`
`First Named Inventor
`
`Attorney Docket No. 2014-0075
`
`Shirou SAWA
`
`Serial No. NEW
`
`Filed January 28, 2014
`
`AQUEOUS LIQUID PREPARATION
`CONTAINING 2-AMIN0-3-(4-
`BROMOBENZOYL )PHENYLACETIC ACID
`(Rule 1.53(b) Divisional
`of Serial No. 13/687,242,
`Filed November 28, 2012)
`
`PRELIMINARY AMENDMENT
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir/Madam:
`
`Prior to examination, please amend the above-identified application as follows:
`
`The USPTO is hereby authorized to charge any fees under 37 C.F.R. §§ 1.16, 1.17, and 1.492, which may be required by this
`paper to Deposit Account No. 23-0975, except fees for multiple dependent claims.
`
`SENJU EXHIBIT 2254
`LUPIN v. SENJU
`IPR2015-01097
`
`Page 1 of 8
`
`
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`AMENDMENTS TO THE CLAIMS
`
`1-18. (Cancelled)
`
`19. (New)
`
`A stable aqueous liquid preparation comprising: (a) a first component; and (b) a
`
`second component; wherein the first component is 2-amino-3-( 4-bromobenzoyl)phenylacetic
`
`acid or a pharmacologically acceptable salt thereof or a hydrate thereof; wherein the hydrate is at
`
`least one selected from a 1/2 hydrate, 1 hydrate, and 3/2 hydrate; the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation and is present in the preparation at
`
`a concentration from about 0.05 w/v% to about 0.2 w/v %; the second component is tyloxapol
`
`and is present in said liquid preparation in an amount sufficient to stabilize said first component;
`
`and wherein said stable liquid preparation is formulated for ophthalmic administration.
`
`20. (New)
`
`The aqueous liquid preparation according to claim 19, further comprising a
`
`quaternary ammonium salt.
`
`21. (New)
`
`The aqueous liquid preparation according to claim 19, wherein the first
`
`component is a 2-amino-3-( 4-bromobenzoyl)phenylacetic acid sodium salt.
`
`22. (New)
`
`The aqueous liquid preparation according to claim 19, wherein the concentration
`
`oftyloxapol is from about 0.01 w/v% to about 0.05 w/v %.
`
`23. (New)
`
`The aqueous liquid preparation according to claim 19, wherein the pH is from
`
`about 7.5 to about 8.5.
`
`24. (New)
`
`The stable aqueous liquid preparation of claim 19; wherein the stable aqueous
`
`liquid preparation consists essentially of: (a) 2-amino-3-(4-bromobenzoyl)phenylacetic acid
`
`sodium salt, (b) tyloxapol, (c) boric acid, (d) sodium tetra borate, (e) EDTA sodium salt, (f)
`
`benzalkonium chloride, (g) polyvinylpyrrolidone, and (h) sodium sulfite, wherein said liquid
`
`preparation is formulated for ophthalmic administration, wherein the concentration of the 2-
`
`amino-3-( 4-bromobenzoyl)phenylacetic acid sodium salt is from about 0.02 w/v% to about 0.1
`
`2
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`Page 2 of 8
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`
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`w/v %, and wherein the concentration oftyloxapol is from about 0.01 w/v% to about 0.05 w/v
`
`%.
`
`25. (New)
`
`A stable aqueous liquid preparation comprising: (a) a first component; and (b) a
`
`second component; wherein the first component is 2-amino-3-( 4-bromobenzoyl)phenylacetic
`
`acid or a pharmacologically acceptable salt thereof or a hydrate thereof; wherein the hydrate is at
`
`least one selected from a 1/2 hydrate, 1 hydrate, and 3/2 hydrate; the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation and is present in the preparation at
`
`a concentration from about 0.05 w/v% to about 0.2 w/v %; the second component is tyloxapol;
`
`wherein said stable liquid preparation is formulated for ophthalmic administration; and wherein
`
`the stable aqueous liquid preparation is characterized in that greater than about 90% of the
`original amount of the first component remains in the preparation after storage at about 60 oc for
`4 weeks.
`
`26. (New)
`
`The aqueous liquid preparation according to claim 25, further comprising a
`
`quaternary ammonium salt.
`
`27. (New)
`
`The stable aqueous liquid preparation of claim 25; wherein the stable aqueous
`
`liquid preparation is characterized in that greater than about 92% of the original amount of the
`first component remains in the preparation after storage at about 60 oc for 4 weeks.
`
`28. (New)
`
`The aqueous liquid preparation according to claim 25; wherein the concentration
`
`oftyloxapol is from about 0.01 w/v% to about 0.05 w/v %; and wherein the first component is a
`
`2-amino-3-( 4-bromobenzoyl)phenylacetic acid sodium salt, wherein the concentration of the 2-
`
`amino-3-( 4-bromobenzoyl)phenylacetic acid sodium salt is from about 0.05 w/v% to about 0.1
`
`w/v%.
`
`29. (New)
`
`The aqueous liquid preparation according to claim 28, wherein the pH is from
`
`about 7.5 to about 8.5.
`
`30. (New)
`
`The stable aqueous liquid preparation of claim 25; wherein the stable aqueous
`
`liquid preparation consists essentially of: (a) 2-amino-3-(4-bromobenzoyl)phenylacetic acid or a
`
`pharmacologically acceptable salt thereof or a hydrate thereof, wherein the hydrate is at least one
`
`3
`
`Page 3 of 8
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`
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`selected from a 1/2 hydrate, 1 hydrate, and 3/2 hydrate; (b) tyloxapol; (c) boric acid; (d) sodium
`
`tetraborate; (e) EDTA sodium salt; (f) benzalkonium chloride; (g) polyvinylpyrrolidone; and (h)
`
`sodium sulfite; and wherein the concentration of the 2-amino-3-( 4-bromobenzoyl)phenylacetic
`
`acid sodium salt is from about 0.05 w/v% to about 0.1 w/v %, and the concentration oftyloxapol
`
`is about 0.02 w/v%.
`
`31. (New)
`
`A stable aqueous liquid preparation comprising: (a) a first component; and (b) a
`
`second component; wherein the first component is 2-amino-3-( 4-bromobenzoyl)phenylacetic
`
`acid or a pharmacologically acceptable salt thereof or a hydrate thereof; wherein the hydrate is at
`
`least one selected from a 1/2 hydrate, 1 hydrate, and 3/2 hydrate; the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation and is present in the preparation at
`
`a concentration from about 0.05 w/v% to about 0.2 w/v %; the second component is tyloxapol;
`
`wherein said stable liquid preparation is formulated for ophthalmic administration; provided that
`
`the liquid preparation does not include mannitol.
`
`32. (New)
`
`The aqueous liquid preparation according to claim 31, further comprising a
`
`quaternary ammonium salt.
`
`33. (New)
`
`The aqueous liquid preparation according to claim 31, wherein the first
`
`component is a 2-amino-3-( 4-bromobenzoyl)phenylacetic acid sodium salt.
`
`34. (New)
`
`The aqueous liquid preparation according to claim 31, wherein the concentration
`
`oftyloxapol is from about 0.01 w/v% to about 0.05 w/v% and the concentration of the 2-amino-
`
`3-(4-bromobenzoyl)phenylacetic acid sodium salt is from about 0.05 to about 0.1 w/v %.
`
`35. (New)
`
`The aqueous liquid preparation according to claim 31, wherein the pH is from
`
`about 7.5 to about 8.5.
`
`36. (New)
`
`The stable aqueous liquid preparation of claim 31; wherein the stable aqueous
`
`liquid preparation consists essentially of: (a) 2-amino-3-(4-bromobenzoyl)phenylacetic acid or a
`
`pharmacologically acceptable salt thereof or a hydrate thereof, wherein the hydrate is at least one
`
`selected from a 1/2 hydrate, 1 hydrate, and 3/2 hydrate; (b) tyloxapol; (c) boric acid; (d) sodium
`
`tetraborate; (e) EDTA sodium salt; (f) benzalkonium chloride; (g) polyvinylpyrrolidone; and (h)
`
`4
`
`Page 4 of 8
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`
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`sodium sulfite; wherein the concentration of the 2-amino-3-( 4-bromobenzoyl)phenylacetic acid
`
`sodium salt is from about 0.02 w/v% to about 0.1 w/v %, and the concentration oftyloxapol is
`
`from about 0.02 w/v% to about 0.05 w/v %.
`
`37. (New)
`
`The stable aqueous liquid preparation of claim 31; wherein the stable aqueous
`
`liquid preparation is characterized in that greater than about 90% of the original amount of the
`first component remains in the preparation after storage at about 60 oc for 4 weeks.
`
`38. (New)
`
`The stable aqueous liquid preparation according to claim 3 7, further comprising a
`
`quaternary ammonium salt.
`
`39. (New)
`
`The stable aqueous liquid preparation of claim 3 7; wherein the stable aqueous
`
`liquid preparation is characterized in that greater than about 92% of the original amount of the
`first component remains in the preparation after storage at about 60 oc for 4 weeks.
`
`40. (New)
`
`The stable aqueous liquid preparation according to claim 39, wherein the
`
`concentration oftyloxapol is from about 0.01 w/v% to about 0.05 w/v %; and wherein the first
`
`component is a 2-amino-3-( 4-bromobenzoyl)phenylacetic acid sodium salt, wherein the
`
`concentration of the 2-amino-3-( 4-bromobenzoyl)phenylacetic acid sodium salt is from about
`
`0.05 w/v% to about 0.1 w/v %.
`
`41. (New)
`
`The aqueous liquid preparation according to claim 40, wherein the pH is from
`
`about 7.5 to about 8.5.
`
`42. (New)
`
`The stable aqueous liquid preparation of claim 31; wherein the stable aqueous
`
`liquid preparation consists essentially of: (a) 2-amino-3-(4-bromobenzoyl)phenylacetic acid or a
`
`pharmacologically acceptable salt thereof or a hydrate thereof, wherein the hydrate is at least one
`
`selected from a 1/2 hydrate, 1 hydrate, and 3/2 hydrate; (b) tyloxapol; (c) boric acid; (d) sodium
`
`tetraborate; (e) EDTA sodium salt; (f) benzalkonium chloride; (g) polyvinylpyrrolidone; and (h)
`
`sodium sulfite; wherein said liquid preparation is formulated for ophthalmic administration; and
`
`wherein the concentration of the 2-amino-3-( 4-bromobenzoyl)phenylacetic acid sodium salt is
`
`from about 0.05 w/v% to about 0.1 w/v %.
`
`5
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`Page 5 of 8
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`43. (New)
`
`The aqueous liquid preparation of claim I9, wherein the aqueous liquid
`
`preparation further satisfies the preservative efficacy standard of US Pharmacopoeia as follows:
`
`viable cell counts ofbacteria (S. aureus, P.aeruginosa) 24 hours and 7 days after inoculation
`
`decrease to not more than Ill 0 and not more than Ill 000, respectively, and thereafter, the cell
`
`count levels off or decreases; and
`
`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.
`
`44. (New)
`
`The aqueous liquid preparation of claim 22, wherein the aqueous liquid
`
`preparation further satisfies the preservative efficacy standard of US Pharmacopoeia as follows:
`
`viable cell counts ofbacteria (S. aureus, P.aeruginosa) 24 hours and 7 days after inoculation
`
`decrease to not more than Ill 0 and not more than Ill 000, respectively, and thereafter, the cell
`
`count levels off or decreases; and
`
`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.
`
`45. (New)
`
`The aqueous liquid preparation of claim 25, wherein the aqueous liquid
`
`preparation further satisfies the preservative efficacy standard of US Pharmacopoeia as follows:
`
`viable cell counts ofbacteria (S. aureus, P.aeruginosa) 24 hours and 7 days after inoculation
`
`decrease to not more than Ill 0 and not more than Ill 000, respectively, and thereafter, the cell
`
`count levels off or decreases; and
`
`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.
`
`6
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`Page 6 of 8
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`46. (New)
`
`The aqueous liquid preparation of claim 27, wherein the aqueous liquid
`
`preparation further satisfies the preservative efficacy standard of US Pharmacopoeia as follows:
`
`viable cell counts ofbacteria (S. aureus, P.aeruginosa) 24 hours and 7 days after inoculation
`
`decrease to not more than Ill 0 and not more than Ill 000, respectively, and thereafter, the cell
`
`count levels off or decreases; and
`
`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.
`
`47. (New)
`
`The aqueous liquid preparation of claim 3I, wherein the aqueous liquid
`
`preparation further satisfies the preservative efficacy standard of US Pharmacopoeia as follows:
`
`viable cell counts ofbacteria (S. aureus, P.aeruginosa) 24 hours and 7 days after inoculation
`
`decrease to not more than Ill 0 and not more than Ill 000, respectively, and thereafter, the cell
`
`count levels off or decreases; and
`
`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.
`
`48. (New)
`
`The aqueous liquid preparation according to claim I9, further comprising one or
`
`more additives selected from the group consisting of a preservative, buffer, thickener, stabilizer,
`
`chelating agent, and pH controlling agent.
`
`7
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`Page 7 of 8
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`
`
`REMARKS
`
`The present application is a divisional of Serial No. 13/687,242 filed November 28, 2012.
`
`The present Preliminary Amendment is submitted to cancel original claims 1-18, add new claims
`
`19-48.
`
`No new matter has been added.
`
`Respectfully submitted,
`a rren
`• Cheek,Jr./
`/w
`M
`Digitally signed by /Warren M.
`h k
`C ee , Jr./
`~:~;2014.01.2810:55:54-05'00'
`Warren M. Cheek
`Registration No. 33,367
`Attorney for Applicant
`
`DN: cn=/Warren M. Cheek, Jr./, o, ou,
`email=wcheek@wenderoth.com,
`
`WMC/dlk
`Washington, D.C. 20005-1503
`Telephone (202) 721-8200
`Facsimile (202) 721-8250
`January 28, 2014
`
`8
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`Page 8 of 8