Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 1 of 32 PageID: 4341
`Case 1:15—cv—O3240—JBS—KMW Document 59 Filed 11/18/15 Page 1 of 32 Page|D: 4341
`
`IN THE UNITED STATES DISTRICT COURT
`
`FOR THE DISTRICT OF NEW JERSEY
`
`SENJU PHARMACEUTICAL CO.,
`
`INC.,
`LTD., BAUSCH & LOMB,
`BAUSCH AND LOMB PHARMA
`
`HOLDINGS CORP.,
`
`V.
`
`Plaintiffs,
`
`LUPIN LTD., LUPIN
`
`INC.,
`PHARMACEUTICALS,
`
`Defendants.
`
`SENJU PHARMACEUTICAL co.,
`
`INC.,
`LTD., BAUSCH & LOMB,
`BAUSCH & LOMB PHARMA HOLDINGS
`
`EHONORABLE JEROME B. SIMANDLE
`
`Civil Action Nos.
`
`14-667 (JBS/KMW)
`
`14-4149 (JBS/KMW)
`
`14-5144 (JBS/KMW)
`
`15-335 (JBS/KMW)
`
`14-6893 (JBS/KMW)
`
`15-3240 (JBS/KMW)
`
`CORP.,
`
`V.
`
`Plaintiffs,
`
`5535555 °PINI°N
`
`LUPIN LTD., LUPIN
`
`INC.,
`PHARMACEUTICALS,
`Defendants.
`
`SENJU PHARMACEUTICAL CO.,
`LTD., BAUSCH & LOMB,
`INC.,
`BAUSCH & LOMB PHARMA HOLDINGS
`
`CORP.,
`
`V.
`
`Plaintiffs,
`
`LUPIN LTD., LUPIN
`
`PHARMACEUTICALS,
`
`INC.,
`Defendants.
`
`SENJU PHARMACEUTICAL CO.,
`
`LTD., BAUSCH & LOMB
`
`INCORPORATED, BAUSCH & LOMB
`
`PHARMA HOLDINGS CORP.,
`
`V-
`
`Plaintiffs,
`
`LUPIN, LTD., LUPIN
`
`PHARMACEUTICALS,
`
`INC.,
`Defendants.
`
`[Caption Continues]
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 2 of 32 PageID: 4342
`
`
`
`
`
`SENJU PHARMACEUTICAL CO.,
`LTD., BAUSCH & LOMB, INC.,
`BAUSCH & LOMB PHARMA HOLDINGS
`CORP.,
`Plaintiffs,
`v.
`
`INNOPHARMA LICENSING, INC.,
`INNOPHARMA LICENSING, LLC,
`INNOPHARMA, INC., INNOPHARMA,
`LLC,
`Defendants.
`SENJU PHARMACEUTICAL CO.,
`LTD., BAUSCH & LOMB
`INCORPORATED, BAUSCH & LOMB
`PHARMA HOLDINGS CORP.,
`Plaintiffs,
`v.
`
`INNOPHARMA LICENSING, INC.,
`INNOPHARMA LICENSING, LLC,
`INNOPHARMA, INC., INNOPHARMA,
`LLC,
`Defendants.
`
`
`APPEARANCES:
`
`Melissa A. Chuderewicz, Esq.
`PEPPER HAMILTON LLP
`Suite 400
`301 Carnegie Center
`Princeton, NJ 08543
`
`-and-
`Bryan C. Diner, Esq.
`Justin J. Hasford, Esq.
`Chiaki Fujiwara, Esq.
`FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER, LLP
`901 New York Avenue, NW
`Washington, DC 20001
`
`-and-
`Jessica M. Lebeis, Esq.
`FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER, LLP
`303 Peachtree Street, NE
`Atlanta, GA 30308
`
`Attorneys for Plaintiffs
`
`Michael E. Patunas, Esq.
`
`
`
`2
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 3 of 32 PageID: 4343
`
`Mayra V. Tarantino, Esq.
`LITE DEPALMA, GREENBERG, LLC
`570 Broad Street, Suite 1201
`Newark, NJ 07102
`
`-and-
`Elizabeth J. Holland, Esq.
`Daniel P. Margolis, Esq.
`Natasha E. Daughtrey, Esq.
`Sarah Fink, Esq.
`GOODWIN PROCTER LLP
`The New York Times Building
`620 Eighth Avenue
`New York, NY 10018
`
`-and-
`Emily L. Rapalino, Esq.
`GOODWIN PROCTER LLP
`53 State Street
`Boston, MA 02109
`
`Attorneys for Defendants Lupin Limited and Lupin
`
`Pharmaceuticals, Inc.
`
`Arnold B. Calmann, Esq.
`Jeffrey Soos, Esq.
`Katherine A. Escanlar, Esq.
`SAIBER LLC
`One Gateway Center, 10th Floor
`Newark, NJ 07102
`
`-and-
`Deepro R. Mukerjee, Esq.
`Lance A. Soderstrom, Esq.
`Leah W. Feinman, Esq.
`ALSTON & BIRD LLP
`90 Park Avenue
`New York, NY 10016
`
`Attorneys for Defendants Innopharma Licensing, Inc.,
`
`Innopharma Licensing, LLC, Innopharma, Inc., and
`
`Innopharma, LLCit only happens
`
`SIMANDLE, Chief Judge:
`
`INTRODUCTION
`
`Plaintiffs Senju Pharmaceutical Co., Ltd., Bausch & Lomb
`
`Inc., and Bausch & Lomb Pharma Holdings Corp. (collectively,
`“Plaintiffs”) brought these various patent infringement actions
`
`
`
`3
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 4 of 32 PageID: 4344
`
`under the Hatch-Waxman Act, 35 U.S.C. §§ 271, 281, against
`Defendants Lupin, Ltd., Lupin Pharmaceuticals, Inc., Innopharma
`Licensing, Inc., Innopharma Licensing, LLC, Innopharma, Inc.,
`and Innopharma, LLC (collectively, “Defendants”) concerning
`Defendants’ submissions of abbreviated new drug applications
`(“ANDAs”) seeking FDA approval to market a generic version of
`Plaintiffs’ drug Prolensa®, which is used to treat patients who
`have undergone cataract surgery. Plaintiffs allege that
`Defendants’ ANDA submissions infringe the various patents
`covering Plaintiffs’ Prolensa® product: U.S. Patent Nos.
`8,129,431 (“the ’431 patent”), 8,669,290 (“the ’290 patent”),
`8,754,131 (“the ’131 patent”), 8,871,813 (“the ’813 patent”),
`and 8,927,606 (“the ’606 patent”) (collectively, the “patents-
`in-suit”).
`
`Before the Court is the parties’ request for claim
`construction of three disputed terms in these patent
`infringement actions:1
`“in an amount sufficient to stabilize said first
`1.
`component,” as it appears in asserted claim 1 of the
`
`1 The parties initially disputed a fourth term, “EDTA sodium
`salt” and “sodium edetate” (which the parties agree are
`equivalent terms), in their Markman briefs, but subsequently
`stipulated to a joint proposed construction of the two terms.
`(See, e.g., Stip. [Docket Item 102], Senju Pharm. Co. Ltd. v.
`Lupin, LTD., Civ. No. 14-667.) The Court will therefore adopt
`the parties’ construction and construe “EDTA sodium salt” and
`“sodium edetate” to mean “A sodium salt of
`ethylenediaminetetraacetic acid. This phrase encompasses, for
`example, the disodium salt of ethylenediaminetetraacetic acid.”
`4
`
`
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 5 of 32 PageID: 4345
`Case 1:15—cv—O3240—JBS—KMW Document 59 Filed 11/18/15 Page 5 of 32 Page|D: 4345
`
`’290 patent, claim 1 of the ’131 patent, claim 1 of
`the ’8l3 patent, and claim 1 of the 606 patent; and
`“stable,” as it appears in asserted claims 1, 7, 8,
`10, 13, 14, 19, 20, 22, 25 of the ’290 patent, claims
`1, 6, 7, 9, 12, 13, 18-22, 24 of the '131 patent,
`claims 1, 7, 9, 13, 19-21 of the '813 patent, claims
`
`1, 9, 11, 12, 18, 19, 25, 26 of the ’606 patent.
`
`“consisting essentially of” and “consists essentially
`of,”2 as they appear in asserted claims 1 and 18 of the
`’431 patent, claims 1, 7, and 13 of the ’813 patent,
`claims 7, 13, 19, and 25 of the ’290 patent, claims 6,
`12, 18, and 24 of the ’131 patent, and claims 9, 18,
`and 25 of the ’606 patent;
`
`“satisfies the preservative efficacy standard of US
`
`Pharmacopoeia as follows: 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;
`
`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,” as it
`appears in asserted claims 25-29 of the ’131 patent.
`
`For the reasons that follow,
`
`the Court construes the
`
`disputed phrases as follows:3
`
` Court’ 8 Construction
`“in an amount sufficient to
`“in an amount sufficient to
`
`stabilize said first
`
`component” and “stable”
`
`stabilize said first component”
`means “an amount sufficient to
`
`confer sufficient resistance to
`
`2 The parties agree that “consisting essentially of” and
`(See Def.
`“consists essentially of” have the same meaning.
`Opening Claim Constr. Br. at 24 n.8.)
`3 The Court held a Markman hearing on November 2, 2015, and
`considered the lengthy Markman submissions by the parties, which
`included thousands of pages of exhibits, along with declarations
`Ph.D. and Dr.
`from Plaintiffs’
`Dr. Robert 0. Williams,
`experts,
`and Defendants’
`Ph.D.,
`
`expert, Dr. Jayne
`
`Thomas K. Green,
`Ph.D.
`Lawrence,
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 6 of 32 PageID: 4346
`
`degradation to be formulated
`and maintained for ophthalmic
`use,” and “stable” means
`“having sufficient resistance
`to degradation and having
`sufficient preservative
`efficacy to be formulated and
`maintained for ophthalmic use”
`Includes the listed ingredients
`and additional unlisted
`ingredients so long as they do
`not materially affect the basic
`and novel characteristics of
`the claimed preparations. May
`include additional active
`ingredients that do not
`materially affect the basic and
`novel properties of the claimed
`preparation.
`
`“satisfies the preservative
`efficacy standard of EP-
`criteria B of the European
`Pharmacopoeia as
`follows: viable cell counts of
`bacteria (S. aureus, P.
`aeruginosa) 24 hours and 7 days
`after inoculation . . .”
`
`“consisting essentially of”
`and “consists essentially of”
`
`“satisfies the preservative
`efficacy standard of US
`Pharmacopoeia as follows:
`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; 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
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 7 of 32 PageID: 4347
`
` BACKGROUND
` Factual and Procedural Background4
`Plaintiff holds the patents for novel formulations of
`
`bromfenac, an active ingredient in Plaintiff’s drug Prolensa®,
`which has been approved by the Food and Drug Administration
`(hereinafter, the “FDA”) for the treatment of postoperative
`inflammation and reduction of ocular pain in patients who have
`undergone cataract surgery. The patents at issue in this case,
`namely, the ’431 patent, the ’290 patent, the ’131 patent, the
`’813 patent, and the ’606 patent, together disclose and claim an
`ophthalmic bromfenac formulation which contains (1) bromfenac
`and (2) tyloxapol, a non-ionic surfactant, and methods of using
`these formulations to treat ocular pain and inflammation.
`
`The ’431, ’290, ’131, ’813, and ’606 patents all share
`essentially the same specification, and all claim an “Aqueous
`Liquid Preparation Containing 2-Amino-3-(4-
`Bromobenzoyl)Phenylacetic Acid.” (See, e.g., ’431 patent, Pl.
`Opening Claim Constr. Br. Ex. 1.)5 2-Amino-3-(4-
`bromobenzoyl)phenylacetic acid is the chemical name of
`
`
`4 For purposes of the pending Markman determination, the Court
`need not retrace the detailed factual and procedural history of
`these complex infringement actions, and writes primarily for the
`parties.
`5 Because the parties acknowledge that the five patents have the
`same specifications (see Pl. Opening Claim Constr. Br. at 1 n.2;
`Def. Opening Claim Constr. Br. at 2 n.2), the Court only cites
`to one illustrative specification, unless otherwise indicated.
`7
`
`
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 8 of 32 PageID: 4348
`
`bromfenac, which is a non-steroidal anti-inflammatory drug
`(“NSAID”) that is used to treat inflammatory diseases of the
`anterior or posterior segment of the eye. (See, e.g., ’431
`patent at 1:24-45.) The patents-in-suit claim the addition of
`tyloxapol to an aqueous liquid preparation of bromfenac. The
`addition of tyloxapol stabilizes the solution within a pH range
`that is non-irritating to the eyes, and inhibits the
`deterioration of the preservative effect of a widely-used
`preservative, benzalkonium choride, allowing for a longer shelf
`life.6 (Id. at 2:35-47.)
`
`The claims in the ’431, ’290, ’131, and ’813 patents are
`directed to the new formulation of bromfenac. Independent claim
`1 of the ’431 patent, for example, states:
`1. An aqueous liquid preparation consisting
`essentially of the following two components, 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 and the second
`component is tyloxapol, wherein said liquid
`preparation
`is
`formulated
`for
`ophthalmic
`administration, and wherein when a quaternary
`ammonium compound is included in said liquid
`preparation, the quaternary ammonium compound is
`benzalkonium chloride.
`
`
`6 Benzalkonium chloride is widely used as a preservative in
`ophthalmic solutions, but has generally been considered
`incompatible with NSAIDs such as bromfenac, because it “lose[s]
`[its] ability to function as [it] forms complexes with the
`charged drug compounds.” (’431 patent at 1:63-2:3.)
`8
`
`
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 9 of 32 PageID: 4349
`
`(’431 patent at 11:66-12:9.) The independent claims of the ’290,
`’131, and ’813 patents contain similar language. Claim 1 of the
`’290 patent, for example, replaces the phrase “consisting
`essentially of” with “comprising,” specifies that the first
`component is the “sole pharmaceutical active ingredient
`contained in the preparation,” and adds limitations that
`tyloxapol be present “in an amount sufficient to stabilize said
`first component,” and that the aqueous liquid preparation be
`“stable.” (’290 patent, Pl. Opening Claim Constr. Br. Ex. 2, at
`12:2-12.) The ’131 patent is a division of the ’290 patent, and
`claim 1 adds the additional limitation that the first component,
`the “sole pharmaceutical active ingredient contained in the
`preparation,” “is present in the preparation at a concentration
`from about 0.05 w/v % to about 0.2 w/v %.” (’131 patent, Pl.
`Opening Claim Constr. Br. Ex. 3.) The ’813 patent is a division
`of the ’290 patent and claim 1 specifies an aqueous liquid
`preparation that consists essentially of five components – the
`first two already specified, plus boric acid, sodium
`tetraborate, and water. (’813 patent, Pl. Opening Claim Constr.
`Br. Ex. 4.)
`
`The ’606 patent is directed to a method for treating an
`inflammatory disease of the eye, by administering a composition
`comprising bromfenac and tyloxapol to the eye “at a dose and a
`
`
`
`9
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 10 of 32 PageID: 4350
`
`frequency effective to treat said inflammatory disease.” (’606
`patent, Pl. Opening Claim Constr. Br. Ex. 5, at 11:30-31.)
`
`Beginning in late 2013, Defendants began to send Notice
`Letters to Plaintiffs, pursuant to 21 U.S.C. § 355(j)(2)(B)(ii),
`informing Plaintiffs that Defendants have submitted ANDAs with
`the FDA with Paragraph IV certifications on the patents-at-issue
`to seek approval to manufacture and sell generic bromfenac
`ophthalmic solution prior to the expiration of the ’431, ’290,
`’131, ’813, and ’606 patents. The certifications notified
`Plaintiffs that their patents were “invalid, unenforceable,
`and/or will not be infringed” by Defendants’ product. (See Pl.
`Opening Claim Constr. Br. Exs. 8-16.)
`
`Plaintiffs filed the first patent infringement action
`before this Court on January 31, 2014, see Senju Pharm. Co.,
`Ltd. v. Lupin, Ltd., Civ. No. 14-667 (JBS/KMW) (filed January
`31, 2014), and the five other related cases followed. See Senju
`Pharm. Co., Ltd. v. Lupin, Ltd., Civ. No. 14-4149 (JBS/KMW)
`(filed June 26, 2014); Senju Pharm. Co., Ltd. v. Lupin, Ltd.,
`Civ. No. 14-5144 (JBS/KMW) (filed Aug. 15, 2014); Senju Pharm.
`Co., Ltd. v. Innopharma Licensing, Inc., Civ. No. 14-6893
`(JBS/KMW) (filed Nov. 3, 2014); Senju Pharm. Co., Ltd. v. Lupin,
`Ltd., Civ. No. 15-335 (JBS/KMW) (filed Jan. 16, 2015); Senju
`
`
`
`10
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 11 of 32 PageID: 4351
`
`Pharm. Co., Ltd. v. Innopharma Licensing, Inc., Civ. No. 15-3240
`(JBS/KMW) (filed May 8, 2015).7
` CLAIM CONSTRUCTION STANDARD
`“It is a bedrock principle of patent law that the claims of
`
`a patent define the invention to which the patentee is entitled
`the right to exclude.” Phillips v. AWH Corp., 415 F.3d 1303,
`1312 (Fed. Cir. 2005) (en banc) (internal quotations omitted).
`Claim construction is a matter of law to be determined solely by
`the court, Markman v. Westview Instruments, Inc., 517 U.S. 370,
`372 (1996), and the Court need not follow the parties’ proposed
`constructions. See Marine Polymer Techs., Inc. v. HemCon, Inc.,
`672 F.3d 1350, 1359 n.4 (Fed. Cir. 2012) (en banc).
`
`In construing a claim term, the Court looks first to the
`intrinsic evidence, “including the claims themselves, the
`specification, and the prosecution history of the patent.”
`Sunovion Pharm., Inc. v. Teva Pharm. USA, Inc., 731 F.3d 1271,
`1276 (Fed. Cir. 2013) (citing Phillips, 415 F.3d at 1315–17;
`
`
`7 Defendants have also filed several petitions against Plaintiffs
`for inter partes review (“IPR”) before the Patent Trial and
`Appeal Board (“PTAB”) seeking a ruling on the validity of the
`patents-in-suit. See Inter Partes Review of U.S. Patent No.
`8,669,290, IPR2015-00902 (filed by Innopharma); Inter Partes
`Review of U.S. Patent No. 8,129,431, IPR2015-00903 (Innopharma);
`Inter Partes Review of U.S. Patent No. 8,754,131, IPR2015-01097
`(Lupin); Inter Partes Review of U.S. Patent No. 8,669,290,
`IPR2015-01099 (Lupin); Inter Partes Review of U.S. Patent No.
`8,927,606, IPR2015-01100 (Lupin); Inter Partes Review of U.S.
`Patent No. 8,871,813, IPR2015-01105 (Lupin).
`11
`
`
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 12 of 32 PageID: 4352
`
`Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed.
`Cir. 1996)). The words of a claim are generally “given their
`plain and ordinary meanings,” Golden Bridge Tech., Inc. v.
`Apple, Inc., 758 F.3d 1362, 1365 (Fed. Cir. 2014), which is “the
`meaning that the term would have to a person of ordinary skill
`in the art in question at the time of the invention,” read in
`the context of the entire patent. Phillips, 415 F.3d at 1312-13
`(internal quotations omitted).
`
`The claims themselves provide “substantial guidance as to
`the meaning of particular claim terms.” Id. at 1314; see also
`ACTV, Inc. v. Walt Disney Co., 346 F.3d 1082, 1088 (Fed. Cir.
`2003) (“[T]he context of the surrounding words of the claim also
`must be considered in determining the ordinary and customary
`meaning of those terms”). The specification is also “highly
`relevant to the claim construction analysis” and it is “entirely
`appropriate for a court, when conducting claim construction, to
`rely heavily on the written description for guidance as to the
`meaning of the claims.” Phillips, 415 F.3d at 1315, 1316-17.
`Finally, the court will consider the patent's prosecution
`history – “the complete record of the proceedings before the PTO
`. . . includ[ing] the prior art cited during the examination of
`the patent.” Id. at 1317. Although the prosecution history is
`“less useful for claim construction purposes,” it may inform the
`meaning of a claim term “by demonstrating how the inventor
`
`
`
`12
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 13 of 32 PageID: 4353
`
`understood the invention, and whether the inventor limited the
`invention in the course of prosecution, making the claim scope
`narrower than it would otherwise be.” Id.
`
`If the intrinsic evidence fails to disclose the meaning of
`a term, the Court may examine extrinsic evidence – all evidence
`external to the patent and prosecution history, including expert
`and inventor testimony, dictionaries, and learned treatises – to
`determine the meaning of particular terminology to those of
`skill in the art of the invention. Id. at 1318. The Court of
`Appeals for the Federal Circuit, however, cautions against
`“heavy reliance” upon extrinsic sources divorced from the
`intrinsic evidence because it “risks transforming the meaning of
`the claim term to the artisan into the meaning of the term in
`the abstract,” and out of the context of the specification. Id.
`at 1321.
`
`“The construction that stays true to the claim language and
`most naturally aligns with the patent’s description of the
`invention will be, in the end, the correct construction.’” Shire
`Dev., LLC v. Watson Pharms., Inc., 746 F.3d 1326, 1330 (Fed.
`Cir. 2014) (quoting Phillips, 415 F.3d at 1316).
`
`
`
`13
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 14 of 32 PageID: 4354
`Case 1:15—cv—O3240—JBS—KMW Document 59 Filed 11/18/15 Page 14 of 32 Page|D: 4354
`
`IV. DISCUSSION
`
`A.“in an amount sufficient to stabilize said first component”
`and “stable”3
`
`Plaintiffs’
`
`Construction
`
`Defendants’
`
`Construction
`
`Court's
`
`Construction
`
`“in an amount
`Indefinite (i.e.,
`“in an amount
`the claim, even read. sufficient to
`sufficient to
`in light of the
`stabilize said first
`stabilize said first
`component” means “an specification and.
`component” means “an
`amount sufficient to the prosecution
`amount sufficient to
`confer sufficient
`history, fails to
`confer sufficient
`resistance to
`inform, with
`resistance to
`degradation to be
`reasonable
`degradation to be
`those
`formulated and
`certainty,
`formulated and
`maintained for
`skilled in the art
`maintained for
`
`ophthalmic use,” and. concerning the scope ophthalmic use,” and
`“stable” means
`of the invention)
`“stable” means
`“having sufficient
`“having sufficient
`resistance to
`resistance to
`
`degradation and
`having sufficient
`preservative
`efficacy to be
`formulated and
`
`maintained for
`
`ophthalmic use”
`
`degradation and
`having sufficient
`preservative
`efficacy to be
`formulated and
`
`maintained for
`
`ophthalmic use”
`
`The term “stable” is used in the context of “stable liquid
`
`preparation” or “stable aqueous liquid preparation” to describe
`
`the patented product. The phrase “in an amount sufficient to
`
`stabilize said first component” describes the amount of the
`
`ingredient tyloxapol in the patented product to stabilize the
`
`these disputed phrases appear in asserted
`3 As stated above,
`claims 1, 7, 8, 10, 13, 14, 19, 20, 22, 25 of the ’290 patent,
`claims 1, 6, 7, 9, 12, 13, 18-22, 24 of the ’l31 patent, claims
`1, 7, 9, 13, 19-21 of the '813 patent, claims 1, 9, 11, 12, 18,
`19, 25, 26 of the ’606 patent.
`
`14
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 15 of 32 PageID: 4355
`
`active ingredient bromfenac from degradation. Claim 1 of the
`‘290 patent illustrates how these terms are used:
`A stable aqueous liquid preparation comprising (a) a
`first component; and (b) a second component, . . . the
`first component is the sole pharmaceutical active
`ingredient contained in the preparation;9 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.
`
`(’290 patent, Pl. Opening Claim Constr. Br. Ex. 2, at 12:2-12.)
`
`Plaintiffs argue that “in an amount sufficient to stabilize
`said first component” refers specifically to tyloxapol’s effect
`on bromfenac, and means “an amount sufficient to confer
`sufficient resistance to degradation to be formulated and
`maintained for ophthalmic use.” They argue that the word
`“stable,” by contrast, modifies the patented product as a whole,
`and refers to “having sufficient resistance to degradation and
`having sufficient preservative efficacy to be formulated and
`maintained for ophthalmic use.” (Pl. Opening Claim Constr. Br.
`at 18-19) (emphasis added). Plaintiffs cite to cases in which
`courts have construed “stable” and “stabilizing” to mean
`“resistant to decomposition,” or that the “active pharmaceutical
`ingredient does not decompose substantially such that that the
`
`
`9 The “first component” refers to 2-amino-3-(4-
`bromobenzoyl)phenylacetic acid [bromfenac], or a
`pharmacologically acceptable salt thereof or a hydrate thereof.
`(’290 patent, at 12:4-6.)
`
`
`
`15
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 16 of 32 PageID: 4356
`
`formulation has a pharmaceutically acceptable shelf life.” (Id.
`at 19-20 (quoting Cadence Pharm., Inc. v. Paddock Labs. Inc.,
`886 F. Supp. 2d 445, 452 (D. Del. 2012) and Rohm & Haas Co. v.
`Lonza Inc., 997 F. Supp. 635, 638 (E.D. Pa. 1998)).) Plaintiffs
`also point to the specification for support, noting that the
`three experimental examples illustrate the preservative efficacy
`of the patented product, and the ability of tyloxapol to make
`the composition stable for eye drops. (Id. at 20-21; see also
`Pl. Resp. Br. at 10-15.)
`
`Defendants contend that the terms “stable” and “stabilized”
`are indefinite because they can refer to many different
`attributes in the context of an ophthalmic preparation, such as
`chemical stability or physical stability. They also argue that
`since the experimental examples in the specification do not
`define the boundary between “stable” and unstable, there is no
`way to know what does or does not fall within the meaning of the
`terms “stable” or “stabilize[d].” (Def. Opening Claim Constr.
`Br. at 18-23; Def Resp. Br. at 2-10.)
`
`Title 35 U.S.C. § 112 requires that every patent’s
`specification “conclude with one or more claims particularly
`pointing out and distinctly claiming the subject matter which
`the applicant regards as his invention.” 35 U.S.C. § 112 ¶ 2
`
`
`
`16
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 17 of 32 PageID: 4357
`
`(2006).10 “A claim fails to satisfy this statutory requirement
`and is thus invalid for indefiniteness if its language, when
`read in light of the specification and the prosecution history,
`‘fail[s] to inform, with reasonable certainty, those skilled in
`the art about the scope of the invention.’” Media Rights Techs.,
`Inc., 800 F.3d 1366, 1371 (Fed. Cir. 2015) (quoting Nautilus,
`Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120, 2124 (2014)).
`The indefiniteness inquiry is governed by the same principles
`that govern claim construction, and the Court must therefore
`evaluate the disputed term in light of the patent’s claim,
`specification, and prosecution history. Nautilus, 134 S. Ct. at
`2128; Interval Licensing LLC v. AOL, Inc., 766 F.3d 1364, 1370
`(Fed. Cir. 2014).
`
`The Supreme Court recently articulated a new test in
`Nautilus and explained that the definiteness standard calls for
`a “delicate balance”: it “must allow for a modicum of
`uncertainty,” but must also be “precise enough to afford clear
`notice of what is claimed.” Id. A claim may prove indefinite if
`its language “might mean several different things and no
`informed and confident choice is available among the contending
`
`
`10 Paragraph 2 of 35 U.S.C. § 112 was replaced by § 112(b) when
`the Leahy–Smith America Invents Act (“AIA”), Pub.L. No. 112–29,
`125 Stat. 284 (2011) took effect on September 16, 2012. Because
`the application resulting in the asserted patent was filed
`before that date, the Court refers to the pre-AIA version of 35
`U.S.C. § 112.
`
`
`
`17
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 18 of 32 PageID: 4358
`
`definitions.” Id. at 2130 n.8. “[W]here different approaches to
`measurements are involved,” “the patent and prosecution history
`must disclose a single known approach or establish that, where
`multiple known approaches exist, a person having ordinary skill
`in the art would know which approach to select.” Dow Chem. Co v.
`Nova Chems. Corp (Canada), ___ F.3d ____, 2015 WL 5060947, at *6
`(Fed. Cir. Aug. 28, 2015) (citation omitted); see also Teva
`Pharms. USA, Inc. v. Sandoz, Inc., 789 F.3d 1335 (Fed. Cir.
`2015); see also Markman Opinion at 33, Otsuka Pharm. Co., Ltd.
`v. Torrent Pharma Inc., Civ. No. 14-1078 (D.N.J. Nov. 16, 2015).
`
`As required by the principles of claim construction, the
`Court looks first at the intrinsic evidence to determine whether
`an ordinary skilled person would understand, with reasonable
`certainty, the scope of the terms “stable” and “in an amount
`sufficient to stabilize said first component.” Because the
`claims themselves provide no explanation of the terms, the Court
`turns to the specification and prosecution history.
`
`Here, Plaintiff cites to the experimental examples in the
`specification. Specifically, Experimental Examples 1 and 2,
`entitled “Stability Test of Sodium 2-amino-3-(4-
`bromobenzoyl)phenylacetate,” test the rate of degradation of
`bromfenac in solutions containing various concentrations of
`tyloxapol. Solutions in both Examples were stored at 60º C for
`four weeks, but at a pH of 7.0 in Example 1 and a pH of around
`
`
`
`18
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 19 of 32 PageID: 4359
`
`8.15 in Example 2. (’290 patent, 7:10-63; 8:11-52.)11 Example 1
`was used by the Patent Examiner in his Notice of Allowance to
`credit the finding that tyloxapol has an “unexpected stabilizing
`effect on an aqueous solution of bromfenac in comparison to
`polysorbate 80.” (Notice of Allowance, Pl. Opening Claim Constr.
`Br. Ex. 49, at 9.) In Example 1, a solution containing 0.15 w/v%
`tyloxapol showed 73.8% remaining rate of bromfenac, while a
`solution containing 0.02 w/v% tyloxapol showed 89.6% remaining
`rate of bromfenac. In Example 2, at a pH of 8.15, the remaining
`rate of bromfenac after four weeks in all three solutions
`containing various levels of tyloxapol was over 90%. Based on
`this data, the specification concludes that “those compositions
`have sufficient stability for eye drops.” (’290 patent, 8:50-
`51.) Thus, the phrase “in an amount sufficient to stabilize said
`first component,” which refers specifically to tyloxapol’s
`effect on bromfenac, is explained by the Examples above, which
`illustrate the concentration of tyloxapol that would create an
`ophthalmically-acceptable solution which prevents the
`degradation of the active ingredient bromfenac. A skilled person
`would know from reading the specification that a solution
`containing tyloxapol would be considered chemically stable when
`
`
`11 The experimental examples appear in the specification of all
`five patents. For simplicity, the Court cites only to the ’290
`patent.
`
`
`
`19
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 20 of 32 PageID: 4360
`
`it shows a remaining rate of bromfenac of over 90% under the
`conditions indicated. Put another way, a preparation that meets
`or exceeds that rate under the same testing conditions would
`have “sufficient stability for eye drops,” i.e., be sufficiently
`resistant to degradation to be formulated and maintained for
`ophthalmic use.
`
`The specification also suggests that the term “stable,”
`which, as noted above, modifies the composition as a whole,
`includes an additional dimension. Example 3 shows that two
`bromfenac preparations containing different amounts of tyloxapol
`sufficiently controls microbial growth in the preparation to
`meet European Pharmacopoeia-Criteria B standards for a long
`shelf life. Example 3 demonstrates that in addition to being
`resistant to chemical degradation, the tyloxapol compositions
`also satisfy preservative efficacy standards for ophthalmic
`use.12
`
`Particularly with the benefit of Experimental Examples that
`illustrate the exact testing conditions and results at which the
`solution would be acceptable for ophthalmic use, the Court finds
`
`
`12 Indeed, expert for Defendants, Dr. Jayne Lawrence, testified
`at deposition that a person of ordinary skill in the art would
`make an aqueous liquid preparation of claim 25 of the ’131
`patent by producing a variety of formulations to their preferred
`specification and then “test those formulations with respect to
`stability which would include, but not totally be, preservative
`stability.” (Pl. Resp. Br. Ex. 3 [Docket Item 101-4], at 110:19-
`111:5; see also id. at 110:6-10.)
`20
`
`
`
`

`
`Case 1:15-cv-03240-JBS-KMW Document 59 Filed 11/18/15 Page 21 of 32 PageID: 4361
`
`that the terms “stable” and “in an amount sufficient to
`stabilize said first component” are not indefinite.
`
`Defendants argue that 90% is not a clear benchmark because
`the word “stable” is also used to describe compositions in
`Experimental Example 1 containing less than 90% retention rate.
`(Def. Opening Claim Constr. Br. at 20-21.) But Experimental
`Example 1 merely shows the relative stabilizing effect of
`tyloxapol. The specification notes that “[bromfenac] in each eye
`drop was stable in the order of tyloxapol-containing
`preparation>polyoxyl 40 stearate-containing
`preparation>polysorbate 80-containing preparation” and that a
`preparation containing 0.02 w/v% of tyloxapol “is more stable
`than [a preparation] containing 0.15 w/v% of tyloxapol.”
`Notably, Example 1 does not conclude, as Example 2 does with
`solutions over 90%, that the 73.8% and 89.6% solutions have
`“sufficient stability for eye drops.” The Patent Examiner used
`Experimental Example 1 to show only that tyloxapol has an
`“unexpected stabilizing effect on an aqueous solution of
`bromfenac in comparison to polysorbate 80.” (Def. Opening Claim
`Constr. Br. Ex. R, at 9.) Thus, contrary to Defendants’
`contention, the phrase “in an amount sufficient to stabilize
`said first component” is most