Exhibit 1025
`
`Coalition For Affordable Drugs XI LLC
`Exhibit 1025
`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
`308548-201
`
`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
`
`11/17/2011
`
`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 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).
`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 15 August 2011.
`
`2a)IZI This action is FINAL.
`
`2b)I:I 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) 1-8 10-29 and 31-143 is/are pending in the application.
`
`5a) Of the above claim(s) 5-8 12-19 24-29 and 33-138 is/are withdrawn from consideration.
`
`6)I:l Claim(s) j is/are allowed.
`
`7)IXl Claim(s) 1-4 10 11 20-23 31 32 and 139-143 is/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)|:l The specification is objected to by the Examiner.
`
`11)IZl The drawing(s) filed on 25 January 2007 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).
`
`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.
`
`.
`
`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) El Notice of References Cited (PTO-892)
`2) El Notice of Draftsperson‘s Patent Drawing Review (PTO-948)
`3) X Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date 8/15/11.
`U.S. Patent and Trademark Office
`PTOL-326 (Rev. 03-11)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20111113
`
`

`
`Application/Control Number: 11/698,739
`
`Art Unit: 1646
`
`Page 2
`
`Detailed Action
`
`Status of Application, Amendments, and/or Claims
`
`Applicants’ Remarks, and the Information Disclosure Statement, sent 15 August 2011,
`
`have been entered into the record.
`
`Claims 1-8, 10-29 and 31-143 are pending. Claims 5-8, 12-19, 24-29 and 33-138 are
`
`withdrawn. Claims 9 and 30 are cancelled.
`
`Claims 1-4, 10, 11, 20-23, 31, 32 and 139-143 are under examination in the Instant
`
`Application.
`
`Withdrawn Rejections/Objections
`
`Claim Rejections - 35 USC § 112- second paragraph
`
`The following is a quotation of the second paragraph of 35 U.S.C. 112:
`
`The specification shall conclude with one or more claims particularly pointing out and distinctly
`claiming the subject matter which the applicant regards as his invention.
`
`The rejection of claims 1-4, 10, 11, 20-23, 31, 32 and 139-143, 35 U.S.C. § 112, second
`
`paragraph, for indefinite claim language is withdrawn based on applicants’ arguments (2 August
`
`2011, pp. 2-4).
`
`

`
`Application/Control Number: 11/698,739
`
`Art Unit: 1646
`
`Page 3
`
`Maintained Claim Rejections/Objections
`
`Claim Rejections - 35 USC § 103
`
`The following is a quotation of 35 U.S.C. l03(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 1-4, 10, 11, 20-23, 31, 32 and 139-143 are rejected under 35 U.S.C. 103(a) as
`
`being unpatentable over Ross (2006, US 2006/0062812, Application No. 11/224,383; referred to
`
`herein as "Ross").
`
`Instant claims 1-4, 10, 11, 20-23, 31, 32 and 139-143 are directed to an oral liquid
`
`fentanyl formulation comprising discrete liquid droplets of at least about 10 microns and
`
`pharmaceutically acceptable liquid carriers, wherein the formulation provides a mean maximum
`
`plasma concentration (Cmax) Of 127pg/ml to 213pg/ml per 100}; g of fentanyl.
`
`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
`
`

`
`Application/Control Number: 11/698,739
`
`Art Unit: 1646
`
`Page 4
`
`discussed in paragraphs 0018-0021 (page 2). Fentanyl concentrations of about 10% (0.1 mg/ml)
`
`are recited in paragraph 0036. 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. 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). In
`
`six patients (two in Table 1 and four in Table 2) Ross obtained Cmax values of about 127pg/ml to
`
`213pg/ml per 100ug of fentanyl after sublingual administration of the formulation.
`
`Ross does not specifically teach a liquid droplet size of at least about 10 microns, nor a
`
`mean Cmax of 127pg/ml to 213pg/ml. However, the broad teachings of Ross cure these
`
`deficiencies, since Ross teaches every aspect of the claimed instant invention, including several
`
`examples of the required blood concentrations of fentanyl.
`
`It would have been prima facie obvious to a person of ordinary skill in the art at the time
`
`of the invention to have used the teachings of Ross to optimize the fentanyl formulation and
`
`means of administration in order to achieve the blood concentrations of fentanyl that are
`
`sufficient to treat acute breakthrough pain, specifically Cmax-S of 127 to 213pg/ml of 100ug
`
`fentanyl. Ross, in fact, did use a dispenser to administer the discrete liquid droplets sublingually
`
`(paragraph 0077); however the size of the drops is not given. In addition, slightly higher blood
`
`concentrations were required in Ross to relieve breakthrough pain, thus raising the Cmax
`
`averages somewhat compared to the instant claims.
`
`Since the formulation of Ross comprises the same ingredients as the instant formulation,
`
`produces overlapping Cmax values, is administered sublingually, and is sprayed into the mouth in
`
`

`
`Application/Control Number: 11/698,739
`
`Art Unit: 1646
`
`Page 5
`
`the form of liquid droplets, the invention as claimed is not obviously distinguishable from that of
`
`Ross.
`
`Applicants argue (Remarks, 2 August 2011, p. 5):
`
`"Each of the present independent claims 1, 20 and 139 recite that the claimed formulation comprises
`
`‘droplets having a mean diameter of at least about 10 microns.‘ Ross is silent with respect to droplet size, an
`
`explicit limitation required by the present claims."
`
`and (Remarks, pp. 5-6):
`
`"The present claims require that the claimed formulations 'provide[] a mean maximum plasma
`
`concentration (Cmax) of fentanyl of about 127 pg/ml to about 213 pg/ml per 100p.g fentanyl after sublingual
`
`administration to humans‘ (see the present claims 1, 20 and 139; emphasis added). [ ] Ross does expressly
`
`disclose mean Cmax values which fall outside the presently claimed range (see, e.g., Tables 1 and 2 of Ross,
`
`which report mean Cmax values significantly higher Ross does expressly disclose mean Cmax values which fall
`
`outside the presently claimed range (see, e.g., Tables 1 and 2 of Ross, which report mean Cmax values
`
`significantly higher."
`
`Applicant's arguments have been fully considered but they are not persuasive for the
`
`following reasons:
`
`Ross (2006, Pub. No. 2006/0062812) conducted experiments with formulations of
`
`fentanyl in order to determine which formulations and delivery systems produced the fastest and
`
`most efficient relief of breakthrough pain in patients requiring such treatment. Ross found that
`
`minimal plasma concentrations of drug needed to relieve pain varies somewhat from patient to
`
`patient. For example, in Para. 0080 of Ross it states:
`
`“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 therefore generally necessary to titrate.“
`
`

`
`Application/Control Number: 11/698,739
`
`Art Unit: 1646
`
`Page 6
`
`Ross then describes two experiments comparing Cmax concentrations of fentanyl using a
`
`"pMDI" aerosol actuator versus a pump—spray actuator (see Tables 1 and 2). Both actuators
`
`produce a mist of fine droplets; both actuators were used to administer the liquid fentanyl
`
`fonnulation sublingually to patients. In both experiments, Ross used 200 micrograms of fentanyl.
`
`The claims are per 100 micrograms. Thus, the Cmax disclosed in the prior art is, on average,
`
`higher than the claimed range of 127 to 213 pg/ml because Ross used a higher dosage in their
`
`experiements. However, it should be noted that Ross specifically teaches [0084] that the dosage
`
`can range from 100 to 3000 micrograms. Absent evidence to the contrary, one of ordinary skill in
`
`the art would reasonably expect that experimental Cmax values would approach the claimed Had
`
`Ross determined that slightly lower values of Cmax are required to treat breakthrough pain,
`
`he/they would have been motivated to make slight modifications in the dosage concentration of
`
`fentanyl in order to achieve lower plasma concentrations.
`
`As far as droplet size, the fact that applicant’s tested their droplet size should not negate
`
`the general obviousness of the prior art. Both the prior art and applicant’s disclosure discuss
`
`using various spray pumps for sublingual delivery which would create a variety of droplet sizes.
`
`Further, applicants are claiming a large range of droplet sizes (from at least 10 microns in claim
`
`1 upwards to about 500 microns in claim 3.).
`
`Since applicants have provided no evidence that the claimed invention is an unexpected
`
`improvement over that disclosed in Ross (as per Dillon, 919 F.2d at 692-93, 16 USPQ2d at 1901)
`
`or that the fonnulation disclosed in Ross failed somehow to produce adequate Cmax's of fentanyl
`
`in the patients’ plasma (as discussed in Graham v. John Deere Co., 383 U.S. at 17, 148
`
`

`
`Application/Control Number: 11/698,739
`
`Art Unit: 1646
`
`Page 7
`
`USPQ at 467), it can be included that the instant claims are unpatentable over Ross.
`
`Conclusion: Claims 1-4, 10, 11, 20-23, 31, 32 and 139-143 are rejected for the reasons recited
`
`above.
`
`THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of
`
`the extension of time policy as set forth in 37 CFR 1.136(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 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 shortened statutory period
`
`will expire on the date the advisory action is mailed, and any extension fee pursuant to 37
`
`CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event,
`
`however, will the statutory period for reply expire later than SIX MONTHS from the date of this
`
`final action.
`
`Advisory information
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Sandra Wegert whose telephone number is (571) 272-0895. The
`
`examiner can normally be reached Monday — Friday from 9:00 AM to 5:00 PM (Eastern Time).
`
`If attempts to reach the examiner by telephone are unsuccessful, the Examiner's S11pC1‘VlSO1', Gary
`
`Nickol, can be reached at (571) 272-0835.
`
`

`
`Application/Control Number: 11/698,739
`
`Art Unit: 1646
`
`Page 8
`
`The fax number for the organization where this application or proceeding is assigned is
`
`571-273-8300.
`
`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.
`
`/SLW/
`
`10 November 2011
`
`/Gary B. Nickol /
`
`Supervisory Patent Examiner, Art Unit 1645