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`CONT/PfUOR
`F
`
`PATENT NUMB~R
`
`6:849180
`
`llllllllllll1111tlllll11111111111111111111111·
`16649;180
`
`U.S. UTILITY Patent Application
`PATENT DATE
`O.I.P.E.
`
`SCANNED i/7-
`
`NOV 18
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`Seinosuke Matsuura
`IYfa~,;at·u Tanjoh
`
`Cellulose Ether Film
`
`PT0-2040
`12/99
`
`/
`I ISSUING CLASSIFICATION
`lt(f
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`--
`
`CROSS REFERENCE(S)
`
`ORIGINAL
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`SUBciAsS
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`CLASS
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`INTERNATIONAL CL~SIFICATION
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`I
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`D Continued on Issue Slip Inside File Jacket
`
`DRAWINGS
`
`CLAIMS ALLOWED
`
`. . TERM!NAL
`·0 DISCLAIMER
`
`Sheets Drwg.
`
`Figs. Drwg.
`
`Print Fig.
`0
`
`Total Claims
`
`5
`
`Print Claim for O.G.
`
`{
`
`NOTICE OF ALLOWANCE MAILED
`
`6' !' ./.P'~ :J.
`(Date)
`
`{, --~C, -0 :>
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`D The term of thit patent ~ #./ufo
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`(Assistant Examiner)
`
`(date)
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`subsequent to - .
`has been disclaimed.
`D The term of this patent shall
`not extend beyond the expira~ion date
`of U.S Patent. No._
`
`D The terminal _·_months of _
`this patent have been disclaimed.
`
`P..:iU~ Thiboda;r::';,
`Sup£ii vbory Patent F _t);;·,!n.s;
`~r(,\.~:hJ~~1~0QV f~en~:·0r ~:: 7\X~
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`Amount Due
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`/
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`lPril ~ary Examiner)
`
`(Date)
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`ISSUE.BATCH NUMBER
`
`ISSUE FEE
`"tl(.. Date Paid
`C~4L4~
`~i $t706·~0 9 ... 213-o ·_7,
`ICl1 ~ 'fit/a_'£
`
`(tlate),r-?
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`(LegU.nstruments Examiner)
`v
`
`WARNING:
`The information disclosed herein may be restricted. Unauthorized disclosure may be prohibited by the United States Code Title 35, Sections 122, 181 and 368.
`Possession outside the U.S. Patent & Trademark Office is restricted to authorized employees and contractors only.
`
`Form PT0-436A
`(Rev. 6/99)
`
`FILED WITH: D DISK (CRF) D FICHE D CD-ROM
`
`(Attached in pocket on right Inside flap)
`
`. (FACE)
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 1
`
`

`
`l,. . PATENT APPLICATION,
`
`II IIIII IIIII 1111111111 1111111111 111111111111111111
`
`09549205
`
`·coNTENTS
`
`Date Received
`(Incl. C. of M.)
`
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 2
`
`

`
`SEARCHED
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`SEARCH NOTES
`(INCLUDING SEARCH STRATEGY)
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 3
`
`

`
`ISSUE SLIP STAPLE AREA (for additional cross references)
`
`POSITION
`
`INITIALS
`
`IDNO.
`
`DATE
`
`FEE DETERMINATION
`O.I.P.E. CLASSIFIER
`FORMALITY REVIEW
`RESPONSE FORMALITY REVIEW
`
`INDEX OF CLAIMS
`N ................................. Non-elected ·
`................................. Rejected
`II'
`= ................................. Allowed
`I ................................. Interference ·
`A ................................. Appeal
`(Through numeral) ... Canceled
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`.
`· staple additional sheet here
`
`(LEFT INSIDE)
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 4
`
`

`
`file:///c:/ APPS/preexamlcorrespondence/1.,
`
`...
`
`UNITED STATES DEPARTMENT OF COMMERCE
`Patent and Trademark Office
`Address: COMMISSIONER OF PATENTS AND TRADEMARKS
`Washington. D.C. 20231
`
`GROUP ART UNIT
`1615
`
`ATTORNEY
`DOCKET NO.
`0171-0675P
`
`1 111~~ m~ ~~~ ~~~ ~~~ m~1 ~~~ m~1 m1 "~''~" ~~~~ ~ 1111
`
`Bib Data Sheet
`
`SERIAL NUMBER
`09/549,205
`
`FIUN~7.0~.'.
`o4t1"3/2'oa· ,: , ... ·
`
`RULE
`
`PPLICANTS
`Seinosuke Matsuura, Kyoto, JAPAN;/
`Masaru Tanjoh, Nara-ken, JAPAN/
`
`• *CONTINUING DATA*"************* ............... ~ VI~ 'iY(J/oj
`
`*FOREIGN APPLICATIONS*"" ...,...,...,.,..., .... .,.,., /
`JAPAN 11-1 06689 04/1 1999
`
`~ '¥"/7 /o-l
`
`. F REQUIRED, FOREIGN
`. * 07/05/2000
`
`lUNG LICENSE GRANTED
`
`.. ~yesDno
`35 USC 119 (a·d) conditions ~ yes 0 no CJ Met after
`nnowance
`~ rr/71~1
`Examiner's Si nature
`
`Initials
`
`• Birch Stewart Kolasch & Birch LLP
`P 0 Box747
`Falls Church ,VA 22040-0747
`
`STATE OR
`COUNTRY
`JAPAN
`
`SHEETS
`DRAWING
`
`TOTAL
`CLAIMS
`8
`
`INDEPENDEN
`CLAIMS
`1
`
`//
`
`/
`
`FILING FEE FEES: Authority has been given in P per
`RECEIVED No.
`to charge/credit D OSIT ACCOUNT
`690
`No.
`for following:
`
`1 of 1
`
`7/5/00 10:28 AM
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 5
`
`

`
`PATENT APPLICATION SERIAL NO.-------.....-...,.
`
`U.S. DEPARTMENT OF COMMERCE
`PATENT AND TRADEMARK OFFICE
`FEE RECORD SHEET
`
`04/25/2000 PALLEN
`'
`01 FC:101
`
`00000019 09549205
`690.00 QP ·
`
`PT0-1556
`(5/87)
`
`'U.S. GPO: 1999-459;082/19144
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 6
`
`

`
`-13-
`
`ABSTRACT
`
`s
`
`10
`
`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
`hydroxyalkoxyl groups in the cellulose ether is limited to
`23-37.6. by weight, which is effective for preventing the
`from precipitating out and maintaining a
`appearance during long-term storage.
`
`~
`
`I
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 7
`
`

`
`-1-
`
`TITLE OF THE INVENTION
`Cellulose Ether Film
`
`5
`
`10
`
`This invention relates to a cellulose ether film
`suited for use in forming pharmaceutical and food hard
`capsules.
`
`15
`
`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
`of a composition comprising gelatin as a base, a plasticizer
`(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 aqueous gelatin solution adhering to the pins, and
`drying the gelatin coats.
`Flexibility and other properties of gelatin-based film
`largely depend on the water content of the film. A film
`with a low water content is too low in impact resistance to
`25 withstand the shocks encountered upon filling of medicament.
`Also, as the water content decreases by drying during
`storage, the film contracts to ~ndesirably loosen the cap(cid:173)
`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 tci 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
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 8
`
`

`
`-2-
`
`~n
`
`::
`
`15
`
`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
`5 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 cellulosic hydroxyl
`groups are replaced by alkyl and hydroxyalkyl groups or
`hydroxyalkyl groups, a gelling agent, and a gelling aid, as
`disclosed in Japanese Patent No. 2,552,937. Some capsules
`10
`l
`£ 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
`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
`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
`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
`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
`at. Especially in the case of colorless clear film, the
`precipitates develop as cloud and sometimes, cloud spots
`
`35
`
`20
`
`25
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 9
`
`

`
`-3-
`
`rather than uniform cloud, exacerbating the outer appearance
`of capsules noticeably.
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`i
`
`SUMMARY OF THE INVENTION
`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 ~elling
`aid, which prevents the gelling aid from precipitating out
`and maintains a favorable outer appearance during long-term
`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 cellulosic hydroxyl groups are replaced by alkyl
`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
`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 cellulosic
`hydroxyl groups are replaced by alkyl groups and/or
`hydroxyalkyl groups, a gelling· agent, and a gelling aid,
`wherein the total content of alkoxyl and hydroxyalk6xyl
`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
`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 o'f
`cellulosic hydroxyl groups are replaced by alkyl groups
`· 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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`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 10
`
`

`
`-4-
`
`groups to 37.6% 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
`
`10
`
`DESCRIPTION OF THE PREFERRED EMBODIMENT
`Briefly stated, the cellulose ether film of the
`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
`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
`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
`(HPMC), hydroxypropyl cellulos~ (HPC), hydroxyethyl methyl
`cellulose (HEMC), and methyl cellulose (MC). Of these, HPMC
`·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 abo~e substituents is limited to
`37.6% by weight or lower. More particularly, the total
`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
`
`15
`
`20
`
`35
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 11
`
`

`
`-5-
`
`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 case of MC. A cellulose
`ether having a total content of such substituents 9f up to
`37.6% by weight is used.
`The lower the total content of alkoxyl and
`hydroxyalkoxyl groups, the better becomes the effect 9f
`preventing precipitation of the gelling aid. However, if
`the total content of alkoX:yl 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 conte~t 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,
`hydroxypropyl methyl cellulose 2208, 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%; 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%, and hyd~oxypropyl
`methyl cellulose 2910 contains 28 to 30 wt% of MO groups and
`7 to_ 12 wt% of HPO groups in a total of 35 to 42 wt%. Any
`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 3 7. 6 wt%. Also acceptable are mixtures in. which
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`Lli. s·-
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 12
`
`

`
`-6-
`
`any two or more of these celluioses are mixed to adjust the
`total content of MO 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, HPC and MC specified therein, and by a well-known
`method for the remaining cellulose ethers.
`The gelling agent used may be selected from among, for
`example, carrageenan, tamarind seed polysaccharide, pectin,
`curdlan, furcellaran, gellan gum, and mixtures thereof. Of
`these, carrageenan 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. While
`there are known three types: kappa-carrageenan or iota(cid:173)
`carrageenan and lambda-carrageenan, the invention recommends
`to use kappa-carrageenan and/or iota-carrageenan which have
`a good gelation ability.
`The amount of the gelling agent 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 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 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 fail to produce a film of a·
`sufficient thickness to enable shell formation by the
`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
`difficuit to form a uniform coat or film.
`As the gelling aid used herein, any substance that can
`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
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`7
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 13
`
`

`
`-7-
`
`ion, and 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(cid:173)
`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
`calcium chloride.
`Like the gelling agent, the amount 0f 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
`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 part of
`the gelling aid may promote gelation of the gelling. agent to
`a less extent and fail to produce a film of a sufffcient
`thickness to enable shell formation by the dipping method.
`More than 25 parts of the gelling aid may form a gel in a
`dipping solution for rendering it difficult to form a film,
`and in addition, adversely affect the disintegration (i.e.,
`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
`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
`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 converitional gelatin capsules.
`In one
`
`5
`
`10
`
`15
`
`F =r
`
`::
`
`2o
`
`25
`
`30
`
`35
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 14
`
`

`
`-8-
`
`In
`
`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.
`this way, the cellulose ether film of the invention is
`obtained in the form of capsule shells. The shells are then
`cut to a predetermined size and mated to construct hard
`capsules of' the cellulose ether film according to the
`invention.
`As mentioned above, the dipping solution is an aqueous
`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 30% by weight, and especially 18 to
`25% by weight of the cellulose ether. Less than 15% by
`20 weight of the cellulose ether may fail 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
`~nd health food fields although the application is not
`limited thereto. The film may find use in applications
`other than hard capsules.
`
`5
`
`10
`
`15
`
`25
`
`30
`
`35
`
`EXAMPLE
`Examples of the invention are given below by way of
`illustration and not by way of limitation.
`1 cellulose 2919 specified in the
`Pharmacopoeia of Japan ("Metolose 60SH
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 15
`
`

`
`-9-
`
`5
`
`15
`
`~ucm··~al Co., ~td.) and hydroxypropyl methyl cellulose 2208
`("Metolose
`by Shin-Etsu Chemical Co., Ltd.) were mixed
`in the proportio
`in Table 1. Using this
`hydroxypropyl methyl ce
`a dipping solution of the
`composition shown below
`dipping method, size
`hydroxypropyl methyl cellulos.e film
`thick were
`therefrom.
`of methoxyl and hydroxypropoxyl
`2919 (Metolose
`(Metolose
`
`By a conventional
`es of colorless clear
`
`groups in
`60SH) and hydroxypropyl
`90SH) were determined by the measurement
`in the Pharmacopoeia of Japan, with the results
`2910 {60SH)
`-OCH3 : 28.8%, -OC3H60H: 9.3%, total: 38.1%
`2208 (90SH)
`-OCH3 : 23.5%, -OC 3H60H: 5.9%, total: 29.4%
`Dipping solution composition
`Hydroxypropyl methyl cellulose
`
`20 wt%
`
`K-carrageenan (gelling agent)
`
`0.1 wt%
`0.1 wt%
`Potassium chloride (gelling aid)
`( 0 • 0 52 wt % of K+ )
`Water
`balance
`The capsules thus obtained were contained in a glass
`
`25 bottle and stored at 40°C for one month. The capsule surface
`
`was visually observed to inspect precipitates of potassium
`chloride thereon. The results are shown in Table 1.
`Table.1
`
`Cellulose
`mixture of
`2910:2208
`(weight ratio)
`100 : 0
`
`Comparison
`
`Example 1
`
`95
`
`: 5
`
`Example 2
`
`Example 3
`
`80
`
`: 20
`
`70
`
`: 30
`
`Example 4
`
`0
`
`: 100
`
`Total content
`of OCH3 + OC 3H60H
`(wt%)
`
`Precipitation of KCl
`on capsule surface
`< 4o•c. 1 month in glass bottle)
`
`38.1%
`
`37.6%
`
`36.4%
`
`35.5%
`
`29.4%
`
`precipitates, locally look white
`
`a few precipitates, but
`acceptable outer appearance
`
`no precipitates
`
`no precipitates
`
`no precipitates
`
`ru
`
`\
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 16
`
`

`
`-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
`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
`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
`described, 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.
`
`-
`
`5
`
`10
`
`15
`
`20
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 17
`
`

`
`-11-
`
`5
`
`10
`
`15
`
`20
`
`cellulo$e ether film formed of a composition
`cellulose ether as a base in which some of the
`hydroxyl groups are replaced by
`hydrogen at
`roxyalkyl groups or both, the content of
`alkyl groups
`alkoxyl and hydroxyal
`groups combined being up to 37.6%
`by weight of
`a gelling agent, and a
`gelling aid.
`
`The
`2.
`cellulose ether, some of the hydrogen
`hydroxyl groups are replaced by alkyl
`groups or only hydroxylalkyl groups.
`
`wherein in said
`
`The cellulose ether film of 'claim 1 wherein the
`alkoxyl and hydroxyalkoxyl groups combined is 23
`
`4.
`groups are methyl and
`hydro~ypropyl or hydroxyethy
`
`film of claim 1 wherein the alkyl
`groups are
`
`The cellulose ether film of clai
`5.
`cellulose ether is hydroxypropyl methyl
`
`25
`
`cellulose ether film of claim 1 wherein said
`n contains 100 parts by weight of the cellulose
`ether, 0.05
`5 parts by weight of the gelling agent, and
`0.05
`of the gelling aid.
`
`the
`The cellulose ether
`7.
`consisting of
`gelling agent is selected from
`, pectin, curdlan,
`carrageenan, tamarind seed polysacchar
`, and the
`furcellaran, gellan gum, and
`gelling aid is selected from the group consisti
`
`30
`
`35
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 18
`
`

`
`-potasslam isR, calcium ian
`
`. thereof.
`
`-12-
`
`ammonium ion, and mixtures
`
`-
`
`8.
`
`5
`
`ther film of claim 1 from which hard
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1010 - Page 19
`
`

`
`BIRCH, STF-·. TART, KOLASCH & B1
`
`-:H, LLP
`
`PLEASE NOTE:
`YOU MUST
`COMPLETE TilE
`FOLLOWING:
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`
`~
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`Insert Title:
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`
`r.O. Box 747 • Falls Church, Virginia 22040-0747
`
`Telephone: (703) 205-8000 • Facsimile: (703) 205-8050
`
`COMBINED DECLARATION AND POWER OF ATTORNEY
`FOR PATENT AND DESIGN APPLICATIONS
`
`As a below named inventor, I hereby declare that: my residence, post office address and citizenship are as stated next to my name; that I
`verily believe that I am the otiginal, first and sole inventor (if only one inventor is named below) or an miginal, first and joint inventor (if
`plural inventors are named below) of the subject matter which is claimed and for which a patent is sought on the invention entitled:
`CelluJ6se Ether film
`
`the specification of which is attached hereto. If not attached hereto,
`the specification was filed on
`United States Application Number
`and amended on - - - - - - - - - - - - - - - - - - - - (i r applicable); and/or
`the specification was filed on
`as PCT
`International Application Number
`; and was
`amended under PCT Article 19 on
`(if applicable)
`
`as
`
`I hereby state that I have reviewed and understand the contents of the above identified specification, including the claims, as
`amended by any amendment referred to above.
`
`I acknowledge the duty to disclose information which is material to patentability as defined in Title 37. Code of Federal Regulations,
`§ 1.56.
`.
`.
`
`I do not know and do not believe the same was ever known or used in the United States of America before my or our invention
`thereof, or patented or described in anyptinted publication in any country before my or our invention thereof or more than one year prior
`to this application, that the same was not in public use or on sale in the United States of Ametica more than one year prior to this
`application, that the invention has not been patented or made the subject of an inventor's certificate issued before the date of this
`application in any country foreign to the United States Of America on an application filed by me or tny legal representatives or assigns
`more than twelve months (six months for designs) ptior to this application, and that no application for patent or inventor's certificate on
`this invention has been filed in any country foreign to the United States of America prior to this application by me or my legal representatives
`or assigns, except as follows.
`
`I hereby claim foreign priority benefits under Title 35, United States Code, § 119 (a)-(d) of any foreign application(s) for patent or
`inventor's certificate listed below and have also identified below any foreign application for patent or inventor's certificate having a
`filing date before that of the application on which priority is claimed:
`Prior Foreign Application(s)
`11-106689
`
`Japan
`(Country)
`
`04/14/1999
`(Month I Day I Year Filed)
`
`Priority Claimed
`mJ D
`Yes
`No
`D D
`Yes
`No
`0
`D
`Yes
`No
`0
`0
`Yes
`No
`
`(Number)
`
`(Number)
`
`(Number)
`
`(Country)
`
`(Country)
`
`(Country)
`
`(Month I Day I Year Filed)
`
`(Month I Day I Year Filed)
`
`(Month I Day I Year Filed)
`
`I hereby claim the benefit under Title 35, United States Code, § 119(e) of any-United States provisional application(s) listed below.
`
`(Application Number)
`
`(Filing Date)
`
`(Filing Date)
`(Application Number)
`All Foreign Applications, if any, for any Patent or Inventor's Certificate Filed More than 12 Months (6 Months for Designs) Ptior to the
`Filing Date -of This Application:
`Country
`
`Date of Filing (Month I Day I Year)
`
`Application Number
`
`I hereby claim the benefit under Title 35, United States Code, § 120 of any United States and/or PCT application(s) listed b~lo"': an~,
`insofar as the subject matter of each of the claims of this application is not disclosed in the prior United States and/or PCT app~iCatto~ m
`the manner provided by the first paragraph of Title 35, United States Code,§ 112, I acknowledge the dut~ to disclose mforma~wn which
`is material to patentability as defined in Title 37, Code of Federal Regulations, § 1.56 which became avmlable between the fihng date of
`the prior application and the national or PCT international filing date of this application:
`
`(Application Number)
`
`(Application Number)
`
`(Filing Date)
`
`(Filing Date)
`
`(Status
`
`patented, pending, abandoned)
`
`(Status- paten