Case 1:20-cv-01630-UNA Document 1 Filed 11/30/20 Page 1 of 37 PageID #: 1
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`Plaintiffs,
`
`
`
`v.
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`AMARIN PHARMA, INC., AMARIN
`PHARMACEUTICALS IRELAND
`LIMITED, MOCHIDA
`PHARMACEUTICAL CO., LTD.,
`
`
`
`
`
`HIKMA PHARMACEUTICALS USA INC.,
`HIKMA PHARMACEUTICALS PLC,
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`
`
`
`
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`Defendants.
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`
`
`
`
`
`
`C.A. No. _________________
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`
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`JURY TRIAL DEMANDED
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`
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`
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`COMPLAINT FOR PATENT INFRINGEMENT AND DEMAND FOR JURY TRIAL
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`Plaintiffs Amarin Pharma, Inc. and Amarin Pharmaceuticals Ireland Limited (“Amarin”)
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`and Mochida Pharmaceutical Co., Ltd. (“Mochida”) (collectively, “Plaintiffs”), by their
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`attorneys, hereby allege as follows:
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`THE NATURE OF THE ACTION
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`This is an action for infringement of U.S. Patent Nos. 9,700,537 (“the ’537 patent”),
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`1.
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`8,642,077 (the “’077 patent”), and 10,568,861 (the “’861 patent”) (collectively, the Asserted
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`Patents”) under the Patent Laws of the United States, 35 U.S.C. § 100 et seq., including § 271(b).
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`In violation of these laws, Defendants are marketing their generic version of Amarin’s ground-
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`breaking VASCEPA® product to reduce the risk of cardiovascular events such as heart attack and
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`stroke (“cardiovascular risk reduction”). VASCEPA® is the first and only innovative omega-3
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`acid-based product approved for cardiovascular risk reduction by the United States Food and Drug
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`Administration.
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`THE PARTIES
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`2. Amarin Pharma, Inc. is a company organized under the laws of Delaware with its
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`principal place of business at 440 Route 22, Suite 330, Bridgewater, NJ 08870.
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`3. Amarin Pharmaceuticals Ireland Limited is a company incorporated under the laws
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`of Ireland with registered offices at 88 Harcourt Street, Dublin 2, Dublin, Ireland.
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`4. Mochida Pharmaceutical Co., Ltd. is a company incorporated under the laws of Japan
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`with its principal place of business at 1-1, Ichigayahonmuracho, Shinjuku-ku, Tokyo 162-0845,
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`Japan.
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`5. On information and belief, Defendant Hikma Pharmaceuticals USA Inc. is a
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`corporation organized and existing under the laws of Delaware with its principal place of business
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`at 246 Industrial Way West, Eatontown, NJ 07724.
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`6. On information and belief, Defendant Hikma Pharmaceuticals PLC is a corporation
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`organized and existing under the laws of the United Kingdom with its principal place of business
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`at 1 New Burlington Place, London W1S 2HR.
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`7. Upon information and belief, Hikma Pharmaceuticals USA Inc. is a wholly-owned
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`subsidiary of Hikma Pharmaceuticals PLC.
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`8. Upon information and belief, Hikma Pharmaceuticals USA Inc. acts at the direction,
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`and for the benefit, of Hikma Pharmaceuticals PLC, and is controlled and/or dominated by Hikma
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`Pharmaceuticals PLC. Hikma Pharmaceuticals USA Inc. and Hikma Pharmaceuticals PLC are
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`hereinafter referred to together as “Defendants” or “Hikma.”
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`9. Upon information and belief, Defendants collaborate with respect to the
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`development, regulatory approval, marketing, sale, and/or distribution of pharmaceutical products.
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`On further information and belief, Defendants are agents of each other and/or operate in concert
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`2
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`as integrated parts of the same business group, and enter into agreements with each other that are
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`nearer than arm’s length.
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`10. Upon information and belief, Hikma Pharmaceuticals USA Inc. is the current owner
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`of ANDA No. 209457 for 1g and 0.5 g icosapent ethyl capsules purportedly bioequivalent to
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`VASCEPA®.
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`11. Upon information and belief, on May 21, 2020, FDA granted final approval for
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`Defendants’ 1g icosapent ethyl capsules under ANDA No. 209457.
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`12. Attached hereto as Exhibit A is a press release issued by Hikma Pharmaceuticals PLC
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`on or about May 22, 2020 announcing that “Hikma Pharmaceuticals USA Inc. has received
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`approval from the US Food and Drug Administration (FDA) for its Icosapent Ethyl Capsules, 1
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`gm, the generic equivalent to Vascepa®.”
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`13. Attached hereto as Exhibit N is a press release issued by Hikma Pharmaceuticals PLC
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`on or about November 5, 2020 announcing the launch of Hikma’s icosapent ethyl capsules. On
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`information and belief, on November 5, 2020, Hikma launched and began offering for sale and/or
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`selling its generic icosapent ethyl capsules in the United States, including this jurisdiction.
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`14. Upon information and belief, Defendants act collaboratively to commercially
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`manufacture, market, distribute, offer for sale, and/or sell Hikma’s icosapent ethyl capsules in the
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`United States, including this jurisdiction.
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`JURISDICTION AND VENUE
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`15. This Court has subject matter jurisdiction over the action under 28 U.S.C. §§ 1331
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`and 1338(a).
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`16. This Court has personal jurisdiction over Hikma Pharmaceuticals USA Inc. because
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`it is incorporated in Delaware and thus is present in and resides in this District, and because Hikma
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`3
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`Pharmaceuticals USA Inc. is doing business in this District and has thus purposefully availed itself
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`to the privileges of conducting business in Delaware.
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`17. Venue is proper in this District over Hikma Pharmaceuticals USA, Inc. under 28
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`U.S.C. § 1400(b).
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`18. This Court has personal jurisdiction over Hikma Pharmaceuticals PLC because, on
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`information and belief, it manufactures, imports, offers for sale, and sells pharmaceutical drugs
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`that are sold in the United States, including in Delaware, and derives substantial income therefrom.
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`19.
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`In the alternative, this Court may exercise personal jurisdiction over Hikma
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`Pharmaceuticals PLC pursuant to Fed. R. Civ. P. 4(k)(2) because (a) Plaintiffs’ claims arise under
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`federal law; (b) Hikma Pharmaceuticals PLC is a foreign company not subject to personal
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`jurisdiction in the courts in any state, and (c) Hikma Pharmaceuticals PLC has sufficient contacts
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`with the United States as a whole, including but not limited to marketing and/or selling generic
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`pharmaceutical products that are distributed and sold throughout the United States, such that this
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`Court’s exercise of jurisdiction over Hikma Pharmaceuticals PLC satisfies due process.
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`20. Venue is proper in this District with respect to Hikma Pharmaceuticals PLC pursuant
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`to 28 U.S.C. § 1391(c)(3) because it is not resident in the United States.
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`FACTUAL BACKGROUND
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`A.
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`VASCEPA®, REDUCE-IT, JELIS and EPA’s Reduction of Cardiovascular
`Risk
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`21. The three types of omega−3 fatty acids involved in human physiology are α-linolenic
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`acid (ALA), found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic
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`acid (DHA), both commonly found in marine (fish) oils.
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`4
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`22. Amarin and Mochida are recognized worldwide as the leading innovation-driven
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`companies committed to the research and development of EPA-based drug products to treat the
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`needs of millions of patients who are at risk of cardiovascular disease
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`23. Mochida developed and markets a prescription pure EPA drug product, Epadel, in
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`Japan.
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`24. Amarin developed and markets VASCEPA®, a prescription drug that contains pure
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`EPA, in the United States.
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`25. Amarin conducted a series of clinical trials to support FDA approval of VASCEPA®.
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`26.
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`In the MARINE trial that led to VASCEPA®’s first approval, VASCEPA® was
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`found to lower triglycerides in patients with severe hypertriglyceridemia (≥500 mg/dL) without
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`raising bad cholesterol, or LDL-C, levels. Upon FDA approval in 2012, VASCEPA® became the
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`first (and still only) approved medication for treating severe hypertriglyceridemia that does not
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`raise LDL-C.
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`27. After that approval to treat severe hypertriglyceridemia, Amarin continued its clinical
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`work towards its primary goal, approval of VASCEPA® for use in cardiovascular risk reduction.
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`Based on an agreed protocol with the FDA, Amarin had conducted a clinical trial known as
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`ANCHOR, in which Amarin examined VASCEPA® as an add-on to statin therapy in patients with
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`persistent high (≥200 mg/dL and <500 mg/dL) triglycerides. As agreed with FDA, Amarin
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`evaluated VASCEPA®’s effect on cardiovascular risk reduction based on triglyceride level
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`lowering as a surrogate, or substitute, for cardiovascular risk reduction while awaiting the results
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`of Amarin’s REDUCE-IT trial.
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`28. While ANCHOR met its clinical endpoints, including the exploratory endpoint of
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`median placebo-adjusted percent change in high-sensitivity C reactive protein (hs-CRP), see Ex.
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`U (Ballantyne), FDA’s view on the use of triglyceride levels as a surrogate for cardiovascular risk
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`changed. Ex. BB. FDA identified several clinical trials where other therapies, including other
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`omega-3 based therapies, lowered triglyceride levels in this patient population but did not show an
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`actual reduction in cardiovascular risk. The trials failing to show a cardiovascular risk reduction
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`included ACCORD-Lipid, AIM-HIGH, and HPS2-THRIVE.
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`29.
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` Accordingly, Amarin proceeded to complete REDUCE-IT, a trial in which the
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`effects of VASCEPA® on cardiovascular risk reduction were evaluated directly. The REDUCE-
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`IT study was completed by Amarin at great cost. In REDUCE-IT, Amarin followed more than
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`8000 patients over a median of five years and evaluated the effectiveness of VASCEPA® as an
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`add-on to statin therapy in reducing major cardiovascular events in patients with persistent elevated
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`triglycerides. See Ex. V (Bhatt).
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`30. The results of REDUCE-IT, first announced in 2018, see Ex. H, were hailed as one
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`of the most important developments in the prevention and treatment of cardiovascular disease since
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`statins. Compared to statins alone on top of other contemporaneous medical therapy, VASCEPA®
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`showed a 25% reduction in major cardiovascular events such as cardiovascular death, myocardial
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`infarction, and stroke. Based on those results, in December 2019, FDA approved VASCEPA®
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`for a second indication as an adjunct to maximally tolerated statin therapy to reduce the risk of
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`myocardial infarction, stroke, coronary revascularization, and unstable angina requiring
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`hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and
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`established cardiovascular disease or diabetes mellitus and 2 or more additional risk factors for
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`cardiovascular disease. Ex. I. Similar to the ANCHOR results, a reduction in hs-CRP was
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`observed in REDUCE-IT which may in part explain the cardiovascular risk benefit. See Ex. V
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`(Bhatt) at 20. This is consistent with the investigators in the ANCHOR trial, who stated that one
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`of the potential explanations for increased cardiovascular risk might be inflammation and
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`VASCEPA® showed a 22% reduction of hs-CRP in the mixed dyslipidemia population studied in
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`ANCHOR. See Ex. U (Ballantyne); see also Exhibit O at col. 18, 1. 11-12.
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`31.
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`In a press release about this additional approval, FDA recognized that “VASCEPA
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`is the first FDA-approved drug to reduce cardiovascular risk among patients with elevated
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`triglyceride levels as an add-on to maximally tolerated statin therapy.” Ex. J. The results of
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`REDUCE-IT were met with widespread enthusiasm and surprise in the field and have been hailed
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`as a “game changer” in medicine. Ex. Y; Ex. Z.
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`32. Amarin’s work in the MARINE, ANCHOR, and REDUCE-IT clinical trials was
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`preceded by other work done by Mochida, in Japan. In the late 1990s and early 2000s, Mochida
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`sponsored a cardiovascular outcomes trial with Epadel in Japan, called JELIS (Japanese EPA Lipid
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`Intervention Study). JELIS was the world’s first large-scale randomized controlled cardiovascular
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`outcomes trial of a prescription pure EPA drug product. The JELIS results reported that pure EPA
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`suppressed coronary artery disease in Japanese hypercholesterolemic patients who routinely
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`consume a large amount of EPA and DHA (another poly unsaturated fatty acid) from fish oil in
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`their diet.
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`33. A further statistical analysis of JELIS was undertaken to assess the effect of EPA on
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`patients with a particular profile of risk factors for coronary artery disease, and reported beneficial
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`effects of the drug in further reducing cardiovascular events in statin-treated, hypercholesterolemic
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`Japanese patients.
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`34. Those effects are published in Saito et al., titled, “Effects of EPA on coronary artery
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`disease in hypercholesterolemic patients with multiple risk factors: Sub-analysis of primary
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`prevention cases from the Japan EPA Lipid Intervention Study (JELIS), 200 Atherosclerosis 135-
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`400 (2008) [hereinafter, the “Saito Article”]. The Saito Article is attached hereto as Exhibit B.
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`35. The Saito Article reports on a statistical analysis of patients studied in the JELIS trial
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`who had no history of coronary artery disease (i.e., the patients had not previously had a
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`cardiovascular event). Ex. B (Saito) at § 2.1. The primary endpoint was major coronary events
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`(MCE): sudden cardiac death, fatal myocardial infarction, nonfatal myocardial infarction, unstable
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`angina pectoris
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`including hospitalization
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`for documented
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`ischemic episodes, and
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`angioplasty/stenting or coronary artery bypass grafting. Ex. B (Saito) at § 2.3.
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`36. The Saito Article reports that the “EPA treatment lowered the risk for MCE for the
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`[studied population] by 53% (HR: 0.47; 95% CI: 0.23-0.98; P = 0.43; Fig. 3).” Ex. B (Saito) at
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`138. By comparison, MCE risk was reduced by 18% in all primary prevention subjects treated in
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`the JELIS clinical study. Ex. B (Saito) at 139.
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`B.
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`The Asserted Patents
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`37. On July 11, 2017, the United States Patent and Trademark Office (“USPTO”) duly
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`and legally issued the ’537 patent, titled “Composition for Preventing the Occurrence of
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`Cardiovascular Event in Multiple Risk Patient,” and naming Mitsuhiro Yokoyama, Hideki
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`Origasa, Masunori Matsuzaki, Yuji Matsuzawa and Yasushi Saito as inventors. A true and correct
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`copy of the ’537 patent is attached to this complaint as Exhibit C.
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`38. The ’537 patent is assigned to Mochida Pharmaceutical Co., Ltd.
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`39. Amarin Pharma, Inc. holds an exclusive license to the ’537 patent.
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`40. The ’537 patent reflects and claims the analysis and outcome published in the Saito
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`Article. See, e.g., Ex. C at Example 1 (col. 13, ll. 1 to col. 15, ll. 61 (including the referenced
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`tables and figures).
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`41. Claim 1 of the ’537 patent recites as follows:
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`in a
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`1. A method of reducing occurrence of a cardiovascular event
`hypercholesterolemia patient consisting of:
`identifying a patient having triglycerides (TG) of at least 150 mg/DL and HDL-C
`of less than 40 mg/dL in a blood sample taken from the patient as a risk factor of
`a cardiovascular event, wherein the patient has not previously had a
`cardiovascular event, and administering ethyl icosapentate in combination with a
`3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,
`wherein said 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor is
`administered to the patient at least one of before, during and after administering
`the ethyl icosapentate; and
`wherein the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor is
`selected from the group consisting of pravastatin, lovastatin, simvastatin,
`fluvastatin, atorvastatin, pitavastatin, rosuvastatin, and salts thereof, and
`wherein daily dose of the 3-hydroxy-3-methylglutaryl coenzyme A reductase
`inhibitor are 5 to 60 mg for pravastatin, 2.5 to 60 mg for simvastatin, 10 to 180
`mg for fluvastatin sodium, 5 to 120 mg for atorvastatin calcium hydrate, 0.5 to
`12 mg for pitavastatin calcium, 1.25 to 60 mg for rosuvastatin calcium, 5 to 160
`mg for lovastatin, and 0.075 to 0.9 mg for cerivastatin sodium.
`
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`42. On February 4, 2014, the USPTO duly and legally issued the ’077, titled “Stable
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`Pharmaceutical Composition and Methods of Using Same,” and naming Mehar Manku, Ian
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`Osterloh, Pierre Wicker, Rene Braeckman, and Paresh Soni as inventors. A true and correct copy
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`of the ’077 patent is attached to this complaint as Exhibit O.
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`43. The ’077 patent is assigned to Amarin Pharmaceuticals Ireland Limited.
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`44. Amarin Pharma, Inc. holds an exclusive license to the ’077 patent.
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`45. Claims 1 and 8 of the ’077 patent recites as follows:
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`1. A method of reducing triglycerides in a subject with mixed dyslipidemia on statin
`therapy comprising, administering to the subject a pharmaceutical composition
`comprising about 2500 mg to 5000 mg per day of ethyl eicosapentaenoate and not
`more than about 5%, by weight of all fatty acids, docosahexaenoic acid or its esters
`to effect a reduction in fasting triglyceride levels in the subject.
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`8. The method of claim 1 wherein the subject exhibits a reduction in hs-CRP
`compared to placebo control.
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`46. On February 25, 2020, the USPTO duly and legally issued the ’861 patent, titled
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`“Methods of reducing the risk of a cardiovascular event in a subject at risk for cardiovascular
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`disease,” and naming Paresh Soni as the inventor. A true and correct copy of the ’861 patent is
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`attached to this complaint as Exhibit P.
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`47. The ’861 patent is assigned to Amarin Pharmaceuticals Ireland Limited.
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`48. Amarin Pharma, Inc. holds an exclusive license to the ’861 patent.
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`49. Claims 1 and 2 of the ’861 patent recite as follows:
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`1. A method of reducing risk of cardiovascular death in a subject with established
`cardiovascular disease, the method comprising administering to said subject about
`4 g of ethyl icosapentate per day for a period effective to reduce risk of
`cardiovascular death in the subject.
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`2. The method of claim 1, wherein the subject has a fasting baseline triglyceride
`level of about 135 mg/dL to about 500 mg/dL and a fasting baseline LDL-C level
`of about 40 mg/dL to about 100 mg/dL.
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`Amarin’s VASCEPA® Receives FDA Approval for Reducing the Risk of
`Certain Cardiovascular Events in Patients with High Triglycerides and Low
`HDL-C Levels Concurrently on Statin Therapy
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`C.
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`50. Amarin Pharmaceuticals Ireland Limited is the current holder of NDA No. 202057
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`for 1 g and 0.5 g icosapent ethyl capsules. Amarin Pharma, Inc. is Amarin Pharmaceuticals Ireland
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`Limited’s agent in the United States for purposes of communicating with the FDA regarding NDA
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`No. 202057. Amarin Pharmaceuticals Ireland Limited and Amarin Pharma, Inc. market both
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`strengths of the approved drug product under the tradename VASCEPA®.
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`51. A true, correct, and complete copy of the current FDA-approved Prescribing
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`Information for VASCEPA®, covering both the 1 g and 0.5 g strengths, is attached as Exhibit D.
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`52. VASCEPA® is indicated as (1) an adjunct to diet to reduce triglyceride levels in adult
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`patients with severe (≥ 500 mg/dL) hypertriglyceridemia (the “Severe Hypertriglyceridemia
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`Indication”), and (2) as an adjunct to maximally tolerated statin therapy to reduce the risk of
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`myocardial infarction, stroke, coronary revascularization, and unstable angina requiring
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`hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and
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`established cardiovascular disease or diabetes mellitus and 2 or more additional risk factors for
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`cardiovascular disease (the “CV Indication”). Ex. D, § 1.
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`53. FDA first approved 1 g strength icosapent ethyl capsules, sold under the trade name
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`VASCEPA®, pursuant to NDA No. 202057 on July 26, 2012.
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`54. A supplement to NDA No. 202057 for the 0.5 g strength of icosapent ethyl capsules
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`was approved on February 16, 2017.
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`55. From July 26, 2012 through December 12, 2019, the sole indication for which
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`VASCEPA® had received FDA approval was the Severe Hypertriglyceridemia Indication. FDA
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`approval was based, in part, on the MARINE clinical trial and information from that trial is
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`included on the VASCEPA® label. See Ex. E (VASCEPA® July 2012 label); Ex. F (VASCEPA®
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`Feb. 2017 label).
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`56. From 2012 through December 12, 2019, the label for VASCEPA® contained the
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`following limitation of use: “The effect of VASCEPA on cardiovascular mortality and morbidity
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`in patients with severe hypertriglyceridemia has not been determined” (the “CV Limitation of
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`Use”). See Ex. E (VASCEPA® July 2012 label); Ex. F (VASCEPA® Feb. 2017 label). The CV
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`Limitation of Use appeared in three places on the VASCEPA® label during that time period. See
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`Ex. E at Highlights of Prescribing Information and Sections 1 and 14; Ex. F (same). The CV
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`Limitation of Use as it appears in the VASCEPA® Label approved by FDA in February 2017 is
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`reproduced below with annotations in red:
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`Ex. F at Highlights of Prescribing Information.
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`Id. § 1.
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`Id. § 14.
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`57. The CV Limitation of use appearing on the VASCEPA® label from 2012 through
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`December 12, 2019 was consistent with other products in the therapeutic category, such as
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`LOVAZA®, a combination of ethyl esters of omega 3 fatty acids including EPA. To illustrate,
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`the version of the LOVAZA® label approved by FDA on April 3, 2019 also contained the CV
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`Limitation of Use, as shown below with an annotation in red:
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`Ex. S at Highlights of Prescribing Information.
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`58. On December 13, 2019, FDA approved VASCEPA® for the CV Indication, based
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`on the results of the REDUCE-IT clinical trial. See Ex. G.
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`59.
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`In conjunction with VASCEPA®’s approval for the CV Indication, the VASCEPA®
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`label was modified to remove the CV Limitation of Use and add the CV Indication, among other
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`changes. Compare Ex. D, with Exs. E and F.
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`60. To illustrate, the Highlights of Prescribing Information of the VASCEPA® label as
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`approved by FDA in December 2019 lacks the CV Limitation of Use:
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`
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`See Ex. D. This is in contrast with the 2019 LOVAZA® label which still contains the CV
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`Limitation of Use. See Ex. S.
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`61. The current VASCEPA® label instructs, recommends, and encourages administering
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`icosapent ethyl in combination with a statin to patients with baseline triglycerides ≥ 150 mg/dL to
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`reduce the risk of a cardiovascular event in a daily dose of 4 grams per day. See Ex. D. Notably,
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`FDA did not include an upper limit on the triglyceride range for the CV Indication.
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`62. FDA’s December 13, 2019 approval of VASCEPA® for the CV Indication was
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`hailed as “a major milestone in cardiovascular prevention.” Ex. I. As the lead investigator for the
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`REDUCE-IT study explained, “Nothing this significant has happened in the world of
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`cardiovascular prevention since the introduction of statins nearly three decades ago. Many patients
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`stand to benefit from this historic advance in care.” Id.
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`63. On information and belief, following VASCEPA®’s approval for the CV Indication
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`and the concurrent removal of the CV Limitation of Use from the VASCEPA® label, healthcare
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`providers rapidly associated administration of icosapent ethyl together with a statin as a method
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`for reducing risk of cardiovascular events in patients with baseline triglycerides ≥ 150 mg/dL.
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`64. On information and belief, Defendants learned that FDA approved VASCEPA® for
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`the CV Indication on or around December 13, 2019 because, on information and belief, Defendants
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`regularly monitor the approval status of brand-name drugs serving as the RLD for its generic drug
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`candidates, and thus learned of VASCEPA® additional approval either from the FDA’s press
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`release announcing the same (Ex. J), Amarin’s press release announcing the same (Ex. I), or in
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`some other form.
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`D.
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`Amarin Listed the Asserted Patents Patent in the FDA’s Orange Book as
`Covering VASCEPA®
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`65.
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`In conjunction with NDA No. 202057, Amarin submitted patent information relating
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`to VASCEPA® to FDA for listing in the “Approved Drug Products with Therapeutic Equivalence
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`Evaluations,” commonly referred to the “Orange Book,” which provides notice concerning patents
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`covering FDA-approved drugs.
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`66. On January 9, 2020, Amarin timely submitted patent information regarding the ’537
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`patent to FDA for listing in the Orange Book as covering methods of using VASCEPA® pursuant
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`to 21 U.S.C. § 355(c)(2) and 21 C.F.R. § 314.53(d)(3).
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`67. The ’537 patent was listed in the Orange Book on or about January 10, 2020 with
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`patent use code U-2707, “Use of VASCEPA as an adjunct to statin therapy to reduce the
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`occurrence of a cardiovascular event in an adult patient with hypercholesteremia.”
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`68. Methods of using VASCEPA® (icosapent ethyl) capsules, 1 g and 0.5 g, for treating
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`patients as provided in the VASCEPA® label are covered by at least one claim of the ’537 patent.
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`69. On January 6, 2020, Amarin timely submitted patent information regarding the ’077
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`patent to FDA for listing in the Orange Book as covering methods of using VASCEPA® pursuant
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`to 21 U.S.C. § 355(c)(2) and 21 C.F.R. § 314.53(d)(3).
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`70. The ’077 patent was listed in the Orange Book on or about January 6, 2020 with
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`patent use code U-2693, “Use of VASCEPA to reduce triglycerides in a mixed dyslipidemia adult
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`patient with elevated triglyceride (TG) levels (>= 150 mg/dL) and on statin therapy.”
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`71. Methods of using VASCEPA® (icosapent ethyl) capsules, 1 g and 0.5 g, for treating
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`patients as provided in the VASCEPA® label are covered by at least one claim of the ’077 patent.
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`72. On March 20, 2020, Amarin timely submitted patent information regarding the ’861
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`patent to FDA for listing in the Orange Book as covering methods of using VASCEPA® pursuant
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`to 21 U.S.C. § 355(c)(2) and 21 C.F.R. § 314.53(d)(3).
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`73. The ’861 patent was listed in the Orange Book on or about March 20, 2020 with
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`patent use code U-2756, “Use of VASCEPA as an adjunct to statin therapy to reduce the risk of
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`cardiovascular death in an adult patient with established cardiovascular disease.”
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`74. Methods of using VASCEPA® (icosapent ethyl) capsules, 1 g and 0.5 g, for treating
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`patients as provided in the VASCEPA® label are covered by at least one claim of the ’861 patent.
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`75. On information and belief, Defendants learned that Amarin listed the ’537, ’077, and
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`’861 patents in the Orange book as covering VASCEPA® at or around their time of listing in the
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`Orange Book because, on information and belief, Defendants regularly monitor the Orange Book
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`for updated patent listings made for brand-name drugs serving as the RLD for their generic drug
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`candidates.
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`ACTS GIVING RISE TO THIS ACTION FOR
`DEFENDANTS’ INFRINGEMENT OF THE PATENT-IN-SUIT
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`76. The Drug Price Competition and Patent Term Restoration Act of 1984, commonly
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`known as the “Hatch-Waxman Act,” amended the Federal Food, Drug, and Cosmetic Act
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`(“FDCA”) and governs approvals of generic drugs. Under Section 505(j) of the amended FDCA,
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`codified at 21 U.S.C. § 355(j), companies wishing to bring a generic version of a branded
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`prescription drug to market can submit an Abbreviated New Drug Application (“ANDA”) to the
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`FDA.
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`77. The ANDA process allows the generic drug company to avoid the expensive clinical
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`trials required of an NDA holder to demonstrate a drug’s safety and effectiveness by relying on
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`the original NDA submission for that purpose. This process results in an enormous cost and time
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`savings to the generic drug company. Reliance on the innovator company’s data and the ability to
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`“free ride” on the innovator company’s development saves the generic drug company millions of
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`dollars and years in development and clinical research costs.
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`78. The Hatch-Waxman Act also contains provisions meant to balance the competing
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`interests of innovator and generic drug companies. When seeking ANDA approval, the generic
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`applicant must consult the Orange Book and make certain certifications with respect to each patent
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`listed for the branded drug. The generic applicant can certify that no patent information appears
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`in the Orange Book (“Paragraph I certification”); that the listed patent has already expired
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`(“Paragraph II certification”); that the applicant will not market the generic version before the date
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`on which the patent will expire (“Paragraph III certification”); or that the patent is invalid or will
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`not be infringed by the manufacture, use, or sale of the drug for which the ANDA is submitted
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`(“Paragraph IV certification”). 21 U.S.C. § 355(j)(2)(A)(vii)(I)-(IV). When a Paragraph IV
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`certification is made, the generic applicant must also provide notice of the certification to the
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`innovator company, who can choose to enforce its patents in federal court.
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`79. When the listed patent is a method-of-use patent, like the Asserted Patents, the
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`generic applicant can attempt to seek FDA approval to label its drug only for uses not covered by
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`the patent, in which case a statement is submitted under 21 U.S.C. § 355(j)(2)(A)(viii), commonly
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`known as a “Section viii statement” or “Section viii carve-out,” in place of a patent certification.
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`The generic applicant is not obligated to provide notice of a Section viii statement to the innovator
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`company.
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`80. For an Orange Book-listed method-of-use patent that has not expired, whether to
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`make a Paragraph III or Paragraph IV certification or a Section viii statement is a calculated
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`business decision the generic applicant makes after evaluating the associated commercial risks.
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`81.
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`It is the generic applicant’s responsibility to ensure that the marketing and sale of its
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`ANDA product (including the associated labeling, not limited to the Indications and Usage section)
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`pursuant to a Section viii statement does not infringe the patents referenced in the Section viii
`
`statement. Indeed, FDA describes its role with respect to patents as “ministerial,” has observed
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`that it “lack[s] expertise in patent matters,” and does not make patent infringement determinations
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`when reviewing the labeling associated with a Section viii statement. 68 Fed. Reg. 36,683. Courts
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`have found generic manufacturer’s labels, approved subject to a Section viii statement, to
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`nonetheless be evidence of patent infringement.
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`82. The Orange Book also contains therapeutic equivalence ratings for multisource
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`prescription drug products. The agency developed these ratings in the 1970s in response to states
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`that requested guidance as they implemented laws to encourage generic substitution. FDA has
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`explained that an AB rating reflects a decision that a generic drug is therapeutically equivalent to
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`a branded drug when the generic drug is used as labeled, and it does not reflect a decision of
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`therapeutic equivalence for off-label uses.
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`83. On information and belief, on or about September 21, 2016, Hikma (through its
`
`predecessor) submitted ANDA No. 209457 for generic copies of VASCEPA® (icosapent ethyl) 1
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`mg under section 505(j) of the FDCA.
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`84. On information and belief, Hikma Pharmaceuticals USA, Inc. is the current owner of
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`ANDA No. 209457.
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`85. As an ANDA filer, Hikma was required to provide to FDA patent certifications or
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`Section viii statements addressing each of the patents timely listed in the Orange Book for
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`VASCEPA® before FDA finally approved ANDA No. 209457. 21 C.F.R. § 314.94(a)(12)