Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 1 of 26 PageID #: 831
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`AMARIN PHARMA, INC., AMARIN
`PHARMACEUTICALS IRELAND
`LIMITED, MOCHIDA
`PHARMACEUTICAL CO., LTD.,
`
`Plaintiffs,
`
`v.
`
`HIKMA PHARMACEUTICALS USA
`INC., HIKMA PHARMACEUTICALS
`PLC,
`
`Defendants.
`
`C.A. No. 20-1630-RGA
`
`PLAINTIFFS’ RESPONSE IN OPPOSITION TO
`DEFENDANTS’ MOTION TO DISMISS
`
`Dated: February 10, 2021
`
`Jeremy D. Anderson (No. 4515)
`FISH & RICHARDSON P.C.
`222 Delaware Avenue, 17th Floor
`Wilmington, DE 19899
`Tel: (302) 652-5070
`janderson@fr.com
`
`Elizabeth M. Flanagan (No. 5891)
`Michael Kane
`Deanna J. Reichel
`60 South Sixth Street, Suite 3200
`Minneapolis, MN 55402
`(612) 335-5070
`eflanagan@fr.com; kane@fr.com;
`reichel@fr.com
`
`Jonathan E. Singer
`12860 El Camino Real, Suite 400
`San Diego, CA 92130
`(858) 678-5070
`singer@fr.com
`
`Attorneys for Plaintiffs
`Amarin Pharma, Inc.; Amarin
`Pharmaceuticals Ireland Limited,
`Mochida Pharmaceutical Co., Ltd.
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1021, p. 1 of 26
`
`

`

`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 2 of 26 PageID #: 832
`
`TABLE OF CONTENTS
`
`Page
`
`I.
`
`II.
`
`NATURE AND STAGE OF THE PROCEEDINGS ............................................. 1
`
`SUMMARY OF THE ARGUMENT ..................................................................... 1
`
`III.
`
`STATEMENT OF THE FACTS ............................................................................ 3
`
`A.
`
`B.
`
`C.
`
`Amarin Surprisingly Demonstrates VASCEPA® Reduces
`Cardiovascular Risk and Obtains Patents for that Use ............................... 3
`
`Upon Approval of the CV Indication, FDA Allowed Amarin to
`Remove the CV Limitation of Use from the VASCEPA® Label .............. 5
`
`Hikma Launches a Generic Copy of VASCEPA® and Promotes
`It for the Patented Uses ............................................................................... 6
`
`1.
`
`2.
`
`3.
`
`Hikma’s Label Promotes and Encourages Use of The Patented
`Methods............................................................................................6
`
`Hikma’s Marketing and Promotional Statements Promote and
`Encourage Use of the Patented Methods .........................................8
`
`Hikma Launched Its Generic with the Intention It Be Used To
`Infringe .............................................................................................9
`
`IV.
`
`LEGAL STANDARD ........................................................................................... 11
`
`V.
`
`ARGUMENT ........................................................................................................ 12
`
`A.
`
`Hikma’s Motion Should Be Denied under Controlling Precedent ........... 12
`
`1.
`
`2.
`
`Amarin Plausibly Alleges that Hikma’s Label Instructs
`Others to Infringe the Patented Methods .......................................13
`
`Amarin Plausibly Alleges that Hikma’s Additional Actions,
`Including Its Marketing Materials, Further
`Support Inducement .......................................................................15
`
`B.
`
`Hikma’s Bases for Dismissal Are Unavailing .......................................... 17
`
`VI.
`
`CONCLUSION ..................................................................................................... 20
`
`i
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1021, p. 2 of 26
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`

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`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 3 of 26 PageID #: 833
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`Cases
`
`Amarin Pharma Inc. v. Hikma Pharms. USA Inc.,
`449 F. Supp. 3d 967 (D. Nev. 2020) ............................................................................14
`
`Arthrocare Corp. v. Smith & Nephew, Inc.,
`406 F.3d 1365 (Fed. Cir. 2005)....................................................................................16
`
`Ashcroft v. Iqbal,
`556 U.S. 662 (2009) .....................................................................................................12
`
`AstraZeneca LP v. Apotex, Inc.,
`633 F.3d 1042 (Fed. Cir. 2010)....................................................................2, 12, 13, 14
`
`AstraZeneca LP v. Apotex, Inc.,
`669 F.3d 1370 (Fed. Cir. 2012)....................................................................................17
`
`Bayer Schering Pharma AG v. Lupin, Ltd.,
`676 F.3d 1316 (Fed. Cir. 2012)....................................................................................17
`
`Bell Atlantic Corp. v. Twombly,
`550 U.S. 544 (2007) ...............................................................................................11, 12
`
`In re Burlington Coat Factory Sec. Litig.,
`114 F.3d 1410 (3d Cir. 1997).......................................................................................12
`
`DSU Med. Corp. v. JMS Co.,
`471 F.3d 1293 (Fed. Cir. 2006)..............................................................................12, 16
`
`Enzo Life Sciences, Inc. v. Digene Corp.,
`295 F. Supp. 2d 424 (D. Del. 2003) .............................................................................11
`
`Ericsson, Inc. v. D-Link Systems, Inc.,
`773 F.3d 1201 (Fed. Cir. 2014)....................................................................................16
`
`Fairchild Semiconductor Corp. v. Power Integrations, Inc.,
`935 F. Supp. 2d 772 (D. Del. 2013) .............................................................................12
`
`GlaxoSmithKline LLC v. Teva Pharm. USA, Inc.,
`976 F.3d 1347 (Fed. Cir. 2020)....................................................................................20
`
`Global-Tech Appliances, Inc. v. SEB S.A.,
`563 U.S. 754 (2011) .....................................................................................................19
`
`
`
`ii
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1021, p. 3 of 26
`
`

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`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 4 of 26 PageID #: 834
`
`TABLE OF AUTHORITIES (cont’d)
`
`Grunenthal GMBH v. Alkem Labs. Ltd.,
`919 F.3d 1333 (Fed. Cir. 2019)..............................................................................18, 19
`
`Page(s)
`
`HZNP Medicines LLC v. Actavis Labs.,
`940 F.3d 680 (Fed. Cir. 2019)................................................................................18, 19
`
`Johns Hopkins Univ. v. Alcon Labs. Inc.,
`No. CV 15-525, 2018 WL 4178159 (D. Del. Aug. 30, 2018) .......................................9
`
`Mentor H/S, Inc. v. Med. Device All., Inc.,
`244 F.3d 1365 (Fed. Cir. 2001)....................................................................................16
`
`Metro-Goldwyn-Mayer Studios Inc. v. Grokster, Ltd.,
`545 U.S. 913 (2005) .......................................................................................2, 3, 12, 15
`
`Novartis Pharm. Corp. v. Actavis, Inc.,
`No. 12–366–RGA–CJB, 2012 WL 6212619 (D. Del. Dec. 5, 2012) ..........................17
`
`Power Integrations, Inc. v. Fairchild Semiconductor International, Inc.,
`843 F.3d 1315 (Fed. Cir. 2016)....................................................................................16
`
`Sanofi v. Watson Labs. Inc.,
`875 F.3d 636 (Fed. Cir. 2017)................................................................................14, 15
`
`Takeda Pharmaceuticals U.S.A., Inc. v. West-Ward Pharmaceuticals
`Corp.,
`188 F. Supp. 3d 367 (D. Del. 2016) .......................................................................17, 18
`
`Takeda Pharmaceuticals U.S.A., Inc. v. West-Ward Pharmaceuticals
`Corp.,
`785 F.3d 625 (Fed. Cir. 2015)................................................................................17, 18
`
`Toshiba Corp. v. Imation Corp.,
`681 F.3d 1358 (Fed. Cir. 2012)....................................................................................16
`
`Statutes
`
`21 U.S.C. § 355(j)(2)(A)(viii) ..............................................................................................6
`
`
`
`
`
`
`
`iii
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1021, p. 4 of 26
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`

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`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 5 of 26 PageID #: 835
`
`TABLE OF AUTHORITIES (cont’d)
`
`Other Authorities
`
`Federal Rule of Civil Procedure 12 ...................................................................................17
`
`Federal Rule of Evidence 407 ..............................................................................................9
`
`Page(s)
`
`
`
`
`
`iv
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1021, p. 5 of 26
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`

`

`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 6 of 26 PageID #: 836
`
`
`
`I.
`
`NATURE AND STAGE OF THE PROCEEDINGS
`
`On November 30, 2020, Amarin Pharma, Inc., Amarin Pharmaceuticals Ireland Limited,
`
`and Mochida Pharmaceutical Co., Ltd. (collectively, “Amarin”) filed suit against Hikma
`
`Pharmaceuticals USA Inc. and Hikma Pharmaceuticals PLC (collectively, “Hikma”) alleging
`
`infringement of U.S. Patent Nos. 9,700,537 (“the ’537 patent”), 8,642,077 (“the ’077 patent”), and
`
`10,568,861 (“the ’861 patent”) (collectively, the “Asserted Patents”). (D.I. 1.) On January 25,
`
`2021, Amarin filed an amended complaint adding an additional defendant. (D.I. 17.) Before the
`
`Court is Hikma’s motion to dismiss Amarin’s claims for induced infringement. (See D.I. 19-20.)
`
`II.
`
`SUMMARY OF THE ARGUMENT
`
`As alleged in Amarin’s complaint, Hikma’s generic EPA product is being marketed by
`
`Hikma in a blatant “switcheroo.” Having secured approval for an indication—severe
`
`hypertriglyceridemia—that amounts to less than 10% of the sales of Amarin’s VASCEPA®,
`
`Hikma’s intent and conduct are aimed principally at capturing the other 90% of VASCEPA®
`
`sales—those for the reduction of cardiovascular (CV) risk. However, because those uses are
`
`patented, Hikma is inducing patent infringement, plain and simple.
`
`Under governing standards, Amarin’s complaint alleges more than sufficient facts to
`
`plausibly state a claim that Hikma has induced infringement. It walks through Hikma’s inducing
`
`conduct in detail, including how Hikma has promoted the patented uses of reducing CV risk and
`
`triglyceride levels (TGs) in its not-skinny-enough drug label, and touted its product as equivalent
`
`to Amarin’s branded drug VASCEPA® through the contents of its press releases and website. The
`
`complaint also presents facts exposing Hikma’s knowledge and intent that its generic be used just
`
`like VASCEPA®, including for the patented uses.
`
`These facts, taken as true, demonstrate induced infringement of the Asserted Patents. As
`
`to Hikma’s label, that label instructs users to administer Hikma’s generic EPA product to patients
`
`
`
`1
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1021, p. 6 of 26
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`

`

`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 7 of 26 PageID #: 837
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`
`
`with triglycerides greater than 150 mg/dL, including those who are taking statins—and thus have
`
`mixed dyslipidemia. (D.I. 17, ¶¶ 103-31, 134.) These are the same groups of patients covered by
`
`the Asserted Patents. The label also omits a prior limitation of use, which was on Hikma’s original
`
`ANDA label, that the product should not be used to reduce CV risk because such effects were not
`
`determined. (Id. ¶¶ 107-08.) As the complaint explains, Hikma’s removal of this use limitation
`
`communicates to the market that Hikma’s product has been proven to reduce CV risk, even though
`
`Hikma has not sought approval for that indication. (Id. ¶¶ 107-08.)
`
`On top of this, Hikma’s marketplace behavior encourages direct infringers to use Hikma’s
`
`generic product in an infringing manner. As the complaint alleges, Hikma has advertised its
`
`product as being useful for all patients with hypertriglyceridemia, and not merely those with
`
`triglycerides greater than 500 mg/dL. (Id. ¶¶ 111, 125-26.) These are the populations covered by
`
`the Asserted Patents. And Hikma’s press releases, far from discouraging infringement, as Hikma
`
`asserts, do the opposite, by both: 1) touting Hikma’s generic product as the “generic equivalent”
`
`of VASCEPA®, which of course is approved to reduce CV risk, while Hikma’s generic product
`
`is not; and 2) bragging about VASCEPA®’s sales across the board, as opposed to the less than
`
`10% of sales associated with the severe hypertriglyceridemia indication for which Hikma obtained
`
`approval. (Id. ¶¶ 12, 111-24.)
`
` The totality of the facts alleged in the complaint thus more than adequately plead an
`
`inducement claim. Federal Circuit precedent makes clear that generic manufacturers that fail to
`
`remove patented uses from their drug labels and otherwise encourage infringement, as Hikma is
`
`doing here, do not get a free pass simply because they relied on a section viii statement.
`
`AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1056 (Fed. Cir. 2010). And, the alleged inducing
`
`conduct here is just what the Supreme Court said in Metro-Goldwyn-Mayer Studios Inc. v.
`
`2
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1021, p. 7 of 26
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`

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`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 8 of 26 PageID #: 838
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`
`
`Grokster, Ltd. constitutes inducement: “[e]vidence of active steps . . . taken to encourage direct
`
`infringement, such as advertising an infringing use or instructing how to engage in an infringing
`
`use, show an affirmative intent that the product be used to infringe.” 545 U.S. 913, 936 (2005).
`
`Hikma’s proffered reasons for dismissal fall short. Hikma harps on the fact that its drug
`
`has not been approved for a particular indication related to CV risk reduction. But, as Hikma
`
`concedes, what matters is whether Hikma has promoted the patented use, whether as part of any
`
`indication its drug has received or not. Hikma’s remaining arguments do not address the relevant
`
`issue of the plausibility of Amarin’s inducement claim, but instead are factual disputes that relate
`
`to the ultimate merits of Amarin’s claims or “straw man” arguments that Amarin is not making.
`
`When Hikma’s conduct is viewed in its entirety, as alleged in the well-pleaded complaint,
`
`Amarin has adequately alleged inducement. The Court should deny Hikma’s motion and require
`
`Hikma to answer for its transparent strategy to capture the ground-breaking, patented uses of
`
`VASCEPA® for reduction of cardiac risk, which constitute over 90% of the potential use of
`
`Hikma’s generic drug.
`
`III.
`
`STATEMENT OF THE FACTS
`
`A.
`
`Amarin Surprisingly Demonstrates VASCEPA® Reduces Cardiovascular
`Risk and Obtains Patents for that Use
`
`CV events such as heart attack and stroke are the leading cause of adult deaths in the United
`
`States.1 (See D.I. 17, ¶ 26; Ex. I at 3.) The presence of excessive lipids, or fats, in the blood,
`
`especially in the form of LDL-C (commonly referred to as “bad” cholesterol), increases the risk of
`
`these CV events. (See D.I. 17, ¶ 30.) High cholesterol levels can be controlled by treatment with
`
`drugs called “statins.” (Id. ¶ 31.) But statins do not completely address the problem of high
`
`triglyceride levels, which themselves are associated with increased CV risk. (See id.)
`
`
`1 All exhibit references refer to exhibits to Amarin’s amended complaint (D.I. 17).
`
`3
`
`Hikma Pharmaceuticals
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`IPR2022-00215
`
`Ex. 1021, p. 8 of 26
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`

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`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 9 of 26 PageID #: 839
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`
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`The FDA approved VASCEPA® in 2012 for treating severe hypertriglyceridemia, a
`
`condition where patients have triglyceride levels greater than 500 mg/dL. (See id. ¶ 30; Ex. E at
`
`2.)
`
` Before VASCEPA®,
`
`the other available EPA-containing
`
`treatment for severe
`
`hypertriglyceridemia, LOVAZA®, had the undesirable effect of increasing LDL-C. (Ex. S § 5.1.)
`
`VASCEPA® is the only drug of any type approved for treating severe hypertriglyceridemia that
`
`does not raise LDL-C. (D.I. 17 ¶ 30.) VASCEPA® is a 4g/day dose of purified EPA
`
`(eicosapentaenoic acid).
`
`Thereafter, Amarin continued investigating VASCEPA® for its primary goal, use in CV
`
`risk reduction. (Id. ¶ 31.) Amarin launched an ambitious clinical trial called REDUCE-IT to prove
`
`VASCEPA®’s beneficial effects on CV risk when given with statins to patients with mixed
`
`dyslipidemia (i.e., abnormal lipid levels). (Id. ¶ 33.) The REDUCE-IT trial met with significant
`
`skepticism because other earlier trials of drug-statin combinations did not show an improvement
`
`in reduction of CV risk beyond that achieved with statins alone. (See id. ¶ 32; Ex. BB at 11.)
`
`The REDUCE-IT trial concluded in 2018 and “surpris[ingly]” showed EPA to reduce CV
`
`events significantly among patients already being treated with a statin. (See, e.g., Ex. Z at 2; see
`
`also D.I. 17, ¶ 34; Ex. V at 3.) These results were hailed as a “game changer” because they showed
`
`“for the first time that triglyceride reduction with . . . [EPA] . . . can make a significant difference”
`
`in CV risk—a 25% reduction in major cardiovascular events. (D.I. 17, ¶¶ 34-35; Ex. Y at 2.) In
`
`December 2019, FDA approved VASCEPA® to reduce the risk of CV events in statin-treated
`
`patients with at least high TG levels (≥ 150 mg/dL). (D.I. 17, ¶ 62; Ex. D at 2.)
`
`VASCEPA®’s remarkable ability to reduce certain CV risk in statin-treated patients with
`
`high TG levels is reflected in the claimed treatment methods of the asserted ’537 and ’861 Patents.
`
`Both of these patents are directed to reducing CV risk, and are listed in the Orange Book as
`
`4
`
`Hikma Pharmaceuticals
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`IPR2022-00215
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`Ex. 1021, p. 9 of 26
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`

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`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 10 of 26 PageID #: 840
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`
`
`covering VASCEPA®. Relatedly, the asserted ’077 patent, also listed in the Orange Book, claims
`
`methods of reducing TG levels in patients with mixed dyslipidemia by administering EPA. (See,
`
`e.g., ’077 patent at cls. 1, 8.) (See D.I. 17, ¶¶ 71-79.)
`
`B.
`
`Upon Approval of the CV Indication, FDA Allowed Amarin to Remove the CV
`Limitation of Use from the VASCEPA® Label
`
`From 2012 through December 12, 2019, VASCEPA®’s label included only the severe
`
`hypertriglyceridemia indication, reciting its use as “an adjunct to diet to reduce triglyceride levels
`
`in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia” (hereinafter, the “SH
`
`Indication”). (D.I. 17, ¶¶ 56, 59.) Importantly, this label also contained a limitation of use with
`
`regard to CV risk reduction (hereinafter, the “CV Limitation of Use”):
`
`The effect of VASCEPA® on cardiovascular mortality and morbidity in patients
`with severe hypertriglyceridemia has not been determined.
`
` (Id. ¶ 60 (emphasis added).)
`
`Notably, this same CV Limitation of Use appears in the FDA-approved label for the other
`
`EPA-containing TG-lowering drug, LOVAZA®, whose benefits on CV risk have never been
`
`shown. (Id. ¶¶ 61, 64.) Thus, as alleged in the complaint, where an EPA-containing, TG-lowering
`
`product has not been shown to reduce CV risk, the label limits the product’s use. (See id. ¶¶ 61-
`
`63.) Indeed, this limitation of use extends to all products in the TG-lowering therapeutic category.
`
`(Id.) It is thus a category-wide limitation, the presence or absence of which, is profound.
`
`With the success of the REDUCE-IT trial, FDA permitted Amarin to remove the CV
`
`Limitation of Use from the VASCEPA® label because VASCEPA®’s effect on CV mortality and
`
`morbidity in patients with severe hypertriglyceridemia had now been determined—it reduced the
`
`risk. In addition, VASCEPA®’s label added a further indication proven by the REDUCE-IT trial.
`
`This additional indication provides for use of the drug “as an adjunct to maximally tolerated statin
`
`therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable
`
`5
`
`Hikma Pharmaceuticals
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`IPR2022-00215
`
`Ex. 1021, p. 10 of 26
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`

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`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 11 of 26 PageID #: 841
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`
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`angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150
`
`mg/dL) and established cardiovascular disease or diabetes mellitus and 2 or more additional risk
`
`factors for cardiovascular disease” (hereinafter, the “CV Indication”). (Id. ¶¶ 56, 62-65.)
`
`C.
`
`Hikma Launches a Generic Copy of VASCEPA® and Promotes It for the
`Patented Uses
`
`On November 5, 2020, Hikma launched a generic copy of VASCEPA® under ANDA No.
`
`209457 containing so-called “section viii statements” for the Asserted Patents. (Id. ¶¶ 11, 13, 105;
`
`D.I. 20 at 7.) By including these statements, Hikma represented that it would not market its generic
`
`product for uses covered by those patents, namely, to reduce CV risk and lower TGs in specific
`
`patient populations. See 21 U.S.C. § 355(j)(2)(A)(viii). But as the complaint alleges, and as
`
`detailed again below, Hikma broke that promise. Instead, Hikma always intended its product be
`
`used to reduce CV risk according to the claimed methods like VASCEPA®, and engaged in a
`
`course of promotional conduct designed to achieve just that. (See, e.g., D.I. 17, ¶¶ 108-09.)
`
`1.
`
`Hikma’s Label Promotes and Encourages Use of The Patented
`Methods
`
`When Hikma submitted its ANDA in 2016,2 the proposed labeling for its generic product
`
`included the SH Indication and the CV Limitation of Use, thereby mirroring the VASCEPA® label
`
`at that time. (Id. ¶ 108.) In 2019, after Amarin updated the VASCEPA® label to remove the CV
`
`Limitation of use and to add the CV Indication, Hikma had to make a choice: copy the CV
`
`Indication onto its own label as well and challenge the Asserted Patents, or attempt to avoid those
`
`patents by implementing a section viii strategy. Hikma chose the latter path. But while Hikma
`
`
`2 Hikma makes much of the first litigation between the parties as evidencing a purported attempt
`by Amarin to “stifle” competition. (See D.I. 20 at 5.) Nonsense. That litigation started in 2017,
`and was conducted under the Hatch-Waxman Act before Hikma ever received approval for its
`product. Obviously, Amarin could not “stifle” competition when Hikma had no approved product
`to sell. We note that the asserted patents in that case involved only the SH Indication. Amarin’s
`ground-breaking CV risk reduction study was ongoing during that litigation, and Amarin did not
`receive FDA approval for that indication until shortly before the January 2020 trial.
`
`6
`
`Hikma Pharmaceuticals
`
`IPR2022-00215
`
`Ex. 1021, p. 11 of 26
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`

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`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 12 of 26 PageID #: 842
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`
`
`omitted the CV Indication from its label, it did not retain the CV Limitation of Use, as the original
`
`VASCEPA® label had. Instead, Hikma removed the CV Limitation of Use from its label. (Id.)
`
`What results is a label that instructs and promotes the patented uses, which Hikma well knows.
`
`The ’537 Patent. Claim 1 of the ’537 patent requires treating hypercholesterolemia
`
`patients with TG levels ≥ 150 mg/dL and HDL-C less than 40 mg/mL, and who are on a statin, in
`
`order to reduce CV risk. (Id. ¶ 45.) Section 14.2 of Hikma’s label describes and encourages
`
`treating patients falling squarely within these limitations, specifically patients with (1) median total
`
`cholesterol of 254 mg/dL, which is hypercholesterolemia; (2) TGs of 680 mg/dL, which is ≥ 150
`
`mg/DL; (3) HDL-C of 27 mg/dL, which is less than 40 mg/dL; and (4) with 25% of patients on
`
`“concomitant stain therapy.” (Id. ¶ 130; Ex. K § 14.2, tbl. 2; id. § 12.3.) The complaint also shows
`
`how Hikma’s label promotes treating patients at risk of having a first CV event (i.e., patients who
`
`have “diabetes with a risk factor for heart (cardiovascular) disease”), thus encouraging treatment
`
`of those patients. (D.I. 17, ¶ 130 (citing Ex. K at Patient Info. Leaflet, § 17).)
`
`As also alleged, Hikma’s choice to omit the CV Limitation of Use from its label cements
`
`this inducement by communicating to the market that Hikma’s generic product has been shown to
`
`reduce CV risk. (Id. ¶ 133.)
`
`The ’861 Patent. Claims 1 and 2 of the ’861 patent cover treating patients with established
`
`CV disease, and claim 2 further specifies treating patients with particular TG levels (about 135-
`
`500 mg/dL) and LDL-C levels (about 40-100 mg/dL). (Id. ¶ 53.) The complaint shows how
`
`Hikma’s label teaches that patients “who have heart (cardiovascular) disease” have taken and can
`
`take the drug, thereby encouraging treatment of such patients. (Id. ¶ 131 (citing Ex. K at Patient
`
`Info. Leaflet, § 17).) Section 14.2 of the label again shows treatment of patients with the claimed
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`TG and LDL-C levels, thereby encouraging treatment of such patients. (Id. (citing Ex. K § 14.2
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`7
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`Hikma Pharmaceuticals
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`IPR2022-00215
`
`Ex. 1021, p. 12 of 26
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`

`

`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 13 of 26 PageID #: 843
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`
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`(“Patients whose baseline TG levels were between 500 and 2,000 mg/dL were enrolled in this
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`study.”); id. § 14.2, tbl. 2 (for treatment group, “baseline” “LDL-C (mg/dL)” is 91)).) And as
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`just explained, Hikma’s label promotes treating these patients with this dosing regimen to reduce
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`CV risk, including due to the conspicuous absence of the CV Limitation of Use.
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`The ’077 Patent. Claims 1 and 8 of the ’077 patent require treating mixed dyslipidemia
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`patients who are on statins with about 4g daily of a highly pure EPA to reduce fasting TG levels
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`and hs-CRP. (Id. ¶ 49.) Section 14.2 of the label promotes and encourages treating patients with
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`abnormal lipid levels, who thus have mixed dyslipidemia, and who are “on concomitant statin
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`therapy.” (Id. ¶ 134 (enrolling patients with TG levels between 500 and 2,000 mg/dL (citing Ex.
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`K § 14.2) with a baseline median LDL-C of 91 mg/dL and HDL-C of 27 mg/dL (citing id. at tbl.
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`2), with 25% of studied patients receiving “concomitant statin therapy,” and teaching
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`administration of EPA with atorvastatin (citing id. §§ 12.3, 14.2).) Further, the complaint alleges
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`that taking EPA according to Hikma’s label inherently results in a reduction of hs-CRP in mixed
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`dyslipidemia patients, which is a possible explanation for the reduction in CV risk in these patients.
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`(See id. ¶¶ 34, 134 (citing Ex. U).)
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`2.
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`Hikma’s Marketing and Promotional Statements Promote and
`Encourage Use of the Patented Methods
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`In addition to its label, Hikma’s public statements also encourage the use of Hikma’s
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`generic EPA product just like VASCEPA®, including to reduce CV risk and TG levels. Hikma
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`issued a press release on March 31, 2020, promoting its EPA as a “generic version of Amarin
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`Corporation’s Vascepa® 1 gm (icosapent ethyl) capsules.” (Id. ¶ 111; Ex. L.) Hikma’s March
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`2020 Press Release also cited VASCEPA® sales figures knowing that these totals included the
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`CV Indication and knowing that the CV Indication comprises the “vast majority” of VASCEPA®
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`prescriptions. (Id. ¶¶ 112-13.) A later press release dated September 2020, includes similar
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`8
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`Hikma Pharmaceuticals
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`IPR2022-00215
`
`Ex. 1021, p. 13 of 26
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`

`

`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 14 of 26 PageID #: 844
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`
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`statements. (See id. ¶¶ 118-20.) Hikma maintained both press releases on its website at the time
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`of and after launching its product in early November 2020. (Id. ¶¶ 117, 124.) The complaint
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`alleges that Hikma’s press releases communicatethat Hikma’s “generic version” of VASCEPA®
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`should be used just like VASCEPA®, including for the infringing uses. (Id. ¶¶ 114-16, 121-23.)
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`The complaint also alleges Hikma’s online product catalogue encourages infringement. At
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`launch, Hikma’s website promoted its generic EPA drug as “AB” rated by FDA in the “Therapeutic
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`Category” of “Hypertriglyceridemia.” (Id. ¶ 125.) This “therapeutic category” does not match
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`the “Severe Hypertriglyceridemia” indication on Hikma’s label, which recites TGs ≥ 500 mg/dL.3
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`(Id. ¶ 126.) Rather, “Hypertriglyceridemia” encompasses much lower TG levels, including the ≥
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`150 mg/dL TGs recited in the CV Indication. (Id.) The complaint alleges that Hikma’s website
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`thus also promotes using its generic drug just like VASCEPA®. (Id. ¶¶ 127-28.)
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`3.
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`Hikma Launched Its Generic with the Intention It Be Used To Infringe
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`In addition to this promotional activity, the complaint alleges Hikma intended for its
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`generic EPA product to completely replace VASCEPA® for all uses. (See, e.g., id. ¶¶ 108-29.)
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`Hikma marketed its product in press releases with messaging based on market assumptions for
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`total sales of VASCEPA® that included the patent-protected uses. (See, e.g., id. ¶¶ 113, 120.)
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`And when Hikma launched its generic EPA, it knew the main reason doctors prescribe
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`VASCEPA® is to reduce CV risk, not the SH Indication. (See, e.g., id. ¶ 110.) Indeed, in early
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`2020, Hikma repeatedly argued through its counsel in federal court that the “vast majority” of
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`3 Hikma asserts that removing the press releases and the “AB” rating reference from its website
`are inadmissible under Federal Rule of Evidence 407 as subsequent remedial measures. (D.I. 20
`at 10, n. 1.) Rule 407 in inapplicable because Hikma has taken no remedial measure and continues
`to induce today. See, e.g., Johns Hopkins Univ. v. Alcon Labs. Inc., No. CV 15-525, 2018 WL
`4178159, at *19 (D. Del. Aug. 30, 2018) (finding “Rule 407 does not support the exclusion of . . .
`evidence” where defendant continued to infringe). If anything, Hikma’s removal of the AB rating
`from its website underscores Hikma’s knowledge that it has promoted infringement.
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`9
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`Hikma Pharmaceuticals
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`IPR2022-00215
`
`Ex. 1021, p. 14 of 26
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`

`

`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 15 of 26 PageID #: 845
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`
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`prescriptions for VASCEPA® are for uses other than for the SH Indication. (Id.; see also Ex. W
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`at 3; Ex. X at 3; Ex. AA at 2; D.I. 17, ¶ 132.) And the current market data shows that, as Hikma
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`understands, the proportion of VASCEPA® prescriptions written for the SH Indication is less than
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`10%. (D.I. 17, ¶ 152; Ex. GG.)
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`Hikma also intended for the market to believe its generic could replace VASCEPA® for
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`all uses, including reducing CV risk. (D.I. 17, ¶ 108.) Before launch Hikma intentionally amended
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`its label to remove the CV Limitation of Use and touted its product as AB-rated in a category that
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`encompasses the infringing uses based on common policies that encourage or require the
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`substitution of AB-rated generic drugs for branded drugs regardless of indication. (See id. ¶¶ 108,
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`129.) Consistent with its intention that VASCEPA® be completely swapped for Hikma’s product,
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`Hikma’s label admits that “[m]edicines are sometimes prescribed for purposes other than those
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`listed in a Patient Information leaflet.” (Ex. K § 17; see also D.I. 17, ¶ 132.)
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`Indeed, Hikma has admitted that some patients treated for the approved indication on its
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`label will be infringing. At the trial on the SH Indication patents in January 2020, Hikma presented
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`a demonstrative exhibit showing that at least a portion of the patient population prescribed
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`VASCEPA® according to the SH Indication overlaps with the CV Indication, and such patients
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`would be treated to reduce cardiovascular risk:
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`10
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`Hikma Pharmaceuticals
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`IPR2022-00215
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`Ex. 1021, p. 15 of 26
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`

`

`Case 1:20-cv-01630-RGA-JLH Document 22 Filed 02/10/21 Page 16 of 26 PageID #: 846
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`
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`(See, e.g., D.I. 17, ¶¶ 110, 130-33; Ex. Q.)
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`
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`While these circles were not drawn to scale by Hikma—the yellow circle should be much
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`smaller than the blue circle—the yellow circle titled “Asserted Claims” refers to the SH Indication,
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`and the blue circle titled “Vascepa Prescriptions” refers to the CV Indication that Hikma admitted
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`is “separately patented.” (Ex. Q (emphasis added).) Because FDA did not include an upper limit
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`on the TG range for the CV Indication (D.I. 17, ¶ 65), the patient populations of CV and SH
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`Indications necessarily overlap. This overlap means the label instructs infringement of the
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`Asserted Patents. (See, e.g., id. ¶¶ 130-34.)
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`The complaint relies on all of these facts, and more, to allege Hikma knowingly induced
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`infringement and possessed specific intent to encourage infringement.
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`IV.
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`LEGAL STANDARD
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`A complaint need only state “enough factual matter (taken as true) to suggest” the required
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`elements of the claims. Bell Atlantic Corp. v. Twombly, 550 U.S. 544, 556 (2007). A full
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`description of every legal theory underlying the claim