PTAB

IPR2022-00215

Hikma Pharmaceuticals USA Inc v. Amarin Pharmaceuticals Ireland Ltd

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Stable Pharmaceutical Composition And Methods Of Using Same
  • Brief Description: The ’077 patent discloses a method for reducing triglycerides in a subject with mixed dyslipidemia who is already on statin therapy. The method involves administering a pharmaceutical composition of about 2500 mg to 5000 mg per day of ethyl eicosapentaenoate (EPA) that contains not more than 5% docosahexaenoic acid (DHA).

3. Grounds for Unpatentability

Ground 1: Anticipation - Claims 1, 8, and 19 are anticipated by Yokoyama I under 35 U.S.C. §102(b).

  • Prior Art Relied Upon: Yokoyama I (WO 2007/142118).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Yokoyama I disclosed every element of independent claim 1. Yokoyama I taught a method of using purified EPA to treat patients with both hypercholesterolemia and hypertriglyceridemia (i.e., mixed dyslipidemia) in combination with a statin (HMG-CoA reductase inhibitor). Petitioner asserted that Yokoyama I disclosed administering a preferred dose of 2,700 mg/day (900 mg, three times a day) for patients with abnormal triglycerides, which falls squarely within the claimed range of 2,500–5,000 mg/day. Furthermore, Yokoyama I taught using high-purity EPA of at least 96.5%, which satisfies the limitations of claim 19 ("at least about 90%") and claim 1 ("not more than about 5%" DHA). For dependent claim 8, Petitioner argued that the claimed reduction in hs-CRP is an inherent result of practicing the method disclosed in Yokoyama I, relying on Patent Owner's own litigation positions and clinical studies.

Ground 2: Obviousness over Mori/Yokoyama II - Claims 1, 8, and 19 are obvious over Mori in view of Yokoyama II under 35 U.S.C. §103(a).

  • Prior Art Relied Upon: Mori (a 2000 clinical nutrition article) and Yokoyama II (a 2007 article in The Lancet).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner contended that Mori disclosed all limitations of claim 1 except for the requirement that the patient be on statin therapy. Mori described a clinical trial where patients with mixed dyslipidemia were administered 4 g/day of purified EPA (≈96% purity), resulting in a significant reduction in triglycerides. The missing element, co-administration with a statin, was supplied by Yokoyama II, which reported the results of the large-scale JELIS clinical trial investigating the combination therapy of purified EPA and statins in over 18,000 patients with mixed dyslipidemia.
    • Motivation to Combine: A POSITA would combine the teachings because, as Yokoyama II explained, statin therapy was the established first-line treatment and standard of care for patients with hyperlipidemia. Yokoyama II further provided strong motivation by demonstrating that combining EPA with statins significantly reduced triglycerides and the risk of major coronary events, suggesting a promising regimen.
    • Expectation of Success: A POSITA would have had a high expectation of success because Mori already demonstrated the triglyceride-lowering effect of the specific drug and dose, and Yokoyama II confirmed the benefits of adding it to the standard of care (statin therapy) in the same patient population.

  • Additional Grounds: Petitioner asserted additional obviousness challenges for the dependent claims. These grounds argued that adding Satoh (a 2007 article) or Grimsgaard (a 1997 article) to the primary combinations rendered the remaining claims obvious. Satoh was cited for its teaching that EPA reduces C-reactive protein (hs-CRP), making claim 8 obvious. Grimsgaard was cited for its disclosure of administering 4 g/day of EPA in 1-gram soft gelatin capsules, making the dosage unit and capsule limitations of claims 14-18 obvious.

4. Key Claim Construction Positions

  • Petitioner argued that the term “a subject with mixed dyslipidemia” should be construed as a subject having both elevated triglycerides (at least 150 mg/dL) and elevated LDL-cholesterol (at least 100 mg/dL).
  • This construction was asserted to be consistent with the patent’s specification, which identifies mixed dyslipidemia with Fredrickson Type IIb dyslipidemia, and with the understanding of a POSITA at the time. The proposed construction is critical because it directly maps to the patient populations described in the prior art references, who were selected for having both conditions.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that the Board should not exercise discretionary denial under §314(a) based on Fintiv factors.
  • Petitioner asserted that multiple factors strongly favored institution. The scheduled trial date in the parallel district court litigation (October 30, 2023) was well after the statutory deadline for a Final Written Decision (FWD) in the inter partes review (IPR) (May/June 2023). Investment in the parallel proceeding was minimal at the time of filing, and the merits of the petition were presented as particularly strong. Petitioner also stipulated that it would not pursue in district court any invalidity ground that was raised or reasonably could have been raised in the IPR, mitigating concerns of duplicative efforts. Petitioner further argued that denial under §325(d) was improper because the key prior art references, while disclosed, were never substantively considered by the Examiner during prosecution.

6. Relief Requested

  • Petitioner requests institution of an IPR and cancellation of claims 1, 8, and 14-19 of the ’077 patent as unpatentable.