DCT

1:20-cv-01630

Amarin Pharma Inc v. Health Net LLC

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Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-01630, D. Del., 01/25/2021
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Hikma Pharmaceuticals USA Inc. is incorporated in Delaware and Defendant Health Net, LLC is organized under the laws of Delaware.
  • Core Dispute: Plaintiff alleges that Defendant Hikma’s marketing and sale of its generic icosapent ethyl capsules, and Defendant Health Net's insurance coverage policies for the generic drug, induce infringement of patents related to methods of reducing cardiovascular risk in specific patient populations.
  • Technical Context: The technology involves the use of highly purified eicosapentaenoic acid (EPA), an omega-3 fatty acid, as a prescription therapy to reduce the risk of cardiovascular events in patients already taking statins.
  • Key Procedural History: The complaint alleges that after Plaintiff’s branded drug, VASCEPA®, received FDA approval for a new cardiovascular (CV) risk reduction indication, Defendant Hikma launched a generic version with a "skinny label" that "carved out" the patented method of use. Plaintiff alleges that despite this carve-out, Hikma’s marketing and label language, combined with Health Net’s formulary tiering, encourage healthcare providers and patients to use the generic drug for the patented CV risk reduction indication.

Case Timeline

Date Event
2006-05-31 ’537 Patent Priority Date
2009-04-29 ’077 Patent Priority Date
2012-06-29 ’861 Patent Priority Date
2012-07-26 FDA first approves VASCEPA® 1g capsules
2014-02-04 ’077 Patent Issues
2016-09-21 Hikma submits ANDA for generic icosapent ethyl capsules
2017-07-11 ’537 Patent Issues
2019-12-13 FDA approves VASCEPA® for the CV Indication
2020-01-06 ’077 Patent is listed in the FDA Orange Book
2020-01-10 ’537 Patent is listed in the FDA Orange Book
2020-02-25 ’861 Patent Issues
2020-03-20 ’861 Patent is listed in the FDA Orange Book
2020-05-21 FDA grants final approval for Hikma’s generic icosapent ethyl capsules
2020-11-05 Hikma launches its generic icosapent ethyl capsules in the U.S.
2021-01-25 First Amended Complaint is filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 9,700,537 - "Composition for Preventing the Occurrence of Cardiovascular Event in Multiple Risk Patient"

  • Patent Identification: U.S. Patent No. 9,700,537, "Composition for Preventing the Occurrence of Cardiovascular Event in Multiple Risk Patient," issued July 11, 2017.

The Invention Explained

  • Problem Addressed: The patent is based on clinical trial data seeking to address the need for therapies that can further reduce cardiovascular events in patients who, despite being treated for high cholesterol with statins, still possess multiple risk factors for coronary artery disease (Compl. ¶¶ 37-39; ’537 Patent, col. 1:29-45).
  • The Patented Solution: The invention is a method of treatment for a specific subgroup of patients with hypercholesterolemia. The method involves identifying patients who have triglycerides of at least 150 mg/dL and HDL-C (high-density lipoprotein cholesterol) of less than 40 mg/dL, and who have not had a prior cardiovascular event, and then administering ethyl icosapentate in combination with a statin to reduce the occurrence of a cardiovascular event (Compl. ¶45; ’537 Patent, col. 16:1-24).
  • Technical Importance: This method provides a targeted therapy for a patient population with specific lipid biomarkers (high triglycerides and low HDL-C) known to be associated with residual cardiovascular risk even after LDL-C ("bad cholesterol") is controlled by statins (Compl. ¶¶ 30, 33-34).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim of the '537 patent, with Claim 1 being the sole independent claim (Compl. ¶165).
  • Claim 1 of the '537 patent requires:
    • A method of reducing occurrence of a cardiovascular event in a hypercholesterolemia patient.
    • The method consists of: identifying a patient having triglycerides (TG) of at least 150 mg/DL and HDL-C of less than 40 mg/dL, wherein the patient has not previously had a cardiovascular event.
    • Administering ethyl icosapentate in combination with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (a statin).
    • The statin is administered at least one of before, during, or after the ethyl icosapentate.
    • The statin is selected from a specific group (pravastatin, lovastatin, etc.) and administered within specified daily dose ranges.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,642,077 - "Stable Pharmaceutical Composition and Methods of Using Same"

  • Patent Identification: U.S. Patent No. 8,642,077, "Stable Pharmaceutical Composition and Methods of Using Same," issued February 4, 2014.

The Invention Explained

  • Problem Addressed: The patent background describes the therapeutic importance of omega-3 fatty acids like EPA, while noting that these polyunsaturated fatty acids are susceptible to oxidative degradation, which can compromise their stability and efficacy (’077 Patent, col. 1:20-30).
  • The Patented Solution: The invention provides a method for reducing triglycerides in subjects with mixed dyslipidemia already on statin therapy. The solution involves administering a pharmaceutical composition containing a high daily dose (about 2500 mg to 5000 mg) of highly pure ethyl eicosapentaenoate that contains not more than about 5% docosahexaenoic acid (DHA) or its esters (’077 Patent, col. 2:50-60). This specific formulation is intended to provide a stable and effective therapeutic agent (Compl. ¶49).
  • Technical Importance: The method established the use of a high-purity, high-dose EPA formulation to lower triglycerides in a specific patient population, distinguishing it from other omega-3 products that contain a mixture of EPA and DHA (Compl. ¶¶ 25, 30).

Key Claims at a Glance

  • The complaint asserts infringement of at least Claim 8 of the '077 patent, which is dependent on Claim 1 (Compl. ¶173).
  • Independent Claim 1 of the '077 patent requires:
    • A method of reducing triglycerides in a subject with mixed dyslipidemia on statin therapy.
    • The method comprises administering to the subject a pharmaceutical composition.
    • The composition comprises about 2500 mg to 5000 mg per day of ethyl eicosapentaenoate.
    • The composition contains not more than about 5%, by weight of all fatty acids, of docosahexaenoic acid or its esters.
    • The administration is to effect a reduction in fasting triglyceride levels in the subject.
  • Dependent Claim 8 adds the limitation: "wherein the subject exhibits a reduction in hs-CRP compared to placebo control."
  • The complaint does not explicitly reserve the right to assert other dependent claims.

U.S. Patent No. 10,568,861 - "Methods of reducing the risk of a cardiovascular event in a subject at risk for cardiovascular disease"

  • Patent Identification: U.S. Patent No. 10,568,861, "Methods of reducing the risk of a cardiovascular event in a subject at risk for cardiovascular disease," issued February 25, 2020.

Technology Synopsis

  • The patent claims a method for reducing the risk of cardiovascular death. The method applies to a subject with established cardiovascular disease and specific baseline levels of triglycerides and LDL-C, and involves administering about 4 grams of ethyl icosapentate per day (’861 Patent, Abstract; Compl. ¶53).

Asserted Claims

  • Claims 1 and 2 (Compl. ¶53).

Accused Features

  • The complaint alleges that Defendant Hikma induces infringement by promoting and selling its generic icosapent ethyl capsules for use in patients with established cardiovascular disease, and that Defendant Health Net induces by providing preferential coverage for such use (Compl. ¶¶ 180-181, 204-205).

III. The Accused Instrumentality

Product Identification

  • The accused products are Hikma Pharmaceuticals USA Inc. and Hikma Pharmaceuticals PLC’s generic icosapent ethyl capsules (Compl. ¶13).

Functionality and Market Context

  • The accused product is a generic version of Plaintiff’s VASCEPA®, containing highly pure icosapent ethyl, an omega-3 fatty acid (Compl. ¶¶ 1, 12, 106). It is FDA-approved as an adjunct to diet to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia (Compl. ¶¶ 82, 106).
  • The complaint alleges that Hikma intentionally designed its product and marketing to be substituted for all uses of VASCEPA®, including the patented use for cardiovascular risk reduction, for which the generic is not approved (Compl. ¶¶ 108-109). The complaint provides a screenshot from Hikma's website listing the drug’s "Therapeutic Category" as "Hypertriglyceridemia," a broader category than its approved indication (Compl. ¶126; Ex. T, p. 29). This broader categorization, the complaint alleges, encourages off-label use for the patented methods (Compl. ¶126). The complaint further alleges that Health Net encourages this infringing use by placing the generic on a lower, more favorable formulary tier than the branded VASCEPA® for all indications, making it cheaper for patients regardless of the prescribed purpose (Compl. ¶¶ 143, 145-146).

IV. Analysis of Infringement Allegations

’537 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of reducing occurrence of a cardiovascular event in a hypercholesterolemia patient consisting of: Hikma’s marketing materials, label, and press releases, together with Health Net's formulary policies, are alleged to instruct and encourage healthcare providers and patients to use Hikma's generic drug to reduce the risk of a cardiovascular event. ¶¶127-128, 164, 188 col. 1:29-32
identifying a patient having triglycerides (TG) of at least 150 mg/DL and HDL-C of less than 40 mg/dL... wherein the patient has not previously had a cardiovascular event Hikma’s label is alleged to encourage and instruct the treatment of patients having baseline TG ≥ 150 mg/dL, baseline HDL-C < 40 mg/dL, and who have not had a previous cardiovascular event. ¶130 col. 2:4-11
and administering ethyl icosapentate in combination with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor The accused product is ethyl icosapentate, and Hikma’s label and marketing are alleged to encourage its use in combination with statin therapy. ¶¶13, 130(d) col. 2:11-14
  • Identified Points of Contention:
    • Scope Questions: A central question will be whether Hikma's and Health Net's actions constitute inducement of the claimed method, particularly the step of "reducing occurrence of a cardiovascular event." Hikma's product has a "skinny label" that carves out this patented indication (Compl. ¶¶ 82, 104-105). The dispute may focus on whether evidence from press releases, website marketing, and the removal of a prior "CV Limitation of Use" from the label is sufficient to show intent to induce infringement despite the carve-out (Compl. ¶¶ 108, 115). The complaint includes a screenshot of Hikma’s product label which, unlike the pre-2019 VASCEPA® label, lacks a disclaimer about effects on cardiovascular mortality, an omission the plaintiff alleges is intended to encourage the infringing use (Compl. pp. 12, 24).
    • Technical Questions: Does Hikma's label, which is only approved for severe hypertriglyceridemia (≥500 mg/dL), provide sufficient instruction to "identify" and treat the specific patient population of Claim 1 (TG ≥ 150 mg/dL and HDL-C < 40 mg/dL)? The complaint cites clinical trial data within Hikma's label as evidence that it does (Compl. ¶130).

’077 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of reducing triglycerides in a subject with mixed dyslipidemia on statin therapy Hikma's label allegedly encourages use in patients with mixed dyslipidemia who are on statin therapy, based on descriptions of patient populations in clinical trials included in the label. ¶134(a), (b) col. 2:50-52
comprising, administering to the subject a pharmaceutical composition comprising about 2500 mg to 5000 mg per day of ethyl eicosapentaenoate The accused product is icosapent ethyl, and Hikma's label allegedly instructs administration of 4 grams (4000 mg) per day. ¶134(c) col. 4:3-10
and not more than about 5%, by weight of all fatty acids, docosahexaenoic acid or its esters The complaint alleges that Hikma’s product is a highly pure form of ethyl eicosapentaenoate containing substantially no DHA. ¶134(c) col. 4:11-17
to effect a reduction in fasting triglyceride levels in the subject. The product's FDA-approved indication is to reduce triglyceride levels. ¶134(d) col. 2:54-56
From Dependent Claim 8: wherein the subject exhibits a reduction in hs-CRP compared to placebo control. The complaint alleges that Hikma's label encourages use in patients who would exhibit a reduction in hs-CRP, citing clinical study data referenced in the label. ¶134(e) col. 18:11-12
  • Identified Points of Contention:
    • Scope Questions: The analysis may turn on whether the patient population described in Hikma's label materials constitutes a subject with "mixed dyslipidemia" as that term is used in the patent. The complaint alleges that the clinical trial data included in Hikma's label, which describes patients with certain triglyceride, LDL-C, and HDL-C levels, meets this definition (Compl. ¶134(a)).
    • Technical Questions: What evidence does the complaint provide that Hikma specifically encourages use of its product to achieve the hs-CRP reduction required by dependent Claim 8? The complaint points to scientific literature and clinical trial data allegedly known to Hikma and referenced in its label as the basis for this allegation (Compl. ¶134(e)).

V. Key Claim Terms for Construction

  • The Term: "reducing occurrence of a cardiovascular event" (’537 Patent, Claim 1)

  • Context and Importance: This term defines the central purpose of the patented method. Its construction is critical because Defendant Hikma's generic product is not FDA-approved for this indication and was launched with a "skinny label" intended to omit it. Practitioners may focus on this term because the plaintiff's inducement case depends on showing that Hikma, through its marketing and labeling choices, nevertheless encouraged users to perform this specific step.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification links the administration of the composition to the outcomes of a clinical study (the JELIS study), which demonstrated a statistically significant reduction in major coronary events (Compl. ¶¶ 39-40; ’537 Patent, col. 13:1-61). This could support a construction tied to achieving a clinically recognized reduction in events.
    • Evidence for a Narrower Interpretation: The claim itself is a method claim requiring the act of "reducing." A defendant may argue that this requires an affirmative step or intent by the administering physician, which is absent if they are prescribing for a different, on-label purpose.

  • The Term: "mixed dyslipidemia" (’077 Patent, Claim 1)

  • Context and Importance: This term defines the patient population to whom the method applies. The scope of this term will determine whether the patients that Hikma allegedly encourages treating fall within the patent's claims. Practitioners may focus on this term to see if the patient characteristics described in the clinical trial data on Hikma's label (e.g., specific levels of TG, LDL-C, and HDL-C) meet the patent's definition of "mixed dyslipidemia."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes subjects suitable for treatment as having elevated triglycerides and being on statin therapy, which often implies other lipid abnormalities are also present, consistent with a broad understanding of mixed dyslipidemia (’077 Patent, col. 17:34-45).
    • Evidence for a Narrower Interpretation: The patent also references specific clinical trials (e.g., the ANCHOR study) whose patient populations had defined lipid parameters, such as triglycerides between 200 and 500 mg/dL (Compl. ¶31). This could support a narrower construction limited to patients meeting similar specific criteria.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement against both Hikma and Health Net. The inducement allegations against Hikma are based on its product label, press releases, and website, which allegedly encourage off-label use for the patented methods (Compl. ¶¶ 115, 122, 127, 133-135). The allegations against Health Net are based on its alleged knowledge of the patents and its decision to place the generic on a more favorable formulary tier than the branded drug for all uses, thereby creating an economic incentive for pharmacies to dispense and patients to use the generic for the patented, off-label purpose (Compl. ¶¶ 142, 145-146, 150).
  • Willful Infringement: The complaint alleges that Defendants' infringement has been and is willful (Prayer for Relief, p. 52, ¶c). The basis for this allegation includes Defendants' alleged knowledge of the patents, which were listed in the FDA's Orange Book, and knowledge of Plaintiff's exclusive rights to the CV indication (Compl. ¶¶ 80, 84, 166, 174, 182). The complaint also alleges that Amarin sent a letter to Health Net's pharmacy benefit manager, putting it on notice of the dispute (Compl. ¶87).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A core issue will be one of induced infringement under the Hatch-Waxman Act: Can a generic manufacturer be found to induce infringement of a patented method of use when it markets its product under a "skinny label" that omits the patented indication, but other evidence—such as press releases, website content, and the omission of prior label warnings—suggests an intent to encourage the infringing use?
  • A second key issue will be one of third-party liability: Can a health insurance provider or pharmacy benefit manager be held liable for inducing infringement by implementing formulary policies, such as preferential tiering, that create a strong economic incentive for pharmacists and patients to substitute a "skinny label" generic for a branded drug for patented, off-label uses?
  • A central evidentiary question will be one of claim scope and labeling: Does the clinical data and patient population information included on the defendant's FDA-approved label provide sufficient instruction to a healthcare provider to practice the specific steps of the patented methods, thereby meeting the requirements for direct infringement by the end-user?