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`IN THE UNITED STATES PATENT AND‘TRADEMARKOFFICE
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`Patentee:
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`Patent No.:
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`Reexamination
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`Control No.:
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`Filed:
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`Dated:
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`Yang et al.
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`US, 7,897,080
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`95/002.170
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`September10, 2012
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`Examiner:
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`Group Art Unit:
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`Confirmation
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`No.
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`H&B Docket:
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`Diamond, Alan D.
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`3991
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`6418
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`1199-26.
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`RCE/CON/REX
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`March 13, 2013
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`M&E Docket:
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`—117'744-00023
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`Mail Stop Inter Partes Reexam
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`Central Reexamination Unit
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`Certificate ofEFS-Web Transmission
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`ihereby certify that this correspondence is being.
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`iransmified via the LL. Patent and Trademark
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`USEDO«an
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`DECLARATION OF B. ARLEE BOGUE, PELD. UNDER37 CLICR. § 1,132
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`Madame:
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`I, B. ArlieBogue, Ph.D., do hereby make the following declaration:
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`Technical Background
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`developenent,for 22 years. Tam+ employed byIMMonoSol Rx,LLC.+ Rebate!snand/or
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`“MonoSol”),theassigneeofissued patent ULS. 7,897,080 (the 080 Patent"), as Senior Director
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`[havea BSin Physical Chemistry from Colorado State University and aPhD. in Chemical and
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`BioEnginecring from Arizona State University. I have participatedin postdoctoral studies in.
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`Biochemical Engineeringatthe University ofVirginia. During mycareer, | have been namedas
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`an inventor on over 23U.S. patents and numerous foreign patents directed to the formulation,
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`Dr. Reddy's - EX1007
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`processing and/or packaging of pharmaceutical oral disintegrating unit-doses (tablets and film
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`strips).I have direct experiencewith the commercial scale processing ofpharmaceuticalfilm
`systems as well as anunderstanding of the uniformity of contentof active and methods for
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`testing the same.
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`Thave read the ‘080Patent and the Office Action issued an November 29, 2012 in thereexamination
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`ofthe ‘080 Patent ("Office Action”) andthereferences cited therein, and 1 have also reviewedthe
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`amendinent asto the independent clatnis setforth in Patentee’s Reply to the OfficeActian
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`concurrentlyfiled herewith,
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`Producing resulting films in accordance with the ‘080Patent
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`Each of the 73 lots ofresulting films (Lots 1-73). containing approximately 2,000,000 individual
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`(4) for commercial use andregulatory
`dosage units per lot discussed herein were manufactured:
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`approval; (ii) in compliance with U.S Food and Drug Administration CFDA") standardsand
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`regulations, including thoserelating to analytical chemical testing for variation inactivein Individual
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`dosage units; and (it) in accordance with the invention disclosedin the ‘080 Patent, andas claimed
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`bythe ‘080 Patent bothas issued and as amended in the Patentee’s Reply to the Office Action; by:
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`(a) forming aflowablepolymer matrix comprisinga water-soluble polymer, a solvent anda
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`pharmaceutical active, said matrix having asubstantially uniformdistribution ofsaidactive;
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`(b) castingsaid flawable polymer matrix, said flowable polymermatrix having a
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`viscosity fromabout400to about 100,000 eps:
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`(ec) controllingdryingthrough a process comprising conveyingsaid pelymermatrix
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`through a drying apparatus and evaporatingat least a partion of said solvent to form a-visco-
`elastic film, having said active substantially uniformly distributed throughout, within about the
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`first 4 minutes byrapidlyincreasing the viscosity ofsaid polymer matrix upon initiation of
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`dryingto maintain saidsubstantially uniformdistribution ofsaid activeby locking-in or
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`substantially preventing migration ofsaid active within said viseo-clastic film wherein the
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`polymer matrix temperature is [00 °C or less;
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`(d) forming the resulting pharmaceuticalfilm from said visco-clastic film, whereinsaid
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`resulting pharmaceutical film has.a water content of10% or less and said substantially uniform
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`distribution of active by said locking-inor substantially preventing migration of saidactive is
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`maintained,such that uniformity ofcontentin the amount ofthe active in substantially equal
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`sized individual dosage units, sampled from different locationsofsaid resulting pharmaceutical
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`film, varies by no more than 10%; and
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`{e) performing analytical chemical tests for uniformity of content of said active in
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`substantially equal sized individual dosageunits of said sampled resulting pharmaceutical film,
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`said tests indicating that uniformityofcontent in the amount of the active varies by no more than
`10%, [see Appendix A] saidresulting pharmaceutical filmsuitable for cormmereial and
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`regulatory approval, wherein said regulatory approval is provided by the U.S. Food andDrug
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`Additionally, the uniformity of content in the amount ofactive as sampled from the 73 lotsof
`resulting film varies no more than 10% fromthe desired amount ofthe active as indicated by
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`said analytical chemicaltests from 4(e) above. [See Appendix B]
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`AnalyticalChemicalTesting forUniformity ofContentofPatentee's Resulting Films
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`To demonstrate the uniformity ofindividual dosage unit films, ] compiled individual dosage unit
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`assaydata for individual Lots 1- 73, all of which weredisclosed inMonoSol's 2012 Annual
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`Product Review to the FDA,
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`Ten (10) individual desage unitsall having the same dimensions were cut out fromdifferent
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`locations ofeach of the 73 lots ofresultingfilms using a commercial packaging machine, thus
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`providing 730 randomly sampled individual dosage.units, ten each fromthe 73 separate lots. All
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`regulations regarding same, using analytical chemical testing, in which the pharmaceuticalactive
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`was extracted andanalyzed by High PerformanceLiquid Chromatography (HPLC) againstan
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`extemal standard to quantify the amount of active present In eachindividual dosage unit.
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`Accordingto the inventive process setforth and claimed in the ‘080 Patent, and in accordance
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`with FDA nomenclature, | have prepared tables shown as Appendices A, B and C, reflecting the
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`unifonmity of contentof active of individual dosage units withinparticularlots and across
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`First, the uniformity of contentof active in a lot is determinedthrough establishingthe amount of
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`active (Ay) } actually present in each sampledindividual dosageunit fromthesame lat (N) as
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`determinedby taking the difference between the amount ofactive in the samplewith the most
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`active (Maxiaren} minus the amountof activein the sample with the least amount ofactive
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`(Min:oray) and dividing the difference by the average amount ofactive in thelot samples (Lotgy
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`Sample Average). Thatis: (Maxnora: - Mintoran)/ ((Anajy+Angy+ ++ Away10) The results
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`are shownin Appendix A.
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`1Q, Second, the uniformity of content across differentlots is determined throughestablishing the
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`amount ofactive actually present in each sampled individual dosage unit from all 73 lots and
`comparingthat amountof active with a “target” or "desired" amount of active contained therein.
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`Thetarget amount ofactive, when itis a pharmaceutical, is referred to.as the “Label Claiin", thus
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`identifying the amount ofpharmaceutical active in the film to a user. The desired amountis
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`100% of the target amount. Each individual dosage unit film eut fromanyindividual lot must
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`have the desired content of pharmaceutical active, varying no morethat 10% fromthetarget or
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`desired amount. See Appendix B.
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`Th,
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`Theresults shown in theappendices establish that the resulting films producedby the inventive
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`method ofthe ‘O80 Patentas disclosed and claimed havetherequired uniformity of content based
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`on analytical chemical testing. First, the amount ofactive varies byno more than 10%between
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`individual dosage units sampled from.a particular lot ofresultingfilm. See Appendix A,
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`Second, the amount of active across different lots of resultingfilm varies no more than [10% from
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`the desired amount of the active. See Appendix B. Finally, the uniformityof content of the73
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`lots ofresulting film meets evenmorestringent standards, for example, the data shows: G) 46
`lots ofresultingfilm whereintheuniformity of content of active is shownwith the amount of
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`active varying by less than 5%; (1) 15 lots efresulting filmwherein the uniformity ofcontent of
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`active is shown with the amountofactive varying by less than 4%; 4 lots of resulting film
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`wherein the uniformity of content ofactive is shown with the amount of activevarying byless
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`amountof active varying by only 2%. See Appendix C.
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`Thereby declare thatall statements made herein of my ownknowledge are true and that
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`all statements made on informationand belief are believed tobe true; and further that these
`statements were made with the knowledge that willful false statements and the like so made are
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`punishable by fine or imprisonment, or both, under Section 1001 ofTitle 18 of the United States
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`Code, and. that such statements may jeopardize the validityof theapplication or any patents
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`pssued thereon.
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`Dated this 13th day afMarch, 2013
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`B.Arlie Bogue
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`(Max-Min)/LotSampleAverage
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`APPENDIX A
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`1
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`[=%differenceS810%]
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`5 88 61-64. 6F 70 73
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`APPENDIXB
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`108.0
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`7 # 13 16 49 22 26 28 34 S4 S7 AD 43 46 49 52 55 5B OT G4 OF 7O 73
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`LesfeatsbeFOR
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`total
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`(cid:9)
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`CERTIFICATE OF FIRST CLASS SERVICE
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`It is certified that a copy of this DECLARATION OF B. ARLIE BOGUE, PH.D.
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`UNDER37 C.F.R.§ 1.132 has been served, by first class mail, on March 13, 2013, in its
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`entirety on the third party requester as provided in 37 CFR § 1.903 and 37 CFR § 1.248 at the
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`addess below.
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`DANIELLE L. HERRITT
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`McCARTER & ENGLISH LLP
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`265 FRANKLIN STREET
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`BOSTON, MASSACHUSETTS 02110
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`/Daniel A. Scola, Jr./
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`Daniel A. Scola, Jr.
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`Registration No.: 29,855
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`Attorney for the Patentee
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`Page 9
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