Page 1 of 33
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`SENJU EXHIBIT 2002
`LUPIN v. SENJU
`IPR2015-01105
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`

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`Page 2
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`
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`December 19, 2013 Keny0n&KenyOn
`
`Pursuant to 21 C.F.R. § 314.95(e), permission from FDA to send this Notice Letter by
`means other than registered or certified mail was requested and received. Specifically,
`permission to send this notice by FedEx°° was requested. FDA granted this request prior to this
`notice being sent. Consequently, the operative date for determining the start of the 45-day clock
`under 21 U.S.C. § 355(i)(5)(B)(iii) begins from the receipt of this Notice Letter sent via FedEx®.
`
`Pursuant to 21 U.S.C. § 355(j)(2)(B)(iv)(I) and 21 C.F.R. § 314.95(c)(1), Lupin
`1.
`advises that FDA has received an Abbreviated New Drug Application (“ANDA”) from Lupin
`for Bromfenac Ophthalmic Solution 0.07%. The ANDA contains the required bioavailability
`and/or bioequivalence data and/or bioequivalence waiver. The ANDA was submitted under 21
`U.S.C. §§ 355(j)(l) and (2)(A), and contains a Paragraph IV certification to obtain approval to
`engage in the commercial manufacture, use or sale of Bromfenac Ophthalmic Solution 0.07%,
`before the expiration of U.S. Patent No. 8,129,431, which is listed in the Patent and Exclusivity
`Information Addendum of FDA’s publication, Approved Drug Products With Therapeutic
`Equivalence Evaluations (commonly known as “the Orange Book”).
`
`Pursuant to 21 C.F.R. § 314.95(c)(2), we advise you that the ANDA submitted by
`II.
`Lupin is assigned the number 206027 by FDA.
`
`Pursuant to 21 C.F.R. § 314.95(c)(3), Lupin advises that the established name of
`III.
`the drug product that is the subject of Lupin’s ANDA is Bromfenac Ophthalmic Solution 0.07%.
`
`Pursuant to 21 C.F.R. § 314.95(c)(4), Lupin advises that the active ingredient in
`IV.
`the proposed drug product is bromfenac sodium; the strength of the proposed drug product is a
`0.07% solution; and the dosage form of the proposed drug product is an ophthalmic solution.
`
`Pursuant to 21 C.F.R. § 314.95(c)(5), Lupin advises that the patent alleged to be
`V.
`invalid, unenforceable and/or not infringed in the Paragraph IV certification is Senju’s U.S.
`Patent No. 8,129,431, which is now listed in the Orange Book in connection with Bausch &
`Lomb’s approved NDA No. 203168 for Prolensa® (Bromfenac Ophthalmic Solution 0.07%).
`
`According to information submitted for listing in the Orange Book, U.S. Patent No.
`8,129,431 will purportedly expire on or about September 11, 2025.
`
`Lupin alleges, and has certified to FDA, that in Lupin’s opinion and to the best of
`VI.
`its knowledge, U.S. Patent No. 8,129,431 is invalid, unenforceable and/or will not be infringed
`by the commercial manufacture, use or sale of the drug products described in Lupin’s ANDA.
`Therefore, pursuant to 21 U.S.C. § 355(i)(2)(B)(iv)(II) and 21 C.F.R. § 314.95(c)(6), Lupin’s
`detailed statement of the legal and factual basis for the Paragraph IV certification set forth in
`Lupin’s ANDA is attached hereto and made part hereof. Lupin reserves the right to demonstrate
`additional grounds, reasons and authorities that the claims of the ’431 patent are invalid,
`unenforceable, and/or not infringed.
`
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`Page 3
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`December 19, 2013 KenyOn&KenyOn
`
`Pursuant to 21 C.F.R. § 314.95(c)(7), the name and address of an agent in the
`VII.
`United States authorized to accept service of process for Lupin, limited to commencement of a
`patent infringement suit based on this notification of certification, is:
`
`Elizabeth J. Holland
`KENYON & KENYON LLP
`
`One Broadway
`New York, NY 10004-1007
`
`eholland@,kenyon.con1
`
`Pursuant to 21 U.S.C. § 355(j)(5)(C), this Notice Letter includes an Offer of
`VIII.
`Confidential Access to Application. As required by § 355(j)(5)(C)(i)(III), Lupin offers to
`provide confidential access to certain information from its ANDA No. 206027 for the sole and
`exclusive purpose of determining whether an infringement action referred to in §355(j)(5)(B)(iii)
`for a patent listed in the Orange Book for NDA No. 203168 can be brought.
`
`Section 35 5(j)(5)(C)(i)(III) allows Lupin to impose restrictions “as to persons entitled to
`access, and on the use and disposition of any information accessed, as would apply had a
`protective order been entered for the purpose of protecting trade secrets and other confidential
`business information.” That provision also grants Lupin the right to redact its ANDA in
`response to a request for Confidential Access under this offer.
`
`As permitted by statute, Lupin imposes the following terms and restrictions on its Offer
`of Confidential Access:
`
`Lupin will permit confidential access to certain information from its
`(1)
`proprietary ANDA No. 206027 to attorneys from one outside law firm representing Bausch &
`Lomb and/or Senju; provided, however, that such attorneys do not engage, formally or
`informally, in any patent prosecution for Bausch & Lomb or Senju, or any FDA counseling,
`litigation or other work before or involving FDA. Such information (hereinafter, “Confidential
`Lupin Information”) shall be marked with the legend “CONFIDENTIAL.”
`
`The attorneys from the designated outside law firm representing Bausch &
`(2)
`Lomb and/or Senju shall not disclose any Confidential Lupin Information to any other person or
`entity, including Bausch & Lomb or Senju employees, outside scientific consultants, and/or other
`outside counsel retained by Bausch & Lomb or Senju, without the prior written consent of Lupin.
`
`As provided by § 355(j)(5)(C)(i)(III), the designated outside law firm
`(3)
`representing Bausch & Lomb and/or Senju shall make use of the Confidential Lupin Information
`for the sole and exclusive purpose of determining whether an action referred to in §
`35 5(j)(5)(B)(iii) can be brought and for no other purpose. By way of example only, the
`Confidential Lupin Information shall not be used to prepare or prosecute any future or pending
`patent applications by Bausch & Lomb or Senju, or in connection with any filing to, or
`communication with, FDA or the United States Pharmacopeia or any similar or related
`organization relating to Lupin’s ANDA No. 206027. The outside law firm for Bausch & Lomb
`
`Page 3 of 33
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`Page 3 of 33
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`P‘ e 4
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`
`
`Dtiember 19, 2013 Kenydn&KenyOn
`
`and/or Senju agrees to take all measures necessary to prevent unauthorized disclosure or use of
`the Confidential Lupin Information. and that all Confidential Lupin Information shall be kept
`confidential and not disclosed in any manner inconsistent with this Offer of Confidential Access.
`
`The Confidential Lupin Information disclosed is, and remains, the
`(4)
`property of Lupin. By providing the Confidential Lupin Information, Lupin does not grant
`Bausch & Lomb, Senju and/or their outside law firm any interest in or license for the
`Confidential Lupin Information.
`
`The designated outside law firm representing Bausch & Lomb and/or
`(5)
`Senju shall, within thirty-five (35) days from the date that it first receives the Confidential Lupin
`Information, return to Lupin all Confidential Lupin Information and any copies thereof. The
`outside law firm of Bausch & Lomb and/or Senju shall return all Confidential Lupin Information
`to Lupin before any infringement suit is filed by Bausch & Lomb and/or Senju, if suit is
`commenced before this 35-day period expires. In the event that Bausch & Lomb and/or Senju
`opts to file suit, none of the information contained in or obtained from any Confidential Lupin
`Information that Lupin provides shall be included in any publicly-available complaint or other
`pleading.
`
`Nothing in this Offer of Confidential Access shall be construed as an
`(6)
`admission by Lupin regarding the validity, enforceability, and/or infringement of any U.S.
`patent. Further, nothing herein shall be construed as an agreement or admission by Lupin with
`respect to the competency, relevance, or materiality of any such Confidential Lupin lnfonnation,
`document, or thing. The fact that Lupin provides Confidential Lupin Information upon request
`of Bausch & Lomb and/or Senju shall not be construed as an admission by Lupin that such
`Confidential Lupin Information is relevant to the disposition of any issue relating to any alleged
`infringement of U.S. Patent No. 8,129,431, or to the validity or enforceability of that patent.
`
`The attorneys from the designated outside law firm representing Bausch &
`(7)
`Lomb and/or Senju shall acknowledge in writing their receipt of a copy of these terms and
`restrictions prior to production of any Confidential Lupin Information. Such written
`acknowledgement shall be provided to Lupin.
`
`ll‘Confidential Lupin Information is disclosed by the designated outside law
`(8)
`firm representing Bausch & Lomb and/or Senju to any person not authorized to receive such
`Confidential Lupin Information pursuant to this Offer of Confidential Access, then the designated
`outside law firm representing Bausch & Lomb and/or Senju must immediately bring all pertinent
`facts relating to such disclosure to the attention of Lupin and, without prejudice to other rights and
`remedies ofLupin. make every effort to prevent further disclosure by it or by the person who was the
`recipient ofsuch Confidential Lupin Information.
`
`Page 4 of 33
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`Page 5
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`December 19, 2013 KCHYOHOCKCHYOH
`
`Section 355(j)(5)(C)(i)(III) provides that any request for access that Bausch & Lomb
`and/or Senju makes under this Offer of Confidential Access “shall be considered acceptance of
`the offer of confidential access with the restrictions as to persons entitled to access, and on the
`use and disposition of any information accessed, contained in [this] offer of confidential access”
`and that the “restrictions and other terms of [this] offer of confidential access shall be considered
`terms of an enforceable contract.” Thus, to the extent that Bausch & Lomb and/or Senju requests
`access to Confidential Lupin Information, they necessarily accept the terms and restrictions
`outlined above. Written notice requesting access under this Offer of Confidential Access should
`be made to:
`
`Elizabeth J. Holland
`KENYON & KENYON LLP
`
`One Broadway
`New York, NY 10004-1007
`
`eholland@kenyon.com
`
`By providing this Offer of Confidential Access, Lupin maintains the right and ability to
`bring and maintain a Declaratory Judgment action under 28 U.S.C. §§ 2201 et seq., pursuant to
`21 U.S.C. § 355(j)(5)(C).
`
`Very truly yours,
`
`
`
`/I 3":
`lie‘
`
`KENYO & KENYON LLP
`
`One Broadway
`New York, NY 10004-1007
`(212) 425-7200
`(212)425-5288 (facsimile)
`
`Counsel for Lupin Ltd.
`
`Enclosure: Lupin Ltd.’s Detailed Factual and Legal Bases for Its Opinion That U .S. Patent No.
`8,129,431 Is Invalid, Unenforceable and/or Not Infringed by the Manufacture, Use or Sale of
`Lupin Ltd.’s Proposed Bromfenac Ophthalmic Solution 0.07%
`
`Page 5 of 33
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`Lupin Ltd.’s Detailed Statement of the Factual and Legal Bases for Its Opinion That U.S.
`Patent No. 8,129,431 Is Invalid, Unenforceable andlor Not Infringed by the Manufacture,
`Use or Sale of Lupin Ltd.’s Proposed Bromfenac Ophthalmic Solution 0.07%
`
`Pursuant to Section 505(i)(2)(B)(ii) of the Food, Drug and Cosmetic Act (codified at 21
`
`U.S.C. § 355(j)(2)(B)(ii)), and 21 C.F.R. § 3 l4.95(c), this is the detailed statement of Lupin Ltd.
`
`(“Lupin”) of the factual and legal bases for its opinion that U.S. Patent No. 8,129,431 (“the ’431
`
`patent”) is invalid, unenforceable, and/or not infringed by the manufacture, use or sale of Lupin’s
`
`proposed bromfenac ophthalmic solution 0.07% described in ANDA No. 206027 (“Lupin’s '
`
`proposed product”). The bases for Lupin’s opinion follow.
`
`I.
`
`U.S. PATENT 8,129,431
`
`The ’431 patent, entitled “AQUEOUS LIQUID PREPARATION CONTAINING 2-
`
`AMINO—3-(4-BROMOBENZOYL)PHENYLACETIC ACID,” issued on March 6, 2012 from
`
`U.S. Application Serial No. 10/525,006, which was filed on March 28, 2005 as a U.S. national
`
`phase application of PCT Application No. PCT/JP2004/000350, which was filed on January 16,
`
`2004, and claims the benefit of Japanese Application No. 2003-12427, which was filed on
`
`January 21, 2003. The ’431 patent lists Shirou Sawa and Shuhei Fujita as inventors, and is
`
`assigned on its face to Senju Pharmaceutical Co., Ltd. The ’43l patent has a patent term
`
`adjustment of 604 days. According to the Orange Book listing for Prolensa, the ’431 patent will
`
`expire on September 11, 2025.
`
`A.
`
`Claims of the ’431 Patent
`
`The ’431 patent issued with 22 claims, which are reproduced below:
`
`1. An aqueous liquid preparation consisting essentially of the following two components,
`wherein the first component is 2-amino—3-(4-bromobenzoyl)phenylaceticacid or a
`pharrnacologically 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 and the second component is tyloxapol,
`wherein said liquid preparation is formulated for ophthalmic administration, and wherein when a
`
`1
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`Page 6 of 33
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`

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`quaternary ammonium compound is included in said liquid preparation, the quaternary
`ammonium compound is benzalkonium chloride.
`
`2. The aqueous liquid preparation according to claim 1, wherein the first component is a
`2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt.
`
`3. The aqueous liquid preparation according to claim 1, wherein the second component is
`tyloxapol and the pharmacologically acceptable salt of 2-amino-3-(4-bromobenzoyl)phenylacetic
`acid is a sodium salt , wherein the concentration of the tyloxapol is from about 0.01 w/v % to
`about 0.5 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 0.01 to about 0.5 w/v %.
`
`4. The aqueous liquid preparation according to claim 3, wherein the concentration of the
`tyloxapol _is from about 0.01 w/v % to about 0.3 w/v % and the concentration of the 2-arnino-3-
`(4-bromobenzoyl)phenylacetic acid sodium salt is fiom about 0.05 to about 0.2 w/v %.
`
`5. The aqueous liquid preparation according to claim 4, wherein the concentration of the
`2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is about 0.1 w/v %.
`
`6. The aqueous liquid preparation according to claim 4, wherein the concentration of the
`tyloxapol is about 0.02 w/v %.
`
`7. The aqueous liquid preparation according to claim 1, wherein the formulation further
`includes one or more additives selected from the group consisting of a preservative, buffer,
`thickener, stabilizer, chelating agent, and pH controlling agent.
`
`8. The aqueous liquid preparation according to claim 7, wherein said preservative is
`benzalkonium chloride; wherein said buffer is boric acid and/or sodium borate; wherein said
`thickener is polyvinylpyrrolidone; wherein said stabilizer is sodium sulfite; wherein said
`chelating agent is sodium edetate; and wherein said pH controlling agent is sodium hydroxide.
`
`9. The aqueous liquid. preparation according to claim 8, wherein the pH is from about 7 to
`about 9.
`
`10. The aqueous liquid preparation according to claim 8, wherein the pH is from about
`7.5 to about 8.5.
`
`11. The aqueous liquid preparation according to claim 4, wherein the concentration of the
`2-amino-3—(4-bromobenzoy1)phenylacetic acid sodium salt is about 0.2 w/v %.
`
`12. The aqueous liquid preparation according to claim 4, wherein the concentration of the
`tyloxapol is about 0.3 w/v %.
`
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`13. The aqueous liquid preparation according to claim 12, wherein the formulation
`further includes one or more additives selected from the group consisting of a preservative,
`bufler, thickener, stabilizer, chelating agent, and pH controlling agent.
`
`14. The aqueous liquid preparation according to claim 13, wherein said preservative is
`benzalkonium chloride; wherein said bufi'er is boric acid and/or sodium borate; wherein said
`thickener is polyvinylpyrrolidone; wherein said stabilizer is sodium sulfite; wherein said
`chelating agent is sodium edetate; and wherein said pH controlling agent is sodium hydroxide.
`
`15. The aqueous liquid preparation according to claim 1 1, wherein the concentration of
`the tyloxapol is about 0.02 w/v %.
`
`16. The aqueous liquid preparation according to claim 15, wherein the formulation
`further includes one or more additives selected from the group consisting of a preservative,
`buffer, thickener, stabilizer, chelating agent, and pH conuolling agent.
`
`17. The aqueous liquid preparation according to claim 16, wherein said preservative is
`benzalkonium chloride; wherein said buffer is boric acid and/or sodium borate; wherein said
`thickener is polyvinylpyrrolidone; wherein said chelating agent is sodium edetate; and wherein
`said pH controlling agent is sodium hydroxide.
`
`18. An aqueous liquid preparation consisting 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) sodimn tetraborate, (e) EDTA sodium salt, (1)
`benzalkonium chloride, (g) polyvinylpyrrolidone, (h) sodium sulfite, wherein said liquid
`preparation is formulated for ophthalmic administration, and wherein benzalkonium chloride is
`the only quaternary ammonium compound which is included in said liquid preparation.
`
`19. The aqueous liquid preparation of claim 18, wherein (a) is a 2-amino-3-(4-
`bromobenzoyl)phenylacetic acid sodium salt.
`
`20. The aqueous liquid preparation of claim 19, wherein the concentration of the 2-
`amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is from about 0.01 to about 0.5 w/v %
`and the concentration of the tyloxapol is about 0.02 w/v %.
`
`21. The aqueous liquid preparation of claim 20, wherein the concentration of the 2-
`amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is about 0.01 w/v %.
`
`22. The aqueous liquid preparation of claim 20, wherein the concentration of the 2-
`amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is about 0.1 w/v %.
`
`B.
`
`Specification of the ’431 Patent
`
`The specification of the ’431 patent acknowledges that ophthalmic solutions containing
`
`brornfenac were described in the prior art. (’431 patent, col. 1, 11. 24-47.) The specification
`
`3
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`quotes a prior art reference (Japanese Patent No. 2,954,356, corresponding to U.S. Patent Nos.
`
`5,603,929 and 5,653,972) for the teaching that benzalkonium chloride (BAC) (a widely used
`
`preservative in ophthalmic solutions) and other quaternary ammonium compounds “are generally
`
`considered to be incompatible” with non-steroidal anti-inflammatory drugs (NSAlDs) with
`
`acidic groups (a —COOH group) because “[t]hese preservatives lose their ability to fimction as
`
`they form complexes with the charged drug compounds.” (’431 patent, col. 1, l. 62 —- col. 2, 1. 3.)
`
`Bromfenac is an NSAID with a —COOH group. ‘Thus, the specification presents the problem to
`
`be overcome as producing an ophthalmic solution containing an NSAID with a —COOH group
`
`and BAC wherein the NSAID and the BAC do not form a complex (i. e. , with improved
`
`stability).
`
`The specification indicates that this problem has been overcome by including an alkyl
`
`aryl polyether alcohol type polymer such as tyloxapol or a polyethylene glycol fatty acid ester
`
`such as polyethylene glycol monostearate in the ophthalmic solution. (’43l patent, col. 2, ll. 34»
`
`49.) The specification describes an experiment (Experimental Example 1) in which formulations
`
`containing bromfenac, BAC and three different surfactants (polysorbate 80, polyoxyl 40 stearate,
`
`land tyloxapol) were prepared and tested for stability. (’431 patent, col. 7, l. 8 — col. 8, l. 2.) Two
`
`formulations containing tyloxapol were the most stable, followed by a formulation containing
`
`polyoxyl 40 stearate, followed by a formulation containing polysorbate 80. The polysorbate 80
`
`formulation was not considered to be part ofthe invention, as indicated by the fact that it was
`
`referred to as “Comparison Example 1.”
`
`C.
`
`Prosecution History of the ’431 Patent
`
`During prosecution, the PTO Examiner cited prior art describing ophthalmic solutions
`
`containing bromfenac, BAC and polysorbate 80 as a surfactant, as well as prior art showing that
`
`4
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`tyloxapol and polysorbate 80 were both known as surfactants in ophthalmic solutions, and
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`rejected the claims on the basis that it would have been obvious to substitute tyloxapol for
`
`polysorbate 80. (May 6, 2011 Office Action at 2-3 [“It would have been obvious to one of
`
`ordinary skill in the art at the time of the invention to interchange polysorbate 80 and tyloxapol.
`
`The motivation comes from the teaching of Guy et al. that both compounds are non-ionic
`
`surfactant surface active agents. Hence, a skilled artisan would have had a reasonable
`
`expectation of successfully producing a composition with similar efficacy and results.’’) In
`
`response, applicants repeatedly argued that they had discovered that substituting tyloxapol for
`
`polysorbate 80 produced unexpected results (i. e., improved stability) and pointed to
`
`Experimental Example 1 from the specification to support this assertion. (See, e.g. , September 6,
`
`2011 Amendment at 7-8 [“The present inventors have discovered that tyloxapol has an
`
`unexpected property in stabilizing an aqueous solution of bromfenac in comparison with
`
`polysorbate 80. Please see the description of Experimental Example 1 and Table 1 on pages 14-
`
`16 of the specification.”].) The PTO Examiner eventually accepted this argument, and allowed
`
`the claims of the ’431 patent on the basis of the alleged unexpected results. (December 23, 2011
`
`Notice of Allowability at 3-4 [“The present inventors have discovered that tyloxapol has an
`
`unexpected property in stabilizing an aqueous solution of bromfenac in comparison with
`
`polysorbate 80. Please see the description of Experimental Example 1 and Table 1 on pages 14-
`
`16 of the specification.’’].)
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`II.
`
`NON-INFRINGEMENT ANALYSIS
`
`A.
`
`Relevant Law
`
`1.
`
`Claim Construction
`
`To ascertain the meaning of claims, the claims, the specification and the prosecution
`
`history must be considered. Markman v. Westview Instruments, Inc., 52 F.3d 967, 979 (Fed. Cir.
`
`1995) (en banc), affd, 517 U.S. 370 (1996); see also Boss Control, Inc. v. Bombardier, Inc., 410
`
`F.3d 1372, 1376 (Fed. Cir. 2005). In interpreting a claim, one looks first to the intrinsic evidence
`
`of record, i. e. , the patent itself, including the claims, the specification and the prosecution
`
`history. See Markman, 52 F.3d at 979; see also, Phillips v. AWH Corp, 415 F.3d 1303, 1312
`
`(Fed. Cir. 2005). “Such intrinsic evidence is the most significant source of the legally operative
`
`meaning of disputed claim language.” Bell Atlantic Network Servs., Inc. v. Covad Commc ’ns
`
`Grp., Inc., 262 F.3d 1258, 1267 (Fed. Cir. 2001) (citing Vitronics Corp. v. Conceptronic, Inc., 90
`
`F.3d 1576, 1582 (Fed. Cir. 1996)). Where construction of claim terms would add clarity to this
`
`detailed statement, it has been provided below.
`
`2.
`
`Law of Infringement
`
`A patent claim is literally infringed if every limitation found in a properly interpreted
`
`claim is present in the accused product or process. See, e. g., Hutchins v. Zoll Medical Corp., 492
`
`F.3d 1377, 1380 (Fed. Cir. 2007); Bowers v. Bayside Techs., Inc., 320 F.3d 1317, 1334 (Fed. Cir.
`
`2003). Thus, literal infringement requires the presence of each and every claim element. See
`
`Amazon com, Inc. v. Barnesandnoblecom, Inc., 239 F. 3d 1343, 1351 (Fed. Cir. 2001); Bayer
`
`AG v. Elan Pharm Research Corp, 212 F.3d 1241, 1247 (Fed. Cir. 2ooo).
`
`Page 11 of 33
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`B.
`
`At Least Claims 5 and 8-22 of the ’431 Patent Would Not Be Infringed by
`Lupin’s Proposed Product
`
`1.
`
`Claims 5, 11, 15-17 and 21-22
`
`At least claims 5, 11, 15-17 and 21-22 ofthe ’431 patent would not be inflinged either
`
`literally or under the doctrine of equivalents by Lupin’s proposed product because the
`
`concentration of bromfenac sodium salt in Lupin’s proposed product (which is equivalent to 0.07
`
`w/v % bromfenac fi'ee acid) is substantially different fiom the concentration of bromfenac
`
`sodium salt required by those claims. Specifically, claims 5 and 22 require a concentration of
`
`bromfenac sodium salt of “about 0.1 w/v %,” claims 11 and 15-17 require a concentration of
`
`“about 0.2 W/v %,” and claim 21 requires a concentration of “about 0.01%”
`
`2.
`
`Claims 12-14
`
`Claims 12-14 of the ’43l patent would not be infringed either literally or under the
`
`doctrine of equivalents by Lupin’s proposed product because each of those claims requires a
`
`concentration of tyloxapol that is different from the concentration of tyloxapol in Lupin’s
`
`proposed product. Specifically, claims 12-14 require a concentration of tyloxapol of “about 0.3
`
`w/v %,” while the concentration of tyloxapol in Lupin’s proposed product is substantially
`
`different.
`
`3.
`
`Claims 8-10, 14 and 17-22
`
`Claims 8, 14 and 17-22 of the ’431 patent would not be infringed by Lupin’s proposed
`
`product because each of those claims requires the inclusion of tetrasodium edetate, but neither
`
`tetrasodium edetate nor an equivalent thereof is contained in Lupin’s proposed product.
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`Specifically, claims 8, 14 and 17 require the inclusion of “sodium edetate,” which refers
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`to tetrasodium edetaxe according to the Handbook of Pharmaceutical Excipients (2000 edition).
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`Claims 18-22 require the inclusion of “EDTA sodium salt,” a term that is not used in the
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`specification of the ’431 patent. However, during the prosecution of the application that issued
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`as the ’431 patent, when the term “EDTA sodium salt” was first included in the claims,
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`applicants indicated that “EDTA sodium salt is also known as sodium edetate.” (March 24, 2010
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`Amendment at 7.) In this way, applicants indicated that “EDTA sodium salt” referred to
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`tetrasodium edetate. Since tetrasodium edetate is not contained in Lupin’s proposed product,
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`that product would not literally infringe claims 8, 14 and 17-22.
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`Nor would Lupin’s proposed product infringe under the doctrine of equivalents since the
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`doctrine of equivalents cannot be employed in a manner that wholly vitiates a claim limitation.
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`See Warner-Jenkinson Co. v. Hilton Davis Chemical Co., 520 U.S. 17, 29-30 (1997); Asyst
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`Techs, Inc. v. Emtrak, Inc., 402 F.3d 1188, 1195 (Fed. Cir. 2005). Moreover, other ingredients
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`in Lupin’s proposed product (i. e., ingredients other than tetrasodium edetate) cannot be
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`considered insubstantially different from tetrasodium edetate given that, for formulations
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`intended for ophthalmic use, FDA generally requires generic versions to contain the same
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`inactive ingredients and in the same concentration as the brand name drug product. See 21
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`C.F.R. § 314.94(a)(9)(iv) (‘‘Generally, a drug product intended for ophthalmic or otic use shall
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`contain the same inactive ingredients and in the same concentration as the reference listed drug
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`identified by the applicant. . .”).
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`III.
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`INVALIDITY ANALYSIS
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`A.
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`Relevant Law
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`A claim is invalid if the differences between the claimed subject matter and the prior art
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`are such that the claimed subject matter as a whole would have been obvious at the time the
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`invention was made to a person having ordinary skill in the pertinent art. 35 U.S.C. § l03(a_).
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`This determination is a question of law based on factual inquiries:
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`Under § 103, the scope and content ofthe prior art are to be
`determined; dilferences between the prior art and the claims at
`issue are to be ascertained; and the level of ordinary skill in the
`pertinent art resolved. Against this background, the obviousness or
`nonobviousness of the subject matter is determined. Such
`secondary considerations as commercial success, long felt but
`unsolved needs, failure of others, etc., might be utilized to give
`light to the circumstances surrounding the origin of the subject
`matter sought to be patented. As indicia of obviousness or
`nonobviousness, these inquiries may have relevancy.
`
`Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966); Ruiz v. A.B. Chance Co., 234 F.3d 654,
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`663 (Fed. Cir. 2000) (“Our precedent clearly establishes that the district court must make
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`Graham findings before invalidating a patent for obviousness”); see also KSR Int '1 Co. v.
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`Teleflex Inc., 550 U.S. 398, 406-07 (2007) (“[T]he [Graham] factors . . . define the inquiry that
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`controls. If a court, or patent examiner, conducts [the Graham] analysis and concludes the
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`claimed subject was obvious, the claim is invalid under § 103.”). Thus, Graham sets out a four-
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`part inquiry including the three elements of the primary consideration of obviousness (the level
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`of ordinary skill in the pertinent art, the scope and content of the prior art, and the difierences
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`between the prior art and the claims at issue), and secondary considerations of nonobviousness.
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`Ruiz, 234 F.3d at 662-63; see also KSR, 550 U.S. at 406.
`
`B.
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`Prior Art
`
`1.
`
`U.S. Patent No. 4,910,225
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`U.S. Patent No. 4,910,225 (“the ’225 patent”) issued on March 20, 1990 and thus is prior
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`art to the ’43l patent under 35 U.S.C. § l02(b). The ’225 patent describes formulations for
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`ophthalmic solutions containing bromfenac sodium monohydrate (referred to in the ’225 patent
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`Page 14 of 33
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`as “sodium 3-(4-bromobenzoyl)-2-aminophenylacetate monohydrate”) as the active ingredient.
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`One such formulation is Example 6, which reads as follows:
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`EXAMPLE 6
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`Ophthalmic Solution
`
`Sodium 3s(4-bromobenzoyl)-2-aminophenyb
`acetate monohydrate
`Boric acid
`Borax
`Disodium edetate
`Benzalkonium chloride
`Polysorbate 80
`Polyvinyl pyrrolidone
`Sodium sulfite
`Sterile purified water
`pH 8
`
`_
`
`-
`
`0.1 g
`.
`1.25 g
`1.0 g
`0.02 g
`0.005 g
`0.15 g
`2.0 g
`0.2 g
`To make 100 ml
`
`Example 6 of the ’225 patent includes each of the elements of independent claim 1 of the
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`’43l patent except for tyloxapol, and includes each of the elements of independent claim 18 of
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`the ’43l patent except for tyloxapol and “EDTA sodium salt.” Specifically, the formulation
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`described in Example 6 of the ’225 patent differs from claim 18 in that Example 6 utilizes (i)
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`polysorbate 80 instead of tyloxapol and (ii) disodium edetate instead of “EDTA sodium sal .”
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`The formulation described in Example 6 of the ’225 patent is very similar to the
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`formulation that was marketed in Japan beginning in 2000 under the brand name Bronuck® and
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`marketed in the United States beginning in 2005 under the brand name Xibrom®.
`
`10
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`2.
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`EP 0 306 984 Al
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`European patent application 88114804.3 was published as EP 0 306 984 A1 (“EP ’984”)
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`on March 15, 1989, and thus is prior art to the ’431 patent under 35 U.S.C. § 102(b). EP ’984
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`describes improved formulations for ophthalmic solutions containing non-steroidal anti-
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`inflammatory drugs (“NSAIDs”) that have a —COOH group (i. e., that are acidic). EP ’984
`
`indicates that benzalkonium chloride (“BAC”) “has been widely used in ophthalmic solutions,
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`and is considered to be the preservative of choice.” (EP ’984, p. 2, 11. 31-33.) EP ’984 further
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`reports that BAC has proven to be incompatible with NSAIDs that contain a —COOH group
`
`because a complex forms between BAC and the —COOH group, thereby reducing the activity of
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`both BAC and the NSAID.
`
`(EP ’984, p. 2, 1L 40-44.) When an ophthalmic solution was made
`
`with ketorolac (an NSAID with 3. —COOH group), BAC and polysorbate 80 as a surfactant, the
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`solution became cloudy or turbid after a short period of time, indicating that a complex had
`
`formed between BAC and the NSAID. (EP ’984, p. 2, 11. 46-49.)
`
`EP ’984 solves this problem by including “a stabilizing amount of an ethoxylated
`
`octylphenol as a nonionic surfactant.” (EP ’984, p. 3, 11. 1-3.) The specific examples of
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`ethoxylated octylphenols given by EP ’984 are Octoxynol 9, Octoxynol 12, Octoxynol 13 and
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`Octoxynol 40. (EP ’984, p. 5,11. 23-28.)
`
`EP ’984 describes an experiment (Example 5) in which three formulations containing an
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`NSAID having a —-COOH group (ketorolac), BAC and a surfactant were tested for their stability.
`
`(EP ’984, p. 9, 11. 1-39.) One formulation included an ethoxylated octylphenol (Octoxynol 40) as
`
`the surfactant, while the other formulations did not include an ethoxylated octylphenol as the
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`surfactant but rather included Polysorbate 80 or Myrj 52. The formulation including the
`
`ethoxylated octylphenol as the surfactant remained clear (and thus were stable), while the other
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`11
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`two formulations became turbid (and thus were not stable). The text of Example 5 of EP ’984
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`reads as follows:
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`EXAMPLE §
`
`Physical stability of the formulations of the present invention