`
`25. A method of treatment of a human or non-human
`
`animal subject by delivery of a substantially insoluble
`or sparingly soluble biologically active agent, said
`method comprising administering to said subject a
`composition as defined any one of claims 3 to 11 or 14
`to 18.
`
`AQUESTIVE EXHIBIT 1004=page 2109
`
`AQUESTIVE EXHIBIT 1004 page 2109
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`1/2
`
`100
`
`~tk— Desmethyl-diazepam
`—l— Diazepam
`
`&0
`
`
`
`Eon
`
`&3coO
`
`0
`
`60
`
`120
`
`180
`
`240
`
`300
`
`Time (min)
`
`Fig. 1
`
`AQUESTIVE EXHIBIT 1004=page 2110
`
`AQUESTIVE EXHIBIT 1004 page 2110
`
`

`

`WO 95/31217
`
`PCT/EP95/01835
`
`2/2
`
`—¢— Diazepam
`~—%i-~ Desmethyl-diazepam
`
`_ o
`
`120
`
`180
`
`240
`
`300
`
`w 3<9
`
`oO
`
`Time (min)
`
`= E
`
`~—
`
`DSe
`
`Fig. 2
`
`AQUESTIVE EXHIBIT 1004
`
`AQUESTIVE EXHIBIT 1004 page 2111
`
`page 2111
`
`

`

`INTERNATIONAL SEARCH REPORT
`
`Internat
`
`| Application No
`
`
`
`Accordingto International Patent Classification (IPC) or to both national classification and [PC
`B. FIELDS SEARCHED
`
`Minimum documentation searched (classification system followed by classification symbols)
`IPC 6
`
`Electronic data base consulted during the international search (name of data base and, where practical, search terms used)
`
`C. DOCUMENTS CONSIDERED TO BE RELEVANT
`
`Citation of document, with indication, where appropriate, of the relevant passages
`
`Relevantto claim No.
`
`WO,A,89 03689 (THE LIPOSOME COMPANY) 5 May
`1989
`see the whole document
`
`WO,A,92 13531 (EASTMAN KODAK COMPANY) 20
`August 1992
`see the whole document
`
`
`
`PCT/EP 95/01835
`
`. CLASSIFICATION OF SUBJECT MA’
`A
`TTER
`
`
`IPC 6
`A61K47/22
`A61K9/00
`A61K9/48
`
`
`
`
`
`A61K
`
` Documentation searched other than minimum documentationto the extent that such documents are included in the fields searched
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`DATABASE WPI
`Section Ch, Week 9437,
`Derwent Publications Ltd., London, GB;
`Class B02, AN 94-302691
`& WO,A,94 20143 (FUJISAWA PHARM CO LTD) 15
`September 1994
`see abstract
`
`J Further documents are listed in the continuation of box C.
`
`[x] Patentfamily members are listed in annex.
`
`
`
`
`
`anne
`T’
`
`.
`.
`.
`:
`* Special categories of cited documents :
`later documentpublished after the international filing date
`or priority date and not in conflict with the application but
`;
`nei
`;
`*A* documentdefining the general state of the art which is not
`citedtounderstand the principle or theory underlying the
`considered to be of particular relevance
`
`
`"X* documentofparticular relevance; the claimed invention
`“E’ earlier documentbut published on or after the international
`cannot be considered novel or cannot be considered to
`filing date
`
`involve an inventive step when the documentis taken alone
`“L’ document which may(hrowdoubtson pnomty claim(s)or
`
`
`"Y’ documentof
`parti
`.
`i
`i
`i
`which
`is cited
`to establish
`the publication
`date of another
`particular relevance;
`the claimed invention
`ioe
`:
`
`
`cannotbe considered to involve an inventive step whenthe
`citation or other special reason (as specified)
`document is combined with one or more other such docu-
`°O* documentreferring to an oral disclosure, use, exhibition or
`
`
`ments, such combination being obviousto a person skilled
`other means
`
`
`in theart.
`"P” documentpublished prior to the international filing date but
`
`"&” document memberofthe samepatent family
`later than the priority date claimed
`
`
`
` Date of mailing of the international search report
`
`Date of the actual completion ofthe international search
`27. 10. 9
`
` 19 October 1995
`Authorized officer
`
`
`Nameand mailing address of the ISA
`EuropeanPatentOffice, P.B. 5818 Patentaan 2
`
`NL - 2280 HV Rijswijk
`
`
`
`Tel. (+ 31-70) 340-2040, Tx. 31 651 epo nl,
`Ventura Amat, A
`
`Fax (+ 31-70) 340-3016
`
`Form PCT/ISA/210 (second sheet) (July 1992)
`AQUESTIVE EXHIBIT 1004=page 2112
`
`
`
`AQUESTIVE EXHIBIT 1004 page 2112
`
`

`

`INTERNATIONAL SEARCH REPORT
`Intormation on patentfamily members
`
`Application No
`
`Patent family
`member(s)
`
`Publication
`date
`
`Patent document
`cited in search report
`
`WO-A-8903689
`
`
`
`Publication
`date
`
`05-05-89
`
`
`
`
`
`
`
`
`WO-A-9213531
`
`
`
`Internau
`
`PCT/EP 95/01835
`
`
`
`
`
`CA-A-
`DE-A-
`DE-T-
`EP-A,B
`JP-T-
`
`CA-A~
`
`
`
`1333360
`06-12-94
`3883246
`16-09-93
`3883246
`02-12-93
`0382779
`22-08-90
`3500651
`14-02-91
`5364631
`15-11-94
`
`
`5179122
`2079325
`12-08-92
`0524308
`
`Form PCT/ISA/2L0 (patent family annex) (July 1992)
`AQUESTIVE EXHIBIT 1004=page 2113
`
`AQUESTIVE EXHIBIT 1004 page 2113
`
`

`

`Electronic AcknowledgementReceipt
`
`16848685
`
`13495942
`
`Application Number:
`
`International Application Number:
`
`Confirmation Number:
`
`Title of Invention:
`
`ADMINISTRATION OF BENZODIAZEPINE COMPOSITIONS
`
`Utility under 35 USC 111)
`
`First Named Inventor/Applicant Name:
`
`Steve Cartt
`
`Customer Number:
`
`21971
`
`Matthew Virgil Grumbling/Melanie O'Donnell
`
`Filer Authorized By:
`
`Matthew Virgil Grumbling
`
`Attorney Docket Number:
`
`35401-716.501
`
`Receipt Date:
`
`Filing Date:
`
`Time Stamp:
`
`Application Type:
`
`13-SEP-2013
`
`13-JUN-2012
`
`14:25:10
`
`Paymentinformation:
`
`Submitted with Payment
`
`File Listing:
`
`3 °
`
`Pages
`Multi
`File Size(Bytes)/
`DocumentDescription
`Document
`
`
`
`Number Message Digest|Part/.zip|P (if appl.)
`152501
`
`zcS8 Information:
`
`Transmittal Letter
`
`Neurelis_35401_716_501_Tran
`“09.13_.2013.pdf
`
`4c016169b0b7872b25f3e7f1 adOb65c5f5ef|
`
`AQUESTIVE EXHIBIT 1004 page 2114
`AQUESTIVE EXHIBIT 1004
`page 2114
`
`

`

`179941 ef30d4b1d2eeae1 16239db41862a0
`
`1029387
`
`f9af283fa0a266521 eN804dafcb3d28elffa8
`35b
`
`2531930
`
`cclac6f7ec3601 9fb5702461 6d5bc68c07a4
`Tbac
`
`Foreign Reference
`
`W09531217.pdf
`
`Non Patent Literature
`
`AU2009228093_OA_19JUL201
`3.pdf
`
`519659
`
`3a88c58d2573d880c604744d25a1 labfe4fy
`cAa6
`
`Non Patent Literature
`
`EP097239065_ESR_09JUN2013.
`pdf
`
`399408
`
`54355fa3e1ca24b3 1b47be395ba396fc525)
`9858
`
`173256
`Information Disclosure Statement (IDS)|Neurelis_35401_716_501_IDS_
`bb30beebdb53bb70d3c7d68eade1d27f11
`Form (SB08)
`09_13_2013.pdf
`e9a494
`
`Information:
`
`This is not an USPTO supplied IDS fillable form
`
`Foreign Reference
`
`W009120933.pdf
`
`Information:
`
`Information:
`
`Information:
`
`Information:
`
`Non Patent Literature
`
`JP2010507633_OA_09JUL2013,
`pdf
`
`105893
`
`AQUESTIVE EXHIBIT 1004=page 2115
`
`AQUESTIVE EXHIBIT 1004 page 2115
`
`

`

`New Applications Under 35 U.S.C. 111
`If a new application is being filed and the application includes the necessary componentsfora filing date (see 37 CFR
`1.53(b)-(d) and MPEP 506), a Filing Receipt (37 CFR 1.54) will be issued in due course and the date shownonthis
`AcknowledgementReceiptwill establish thefiling date of the application.
`
`National Stage of an International Application under 35 U.S.C. 371
`If a timely submission to enter the national stage of an international application is compliant with the conditions of 35
`U.S.C. 371 and other applicable requirements a Form PCT/DO/EO/903indicating acceptanceof the application as a
`national stage submission under 35 U.S.C. 371 will be issued in addition to the Filing Receipt, in due course.
`
`This AcknowledgementReceipt evidences receipt on the noted date by the USPTOofthe indicated documents,
`characterized by the applicant, and including page counts, where applicable.It serves as evidence of receipt similar to a
`Post Card, as described in MPEP 503.
`
`the application.
`
`New International Application Filed with the USPTO as a Receiving Office
`If a new international application is being filed and the international application includes the necessary components for
`an international filing date (see PCT Article 11 and MPEP 1810), a Notification of the International Application Number
`and of the International Filing Date (Form PCT/RO/105)will be issued in due course, subject to prescriptions concerning
`national security, and the date shownon this AcknowledgementReceiptwill establish the international filing date of
`
`AQUESTIVE EXHIBIT 1004=page 2116
`
`AQUESTIVE EXHIBIT 1004 page 2116
`
`

`

`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Attorney Docket No. 35401-716.501
`PATENT
`
`Inventor:
`
`Steve Cartt
`
`Group Art Unit:
`
`1612
`
`Serial Number:
`
`13/495,942
`
`Examiner:
`
`Milligan, Adam C.
`
`
`
`Filing Date: CONFIRMATION NO:—73996/13/2012
`
`
`
`Title: ADMINSTRATION OF
`BENZODIAZEPINES COMPOSITIONS
`
`
`
`FILED ELECTRONICALLYON: September13, 2013
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria VA 22313-1450
`
`INFORMATION DISCLOSURE STATEMENT
`UNDER37 CFR §1.97
`
`Madam:
`
`An Information Disclosure Statement along with attached PTO/SB/08 is hereby submitted. A
`
`copy of each listed publication is submitted, if required, pursuant to 37 CFR §§1.97-1.98, as indicated
`
`below.
`
`The Examiner is requested to review the information provided and to make the information of
`
`record in the above-identified application. The Examiner is further requested to initial and return the
`
`attached PTO/SB/08 in accordance with MPEP §609.
`
`The right to establish the patentability of the claimed invention over any of the information
`
`provided herewith, and/or to prove that this information may not beprior art, and/or to prove that this
`
`information may not be enabling for the teachings purportedly offered, is hereby reserved.
`
`This statement is not intended to represent that a search has been made orthat the information
`
`cited in the statement is, or is considered to be, prior art or material to patentability as defined in §1.56.
`
`A. &] 37 CFR §1.97(b). This Information Disclosure Statement should be considered by the Office
`because:
`
`C]
`
`(1)
`
`It is being filed within 3 monthsofthe filing date of a national application and is
`other than a continued prosecution application under §1.53(d);
`
`--OR --
`
`C]
`
`(2)
`
`It is being filed within 3 months of entry of the national stage as set forth in
`§1.491 in an international application;
`
`Attorney Docket No. 35410-716.501
`
`-l-
`
`5802872_1.DOCX
`
`AQUESTIVE EXHIBIT 1004=page 2117
`
`AQUESTIVE EXHIBIT 1004 page 2117
`
`

`

`--OR --
`
`Xx
`
`(3)
`
`It is being filed before the mailing ofa first Office action on the merits;
`
`--OR --
`
`C]
`
`(4)
`
`It is being filed before the mailing of a first Office action after the filing of a
`request for continued examination under §1.114.
`B. L] 37 CFR §1.97(c). Although this Information Disclosure Statement is being filed after the period
`specified in 37 CFR $1.97(b), above, it is filed before the mailing date of the earlier of (1) a final
`office action under §1.113, (2) a notice of allowance under §1.311, or (3) an action that otherwise
`closes prosecution on the merits, this Information Disclosure Statement should be considered because
`it is accompanied by oneof:
`C]
`a statement as specified in §1.97(e) provided concurrently herewith;
`
`--OR --
`
`LC]
`
`a fee of $180.00 as set forth in §1.17(p) authorized below, enclosed, or included with the
`paymentof other papers filed together with this statement.
`C. [] 37 CFR §1.97(d). Although this Information Disclosure Statementis being filed after the mailing
`date of the earlier of (1) a final office action under §1.113 or (2) a notice of allowance under §1.311,
`it is being filed before payment of the issue fee and should be considered because it is accompanied
`by:
`
`i.
`
`astatement as specified in §1.97(e);
`
`-- AND --
`
`ii.
`
`a fee of $180.00 as set forth in §1.17(p) is authorized below, enclosed, or included
`with the paymentof other papers filed together with this Statement.
`LC] 37 CFR §1.97(e). Statement.
`C]
`A statement is provided herewith to satisfy the requirement under 37 CFR §§1.97(c);
`
`D.
`
`-- AND/OR--
`
`C]
`
`A statement is provided herewith to satisfy the requirement under 37 CFR §§1.97(d);
`
`-- AND/OR--
`
`C]
`
`A copy of a dated communication from a foreign patent office clearly showing that the
`information disclosure statement is being submitted within 3 months ofthe filing date on
`the communication is provided in lieu of a statement under 37 C.F.R. § 1.97(e)(1) as
`provided for under MPEP 609.04(b) V.
`E. [] Statement Under 37 C.F.R. §1.704(d). Each item of information contained in the information
`disclosure statement wasfirst cited in a communication from a foreign patent office in a counterpart
`application that was received by an individual designated in § 1.56(c) not more than thirty (30) days
`prior to the filing of this information disclosure statement. This statement is made pursuant to the
`requirements of 37 C.F.R. §1.704(d) to avoid reduction of the period of adjustment of the patent term
`for Applicant(s) delay.
`F. X] 37 CFR §1.98(a)(2). The contentofthe Information Disclosure Statementis as follows:
`C]
`Copies of each of the references listed on the attached Form PTO/SB/08 are enclosed
`herewith.
`
`Attorney Docket No. 35410-716.501
`
`-2-
`
`5802872_1.DOCX
`
`AQUESTIVE EXHIBIT 1004=page 2118
`
`AQUESTIVE EXHIBIT 1004 page 2118
`
`

`

`-- OR --
`
`X
`
`xX
`
`Copies of U.S. Patent Documents (issued patents and patent publications) listed on the
`attached Form PTO/SB/08 are NOT enclosed.
`
`-- AND/OR--
`
`Copies of Foreign Patent Documents and/or Non Patent Literature Documents listed on
`the attached Form PTO/SB/08 are enclosed in accordance with 37 CFR §1.98 (a)(2).
`
`-- AND/OR--
`
`C]
`
`Copies of pending unpublished U.S. patent applications are enclosed in accordance with
`37 CFR §1.98(a)(2)(iii).
`G. L] 37 CFR §1.98(a)(3). The Information Disclosure Statement includes non-English patents and/or
`references.
`
`C]
`
`Pursuant to 37 CFR §1.98(a)(3)(i), a concise explanation of the relevance of each patent,
`publication or other information providedthat is not in English is provided herewith.
`C]
`Pursuant to MPEP 609(B), an English language copy of a foreign search report is
`submitted herewith to satisfy the requirement for a concise explanation where
`non-English language informationis cited in the searchreport.
`
`-- OR --
`
`C]
`
`C]
`
`A concise explanation of the relevance of each patent, publication or other
`information providedthat is not in Englishis as follows:
`Pursuant to 37 CFR §1.98(a)(3)(i), a copy of a translation, or a portion thereof, of the
`non-English language reference(s) is provided herewith.
`H. [J 37 CFR §1.98(d). Copiesof patents, publications and pending U.S. patent applications, or other
`information specified in 37 C.F.R. § 1.98(a) are not provided herewith because:
`C]
`Pursuant
`to 37 CFR §1.98(d)(1)
`the information was previously submitted in an
`Information Disclosure Statement, or cited by examiner, for another application under
`which this application claims priority for an earlier effective filing date under 35 U.S.C.
`120.
`
`Application in which the information was submitted:
`
`Information Disclosure Statement(s)filed on:
`
`AND
`
`C]
`
`The information disclosure statement submitted in the earlier application complied with
`paragraphs(a) through (c) of 37 CFR §1.98.
`
`Attorney Docket No. 35410-716.501
`
`-3-
`
`5802872_1.DOCX
`
`AQUESTIVE EXHIBIT 1004=page 2119
`
`AQUESTIVE EXHIBIT 1004 page 2119
`
`

`

`1. & Fee Authorization. The Commissioneris hereby authorized to charge the above-referenced fees
`of $0.00 and charge any additional
`fees or credit any overpayment associated with this
`communication to Deposit Account No. 23-2415 (Docket No.35401-716.501).
`
`Respectfully submitted,
`
`WILSON SONSINI GOODRICH & ROSATI
`
`By:_/Matthew V. Grumbling/
`Matthew V. Grumbling, Attorney for Applicant
`Reg. No. 44,427
`
`Dated: 9/11/2013
`
`650 Page Mill Road
`Palo Alto, CA 94304-1050
`(650) 493-9300
`Customer No. 021971
`
`Attorney Docket No. 35410-716.501
`
`-4-
`
`5802872_1.DOCX
`
`AQUESTIVE EXHIBIT 1004=page 2120
`
`AQUESTIVE EXHIBIT 1004 page 2120
`
`

`

`
`
`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
`Alexandria, Virginia 22313-1450
`www.uspto.gov
`
`APPLICATION NO.
`
`
`
`
` FILING DATE
`
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`
`
`
`CONFIRMATIONNO.
`
`
`13/495,942
`
`06/13/2012
`
`Steve Cartt
`
`35401-716.501
`
`7399
`
`21971
`
`7590
`
`10/01/2013
`
`WILSON, SONSINI, GOODRICH & ROSATI
`650 PAGE MILL ROAD
`PALO ALTO, CA 94304-1050
`
`MILLIGAN, ADAM C
`
`ART UNIT
`
`1612
`
`MAIL DATE
`
`10/01/2013
`
`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.
`
`AQUESTIVE EXHIBIT 1004=page 2121
`PTOL-90A (Rev. 04/07)
`
`AQUESTIVE EXHIBIT 1004 page 2121
`
`

`

` Attachment(s)
`
`Status
`1)X] Responsive to communication(s)filed on 9/6/2013.
`LJ A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/werefiledon__
`2a)L] This action is FINAL.
`2b) This action is non-final.
`3)L] Anelection was made bythe applicant in responsetoarestriction requirementset forth during the interview on
`
`
`; the restriction requirement and election have been incorporatedinto this action.
`4)[] Since this application is in condition for allowance exceptfor formal matters, prosecution as to the merits is
`closed in accordance with the practice under Ex parte Quayle, 1935 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims
`5)KX] Claim(s) 1-65 is/are pending in the application.
`5a) Of the above claim(s) 23-56 and 60-65 is/are withdrawn from consideration.
`
`6)L] Claim(s)
`is/are allowed.
`7) Claim(s) 1-22 and 57-59 is/are rejected.
`8)L] Claim(s)____is/are objectedto.
`
`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
`or send an inquiry to PPHieedback@uspto.qoy.
`
`Application Papers
`10)L] The specification is objected to by the Examiner.
`
`11)L] The drawing(s)filed on
`is/are: a)L_] accepted or b)[_] 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)L] All
`b)[-] Some * c)L] None ofthe:
`1..] Certified copies of the priority documents have been received.
`2.L] Certified copies of the priority documents have been received in Application No.
`3.L] Copies of the certified copies of the priority documents have been receivedin 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.
`
`
`Application No.
`Applicant(s)
`
` 13/495,942 CARTT ETAL.
`Office Action Summary
`Examiner
`Art Unit
`AIA (First Inventorto File)
`
`
`1612ADAM C. MILLIGAN Na
`-- The MAILING DATEof this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLYIS 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 (6) 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).
`Anyreply 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).
`
`3) CT] Interview Summary (PTO-413)
`1) CT] Notice of References Cited (PTO-892)
`Paper No(s)/Mail Date. __
`2) XJ Information
`Disclosure
`Statement(s)
`(PTO/SB/08
`)
`4 O Other
`)
`nformation Disclosure
`Statement(s) (
`Paper No(s)/Mail Date 6pqs(4/15/2013), 1pq(9/13/2013).
`U.S. Patent and Trademark Office
`AQUESTIVE EXHIBIT 1004 page 2122
`PTOL-326 (Rev. 08-13)
`
`AQUESTIVE EXHIBEF £004021epage22122
`
`Office Action Summary
`
`

`

`Application/Control Number: 13/495,942
`Art Unit: 1612
`
`Page 2
`
`The present application is being examined underthe pre-AlA first to invent
`
`provisions.
`
`DETAILED ACTION
`
`Election/Restrictions
`
`Applicant’s election of Group I, claims 1-22 and 57-59, in the reply filed on
`
`9/6/2013 is acknowledged. Because Applicant did not distinctly and specifically point
`
`out the supposederrorsin the restriction requirement, the election has been treated as
`
`an election without traverse (MPEP § 818.03(a)).
`
`Claims 23-56 and 60-65 are withdrawn from further consideration pursuant to 37
`
`CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable
`
`generic or linking claim.
`
`Claim Rejections — 35 U.S.C. § 112 - 2°" Paragraph
`
`The following is a quotation of 35 U.S.C. 112(b):
`
`(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out
`and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
`
`The following is a quotation of 35 U.S.C. 112 (pre-AlA), second paragraph:
`
`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.
`
`Claims 10-12, 17, 19 and 57-59 are rejected under 35 U.S.C. 112(b) or
`
`35 U.S.C. 112 (pre-AlA), second paragraph, as being indefinite for failing to particularly
`
`point out and distinctly claim the subject matter which the inventor or a joint inventor, or
`
`for pre-AlA the applicant regards as the invention.
`
`AQUESTIVE EXHIBIT 1004=page 2123
`
`AQUESTIVE EXHIBIT 1004 page 2123
`
`

`

`Application/Control Number: 13/495,942
`Art Unit: 1612
`
`Page 3
`
`Claims 10-12, 17, and 57-59 include values in parenthesis. It is not clear whether
`
`the values in parenthesesare part of the claimed invention. If Applicants intend the
`
`values to belimiting on the respective claims, Examiner suggests removing the values
`
`from the parentheses.
`
`Similarly, regarding claim 19, the phrase "such as" rendersthe claim indefinite
`
`becauseit is unclear whetherthe limitations following the phrase are part of the claimed
`
`invention. See MPEP § 2173.05(d).
`
`Claim Rejections — 35 U.S.C. § 103
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis forall
`
`obviousnessrejections setforth 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 ofthis 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.
`
`The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148
`
`USPQ 459 (1966), that are applied for establishing a background for determining
`
`obviousness under 35 U.S.C. 103(a) are summarized asfollows:
`
`PoNn>
`
`Determining the scope and contentsof the prior art.
`Ascertaining the differences betweentheprior art and the claimsat issue.
`Resolving the level of ordinary skill in the pertinentart.
`Considering objective eviden