qP 2093-012427
`
`Page: 13/
`
`[0019]
`
`Although the content of the polyethylene glycol fatty
`
`acid ester in the aqueous liquid preparation of the present
`
`invention depends on the kind of compounds used. it is within
`
`a range of about 0.02 w/v % of minimum concentration to about
`
`0.1 W/V % of maximum concentration. For example,
`
`the content
`
`of polyethylene glycol.monostearate is within a range of about
`
`0 . 02 w/v % of minimum content to about 0 . 1 w/v of maximum content ,
`
`and preferably within a range of about 0 . 02 w/v % of the minimum
`
`content to about 0.05 w/v % of the maximum content.
`
`[0020]
`
`The incorporation ratio of
`
`tyloxapol
`
`in the aqueous
`
`liquid preparation of the invention is within a range of the
`
`minimum content of about 0 . 1 or 0 . 2 part by weight to the maximum
`
`content of about 0.5, 1, 3 or 5 parts by weight, relative to
`
`1 part by weight of 2-amino—3—(4-bromobenzoyl)phenylacetic
`
`acid or its pharmacologically acceptable salt or a hydrate
`
`thereof.
`
`[0021]
`
`The
`
`incorporation
`
`ratio of
`
`polyethylene
`
`glycol
`
`monostearate in the aqueous liquid preparation of the present
`
`invention is within.a:range of therninimunlcontent of about 0.2
`
`part by weight to the maximum content of about 0.5 or 1 part
`
`by weight.
`
`relative
`
`to
`
`1
`
`part
`
`by
`
`weight
`
`of
`
`2—amino-3-(4—bromobenzoyl)phenylacetic
`
`acid
`
`or
`
`its
`
`pharmacologically acceptable salt or a hydrate thereof.
`
`[0022]
`
`The preservative used in the present invention includes ,
`
`10
`
`15
`
`20
`
`25
`
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`

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`.3‘
`
`qP 2093—0l2427
`
`-
`
`Page: 14/
`
`for example, quaternary ammonium salts (e.g. benzalkonium
`
`chloride,
`
`benzethonium chloride,
`
`etc.),
`
`chlorhexidine
`
`gluconate, and the like, among which benzalkonium chloride is
`
`especially preferable.
`
`[0023]
`
`Further, so long as the purpose of the present invention
`
`is achieved, conventional.various additives such as isotonics,
`
`buffers,
`
`thickners,
`
`stabilizers,
`
`chelating agents,
`
`pH
`
`controlling agents, perfumes and the likelnay be appropriately
`
`added to the aqueous liquid preparation of the present invention.
`
`The isotonics include sodium chloride, potassium chloride,
`
`glycerine, mannitol, sorbitol, boric acid, glucose, propylene
`
`glycol and the like.
`
`The-buffers include,
`
`for example,
`
`phosphate buffer, borate buffer, citrate buffer,
`
`tartarate
`
`buffer, acetate buffer, boric acid, borax, amino acids, and the
`
`like.
`
`The
`
`thickners
`
`include
`
`polyvinylpyrrolidone,
`
`carboxymethylcellulose,
`
`carboxypropylcellulose,
`
`hydroxyethylcellulose,
`
`hydroxypropylcellulose,
`
`hydroxypropylmethylcellulose,
`
`polyvinyl
`
`alcohol,
`
`sodium
`
`polyacrylate, and the like. The stabilizers include sulfites
`
`such as sodium sulfite and the like.
`
`The chelating agents
`
`include sodium edetate,
`
`sodium citrate,
`
`condensed sodium
`
`phosphate and the like.
`
`The pH controlling agents include
`
`hydrochloric acid, sodium hydroxide, phosphoric acid, acetic
`
`acid and the like. The perfumes include 1-menthol, borneol,
`
`camphor, Eucalyptus oil, and the like.
`
`[0024]
`
`With respect to the concentrations of the above various
`
`10
`
`15
`
`20
`
`25
`
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`

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`my
`
`JP 2003—012427
`
`Page: 15/
`
`additives in the aqueous liquid preparation of the present
`
`invention,
`
`the isotonic is incorporated into an osmotic
`
`pressure ratio of about 0.8 to 1.2, and the concentrations of
`
`the buffer and the thickner to be added are about 0 . 01 to 2 w/v %
`
`and 0.1 to 10 w/v %, respectively.
`
`[0025]
`
`The pH of the aqueous liquid preparation of the present
`
`invention is adjusted to about 7 to 9, preferably about 7.5 to
`
`8.5.
`
`10
`
`[0026]
`
`So long as the purpose of the present invention is achieved,
`
`other same or different kind of active ingredients may be
`
`appropriately added.
`
`[0027]
`
`15
`
`The aqueous liquid preparation of the present invention
`
`can be prepared by per se known method or according to the method
`
`as described in the Japanese Pharmacopoeia. 14”‘ Edition,
`
`General Rules
`
`for Preparations, Solutions or Ophthalmic
`
`solutions.
`
`20
`
`[0028]
`
`The aqueous liquid preparation of the present invention
`
`can be applied to warm~blooded animals such as human, rat , mouse ,
`
`rabbit, cow, pig, dog, cat, and the like.
`
`[0029]
`
`25
`
`The aqueous liquid preparation of the present invention,
`
`for example,
`
`in the form of an eye drop, can be used for the
`
`treatment of inflammatory diseases in anterior or posterior
`
`segment of
`
`the eye such as blepharitis, conjunctivitis,
`
`Page 253 of 752
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`

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`Q):
`
`gp 2093-012427
`
`Page: 16/
`
`scleritis, postoperative inflammation. and.the like. The.dose
`
`of the aqueous liquid preparation containing 0 . 1 w/V % of sodium
`
`2—amino-3-(4-bromobenzoyl)pheny1acetate
`
`hydrate
`
`is,
`
`for
`
`example, administered to an adult 3 to 6 times daily in an amount
`
`of 1 to 2 drops per one time. Depending on the degree of diseases ,
`
`frequency of dosing is appropriately controlled.
`
`[0030]
`
`[Examples]
`
`The present
`
`invention is illustrated by way of
`
`the
`
`10
`
`following Experimental Examples and Working Examples, but the
`
`present invention is not restricted to these Examples.
`
`[0031I
`
`Experimenta1.Example 1: Stability test of sodiun12—amino-3—(4—
`
`bromobenzoyl)phenylacetate
`
`15
`
`(Experimental Method)
`
`Four
`
`eye
`
`drops
`
`of
`
`sodium
`
`2—amino-3—(4—
`
`bromobenzoyl)pheny1acetate.comprising the components as shown
`
`in Table
`
`1 were prepared,
`
`filled respectively into a
`
`polypropylene container and subjected to stability test at 60°C .
`
`20
`
`[0032]
`
`Page254of752
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`

`
`
`
`
`
`
`
`%P 2093-012427
`
`[Table 1]
`
`
`
`Comparison
`
`
`
`Example 1
`
`Sodium 2-amino—3—(4—
`
`bromobenzoyl)pheny1acetate
`
`
`
`jT
`
`
`
`100 mL
`
`
`
`Total volume
`
`1
` Sterile purified water
` 31
`
`
`
`
`100 mL
`
`100 mL
`
`100 mL
`
`
`
`60°C-4W
`
`[0033]
`
`The remaining rate (%)
`
`in the above Table 1 indicates
`
`values
`
`obtained by
`
`correcting
`
`the
`
`content
`
`of
`
`sodium
`
`2-amino—3-(4-bromobenzoyl)phenylacetate taking into account
`
`moisture vaporization from the container. As is apparent from
`
`the Table 1 , stability test was carried out under the conditions
`
`of
`
`pH
`
`7.0
`
`at
`
`60°C
`
`for
`
`4
`
`weeks,
`
`and
`
`sodium
`
`2—amino—3—(4—bromobenzoyl)phenylacetate in each eye drop was
`
`stable in the order of
`
`tyloxapol—containing preparation >
`
`polyoxyl 40 stearate-containing preparation > polysorbate
`
`80-containing preparation.
`
`Further, with.respect to eye drops containing tyloxapol,
`
`sodium
`
`2—amino—3—(4—bromobenzoy1)phenylacetate
`
`in
`
`the
`
`composition containing 0.02 w/v % of tyloxapol is more stable
`
`10
`
`15
`
`Page 255 of 752
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`

`
`QP 2093—Ol2427
`
`Page: 18/
`
`than that in the composition containing 0 . 15 w/v % of tyloxapol.
`
`[0034]
`
`Experimental.Example 2: Stability test of sodiunl2—amino-3—(4-
`
`bromobenzoyl)phenylacetate
`
`(Experimental Method)
`
`Five
`
`eye
`
`drops
`
`of
`
`sodium
`
`2—amino—3-(4-
`
`bromobenzoyl)phenylacetate comprising the components as shown
`
`in Table
`
`2 were prepared,
`
`filled respectively into a
`
`polypropylene container and preserved at 60°C for 4 weeks, and
`
`then the content of 2—amino—3-(4-bromobenzoyl)phenylacetic
`
`acid and the pH in each eye drop were measured.
`
`Table 2 shows the remaining rate and the pH of sodium
`
`2-amino—3- ( 4- bromobenzoyl)phenylacetate after storage at 60°C
`
`for 4 weeks, when the remaining rate of sodium 2—amino—3-(4-
`
`bromobenzoyl)phenylacetate at the time of production of eye
`
`drops is set to 100%. The remaining rate is a corrected value
`
`taking into account moisture vaporization from the container.
`
`10
`
`15
`
`[0035]
`
`Page 256 of 752
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`
`

`
`JP 2093-012427
`
`Page: 19/
`
`H4
`
`“T o m
`
`I
`
`>
`
`0 \l
`
`NooHPQ
`
`O L» m
`
`1.1 g
`
`1.1 g
`
`o.oo5g
`
`0.05g
`
`N 2:
`
`co
`
`1.1 g
`
`1.1 g
`
`0.005g
`
`No‘oE.-DQ
`
`0.03g
`
`O 3-: Q
`
`|-'}-' I-L unto
`
`o.oo5g
`
`1.1 g
`
`0.005g
`
`NHo‘ot-'LQQQ
`
`0.02 g
`
`
`
`
`
`0.02g
`
`0.02g
`
`0.02g
`
`o.o2g
`
`0.02g
`
`100 mL
`
`100nm 100 mL
`
`100 mL
`
`100 mL
`
`8.17
`
`N |-' 0%
`
`Q 9-‘ U1
`
`(D H D
`
`8.19
`
`92.6
`
`90.9
`
`92.0
`
`93.4
`
`93.1
`
`[Table 2]
`
`
`
`
`Sodium 2-amino-3—(4-
`
`bromobenzoyl)phenyl—
`
`acetate
`
`
`
`Polyvinyl-
`
`pyrrolidone (K-30)
`
`
`
`Sodium edetate
`
`Sodium hydroxide
`
`Sterile purified
`
`water
`
`Remaining
`
`
`
` Total volume
`
`
`
`60°C—4W
`
` rate
`
`
`
`[0036]
`
`As is apparent fron1Table 2, the remainingzrate of sodium
`
`2-amino—3—(4-bromobenzoyl)pheny1acetate in the compositions
`
`containing 0.02 w/V %, 0.03 W/V % and 0.05 w/v % of tyloxapol
`
`or 0.02 w/v % and 0.05 w/v % of polyoxyl 40 stearate is not less
`
`than 90 % after storage at 60°C for 4 weeks, which indicates
`
`Page257of752
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`
`

`
`JP 20Q3—012427
`
`Page: 20/
`
`that
`
`those compositions have sufficient stability for eye
`
`drops.
`
`[0037]
`
`Experimental Example 3: Preservative effect test of aqueous
`
`liquid
`
`preparation
`
`containing
`
`sodium
`
`2—amino-3-(4-
`
`bromobenzoyl)phenylacetate
`
`Preservative effect test of compositions A-04, A-05 and
`
`A-07 of Experimental Example 2 was carried out.
`
`The results are shown in Table 3.
`
`10
`
`[0038]
`
`Page258of752
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`

`
`qP 2093-012427
`
`Page: 21/
`
`[Table 3]
`
`Table 3-1
`
`aureus
`
`coli
`
`aeruginosa
`
`albicans
`
`Unit: CFU/mL
`
`Table 3-2
`
`aureus
`
`coli
`
`aeruginosa
`
`albicans
`
`IiiiillIIIiiII|IIii||IIiii||lI|iII|
`
`0
`
`0
`
`0
`
`0
`
`niger
`niger
`niger
`
`Unit: CFU/mL
`
`Table 3-3
`
`Inoculum
`
`count
`
`aureus
`
`coll
`
`aeruginosa
`
`albicans
`
`Unit: CFU/mL
`
`Page259of752
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`

`
`qp 2o93—o12427
`
`Page: 22/
`
`[0039]
`
`As
`
`is apparent
`
`from Tables 3-1,
`
`3-2 and 3-3,
`
`the
`
`preservative effect of composition .A—04 was
`
`found.
`
`to be
`
`compatible with EP-criteria A 1
`
`)
`
`, and those of compositions A-05
`
`and A-07 were found to be compatible with EP-criteria B 2).
`
`[0040]
`
`1) EP(European Pharmacopoeia)-criteria A
`
`Viable cell counts of bacteria (S. aureus, P.aeruginosa)
`
`6 hours, 24 hours, and 28 days after inoculation decrease to
`
`10
`
`not more than 1/100, not more than 1/1000, and undetectable,
`
`respectively.
`
`Viable cell count of fungi (C. albicans, A. niger) 7 hours
`
`after‘
`
`inoculation decreases to not more than 1/100,
`
`and
`
`thereafter,
`
`the cell count levels off or decreases.
`
`15
`
`2) EP-criteria B
`
`Viable cell counts of bacteria (S. aureus, P.aeruginosa)
`
`24 hours and 7 days after inoculation decrease to not more than
`
`1/10 and not more than 1/1000, respectively, and thereafter,
`
`the cell count levels off or decreases.
`
`20
`
`Viable cell count of fungi (C. albicans, A. niger) 14 days
`
`after
`
`inoculation decreases
`
`to not more
`
`than 1/10,
`
`and
`
`thereafter, the cell count keeps the same level as that of 14
`
`days after inoculation.
`
`[0041]
`
`Page260of752
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`
`

`
`QP 2093—Ol2427
`
`Page: 23/
`
`Example 1: Eye Drop
`
`Sodium 2—amino-3-(4-bromobenzoyl)
`
`phenylacetate 3/2 hydrate
`
`Polyvinylpyrrolidone (K-30)
`
`Sodium edentate
`
`tolnake total volume
`
`of 100 mL
`
`An eye drop is prepared using the above components in a
`
`conventional manner.
`
`[0042]
`
`Page261of752
`q‚ˆ† SWR ‡ XVS
`
`

`
`qp 2093-012427
`
`Example 2: Eye Drop
`
`Sodium 2—amino—3-(4-bromobenzoyl)
`
`Page: 24/
`
`0.1 g
`
`Sodium edetate
`
`Sodium hydroxide
`
`0.02 g
`
`q.s.
`
`Sterile purified water
`
`to make total volume
`
`of 100 mL
`
`An eye drop is prepared using the above components in a
`
`conventional manner.
`
`[0043]
`
`Page 262 of 752
`q‚ˆ† SWS ‡ XVS
`
`

`
`{P 2093-012427
`
`Page: 25/
`
`Example 3: Eye Drop
`
`Sodium 2-amino—3-(4-bromobenzoyl)
`
`phenylacetate 3/2 hydrate
`
`Boric acid
`
`Borax
`
`Polyoxyl 40 stearate
`
`Polyvinylpyrrolidone (K-30)
`
`to make total volume
`
`-of 100 mL
`
`An eye drop is prepared using the above components in a
`
`conventional manner.
`
`[0044]
`
`[Effect of the Invention]
`
`According to the present
`
`invention, a stable aqueous»
`
`liquid
`
`preparation
`
`containing
`
`2—amino—3-(4-
`
`bromobenzoyl)phenylacetic
`
`acid
`
`or
`
`a
`
`pharmacologically
`
`acceptable salt thereof or a hydrate thereof can be prepared
`
`10
`
`15
`
`by incorporating an alkyl aryl polyether alcohol type polymer
`
`such as tyloxapol, or a polyethylene glycol fatty acid ester
`
`such as polyethylene glycol monostearate into an aqueous liquid
`
`preparationcontaining2—amino-3-(4—bromobenzoyl)phenylacetic
`
`acid or a pharmacologically acceptable salt thereof or a hydrate
`
`thereof. Also, an aqueous liquid preparation of the present
`
`invention, wherein a preservative is incorporated, has a
`
`Page263of752
`q‚ˆ† SWT ‡ XVS
`
`

`
`JP 2003-012427
`
`Page: 26/E
`
`sufficient preservative effect.
`
`Therefore, the aqueous liquid preparation.of the present
`
`invention is advantageously used as an eye drop for the
`
`treatment of,
`
`for
`
`example, blepharitis, conjunctivitis,
`
`scleritis, and.postoperative inflammation.
`
`In addition, such
`
`aqueous liquid.preparation can be used.as a nasal drop for the
`
`treatment of, for example, allergic rhinitis and inflammatory
`
`rhinitis (e.g. chronic rhinitis, hypertrophic rhinitis, nasal
`
`po1YP. etc.).
`
`Page 264 of 752
`q‚ˆ† SWU ‡ XVS
`
`

`
`s
`
`-s
`ax
`
`..
`
`mn-
`JP 2093-012427
`
`Page: 1/E
`
`[Name of Document] Abstract
`
`[Abstract]
`
`[Problem]
`
`To provide an aqueous
`
`liquid preparation containing
`
`5
`
`stabilized2—amino—3—(4-bromobenzoyl)phenylaceticacidcnrits
`
`pharmacologically acceptable salt or'a hydrate thereof, which
`
`is stable and exhibits a sufficient preservative effect.
`
`[Means for solving the problem]
`
`An
`
`aqueous
`
`liquid
`
`preparation
`
`containing
`
`10
`
`2—amino-3-(4—bromobenzoyl)phenylacetic
`
`acid
`
`or
`
`its
`
`pharmacologically acceptable salt or a hydrate thereof and an
`
`alkyl aryl polyether alcohol type polymer such as tyloxapol,
`
`or a polyethylene glycol fatty acid ester such as polyethylene
`
`glycol monostearate.
`
`15
`
`[Chosen Drawing] None
`
`Page 265 of 752
`q‚ˆ† SWV ‡ XVS
`
`

`
`;‘0
`
`'o
`
`'3In
`
`JP 2003-012427
`«I ‘O
`
`Page:
`
`1/E
`
`Applicant's History Information
`
`Identification Number:
`
`[0O0199175]
`
`1. Date of Change
`
`August 22, 1990
`
`[Reason for Change]
`Address:
`
`Newly recorded
`
`5-8, Hiranomachi 2-chome,
`
`Chuo-ku,
`
`Name:
`
`SENJU PHARMACEUTICAL CO.,
`
`LTD.
`
`Osaka—shi, OSAKA
`
`Page 266 of 752
`q‚ˆ† SWW ‡ XVS
`
`

`
` .v -_..-._'.
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`-. Max M
`
`In re application of
`
`Shirou SAWA et al.
`
`Serial No. 10/525,006
`
`Filed March 28, 2005
`
`AQUEOUS LIQUID PREPARATION
`CONTAINING 2-AMINO-3-(4-
`BROMOBENZOYL)PHENYLACETIC ACID
`
`Attorney Docket No. 2005_0232A
`
`Confirmation No. 1756
`
`Group Art Unit 1614
`
`Examiner Donna A. Jagoe
`
`Mail Stop: RCE
`
`PATENT OFFICE FEE TRANSMITTAL FORM
`
`I
`
`Commissioner for Patents
`
`P.O. Box 1450
`
`Alexandria, VA 22313-1450
`
`Sir:
`
`Attached hereto is a Credit Card Payment Form authorizing payment in the amount of
`$940.00 to cover Patent Office fees relating to filing the following attached papers:
`
`Request for Continued Examination (RCE)
`Petition for Extension of Time
`
`$810.00
`
`$130.00
`
`Respectfully submitted,
`
`Shirou SAWA et al.
`
`By
`
`¢£}d«0&Lu(<
`Warren M. Cheek
`
`Registration No. 33,367
`Attorney for Applicants
`
`WMC/dlk
`Washington, D.C. 2005-1503
`Telephone (202) 721-8200
`Facsimile (202) 721-8250
`October 5, 2009
`
`The Commissioner is authorized to charge any deficiency or to credit any overpayment associated with this communication to
`Dep|gécgeA2cé:_;;1é%1t7é\’2o. 23-09 75.
`q‚ˆ† SWX ‡ XVS
`
`

`
`
`
`'2'
`
`« n
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re application of
`
`Shirou SAWA et al.
`
`Serial No. 10/525,006
`
`Filed March 28, 2005
`
`AQUEOUS LIQUID PREPARATION
`CONTAINING 2-AMINO-3-(4-
`BROMOBENZOYL)PHENYLACETIC ACID
`
`:
`
`:
`
`:
`
`:
`
`2
`
`Attorney Docket No. 2005_0232A
`
`Confirmation No. 1756
`
`Group Art Unit 1614
`
`Examiner Donna A. Jagoe
`
`Mail Stop: RCE
`
`PETITION FOR EXTENSION OF TIME
`
`Commissioner for Patents
`
`P.O. Box 1450
`
`Alexandria, VA 22313-1450
`Sir:
`
`_
`Petition hereby is made for a one month extension of time to respond to the
`communication of June 3, 2009.
`
`The fee of$130.00 is
`
`(X) '
`()
`is enclosed.
`
`A
`
`to be charged to Credit Card (per attached Credit Card Authorization Form).
`to be charged to Deposit Account No. 23-0975. A duplicate copy of this Petition
`
`Small entity status of this application is established by a Small Entity Status
`()
`Assertion which
`
`()
`()
`()
`
`is enclosed.
`hasbeen previously submitted.
`has been previously asserted.
`
`Respectfully submitted,
`Shirou SAWA et al.
`'
`
`BY
`Warren M. Cheek
`
`Registration No. 33,367
`Attorney for Applicants
`
`10/B6/E009 SZEHDIE1 08983928 10525986
`31 “H331
`316.33 DP
`
`WMC/dlk
`Washington, D.C. 20005-1503
`Telephone (202) 721-8200
`Facsimile (202) 721-8250
`October 5, 2009
`
`The Commissioner is authorized to charge any deficiency or to credit any overpayment associated with this communication to
`Deposit Account No. 23-09 75.
`Page 268 of 752
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`

`
`PTO/SB/06 (O7-O6)
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`PATENT APPLICATION FEE DETERMINATION RECORD
`Substitute for Form PTO-875
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`APP“°3“°“ °’ D°°"eI Number
`10/525,006
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`IXI To be Mailed
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`APPLICATION AS FILED — PART I
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`(Column 1)
`NUMBER FILED
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`NUMBER EXTRA
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`sivi/.\I_I_ ENTITY |:|
`FEE ($)
`RATE (39)
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`OTHER THAN
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`OR
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`SMALL ENTITY
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`El SEARCH FEE
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`(37 CFR1.16( ), (p), or (q))
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`37 CFR 1.16i
`INDEPENDENT CLAIMS
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`DAPPLICATIONSIZEFEE
`(37 CFR Mas»
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`N/A
`
`N/A
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`N/A
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`N/A
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`N/A
`
`_
`,
`m'”“S 20‘
`,
`_
`”"”“S3‘
`If the Specification and drawings exceed 100
`h
`t
`f
`th
`I‘
`t'
`'
`f
`d
`"9
`is$§5%‘E$‘IZ2‘?2is%ZI?%Iifi;§’?o?':§cfie
`additional 50 Sheets or fraction thereof. See
`35 U.S.C. 41 a 1 G and 37 CFR 1.16 S.
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`I:I MULTIPLE DEPENDENT CLAIM PRESENT (37 CFR1.16(j))
`* If the difference in column 1 is less than zero, enter“0“ in column 2.
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`APPLICATION AS AMENDED — PART II
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`(Column 1)
`CLAIMS
`REMAINING
`AFTER
`AMENDMENT
`
`(Column 2)
`HIGHEST
`NUMBER
`PREVIOUSLY
`PAID FOR
`
`(Column 3)
`
`PRESENT
`EXTRA
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`10/05/2009
`
`Minus
`I?£?'“’°”‘
`Minus
`'2S:*;:“:fi:“I
`I:I Application Size Fee (37 CFR 1.16(s))
`
`D FIRST PRESENTATION OF MULTIPLE DEPENDENT CLAIM (37 CFR1.16(j))
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`SMALL ENTITY
`
`OTHER THAN
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`SMALL ENTITY
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`ADDITIONAL
`FEE ($)
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`RATE“)
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`X $
`
`X $
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`=
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`=
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`RATE ($)
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`$52:
`
`$220:
`
`ADDITIONAL
`FEE W
`
`I-
`
`ZU
`
`JEDZU
`
`J E<
`
`(Column 1)
`CLAIMS
`REMAINING
`AFTER
`AMENDMENT
`H
`-
`,,
`2 Minus 2
`Minus
`
`HIGHEST
`NUMBER
`PREVIOUSLY
`PAID FOR
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`Total (37 CFR
`
`37 CFR 1.16 h
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`PRESENT
`EXTRA
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`ADDITIONAL
`FEE ($)
`
`RATE ($)
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`X 99
`
`ADDITIONAL
`FEE ($)
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`RATE ($)
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`X 99
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`D Application Size Fee (37 CFR 1.16(s))
`
`D FIRST PRESENTATION OF MULTIPLE DEPENDENT CLAIM (37 CFR1.16(j))
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`- OR 2
`OR
`ADD‘L
`FEE
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`AMENDMENT
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`If the Highest Number Previously Paid For IN THIS SPACE is less than 20, enter 20 .
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`This collection of information is required by 37 CFR 1.16. The information is required to obtain or retain a benefit by the public which is to file (and by the USPTO to
`process) an application. Confidentiality is governed by 35 U.S.C. 122 and 37 CFR 1.14. This collection is estimated to take 12 minutes to complete, including gathering,
`preparing, and submitting the completed application form to the USPTO. Time will vary depending upon the individual case. Any comments on the amount of time you
`require to complete this form and/or suggestions for reducing this burden, should be sent to the Chief Information Officer, U.S. Patent and Trademark Office, U.S.
`Department of Commerce, P.O. Box 1450, Alexandria, VA 22313-1450. DO NOT SEND FEES OR COMPLETED FORMS TO THIS
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`Legal Instrument Examiner:
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`Page 269 of 752
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`

`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`www.uspto.goV
`
`APPLICATION NO.
`
`F ING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONF {MATION NO.
`
`10/525,006
`
`03/28/2005
`
`Shirou Sawa
`
`2005_0232A
`
`1756
`
`513
`7590
`06/03/2009
`WENDEROTH, LIND&PONACK, 1.1.1».
`1030 15th Street, N.W.,
`Suite 400 East
`
`Washington, DC 20005-1503
`
`JAGOE, DONNAA
`PAPER NUMBER
`
`ART UNIT
`
`1614
`
`MAIL DATE
`
`06/03/2009
`
`DELIVERY MODE
`
`PAPER
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Pa e 270 of 752
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`PTOL—90A ( ev. 04/07)
`
`

`
`Office Action Summary
`
`Application No.
`
`10/525,006
`
`Examine,
`
`App|icant(s)
`
`SAWA ET AL.
`
`A,, Unit
`
`1614 —
`
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTH(S) OR THIRTY (30) DAYS,
`WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.
`- Extensions of time may be available under the provisions of 37 CFR 1.136(a).
`In no event, however, may a reply be timely filed
`after SIX (6) MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`-
`- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1)IXI Responsive to communication(s) filed on 15 January 2009.
`
`2a)IXI This action is FINAL.
`
`2b)I:I This action is non-final.
`
`3)I:I Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`
`closed in accordance with the practice under Ex parte Quayle, 1935 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims
`
`4)IZ C|aim(s) 19-29 31-34 36-51 53-56 and 58-63 is/are pending in the application.
`
`4a) Of the above c|aim(s) 39,40,61 and 62 is/are withdrawn from consideration.
`
`5)I:I C|aim(s) j is/are allowed.
`
`6)IXI C|aim(s) 19-29 31 -34 36-38 41-51 53-56 58-60 and 63 is/are rejected.
`
`7)I:I C|aim(s) j is/are objected to.
`
`8)I:I C|aim(s) j are subject to restriction and/or election requirement.
`
`Application Papers
`
`9)I:I The specification is objected to by the Examiner.
`
`10)I:I The drawing(s) filed on
`
`is/are: a)I:I accepted or b)I:I objected to by the Examiner.
`
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).
`
`11)I:I The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-152.
`
`Priority under 35 U.S.C. § 119
`
`12)I:I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`
`a)I:I All
`
`b)I:I Some * c)I:I None of:
`
`1.I:I Certified copies of the priority documents have been received.
`
`2.I:I Certified copies of the priority documents have been received in Application No.
`
`3.I:I Copies of the certified copies of the priority documents have been received in this National Stage
`
`application from the International Bureau (PCT Rule 17.2(a)).
`
`* See the attached detailed Office action for a list of the certified copies not received.
`
`Attach ment(s)
`
`1) D Notice of References Cited (PTO-892)
`2) D Notice of Draftsperson's Patent Drawing Review (PTO-948)
`3) IXI Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date 3/11/09.
`U.S. Patent and Trademark Office
`
`4) D Interview Summary (PTO-413)
`Paper N0(S)/IVI3” Data E
`5) I:I Noiice Oi informal Paieiii Appiicaiion
`6) D Other:
`.
`
`PTOL-326
`
`ev. 98-06
`age
`1 o 752
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`Office Action Summary
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`Part of Paper No./Mail Date 20090528
`
`

`
`Application/Control Number: 10/525,006
`
`Page 2
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`Art Unit: 1614
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`DETAILED ACTION
`
`Claims 19-29, 31-34, 36-51, 53-56 and 58-63 are pending in this application.
`
`Claims 39, 40, 61 and 62 are withdrawn from further consideration.
`
`Claims 19-29, 31-34, 36-38, 41-51, 53-56, 58-60 and 63 are rejected.
`
`Applicants’ arguments filed January 15, 2009 have been fully considered but they
`
`are not deemed to be persuasive. Rejections and/or objections not reiterated from
`
`previous office actions are hereby withdrawn. The following rejections and/or objections
`
`are either reiterated or newly applied. They constitute the complete set presently being
`
`applied to the instant application.
`
`Change of Examiner
`
`The examiner assigned to the instant application has changed. The new
`
`examiner is Donna Jagoe. Contact information is provided at the end of this Office
`
`Action.
`
`Priority
`
`As recited in the Office Action dated September 27, 2007, Applicant is reminded
`
`that a certified translation has not been proved for the claim to foreign priority of
`
`JP2003—012427, filed 1/21/2003. Since no translation has been provided, prior art
`
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`Application/Control Number: 10/525,006
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`Page 3
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`Art Unit: 1614
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`dates have been determined with reference to the priority date for the PCT application
`
`date, PCT/JP04/00350, filed 1/16/2004.
`
`Claim Rejections - 35 USC § 112
`
`The following is a quotation of the second paragraph of 35 U.S.C. 112:
`
`The specification shall conclude with one or more claims particularly pointing out and distinctly
`claiming the subject matter which the applicant regards as his invention.
`
`Claims 19-29, 31-34, 36-38, 41-51, 53-56, 58-60 and 63, are rejected under 35
`
`U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and
`
`distinctly claim the subject matter which applicant regards as the invention.
`
`Claims 19 and 41 recite an aqueous liquid preparation comprising at least 2-
`
`amino-3-(4-bromobenzoyl)phenylacetic acid (bromfenac) and an alkyl aryl polyether
`
`alcohol type polymer or polyethylene glycol fatty acid ester “wherein said liquid
`
`preparation is in the form of an eye drop”.
`
`It is unclear what is meant by “in the form of
`
`an eye drop.
`
`is this aqueous liquid preparation in a container shaped like an eye drop?
`
`It is suggested that the claim be amended to recite "wherein said liquid preparation is
`
`formulated for ophthalmic administration".
`
`Claim Rejections - 35 USC § 103
`
`The text of those sections of Title 35, U.S. Code not included in this action can
`
`be found in a prior Office action.
`
`Claims 19-29, 31-34, 36-38, 41-51, 53-56, 58-60 and 63 are rejected under 35
`
`U.S.C. 103(a) as being unpatentable over Hellberg et al. (US 5,998,465; 1999) and
`
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`Application/Control Number: 10/525,006
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`Page 4
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`Art Unit: 1614
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`Nolan, et al. (“The topical anti—inflammatory and analgesic properties of bromfenac in
`
`rodents; Agents and Actions; 1988 Aug; 25(1—2):77—85; cited with previous Interview
`
`Summary).
`
`Hellberg teaches pharmaceutical compositions of anti—inflammatory compounds
`
`(abstract); the compounds include a non—steroidal anti—inflammatory moiety (NSAIA)
`
`and an antioxidant moiety linked through an ester bond formed by the carboxylic acid
`
`moiety of the NSAIA (col. 2, lines 20-24); NSAIA moieties include bromfenac (col. 3, line
`
`57; claim 5); examples 2 and 3 (col. 11) teach topical ophthalmic formulations useful for
`
`treating inflammation, both of these formulations include tyloxapol at 0.01-0.05 w/v %,
`
`HPMC (thickener), benzalkonium chloride (preservative), edetate disodium (chelating
`
`agent) (col. 11, Examples 2-3); the pH is adjusted to 7.4 (about 7.5; col. 11, line 64);
`
`topical formulations administered by drops (eye drops; col. 10, lines 15-18). Hellberg
`
`does not teach bromfenac (only the ester of bromfenac). Nolan teaches bromfenac (the
`
`sodium salt, sesquihydrate form) was effective as a topical analgesic at concentrations
`
`of 0.1—0.32 % in mice and more potent than the other drugs tested (abstract).
`
`It would
`
`have been obvious for one of ordinary skill in the art at the time of the invention to
`
`substitute bromfenac, taught by Nolan for the compounds of Hellberg in the example
`
`formulation giving formulations of the instant claims and to select concentrations of
`
`bromfenac sodium, sesquihydrate of 0.1, about 0.2 and about 0.32 %, in the invention
`
`of Gamache, since these values have demonstrated efficacy for topical use.
`
`It would
`
`also have been obvious to adjust the concentration of tyloxapol, to optimize the
`
`formulations for the effect would on the solubility and stability of the aqueous
`
`Page 274 of 752
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`Application/Control Number: 10/525,006
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`Page 5
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`Art Unit: 1614
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`preparations, which would have resulted in the effective tyloxapol concentrations of
`
`about 0.02 and 0.3 w/v%, recited in claims 25 and 32. The motivation to substitute
`
`bromfenac in the Hellberg formulations would have bee the art—recognized equivalent
`
`activity of bromfenac as an anti—inflammatory agent in topical usage. The motivation to
`
`adjust concentrations would have been the routine optimization of these topical
`
`ophthalmic formulations for anti—inflammatory use in the eye.
`
`Claims 19-29, 31-34 and 36-38 are rejected under 35 U.S.C. 103(a) as being
`
`unpatentable over Gamache, et al. (WO 01/15677 A2; 03/2001; previously cited) and
`
`ISTA Pharmaceuticals (“New Drug Applications: Xibrom”,
`
`http://vvwwdrugscom/nda/xibrom 040525.htmi, accessed online 9/19/2007; previously
`
`cited) or Nolan, et al. (“The topical anti—inflammatory and analgesic properties of
`
`bromfenac in rodents; Agents and Actions; 1988 Aug; 25(1—2):77—85; provided with
`
`Interview Summary).
`
`Gamache teaches compositions for otic and intranasal use (p.6, lines 5-6) that
`
`contain a combination of a 5-HT agonist and an anti—inflammatory agent (p. 6, lines 1-4;
`
`p. 12 lines 9-10) or alternatively sequential or concurrent dosing of separate
`
`compositions that contain the 5-HT antagonist in one composition and the anti-
`
`inflammatory agent in a second composition (p. 12, lines 9-11); specifically claimed is
`
`the anti-inflammatory specie bromfenac (2-amino-3-(4-bromobenzoyl)phenylacetic
`
`acid). Typical concentrations of anti—inflammatory agents, such as bromfenac, are
`
`taught in the range 0.01-1.0 % (w/v) (overlapping with 0.01-0.5; p. 13, lines 6-8);
`
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`Application/Control Number: 10/525,006
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`Page 6
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`Art Unit: 1614
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`aqueous formulations are preferred (p. 10, lines 11-14);
`
`tyloxapol is taught in a
`
`concentration of 0.05 % (w/v) (p. 16, line 30).
`
`It is noted that instant claim 21 and
`
`further dependent claims limit the options for the salt of bromfenac to the sodium salt,
`
`and that the specific concentrations recited in dependent claims apply to the sodium
`
`salt; the other options (bromfenac or a hydrate of bromfenac) are still viable choices that
`
`are part of instant claim 21 claims depending therefrom (which depend on and include
`
`the options of claim 20). Gamache teaches bromfenac in the concentration range of
`
`claim 20 (which is also an option of claims 21-24 and 31). The salt form of bromfenac in
`
`solution will be the same when the acid is dissolved in a solution followed by adjustment
`
`to the desired pH with NaOH/HCl (Gamache, p. 15, line 33) as when the sodium salt is
`
`dissolved in solution adjusted to the same pH; in this case Gamache also teaches the
`
`sodium salt limitation of instant claim 21, albeit not the sodium salt concentration
`
`limitation of instant claim 22 and further dependent claims, since the claim is drawn to
`
`an aqueous liquid preparation, irrespective of how it is prepared. However, the
`
`concentration range of 0.01—1 .0% overlaps and encompasses the claimed concentration
`
`range of the sodium salt of bromfenac instantly claimed.
`
`The ISTA Pharmaceuticals news release demonstrates that products containing
`
`0.1 % bromfenac sodium acquired US marketing rights for Xibrom in May 2002 (were
`
`known by others in this country before applicant’s priority date, a 35 USC 102(a) date).
`
`Nolan teaches bromfenac (the sodium salt, sesquihydrate form) was effective as a
`
`topical analgesic at concentrations of 0.1—0.32 % in mice and more potent than the other
`
`drugs tested (abstract).
`
`It would have been obvious for one of ordinary skill in the art at
`
`Page 276 of 752
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`Application/Control Number: 10/525,006
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`Page 7
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`Art Unit: 1614
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`the time of the invention to select concentrations of bromfenac sodium, sesquihydrate of
`
`0.1, about 0.2 and about 0.32 %, in the invention of Gamache, since these values have
`
`demonstrated efficacy for topical use.
`
`It would have been obvious to adjust the
`
`concentration of tyloxapol, to see what the effect would be on the solubility and stability
`
`of the aqueous preparations, w