DCT

2:24-cv-06389

Esperion Therap Inc v. Hetero USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: Esperion Therapeutics, Inc. v. Hetero USA Inc., et al., 2:24-cv-06389, D.N.J., 05/23/2024
  • Venue Allegations: Venue for Defendant Hetero USA Inc. is based on its principal place of business in New Jersey. Venue for the foreign-domiciled defendants is based on their status as non-U.S. residents, which permits suit in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the cholesterol-lowering drug NEXLETOL® constitutes an act of infringement of three patents covering the active ingredient bempedoic acid, as well as highly purified compositions and crystalline forms thereof.
  • Technical Context: The technology concerns bempedoic acid, an adenosine triphosphate-citrate lyase (ACL) inhibitor used for managing cholesterol, which is a significant therapeutic area dominated by statin drugs.
  • Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendants' filing of ANDA No. 219449, which included a Paragraph IV certification asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed. The complaint notes this action is being filed within the 45-day window following receipt of Defendants' notice letter, triggering a potential 30-month stay of FDA approval for the generic product.

Case Timeline

Date Event
2003-01-23 Priority Date for U.S. Patent No. 7,335,799
2008-02-26 Issue Date for U.S. Patent No. 7,335,799
2019-06-21 Priority Date for U.S. Patent No. 11,760,714
2019-06-21 Priority Date for U.S. Patent No. 11,613,511
2023-03-28 Issue Date for U.S. Patent No. 11,613,511
2023-09-19 Issue Date for U.S. Patent No. 11,760,714
2024-04-09 Date of Defendants' Notice Letter regarding ANDA submission
2024-05-23 Complaint Filing Date

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

U.S. Patent No. 7,335,799 - "Hydroxyl Compounds and Compositions for Cholesterol Management and Related Uses"

The Invention Explained

  • Problem Addressed: The patent background describes the link between conditions like obesity, hyperlipidemia, and diabetes and the prevalence of atherosclerotic cardiovascular diseases, along with the limitations of existing treatments for managing cholesterol and related metabolic disorders (’799 Patent, col. 2:23-52).
  • The Patented Solution: The invention provides a class of novel hydroxyl compounds, defined by a general chemical structure (Formula I), intended for treating these metabolic conditions (’799 Patent, Abstract). These compounds are characterized as long-chain dicarboxylic acids with specific alkyl substitutions and a hydroxyl group positioned along the carbon backbone, a structure designed to manage cholesterol and related disorders (’799 Patent, col. 3:45-60).
  • Technical Importance: The claimed compounds represent a class of non-statin therapies for managing lipid levels, addressing a need for alternatives or adjuncts to existing cholesterol treatments.

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 12 (Compl. ¶¶ 79, 80, 82).
  • Independent Claim 1 claims a compound of the formula (I), or a pharmaceutically acceptable salt, hydrate, solvate or mixture thereof, having the following essential elements:
    • A central core structure X, which is either an alkyl chain (CH2)z or a phenyl group Ph.
    • Two symmetric side chains attached to the core, each containing (CH2)n and (CH2)m linkers.
    • A central hydroxyl group (OH) attached to the core structure.
    • Terminal groups Y¹ and Y², which can be one of several specified chemical moieties including COOH.
    • Four specific substituent groups (R¹, R², R¹¹, and R¹²), which can be hydrogen or various organic groups, attached near the terminal ends.
  • The complaint reserves the right to assert additional claims (Compl. p. 1).

U.S. Patent No. 11,760,714 - "Methods of Making Bempedoic Acid and Compositions of the Same"

The Invention Explained

  • Problem Addressed: The patent addresses the significant technical challenge of developing robust, cost-effective, and efficient manufacturing methods for producing active pharmaceutical ingredients, such as bempedoic acid, with the high yield and purity required by regulatory agencies (’714 Patent, col. 1:17-29).
  • The Patented Solution: The invention is a pharmaceutical composition containing a highly purified crystalline form of bempedoic acid (identified as formula V). The solution specifies a composition where bempedoic acid constitutes greater than 98% by weight of the pharmaceutical material and, critically, limits the presence of a specific di-hydroxy impurity (formula VI) to a narrow range of 0.0001% to 0.15% (’714 Patent, col. 2:29-41).
  • Technical Importance: Claiming specific, high-purity compositions with defined low levels of a particular impurity provides a basis for patentability and market exclusivity separate from the compound itself, reflecting the technical achievement of a superior manufacturing process.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶¶ 92, 94).
  • Independent Claim 1 claims a pharmaceutical composition with the following essential elements:
    • A pharmaceutical material comprising a crystalline form of the compound of formula (V) (bempedoic acid) or its salt.
    • The compound of formula (V) is present in an amount greater than 98% by weight of the pharmaceutical material.
    • The pharmaceutical material comprises 0.0001% to less than or equal to 0.15% of a compound of formula (VI) (a specified impurity).
    • The composition includes a pharmaceutically acceptable excipient.
  • The complaint reserves the right to assert additional claims (Compl. p. 1).

U.S. Patent No. 11,613,511 - "Methods of Making Bempedoic Acid and Compositions of the Same"

  • Technology Synopsis: Like the ’714 Patent, this patent addresses the need for efficient manufacturing of high-purity bempedoic acid (’511 Patent, col. 1:17-29). The patented solution is a pharmaceutical material containing bempedoic acid at greater than 99.0% purity, limiting the same impurity as the ’714 Patent to less than 0.15%, and further defining the crystalline form by a specific set of X-ray powder diffraction (XRPD) peaks (’511 Patent, col. 2:41-54).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶¶ 104, 106).
  • Accused Features: The complaint alleges that Hetero's ANDA Product is a pharmaceutical material that will, upon manufacture, meet the specific purity, impurity, and crystalline structure (XRPD peak) requirements of claim 1 of the ’511 Patent (Compl. ¶¶ 104-105).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the "Hetero ANDA Product," a generic version of NEXLETOL® (bempedoic acid) for which Defendants have filed Abbreviated New Drug Application No. 219449 with the FDA (Compl. ¶¶ 1, 70).

Functionality and Market Context

  • The Hetero ANDA Product is alleged to have the same active pharmaceutical ingredient, dosage form, and strength as Plaintiff's NEXLETOL® product and is represented to the FDA as being bioequivalent (Compl. ¶72). NEXLETOL® is an ACL inhibitor used to lower LDL-C and reduce the risk of myocardial infarction and coronary revascularization in certain adult populations, positioning it as an alternative or adjunct to statin therapy (Compl. ¶66).

IV. Analysis of Infringement Allegations

U.S. Patent No. 7,335,799 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a compound of the formula (I) . . . or a pharmaceutically acceptable salt, hydrate, solvate or mixture thereof The complaint alleges the Hetero ANDA product contains bempedoic acid, which has the specific structure recited in dependent claim 12 and falls within the genus of compounds defined by formula (I). The complaint provides the chemical structure of bempedoic acid (Compl. ¶80). ¶79, ¶80 col. 3:45-60
wherein: . . . (b) each occurrence of n is independently an integer ranging from 3 to 7 The bempedoic acid molecule contains alkane chains corresponding to this requirement. ¶79 col. 4:1-2
(d) each occurrence of R¹, R², R¹¹, and R¹² is independently H, (C₁-C₆)alkyl . . . The bempedoic acid molecule has four methyl groups (-CH₃), which are (C₁-C₆)alkyl groups, at the specified positions. ¶79 col. 4:6-12
(e) each occurrence of Y¹ and Y² is independently . . . COOH . . . The bempedoic acid molecule has two terminal carboxylic acid (-COOH) groups. ¶79 col. 4:15-18
  • Identified Points of Contention:
    • Scope Questions: The complaint asserts both the broad genus claim (Claim 1) and the specific species claim (Claim 12) that explicitly recites the structure of bempedoic acid. A primary infringement question will be whether Defendants' product is, in fact, bempedoic acid. The dispute may focus more on the validity of the claims rather than direct infringement, should the product composition be confirmed.
    • Technical Questions: A key technical question is one of chemical identity: does the active pharmaceutical ingredient in the Hetero ANDA Product possess the exact chemical structure of 8-Hydroxy-2,2,14,14-tetramethyl-pentadecanedioic acid, as required by claim 12 and alleged by the complaint (Compl. ¶80)?

U.S. Patent No. 11,760,714 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition, comprising: a pharmaceutical material comprising a crystalline form of the compound of formula (V) . . . or a pharmaceutically acceptable salt thereof The complaint alleges that the Hetero ANDA Product is a pharmaceutical composition containing a crystalline form of bempedoic acid (formula V). The complaint includes a chemical structure diagram for formula (V) (Compl. ¶92). ¶92 col. 2:29-35
wherein the pharmaceutical material comprises the compound of formula (V) . . . in an amount greater than 98% by weight . . . The complaint alleges on information and belief that upon commercial manufacture, the Hetero ANDA Product will meet this purity requirement. ¶92, ¶95 col. 2:35-39
and the pharmaceutical material comprises 0.0001% to less than or equal to 0.15% of a compound of formula (VI) The complaint alleges on information and belief that upon commercial manufacture, the Hetero ANDA Product will contain the specified impurity (formula VI) within this narrow percentage range. The complaint provides a chemical structure for formula (VI) (Compl. ¶92). ¶92, ¶95 col. 2:39-42
and a pharmaceutically acceptable excipient. The complaint alleges the Hetero ANDA product, as a pharmaceutical composition, necessarily includes one or more pharmaceutically acceptable excipients. ¶92 col. 2:42-43
  • Identified Points of Contention:
    • Scope Questions: A central question is whether the phrase "comprising a crystalline form" requires only that some portion of the active ingredient be crystalline, or if it must be substantially or entirely crystalline.
    • Technical Questions: A key evidentiary question is what proof exists that the Hetero ANDA Product, as described in the ANDA and as will be commercially manufactured, will necessarily meet the specific purity (>98%) and impurity (0.0001% - 0.15%) limitations of claim 1. The dispute will likely turn on analytical testing data and the specifications contained within ANDA No. 219449.

V. Key Claim Terms for Construction

  • The Term: "crystalline form" (from ’714 Patent, Claim 1 and ’511 Patent, Claim 1)
  • Context and Importance: This term is critical because infringement of the ’714 and ’511 patents requires the accused product to contain bempedoic acid in a "crystalline form." Practitioners may focus on this term because a defendant could potentially design around the patents by formulating the drug in an amorphous (non-crystalline) state or in a different, unclaimed polymorphic crystalline form.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: Claim 1 of the ’714 Patent broadly recites "a crystalline form" without specifying any particular polymorph, which may suggest that any crystalline structure of bempedoic acid meets the limitation (’714 Patent, col. 82:12-14).
    • Evidence for a Narrower Interpretation: The ’511 Patent specification and claims define a specific crystalline form by its characteristic X-ray powder diffraction peaks (’511 Patent, col. 10:20-25; col. 22:41-47). A defendant may argue that the term "crystalline form" in the related ’714 patent should be interpreted in light of these more specific disclosures, or that the term as used in the ’511 patent is strictly limited to the form exhibiting the recited peaks.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will induce and contribute to infringement of all asserted patents. The allegations are based on Defendants’ knowledge of the patents, evidenced by the Orange Book listing and the notice letter, coupled with their intent to market the generic product with instructions that will encourage doctors and patients to make, use, or sell the claimed inventions (Compl. ¶¶ 85-86, 97-98, 109-110). It is also alleged that the Hetero ANDA Product is not suitable for substantial non-infringing use (Compl. ¶¶ 86, 98, 110).
  • Willful Infringement: While the complaint does not explicitly use the term "willful," it alleges that Hetero had knowledge of the Asserted Patents at the time it submitted its ANDA (Compl. ¶74). It further alleges knowledge based on the patents' listing in the FDA's Orange Book and the receipt of Esperion's notice letter, establishing a basis for pre-suit knowledge (Compl. ¶¶ 84, 96, 108). The prayer for relief seeks a declaration that this is an "exceptional case" warranting an award of attorneys' fees, which is often predicated on findings of willful infringement or other litigation misconduct (Compl. ¶120).

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

  • A core issue will be one of evidentiary proof: For the composition patents (’714 and ’511), can Plaintiff demonstrate that Defendants’ product, as detailed in its ANDA and intended for commercial sale, will necessarily meet the very specific quantitative thresholds for purity (>98% or >99%) and a particular impurity (<0.15%)? The outcome may depend heavily on the analytical chemistry data within the confidential ANDA filing.
  • A key technical question will be one of structural identity: For the ’511 patent, which claims a specific crystalline polymorph defined by XRPD peaks, does the accused product actually exhibit that precise crystal structure? This will likely be resolved by a direct comparison of analytical data and may involve disputes over the significance of minor variations in XRPD patterns.
  • The central legal question will likely be one of validity: Given that the active ingredient bempedoic acid is known, can Defendants successfully argue that claims to the compound itself (’799 Patent) or to highly purified, specific crystalline compositions thereof (’714 and ’511 patents) are invalid as anticipated by or obvious in view of the prior art?