Exhibit 1027
`
`Coalition For Affordable Drugs XI LLC
`Exhibit 1027
`Coalition For Affordable Drugs XI LLC v Insys Pharma, Inc.
`IPR2015-01800
`
`

`
`
`
`UNITED STATES PATENT AND TRADEMARK OEEICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trzuleinark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1430
`www usplo gov
`
`APPLICATION NO.
`
`FILING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONF MATION NO.
`
`11/698.739
`
`01/25/2007
`
`S. George Kottayil
`
`INTH—001/01US
`308548-2014
`
`4756
`
`Sééifm LLp”°°
`ATTN: Patent Group
`Suite 1 100
`777 - 6th Street, NW
`WASHINGTON, DC 20001
`
`WEGERT, SANDRA L
`ART UNIT
`PAPER NUMBER
`‘
`1646
`
`MAIL DATE
`
`06/08/2012
`
`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.
`
`PTOI.—90A (Rev. 04/07)
`
`

`
`Office Action Summary
`
`Application No.
`
`Applicant(s)
`
`11/698,739
`
`Examiner
`SANDRA WEGERT
`
`KOTTAYIL ET AL.
`
`Art Unit
`1646
`
`-- 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 § 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).
`Any reply received bythe Office later than three months afterthe mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1)IXl Responsive to communication(s) filed on 26 February 2012.
`
`2a)I:I This action is FINAL.
`
`2b)IZ This action is non-final.
`
`3)I:l 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 Exparte Quayle, 1935 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims
`
`5)IXI Claim(s) L475/are pending in the application.
`
`5a) Of the above Claim(s) j is/are withdrawn from consideration.
`
`6)I:l Claim(s) j is/are allowed.
`
`7)IXl Claim(s) 144-147is/are rejected.
`
`8)I:l Claim(s) j is/are objected to.
`
`9)I:l Claim(s) j are subject to restriction and/or election requirement.
`
`Application Papers
`
`10)I:l The specification is objected to by the Examiner.
`
`11)IZl The drawing(s) filed on 25 January 2007 is/are: a)IXI 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).
`
`12)I:l The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO—152.
`
`Priority under 35 U.S.C. § 119
`
`13)I:| Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)—(d) or (f).
`
`a)I:I All
`
`b)D Some * c)I:l None of:
`
`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. j.
`
`3.I: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)
`
`4) El Interview Summary (PTO-413)
`Papel N°(5)/M3” D319 L
`5) I:I N0TICe Of Informal PaT9“T APPIIC-3TI°“
`6) D Other:
`.
`
`1) E Notice of References Cited (PTO-892)
`2) El Notice of Draftsperson‘s Patent Drawing Review (PTO-948)
`3) D Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date
`.
`U.S. Patent and Trademark Office
`PTOL-326 (Rev. 03-11)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20120322
`
`

`
`Application/Control Number: 11/698,739
`
`Art Unit: 1646
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`Page 2
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`Detailed Action
`
`Status of Application, Amendments, and/or Claims
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`A request for continued examination (RCE) under 37 CFR 1.114, including the fee set
`
`forth in 37 CFR 1.17(e), was filed in this application after final rejection. This application is
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`eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e)
`
`has been timely paid.
`
`Applicants’ Remarks and the Declarations submitted under 37 C.F.R. § 1.132, sent 17
`
`February 2012, have been entered into the record.
`
`Claims 1-143 are cancelled. Claims 144-147 are new.
`
`Claims 144-147 are under examination in the Instant Application.
`
`Informalities
`
`Specification
`
`The use of trademarks has been noted in this application (for example, "Duragesic ®,"
`
`p. 1, last paragraph). Trademark names should be capitalized Wherever they appears and be
`
`accompanied by the generic terminology.
`
`Although the use of trademarks is permissible in patent applications, the proprietary
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`nature of the marks should be respected and every effort made to prevent their use in any manner
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`which might adversely affect their validity as trademarks.
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`

`
`Application/Control Number: 11/698,739
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`Art Unit: 1646
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`Page 3
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`Maintained Claim Rejections/Objections
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`Claim Rejections - 35 USC § 103
`
`The following is a quotation of 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.
`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 as follows:
`
`Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior
`art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering
`objective evidence present in the application indicating obviousness or nonobviousncss.
`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).
`
`Claims 144-147 are rejected under 35 U.S.C. 103(a) as being unpatentable over Ross
`
`(2006, US 2006/0062812; hereinafter, "Ross").
`
`Instant claims 144-147 are directed to a unit dose of a non—propellant sublingual fentanyl
`
`fonnulation comprising discrete liquid droplets of about 5 to about 500nm, and ethanol, water
`
`and ethylene glycol as carriers, wherein the formulation provides a mean maximum plasma
`
`concentration (Cmax) of about 158pg/ml to about 177pg/ml per 100ug of fentanyl. The mean
`
`droplet size of the formulation is about 20 to about 200um; the formulation provides a mean
`
`Tmax of about 10 minutes to about 60 minutes, while the mean area under the curve (AUC) of
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`fentanyl ranges from 715pg° hour/mL to about 1061 pg° hour/mL. Dependent claims narrow the
`
`ranges of the droplet sizes.
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`

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`Application/Control Number: 11/698,739
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`Art Unit: 1646
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`Page 4
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`Ross teaches compositions of a liquid fentanyl formulation for sublingual administration
`
`to treat breakthrough pain (Abstract) and also teaches that sublingual spray delivery is preferred
`
`over other types of drug delivery (paragraph 0014). Liquid carriers, such as oils and alcohols, are
`
`discussed in paragraphs 0018-0021. Fentanyl concentrations of about 0.3% by weight (paragraph
`
`0096, Example 1) are also recited. Use of ethanol in the formulation, in the range of 6 to 50%, is
`
`recited at paragraph 0037, While propylene glycol is discussed at paragraph 0055 as a nonionic
`
`surfactant. Both are described as preferred solvents (paragraphs 0038 and 0040). Sublingual
`
`administration of the formulation to human beings is discussed throughout (see for example the
`
`results in Table 1). Ross obtained mean Cmax values of 256—258pg/ml per 100ug of fentanyl after
`
`sublingual administration of the fonnulation (note that the Cmax values are expressed per 200ug
`
`in Ross), depending on the atomizer used (compare the pMDl device in Table 1 with the pump
`
`actuator in Table 2).
`
`The variability of the data disclosed in Ross is large. Patients reported relief of pain at
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`Cmax values as low as 130pg/ml (normalized to 100ug fentanyl) (Table 1) and as high as
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`380pg/ml (Table 1). Tmax values disclosed in Ross overlap broadly with instant claimed Tmax
`
`values (Tables 1 and 2). Area under the curve (AUC) of blood concentrations is discussed in
`
`paragraph 0082 as an indicator of bioavailability. Although AUC concentrations were not
`
`measured in the experiments described in Ross, the sublingual doses of fentanyl were described
`
`as providing 50% or greater bioavailability compared to intravenous administration, which is in
`
`the range of that disclosed in the instant specification (Tables 11, 12 and 13). The device used for
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`atomizing the liquid fentanyl formulation is shown in Figure 1. Figure 5 shows the spray nozzle
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`having three orifices in order to regulate spray droplet diameter. The bottle and actuator used
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`

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`Application/Control Number: 11/698,739
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`Art Unit: 1646
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`Page 5
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`were the Purgard Schott bottle and the Bespak BK357 actuator, respectively, which together
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`form a "pMDI" atomizer. Such atomizers or inhalers produce droplet sizes from about 6pm to
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`approximately 200pm (Smyth & Hickey, 2003; submitted in the IDS of 9/ 15/2012, Figure 1;
`
`see also the related application, also by Ross, et al, 2006, application 2006/0062812, examples 2
`
`and 6).
`
`Ross does not specifically teach a required liquid droplet size of at least about 5 to
`
`500um, nor a specific weight of propylene glycol, nor a mean Cmax for all patients of 158pg/ml
`
`to 177pg/ml. However, the broad teachings of Ross cure these deficiencies, since Ross teaches or
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`suggests every aspect of the claimed instant invention, including several examples of blood
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`concentrations of fentanyl both higher and lower than the instant claimed range of mean Cmax's.
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`Ross also disclosed very similar Tmax's, and suggested AUC's similar to those disclosed by
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`applicants, based on bioavailability measurements. Ross also utilized the same or similar
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`actuators to dispense the liquid formulations (see the discussion concerning Smyth & Hickey,
`
`2003, above). One would be motivated to use the pMDI actuators disclosed in Smyth & Hickey,
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`because Ross teaches that the orifices of the actuator are well adapted to dispense particles of
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`chosen size (paragraph 0066), and the actuators have been shown to produce liquid particles of a
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`superior average diameter based on blood concentrations of fentanyl delivered to sublingual
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`tissues.
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`It would have been prima facie obvious to a person of ordinary skill in the art at the time
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`of the invention to have used the teachings of Ross to optimize the fentanyl formulation and
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`means of administration in order to achieve the blood concentrations of fentanyl that are
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`

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`Application/Control Number: 11/698,739
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`Art Unit: 1646
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`Page 6
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`sufficient to treat acute breakthrough pain, specifically Cmaxvs of 158 to 177pg/ml of 100pg
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`fentanyl. Ross, in fact, did use a spray dispenser to administer the aqueous formulation
`
`sublingually (paragraph 0077); however the sizes of the droplets emitted from the atomizer are
`
`not given in Ross, but are evinced by Smyth & Hickey (2003). In addition, slightly higher blood
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`concentrations were required in Ross to relieve breakthrough pain, thus raising the mean Cmax
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`values somewhat compared to the instant claims.
`
`Since the formulation of Ross: 1) comprises the same active ingredients as the instant
`
`formulation, as well as similar carriers; 2) produces Cmax values that are higher than those
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`disclosed by applicants, but not significantly so; 3) produces widely overlapping Tmax values; 4)
`
`is administered sublingually; and 5) is sprayed sublingually into the mouth in the form of small
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`liquid droplets in the same size range as that given by applicants, the invention as described in
`
`Ross is not obviously distinguishable from that claimed by applicants.
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`Applicants argue (Remarks, 17 February 2012, p. 7):
`
`"Ross fails to disclose any droplet size, or even recognize the importance of controlling droplet size or
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`droplet size distribution. However, Ross does expressly teach a mean Cmax for a "non- pressurized pump spray"
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`formulation of 516.3 pg/mL per 200 pg fentanyl (258.15 pg/mL per 100 pg fentanyl) which is substantially larger
`
`(i.e., 22% larger than the largest mean Cmax value described in the present specification, 213 pg/ml per 100 pg
`fentanyl; see paragraph [0079] of the present specification) and 45% larger than the maximum mean Cmax value
`
`claimed, 177 pg/mL per 100 pg fentanyl. See Ross, Tables 1 and 2, first column, page 8."
`
`A footnote to the paragraph above states:
`
`"As demonstrated in Table 18 of the present specification, sublingual fentanyl spray formulations
`
`having widely varying doses of, respectively, 100 pg, 400 pg, and 800 pg, all exhibit roughly similar
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`[pharmacokinetic] values when normalized to 100 pg of fentanyl. Accordingly, it is reasonable to normalize the
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`[pharmacokinetic] parameters of the formulations of Ross to the same 100 pg fentanyl basis as in the present
`claims. See also the Dillaha Declaration at 111] 11-12."
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`

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`Application/Control Number: 11/698,739
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`Art Unit: 1646
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`Page 7
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`Firstly, the examiner agrees completely with the footnote (above). Blood concentrations
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`of drug E the most meaningful measurement of the efficiency of drug delivery, and the
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`pharmacokinetics of drug distribution in the body is unrelated to the concentration of fentanyl in
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`a particular dosage forrnulation—across a wide range of concentrations. Thus, it is reasonable to
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`compare the fonnulation of Ross to the disclosed formulation, even though the concentration —
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`not the dose— of fentanyl may differ.
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`Secondly, applicants have not disclosed how or why droplet size is important to the
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`invention. Although applicants have measured the size of the liquid droplets in the fentanyl
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`fonnulation quite accurately (see Table 44, p. 86, for example), they have not demonstrated that
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`a particular range of droplet sizes produces an advantage in tenns of drug delivery. In fact, the
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`ACTIQ® dispenser and formulation disclosed in the instant specification and in the Prescribing
`
`Information (submitted 17 February 2012) appear to deliver fentanyl to a patient somewhat less
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`efficiently than the fonnulation and dispenser disclosed in Ross. If, for example, droplet size
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`equates to surface area of the aqueous mist delivered into the mouth, than Ross‘s formulation is
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`probably comprised of mostly smaller droplets (thus having a larger surface area), since more
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`drug was delivered to those patients‘ bloodstreams. In fact, Smyth & Hickey (2003) show that
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`pMDI actuators produce droplet diameters mostly smaller than 100um (Figure 1). If a larger
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`droplet size is desirable, applicants are asked to state why that is so.
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`The same point can be made about the use of 4% to 6% propylene glycol. Applicants
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`maintain that propylene glycol imparts certain properties to the liquid formulation:
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`"Propylene glycol, in the presently claimed amount, confers certain rheological properties (e.g., density,
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`viscosity) on the formulation of the present unit dose which enable the formation of discrete liquid droplets
`having the presently claimed size distribution of from about 5 pm to about 500 pm and a mean diameter of
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`about 20 pm to about 200 pm."
`
`

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`Application/Control Number: 11/698,739
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`Art Unit: 1646
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`Page 8
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`(Goskonda Decl, p. 2).
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`However, applicants have not demonstrated why droplet size is critically important;
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`therefore, the necessity of propylene glycol in the formulation to produce a certain droplet size
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`has also not been shown by applicants. Ross, in fact, does suggest the use of propylene glycol as
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`a possible surfactant (discussed above), but instead found that a solution of buffers, water and
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`ethanol was adequate for dispensing the dose of fentanyl.
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`Applicants further argue (Remarks, 17 February 2012, p. 7):
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`"As evidenced by the Dillaha Declaration, mean Cmax values and discrete Cmax values are distinct
`
`measurements with distinct clinical significance. For example, individual Cmax values for individual patients may
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`vary widely as a function of, e.g., patient body weight, differences in efficiency of metabolism of the compound
`
`in question (e.g., fentanyl), consistency of administration of the drug between patients, etc. Conversely, a mean
`Cmax provides an average Cmax value for a drug across a patient population. Such an average incorporates both
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`typical Cmax values and "outliers" (e.g., those values which are significantly higher or lower than those Cmax
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`values typically observed) in the patient population, and averages those values to provide a mean Cmax which is
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`statistically valid and predictive of what Cmax values will be observed across the majority of a patient
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`population. Thus, a single, individual Cmax value in any single patient and the mean Cmax value for a patient
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`population provided by a formulation can differ significantly, and are distinct. See the Dillaha Declaration at
`1111."
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`In addition, applicants argue (p. 8):
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`"Even if it were reasonable to compare individual Cmax values to mean Cmax values (which Applicants
`
`do not concede),the present claims now recite a mean Cmax range (about 158-177 pg/mL per 100 pg fentanyl)
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`which excludes all Cmax values taught in Ross, including mean Cmax and individual Cmax values."
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`The examiner agrees with the assessment of individual measurements versus mean
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`measurements of a population (Declaration of Dillaha filed under 37 CFR 1.132 at p. 4). Since
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`the examiner does not have access to individual measurements in the applicants’ specification,
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`measurements of variability will have to suffice. In both Ross and in the applicants’ experiments,
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`

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`Application/Control Number: 11/698,739
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`Art Unit: 1646
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`Page 9
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`sublingual administration of fentanyl produced Cmax's that were highly variable, at least
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`compared to intravenous dosing regimens (compare instant Figure 10 with Figure 9; in Ross the
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`highest recorded standard deviation was 181.5pg/ml). Note, the examiner is not arguing that the
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`mean Cmax's produced are not different between applicants’ formulation and that of Ross, only
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`that applicants have not identified the source of the somewhat lower Cmax values disclosed in
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`the instant application. The examiner is instead arguing that the source of the diflerertce may not
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`be present in applicants’ formulation as claimed, and that modifying the formulation of Ross
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`slightly, or taking Cmax measurements earlier or later, or changing the pain threshold reporting
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`criteria, or using a different actuator, could result in the same lower mean Cmax. In fact, we do
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`know that the actuators used to dispense the two formulations are different; yet applicants are not
`
`claiming the actuator.
`
`Applicants further argue (Remarks, p. 11):
`
`''In summary, Ross does not disclose the claimed mean Cmax and AUC°° range, the claimed amount of
`
`propylene glycol, or the claimed droplet size and droplet size distribution. Indeed, Ross fails to even recognize
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`that formulation components may affect droplet size, much less that droplet size and droplet size distribution
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`affect the [pharmacokinetic] characteristics of sublingual fentanyl spray compositions upon administration.
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`Since Ross fails to disclose or recognize the importance of the formulation composition in the present unit dose,
`
`or the relationship between droplet size and clinical efficacy, Ross cannot recognize the unexpectedly low Cmax
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`values provided by the present formulations, or clinical advantages provided thereby. Thus, Ross clearly fails to
`
`suggest the claimed invention. Accordingly, Applicants respectfully request that the rejection be withdrawn."
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`Applicant's arguments have been fully considered but they are not persuasive for the
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`following reasons:
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`Ross conducted experiments with formulations of fentanyl in order to determine which
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`fonnulations and delivery systems produced the fastest and most efiicient relief of breakthrough
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`pain in patients requiring such treatment. Ross found that minimal plasma concentrations of drug
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`

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`Application/Control Number: 11/698,739
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`Page 10
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`Art Unit: 1646
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`needed to relieve pain varies somewhat from patient to patient. For example, in Para. 0080 of
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`Ross it states:
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`''In order for the opioid analgesic to have a pain-relieving effect, a plasma concentration of between
`
`250 pg/ml and 2 ng/ml is required. The therapeutically effective concentrations vary between patients and it is
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`therefore generally necessary to titrate."
`
`Ross then describes two experiments comparing Cmax concentrations of fentanyl using a
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`"pMDI" aerosol actuator versus a pump—spray actuator (see Tables 1 and 2). Both actuators
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`produce a mist of fine droplets; both actuators were used to administer the liquid fentanyl
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`formulation sublingually to patients. In both experiments, Ross used 200 micrograms of fentanyl.
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`However, it should be noted that Ross specifically teaches [0084] that the dosage can range from
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`100 to 3000 micrograms. Absent evidence to the contrary, one of ordinary skill in the art would
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`reasonably expect that experimental Cmax values would approximate those disclosed in Ross.
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`Had Ross determined that slightly lower values of Cmax are required to treat breakthrough pain,
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`there would have been motivation to make slight modifications in the dosage concentration of
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`fentanyl in order to achieve lower plasma concentrations.
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`As far as droplet size, the fact that applicants tested their droplet size should not negate
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`the general obviousness of the prior art. Both the prior art and applicants’ disclosure discuss
`
`using various spray pumps for sublingual delivery. Different actuators would create a variety of
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`droplet sizes. Further, applicants are claiming a large range of droplet sizes (from 5 to 500um).
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`Ross does not measure droplet sizes emanating from the atomizers disclosed, but they no doubt
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`span the lower ranges of those claimed (as discussed above and evinced by Smyth & Hickey,
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`2003).
`
`

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`Application/Control Number: 11/698,739
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`Page 11
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`Art Unit: 1646
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`Applicants also argue:
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`"[The] present formulations provide efficacious pain relief at unexpectedly low Cmax values, and
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`accordingly, such unexpected results render the present claims non-obvious. As a result, the present claims are
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`patentable over Ross."
`
`(Remarks, p. 6)
`
`Similarly:
`
`"Since the present unit dose provides efficacious pain relief at significantly lower Cmax values, the
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`incidence of serious, potentially fatal side effects associated with higher Cmax values is minimized in the
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`presently claimed unit dose relative to other sublingual fentanyl formulations (e.g., that described by Ross)."
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`(Decl of Dillaha, p. 6).
`
`However, applicants have not demonstrated the same pain relief at lower doses than
`
`those used in Ross. Ross performed experiments in which doses were titrated to a point to
`
`maximize each patient's pain relief. The fact that the resulting Cmax's were 20-50% higher, on
`
`average, than those disclosed by applicants (Specification, Table 18, p. 47) is no doubt caused by
`
`different experimental protocol. This is also demonstrated by the recent data submitted by
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`applicants (see Reynolds, et al, 2011, Exhibit B, submitted 17 February 2012, pp. 7 and 8).
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`When limiting the dose to 100ug, there was some average level of pain relief that was
`
`significantly greater than placebo (Figure 2). However, applicants also performed a dosing
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`experiment more similar to that of Ross (Figure 3). Comparing the experiments supports the
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`examiner's position, since:
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`"4 patients were successfully titrated to the lowest dose of Fentanyl SL Spray available"
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`and:
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`"Median (range) dose of Fentanyl SL Spray in the double-blind period was 800 [] mcg"
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`(Exhibit B, p. 8).
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`

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`Application/Control Number: 11/698,739
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`Page 12
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`Art Unit: 1646
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`Thus, out of 92 patients in the experiment in which the dose of fentanyl was limited to
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`100}; g, only four patients reported complete pain relief. Doses 8X higher, in fact, were needed,
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`on average, for total pain relief across the population. However, since Cmax's were not measured
`
`in the disclosed recent data, a comparison between the Cmax's in Ross and the now more
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`comparable pain—relief experiments shown in Exhibit B cannot be performed.
`
`Since applicants have provided no evidence that the claimed invention is an unexpected
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`improvement over that disclosed in Ross (as per Dillon, 919 F.2d at 692-93, 16 USPQ2d at 1901)
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`or that the formulation disclosed in Ross failed somehow to produce adequate Cmax's of fentanyl
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`in the patients’ plasma (as discussed in Graham v. John Deere Co., 383 U.S. at 17, 148
`
`USPQ at 467), it can be concluded that the instant claims are unpatentable over Ross.
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`Conclusion: Claims 144- 147 are rejected for the reasons recited above.
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`Advisory information
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`Any inquiry concerning this communication or earlier communications from the
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`examiner should be directed to Sandra Wegert whose telephone number is (571) 272-0895. The
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`examiner can normally be reached Monday - Friday from 9:00 AM to 5:00 PM (Eastern Time).
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`If attempts to reach the examiner by telephone are unsuccessful, the Examiner's supervisor,
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`Vanessa Ford, can be reached at (571)272-0857.
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`

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`Application/Control Number: 11/698,739
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`Page 13
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`Art Unit: 1646
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`The fax number for the organization where this application or proceeding is assigned is
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`571-273-8300.
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`Information regarding the status of an application may be obtained from the Patent
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`Application Information Retrieval (PAIR) system. Status information for published applications
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`may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
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`applications is available through Private PAIR only. For more information about the PAIR
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`system, see http://pair—direct.uspto.gov. Should you have questions on access to the Private
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`PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you
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`/SLW/
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`19 May 2012
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`/VANESSA L. FORD/
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`Supervisory Patent Examiner, Art Unit 1646