DCT
2:24-cv-05921
Esperion Therap Inc v. Micro Labs USA Inc
Key Events
Amended Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Esperion Therapeutics, Inc. (Delaware)
- Defendant: Micro Labs USA, Inc. (New Jersey) and Micro Labs Limited (India)
- Plaintiff’s Counsel: Walsh Pizzi O'Reilly Falanga LLP
- Case Identification: 2:24-cv-05921, D.N.J., 06/21/2024
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Micro Labs USA, Inc. is a New Jersey corporation, and Defendant Micro Labs Limited, as a foreign corporation, may be sued in any judicial district. The complaint further alleges that both 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 the cholesterol-lowering drug NEXLETOL® constitutes an act of infringement of three U.S. patents covering purified compositions of bempedoic acid and methods of their use.
- Technical Context: The dispute centers on 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 Hatch-Waxman action was triggered by Defendants' notification to Plaintiff, via Paragraph IV certification letters, of their intent to market a generic version of NEXLETOL® prior to the expiration of the asserted patents. The complaint alleges Defendants contend the asserted patents are invalid, unenforceable, and/or will not be infringed.
Case Timeline
| Date | Event |
|---|---|
| 2019-06-21 | Earliest Priority Date for ’714, ’511, and ’584 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 |
| 2024-03-26 | Plaintiff receives First Notice Letter from Defendants regarding ’714 and ’511 Patents |
| 2024-04-09 | Plaintiff submits '584 Patent for Orange Book listing |
| 2024-04-26 | Defendants produce portions of ANDA No. 219182 to Plaintiff |
| 2024-05-08 | Plaintiff files original complaint |
| 2024-06-06 | Plaintiff receives Second Notice Letter from Defendants regarding ’584 Patent |
| 2024-06-21 | Plaintiff files First Amended Complaint |
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"
- Issued: September 19, 2023
The Invention Explained
- Problem Addressed: The patent addresses the challenge of developing robust, cost-effective, and efficient manufacturing methods for producing active pharmaceutical ingredients that meet the high yield and purity profiles required by regulatory agencies for commercial drug products (’511 Patent, col. 1:17-31).
- The Patented Solution: The invention is a pharmaceutical composition containing bempedoic acid (identified as the compound of formula (V)) in a crystalline form, characterized by a specific purity and impurity profile. The solution requires the bempedoic acid to be present in an amount greater than 98% by weight of the pharmaceutical material, while simultaneously limiting a specific diol impurity (the compound of formula (VI)) to a concentration between 0.0001% and 0.15% (Compl. ¶63; ’714 Patent, claim 1). The complaint provides a chemical structure diagram illustrating the active ingredient and the controlled impurity (Compl. ¶63).
- Technical Importance: For pharmaceutical products, controlling the purity of the active ingredient and minimizing specific impurities is critical for ensuring safety, efficacy, and stability, which are central requirements for regulatory approval and commercialization (’511 Patent, col. 1:26-31).
Key Claims at a Glance
- The complaint asserts infringement of at least Claim 1 (’714 Patent, claim 1; Compl. ¶65).
- Essential elements of independent Claim 1 include:
- A pharmaceutical composition, comprising:
- a pharmaceutical material comprising a crystalline form of the compound of formula (V) (bempedoic acid), or a pharmaceutically acceptable salt thereof;
- wherein the pharmaceutical material comprises the compound of formula (V) in an amount greater than 98% by weight based on the total weight of the pharmaceutical material;
- and the pharmaceutical material comprises 0.0001% to less than or equal to 0.15% of a compound of formula (VI);
- and a pharmaceutically acceptable excipient.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 11,613,511 - "Methods of Making Bempedoic Acid and Compositions of the Same"
- Issued: March 28, 2023
The Invention Explained
- Problem Addressed: As with the ’714 Patent, this patent addresses the need for high-purity bempedoic acid suitable for commercial pharmaceutical use (’511 Patent, col. 1:17-31).
- The Patented Solution: This invention narrows the composition by requiring not just high purity and low impurity levels, but also a specific crystalline form of bempedoic acid. The claimed crystalline form is defined by an X-ray powder diffraction (XRPD) pattern comprising peaks at specific diffraction angles, ensuring a particular solid-state structure, or polymorph, of the drug substance (’511 Patent, claim 1). The patent specification provides an exemplary XRPD pattern in Figure 4 that illustrates this crystalline structure (’511 Patent, Fig. 4).
- Technical Importance: Defining a specific crystalline polymorph of a drug is significant because different polymorphs can have different physical properties, such as solubility, stability, and bioavailability, which can directly impact a drug's performance and shelf-life.
Key Claims at a Glance
- The complaint asserts infringement of at least Claim 1 (’511 Patent, claim 1; Compl. ¶77).
- Essential elements of independent Claim 1 include:
- A pharmaceutical material comprising a crystalline form of the compound of formula (V), or a pharmaceutically acceptable salt thereof;
- wherein 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);
- 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 does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 11,926,584 - "Methods of Making Bempedoic Acid and Compositions of the Same"
- Issued: March 12, 2024 (the “’584 Patent”)
- Technology Synopsis: The ’584 Patent claims a method of treating a human patient to lower LDL-C. The claimed method requires administering a therapeutically effective amount of a pharmaceutical material that has the same high-purity (>99.0%) and low-impurity (≤0.15% of formula VI) profile as defined in the ’511 Patent (Compl. ¶86).
- Asserted Claims: The complaint asserts infringement of at least Claim 1 (Compl. ¶88).
- Accused Features: The accused features are the instructions for use that will allegedly be included in the proposed package insert for Defendants' generic product. The complaint alleges these instructions will direct patients and medical practitioners to administer the product for lowering LDL-C, thereby inducing infringement of the claimed method (Compl. ¶¶91, 93).
III. The Accused Instrumentality
Product Identification
- Defendants' proposed generic version of NEXLETOL® (bempedoic acid), which is the subject of ANDA No. 219182 submitted to the FDA (Compl. ¶1, ¶13).
Functionality and Market Context
- The accused product is a generic pharmaceutical intended to be a substitute for Plaintiff's NEXLETOL®. The complaint alleges that by submitting the ANDA, Defendants have represented to the FDA that their product contains the same active ingredient (bempedoic acid), has the same dosage form and strength as NEXLETOL®, and is bioequivalent to NEXLETOL® (Compl. ¶49).
- The product is an ACL inhibitor intended to lower LDL-C in adults with primary hyperlipidemia or who are at risk for cardiovascular events, to be used as an adjunct to diet and other therapies (Compl. ¶43). The complaint alleges Defendants seek approval to manufacture and sell the product before the expiration of the Asserted Patents (Compl. ¶48).
IV. Analysis of Infringement Allegations
11,760,714 Patent 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 | Defendants' ANDA product contains bempedoic acid, the compound of formula (V), which is alleged to be in a crystalline form. | ¶49, ¶63-¶64 | col. 52:32-34 |
| wherein the pharmaceutical material comprises the compound of formula (V)...in an amount greater than 98% by weight based on the total weight of the pharmaceutical material | It is alleged on information and belief that Defendants' ANDA product will contain bempedoic acid at a purity level of greater than 98% by weight. | ¶49, ¶63-¶64 | col. 52:43-47 |
| and the pharmaceutical material comprises 0.0001 % to less than or equal to 0.15% of a compound of formula (VI) | It is alleged on information and belief that Defendants' ANDA product will contain the specified impurity of formula (VI) within the claimed range of 0.0001% to 0.15%. A diagram of the formula (VI) impurity is shown in the complaint. | ¶63-¶64 | col. 52:51-55 |
| and a pharmaceutically acceptable excipient | Defendants' ANDA product is a formulated pharmaceutical composition that will necessarily contain one or more pharmaceutically acceptable excipients. | ¶49, ¶63-¶64 | col. 52:32-34 |
Identified Points of Contention
- Evidentiary Questions: A central issue will be whether Defendants’ ANDA product factually meets the quantitative limitations of Claim 1. What evidence, based on Defendants' ANDA filing, supports the allegation that the product contains >98% bempedoic acid and ≤0.15% of the specific formula (VI) impurity?
- Scope Questions: What is the scope of "crystalline form" in the context of this patent, which, unlike the ’511 Patent, does not define the term with specific XRPD peaks?
11,613,511 Patent 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) | Defendants' ANDA product contains bempedoic acid, which is alleged to be in the claimed crystalline form. - | ¶49, ¶75-¶76 | col. 52:1-2 |
| wherein the pharmaceutical material comprises the compound of formula (V)...in an amount greater than 99.0% by weight | It is alleged on information and belief that Defendants' ANDA product will contain bempedoic acid at a purity level of greater than 99.0% by weight. - | ¶49, ¶75--¶76 | col. 52:4-7 |
| the pharmaceutical material comprises 0.0001 % to less than or equal to 0.15% of a compound of formula (VI) | It is alleged on information and belief that Defendants' ANDA product will contain the specified impurity of formula (VI) within the claimed range. - | ¶49, ¶75-¶76 | col. 52:7-11 |
| 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 | It is alleged on information and belief that the crystalline form of bempedoic acid in Defendants' ANDA product will exhibit an XRPD pattern with peaks at the recited diffraction angles. | ¶75-¶76 | col. 52:12-17 |
Identified Points of Contention
- Technical Questions: Does the specific crystalline form of bempedoic acid in Defendants' ANDA product exhibit an XRPD pattern that includes peaks at all of the angular locations recited in Claim 1? The analysis may focus on whether there is a literal match for each recited peak within the claimed ±0.2 degree margin.
- Evidentiary Questions: As with the ’714 Patent, a key point of contention will be the factual evidence from the ANDA supporting the alleged purity (>99.0%) and impurity (≤0.15%) levels.
V. Key Claim Terms for Construction
- The Term: "pharmaceutical material"
- Context and Importance: This term appears in the preambles of the asserted composition claims of both the ’714 and ’511 patents and serves as the basis for the weight percentage calculations of purity and impurity. The definition of this term is critical because it determines the denominator for the claimed purity ratios (e.g., >98% or >99%). Practitioners may focus on this term because its scope—whether it is limited to the bempedoic acid API itself or could include other substances like processing aids or related compounds—directly impacts the infringement analysis.
- Intrinsic Evidence for Interpretation:
- Evidence for a Narrower Interpretation: The claims distinguish the "pharmaceutical material" from the "pharmaceutically acceptable excipient," suggesting the "pharmaceutical material" is the API portion of the final drug product, not the entire composition (Compl. ¶63, ¶75). The specification of the related ’511 Patent describes preparing a "pharmaceutical material comprising a compound of formula (V)...where the pharmaceutical material includes the compound...in an amount greater than 99.0% by weight based on the total weight of the pharmaceutical material," which may suggest that the "pharmaceutical material" is the high-purity API substance itself (’511 Patent, col. 2:48-55).
- Evidence for a Broader Interpretation: The complaint does not provide sufficient detail to identify intrinsic evidence supporting a broader interpretation.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all three patents. For the ’584 method of use patent, inducement is based on the allegation that Defendants' proposed package insert will instruct and encourage medical professionals and patients to administer the generic product to lower LDL-C (Compl. ¶¶91, 93). For the composition patents (’714 and ’511), inducement is alleged based on marketing and encouragement of infringing uses (Compl. ¶¶68, 80). Contributory infringement is alleged on the basis that Defendants know their product is especially made for an infringing use and is not suitable for substantial noninfringing use (Compl. ¶¶69, 81, 97).
- Willful Infringement: The complaint does not contain a formal count for willful infringement but alleges facts that may support such a claim. It asserts that Defendants had knowledge of the ’714 and ’511 Patents through their listing in the Orange Book and through the First Notice Letter (Compl. ¶¶67, 79). For the ’584 Patent, knowledge is alleged based on its Orange Book listing and the Second Notice Letter, and the complaint further alleges Defendants are "willfully blind to the fact that patients, medical practitioners, and/or other third parties will...directly infringe" (Compl. ¶¶95, 96).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: What do the technical specifications within Defendants' confidential ANDA submission reveal about their generic product? The case for the ’714 and ’511 patents will likely depend on whether that data demonstrates that the product meets, or will meet, the specific quantitative claim limitations for purity, impurity, and (for the ’511 patent) crystalline structure.
- A key legal and factual question for the ’584 patent will be one of induced infringement: Assuming the product itself is infringing, will the label and marketing materials for Defendants' generic product contain sufficient instruction and encouragement to establish the specific intent required to hold Defendants liable for inducing doctors and patients to perform the claimed method of lowering cholesterol?