Amarin Pharma, Inc. v. Hikma Pharm. USA Inc.

104 F.4th 1370

AMARIN PHARMA, INC., Amarin Pharmaceuticals Ireland Limited,Mochida Pharmaceutical Co., Ltd., Plaintiffs-Appellants v. HIKMA PHARMACEUTICALS USA INC., Hikma Pharmaceuticals PLC, Defendants-AppelleesHealth Net LLC, Defendant

2023-1169

United States Court of Appeals, Federal Circuit

Decided: June 25, 2024

Appeal from the United States District Court for the District of Delaware in No. 1:20-cv-01630-RGA-JLH, Judge Richard G. Andrews.

Nathan K. Kelley, Perkins Coie LLP, Washington, DC, argued for plaintiffs-appellants. Also represented by Nathanael D. Andrews.

Charles B. Klein, Winston & Strawn LLP, Washington, DC, argued for defendants-appellees. Also represented by Claire A. Fundakowski; Alison Michelle King, Chicago, IL; Eimeric Reig-Plessis, San Francisco, CA.

Sara Wexler Koblitz, Hyman, Phelps & McNamara, Washington, DC, for amicus curiae Association for Accessible Medicines.

Before Moore, Chief Judge, Lourie, Circuit Judge, and Albright, District Judge.¹

Lourie, Circuit Judge.

Amarin Pharma, Inc., Amarin Pharmaceuticals Ireland Limited, and Mochida Pharmaceutical Co., Ltd. (collectively, "Amarin") appeal from a decision of the United States District Court for the District of Delaware granting Hikma Pharmaceuticals USA Inc.'s and Hikma Pharmaceuticals PLC's (collectively, "Hikma") motion to dismiss Amarin's complaint for failure to state a claim. Amarin Pharma, Inc. v. Hikma Pharms. USA Inc., 578 F. Supp. 3d 642 (D. Del. 2022) ("Decision").² Because Amarin's allegations against Hikma plausibly state a claim for induced infringement, we reverse.

BACKGROUND

I

Amarin markets and sells icosapent ethyl, an ethyl ester of an omega-3 fatty acid commonly found in fish oils, under the brand name Vascepa&reg. In 2012, the U.S. Food and Drug Administration ("FDA") approved Vascepa for the treatment of severe hypertriglyceridemia ("the SH indication"), a condition in which a patient's blood triglyceride level is at least 500 mg/dL. As part of its labeling for Vascepa, Amarin included an express "limitation of use," disclosing that "[t]he effect of VASCEPA on cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined." J.A. 650 ("the CV Limitation of Use"). But observing that clinical testing data demonstrated that Vascepa was capable of lowering triglyceride levels without increasing "bad" cholesterol (i.e., LDL-C), Amarin continued its research into potential cardiovascular uses of the drug.

In 2019, following the success of Amarin's additional research and clinical trials, the FDA approved Vascepa for a second use: as a treatment to reduce cardiovascular risk (i.e., myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization) in patients having blood triglyceride levels of at least 150 mg/dL ("the CV indication"). Upon receiving that approval, Amarin added the CV indication to its label and removed the CV Limitation of Use. Compare J.A. 650 (pre-CV indication approval), and J.A. 663 (same), with J.A. 635 (post-CV indication approval). It also timely listed U.S. Patent 9,700,537 ("the '537 patent") and U.S. Patent 10,568,861 ("the '861 patent") (collectively, "the asserted patents"), which each claim methods directed to the CV indication, in the Orange Book.³

In 2016, when Vascepa was still only approved for the SH indication, Hikma submitted an Abbreviated New Drug Application ("ANDA") for approval of its generic icosapent ethyl product.⁴ That ANDA remained pending in 2019 when the FDA approved the use of icosapent ethyl for the CV indication. At that juncture, Hikma was required to either amend its proposed label to match the revised Vascepa label including the CV indication and corresponding information, see 21 U.S.C. § 355(j)(2)(A)(vii), or file a "section viii statement" to "carve-out" that indication, see id. § 355(j)(2)(A)(viii). Hikma opted for the latter and submitted a statement seeking FDA approval only for uses not covered by Amarin's newly listed CV indication patents. In other words, Hikma sought the FDA's approval of a "skinny label" for its generic product that would include only the SH indication and not the CV indication. The FDA approved Hikma's ANDA, including its proposed skinny label, on May 21, 2020.

Hikma's approved label refers only to the SH indication in the "Indications and Usage" section. J.A. 694 (providing that the drug is indicated only "as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (= 500 mg/dL) hypertriglyceridemia"). It further identifies potential side effects, stating that people with cardiovascular disease or diabetes with a risk factor for cardiovascular disease may experience "[h]eart rhythm problems (atrial fibrillation and atrial flutter)." Id. at 704-05. And it acknowledges that "[m]edicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet." Id. at 705. Like the current Vascepa label, Hikma's ap proved label does not include the CV Limitation of Use that was present on the Vascepa label during the time when icosapent ethyl was approved for only the SH indication. Compare id. at 694 (Hikma label), and id. at 635 (current Vascepa label), with id. at 650 (Vascepa label pre-CV indication approval). Although Hikma's original proposed label included the CV Limitation of Use, Hikma later amended the label to remove that limitation around the same time it submitted its section viii statement carving out the uses covered by the asserted patents.

Throughout 2020, Hikma issued a series of press releases regarding its efforts to provide a generic icosapent ethyl product. First, in March, it publicly announced the favorable district court outcome in the Nevada litigation against Amarin regarding the SH indication ("the March 2020 Press Release"). J.A. 709; see supra note 4. That press release referred to Hikma's product as the "generic version" of Vascepa, which it described as "medicine that is indicated, in part, [to treat] severe (= 500 mg/dL) hypertriglyceridemia." J.A. 709. It also provided sales data for Vascepa, stating that sales of the product in the United States "were approximately $919 million in the 12 months ending February 2020." Id.

Then, the day after the FDA granted Hikma's ANDA, Hikma issued a press release announcing the approval ("the May 2020 Press Release"). Id. at 613. The press release stated that Hikma had received FDA approval for its icosapent ethyl tablets, "the generic equivalent to Vascepa&reg." Id. It further included a quote from Hikma's President of Generics that "[t]he approval for our generic version of Vascepa® is an important milestone towards bringing this product to market." Id.

A little over three months later, on September 3, 2020, Hikma issued a press release announcing the positive outcome in the appeal of the Nevada litigation regarding its alleged infringement of Amarin's SH indication patents ("the September 2020 Press Release"). J.A. 712; see supra note 4. Similar to the prior press releases, the September 2020 Press Release referred to Hikma's product as "Hikma's generic version of Vascepa®" and "generic Vascepa&reg." J.A. 712. And, like the March 2020 Press Release, it further provided the following description of Vascepa:

Vascepa® is a prescription medicine that is indicated, in part, as an adjunct to diet to reduce triglyceride levels in adult patients with severe (= 500 mg/dL) hypertriglyceridemia. According to IQVIA, US sales of Vascepa® were approximately $1.1 billion in the 12 months ending July 2020.

Id. The $1.1 billion referenced in the press release (and the $919 million referenced in the March 2020 Press Release) accounted for sales of Vascepa for all uses, including the CV indication, which undisputedly made up more than 75% of the drug's sales.

Hikma issued a final press release upon its official launch of its generic product ("the November 2020 Press Release"). J.A. 715. That press release stated:

Hikma's FDA-approved Icosapent Ethyl Capsule product is indicated for the following indication: as an adjunct to diet to reduce triglyceride levels in adult patients with severe (= 500 mg/dL) hypertriglyceridemia. Hikma's product is not approved for any other indication for the reference listed drug VASCEPA&reg.

Id.

Following the approval of its ANDA, Hikma also began marketing its product on its website. There, Hikma listed its generic icosapent ethyl capsules in the "Therapeutic Category: Hypertriglyceridemia" and indicated that it was "AB" rated. J.A. 820. That rating, developed and assigned by the FDA, reflects the FDA's determination that a generic drug is therapeutically equivalent to a branded drug when the generic drug is used as labeled. It does not reflect a decision of therapeutic equivalence for off-label use. Below the product summary on the website, in small lettering, is a disclaimer that reads: "Hikma's generic version is indicated for fewer than all approved indications of the Reference Listed Drug." Id.

II

In November 2020, less than a month after Hikma launched its generic icosapent ethyl product, Amarin sued under 35 U.S.C. § 271(b), alleging that Hikma had induced infringement of at least claim 1 of the '537 patent, and at least claims 1 and 2 of the '861 patent. Claim 1 of the '537 patent recites:

1. A method of reducing occurrence of a cardiovascular event in a 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

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