deposition
`EXHIBIT O
`
`J-2-2-/7
`
`W 757iaC0
`
`IMDACP.IMDTKgOMr'iaiaSSC! BBESEPgiSt «CTATflt.<a9M<B!;t
`
`UNITED STATES DEPARTMENT OF COMMERCE
`
`United States Patent and Trademark Office
`
`February 25,2016
`
`THIS IS TO CERTIFY THAT ANNEXED IS A TRUE COPY FROM THE
`
`RECORDS OF THIS OFFICE OF THE FILE WRAPPER AND CONTENTS
`
`OF:
`
`APPUCATION NUMBER: 09/549,205
`FILING DATE: April 13,2000
`PATENT NUMBER: 6,649,180
`
`ISSUE DATE: November IS, 2003
`
`By Authority of the
`Under Secretary of Commerce for fatellectual Property
`and Director of the United Siates^atent and Tcademark OfGce
`
`SYDVIA HOLLEV
`ing Oflicer
`
`WCDELZ 00029766
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 - 1/232
`
`

`

`PATCNI^UMBER
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`SUBCLAni^2| AnTUNIT
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`Seirldsiike' Platsuura
`Masaru Tahjoh
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`C«> j-'/'t-
`
`Cellulose Ether Film
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`WCDELZ_00029767
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`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 - 2/232
`
`

`

`Q}«:///e:/APPS/{>fe«xain/corr«pon(lencc/ (.
`
`aa> Data Sheet
`
`UNrrED STATES DEPARTMENT OF COMMERCE
`Patent and Trademark Oflicc
`
`Addran: C0MM1SSK)NBR OF PATENTS AKDTRADEXURKS
`W«in^0.C.2QD1
`
`^
`
`SERIAL NUMBER
`09/549^5
`
`FILING DATE
`
`04/13/2000
`
`RULE
`
`c^s
`
`GROUP ART UNIT
`
`1615
`
`ATTORNEY
`DOCKET NO.
`
`0171-0675P
`
`APPUCANTS
`Sebiosuke Matsuura, Kyoto, J/VPAN;^
`Masaru Tanjoh, Nara-ken, JAPAN;/
`
`"CONTINUING DATA* ^ ^
`
`JAPAN 11-106689 04/14/l999
`
`V/"
`
`IF REQUIRED, FORBGN/IUNG UCENSE GRANTED
`•* 07/D5/2000
`
`Foreign Prioifty ctalmed
`
`35 use 119 (a-d) ccndilions
`met
`
`Byes^no
`B yoB Q no Q M«( after
`
`llowanca
`
`i/arlRedand
`
`ADDRESS
`
`tnihsls
`
`Birch Stewart Kolasch & BIriJi LLP
`
`PO Box 747
`122040-0747
`Falls Church .VA 22040-0747
`TITLE
`(L
`
`SeHtttesa Ethar Film-
`
`STATE OR
`COUNTRY
`JAPAN
`
`SHEETS
`DRAWING
`
`-
`
`TOTAL INDEPENDENT
`CLAIMS
`CLAIMS
`8
`1
`
`/
`
`FEES: Authority has been given in F er
`FILING FEE
`, to charge/credit 01
`SIT ACCOUNT
`RECEIVED No
`, for following; /
`No.
`690
`/
`
`I Fees
`□ 1.16 Fees (Flllno)
`Q 1.17 Fees {Processing ExL of
`dme)
`D 1.16 Fees (Issue)
`Q Other
`B Credit
`
`l/SflK) 10;2SAM
`
`WCDELZ 00029768
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 - 3/232
`
`

`

`PATENT APPUCATION SERIAL NO.
`
`U.S. DEPARTMENT OF COMMERCE
`PATENT AND TRADEMARK OFHCE
`FEE RECORD SHEET
`
`!S/2000 PMIEN 0MC0019 09549S0S
`
`•CslOl
`
`690.00 OP
`
`PTO-1556
`(5/87)
`
`'U3 CPO: iga9.<Sft«<U(l»IM
`
`WCDELZ_00029769
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 - 4/232
`
`

`

`;n
`
`BiRa
`
`KRREUC.8ffiCH
`|C flAYMONOC.$TlWWIir
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`S^'UCHAELIC MUTTER
`I 2 CKARLES CORENSTEOi
`s o GERALD M.MURfHV. JR.
`' leOHAROASVENSGON
`TERRY LCURK
`ANOREWaMERae
`UAftCAMEDIER
`JOEMCKMKEVMIPICY
`R0SERT4.IMfeY
`CONALOJ.DAL£Y
`JOHNWaAILEY
`JOKNACASrmAKO. 01
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`•MJMTTCO TO A OM OTHCR THAN VA,
`
`.EWART, KOLASCH & BiRi
`INTELLECTUAL PROPERTY UW
`8110 Qatehouss Road
`Suite 500 East
`Falls Church, va 22042-1210
`USA
`(703) 20S4000
`
`tLP
`
`FAX:{nn)20$-si)S0
`<703)6«»«Sa0(0IV)
`
`e-<naa; manroom^bsUxoom
`wQb: http'i^vwM.bAMi.cofli
`
`CAllPORNtA OrPTCS:
`COVTAMUA. CAUrOltNM
`
`TNCMA9 & AUCHTERLOMS-
`MICNAB.R. CMCMARATA
`JAMES T.ELLER. JR.
`SCOTTLUmS ' 1/1
`UA»(AMJEU.PN.O.o(
`OARM 6. BARTHOlOftT ~
`0. RICHARD AN0ERS9
`PAULCLCMS
`W.KARLHENKCR
`MARKW Ma.STeAD? •
`JOHHCAMRA*
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`REaPATCNTA _
`nUDfiR9CRR.HAN0T
`AHOREWATELCSLJ
`MARYANNE ARMSTROHb. I
`MAKlHATSUMr
`MUQES. RYU
`CRAlOiLMcROBBie
`GAICm U. DAKLEN. Pita
`LAURA C.LUTZ
`H086HTC. COOBNER. PNO.
`imM6N.80HN
`MATTKeV»J,iATTIG
`AUN PeOERSEN^Iies
`JUSTMD.KAIUALA
`C KEITH KONTOOUERY
`
`Date: April 13. 2QQ0
`Docket No. : 0171-Q675P
`
`AssiBtant ContmisBioner for Patents
`Box PATENT APPLICATION
`Washington, D.C. 20231
`
`□t
`
`S
`
`•P
`
`P Transmitted herewith for filing is the patent appJ.ication of
`II
`Inventor(s) : MATSUURA, Seinosuke
`Q
` TANJOH, Maseru
`.S
`
`For;
`
`CELLULOSE ETHER FILM
`
`Enclosed are:
`
`\/jL.
`
`_2S_
`v6l.
`\A-
`\/jL.
`
`Jy
`
` X
`
`A specification consisting of
`
`pages
`
`sheet(s) of
`
`drawings
`
`An assignment of the invention
`
`Certified copy of Priority Document(s)
`
`Executed Declaration
`
`Photocopy
`A verified statement to establish small entity status under 37
`CFR 1.9 and 37 CFR 1.27
`
`X Original
`
`Preliminary Amendment
`
`Information Disclosure Statement. PTO-1449 and reference(s)
`
`MailADOKCSS: P.O. 80X747, Falls CHURCH, VIROINIA, USA 23040-0747
`
`WCDELZ 00029770
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 - 5/232
`
`

`

`Other
`
`The filing fee has been calculated, as shown below:
`
`0171-0675P
`
`LARGE ENTITT
`
`SMALL ENTITY
`
`FOR
`
`NO. PILED
`
`NO. EXTRA
`
`RATE
`
`FEE
`
`RATE
`
`FEE
`
`BASIC FEE
`
`TOTAL
`CLAIMS
`
`8 - 20 =
`
`INDEPENDENT
`
`1 -
`
`3 =
`
`MULTIPLE DEPENDENT
`CLAIM PRESENTED
`
`_
`
`0
`
`0
`
`or
`
`$345.00
`
`Xl8 =$
`
`0.00 or X
`
` 9 = $
`
`0.00
`
`x78 =$
`
`0.00 or X 39 = $
`
`0.00
`
`+260 = $
`
` 0.00 or +130 - $
`
`0.00
`
`TOTAL $ 690.00
`
`TOTAL $
`
`0.00
`
`to cover the filing fee and
`A check in the amount of S 730.00
`recording fee (if applicable) is enclosed.
`
`Please charge Deposit Account No. 02-244B in the amount of
`$
` . A triplicate copy of this transmittal form is
`enclosed.
`
`No fee is enclosed.
`
`If necessary, the Commissioner is hereby authorized in this,
`concurrent, and future replies, to charge payment or credit any
`overpayment to Deposit Accoimt No. 02-2448 for any additional
`fees required under 37 C.F.R. 1.16 or under 37 C.F.R. 1.17;
`particularly, extension of time fees.
`
`Respectfully submitted,
`
`BIRCH, STEWART, KOLASCH & BIRCH, LLP
`
`□ i
`
`/5
`
`'3
`lU
`
`•P.
`
`"'ii
`□
`
`(703) 205-8000
`GMM/cw
`
`HY, JR.
`
`Falls Chtfrch, Virginia 22040-0747
`
`WCDELZ 00029771
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 - 6/232
`
`

`

`TITLE OF THE INVENTION
`
`Cellulose Ether Film
`
`This invention relates to a cellulose ether film
`
`suited for use in forming pharmaceutical and food hard
`
`capsules.
`
`10
`
`BACKGROUND OF THE INVENTION
`Hard capsules are commonly used in the pharmaceutical
`and health food fields. Of the hard capsules, gelatin
`
`capsules are most widely used. They are formed from a film
`15 of a composition comprising gelatin as a base, a plasticizer
`
`LI
`•P
`lU
`G
`
`□
`
`(e.g., glycerin or sorbitol}, opacifying agent, dye.
`pigment, and other addenda. Typically, gelatin capsules are
`manufactured by dipping pins in an aqueous gelatin solution
` having the above components blended, drawing out the pins
`20 with the acpieous gelatin solution adhering to the pins, and
` drying the gelatin coats.
`Flexibility and other properties of gelatin-based film
`Kjjj
`largely depend on the water content of the film. A film
` with a low water content is too low in Impact resistance to
`Q
`□ 25 withstand the shocks encountered upon filling of medicament.
`Also, as the water content decreases by drying during
`storage, the film contracts to undesirably loosen the oap-
`to-body engagement. To prevent such inconvenience, gelatin
`capsules must be kept at an optimum water content of about
`13 to 15% by weight. Because of the necessity to have such
`a relatively high water content, it is restricted to apply
`the gelatin capsules to those medicaments which give rise to
`a problem upon contact with water. When the gelatin
`capsules contain a hygroscopic fill, the capsules gradually
`lose the water content and hence, the strength, inviting the
`risk of failure.
`
`30
`
`35
`
`WCDELZ_00029772
`
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`
`

`

`-2-
`
`5
`
`Under the circumstances, studies have been made on the
`capsules which can avoid the problems associated with water
`contents and which are applicable to any type of fill. One
`exemplary substitute for the gelatin capsules Is capsules
` whose film Is formed of a cellulose ether composition
`comprising a water-soluble cellulose ether as a base In
`which some of the hydrogen atoms of celluloslc hydroxyl
`groups are replaced by alkyl and hydroxyalkyl groups or
`hydroxyalkyl groups, a gelling agent, and a gelling aid, as
`10 disclosed in Japanese Patent Ho. 2,552,937. Some capsules
`based on hydroxypropyl methyl cellulose (HPMC) have been
`used in practice. These capsules of cellulose ether film
`maintain a sufficient strength even at a low water content,
`and their behaviors such as dissolution are equivalent to
` 15 those of conventional gelatin capsules. Additionally, they
`can be manufactured by the so-called dipping method as are
`conventional gelatin capsules.
`However, the capsules of cellulose ether film suffer
`from the problem that the gelling aid which Is blended for
`20 assisting in film formation will precipitate out on the film
`surface during long-term storage.
` More particularly, in one appropriate formulation of
`the cellulose ether film for forming capsules, carrageenan
`is used as a gelling agent for HPMC, and a potassium or
`25 calcium Ion Is Incorporated as a gelling aid In the form of
`
`a water-soluble compound such as potassium chloride or
`calcium chloride. During long-term storage of these
`
`cellulose ether film capsules, the water content of the film
`can be lowered owing to the storage environment or the water
`30 absorption of the fill. Then the potassium or calcium Ion
`as the gelling aid will re-form potassium chloride or
`
`calcium chloride which precipitates out on the film surface.
`The precipitates of the gelling aid give rise to no
`problem to the practical usage, but are unpleasant to look
`35 at. Especially In the case of colorless cle2u; film, the
`precipitates develop as cloud and sometimes, cloud spots
`
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`
`

`

`-3-
`
`ratber tban uniform cloud, exacerbating the outer appearance
`
`of capsules noticeably.
`
`SUMMARY OP THE INVENTION
`
`s
`
` An object of the Invention Is to provide a novel and
`
`Improved cellulose ether film of a composition comprising a
`
`cellulose.ether as a base, a gelling agent, and a gelling
`aid, which prevents the gelling aid from precipitating out
`
`and maintains a favorable outer appearance diirlng long-term
`
`10 storage.
`It has been found that when a film, typically a
`
`capsule film Is formed of a composition comprising a
`
`cellulose ether as a base in which some of the hydrogen
`
`atoms of celluloslc hydroxyl groups are replaced by allcyl
`
`IS groups and/or hydroxyalkyl groups, a gelling agent, and a
`gelling aid, the use of the cellulose ether having an
`
`alkoxyl and hydroxyalkoxyl content of up to 37.6% by weight
`
`Is effective for preventing precipitation of the gelling
`
`aid, thereby maintaining a favorable outer appearance even
` 20 after long-term storage.
`Accordingly, the Invention provides a cellulose ether
`film formed of a composition comprising a cellulose ether as
`a base In which some of the hydrogen atoms of celluloslc
`hydroxyl groups are replaced by alkyl groups and/or
`25 hydroxyalkyl groups, a gelling agent, and a gelling aid,
`wherein the total content of alkoxyl and hydroxyalkoxyl
`groups In the cellulose ether Is up to 37.6% by weight.
`Although the reason why precipitation of the gelling
`aid can be restrained by limiting the total content of
`30 alkoxyl and hydroxyalkoxyl groups in the cellulose ether to
`37.6% by weight or lower Is not well understood, the
`following mechanism Is Inferred.
`In the cellulose ether
`used as the film base, some of the hydrogen atoms of
`celluloslc hydroxyl groups are replaced by alkyl groups
`35 and/or hydroxyalkyl groups whereby the hydroxyl groups are
`converted Into alkoxyl or hydroxyalkoxyl groups. By
`limiting the total content of alkoxyl and hydroxyalkoxyl
`
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`QUALICAPS EX. 2066 - 9/232
`
`

`

`-4-
`
`groups to 3 7•6 % by weight or lower, the proportion of
`(remaining) hydroxyl groups having high affinity to water
`becomes relatively high so that the water-holding force of
`the film is effectively improved. This ensures that
` potassium or calcium as the gelling aid is retained in ion
`form within the water held in the film, effectively
`restraining precipitation of the gelling aid.
`
`5
`
`to
`
`Briefly stated, the cellulose ether film of the
`
`DESCRIPTION OF THE PREFERRED EMBODIMENT
`
`invention is manufactured by using a cellulose ether as a
`base, blending a -gelling agent and a gelling aid therein,
`and forming the composition into a film.
`
`The cellulose ether used as the base is one in which
` IS some of the hydrogen atoms of cellulosic hydroxyl groups are
`replaced by alkyl groups and/or. hydroxyalkyl groups whereby
`alkoxyl and/or hydroxyalkoxyl groups are created.
`Though not critical, the cellulose ether is preferably
`one. in which some of the hydrogen atoms of cellulosic
` 20 hydroxyl groups are replaced by alkyl groups and
` hydroxyalkyl groups or by only hydroxyalkoxyl groups. Of
`the alkyl groups, methyl is preferred. Of the hydroxyalkyl
` groups, hydroxypropyl or hydroxyethyl is preferred.
` Illustrative examples of the cellulose ether substituted
`25 with these groups include hydroxypropyl methyl cellulose
`(HFHC), hydroxypropyl cellulose (HPC), hydroxyethyl methyl
`
`cellulose (HEMC), and methyl cellulose (MC). Of these. HPHC
`
`is best suited for capsule film application because of
`
`effective film formation and mechanical strength at low
`
`30 water contents.
`
`According to the invention, the total content of
`alkoxyl and hydroxyalkoxyl groups created in the cellulose
`
`ether by introducing the above substituents is limited to
`37.6% by weight or lower. More particularly, the total
`
`35 content corresponds to the total content of methoxyl groups
`(abbreviated as "MO groups") and hydroxypropoxyl groups
`(abbreviated as "HPO groups") in -the case of HPMC, the
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`QUALICAPS EX. 2066 -10/232
`
`

`

`-5-
`
`5
`
`10
`
`content of HPO groups in the case of HPC, the total content
`of MO groups and hydroxyethoxyl groups in the case of HEMC.
`and the content of MO groups in the ease of MC. A cellulose
`ether having a total content of such substituents of up to
` 37.6% by weight is used.
`The lower the total content of alkoxyl and
`hydroxyalkoxyl groups, the better becomes the effect of
`preventing precipitation of the gelling aid. However, if
`the totcJ. content of alkoxyl and hydroxyalkoxyl■groups is
`too low. the resulting film may lose flexibility, strength
`or other performance, which is inconvenient in some
`applications. Therefore, the total content of alkoxyl and
`hydroxyalkoxyl groups is preferably in the range of 23 to
` 37.6% by weight though not limited thereto. Especially when
`the film is used as capsule shells, the total content of
`alkoxyl and hydroxyalkoxyl groups is preferably in the range
` of 29 to 37% by weight for finding a good compromise between
`the film.strength and the effect of preventing precipitation
`of the gelling aid.
`Of the above-described cellulose ethers, HPMC, HPC,
` and MC are specified in the Pharmacopoeia of Japan.
`In the
`capsule shell application, it is recommended to use the
`pharmacopoeia-specified products.
` For HPMC, the Pharmacopoeia specifies three types,
`25 hydroxypropyl methyl cellulose 220*8, hydroxypropyl methyl
`cellulose 2906, and hydroxypropyl methyl cellulose 2910,
`depending on the contents of MO and HPO groups. It is
`specified that hydroxypropyl methyl cellulose 2208 contains
`19 to 24 wt% of MO groups and 4 to 12 wt% of HPO groups in a
`total of 23 to 36 wt%j hydroxypropyl methyl cellulose 2906
`contains 27 to 30 wt% of MO groups and 4 to 7.5 wt% of HPO
`groups in a total of 31 to 37.5 wt%, smd hydroxypropyl
`methyl cellulose 2910 contains 28 to 30 wt% of HO groups and
`7 to 12 wt% of HPO groups in a total of 35 to 42 wt%. Any
`35 of these celluloses may be used in the practice of the
`Invention as long as the total content of MO and HPO groups
`is up to 37.6 wt%. Also acceptable are mixtures in which
`
`15
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` 20
`
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`QUALICAPS EX. 2066 - 11/232
`
`

`

`-6-
`
`5
`
`any two or more of these celluloses eire mixed to adjust the
`total content of HO and HPO groups to that range.
`It Is noted that the contents of alkoxyl and
`hydroxyalkoxyl groups In cellulose ether can be determined
` by the measurement method described In the Pharmacopoeia for
`the HPMC, HFC and MC Specified therein, eurid by a well-known
`method for the remaining cellulose ethers.
`The gelling agent used may be selected from among, for
`,example, carrageenan, tamarind seed polysaccharlde, pectin,
`10 curdlan, furcellaran, gellan gum, and mixtures thereof. Of
`these, carrageenem Is especially preferred because It has a
`high gel strength and exhibits good gelling properties in
`the co-presence of a specific ion so that It may achieve
` effective gelation even when added in small amounts. Hhile
`15 there are known three types: kappa-carrageenan or tota
`carrageenan and lambda-carrageenan, the invention recommends
`to use kappa-carrageenan and/or lota-carrageenan. which have
`a good gelation ability.
`The amount of the gelling agent used Is not critical
`20 and may be suitably determined in accordance with the type
`of cellulose ether and gelling agent, the Intended
`application of film, and film forming method. Wien capsule
` shells are formed by the well-known dipping method, for
`example, it is recommended to use about 0.05 to 25 parts,
`2S and.especially about 0.25 to 15 parts by weight of the
`gelling agent per 100 parts by weight of the cellulose ether.
`Less than 0.05 part of the gelling agent may achieve a lower
`degree of gelation and fall to produce a film of a
`sufficient thickness to enable shell formation by- the
`30 dipping method. More than 25 parts of the gelling agent may
`achieve a too high degree of gelation and provide a dipping
`solution with a viscosity higher than necessity, making it
`
`difficult to form a uniform coat or film.
`As the gelling aid used herein, any substance that can
`35 promote gelation by the gelling agent may be employed.
`
`Depending on the type of the gelling agent, the gelling aid
`
`may be selected from a potassium Ion, calcium Ion, ammonium
`
`p
`tfl
`ls
`iQ
`ItJ
`
`P
`
`W
`
`WCDELZ_00029777
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 -12/232
`
`

`

`-7-
`
`ion, euid various organic compounds which can promote
`gelation by the gelling agent. Especially when capsule
`shells are formed using carrageenan as the gelling agent, a
`potassium ion or calcium ion or both are preferably used.
` The potassium ion may be blended in the form of its water-
`soluble compound such as potassium chloride, potassium
`phosphate or potassium citrate. The calcium ion may be
`blended in the form of its water-soluble compound such as
`
`5
`
`calcium chloride.
`
`10
`
`ly
`
`Like the gelling agent, the amoimt of the gelling aid
`used is not critical and may be suitably determined in
`accordance with the type of cellulose ether and gelling
`agent, the intended application of film, and film forming
`method. When capsule shells are formed by the well-known
`^ 15 dipping method, for example, it is recommended to use about
`0.05 to 25 parts, and especially about 0.25 to 15 parts by
`weight, calculated as ion, of the gelling aid per 100 parts
`by weight of the cellulose ether. Less than 0.05 peirt of
`the gelling aid may promote gelation of the gelling agent to
`20 a less extent and fall to produce a film of a sufficient
` thickness to enable shell formation by the dipping method.
`More than 25 parts of the gelling aid may form a gel in a
`
`D I
`
`Jt
`
`9
`
`W
`(3
`
` dipping solution for rendering It difficult to form a film,
`and in addition, adversely affect the disintegration (I.e.,
`25 dissolution after administration) of the resulting film,
`
`which Is Inconvenient as the capsule shells.
`
`While the cellulose ether film of the invention
`
`contains the cellulose ether as the base, the gelling agent
`and the gelling aid, there may be added appropriate amounts
`30 of various additives including coloring agents such as dyes
`
`and pigments, opacifying agents, and perfumes.
`
`The cellulose ether film can be manufactured by any
`well-known method depending on its application. When hard
`
`capsules are formed from the cellulose ether film of the
`
`35 invention, for example, the film can be prepared in the form
`
`of capsule shells by a well-known dipping method as in the
`
`manufacture of conventional gelatin capsules. In one
`
`WCDELZ 00029778
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 - 13/232
`
`

`

`5
`
`exemplary process, the cellulose ether, gelling agent,
`gelling aid and optional additives are dissolved in water in
`appropriate amounts as mentioned above to form a dipping
`solution, capsule-forming pins are dipped in the dipping
` solution", then drawn out of the solution. The solution
`adhering to the outside surface of the pins is dried to form
`capsule shells (caps or bodies) on the outside surface of
`the pins whereupon the shells are removed from the pins, in
`this way, the cellulose ether film of the invention is
`10 obtained in the form of capsule shells. The shells are then
`cut to a predetermined size £ind mated to construct hard
`capsules of the cellulose ether film according to the
`invention.
`
` ^ mentioned above, the dipping solution is an aqueous
`IS solution having predetermined amounts of the cellulose ether,
` gelling agent, gelling aid and optional additives blended
`therein. This aqueous solution is preferably prepared to a
` concentration of 15 to 30ft by weight, and especially 18 to
`weight of the cellulose ether. Less t-han 15s by
` 20 weight of the cellulose ether may fall to form a film of a
` sufficient thickness to serve as capsule shells whereas more
` than 30% by weight of the cellulose ether may provide the
` dipping solution with too high a viscosity to form a uniform
` film. The remaining conditions may be the same as those
`customarily used in the manufacture of cellulose ether-based
`capsules.
`The cellulose ether film of the invention is suitable
`as the shell of hard capsules for use in the pharmaceutical
`and health food fields although the application is not
`limited thereto. The film may find use in applications
`other than hard capsules.
`
`25
`
`30
`
`□
`p
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`B
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`p
`
`35
`
`EXAMPLE
`Examples of the invention are given below by way of
`illustration and not by way of limitation.
`*'Jlvni i
`i ifY|iMi|;ni| Iiii' ll^yl 1 ellulose^ 2919 specified in the
`Pharmacopoeia of Japan f'MetoioaA hOMH" h-yewx,.-p|.p..
`
`■'/
`
`WCDELZ_00029779
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 -14/232
`
`

`

`-9-
`
`clremi^^Co,, Ltd.) and hydroxypropyl methyl cellulose 2208
`("Metolos§"Si()SH^" by Shln-Etsu Chemical Co., Ltd.) were mixed
`in the proportioh-^s^ovm in Table 1. Using this
`hydroxypropyl methyl o&Hn^se, a dipping solution of the
`composition shovm below was pt^ep^red. By a conventional
`dipping method, size No. 2 hard cap&ul^ of colorless cleeu:
`hydroxypropyl methyl cellulose film of afibut^OO microns
`thick were prepared therefrom.
`
`^e contents of methoxyl and hydroxypropoxyl
`groups in hydroxypr^yTTnothxl^elluloso 2919 (Metolose
`60SH) and hydroxypropyl methyl^elBiis5ft_^08 (Metolose
`90SH} ware determined by the measurement metBbct~Q^^cribed
`in the Pharmacopoeia of Japeui, with the results sbovm'*beJU2>7.
`
`29IQ fOOSH)
`-OCH,! 28.8%, -OC3H4OH! 9.3%, totals 38.1%
`
`aaoH fgoRH^
`
`-OCHj: 23.5%. -OC^OH: 5.9%, totals 29.4%
`Dipping solsitinn comnoBition
`
`Hydroxypropyl methyl cellulose
`
`K^carrageenein (gelling agent)
`
`Potassium chloride (gelling aid)
`
`20 wt%
`
`O.I wt%
`
`0.1 wt%
`
`Water
`
`(0.052 wt % of K')
`
`balance
`
`The capsules thus obtained were contained in a glass
`
`25
`
`bottle and stored at 40°C for one month. The capsule suirface
`
`was visually observed to inspect precipitates of potassium
`
`chloride thereon. The results are shown in Table 1.
`
`Vn
`
`tfl "
`
`m •
`
`p
`>0
`\v
`15~
`
`f w 1
`
`2.
`a
`
`A\A
`
`\
`
`A"
`
`CsUalose
`mlsctore o£
`291012206
`(weight ratio]
`
`Total CODtBDt
`o£ OCH, ^ OC,H,OH
`(Wtt)
`
`PrsclpitatlOD oe KCl
`OD capsula sux£ace
`<40*C, 1 noath Isi glass bottle)
`
`Comparlaon
`
`100 > 0
`
`38.lt
`
`precipitates, locally look white
`
`Sxasqila 1
`
`95 1 S
`
`Bscaisple 2
`
`60 t 20
`
`Escaiaple 3
`
`70 : 30
`
`Bscanple 4
`
`0 I 100
`
`37.6t
`
`36.4t
`
`35.St
`
`29.4t
`
`a few precipitates, but
`acceptable outer appoarance
`
`sio preolpltates
`
`sio precipitates
`
`no precipitates
`
`I .
`
`WCDELZ 00029780
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 -15/232
`
`

`

`-10-
`
`As seen from Table 1, controlling the total content of
`alkoxyl and hydroxyalkoxyl groups In the cellulose ether to
`37.6% by weight or lower is effective for preventing the
`gelling aid {potassium chloride in these examples) from
`•5 precipitating on the film surface.
`There has been described a cellulose ether film in
`which the cellulose ether used as the base has an optimum
`content of alkoxyl and hydroxyalkoxyl groups, which is
`effective for preventing the gelling aid from precipitating
`10 out and maintaining a favorable outer appearance during
`long-term storage. The cellulose ether film is thus
`suitable as the shell of hard capsules for use in the
`pharmaceutical and health food fields.
`Japanese Patent Application No. 11-106689 is
`Incorporated herein by reference.
`Although some preferred embodiments have been
`^©scribed, many modifications and variations may be made
`thereto in light of the above teachings. It is therefore to
`be understood that the invention may be practiced otherwise
`than as specifically described without departing from the
` scope of the appended claims.
`
`15
`
`20
`
`►
`
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`
`WCDELZ_00029781
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 -16/232
`
`

`

`-11-
`
`CLAIMS:
`
`A cellulose ether film formed of a composition
`somprlslng a cellulose ether as a base In which some of the
`of>celluloslc hydroxyl groups are replaced by
`aUcyl groups orliy^oxyeilkyl groups or both, the content of
`alkoxyl and hydroxyaifcciOTl groups combined being up to 37-6%
`by weight of the celluloses^ther, a gelling agent, and a
`gelling aid.
`
`The cellulose ether film of clklm 1 wherein in said
`2.
`cellulose ether, some of the hydrogen arbqs of celluloslc
`hydroxyl groups are replaced by alkyl and l^d^oxyalkyl
`groups or only hydroxylalkyl groups.
`
`The cellulose ether film of claim 1 wherein the
`contehts.^ alkoxyl and hydroxyalkoxyl groups combined Is 23
`to 37.6% ^vtrelght of tthe cellulose ether.
`4.
`The cellulosem:^^ film of claim 1 wherein the alkyl
`groups are methyl and tnfesjwdroxyalkyl groups are
`hydroxypropyl or hydroxyethylvs,^^
`
`The cellulose ether film of clalittvj. wherein said
`5.
`cellulose ether Is hydroxypropyl methyl ce^lqlose.
`
`The cellulose ether film of claim 1 wherein said
`composition contains 100 parts by weight of the cellulose
`ether. 0.05 tbvlgS parts by weight of the gelling agent, and
`0.05 to 25 parts ^^^-wplgbt of the gelling aid.
`
`The cellulose ether fllhu.^ claim 1 wherein the
`7.
`gelling agent Is selected from th^<>group consisting of
`carrageenan. tamarind seed polysaccharld^ pectin, curdlan,
`furcellaran, gellan gum, and mixtures ther^Jf. and the
`gelling aid is selected from the group conslstihg^of a
`
`10
`
`IS
`
`20
`
`25
`
`30
`
`35
`
`D I
`
`/!
`•P
`>8
`ru
`
`o 1
`
`8
`
`U 0■
`
`p uQ
`
`WCDELZ 00029782
`
`Mylan v. Qualicaps, 1PR2017-00203
`QUALICAPS EX. 2066 - 17/232
`
`

`

`-12-
`
`-i
`
`Ion, and mixtures
`
`The oelluloseyfether film of claim 1 from which hard
`
`8.
`
` capsules are formeos^a.
`
`5
`
`O <
`
`£i
`1/i
`
`'S
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`
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`
`WCDELZ 00029783
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 - 18/232
`
`

`

`-13-
`
`ABSTRACT
`
`A cellulose ether film is formed of a composition
`
`comprising a cellulose ether as a base in which some of the
`hydrogen atoms of cellulosic hydroxyl groups are replaced by
`alkyl groups and/or hydroxyalkyl groups, a gelling agent,
`and a gelling aid. The total content of alkoxyl and
`hydroxyaJ^xyl groups in the cellulose ether is limited to
`23-37.6^by weight, which is effective for preventing the
`gelll)3(g aid from precipitating out and maintaining a
`fav^able outer appearance during long-term storage.
`
`W Q D
`
`WCDELZ 00029784
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066 - 19/232
`
`

`

`J
`
`BIRCH, STK?(A.RT, KOLASCH & BlTCH, LLP
`
`PLBASEKOTE:
`YOU MUST
`complete THE
`FOLLOWING:
`
`rio. Box 747 • Fsllj Church, Viiginii 22040-0747
`Telephooe; (703) 20S-SOOO • Facsimile: (703) 205-8030
`
`ATTORNEY DOCKET NO.
`
`Ot7^-q675?
`
`COMBINED DECLARA.TION AND POWER Of ATTORNEY
`POR PATENT AND DESIGN APPLICATIONS
`
`As a below nomed inventor. 1 henby <)tdan due mjr residence, posl oflice nfafaen and chiuoship ne 01 tuted next to my rams; Ihod
`vedly believe that 1 am the otigiiul, first and sole inventor (if only one Inventor is named below) or an oiiginai, first and joint inventor (if
`plural inventors are oamed below) of the subject matter wblch is claimed and for which a potent is scught on the invention entitled'.
`
`IfOCRTUIs
`
`Cellulose Ether Film
`
`Pl]iiiAp|in|iiiaie
`Infennato—
`ForUse ' "*
`Vfiteuc
`Spodficaoan
`Asadied:
`
`the specificBtlon of which is auocfaed hereto. If not enacfaed heielo,
`the specificalion was filed on
`United Stales Application Number
`and amended on
`the specification was filed on
`Iniemaiional Application Number _
`' amended under PCT Article 19 on .
`
`(if applicable); and/or
`OS PCT
`; and was
`. (if applicable)
`
`' I hereby state that 1 have levictved and uadecstand the contents of the above ideatified specification, including the claims, as
`amended by any aiuendintntfeleiied to above.
`ladtnowledge the duty to disclose mfiiRnalion which is material to palaalabilily as defined in lltle 37, Code of Federal Regulations.
`tlJd.
`I do not know and do not believe the same was ever known or used in the United Slilei of America before my or our invention
`Ibeteof, Of paleated or described in any piinied paUicetittD in any eounlty before my or our inveaiioa llieieof or more then one year prim
`to Ibis applicaiioii, that the same was not in public use or oo sale in the United States of Anuitci more then one year prior to this
`epplicatipn. Ihet the iovenlion has not been patented or nude the subject of an mventor's cestificate issued before the date of this
`eppUceiioa tn any eounuy fcieign to the United Stetee of America oa an applicaiinn fried by me or my legal lepresenlatives or osrigas
`'more than twelve nwndis (six moitdu for designs) prior to this oppllcaiion, end tbat IM appUcetion for patent or inventor's cettiCcaie on
`this invention Jus been filed in onycoumiyfcreign.la the UniledStates of Ameiictt prior to this applfcalian by me or my legal lepteaenlalives
`or assigos. except OS follows.
`1 beidiy claim tbceigo pticrify benefits under Tide 33, United Sutes Code. 1119 (a).(d) of loy fineign applicalion(s) for patent or
`bveolot's certificate listed below and have also identified below any foreign applicalian for patent or inventor's certificate having a
`Cling dale befoie that of lIis.Bpplicalion on which priority is clamed:
`Pilor Foreign Applicadon(s)
`11-106689
`(NombesI
`
`Japan
`(Cesnoy)
`
`04/14/1999
`(Moodi/Day/Year Filed)
`
`(Number)
`
`(Nomber)
`
`(Number)
`
`(Couniiy)
`
`(Counoy)
`
`(Counoy)
`
`(Month/Day/Year Filed)
`
`(Month / Oey / Year Filed)
`
`(Monlh/Oey/YearFtltd)
`
`Priority Claimixl
`
`Yes
`□
`Yes
`□
`Yes
`□
`
`No
`□
`No
`□
`No
`□
`
`I hereby claim the benefit under title 33, United States Code, SI 19(e) of any United Sates psovtsiona) appliceiicn(s) listed below.
`
`(AppUcaiim Niueber)
`
`(FibngDaie)
`
`(HlingDalc)
`(AppticatioaNiuntiec}
`All Foieiga AppUcatioos, if any, for any Patent or InveolorY Certificate Piled More than 12 Months (6 Months for Designs) Prior to the
`Filiiig Dale of This Application:
`Couatiy
`
`Date of Filing (Month/Day'Yen)
`
`ApplisaiionMimba
`
`I hereby claim the beaefit under Title 33, United Stales Code. $120 of any United Stales oodAsr PCT applicationfs) listed below and,
`insofar as the subject nutter of each of the chriim of this apidicetion is not disclosed hi the ptior United Sinla indfor PCrr applkation in
`the manner pntvided by the Gat pangtaph of Ulle 33, United Stales Code, S112,1 acknowledge the duty to disclose iofbtmition which
`Is material to patcnabllily as defined in Title 37, Code of Federal Regulations, S1 Jlj which became available between the filing dele of
`the prior epplicatian and the notional or PCT inteiualionel filing date of this application:
`
`(A(plk«tloaNwinbor>
`
`(nflasD«u>
`
`{SCiun—pJMKiodvptiKHiis. ibasdontdj
`
`WCDELZ 00029785
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2066