DCT
2:24-cv-06348
Esperion Therap Inc v. Aurobindo Pharma Ltd
Key Events
Amended Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Esperion Therapeutics, Inc. (Delaware)
- Defendant: Aurobindo Pharma Limited (India); Apitoria Pharma Private Limited (India)
- Plaintiff’s Counsel: Walsh Pizzi Oreilly Falanga LLP
- Case Identification: 2:24-cv-06348, D.N.J., 06/25/2024
- Venue Allegations: Plaintiff alleges venue is proper because Defendants are corporations organized under the laws of India, are not residents of the United States, and thus may be sued in any jurisdiction. The complaint also alleges that Defendants have a regular and established place of business in New Jersey.
- Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's cholesterol-lowering drug NEXLETOL® constitutes an act of infringement of three U.S. patents covering compositions and methods of using bempedoic acid.
- Technical Context: The technology concerns pharmaceutical compositions of bempedoic acid, an inhibitor of adenosine triphosphate-citrate lyase (ACL) used to lower low-density lipoprotein cholesterol (LDL-C) in adults.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 219349 and issuance of Paragraph IV certifications asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed. The complaint notes that Defendants sent two separate notice letters, one for U.S. Patent Nos. 11,760,714 and 11,613,511, and a later one for U.S. Patent No. 11,926,584 after it was listed in the FDA's Orange Book.
Case Timeline
| Date | Event |
|---|---|
| 2019-06-21 | Earliest Patent Priority Date for all Asserted Patents |
| 2020-02-21 | FDA approves Plaintiff's New Drug Application for NEXLETOL® |
| 2023-03-28 | U.S. Patent No. 11,613,511 issues |
| 2023-09-19 | U.S. Patent No. 11,760,714 issues |
| 2024-03-12 | U.S. Patent No. 11,926,584 issues |
| 2024-04-09 | Plaintiff submits U.S. Patent No. 11,926,584 for Orange Book listing |
| 2024-04-10 | Plaintiff receives "First Notice Letter" regarding ANDA submission |
| 2024-05-22 | Original complaint filed by Plaintiff |
| 2024-06-07 | Plaintiff receives "Second Notice Letter" for the '584 Patent |
| 2024-06-25 | First Amended Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,760,714 - "Methods of Making Bempedoic Acid and Compositions of the Same"
- Patent Identification: U.S. Patent No. 11,760,714, "Methods of Making Bempedoic Acid and Compositions of the Same," issued September 19, 2023 (’714 Patent). (Compl. ¶40).
The Invention Explained
- Problem Addressed: The patent background describes the "significant challenge" in developing robust, cost-effective, and efficient manufacturing methods for pharmaceutical compounds that achieve the yield and purity required by regulatory agencies (’714 Patent, col. 1:19-29).
- The Patented Solution: The invention claims to provide a pharmaceutical composition containing bempedoic acid (formula V) that is highly pure and contains a very low, specified amount of a particular diol impurity (formula VI) (’714 Patent, Abstract; col. 2:30-41). This is intended to create a product suitable for use as an active pharmaceutical ingredient that meets regulatory standards (’714 Patent, col. 1:26-29).
- Technical Importance: Controlling specific impurities to very low levels is critical in pharmaceutical manufacturing to ensure product safety, efficacy, and stability, and to secure regulatory approval for commercial sale (’714 Patent, col. 1:26-29).
Key Claims at a Glance
- The complaint asserts at least Claim 1 of the ’714 Patent (Compl. ¶74).
- The essential elements of independent Claim 1 are:
- A pharmaceutical composition comprising a pharmaceutical material, which in turn comprises a crystalline form of bempedoic acid (formula V) or its salt.
- The pharmaceutical material contains the bempedoic acid or its salt in an amount greater than 98% by weight.
- The pharmaceutical material comprises between 0.0001% and 0.15% of a diol impurity (formula VI).
- The composition further comprises a pharmaceutically acceptable excipient.
U.S. Patent No. 11,613,511 - "Methods of Making Bempedoic Acid and Compositions of the Same"
- Patent Identification: U.S. Patent No. 11,613,511, "Methods of Making Bempedoic Acid and Compositions of the Same," issued March 28, 2023 (’511 Patent). (Compl. ¶43).
The Invention Explained
- Problem Addressed: The patent addresses the same challenge as the ’714 Patent: the difficulty of producing high-purity bempedoic acid suitable for commercial pharmaceutical use (’511 Patent, col. 1:19-29).
- The Patented Solution: This invention defines not only a high-purity composition with low levels of a specific diol impurity, but also specifies a particular crystalline form of the bempedoic acid, characterized by a unique X-ray powder diffraction (XRPD) pattern (’511 Patent, Abstract; col. 2:30-56). By claiming a specific polymorph, the patent aims to secure a stable and consistently manufacturable form of the drug substance.
- Technical Importance: Identifying and claiming a specific, stable crystalline polymorph of a drug is crucial for ensuring consistent dissolution rates, bioavailability, and manufacturability of the final drug product (’511 Patent, col. 5:1-10).
Key Claims at a Glance
- The complaint asserts at least Claim 1 of the ’511 Patent (Compl. ¶86).
- The essential elements of independent Claim 1 are:
- A pharmaceutical material comprising a crystalline form of bempedoic acid (formula V) or its salt.
- The material contains the bempedoic acid or its salt in an amount greater than 99.0% by weight.
- The material comprises between 0.0001% and 0.15% of a diol impurity (formula VI).
- The crystalline form exhibits an X-ray powder diffraction pattern with peaks at specific 2θ angles: 10.3±0.2, 10.4±0.2, 17.9±0.2, 18.8±0.2, 19.5±0.2, and 20.7±0.2.
U.S. Patent No. 11,926,584 - "Methods of Making Bempedoic Acid and Compositions of the Same"
- Patent Identification: U.S. Patent No. 11,926,584, "Methods of Making Bempedoic Acid and Compositions of the Same," issued March 12, 2024 (’584 Patent). (Compl. ¶46).
Technology Synopsis
This patent claims a method of lowering low-density lipoprotein cholesterol (LDL-C) in a human. The method comprises administering a pharmaceutical material that is defined by the same high-purity (>99.0%) and low-impurity (<0.15% of formula VI) characteristics as the composition claimed in the ’511 Patent (Compl. ¶95).
Asserted Claims
At least Claim 1 is asserted (Compl. ¶97).
Accused Features
Plaintiff alleges that Defendants will induce infringement of this method patent by marketing their ANDA product with a package insert that instructs patients and medical practitioners to administer the drug for lowering LDL-C (Compl. ¶¶99-102).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendants’ proposed generic version of NEXLETOL® (bempedoic acid), for which Abbreviated New Drug Application No. 219349 was submitted to the FDA (Compl. ¶¶1, 14).
Functionality and Market Context
The complaint alleges that the "Aurobindo ANDA Product" contains the same active pharmaceutical ingredient, bempedoic acid, and is represented to have the same dosage form, strength, and bioequivalence as NEXLETOL® (Compl. ¶58). NEXLETOL® is an ACL inhibitor used to lower LDL-C in certain adults (Compl. ¶52). Defendants seek FDA approval to manufacture and sell this generic product in the United States prior to the expiration of the Asserted Patents (Compl. ¶14). The complaint provides a chemical structure diagram of the active ingredient, bempedoic acid (formula (V)) (Compl. ¶53).
IV. Analysis of Infringement Allegations
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 on information and belief that the Aurobindo ANDA Product is a pharmaceutical composition containing a crystalline form of bempedoic acid. | ¶¶72, 73 | col. 2:42-45 |
| 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 the pharmaceutical material in the Aurobindo ANDA Product will contain bempedoic acid at a purity level greater than 98% by weight. | ¶¶72, 73 | col. 2:48-52 |
| 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 the pharmaceutical material in the Aurobindo ANDA Product will contain the specified diol impurity (formula VI) within the claimed range of 0.0001% to 0.15%. | ¶¶72, 73 | col. 51:40-52 |
| and a pharmaceutically acceptable excipient. | The complaint alleges on information and belief that the Aurobindo ANDA Product, as a pharmaceutical composition, will contain one or more pharmaceutically acceptable excipients. | ¶¶72, 73 | col. 4:5-9 |
U.S. Patent No. 11,613,511 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a pharmaceutical material comprising a crystalline form of the compound of formula (V) ... or a pharmaceutically acceptable salt thereof; | The complaint alleges on information and belief that the Aurobindo ANDA Product is a pharmaceutical material containing a crystalline form of bempedoic acid. | ¶¶84, 85 | col. 2:42-45 |
| wherein the pharmaceutical material comprises the compound of formula (V) ... in an amount greater than 99.0% by weight ... | The complaint alleges on information and belief that the material in the Aurobindo ANDA Product will have a bempedoic acid purity level greater than 99.0% by weight. | ¶¶84, 85 | col. 2:48-52 |
| 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 the material in the Aurobindo ANDA Product will contain the specified diol impurity (formula VI) within the claimed range. | ¶¶84, 85 | col. 51:40-52 |
| and the crystalline form of the compound of formula (V) exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 10.3±0.2, 10.4±0.2, 17.9±0.2, 18.8±0.2, 19.5±0.2, and 20.7±0.2. | The complaint alleges on information and belief that the crystalline bempedoic acid in the Aurobindo ANDA Product will exhibit an XRPD pattern with the claimed peaks. | ¶¶84, 85 | col. 10:35-40 |
Identified Points of Contention
- Evidentiary Questions: The complaint's infringement allegations are based on "information and belief" stemming from the ANDA submission. The central points of contention will be factual and evidentiary: does the Aurobindo ANDA Product, upon testing and analysis during discovery, actually meet the specific quantitative limitations for purity (>98% for ’714; >99.0% for ’511), the narrow range for the diol impurity (<0.15%), and the specific XRPD peaks required by the ’511 Patent?
- Scope Questions: A potential area of dispute for the ’511 Patent may involve polymorphism. A question for the court could be whether the term "crystalline form" in conjunction with the listed XRPD peaks is limited to the specific polymorph characterized in the patent's specification, and whether Defendants' product contains that exact form or a different one that may or may not fall within the claim's scope.
V. Key Claim Terms for Construction
"crystalline form"
- Context and Importance: This term is fundamental to the composition claims of both the ’714 and ’511 Patents. For the ’511 Patent, its construction is critical because infringement requires that the accused product not only be crystalline but also exhibit a specific XRPD pattern. Practitioners may focus on whether this term, as used in the patents, is limited to a single, specific polymorph or could encompass other crystalline structures of bempedoic acid.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discloses various crystalline salt forms of bempedoic acid, such as calcium salt and lysine salt forms, each with unique characterizations (’511 Patent, col. 12:31-36). A party could argue this shows the inventors did not intend to limit the general term "crystalline form" to a single structure unless further specified by limitations like XRPD peaks.
- Evidence for a Narrower Interpretation: The specification provides a highly detailed characterization of one specific crystalline form of bempedoic acid, including its monoclinic crystal system, P2₁/c space group, and specific unit cell parameters (’511 Patent, Table 2, col. 11:29-41). A party could cite this detailed disclosure as evidence that the inventors' contribution was this specific polymorph, suggesting a narrower construction.
"pharmaceutical material"
- Context and Importance: The purity (>98% or >99.0%) and impurity (<0.15%) limitations are measured against the "total weight of the pharmaceutical material." The definition of this term is therefore critical for the infringement analysis. The dispute will likely center on what components are included in the denominator for this percentage calculation—is it the pure API alone, or the API plus any residual solvents, reagents, or related substances from the manufacturing process?
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims distinguish between the "pharmaceutical material" and the "pharmaceutically acceptable excipient" (Compl. ¶72). This suggests the "material" is the drug substance before it is formulated with fillers and binders, and could therefore include more than just the pure bempedoic acid molecule.
- Evidence for a Narrower Interpretation: The patent abstract describes methods of making a "pharmaceutical material comprising a purified amount of 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid" (’511 Patent, Abstract). This language could support an argument that the "pharmaceutical material" is defined by and coextensive with the purified API itself, which would narrow the basis for the weight percentage calculations.
VI. Other Allegations
Indirect Infringement
The complaint alleges both induced and contributory infringement for all three patents (Compl. ¶¶74, 77, 78, 86, 89, 90). For the ’584 method patent, inducement is based on allegations that Defendants' proposed product label will instruct and encourage medical professionals and patients to administer the drug for lowering LDL-C, which is the claimed method (Compl. ¶¶99, 102). For all patents, contributory infringement is based on allegations that the Aurobindo ANDA Product is especially made for an infringing use and is not suitable for a substantial noninfringing use (Compl. ¶¶78, 90, 106).
Willful Infringement
The complaint does not use the term "willful," but it lays the foundation for such a claim by alleging pre-suit knowledge. It asserts that Defendants had knowledge of the Asserted Patents through their listing in the FDA's Orange Book and, specifically, from the dates they sent their Paragraph IV certification notice letters to Esperion (Compl. ¶¶76, 88, 104). The prayer for relief requests a finding of an "exceptional case" under 35 U.S.C. § 285 (Compl. ¶116).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: what does a technical analysis of the Aurobindo ANDA Product reveal about its exact chemical composition and solid-state structure? Specifically, does the evidence show that the product meets the stringent quantitative claim limitations for purity, the specific diol impurity, and the crystallographic fingerprint defined by the XRPD peaks?
- A key question of claim scope related to the ’511 Patent will be the definition of the claimed "crystalline form." The case may turn on whether the claim covers only the specific polymorph detailed in the specification or is broad enough to read on other crystalline forms of bempedoic acid, and whether the accused product embodies the former or the latter.
- A dispositive issue for the ’584 method patent will be indirect infringement: assuming the Aurobindo product is found to meet the composition limitations recited in the method claim, will the instructions in its proposed product label be sufficient to establish that Defendants actively induced doctors and patients to perform the patented method of lowering LDL-C?