IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Patentee:.
`Patent. No.:
`Reexamination
`Control No.:
`Filed:
`
`Yang et al.
`U.S. 7,897,080
`9%02,170
`
`September 10, 2012
`
`Diamond, Alan D.
`Examiner:
`Group Art Unit: 3991
`Confirmation
`6418
`No.
`H&B Docket:
`
`1199-26
`RCE/CON/REX.
`117744-00023
`
`Dated:
`
`March 13, 2013
`
`M&E Docket:
`
`Mail Stop Inter Partes Reexam
`Central Reexamination Unit
`Commissioner for Patents
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Certificate of EFS-Web Transmission
`I hereby cell* that this correspondence is being
`transmitted via the US. Patent and Trademark
`Office electronic filing.system (EFS-Web) to the
`USPTO on
`March 13, 2013.
`Signed; Michael Chakansky /Michael 1
`Chakanskyi
`
`DECLARATION OF B. ARLIE BOGUE, PH.D. UNDER 37 C.F.R. § 1.132
`
`, B. Arlie Bogue, Ph.D., do henthy make the following declaration:
`
`I. (cid:9)
`
`Technical Background
`
`I have worked in the field of pharmaceutical development, and particularly oral dosage form
`development, for 22 years. I am employed by MonoSol Rx, LLC. ('SPatentee" and/or
`"MonoSol"), the assignee of issued patent U.S. 7,897,080 ("the '080 Patent"), as Senior Director
`for Manufacturing Strategy and Innovation.
`
`2. I have a BS Physical Chemistry from Colorado State University and a Ph.D. in Chemical and
`BioEngineering from Arizona State University. I have participated in postdoctoral studies in:
`Biochemical Engineering at the University of Virginia. During my career, I have been named as
`au inventor on over 23 U.S. patents and numerous foreign patents directed to the formulation,
`
`Par Pharm., Inc., et al.
`Exhibit 1007
`Page 001
`
`

`

`processing and/or packaging of pharmaceutical oral disintegrating unit doses (tablets and film
`strips). I have direct experience with the commercial scale processing of pharmaceutical film
`systems as well as an understanding of the uniformity of content of active and methods for
`testing the same.
`
`3, I have read the 'NO Patent and the Office Action issued on November 29, 2012 in the reexamination
`of the '080 Patent ("Office Action") and the references cited therein,. and I have also reviewed the
`amendment as to the independent claims set fmth in Patentee's Reply to the Office Action
`concurrently filed herewith.
`
`Producing resulting films in accordance with the '080 Patent
`
`4. (cid:9) Each of the'73 lots of resulting films. (Lots 1-73) containing approximately 2,000,000 individual
`dosage units per lot discussed herein were. manufacture& (1) for commercial use and regulatory
`approval; (ii) in compliance with U.S Food and Drug Administration ("FDA") standards and,
`regulations, including those relating to analytical chemical testing for variation in active in individual
`dosage units; and (iii) in accordance with the invention disclosed in the '080 Patent, and as claimed
`by the '080 Patent both as issued and as amended in the Patentee's Reply to the Office Action; by:
`
`(a) forming a flowable polymer matrix comprising a water-soluble polymer, a solvent and a
`pharmaceutical active, said matrix having a. substantially uniform distribution of said active;
`
`(b) casting said flowable polymer matrix, said flowable poker matrix having a
`viscosity from about 400 to about 100,000 cps;
`
`(c) controlling drying through a process comprising conveying said polymer matrix
`through a drying apparatus and evaporating at least a portion of said solvent to form a visco-
`elastic film, having said active substantially uniformly distributed throughout, within about the
`first 4 minutes by rapidly increasing the viscosity of said polymer matrix upon initiation of
`drying to maintain said substantially tinifonn distribution of said active by locking-in or
`substantially preventing migration of said active within said visco-elastic film wherein the
`
`polymer matrix temperature is 100 °C or less;
`
`Par Pharm., Inc., et al.
`Exhibit 1007
`Page 002
`
`

`

`(d) forming the resulting pharmaceutical film from said visco-elastic film, wherein said
`resulting pharmaceutical film has .a water content of 10% or less and said substantially uniform
`distribution of active by said lacking-in or substantially preventing migration of said active is
`maintained, such that uniformity of content in the amount of the active in substantially equal
`sized individual dosage units, sampled from different locations of said resulting pharmaceutical
`film, varies by no more than 10%; and
`
`(e) performing analytical chemical tests for uniformity of content of said active in
`substantially equal sized individual dosage units of said sampled resulting pharmaceutical film,
`said tests indicating that uniformity of content in the amount of the active varies by no more than
`10%, [see Appendix Al said resulting pharmaceutical film suitable for commercial and
`regulatory approval, wherein said regulatory approval is provided by the U.S, Food and Drug
`Administration,
`
`5. Additionally, the uniformity of content in the amount of active as sampled from the 73 lots of
`resulting film varies no more than 10% from the desired amount of the active as indicated by
`said analytical chemical tests from 4(e) above. [See. Appendix 131
`
`III. (cid:9)
`
`Analytical. Chemical Testing for Unitbrmity of Content-of:Patentees Restiltinu Films
`
`6. To demonstrate the uniformity of individual dosage unit films, I compiled individual dosage unit
`assay data for individual Lots 1- 73, all of which were disclosed in ManoSol's 2012 Annual
`Product Review to the FDA.
`
`Ten (10) individual dosage units all having the same dimensions were cut out from different
`locations of each of the 73 lotsaresulting films using a commercial packaging machine, thus
`providing 730 randomly sampled individual dosage units, ten each from the 73 separate lots. All
`samples were analyzed by a validated method, in compliance with FDA guidelines and
`regulations regarding same, using analytical chemical testing, in which the pharmaceutical active
`
`Par Pharm., Inc., et al.
`Exhibit 1007
`Page 003
`
`

`

`was extracted and analyzed by High Performance Liquid. Cluomatography (HPLC) against an
`external standard to quantify the amount of active present in each individual dosage unit.
`
`8. According to the inventive process set forth and claimed in the '080 Patent, and in accordance
`with FDA nomenclature, I have prepared tables shown as Appendices A, B and C, reflecting the
`uniformity of content of active of individual dosage units within particular lots and across
`different lots,
`
`9. First, the uniformity of content of active in a lot is determined through establishing the amount of
`active (AN 0)) actually present in each sampled individual dosage unit from. the URIC lot (N) as
`determined by taking the difference between the amount of active in the sample with the most
`active (Maxicaxa)) minus the amount of active in the sample with the least amount of active
`(MinIDT(N)) and dividing the difference by the average amount of active in the lot samples (Lott
`
`Sample Average). That is: (Max
`-RN - MilltorK))/ (AN(1)+ ANA)+4+ AN00))/10). The mutts
`are shown in Appendix A.
`
`10. Second, the uniformity of content across different lots is determined through establishing the
`amount of active actually present in each sampled individual dosage unit from all 73 lots and
`comparing that amount of active with a "target" or "desired" amount of active contained therein.
`The target amount of active, when it is a pharmaceutical, is referred to as the "Label Claim", thus
`identifying the amount of pharmaceutical active in the film to a user. The desired amount is
`100% of the target amount Each individual dosage unit film cut from any individual lot must
`have the desired content of pharmaceutical active, varying no more that 10% from the target or
`desired amount. Set Appendix B.
`
`I (cid:9)
`
`'080 Patent Process Produces Films With Required Uniformity of Content of Active
`
`11. The results shown in the appendices establish that the resulting films produced by the inventive
`method of the '080 Patent as disclosed and claimed have the required uniformity of content based
`on analytical chemical testing. First, the amount of active varies by no more than JO% between
`individual dosage units sampled from :a particular lot of resulting film. See: Appendix A.
`
`Par Pharm., Inc., et al.
`Exhibit 1007
`Page 004
`
`

`

`Second, the amount of active across different lots of resulting film varies no more than 10% from
`the desired amount of the active. See. Appendix B. Finally, the uniformity`of content of the 73
`lots of resulting film meets even more stringent standards, for example, the data shows: 0) 46
`lots of resulting film wherein the uniformity of content of active is shown with the amount of
`active varying by less than 5%; (ii) 15 lots of resulting film wherein the uniformity of content of
`active is shown with the amount of active varying by less than 4%; 4 lots of resulting film
`wherein the uniformity of content of active is shown with the amount of active varying by less
`than 3%; and l lot of resulting film wherein the uniformity of content of active is shown with the
`amount of active varying by only 2%. See Appendix C.
`
`1 hereby declare that all statements made herein of my own knowledge are true and that
`all statements made on information and belief are believed to be true; and further that these:
`statements were made with the knowledge that willful false statements and the like so made are
`punishable by fine or imprisonment, or both, under Section 1001 of Title 18 of the United States
`Code, and. that such statements may jeopardize the validity of the application or any patents
`issued thereon.
`
`Dated this 13th day of March, 2013
`
`B. Arlie Rogue
`
`Par Pharm., Inc., et al.
`Exhibit 1007
`Page 005
`
`

`

`APPENDIX A
`
`10 13 It 19 22 25 (cid:9)
`
`31 34 37 40 49: 40. 49 5 SS 50 el 04 07 70 73
`Lot Number
`
`% difference40-11.
`
`Par Pharm., Inc., et al.
`Exhibit 1007
`Page 006
`
`

`

`APPENDIX B
`
`I 4
`
`Lot Number
`
`-4--max EtVen,.9.p. 7A1r1
`
`7
`
`Par Pharm., Inc., et al.
`Exhibit 1007
`Page 007
`
`

`

`APPENDIX C
`
`lots 5% to 10%
`% Difference
`Lot #
`10
`5.0%
`5.0%
`25
`5.0%
`39
`5.2%.
`41.
`5.2%
`13
`5.3%
`35
`5.4%
`5
`5.5%
`63
`5.5%
`34
`5.6%
`38
`5.6%
`40
`5.7%
`73
`5.8%
`5.9%
`6.2%
`6.3%
`6.3%
`6.7%
`6.7%
`6.7%
`7.1%
`7.4%
`7.8%
`8.2%.
`8,3%
`8.9%
`9.5%
`
`6
`11
`55
`69
`
`12
`7,0
`32
`49
`27
`64
`
`37
`
`Lots less than 5%
`% Difference
`Lot # (cid:9)
`2.0%
`24
`2.6%
`45
`2.8%
`17
`2.8%
`21
`3.1%
`22
`3.1%
`16
`3.2%
`60
`3.4%
`50
`3.4%
`72
`3.6%
`33
`3.6%
`43
`3.7%
`19
`3.8%
`46
`3.9%
`29
`3.9%
`2
`4.0%
`4.0%
`4.0%
`41%
`4.1%
`4.2%
`4.2%
`4.2%
`4.3%
`4.3%
`4.3%
`4.4%
`4.4%
`4.4%
`4.4%
`4.4%
`4.4%
`4.5%
`4.5%
`4.6%
`4.6%
`4.6%
`4.6%
`4.7%
`4.8%
`4.8%
`4.8%
`4.9%
`4.9%
`4.9%
`4.9%
`
`61
`30
`48
`15
`52
`54
`51
`44
`62
`56
`31
`28
`14
`68
`42
`18
`66
`47
`23
`20
`9
`58
`65
`26
`53
`36
`1
`59
`67
`71
`
`total
`
`4
`
`total
`
`27
`
`Par Pharm., Inc., et al.
`Exhibit 1007
`Page 008
`
`(cid:9)
`(cid:9)
`

`

`CERTIFICATE OF FIRST CLASS SERVICE
`
`It is certified that a copy of this DECLARATION OF B. ARLIE BOGUE, PH.D.
`
`UNDER 37 C.F.R. § 1.132 has been served, by first class mail, on March 13, 2013, in its
`
`entirety on the third party requester as provided in 37 CFR § 1.903 and 37 CFR § 1.248 at the
`
`addess below.
`
`DANIELLE L. HERRITT
`McCARTER & ENGLISH LLP
`265 FRANKLIN STREET
`BOSTON, MASSACHUSETTS 02110
`
`/Daniel A. Scola, Jr./
`Daniel A. Scola, Jr.
`Registration No.: 29,855
`Attorney for the Patentee
`
`Par Pharm., Inc., et al.
`Exhibit 1007
`Page 009
`
`