Case 1:15-cv-00335-JBS-KMW Document 1 Filed 01/16/15 Page 1 of 9 PageID: 1
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`
`
`Melissa A. Chuderewicz
`PEPPER HAMILTON LLP
`(A Pennsylvania Limited Liability Partnership)
`Suite 400
`301 Carnegie Center
`Princeton, NJ 08543
`Tel: (609) 951-4118
`Fax: (609) 452-1147
`chuderem@pepperlaw.com
`
`Attorneys for Plaintiffs
`SENJU PHARMACEUTICAL CO., LTD.,
`BAUSCH & LOMB INCORPORATED and
`BAUSCH & LOMB PHARMA HOLDINGS CORP.
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
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`Civil Action No.:
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`SENJU PHARMACEUTICAL CO., LTD.,
`BAUSCH & LOMB INCORPORATED and
`BAUSCH & LOMB PHARMA HOLDINGS
`CORP.
`
`
`Plaintiffs,
`
`v.
`
`LUPIN, LTD. and LUPIN
`PHARMACEUTICALS, INC.,
`
`
`Defendants.
`
`
`
`
`
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`COMPLAINT FOR PATENT INFRINGEMENT
`
`Plaintiffs Senju Pharmaceutical Co., Ltd., Bausch & Lomb Incorporated and Bausch &
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`Lomb Pharma Holdings Corp. (collectively “Plaintiffs”) by way of Complaint against
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`Defendants Lupin, Ltd. (“Lupin”) and Lupin Pharmaceuticals, Inc. (collectively “Defendants”)
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`allege as follows:
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`#32159347 v1
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`Page 1 of 33
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`SENJU EXHIBIT 2010
`LUPIN v. SENJU
`IPR2015-01099
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`

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`Case 1:15-cv-00335-JBS-KMW Document 1 Filed 01/16/15 Page 2 of 9 PageID: 2
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`
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`THE PARTIES
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`1.
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`Plaintiff Senju Pharmaceutical Co., Ltd. (“Senju”) is a corporation organized and
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`existing under the laws of Japan, with a principal place of business at 2-5-8, Hirano-machi,
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`Chuo-ku, Osaka 541-0046, Japan.
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`2.
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`Plaintiff Bausch & Lomb Incorporated (“B+L”) is a corporation organized and
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`existing under the laws of New York, with a place of business at 1400 North Goodman St.,
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`Rochester, New York 14609. B+L is the registered holder of approved New Drug Application
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`No. 203168, which covers Prolensa®.
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`3.
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`Plaintiff Bausch & Lomb Pharma Holdings Corp. (“B+L Pharma Holdings”) is a
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`corporation organized and existing under the laws of Delaware, with a place of business at 700
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`Route 202/206, Bridgewater, New Jersey 08807. B+L Pharma Holdings is a wholly-owned
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`subsidiary of B+L.
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`4.
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`Upon information and belief, defendant Lupin, Ltd. is a corporation organized and
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`existing under the laws of India, having a corporate headquarters at C/4 Laxmi Towers, Bandra
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`Kurla Complex, Bandra (E), Mumbai 400 051.
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`5.
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`Upon information and belief, defendant Lupin Pharmaceuticals, Inc. is a
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`corporation organized and existing under the laws of Virginia, having a principal place of
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`business at 111 S. Calvert Street, 21st Floor, Baltimore, MD 21202. Upon information and belief,
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`Lupin Pharmaceuticals, Inc. is a wholly-owned subsidiary of Lupin, Ltd.
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`NATURE OF THE ACTION
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`6.
`
`This is an action for infringement of United States Patent Nos. 8,871,813 (“the
`
`’813 patent”) and 8,927,606 (“the ʼ606 patent”), arising under the United States patent laws,
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`Title 35, United States Code, § 100 et seq., including 35 U.S.C. §§ 271 and 281. This action
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`relates to Lupin’s filing of an Abbreviated New Drug Application (“ANDA”) under Section
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`
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`505(j) of the Federal Food, Drug, and Cosmetic Act (“the Act”), 21 U.S.C. § 355(j), seeking U.S.
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`Food and Drug Administration (“FDA”) approval to market generic Bromfenac Ophthalmic
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`Solution 0.07% (“Lupin’s generic bromfenac ophthalmic solution”).
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`JURISDICTION AND VENUE
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`7.
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`8.
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`This Court has subject matter jurisdiction under 28 U.S.C. §§ 1331 and 1338(a).
`
`Upon information and belief, this Court has jurisdiction over Lupin. Upon
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`information and belief, Lupin is in the business of manufacturing, marketing, importing and
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`selling pharmaceutical drug products, including generic drug products. Upon information and
`
`belief, Lupin directly manufactures, markets and sells generic drug products throughout the
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`United States and in this judicial district, and this judicial district is a likely destination for
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`Lupin’s generic bromfenac ophthalmic solution. Upon information and belief, Lupin
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`purposefully has conducted and continues to conduct business in this judicial district.
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`9.
`
`Upon information and belief, this court has jurisdiction over Lupin
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`Pharmaceuticals, Inc. Upon information and belief, Lupin Pharmaceuticals, Inc. directly, or
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`indirectly, manufactures, markets and sells generic drug products, including generic drug
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`products manufactured by Lupin, throughout the United States and in this judicial district. Upon
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`information and belief, Lupin Pharmaceuticals, Inc. purposefully has conducted and continues to
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`conduct business in this judicial district.
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`10.
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`Upon information and belief, venue is proper in this judicial district under 28
`
`U.S.C. §§ 1391(c) and (d), and § 1400(b).
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`THE PATENTS IN SUIT
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`11.
`
`The U.S. Patent and Trademark Office (“PTO”) issued the ’813 patent on
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`October 28, 2014. The ’813 patent claims, inter alia, formulations of bromfenac for ophthalmic
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`administration. Plaintiffs hold all substantial rights in the ’813 patent and have the right to sue
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`for infringement thereof. Senju is the assignee of the ’813 patent. A copy of the ’813 patent is
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`attached hereto as Exhibit A.
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`12.
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`The U.S. Patent and Trademark Office (“PTO”) issued the ’606 patent on
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`January 6, 2015. The ’606 patent claims, inter alia, formulations of bromfenac for ophthalmic
`
`administration. Plaintiffs hold all substantial rights in the ’606 patent and have the right to sue
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`for infringement thereof. Senju is the assignee of the ’606 patent. A copy of the ’606 patent is
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`attached hereto as Exhibit B.
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`13.
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`B+L is the holder of New Drug Application (“NDA”) No. 203168 for Prolensa®,
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`which the FDA approved on April 5, 2013. In conjunction with NDA No. 203168, the ’290
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`patent is listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations
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`(“the Orange Book”).
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`14.
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`Bromfenac Ophthalmic Solution 0.07% is sold in the United States under the
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`trademark Prolensa®.
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`LUPIN’S INFRINGING ANDA SUBMISSION
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`15.
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`Upon information and belief, Lupin filed with the FDA ANDA No. 206027,
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`under Section 505(j) of the Act and 21 U.S.C. § 355(j).
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`16.
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`Upon information and belief, Lupin’s ANDA No. 206027 seeks FDA approval to
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`sell in the United States Lupin’s generic bromfenac ophthalmic solution, intended to be a generic
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`version of Prolensa®.
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`17.
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`Bausch & Lomb received a letter from Lupin dated December 17, 2014,
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`purporting to be a Notice of Certification for ANDA No. 206027 (“Lupin’s notice letter”) under
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`Section 505(j)(2)(B)(ii) of the Act, 21 U.S.C. § 355(j)(2)(B)(ii), and 21 § C.F.R. 314.95(c).
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`18.
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`Lupin’s notice letter alleges that Lupin has submitted to the FDA ANDA No.
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`206027 seeking FDA approval to sell generic bromfenac ophthalmic solution, intended to be a
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`generic version of Prolensa®.
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`19.
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`Upon information and belief, ANDA No. 206027 seeks approval of Lupin’s
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`generic bromfenac ophthalmic solution that is the same, or substantially the same, as Prolensa®.
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`20.
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`Upon information and belief, Lupin’s actions relating to ANDA No. 207584
`
`complained of herein were done with the cooperation, the participation, the assistance of, and at
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`least in part for the benefit of Lupin Pharmaceuticals, Inc.
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`COUNT I
`
`Infringement of the ’813 patent under § 271(e)(2)
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`Paragraphs 1-20 are incorporated herein as set forth above.
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`Under 35 U.S.C. § 271(e)(2), Lupin has infringed at least one claim of the ’813
`
`21.
`
`22.
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`patent by submitting, or causing to be submitted to the FDA, ANDA No. 206027 seeking
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`approval for the commercial marketing of Lupin’s generic bromfenac ophthalmic solution before
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`the expiration date of the ’813 patent.
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`23.
`
`Upon information and belief, Lupin’s generic bromfenac ophthalmic solution
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`will, if approved and marketed, infringe at least one claim of the ’813 patent.
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`24.
`
`Upon information and belief, Lupin will, through the manufacture, use import,
`
`offer for sale and/or sale of Lupin’s generic bromfenac ophthalmic solution, directly infringe,
`
`contributorily infringe and/or induce infringement of at least one claim of the ’813 patent.
`
`COUNT II
`
`Declaratory Judgment of Infringement of the ’813 Patent
`
`25.
`
`Paragraphs 1-24 are incorporated herein as set forth above.
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`2202.
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`26.
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`These claims arise under the Declaratory Judgment Act, 28 U.S.C. §§ 2201 and
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`27.
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`There is an actual case or controversy such that the Court may entertain Plaintiffs’
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`request for declaratory relief consistent with Article III of the United States Constitution, and this
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`actual case or controversy requires a declaration of rights by this Court.
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`28.
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`Lupin has made, and will continue to make, substantial preparation in the United
`
`States to manufacture, use, offer to sell, sell and/or import Lupin’s generic bromfenac
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`ophthalmic solution before the expiration date of the ’813 patent, including Lupin’s filing of
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`ANDA No. 206027.
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`29.
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`Upon information and belief, any commercial manufacture, use, offer for sale,
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`sale, and/or importation of Lupin’s generic bromfenac ophthalmic solution will directly infringe,
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`contributorily infringe and/or induce infringement of at least one claim of the ’813 patent.
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`
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`30.
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`Plaintiffs are entitled to a declaratory judgment that future commercial
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`manufacture, use, offer for sale, sale, and/or importation of Lupin’s generic bromfenac
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`ophthalmic solution will constitute infringement of at least one claim of the ’813 patent.
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`COUNT III
`
`Infringement of the ’606 patent under § 271(e)(2)
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`Paragraphs 1-30 are incorporated herein as set forth above.
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`Under 35 U.S.C. § 271(e)(2), Lupin has infringed at least one claim of the ’606
`
`31.
`
`32.
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`patent by submitting, or causing to be submitted to the FDA, ANDA No. 206027 seeking
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`approval for the commercial marketing of Lupin’s generic bromfenac ophthalmic solution before
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`the expiration date of the ’606 patent.
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`33.
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`Upon information and belief, Lupin’s generic bromfenac ophthalmic solution
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`will, if approved and marketed, infringe at least one claim of the ’606 patent.
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`34.
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`Upon information and belief, Lupin will, through the manufacture, use import,
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`offer for sale and/or sale of Lupin’s generic bromfenac ophthalmic solution, directly infringe,
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`contributorily infringe and/or induce infringement of at least one claim of the ’606 patent.
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`COUNT IV
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`Declaratory Judgment of Infringement of the ’606 Patent
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`Paragraphs 1-34 are incorporated herein as set forth above.
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`These claims arise under the Declaratory Judgment Act, 28 U.S.C. §§ 2201 and
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`35.
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`36.
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`2202.
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`37.
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`There is an actual case or controversy such that the Court may entertain Plaintiffs’
`
`request for declaratory relief consistent with Article III of the United States Constitution, and this
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`actual case or controversy requires a declaration of rights by this Court.
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`38.
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`Lupin has made, and will continue to make, substantial preparation in the United
`
`States to manufacture, use, offer to sell, sell and/or import Lupin’s generic bromfenac
`
`ophthalmic solution before the expiration date of the ’606 patent, including Lupin’s filing of
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`ANDA No. 206027.
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`39.
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`Upon information and belief, any commercial manufacture, use, offer for sale,
`
`sale, and/or importation of Lupin’s generic bromfenac ophthalmic solution will directly infringe,
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`contributorily infringe and/or induce infringement of at least one claim of the ’606 patent.
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`
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`40.
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`Plaintiffs are entitled to a declaratory judgment that future commercial
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`manufacture, use, offer for sale, sale, and/or importation of Lupin’s generic bromfenac
`
`ophthalmic solution will constitute infringement of at least one claim of the ’606 patent.
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`PRAYER FOR RELIEF
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`WHEREFORE, Plaintiffs respectfully request that the Court enter judgment in their
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`favor and against Defendants on the patent infringement claim set forth above and respectfully
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`request that this Court:
`
`1.
`
`enter judgment that, under 35 U.S.C. § 271(e)(2), Lupin has infringed at least one
`
`claim of the ’813 patent through Lupin’s submission of ANDA No. 206027 to the FDA to obtain
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`approval for the commercial manufacture, use, import, offer for sale and/or sale in the United
`
`States of Lupin’s generic bromfenac ophthalmic solution before the expiration of the ’813 patent;
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`2.
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`enter judgment that, under 35 U.S.C. § 271(e)(2), Lupin has infringed at least one
`
`claim of the ’606 patent through Lupin’s submission of ANDA No. 206027 to the FDA to obtain
`
`approval for the commercial manufacture, use, import, offer for sale and/or sale in the United
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`States of Lupin’s generic bromfenac ophthalmic solution before the expiration of the ’606 patent;
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`3.
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`order that the effective date of any approval by the FDA of Lupin’s generic
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`bromfenac ophthalmic solution be a date that is not earlier than the expiration of the ’813 patent
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`and the ʼ606 patent, or such later date as the Court may determine;
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`4.
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`enjoin Defendants from the commercial manufacture, use, import, offer for sale
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`and/or sale of Lupin’s generic bromfenac ophthalmic solution until expiration of the ’813 patent
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`and the ʼ606 patent, or such later date as the Court may determine;
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`5.
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`enjoin Defendants and all persons acting in concert with Defendants from
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`seeking, obtaining or maintaining approval of Lupin’s ANDA No. 206027 until expiration of the
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`’813 patent and the ʼ606 patent;
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`6.
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`declare this to be an exceptional case under 35 U.S.C. §§ 285 and 271(e)(4) and
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`award Plaintiffs costs, expenses and disbursements in this action, including reasonable attorneys
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`fees; and
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`7.
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`award Plaintiff such further and additional relief as this Court deems just and
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`proper.
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`Dated: January 16, 2015
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`Respectfully submitted,
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`
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`s/ Melissa A. Chuderewicz
`Melissa A. Chuderewicz
`PEPPER HAMILTON, LLP
`(A Pennsylvania Limited Liability Partnership)
`301 Carnegie Center
`Suite 400
`Princeton, NJ 08543-5276
`(609) 951-4118
`chuderem@pepperlaw.com
`
`Attorneys for Plaintiffs
`SENJU PHARMACEUTICAL CO., LTD.,
`BAUSCH & LOMB INCORPORATED and
`BAUSCH & LOMB PHARMA HOLDINGS CORP.
`
`
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`Of Counsel:
`Bryan C. Diner
`Justin J. Hasford
`FINNEGAN, HENDERSON,
`FARABOW, GARRETT & DUNNER, LLP
`901 New York Avenue, NW
`Washington, DC 20001-4413
`(202) 408-4000
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`Case 1:15-cv-00335-JBS-KMW Document 1-1 Filed 01/16/15 Page 1 of 10 PageID: 10
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`
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`EXHIBIT A
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`Page 10 of 33
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`Case 1:15-cv-00335-JBS-KMW Document 1-1 Filed 01/16/15 Page 2 of 10 PageID: 11
`I IIIII
`1111111111111111111111111111111111111111111111111111111111111
`US008871813B2
`
`c12) United States Patent
`Sawa et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 8,871,813 B2
`*Oct. 28, 2014
`
`(54) AQUEOUS LIQUID PREPARATION
`CONTAINING
`2-AMIN0-3-( 4-BROMOBENZOYL)PHENYL(cid:173)
`ACETICACID
`
`(71) Applicant: Senju Pharmaceutical Co., Ltd., Osaka
`(JP)
`
`(72)
`
`Inventors: Shirou Sawa, Hyogo (JP); Shuhei
`Fujita, Hyogo (JP)
`
`(73) Assignee: Senju Pharmaceutical Co., Ltd., Osaka
`(JP)
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`This patent is subject to a terminal dis(cid:173)
`claimer.
`
`(21) Appl. No.: 14/261,720
`
`(22) Filed:
`
`Apr. 25, 2014
`
`(65)
`
`Prior Publication Data
`
`US 2014/0235721 Al
`
`Aug. 21, 2014
`
`Related U.S. Application Data
`
`(62) Division of application No. 14/165,976, filed on Jan.
`28, 2014, now Pat. No. 8,754,131, which is a division
`of application No. 13/687,242, filed on Nov. 28, 2012,
`now Pat. No. 8,669,290, which is a division of
`application No. 13/353,653, filed on Jan. 19, 2012,
`now Pat. No. 8,497,304, which is a division of
`application No. 10/525,006, filed as application No.
`PCT/JP2004/000350 on Jan. 16, 2004, now Pat. No.
`8,129,431.
`
`(30)
`
`Foreign Application Priority Data
`
`Jan. 21, 2003
`
`(JP) ................................. 2003-012427
`
`(51)
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`Int. Cl.
`A01N37118
`A61K 311165
`A01N37144
`A61K 31124
`A01N37110
`A61K 31119
`(52) U.S. Cl.
`USPC ............ 514/619; 514/535; 514/570; 514/618
`(58) Field of Classification Search
`USPC .......................................... 514/619, 535, 570
`See application file for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`2,880,130 A
`2,880,138 A
`4,045,576 A
`4,683,242 A
`4,910,225 A
`
`3/1959 Johnson
`3/1959 Johnson
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`7/1987 Poser
`3/1990 Ogawa eta!.
`
`5,110,493 A
`5,475,034 A
`5,540,930 A
`5,558,876 A
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`5,603,929 A
`5,653,972 A
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`5,998,465 A
`6,071,904 A
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`6,162,393 A
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`8,129,431 B2
`200110056098 A1
`2007/0082857 A1
`
`5/1992 Cherng-Chyi eta!.
`12/1995 Yanni et al.
`7/1996 Guyet a!.
`9/1996 Desai eta!.
`111997 Bergamini et a!.
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`6/2000 Ali eta!.
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`12/2000 De Bruiju et al.
`8/2001 Sawa
`8/2001 Yasueda eta!.
`1112001 Dobrozsi
`4/2002 Xi a
`5/2002 Chen eta!.
`5/2002 Cagle eta!.
`3/2012 Sawa eta!.
`12/2001 Sawa
`4/2007 Sawa
`
`FOREIGN PATENT DOCUMENTS
`
`AU
`AU
`CA
`CA
`EP
`EP
`JP
`JP
`
`22042/88
`3/1989
`707 119
`9/1995
`2 013 188
`9/1990
`2383971
`3/2001
`7/1988
`0 274 870
`3/1989
`0 306 984
`6/1987
`62-126124
`4/1989
`1-104023
`(Continued)
`
`OTHER PUBLICATIONS
`
`New Drugs in Japan, 2001, 2001 Edition, Published by Yakuji Nippo
`Ltd., May 11, 2001, pp. 27-29, and its English translation of the
`material portions.
`
`(Continued)
`
`Primary Examiner- Layla Soroush
`(7 4) Attorney, Agent, or Firm - Wenderoth, Lind & Ponack,
`L.L.P.
`
`(57)
`
`ABSTRACT
`
`An aqueous liquid preparation of the present invention con(cid:173)
`taining 2-amino-3-( 4-bromobenzoyl)phenylacetic acid or its
`pharmacologically acceptable salt or a hydrate thereof, an
`alkyl aryl polyether alcohol type polymer such as tyloxapol,
`or a polyethylene glycol fatty acid ester such as polyethylene
`glycol mono stearate is stable. Since even in the case where a
`preservative is incorporated into said aqueous liquid prepa(cid:173)
`ration, the preservative exhibits a sufficient preservative
`effect for a long time, said aqueous liquid preparation in the
`form of an eye drop is useful for the treatment of blepharitis,
`conjunctivitis, scleritis, and postoperative inflammation.
`Also, the aqueous liquid preparation of the present invention
`in the form of a nasal drop is useful for the treatment of
`allergic rhinitis and inflammatory rhinitis (e.g. chronic rhini(cid:173)
`tis, hypertrophic rhinitis, nasal polyp, etc.).
`
`27 Claims, No Drawings
`
`Page 11 of 33
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`

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`Case 1:15-cv-00335-JBS-KMW Document 1-1 Filed 01/16/15 Page 3 of 10 PageID: 12
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`US 8,871,813 B2
`Page 2
`
`(56)
`
`References Cited
`
`FOREIGN PATENT DOCUMENTS
`
`JP
`JP
`JP
`JP
`JP
`JP
`wo
`wo
`wo
`wo
`wo
`wo
`
`02083323
`2-124819
`5-223052
`9-503791
`11-228404
`2002-308764
`94/05298
`94/15597
`96/14829
`00/59475
`01/15677
`02/13804
`
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`5/1990
`8/1993
`4/1997
`8/1999
`10/2002
`3/1994
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`5/1996
`10/2000
`3/2001
`212002
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`
`Page 12 of 33
`
`

`
`Case 1:15-cv-00335-JBS-KMW Document 1-1 Filed 01/16/15 Page 4 of 10 PageID: 13
`
`US 8,871,813 B2
`
`2
`preservative effect of benzalkonium chloride and other qua(cid:173)
`ternary ammonium compounds.
`
`Disclosure Of The Invention
`
`1
`AQUEOUS LIQUID PREPARATION
`CONTAINING
`2-AMIN0-3-( 4-BROMOBENZOYL)PHENYL(cid:173)
`ACETICACID
`
`TECHNICAL FIELD
`
`The present invention relates to an aqueous liquid prepa(cid:173)
`ration containing 2-amino-3-( 4-bromobenzoyl)phenylacetic
`acid or a pharmacologically acceptable salt thereof or a
`hydrate thereof. More particularly, the present invention
`relates to an aqueous liquid preparation containing 2-amino-
`3-( 4-bromobenzoyl)phenylacetic acid or a pharmacologi(cid:173)
`cally acceptable salt thereof or a hydrate thereof and an alkyl
`aryl poly ether alcohol type polymer or a polyethylene glycol
`fatty acid ester.
`
`BACKGROUND ART
`
`Benzoylphenylacetic acid derivatives including bromfenac
`(generic name) offormula (I):
`
`COOH
`
`Br
`
`It is an object of the present invention to provide an aque(cid:173)
`ous liquid preparation comprising 2-amino-3-( 4-bromoben(cid:173)
`zoyl) phenylacetic acid or a pharmacologically acceptable
`salt thereof or a hydrate thereof, which is stable within a pH
`10 range giving no irritation to eyes and in which, when a pre(cid:173)
`servative such as benzalkonium chloride is incorporated
`therein, preservative effect of the preservative does not sub(cid:173)
`stantially deteriorate.
`Another object of the invention is to provide a method for
`15 ~~~~~~~:z~l)ph::~~~!£i~ida~f~P~~at~onp~!~::~~~j~~lt
`acceptable salt thereof or a hydrate thereof.
`Further object of the invention is to provide an aqueous
`liquid preparation comprising 2-amino-3-( 4-bromobenzoyl)
`phenylacetic acid or a pharmacologically acceptable salt
`20 thereof or a hydrate thereof and a preservative wherein, when
`specifically a quaternary ammonium salt such as benzalko(cid:173)
`nium chloride is incorporated as a preservative, decrease in
`preservative effect of said preservative is inhibited.
`As a result of various studies, the inventors of the present
`25 invention have found that, by adding, for example, an alkyl
`aryl polyether alcohol type polymer such as tyloxapol, or a
`polyethylene glycol fatty acid ester such as polyethylene
`glycol monostearate to an aqueous liquid preparation of
`2-amino-3-( 4-bromobenzoyl)phenylacetic acid or a pharma(cid:173)
`cologically acceptable salt thereof or a hydrate thereof, the
`30 aqueous solution becomes stable within a pH range giving no
`irritation to eyes, and change of the 2-amino-3-( 4-bromoben(cid:173)
`zoyl)phenylacetic acid over time can be inhibited, and fur(cid:173)
`thermore, when the aqueous solution contains a preservative,
`deterioration in the preservative effect of said preservative
`35 can be inhibited for a long period of time. The inventors of the
`present invention have further studied extensively and com(cid:173)
`pleted the present invention.
`Namely, the present invention relates to:
`(1) An aqueous liquid preparation comprising 2-amino-3-( 4-
`bromobenzoyl)phenylacetic acid or a pharmacologically
`acceptable salt thereof or a hydrate thereof, and an alkyl
`aryl poly ether alcohol type polymer or a polyethylene gly-
`col fatty acid ester,
`(2) The aqueous liquid preparation according to the above (1 ),
`wherein the alkyl aryl polyether alcohol type polymer has
`a polymerization degree of3 to 10, the alkyl contains 1 to
`18 carbon atoms, the aryl is a phenyl residue, and the
`the
`formula
`represented by
`polyether alcohol
`is
`O(CH2CH20)xH in which X is an integer of 5 to 100,
`(3) The aqueous liquid preparation according to the above (1)
`or (2), wherein the alkyl aryl polyether alcohol type poly(cid:173)
`mer is tyloxapol,
`( 4) The aqueous liquid preparation according to the above (1 ),
`wherein the carbon number of the fatty acid in the polyeth(cid:173)
`ylene glycol fatty acid ester is 12 to 18,
`(5) The aqueous liquid preparation according to the above (1)
`or ( 4), wherein the polyethylene glycol fatty acid ester is
`polyethylene glycol monostearate,
`(6) The aqueous liquid preparation according to any one of
`the above (1) to (3), wherein the concentration of the alkyl
`aryl polyether alcohol type polymer is selected from a
`range of minimum concentration of 0. 01 w /v to maximum
`concentration of0.5 w/v
`(7) The aqueous liquid preparation according to any one of
`the above (1), (2) or (4), wherein the concentration of the
`polyethylene glycol fatty acid ester is selected from a range
`of minimum concentration of 0.02 w/v % to maximum
`concentration of0.1 w/v %,
`(8) The aqueous liquid preparation according to any one of
`the above (1) to (7), wherein the concentration of the
`
`60
`
`of which chemical name is 2-amino-3-( 4-bromobenzoyl)
`phenylacetic acid are known as disclosed in JP-A-23052/
`1977 and its corresponding U.S. Pat. No. 4,045,576.
`2-Amino-3-( 4-bromobenzoyl)phenylacetic acid, its pharma(cid:173)
`cologically acceptable salt and a hydrate thereof are known as
`a non-steroidal anti-inflammatory agent, and they are effec(cid:173)
`tive against inflammatory diseases of anterior or posterior
`segment of the eye, such as blepharitis, conjunctivitis, scleri-
`tis, and postoperative inflammation in the field of ophthal(cid:173)
`mology, and its sodium salt has been practically used in the
`form of eye drops ("New Drugs in Japan, 2001", 2001 Edi(cid:173)
`tion, Published by Yakuji Nippo Ltd., May 11, 2001, p. 40
`27-29).
`The eye drop as mentioned above is designed to stabilize
`2-amino-3-( 4-bromobenzoyl)phenylacetic acid by means of
`addition of a water-soluble polymer (e.g. polyvinylpyrroli(cid:173)
`done, polyvinyl alcohol, etc.) and a sulfite (e.g. sodium 45
`sulfite, potassium sulfite, etc.) (Japanese patent No. 2,683,
`676 and its corresponding U.S. Pat. No. 4,910,225).
`In addition, as an eye drop other than the above-mentioned
`one, Japanese patent No. 2,954,356 (corresponding to U.S.
`f:~i~~~o~~~~i~i~ ~~Zh~~~~~;e~~~~~:;~r:tf~~b: :!~ 50
`bacterial quaternary ammonium polymer and boric acid into
`an acidic ophthalmic agent. The acidic agent described
`therein includes, for example, 2-amino-3-( 4-bromobenzoyl)
`phenylacetic acid.
`Further, in Japanese patent No. 2,954,356, there is the 55
`following description-"Benzalkonium chloride is a widely
`used preservative in ophthalmic solutions. However, benza(cid:173)
`lkonium chloride and other quaternary ammonium com(cid:173)
`pounds are generally considered to be incompatible with
`ophthalmic compositions of drugs with acidic groups, such as
`nonsteroidal anti-inflammatory drugs. These preservatives
`lose their ability to function as they form complexes with the
`charged drug compounds".
`In these prior art references, there is no disclosure that alkyl
`aryl polyether alcohol type polymers or polyethylene glycol
`fatty acid esters are able to stabilize an aqueous liquid prepa- 65
`ration of 2-amino-3-(4-bromobenzoyl)