DCT
2:24-cv-06387
Esperion Therap Inc v. Sandoz Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Esperion Therapeutics, Inc. (Delaware)
- Defendant: Sandoz Inc. (Delaware)
- Plaintiff’s Counsel: Walsh Pizzi Oreilly Falanga LLP
- Case Identification: 2:24-cv-06387, D.N.J., 05/23/2024
- Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Sandoz is a corporation with its principal place of business in New Jersey, is subject to personal jurisdiction, and has committed acts of infringement in the district.
- Core Dispute: Plaintiff alleges that Defendant’s submission of Abbreviated New Drug Applications (ANDAs) to seek approval for generic versions of Plaintiff's NEXLETOL® and NEXLIZET® products constitutes infringement of five patents related to the active pharmaceutical ingredient bempedoic acid, its compositions, and methods of use.
- Technical Context: The technology relates to pharmaceutical treatments for high cholesterol, a significant risk factor for cardiovascular disease, by providing specific high-purity forms of bempedoic acid and fixed-dose combinations with ezetimibe.
- Key Procedural History: The action arises from Defendant’s submission of ANDAs containing Paragraph IV certifications, which assert that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by the proposed generic products. The filing of such an application is a statutory act of infringement under the Hatch-Waxman Act.
Case Timeline
| Date | Event |
|---|---|
| 2015-03-31 | Priority Date for ’751 and ’816 Patents |
| 2019-06-21 | Priority Date for ’584, ’714, and ’511 Patents |
| 2020-02-21 | FDA approves Esperion’s NEXLETOL® product |
| 2020-02-26 | FDA approves Esperion’s NEXLIZET® product |
| 2021-02-09 | U.S. Patent No. 10,912,751 issues |
| 2023-03-28 | U.S. Patent No. 11,613,511 issues |
| 2023-09-05 | U.S. Patent No. 11,744,816 issues |
| 2023-09-19 | U.S. Patent No. 11,760,714 issues |
| 2024-03-12 | U.S. Patent No. 11,926,584 issues |
| 2024-04-08 | Sandoz sends Paragraph IV Notice Letter for NEXLETOL® |
| 2024-04-24 | Sandoz sends amended Notice Letter for NEXLETOL® |
| 2024-04-24 | Sandoz sends Paragraph IV Notice Letter for NEXLIZET® |
| 2024-05-23 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,926,584 - “Methods of Making Bempedoic Acid and Compositions of the Same”
- Issued: March 12, 2024
The Invention Explained
- Problem Addressed: The complaint does not contain the patent specification, but the asserted claim addresses the medical problem of lowering low-density lipoprotein cholesterol (LDL-C) in humans (Compl. ¶80). Pharmaceutical development often faces the challenge of producing an active pharmaceutical ingredient with high purity and a well-controlled, minimal impurity profile to ensure safety and efficacy.
- The Patented Solution: The patent claims a method of lowering LDL-C by administering a pharmaceutical material containing a crystalline form of bempedoic acid (identified as formula V) that meets stringent purity requirements (’584 Patent, col. 29:56–col. 30:23). Specifically, the material must contain more than 99.0% bempedoic acid by weight, while also containing a specific dihydroxy impurity (formula VI) within a narrow range of 0.0001% to 0.15% (Compl. ¶80). The chemical structure for the claimed compound of formula (V) and the impurity of formula (VI) are depicted in the complaint (Compl. ¶80).
- Technical Importance: Controlling the purity and specific impurity profile of an active pharmaceutical ingredient is critical for regulatory approval and ensuring consistent clinical performance and safety.
Key Claims at a Glance
- The complaint asserts at least Claim 1 (Compl. ¶¶82, 96).
- Essential elements of independent Claim 1 include:
- A method of lowering low-density lipoprotein cholesterol (LDL-C) in a human in need thereof.
- Comprising administering a therapeutically effective amount of a pharmaceutical material.
- The pharmaceutical material comprises a crystalline form of the compound of formula (V) (bempedoic acid).
- The pharmaceutical material comprises the compound of formula (V) in an amount greater than 99.0% by weight.
- The pharmaceutical material comprises 0.0001% to less than or equal to 0.15% of a compound of formula (VI) (an impurity).
U.S. Patent No. 11,760,714 - “Methods of Making Bempedoic Acid and Compositions of the Same”
- Issued: September 19, 2023
The Invention Explained
- Problem Addressed: Similar to the ’584 Patent, the invention addresses the technical challenge of creating a stable and effective pharmaceutical composition with a highly pure active ingredient for treating cholesterol-related conditions (’714 Patent, col. 1:19–29).
- The Patented Solution: The patent claims a pharmaceutical composition, rather than a method of use, that contains the highly purified bempedoic acid (’714 Patent, col. 29:60–col. 30:25). The claimed composition includes a pharmaceutical material comprising a crystalline form of bempedoic acid (formula V) at a purity of greater than 98%, a specified limit on the dihydroxy impurity (formula VI) of 0.0001% to 0.15%, and a pharmaceutically acceptable excipient (Compl. ¶112).
- Technical Importance: Defining a drug product by the purity of its active ingredient and the level of a specific impurity provides a distinct way to claim a composition, potentially distinguishing it from prior art that may disclose the compound without such rigorous purity controls.
Key Claims at a Glance
- The complaint asserts at least Claim 1 (Compl. ¶¶114, 124).
- Essential elements of independent Claim 1 include:
- A pharmaceutical composition.
- Comprising a pharmaceutical material, which in turn comprises a crystalline form of the compound of formula (V).
- The pharmaceutical material comprises the compound of formula (V) in an amount greater than 98% by weight.
- The pharmaceutical material comprises 0.0001% to less than or equal to 0.15% of a compound of 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”
- Issued: March 28, 2023
- Technology Synopsis: This patent claims a pharmaceutical material, distinguished not only by its high purity (>99.0% bempedoic acid) and low impurity levels (0.0001-0.15% of formula VI), but also by a specific crystalline structure identified by a unique X-ray powder diffraction (XRPD) pattern (’511 Patent, col. 30:5-24). This links the specific purity profile to a defined solid-state form of the drug substance.
- Asserted Claims: At least Claim 1 (Compl. ¶¶138, 149).
- Accused Features: The Sandoz NEXLETOL® and NEXLIZET® ANDA products are alleged to be or contain the claimed high-purity, specific crystalline pharmaceutical material (Compl. ¶¶137, 148).
U.S. Patent No. 10,912,751 - “Fixed Dose Combinations and Formulations Comprising ETC1002 and Ezetimibe and Methods of Treating or Reducing the Risk of Cardiovascular Disease”
- Issued: February 9, 2021
- Technology Synopsis: The patent addresses treatment for familial hypercholesterolemia, a genetic disorder causing very high cholesterol levels (’751 Patent, Abstract). The invention is a method of treatment comprising administering a fixed-dose combination of 180 mg of bempedoic acid and 10 mg of ezetimibe (’751 Patent, col. 25:40-49).
- Asserted Claims: At least Claim 1 (Compl. ¶160).
- Accused Features: The Sandoz NEXLIZET® ANDA product, which is a fixed-dose combination of bempedoic acid and ezetimibe, is alleged to infringe, and its proposed label is alleged to induce infringement of the claimed method (Compl. ¶¶159, 162-163).
U.S. Patent No. 11,744,816 - “Fixed Dose Combinations and Formulations Comprising ETC1002 and Ezetimibe and Methods of Treating or Reducing the Risk of Cardiovascular Disease”
- Issued: September 5, 2023
- Technology Synopsis: This patent, related to the ’751 Patent, also claims a method of lowering LDL-C in subjects with familial hypercholesterolemia (’816 Patent, Abstract). The claimed method requires administering a combination of 180 mg of bempedoic acid and 10 mg of ezetimibe (’816 Patent, col. 25:40-47).
- Asserted Claims: At least Claim 1 (Compl. ¶176).
- Accused Features: Sandoz’s NEXLIZET® ANDA product is alleged to infringe the claimed method, with infringement induced by the product's proposed label instructing administration for the claimed purpose (Compl. ¶¶175, 178-179).
III. The Accused Instrumentality
Product Identification
Sandoz’s proposed generic drug products to be marketed under ANDA No. 219347 (a generic version of NEXLETOL®) and ANDA No. 219346 (a generic version of NEXLIZET®) (Compl. ¶¶8, 12).
Functionality and Market Context
- The Sandoz NEXLETOL® ANDA Product is alleged to contain bempedoic acid as its active pharmaceutical ingredient and to be bioequivalent to Esperion’s NEXLETOL® (Compl. ¶62). NEXLETOL® is an adenosine triphosphate-citrate lyase (ACL) inhibitor indicated to reduce LDL-C and the risk of certain cardiovascular events (Compl. ¶47).
- The Sandoz NEXLIZET® ANDA Product is alleged to be a combination of bempedoic acid and ezetimibe and to be bioequivalent to Esperion's NEXLIZET® (Compl. ¶70). NEXLIZET® combines an ACL inhibitor with a cholesterol absorption inhibitor for lowering LDL-C (Compl. ¶52).
- The complaint alleges that by filing its ANDAs, Sandoz seeks FDA approval to engage in the commercial manufacture, use, and sale of these products prior to the expiration of the patents-in-suit (Compl. ¶¶61, 69).
IV. Analysis of Infringement Allegations
'584 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of lowering low-density lipoprotein cholesterol (LDL-C) in a human in need thereof | Sandoz’s proposed package insert will allegedly instruct patients and medical practitioners to administer the Sandoz NEXLETOL® and NEXLIZET® ANDA products for the purpose of lowering LDL-C. | ¶87, ¶103 | col. 29:56-58 |
| comprising administering to the human a therapeutically effective amount of a pharmaceutical material | The package insert will allegedly instruct administration of the ANDA products, which contain what is alleged to be the claimed pharmaceutical material. | ¶87, ¶103 | col. 29:58-60 |
| comprising a crystalline form of the compound of formula (V) | Sandoz’s ANDA products allegedly contain a crystalline form of bempedoic acid (formula V), the active pharmaceutical ingredient. | ¶87, ¶103 | col. 29:60-65 |
| wherein the pharmaceutical material comprises the compound of formula (V) ... in an amount greater than 99.0% by weight | The pharmaceutical material in Sandoz's ANDA products allegedly contains bempedoic acid at a purity level of greater than 99.0% by weight. | ¶87, ¶103 | col. 30:6-10 |
| and the pharmaceutical material comprises 0.0001 % to less than or equal to 0.15% of a compound of formula (VI) | The pharmaceutical material in Sandoz’s ANDA products allegedly contains the specified impurity of formula (VI) within the claimed narrow range. | ¶87, ¶103 | col. 30:10-23 |
Identified Points of Contention:
- Scope Questions: A central question for this method claim will be whether Sandoz’s proposed product label will be found to encourage, recommend, or promote an infringing use, thereby meeting the legal standard for inducement.
- Technical Questions: The factual dispute will likely center on the composition of Sandoz's products. Does the pharmaceutical material in Sandoz's ANDA products meet both the >99.0% purity threshold for bempedoic acid and the 0.0001-0.15% window for the formula (VI) impurity, as alleged by the complaint?
'714 Patent 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) | Sandoz's NEXLETOL® and NEXLIZET® ANDA products are alleged to be pharmaceutical compositions that contain a pharmaceutical material comprising a crystalline form of bempedoic acid. | ¶112, ¶124 | col. 29:60-65 |
| wherein the pharmaceutical material comprises the compound of formula (V) ... in an amount greater than 98% by weight | The pharmaceutical material within Sandoz’s products allegedly contains bempedoic acid at a purity level greater than 98%. | ¶112, ¶124 | col. 30:1-5 |
| and the pharmaceutical material comprises 0.0001 % to less than or equal to 0.15% of a compound of formula (VI) | The pharmaceutical material within Sandoz’s products allegedly contains the specified impurity of formula (VI) within the claimed narrow concentration range. | ¶112, ¶124 | col. 30:5-18 |
| and a pharmaceutically acceptable excipient. | Sandoz's ANDA products are formulated as drug products and therefore allegedly contain at least one pharmaceutically acceptable excipient. | ¶112, ¶124 | col. 30:19-20 |
Identified Points of Contention:
- Scope Questions: A potential dispute may arise over the definition of "pharmaceutical material" and whether the purity calculations are based on the active ingredient alone or in combination with other substances. The claim's structure, which lists the "excipient" as a separate element from the "pharmaceutical material," may support a narrower interpretation that the purity is measured on the active ingredient before formulation.
- Technical Questions: What evidence does the complaint provide that Sandoz's products will meet the specific purity (>98%) and impurity (0.0001%-0.15%) limitations? This is an issue that will likely be resolved through expert analysis of the ANDA filings and product samples.
V. Key Claim Terms for Construction
The Term: "crystalline form"
- Context and Importance: This term appears in the independent claims of the ’584, ’714, and ’511 patents. The ’511 Patent explicitly defines a crystalline form with specific X-ray powder diffraction peaks (Compl. ¶136), but the ’584 and ’714 patents do not. The infringement analysis will depend heavily on whether Sandoz's generic product, which must be the "same" active ingredient, is considered to have the same "crystalline form" as that protected by the patents. Practitioners may focus on this term because Sandoz could argue its product utilizes a different, non-infringing polymorph of bempedoic acid.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party could argue that, in the context of the ’584 and ’714 patents, the term should be given its plain and ordinary meaning, covering any form of bempedoic acid that is crystalline, as opposed to amorphous.
- Evidence for a Narrower Interpretation: A party could point to the specification of the related ’511 Patent, which discloses a specific polymorph with characteristic XRPD peaks (’511 Patent, col. 30:12-24). This could be used to argue that "crystalline form" across the patent family should be construed more narrowly to refer to the specific polymorph(s) disclosed and enabled in the patent specifications.
The Term: "pharmaceutical material"
- Context and Importance: This term is the basis for the purity limitations in the ’584, ’714, and ’511 patents (e.g., >99.0% by weight based on the total weight of the pharmaceutical material). The definition is critical to the infringement analysis, as the denominator in the purity calculation depends on what is included in the "material."
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue this term encompasses the active ingredient plus any residual processing aids or synthesis byproducts, providing a larger "total weight" and making the purity threshold harder to meet.
- Evidence for a Narrower Interpretation: The structure of Claim 1 of the ’714 Patent recites "a pharmaceutical material ... and a pharmaceutically acceptable excipient" as distinct elements of the overall "pharmaceutical composition" (Compl. ¶112). This suggests the "pharmaceutical material" is the drug substance (API) itself, separate from the excipients it is later formulated with, supporting a construction where purity is measured on the API alone.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement. Induced infringement allegations are based on the assertion that Sandoz’s proposed package inserts will instruct and encourage medical professionals and patients to administer the generic products in a manner that directly infringes the asserted method claims (Compl. ¶¶84, 100, 117, 129, 162, 178). Contributory infringement is alleged on the basis that Sandoz’s products are especially made for an infringing use and have no substantial non-infringing use (Compl. ¶¶91, 107, 118, 130).
- Willful Infringement: The complaint does not use the word “willful” in its counts but alleges facts that could support such a claim. It asserts that Sandoz has knowledge of the patents-in-suit through their listing in the FDA’s Orange Book and through the Paragraph IV notice letters sent to Esperion (Compl. ¶¶89, 116, 128, 140, 151, 167, 183). The complaint further alleges Sandoz is "willfully blind" to the fact that third parties will directly infringe (Compl. ¶¶90, 106, 168).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary issue will be one of analytical chemistry: Do the active pharmaceutical ingredients in Sandoz's ANDA products, upon chemical analysis, actually meet the specific purity (>98% or >99%) and impurity (0.0001%-0.15%) limitations recited in the claims, and do they possess the specific crystalline structure required by the ’511 patent?
- A key legal issue will be one of claim construction: Can the term "crystalline form," which is not explicitly defined by physical characteristics in the ’584 and ’714 patents, be construed narrowly to cover only the specific polymorph disclosed in the related ’511 patent, or will it be interpreted more broadly?
- A dispositive question for the method of treatment claims will be whether Sandoz's proposed product labels will be found to affirmatively instruct or encourage the specific methods of use claimed in the ’584, ’751, and ’816 patents, thereby satisfying the requirements for induced infringement.