Application No. 14/515,857
`
`DocketNo.: 241957.000508
`(TRACK 1)
`
`Docket No.: 241957.000508
`(PATENT)(TRACK 1)
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Patent Application of:
`WiHiam H. McKenna et aL
`
`Application No.: 14i515,857
`
`Filed: October 16, 2014
`
`Customer No. 06980
`
`Confirmation No.: 6255
`
`Art Unit: 1613
`
`For; TAMPER RESIST ANT DOSAGE FORMS
`
`Examiner: AKHOON, Kauser M.
`
`DE CLARA. TION OF' RIClli\.RD 0. MANl"'ION UNDER 37 C.F.R. § 1.132
`
`1.
`I, Richard 0. Mannion, am a citizen of the United States and ram more than twenty-one
`(21) years of age.
`
`All statements made herein of my own knowledge are true, and all statements made herein
`2.
`on information and belief are believed to be true.
`
`Jam an employee and Executive Director ofPhannaceutical & Analytical Development at
`3.
`Purdue Ph anna L.P ., which is the assignee of this application. I am a co-inventor .ofthis patent
`application. l receive a salary, bonus and benefits from Purdue Pharma LP. ln my position at
`Purdue, my goals include initiating and supporting JP fil·ings.
`
`I make this declaration in support of the patentability of the above-identified patent
`4.
`application.
`
`Each pending claim of this application provides a dosage form (tablets) having at least (1)
`5.
`an opioid or a pharmaceutically acceptable salt thereof (such as bydrocodone bitartrate); (2) at
`least one lovv molecular weight polyethylene oxide having, based on rheological measurements,
`
`-1-
`
`KASHIV1036
`IPR of Patent No. 9,492,392
`
`

`

`Application No. 14/515,857
`
`Docket No.: 24!957.000508
`(Tiv\CK 1)
`
`an approximate molecular weight of less than 1,000,000 (sqch as a PEO having a molecular
`weight of 600,000); and (3) at least one high molecular weight polyethylene oxide having, based
`on rheological measurements, an approximate molecular weight of 7,000,000. Each such tablet is
`a cured tablet, and is cured at a temperature from about 60 to about 90 oc for about 15 minutes to
`about 10 hours. Each cured tablet has at least 79% by weight, based upon the total weight of said
`composition, ofthe total combined weight ofthe high and low molecular weight polyethylene
`oxides. The experiment described below \Vas conducted using tablets having these features.
`Consequently, the samples in the experiment are tablets of the invention clain:1ed in this
`application.
`
`The density of uncured and cured hydrocodone tablets was determined under my direction.
`6.
`These tablets contained hydrocodone salt; low molecular w·eight polyethylene oxide ("PEO")
`having, based on rheological measurements, an average molecular weight of 600;000; and high
`molecular weight PEO having, based on rheological measurements, an average molecular weight
`of 7 ,000~000. The tablets contained either 20 mg or 120 mg ofhydrocodone bitartrate.
`
`The 20 mg tablets contained 40% by weight, based upon total weight of the tablet absent
`7.
`cosmetic coating, of the low molecular weight PEO and 56~·'0 by weight, based upon total weight
`of the tablet absent cosmetic coating, of the high molecular weight PEO, which means that the 20
`mg tablets contained 96% total combined weight, based upon total \veight of the tablet absent
`cosmetic coating, of high and low molecular weight PEO.
`
`The J 20 mg tablets contained 27% by vveight, based upon total weight of the tablet absent
`8.
`cosmetic coating, of the low molecular weight PEO and 53% by weight, based upon total weight
`of the tablet absent cosmetic coating, ofthe high molecular weight PEO, which means that the
`120 mg tablets contained 80% total combined weight, based upon total weight of the tablet absent
`cosmetic coating, of high and low molecular weight PEO.
`
`The density ofthe tablets w-as determined by Archimedes' principle using hexane, a liquid
`9.
`of known density. The tablet was first weighed in air, and then was immersed in hexane and
`weighed. From these two weights, the density of the tablet p was determined as follows:
`
`-2-
`
`KASHIV1036
`IPR of Patent No. 9,492,392
`
`

`

`Application No. 14/515,857
`
`Docket No.: 241957.000508
`(IRACK 1)
`
`A
`p=--·po
`A·--·11
`
`P:
`A:
`B:
`p0:
`
`Density of the tablet
`Weight of the tablet in air
`Weight of the tablet when immersed in the liquid
`Density ofthe liquid at a given temperature.
`
`The equipment used was a Top-loading Mettler Toledo balance Model # AE50/M87731
`l 0.
`Serial #30000832, a glass beaker, and a thetmorneter.
`
`The materials used were (a) hexane (the density of Hexane at 20°C ''" 0.660 g/ml); (b)
`1 L
`uncured 20 mg hydrocodone bitartrate tablets as described above (Batch No. XWSF90); (c)
`uncured 120 rng hydrocodone bitartrate tablets as described above (Batch No. XWSGOO); and (d)
`cured and cosmetically coated 20 rng and 120 mg tablets (Lot Nos. 2141-001, 2141-006, 2141-
`011, 2141-0 16; 2141-021, 2141-026, 2141-031, 2141-036).
`
`12.
`
`The procedure used was as follows:
`a.
`Set up Mettler Toledo balance with Mettler Density Determination Kit No. 33360.
`b.
`Fill an appropriate sized beaker with hexane.
`c.
`Weigh the tablet in air andrecord the weight as Weight A.
`d.
`Transfer the same tablet onto the lower coil within the beaker filled with hexane.
`e.
`Determine the weight ofthe tablet in liquid and record the vveight as Weight H.
`f
`Perform the density calculation as above and record the density.
`
`Three tabiets of each type were measured thr density. The average of each set of three
`13.
`tablets is reported in the Tables below.
`
`Table 1. Density ofHYD 20mg Tablet Before and After Curing at 70°Cil5min
`!}'(! Density Change After
`Uncured Tablet Density
`Cured and Coated Tablet
`Curino-b
`_____ Q~I1~~i~~_(g£~m3)
`~f£~~~13.)
`---
`1.158
`1.073
`-7.4
`
`~~~~--·
`
`KASHIV1036
`IPR of Patent No. 9,492,392
`
`

`

`Application No. 14/515,857
`
`Docket No.: 24!957.000508
`(TI0\CK 1)
`
`Table 2. Density ofHYD 20mg Tab1et Before and After Curing at 70°C/45min.
`
`u~:~~ti~e~i~~~~~~;-r>~~;sity ________ ------cli~~~~~~~~~~~~~~1~;.-i1i~i:-----r-----o;~--ne_P:_~i--~-~l_S_-~_,~"-~g---~----A_----_:r_i~_-i:·_---""'---
`L
`
`-6.2
`l.1ss
`1.087
`-·····-·········-·--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
`
`Table 3. Density ofHYD 20mg Tablet Before and After Curing at 78°C/15min
`, ......................................................................... , ......................................................................... , ......................................................................... 1
`! Uncured Tablet Density
`! % Density Change Atler
`! Cured and Coated Tablet
`!
`i
`I
`Density (g/cm3)
`!
`(g/cm3)
`Curing -
`1.1ss
`1.089
`-6.o
`1
`1
`!. .................................................................................................................................... ______________ -----------------------------------------------------------------------J
`
`Table 4. Density ofHYD 20mg Tablet Bethre and After Curing at 78°C/45min
`~ nc-ii'r~ct--1~~-b'i~t'-15~;-;Tty ____ ---··c;-~:~·d";.·;-cTc;~~tici--f~b'i~t------· ----·--%;·15'~~sity-·c:·h·~;ge -i\'ti:~~--
`Density (g/cm3)
`(g!cm3)
`Curing
`L 158
`1.089
`-6.0
`
`Table 5. Density of HYD 120mg Tablet Be.tore and After Curing at 70°C/15min
`I Cured and Coated Tablet
`l
`- Uncureti Tablet Density
`l% Density Change A.fter
`I
`I
`I
`3
`1
`:
`(g/cm·)
`:
`Density (g/cm )
`Curing
`r-----------------------------------:----------------------------r---------------------------------------------------------------,--------------------------------------------------------------:
`I
`I
`I
`1.100
`1.177
`-6,5
`------------~~------------
`--~
`
`1 1'
`
`
`
`'
`
`'I
`
`r-
`
`Table 6. Density ofHYD 120mg Tablet Before and After Curing at 70°C/45m1n
`! Uncured Tablet Density
`Cured and Coated Tablet
`%Density Change After
`I
`(g/cm3
`Density (g/cm3
`Curing
`)
`)
`J
`1------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------:--------------------------------·-,
`1.177
`Lll2
`-5.5
`!
`i
`
`!
`
`!
`!
`
`Table 7. Density ofHYD 120mg Tablet Before and After Curing at 78°Cil5min
`Uncured Tablet Density
`Cured and Coated Tablet
`%Density Change After
`___________________________ (WS!!!~L ......................... ________________ Q_~~~-!,~ __ (g{~!!~-~-L.............. -----·····-··------------~:Y!!.~K .............. __________ _
`1.177
`Ll 02
`-6.4
`
`Table 8. Density ofHYD 120mg Tablet Before and After Curing at 78°C/4-5min
`~--'0 Density Change After
`Uncured Tablet Density
`Cured and Coated Tablet
`(g/cm3
`Density (g/cm3)
`C~u~ing
`)
`···---------------
`-5A
`1.177
`1.113
`----------------------
`
`i
`I
`
`-4-
`
`KASHIV1036
`IPR of Patent No. 9,492,392
`
`

`

`ApplicationNo. 14/515,857
`
`Docket No.: 241957.000508
`(TRACK 1)
`
`The densities ofail ofthe cured tablets were 1owerthan the densities ofthe corresponding
`14.
`uncured tablets.
`
`I have been warned and acknowledge that \ViHful false statements and the like made by me are
`punishable by fine or imprisonment, or both ~- U.S.C. 1 001) and may jeopardize the validity of
`the above-identified application or any patent issuing thereon.
`
`I declare under penalty of perjury under the laws of the United States of America thatthe
`foregoing is true and correct.
`
`Executed on March 27,2015.
`
`Richard 0. Mannion
`
`-5-
`
`KASHIV1036
`IPR of Patent No. 9,492,392
`
`