Otsuka Pharmaceutical Co. v. Torrent Pharmaceuticals Ltd. (99 F. Supp. 3d 461, 2015)

United States District Court for the District of New Jersey 2015-04-16

Food and Drugs Patents

Citations

Full opinion text

REDACTED OPINION

SIMANDLE, Chief Judge:

I.INTRODUCTION. .!.468

II. BACKGROUND.470

A. Factual and Procedural Background.470

III. PRELIMINARY ISSUES .472

A. Otsuka’s Motions to Amend .472

B. Informal Applications to Strike.474

IV. STANDARD OF REVIEW APPLICABLE TO MOTIONS FOR

TEMPORARY RESTRAINING ORDER.475

V. DISCUSSION. *Ñ1 cn

A. Likelihood of Success “.....475

1. Otsuka Has Not Demonstrated a Likelihood of Success on its

476 Induced Infringement Claims.

477 a.Standard for Induced Infringement.

i. Claim Construction: Claim 1 of the '350 Patent

478 Discloses a Composition, Namely a Tablet, Comprised of a Single Dosage that Contains At Least Two Active Ingredients.

ii. Otsuka Has Not Demonstrated That Defendants’

483 Proposed ANDA Products Directly Infringe Construed Claim 1 of the '350 Patent.

in. Otsuka Has Not Shown that Defendants Actively and

484 Purposefully Encouraged Infringement.

a. Defendants’ “Carve Out” of the Relevant Indication

485 Significantly Diminishes Any Suggestion of Intentional Action.

b. Defendants’ Proposed Labels Do Not Reflect Actual

486 Instruction in Furtherance of Inducing Infringement.

c. The Substantial Non-Infringing Uses Further

Diminish Any Inference of the Requisite Specific Intent to Induce Infringement. LO s

2. Defendants Have Raised a Substantial Question of Invalidity. §

B. Otsuka Has Not Demonstrated that it Will Suffer Immediate and

Irreparable Harm in the Absence of an Injunction as a result of the Market Entry of these Defendants’ Aripiprazole Products. ^ o

1. Otsuka’s Alleged Harms Are Quantifiable. cn o O

Otsuka Has Not Met the “Causal Nexus” or © to

3. Otsuka’s Delay in Requesting Injunctive Relief Suggests Lack of Urgency . or o 00

C. The Balance of Hardships Favors these Defendants. cjx o CR

D. The Public Interest Counsels against the Issuance an Injunction

VI. CONCLUSION. .507

I. INTRODUCTION

These related patent infringement actions under the Hatch-Waxman Act, 35 U.S.C. §§ 271, 281, generally concern Plaintiff Otsuka Pharmaceutical Co., Ltd.’s (hereinafter, “Otsuka”) position that various defendants’ submissions of abbreviated new drug applications (hereinafter, “AN-DAs”) infringe one or more claims of the various patents covering Otsuka’s Ability® aripiprazole product, U.S. Patent Nos. 5,006,528 (“the '528 patent”), 7,053,092 (“the '092 patent”), 8,017,615 (“the '615 patent”), 8,580,796 (“the '796 patent”), 8,642,600 (“the '600 patent”), 8,642,760 (“the '760 patent”), and 8,759,350 (“the '350 patent”).

As the lengthy exclusivity period for the original compound patent covering Ability®, the '528 patent, comes to close on April 20, 2015, Otsuka moves to enjoin these Defendants from launching generic aripiprazole products on or after-April 20, 2015. Otsuka’s present motions for a Temporary Restraining Order and preliminary injunctive relief concern, in particular, the following generic Defendants and their requests for FDA approval of the following AND As:

1. Torrent Pharmaceuticals Limited, Inc., Torrent Pharma Inc., and Hetero Labs Limited (collectively, “Torrent”), Civil Action Nos. 14-1078 ' (JBS/KMW), 144671 (JBS/KMW), seek FDA approval to sell generic aripiprazole [redacted];

2. Alembic Pharmaceuticals Limited, Alembic Limited, Alembic Global Holding Sa, and Alembic Pharmaceuticals Inc. (collectively, “Alembic”), Civil Action Nos. 142982 (JBS/KMW), 14-7405 (JBS/KMW), seek FDA approval to sell generic aripiprazole [redacted];

3. Zydus Pharmaceuticals USA, Inc., and Cadila Healthcare Limited (collectively, “Zydus”), Civil Action No. 143168 (JBS/KMW), seek FDA approval to sell generic aripiprazole [redacted];

4. Sun Pharmaceutical Industries Ltd., Sun Pharma Global Inc., Sun Phar-ma Global Fze, Sun Pharma USA, Sun Pharmaceuticals Industries, Inc., and Caraco Pharmaceutical Laboratories (collectively, “Sun”), Civil Action Nos. 14-4307 (JBS/KMW), 14-6397 (JBS/KMW), seek FDA approval to sell generic aripiprazole [redacted];

5. Teva Pharmaceuticals USA, Inc. (hereinafter, “Teva”), Civil Action Nos. 14-5878 (JBS/KMW), 14-6398 (JBS/KMW), seeks FDA approval to sell generic aripiprazole [redacted];

6. Actavis Elizabeth LLC, Actavis, Inc., Actavis PLC, Jubilant Life Sciences Limited, Jubilant Generics Limited, and Jubilant Life Sciences (USA) Inc. (collectively, “Acta-vis”), Civil Action No. 14-7106 (JBS/KMW), seek FDA approval to sell generic aripiprazole [redacted];

7. Apotex Corp., Apotex Inc., Apotex Pharmachem Inc., and Hetero Labs Limited (collectively, “Apotex”), Civil Action No. 14-8074 (JBS/KMW), seek FDA approval to sell generic aripiprazole [redacted];

8. Hetero Drugs Limited, Hetero Labs Limited, and Hetero USA, Inc. (collectively, “Hetero”) Civil Action No. 15-161 (JBS/KMW), seek FDA approval to sell generic aripiprazole [redacted]; and

9. Sandoz Inc., Sandoz Private Ltd., and Sandoz International Gmbh. (collectively, “Sandoz”), Civil Action No. 15-1716 (JBS/KMW), seek FDA approval to sell generic aripi-prazole [redacted].

In support of its request for temporary restraining orders, Otsuka claims that Defendants’ generic aripiprazole tablets and/or orally disintegrating tablets infringe Claim 1 of the '350 Patent, a follow-on composition patent indicated for the treatment of major depressive disorder. (See generally Otsuka’s Br. at 4-5; see also Ex. 4 to Fues Dec.) Claim 1, however, discloses only a combination aripiprazole and escitalopram/citalopram product, and each of these Defendants seek approval for a generic product containing only aripipra-zole. (See generally Ex. 4 to Fues Dec.)

Nevertheless, in relying upon Claim 1 in connection with its request for a temporary restraining order, Otsuka argues that Defendants’ proposed generics will induce infringement of Claim 1 of the '350 patent, because Defendants’ proposed package inserts or labels amply “teach[ ] and encourage! ]” the co-administration of ari-piprazole with an antidepressant like cital-opram and escitalopram for the treatment of major depressive disorder. (Otsuka’s Reply at 4.) In addition, Otsuka argues that the entry of Defendants’ infringing generic aripiprazole products would result in the severe loss of Otsuka’s market share, permanent and irreversible erosion of Abilify®’s price, and potentially a partial or complete cessation of Otsuka’s Abi-lify®-oriented operations. (See generally Otsuka’s Br. at 13-29; Otsuka’s Reply at 3-12.)

These generic Defendants have mounted substantively identical oppositions to Otsu-ka’s motions, and indeed argued their opposition collectively through designated counsel at the April 10, 2015 hearing. These Defendants, in particular, uniformly argue that Otsuka’s infringement theory reads a critical element out of Claim 1, and ignores the fact that Claim l’s plain language purportedly covers only a single dosage form, i.e., a single drug product, containing aripiprazole in combination with escitalopram and/or citalopram. (See, e.g., Actavis’s Opp’n at 7; Teva’s Opp’n at 10-12; Apotex’s Opp’n at 4-8.) As a result, because each Defendant seeks to market only an aripiprazole tablet, and not an aripiprazole tablet coupled with the additional active ingredients of escitalopram and/or citalopram, Defendants insist that Otsuka cannot, under any set of facts, prove a claim of induced infringement of its '350 patent as against any ■ of them. (See, e.g., Torrent’s Opp’n at 2; Actavis’s Opp’n at 19; Hetero’s Opp’n at 8 n. 10; Zydus’s Opp’n at 19 — 20; Alembic’s Opp’n at 9-13.)

In addition, and in the alternative, Defendants argue that their respective package inserts deliberately “carved out” the basis for Otsuka’s claim of induced infringement by omitting the treatment indication claimed by the '350 patent, and omitting instruction on the use of aripipra-zole in conjunction with either citalopram or escitalopram, thereby negating the intent prerequisite for inducing infringement, and otherwise eliminating any active or implied instruction or encouragement of any infringing aripiprazole composition and/or use.

The primary issues before the Court concern whether Otsuka has demonstrated a likelihood of success on its claims of induced infringement, and whether Otsuka has demonstrated that it will, in the absence of an injunction, suffer irreparable harm as a result of these generic Defendants’ entry into the aripiprazole market.

For the reasons that follow, Otsuka’s motion for a temporary restraining order will be denied.

II. BACKGROUND

A. Factual and Procedural Background

Otsuka, a pharmaceutical company organized and existing under the laws of Japan, holds New Drug Application (hereinafter, “NDA”) No. 21-436, approved by the FDA, for aripiprazole tablets, which Otsu-ka markets under the trademark Ability®.

In connection with Ability’s® listing in the Orange Book, the FDA’s book of drug products approved under the Food, Drug, and Cosmetic Act (hereinafter, the “Orange Book”), 21 U.S.C. § 3550'), Otsu-ka identifies the '528 patent, the '092 patent, the '615 patent, the '796 patent, the '600 patent, the '760 patent, and the '350 patent, all of which Otsuka owns by virtue of assignment.

Prior litigation involving these and related generic defendants, and concerning the '528 patent covering the aripiprazole compound, compositions, and methods of treatment, resulted in a decision that, in effect, precludes any generic competition in aripi-prazole market prior to the expiration of the '528 patent (inclusive of its pediatric exclusivity period) on April 20, 2015. See generally Otsuka Pharm. Co. v. Sandoz, Inc., No. 07-1000(MLC), 2010 WL 4596324, at *4-5 (D.N.J. Nov. 15, 2010). As a result of this exclusivity, Otsuka has enjoyed an extended and incredibly lucrative monopoly over the aripiprazole market.

Moreover, in the aftermath of that decision (and indeed during the litigation), Ot-suka sought and obtained FDA approval for an array of “follow on” patents, all of which generally concern the aripiprazole drug substance, and seek to elongate Otsu-ka’s long-held monopoly over the aripipra-zole market. As relevant here, the '350 patent, a product patent which the FDA issued on June 24, 2014, generally discloses a combination aripiprazole product comprised of aripiprazole together with serotonin reuptake inhibitors in a pharma-ceutically acceptable carrier, for the “Ad-junctive Treatment of Major Depressive Disorder.”

As Otsuka’s patent plateau approached, a flurry of generic Defendants, many if not all of which are implicated in these related patent infringement actions, filed ANDAs seeking approval to market an array of aripiprazole products. As a result of the ANDA filings, Otsuka filed Complaints in this District, alleging that these Defendants proposed generic aripiprazole products will, if approved and marketed, infringe some combination of the follow on patents, e.g., at least one specific claim of the '615, '796, '760, '092, '600, and/or the '350 patents.

After nearly one year of litigation in certain cases, see, e.g., Otsuka Pharm. Co., Ltd. v. Torrent Pharm. Ltd., Civil Act. No. 14-1078 (filed March 18, 2014); Otsuka Pharma Co., Ltd. v. Alembic Pharm. Ltd., Civil Act. No. 14-2982 (filed May 9, 2014), and despite long knowing the April 20, 2015 date certain of the '528 patent’s expiration, Otsuka first referenced its proposal in these related cases to file motions for temporary restraining orders and preliminary injunctions on March 9, 2015.

Faced with the prospect of such motions with regard to potential at-risk launches by as many as two-dozen Defendants on or after April 20, 2015, the Court promptly convened an in-person conference with all counsel in the related actions on March 16, 2015, in order to enter a global schedule for Otsuka’s seemingly long-anticipated motions for preliminary injunctions.

During the conference, the nature of Otsuka’s proposed motions came into focus. Critically, despite these related Defendants’ ANDA filings, Otsuka did not know which, if any, of the generic defendants intended to launch generic aripipra-zole products “at risk” at the expiration of the '528 patent’s pediatric exclusivity on April 20, 2015, and therefore did not know against whoim to seek injunctive relief. The Court, in turn, faced the prospect (for generic defendants not intending to launch at this time) of addressing motions without live controversies, but recognized the confidential and sensitive nature of these defendants’ launch intentions. Therefore; following arguments of counsel, the Court entered a Scheduling Order on March 17, 2015, that observed the principle that the generic defendants would not be required to provide notice of intent to launch at risk, all while avoiding unnecessary adjudication by permitting defendants without intention to launch at risk to opt out of the briefing associated with Otsuka’s motion for temporary restraining order. [See, e.g., Docket Item 76 in 14-1078.]

The Scheduling Order, in particular, permitted any defendant to file, in lieu of opposition to Otsuka’s motion, a statement that such defendant did not intend to launch its aripiprazole product prior to June 20, 2015, in which case Otsuka’s motion would be dismissed without prejudice to renewal, and that opt out defendant would be deemed precluded from launching prior to June 20, 2015, unless otherwise ordered by the Court. [See id. at ¶ 2.] In accordance with the Court’s Scheduling Order, briefing followed in these cases.

The Court heard arguments and proffers of evidence on behalf of all parties at the hearing upon these motions for temporary restraining order on April 10, 2015, in which the parties have amassed a record of thousands of pages spanning the 13 above-captioned dockets.

III. PRELIMINARY ISSUES

Prior to addressing Otsuka’s motions for a temporary restraining order, the Court must address two threshold issues.

A. Otsuka’s Motions to Amend

First, Otsuka has very recently moved to amend its Complaints in Otsuka Pharm. Co., Ltd. v. Torrent Pharm,., Inc., Civil Action No. 14-4671 (JBS/KMW), Otsuka Pharm. Co., Ltd. v. Zydus Pham. USA Inc., Civil Action No. 14-3168 (JBS/KMW), Otsuka Pharm. Co., Ltd. v. Zydus Pham. USA Inc., Civil Action No. 147252 (JBS/KMW), Otsuka Pharm. Co., Ltd. v. Teva Pharm. USA Inc., Civil Action No. 14-5878 (JBS/KMW), and Otsuka Pharm. Co., Ltd. v. Teva Pharm. USA, Inc., Civil Action No. 14-6398 (JBS/KMW), in order to assert the '350 patent, for the first time, against Torrent, Zydus, and Teva.

Under Federal Rule of Civil Procedure 15, leave to amend should be “freely give[n] when justice so requires.” Fed. R.Crv.P. 15(a)(2). Therefore, in the absence of undue prejudice, unfair prejudice, or futility, motions to amend must be granted. See Arthur v. Maersk, Inc., 434. F.3d 196, 204 (3d Cir.2006) (stating that generally, leave to amend should be granted “unless equitable considerations render it otherwise unjust.”).

Torrent, Zydus, and Teva, challenge Otsuka’s motions to amend on futility, prejudice, and delay grounds. (See Torrent’s Opp’n to Mot. to Amend at 2-5; Zydus’s Opp’n to Mot. to Amend at 6-13; Teva’s Opp’n to Mot. to Amend at 6-19.) The Court, however, finds that Otsuka’s proposed amendments provide sufficient factual matter, if accepted as true, to state plausible, non-futile claims for relief. See Ashcroft v. Iqbal, 556 U.S. 662, 678, 129 S.Ct. 1937, 173 L.Ed.2d 868 (2009). The Court is reluctant to conclude in expedited motion practice on these amendments that Otsuka could never prevail on such claims under its '350 patent. There is further the practical consideration that the contours of the '350 patent and the defendants’ products are being explored in detail in those other closely related cases, with the benefit of an elaborate record.

In addition, the Court does not find that Otsuka unduly delayed in seeking to amend, nor that its motions have caused unfair prejudice to these Defendants in connection with Otsuka’s motions for temporary restraining orders. Delay was not undue in these cases because Otsuka had asserted the '350 patent, among others, against all ANDA-filers in the many companion cases which had filed Paragraph IV certifications under 21 U.S.C. § 355(j)(2)(A)(vii), asserting their positions that their ANDAs would not infringe the patents at issue, and/or their position on the invalidity of the patents at issue. Otsuka claims it did not initially assert the '350 patent against these remaining ANDA filers because they had instead filed section viii statements under 21 U.S.C. § 355(j)(2)(A)(viii), certifying that they only intended to offer an aripiprazole product, and had not requested approval for any patented indications, particularly any approval related to the combination of aripiprazole with antidepressants citalo-pram and/or escitalopram. Otsuka claims that it asked for clarification from these section viii filers of exactly what their product and labels/package inserts would entail, and that Otsuka never received the desired clarifications thus prompting the need to assert the '350 patent against them in these motions to amend. By holding their cards so close to the vest as litigation progressed, these defendants contributed to Otsuka’s delay in joining the '350 patent to this litigation.

With respect to prejudice, the Court notes that, despite the short notice, these Defendants have shown the ability to address these claims through their filing of oppositions and sur-replies equivalent and substantively identical to those of the generic defendants against whom Otsuka asserted the '350 patent far earlier. Given this, it can fairly be concluded that these parties anticipated that the '350 patent would be in play just as it was in the related cases.

Consequently, for the reasons stated above and on the oral argument record on April 10, 2015, Otsuka’s motions to amend will be granted.

B. Informal Applications to Strike

Second, the Court addresses Defendants’ application to strike the supplemental declarations of Otsuka’s experts, Dr. Roth and Mr. Jarosz [see, e.g., Docket Item 103 in 14-1078], and Otsuka’s application to strike Defendants’ “improperly” raised claim construction arguments. [See, e.g., Docket Item 104 in 14-1078.] Defendants, in particular, challenge Otsuka’s supplemental declarations to the extent Dr. Roth’s and Mr. Jarsoz’s supplemental declarations present new factual and legal arguments concerning claim construction, patent validity, and the financial harm to Otsuka in the absence of an injunction. [See, e.g., Docket Item 103 in 14-1078.] Otsuka, in turn, seeks to strike Defendants’ sur-replies and accompanying supplemental declarations, principally to the extent Defendants’ sur-replies’ “distort! ] and misrepresent! ] the prosecution history” of the '350 patent. [See, e.g., Docket Item 104 in 14-1078.]

In that respect, both applications concern, at their cores, the purportedly improper expansion of the factual record on substantive issues implicated in Otsuka’s pending motions. Nevertheless, the Court finds that all issues relevant to Otsuka’s pending motions for temporary restraining orders, including, all issues with respect to claim construction, invalidity, and irreparable harm, have been amply dealt with in the parties’ voluminous submissions, and through counsels’ lengthy presentations at the April 10, 2015 hearing. Indeed, counsels’ comprehensive oral arguments mitigated any arguable prejudice associated with the new assertions in supplemental declarations and/or sur-replies. The Court will, however, strike Otsuka’s supplemental declarations to the extent the experts, in their declarations, set forth their own legal conclusions (as opposed to a reiteration of a legal conclusion). See L. Civ. R. 7.2(a) (“Legal arguments and summation in [affidavits, declarations, and certifications] will be disregarded by the Court and may subject the signatory to appropriate censure, sanctions or both.”).

For these reasons, and those set forth during the April 10, 2015 hearing, Defendants’ application to strike will be granted in part only with respect to certain legal arguments of Otsuka’s experts and denied with respect to Defendants’ remaining challenges, and Otsuka’s application to strike will be denied in its entirety.

Therefore, the Court turns to the merits of Otsuka’s motions for temporary restraining orders to prohibit at-risk launches by these generic product defendants.

IV. STANDARD OF REVIEW APPLICABLE TO MOTIONS FOR TEMPORARY RESTRAINING ORDER

“The decision to grant or deny ... injunctive relief is an act of equitable discretion by the district court.” eBay, Inc. v. MercExchange, LLC, 547 U.S. 388, 391, 126 S.Ct. 1837, 164 L.Ed.2d 641 (2006); see also 35 U.S.C. § 283 (generally providing that courts “may grant injunctions in accordance with the principles of equity to prevent the violation of any right secured by patent, on such terms as the court deems reasonable”). Injunctive relief, however, remains “ ‘an extraordinary remedy never awarded as of right.’ ” Wind Tower Trade Coalition v. United States, 741 F.3d 89, 95 (Fed.Cir.2014) (citations omitted).

A party seeking a temporary or preliminary injunction must therefore demonstrate: (1) a reasonable likelihood of success on the merits; (2) the prospect of irreparable harm in the absence of an injunction; (3) that this harm would exceed harm to the opposing party; and (4) that the public interest favors such relief. See, e.g., Sciele Pharma Inc. v. Lupin Ltd., 684 F.3d 1253, 1259 (Fed.Cir.2012); Antares Pharma, Inc. v. Medac Pharma, Inc., 55 F.Supp.3d 526, 529-30, 2014 WL 3374614, at *2 (D.Del.2014). These considerations apply equally to requests for temporary restraining orders and preliminary injunctions. See Takeda Pharm. USA, Inc. v. West-Ward Pharm. Corp., No. 14-1268, 2014 WL 5088690, at *1 (D.Del. Oct. 9, 2014) (“A request for a TRO is governed by the same general standards that govern the issuance of a preliminary injunction.”) (citation omitted).

In determining whether to issue injunctive relief, no one factor, taken individually, proves dispositive. See Hybritech v. Abbott Labs., 849 F.2d 1446, 1451 (Fed.Cir.1988); see also AstraZeneca LP v. Apotex, Inc., 623 F.Supp.2d 579, 587 (D.N.J.2009). Rather, the Court “must weigh and measure each factor against the other factors and against the form and magnitude of the relief requested.” Hybritech, 849 F.2d at 1451. Nevertheless, no injunction will issue, temporary or otherwise, unless the movant “ ‘establishes both of the first two factors, i.e., likelihood of success on the merits and irreparable harm.’” PHG Tech., LLC v. St. John Cos., Inc., 469 F.3d. 1361, 1365 (Fed.Cir.2006) (quoting Amazon.com, Inc. v. Barnesandnoble.com, Inc., 239 F.3d 1343, 1350 (Fed.Cir.2001)).

The Court will address each of the four, factors in turn.

V. DISCUSSION

A. Likelihood of Success

Otsuka claims that nine groups of generic Defendants in these 13 cases should be enjoined from launching their aripiprazole products on or after April 20, 2015 because their aripiprazole products will infringe Claim 1 of the '350 patent, the only patent asserted in these preliminary injunction motions.

In order to establish a likelihood of success on the merits, the “patentee seeking a preliminary injunction in a patent infringement suit must show that it will likely prove infringement, and that it will likely withstand challenges, if any, to the validity of the patent.” Titan Tire v. Case New Holland, 566 F.3d 1372, 1376 (Fed.Cir.2009).

As relevant here, Otsuka must demonstrate that, “in light of the presumptions and burdens that will inhere at trial on the merits,” it will likely prove that these generic Defendants’ aripiprazole products infringe the '350 patent and that Otsuka will withstand these generic Defendants’ challenges to the validity of the '350 patent. Sciele Pharma Inc., 684 F.3d at 1259. If, however, these generic Defendants raise “substantial question[s] concerning either infringement or validity, i.e., assert[] an infringement or invalidity defense[s] that [Otsuka] cannot prove ‘lack[] substantial merit,’ the preliminary injunction should not issue.” Amazon.com, Inc., 239 F.3d at 1350-51 (citation omitted); see also Trebro Mfg., Inc. v. Firefly Equipment, LLC, 748 F.3d 1159, 1166 (Fed.Cir.2014) (same).

Here, the Court will first address the issue of infringement, prior to turning to invalidity.

1. Otsuka Has Not Demonstrated a Likelihood of Success on its Induced Infringement Claims

For purposes of these requests for injunction relief, Otsuka argues that it will likely prevail at trial on its position that all of Defendants’ labels induce infringement of Claim 1 of the '350 patent. (Otsuka’s Reply at 1-2.) Otsuka, in particular, insists that Defendants’ inserts unquestionably instruct physicians “to prescribe aripiprazole in combination with an antidepressant like citalopram and es-citalopram” and provide “information” concerning “issues to consider” when prescribing such a combination. (Otsuka’s Reply at 4-5.) In so arguing, Otsuka recognizes that these Defendants’ proposed labels have “carved out” the indication covered by the '350 patent, i.e., the use of aripiprazole for the adjunctive treatment of major depressive disorder, that Defendants’ labels do not specifically direct or prescribe the adjunctive administration of aripiprazole with escitalopram and/or citalopram, and that none of the labels contain any reference to citalopram. (See generally Otsuka’s Reply at 10-12, 15-17.)

Nevertheless, based upon certain warning and safety information concerning the coadministration of aripiprazole with antidepressants, particularly in the Defendants’ various “ ‘black box’ warning[s],” Otsuka submits that each label implicitly teaches and encourages the beneficial nature of co-administering aripiprazole in the manner protected by the '350 patent. (Otsuka’s Br. at 11, 15-17; Otsuka’s Reply at 4-6; see.also Roth Dec.) As a result, Otsuka asserts that Defendants’ package inserts induce infringement of Claim 1 of the '350 patent, because Claim 1 purportedly “discloses and claims novel pharmaceutical compositions comprising aripiprazole in combination with serotonin reuptake inhibitors ” (as opposed to only escitalopram and/or citalopram), and “encompasses any use of that composition,” particularly the use of the composition “as an adjunctive therapy for major depressive disorder.” (Otsuka’s Br. at 4-5 (emphasis added).)

These Defendants, however, uniformly counter that Otsuka’s inducement claim fails, even at this preliminary stage, and would ultimately fail at a trial on the merits, for at least two reasons.

First, Defendants claim that Otsuka’s infringement claim lacks merit, because Defendants’ ANDA products seek only to' market aripiprazole, without any accompanying ingredient. Therefore, because no Defendant seeks to market and/or distribute a “pharmaceutical composition” comprised of aripiprazole and citalopram and/or escitalopram, Defendants argue that they will not make, use, offer for sale or sell a product within the scope of Claim 1 (See, e.g., Actavis’s Opp’n at 6; Sun’s Opp’n at 9-10; Sandoz’s Opp’n at 1, 15; Hetero’s Opp’n at 8 n.10; Apotex’s. Opp’n at 8-9), and, as a result, could never directly infringe the '350 patent, a threshold requirement for a finding of inducement. {See, e.g., Alembic’s Opp’n at 1013; Torrent’s Opp’n at 8-10; Zydus’s Opp’n at 19-21; Sandoz’s Sur-reply at 1-3.) Second, Defendants argue that Otsuka has failed to demonstrate that their package inserts or prescribing information reflect the requisite specific intent to induce infringement. {See, e.g., Actavis’s Opp’n at 13-18; Hetero’s Sur-reply at 2-4.)

In order to properly frame the issues implicated by the pending motions — namely, the parties’ disputes concerning whether Otsuka sufficiently demonstrated the threshold elements of an induced infringement claim — the Court must briefly discuss the relevant framework,

a. Standard for Induced Infringement

“Whoever actively induces infringement of a patent shall be liable as an infringer.” 35 U.S.C. § 271(b) (emphasis added). In order to establish inducement, the patentee must show “direct infringement, and that the alleged infringer ‘knowingly induced infringement and possessed specific intent to encourage another’s infringement.’ ” i4i Ltd. P’ship v. Microsoft Corp., 598 F.3d 831, 851 (Fed.Cir.2010). In other words, Otsuka’s theory of induced infringement will be viable “if, but only if,” Otsuka demonstrates “direct infringement,” Limelight Networks, Inc. v. Akamai Techs., Inc., — U.S. —, 134 S.Ct. 2111, 2117, 189 L.Ed.2d 52 (2014) (citation omitted), and if Otsuka presents affirmative evidence that any Defendant knowingly induced infringing acts and possessed a specific intent to encourage another to infringe the '350 patent. See Vita-Mix Corp. v. Basic Holding, Inc., 581 F.3d 1317, 1328 (Fed.Cir.2009); Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1364 (Fed.Cir.2003). In that regard, induced infringement premises liability upon “purposeful, culpable expressions and conduct” and “active steps” taken to encourage direct infringement, including advertising and/or instructions. DSU Med. Corp. v. JMS Co., 471 F.3d 1293, 1305-1306 (Fed.Cir.2006) (en banc in relevant part).

As relevant here, in order to obtain a preliminary injunction, Otsuka must prove that it will “ ‘more likely than not’ ” succeed in establishing the elements of induced infringement. Trebro Mfg., Inc., 748 F.3d at 1166 (citation omitted). Given the parties’ dispute, the infringement analysis for purposes of the pending motion requires two steps. See Abbott Labs. v. Sandoz, Inc., 566 F.3d 1282, 1288 (Fed.Cir.2009). First, the Court must construe the disputed claim of the '350 patent, in order to determine the scope of the claimed infringement. Second, the Court must compare the generic Defendants’ proposed product with the relevant portion of the construed '350 patent. Novartis Pharm. Corp. v. Eon Labs Mfg., Inc., 234 F.Supp.2d 464 (D.Del.2002) (conducting the two-part inquiry), aff’d, 363 F.3d 1306 (Fed.Cir.2004). The Court will address each step in turn.

i. Claim Construction: Claim 1 of the '350 Patent Discloses a Composition, Namely a Tablet, Comprised of a Single Dosage that Contains At Least Two Active Ingredients

In its submissions, Otsuka makes little mention of the need to construe Claim 1 of the '350 patent. (See Otsuka’s Br. at 4-5, 10.) Rather, Otsuka asserts, without explanation, that Claim 1 of the '850 patent discloses “novel pharmaceutical compositions comprising aripiprazole in combination with serotonin reuptake inhibitors,” and argues that, despite the claim language, the specification of the '350 patent clarifies the “understanding that the claimed pharmaceutical composition” claim broadly discloses “multiple dosage forms,” and that aripiprazole and the relevant serotonin reuptake inhibitors “need not be present in the same pill or dosage form.” (Id. at 4-5; see also Otsuka’s Reply at 3-4 (arguing that, “the specification unambiguously explains that aripiprazole and at least one SRI may be in the same dosage form or in separate dosage forms”).)

These generic Defendants, however, uniformly characterize Otsuka’s proposed construction as untenably broad, and argue, based upon the plain claim language, that Claim 1 should be construed to require a single pharmaceutical composition or dosage form, i.e., a single tablet, comprised of at least two different active ingredients: (a) aripiprazole and (b) either citalopram or escitalopram. (See, e.g., Apotex’s Opp’n at 6; Sandoz’s Opp’n at 7-15; Teva’s Br. at 10-12; Hetero’s Br. at 9-17; Actavis’s Opp’n at 7-9.)

In construing claim terms, courts “look to, and primarily rely on, the intrinsic evidence, including the claims themselves, the specification, and the prosecution history of the patent.” Sunovion Pharm., Inc. v. Teva Pharmaceuticals, USA Inc., 731 F.3d 1271, 1276 (Fed.Cir.2013). Generally, however, claim terms are “given their plain and ordinary meanings to one of skill in the art when read in the context of the specification and prosecution history.” Golden Bridge Tech., Inc. v. Apple Inc., 758 F.3d 1362, 1365 (Fed.Cir.2014) (citing Phillips v. AWH Corp., 415 F.3d 1303, 1315-17 (Fed.Cir.2005) (en banc)). Nevertheless, “ ‘[t]he 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).

The disputed composition claim in this instance, Claim 1 of the '350 patent, requires no complex construction. Indeed, the limited claim language leaves little to the imagination, and requires no more than “the application of the widely accepted meaning of commonly understood words.” Phillips, 415 F.3d at 1314.

Claim 1 of the '350 patent specifically discloses, in its entirety, as follows: “A pharmaceutical composition comprising (a) aripiprazole in combination with (b) at least one serotonin reuptake inhibitor selected from citalopram, escitalopram and salts thereof.” ('350 patent, reprinted at Ex. 4 to Fues Dec. at col. 28, In. 64-67 (emphases added).) In that regard, Claim 1 discloses, on its face, only a composition product comprised of the identi-lied active pharmaceutical ingredients, but not any method of administration, particular molecular structure, nor ’any method of use.

Moreover, despite the brevity of the claim language, several features critically relevant to construction immediately emerge from even an cursory review of Claim l’s brief language, namely, the inclusion of “a pharmaceutical composition ” in the singular, followed by grammatically uninterrupted identification of the composition’s at least two component parts. (Id. (emphasis added).) See Credle v. Bond, 25 F.3d 1566, 1571 (Fed.Cir.1994) (stating that “grammatical structure and syntax” of the claim can be important evidence for claim construction). Taken together, the phrases “a pharmaceutical composition” and “in combination with,” when followed by a lettered delineation of the required parts (Ex. 4 to Fues Dec. at col. 28, In. 64-67 (emphasis added)), provide a clear indication that the claim refers to a single pharmaceutical composition or dosage comprised of multiple active pharmaceutical ingredients. Indeed, given the grammatical structure and use of commonly understood terms, a lay person would immediately understand that “[a] pharmaceutical composition” comprised of “(a)” and “(b) ” means that the claimed “composition” requires a single dosage of the identified ingredients — specifically, aripi-prazole as the first ingredient, and citalo-pram, escitalopram and salts therefore as the second ingredient. (Ex. 4 to Fues Dec. at col. 28, In. 64-67.) A plain reading of the Claim language permits no broadened interpretation.

Moreover, the Court’s commonsense, plain language construction finds further support in dependent Claim 18, which discloses “[t]he composition of Claim 1, wherein the amount of (a) aripiprazole in combination with (b) at least one serotonin reuptake inhibitor selected from cítalo-pram, escitalopram and salts thereof is 1 to 70 parts by weight of the total composition.” (’350 patent at col. 30, In. 44-48 (emphasis added).) Claim 18 therefore describes the single “pharmaceutical composition ” of Claim 1 in terms of the combined weight of its active ingredients formulated together in a “total composition.” (Id. (emphases added).) By claiming a specific weight ratio (i.e., “1 to 70 parts”), dependent Claim 18 recites subject matter admittedly narrower than Claim 1. Nevertheless, the Claims’ consistent language makes clear that both disclose aripiprazole and citalopram or escitalopram formulated together in a single dosage form, even if at slightly varied weights. Indeed, Claim 18’s disclosure of a specific ingredient ratio explicitly teaches that Claim l’s “pharmaceutical composition” necessarily occurs in a single dosage format. See, e.g., Research Plastics, Inc. v. Fed. Packaging Corp., 421 F.3d 1290, 1295 (Fed.Cir.2005) (“[C]laim terms are presumed to be used consistently throughout the patent, such that the usage of a term in one claim can often illuminate the meaning of the same term in other claims.”); see also Phillips, 415 F.3d at 1314 (noting that “the use of a term within the claim [can] provide a firm basis for construing the term”).

The overall structure of the patent, throughout its various sequential components, then consistently .and repeatedly teaches that the claimed invention concerns a single dosage form, comprised of two active ingredients.

Indeed, the '350 patent describes the invention at the outset in its abstract as a “pharmaceutical composition” comprised of “(1) a carbostyril derivative,” either “aripi-prazole or a metabolite,” together with “(2) a serotonin reuptake inhibitor,” e.g., citalo-pram and/or escitalopram, “in a [single] pharmaceutically acceptable carrier.” (See Ex. 4 to Fues Dec. at Abstract (emphasis added).) In the disclosure of the invention, the '350 patent then reiterates that the claimed invention consists of at least two ingredients “in a pharmaceutically acceptable carrier.” (Id. at col. 2, In. 66 to col. 6, In. 17.)

Identical disclosures appear in the Detailed Description, which describes in detail the “first” and “second” ingredients, “contained,” “combined,” or “mixed” in the single “pharmaceutical composition.” (See, e.g., id. at col. 6, In. 4755; col. 10, In. 52-57; col. 11, In. 47-48 (“Combination of the First Ingredient with the Second Ingredient”); col. 13, In. 5662 (“the amounts of the first ingredient and the second ingredient to be contained in the pharmaceutical composition of the present invention ... ”); col. 20, In. 27-41 (describing aripi-prazole in a combined administration with citalopram and/or eseitalopram).) Indeed, the introduction of the Detailed Description states that, “[t]he pharmaceutical composition of the present invention comprises a first ingredient comprising a car-bostyil derivative active as' a dopamine-serotonin system stabilizer and a second ingredient comprising a serotonin reup-take inhibitor, in a pharmaceutically acceptable carrier.” (Id. at col. 6, In. 47-51 (emphasis added).) In that regard, the syntax of the introduction alone indicates that the single “pharmaceutically acceptable carrier” describes and limits the preceding composition to a carrier, or dosage, comprised of two ingredients. Even more, however, the Detailed Description contains the following illustrative subheadings: “The Pharmaceutical Composition: The First Ingredient,” i.e., aripiprazole, “The Pharmaceutical Composition: The Second Ingredient,” i.e., a serotonin reuptake inhibitor, and “Combination of the First Ingredient with the Second Ingredient,” i.e., a combination of aripiprazole and an SRI, and preferably “a combination of aripipra-zole/citalopram.” (Id. at col. 6, In. 56, col. 10, In. 52, col. 11, In. 47-59.) Imbedded within these six columns, the Patent uniformly treats the claimed invention as a single “combination” dosage, and specifically delineates the preferred weight ratio “of the first ingredient to the second ingredient” as generally, “about 1 to 70 parts by weight, preferably about 1 to 30 parts by weight of the first ingredient and the second ingredient in the total amount on the basis of the pharmaceutical composition.” (See id. at col. 11, 58-59, col. 12, In. 61-63, col. 13, In. 59-61.)

The eighteen “non-limiting formulation examples of aripiprazole” then uniformly disclose formulations for “the [claimed] tablet” that contain multiple active pharmaceutical ingredients, namely aripipra-zole combined with at least one SRI, together in a single “tablet.” (Id. at Col. 20, In. 46-Col. 25, In. 17 (emphases added); see also Col. 11, In. 54-58 (setting forth a non-exhaustive list of the relevant SRIs).)

Given the volume and pervasiveness of these consistent references to a composition in a single dosage form, the Court finds no support for Otsuka’s position that the “pharmaceutical composition” of Claim 1 should be construed, for purposes of the pending motions, to teach that aripiprazole and the at least one SRI (namely, escitalo-pram and/or citalopraip) may be presented in separate and/or multiple dosage forms. (See Otsuka’s Br. at 4; Otsuka’s Reply at 3.)

Nor does Otsuka’s citation to limited portions of the specification support any contrary construction. At the outset, the Court notes that Otsuka cannot cherry pick portions of the specification to support its argument that the '350 patent teaches a broadened definition of Claim l’s “pharmaceutical composition,” all while ignoring the actual wording of Claim 1 and the other and numerous portions of the specification that provide a clear contrary indication that better comports with the plain claim language. Moreover, when viewed in context, the relied-upon passages lend additional support to the position that Claim 1 refers to a single composition or tablet comprised of two active ingredients.

Otsuka, in particular, relies upon the following portions of the specification:

The novel compositions of [the] present invention comprising at least one carbos-tyril derivative ... and at least one serotonin reuptake inhibitor in a pharma-ceutically acceptable carrier may be combined in one dosage form, for example a pill. Alternatively the at least one carbostyril derivative ... and the at least one serotonin • reuptake inhibitor may be in separate dosage forms, each in a pharmaceutically acceptable carrier.

(Id. at col. 3, In. 52-60 (emphases added).)

Administration forms of the pharmaceutical composition of the present invention may be any type by which the effective levels of both carbostyril derivatives and serotonin reuptake inhibitors can be provided in vivo at the same time. In one embodiment, a carbostyril derivative together with a serotonin reuptake inhibitor are contained in one pharmaceutical composition and this composition may be administered. On the other hand, each one of carbostyril derivative and a serotonin reuptake inhibitor are contained individually in a pharmaceutical preparation respectively, and each one of these preparations may be administered at the same time or in suitable intervals.

(Id. at col. 14, In. 17-21 (emphases added).)

The aripiprazole can be administered in one dosage form, for example a tablet, and the serotonin reuptake inhibitor may be administered in a separate one dosage form, for example a tablet. The administration may occur at about the same time or at different times during the day.

Alternatively, a dosage form containing aripiprazole in combination with at least one serotonin reuptake inhibitor may be administered. Such combinations include without limitation the following: aripiprazole/fluoxetine, aripipra-zole/duloxetine, aripiprazole/venlafaxine, aripiprazole/milnacipran, aripiprazole/ci-talopram, aripiprazole/fluvoxamine, ari-piprazole/paroxetine, and aripipra-zole/sertraline. A preferred embodiment comprises a combination of aripi-prazole and citalopram.

(Id. at col. 26, In. 15-20 (emphases added).)

These passages, particularly the emphasized portions, make plain a distinction between the preferred “combined” composition, e.g.,, the composition otherwise disclosed in the remainder of the specification, and an alternative composition in which the aripiprazole and the at least one SRI exists “in separate dosage forms, each in a pharmaceutically acceptable carrier.” (Id.) Beyond recognizing this critical distinction, these passages further reflect the patent drafter’s appreciation of the language necessary to disclose the potential for separate or multiple administrations. Nevertheless, the patent drafter included no sufficiently flexible or broad language in Claim 1 or in the “Detailed Description,” choosing instead to refer to the singular claim term “pharmaceutical composition.” In that respect, these passages appear to disclose, at most, “alternative” or “on the other hand” embodiments. The Court, however, need not credit alternatively disclosed embodiments that, as here, “contradict” the relevant claim language. TIP Sys., LLC v. Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1373 (Fed.Cir.2008) (declining to include alternatively disclosed embodiment because it “would contradict the language of the claims”); Rolls-Royce, PLC v. United Techs. Corp., 603 F.3d 1325, 1334-35 (Fed. Cir.2010) (omitting certain disclosed embodiments to avoid a construction that “outweighs the language of the claim.”). Moreover, even if the Court otherwise accepted Otsuka’s interpretation of these specific portions of the specification, the specification itself cannot be “a substitute for, nor can [it] be used to rewrite, the chosen claim language.” SuperGuide Corp. v. DirectTV Enters., Inc., 358 F.3d 870, 875 (Fed.Cir.2004) (“[specifications teach,” “[c]laims claim”).

As stated above, the amount of intrinsic evidence that consistently discloses that Claim 1 refers to a single dosage form can hardly be described as anything less than substantial, and the Court finds Otsuka’s broadened construction without support in the Claim language. For all of these reasons, the Court construes Claim 1 for the purposes of the pending motion to refer to a single dosage form, or “pharmaceutical composition,” containing at least two active ingredients: (a) aripiprazole and (b) at least one of citalopram, escitalopram and salt thereof. The Court turns to whether this construed Claim preliminarily supports Otsuka’s infringement claims.

ii. Otsuka Has Not Demonstrated That Defendants’ Proposed ANDA Products Directly Infringe Construed Claim 1 of the '350 Patent

A claim of induced infringement requires Otsuka, as stated above, to make a threshold showing of direct infringement — through either evidence “of specific instances of direct infringement” or through evidence “that the accused products necessarily infringe.” Ricoh Co., Ltd. v. Quanta Computer Inc., 550 F.3d 1325, 1341 (Fed.Cir.2008); see also Meyer Intellectual Props. Ltd. v. Bodum, Inc., 690 F.3d 1354, 1366 (Fed.Cir.2012) (“It is well-established that a finding of direct infringement is a prerequisite to a finding of inducement.”) (citation omitted).

Here, while the Court has preliminarily determined that Claim 1 requires a single composition, or tablet, containing aripiprazole in combination with either citalopram and/or escitalopram, Defendants’ proposed generic products indisputably contain, as stated above, only one active ingredient-aripiprazole. (See, e.g., Torrent’s Opp’n at 8; Alembic’s Opp’n at 2; Zydus’s Opp’n at 1; Sun’s Opp’n at 3; Teva’s Opp’n at 1-3; Actavis’s Opp’n at 6; Apotex’s Opp’n at 8; Hetero’s Opp’n at 8 n.10; Sandoz’s Opp’n at 1.) As a result, Defendants’ proposed products fundamentally cannot, on their face, directly infringe Claim 1, and Otsuka has failed to identify any other underlying act of direct infringement — an express requirement for establishing inducement under 35 U.S.C. § 271(b). See Limelight Networks, Inc., 134 S.Ct. at 2117 (noting that induced infringement lies “if, but only if,” the patentee makes a showing of direct infringement); see also Warner-Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17, 29, 117 S.Ct. 1040, 137 L.Ed.2d 146 (1997) (noting that a direct infringement claim only lies where the patentee shows that the infringing product contains each and every claim limitation). For that reason alone, Otsuka has not met its burden of demonstrating it is ultimately likely to succeed in demonstrating this critical, first element of its theory of induced infringement. Stated differently, these Defendants have raised a powerful showing that Otsuka’s theory of infringement is incorrect.

Nevertheless, even if Otsuka could meet this threshold requirement, Otsuka has not established that any of these Defendants specifically and actively intend to induce infringement of asserted Claim 1, the second requirement of an induced infringement claim, for reasons next discussed,

iii. Otsuka Has Not Shown that Defendants Actively and Purposefully Encouraged Infringement

Otsuka argues that Defendants’ proposed package inserts or labels teach that aripiprazole should be co-administered with an antidepressant like citalopram and/or escitalopram, thereby inducing infringement of Claim 1 of the '350 patent. {See Otsuka’s Br. at 13-17; Otsuka’s Reply at 4-6.)

The Court, however, need not belabor Otsuka’s position, because the Defendants’ labels fail to contain, even under the reading most generous to Otsuka, any sufficiently significant specific and active instruction to, and/or encouragement of, an infringing use.

Inducement requires, as stated above, that the alleged infringer “ ‘knowingly induced infringement and possessed [the] specific intent to encourage another’s infringement.’ ” Ericsson, Inc. v. D-Link Sys., Inc., 773 F.3d 1201, 1219 (Fed.Cir.2014) (citation omitted). Critically, however, “mere knowledge of possible infringement by others does not amount to inducement.” Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1363-64 (Fed.Cir.2003). Rather, the patentee must produce evidence of active steps “taken to encourage direct infringement, such as advertising an infringing use or instructing how to engage in an infringing use.” MGM Studios Inc. v. Grokster, Ltd., 545 U.S. 913, 936, 125 S.Ct. 2764, 162 L.Ed.2d 781 (2005) (citation omitted). The relevant inquiry for purposes of inducement is not, however, “whether a user following the instructions may end up using the device in an infringing way.” Vita-Mix Corp. v. Basic Holding, Inc., 581 F.3d 1317, 1329 n. 2 (Fed.Cir.2009) (emphasis added). Rather, the operative inquiry concerns “whether [the] instructions [actively] teach an infringing use of the [product] such that [courts can] infer from those instructions an affirmative intent” that the product be used to infringe. Id.; see also AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1060 (Fed.Cir.2010) (explaining that the “pertinent question” concerns “whether the proposed label instructs users to perform the patented method”) (emphasis added).

As generics of Ability®, these Defendants’ ANDA products have the same active ingredient (aripiprazole), dosage strengths, and route of administration (oral or oral disintegrating tablets) as Ability®. Nevertheless, these generic Defendants’ proposed package inserts differ, in material respects, from the approved Ability® label for at least two reasons, both of which prove fatal to Otsuka’s assertions of intentional action.

a. Defendants’ “Carve Out” of the Relevant Indication Significantly Diminishes Any Suggestion of Sufficiently Intentional Action

Critically absent from each proposed label is any indication that the generic aripi-prazole products should be used for ad-junctive treatment of major depressive disorder, the primary indication for the '350 patent. Indeed, each generic Defendant specifically “carved-out” the pertinent indication (e.g., “adjunctive treatment for major depressive disorder”) from their respective generic Ability® labels, affirmatively relinquishing the right to actively promote use of their aripiprazole products with any antidepressants, including citalo-pram and escitalopram. (See, e.g., Torrent’s Opp’n at 1-2; Alembic’s Opp’n at 2, 3, 6, 14,18; Zydus’s Opp’n at 22-23; Sun’s Opp’n at 12; Teva’s Opp’n at 2, 13-14; Actavis’s Opp’n at 13-14; Apotex’s Opp’n at 11-12; Hetero’s Opp’n at 17-18; San-doz’s Opp’n at 4, 18.) Indeed, given these Defendants’ “carve outs,” Defendants cannot, as a matter of law, instruct patients and/or prescribers to use their aripiprazole products for purposes of “adjunctive treatment for major depressive disorder,” a use or indication for. which only Otsuka holds approval. See Caraco Pharm. Labs., 132 S.Ct. at 1677 (noting that, following the FDA’s acceptance of the carve-out label, the generic company may “place its drug on the market, (assuming the [applicant] meets other requirements), but only for a subset of approved uses — i.e., those not covered by the brand’s patents ”) (emphasis added); see also Bayer Schering Pharma AG v. Lupin, Ltd., 676 F.3d 1316, 1322-23 (Fed.Cir.2012) (generally noting that the applicable FDA regulations prohibit generic pharmaceutical companies from implying or suggesting that the generic product has indications .or uses other than those approved by the FDA).

The fact that all of these Defendants actively and voluntarily removed any reference to the allegedly infringing indication, in turn, belies any suggestion that these Defendants acted with the specific intention to encourage infringement. Indeed, this affirmative action would seem to negate any reasonable inference of an active intent to induce infringement. See Acorda Therapeutics Inc. v. Apotex Inc., No. 07-4937, 2011 WL 4074116, at *16 (D.N.J. Sept. 6, 2011), aff’d, 476 Fed.Appx. 746 (Fed.Cir.2012). For that reason, Ot-suka has not demonstrated a likelihood of success on its claim that these Defendants induce infringement of Claim 1 of the '350 patent. See AstraZeneca Pharmaceuti cals LP v. Apotex Corp., 669 F.3d 1370, 1377-78 (Fed.Cir.2012) (“[a] patented method of using a drug can only be infringed under § 271(e)(2) by filing an ANDA that seeks approval to market the drug for that use.”); Warner-Lambert Co., 316 F.3d at 1364-65 (“[T]he request to make and sell a drug labeled with a permissible (non-infringing) use cannot reasonably be interpreted as an act of infringement (induced or otherwise) with respect to a patent on an unapproved use” (emphasis added)).

b. Defendants’ Proposed Labels Do Not Reflect Actual Instruction in Furtherance of Inducing Infringement

In addition, the Court also finds significant deficiencies in Otsuka’s positions concerning the substance of Defendants’ actual labels. Critically, Otsuka does not claim that any individual Defendant instructs and/or encourages the infringing use of its aripiprazole product in either of the key sections of the package inserts: “INDICATIONS AND USAGE” or “DOSAGE AND ADMINISTRATION.” See Bayer Sobering Pharma AG, 676 F.3d at 1321 (discussing the substantive importance of the “Indications and Usage” portion of a product label). Nor does Otsuka dispute that none of the Defendants’ labels even refer to citalopram, much less the coadministration of aripiprazole with eital-opram.

Rather, Otsuka’s position on induced infringement hinges upon the fact that the black box warnings and related sections of Defendants’ labels purportedly imply that the adjunctive use of aripiprazole with any antidepressant results in reduced rates of suieidality in patients aged 65 and older; identify escitalopram and/or “substrates of CYP2C19” as drugs without any clinically important interactions with aripiprazole; and otherwise discuss and/or reference the use of antidepressants, generally, in conjunction with aripiprazole.

Otsuka specifically points to the following emphasized portions of Defendants’ proposed package inserts which the Court has grouped for convenience into representative examples of the relevant sections of Defendants’ labels:

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT DRUGS

_[redacted], and [redacted]_ _!redacted1_

Anyone considering the use of adjunctive aripiprazole or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suieidality with antidepressants com pared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant theraphy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriben Aripiprazole is not approved for use in pe-deatric patients unth depression.

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term, studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressants use in patients over ager 24; there was a reduction in risk with antidepressant use in patients aged 65 and older [see Warnings and Precautions (5.2) ].

WARNINGS AND PRECAUTIONS

Clinical Worsening of Depression and Suicide Risk/Suicidal Thoughts and Behaviors in _Children, Adolescents, and Young Adults_

_._[redacted!_

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases._

[redacted![redacted!

Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

It should be noted that aripiprazole is not approved for use in treating depression in the pediatric population.

Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder, such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

_Metabolic Changes Weight Gain_

_[redacted] _

In the trials adding aripiprazole to antidepressants, patients first received 8 weeks of antidepressant treatment followed by 6 weeks of adjunctive aripiprazole or placebo in addition to their ongoing antidepressant treatment. The mean change in body weight in patients receiving adjunctive aripiprazole was + 1.7 kg (N=Sf7) compared to + O.f kg (N=SS0) in patients receiving adjunctive placebo.

_ADVERSE REACTIONS 6.1 Overall Adverse Reactions Profile_

_íredactedl_

The conditions and duration of treatment with aripiprazole (monotherapy and adjunctive therapy with antidepressants or mood stabilizers) included (in overlapping categories) double-blind, comparative and noncomparative open-label studies, inpatient and outpatient studies, fixed- and flexible-dose studies, and short- and longer-term exposure.

7.2 Drugs Having No Clinically Important Interactions with Aripiprazole

[redacted] . [redacted] [redacted]

Escitalopram

Coadministration of 10mg/day oral does of aripiprazole for If days to healthy s