DCT
2:24-cv-06386
Esperion Therap Inc v. MSN Pharma Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Esperion Therapeutics, Inc. (Delaware)
- Defendant: MSN Pharmaceuticals Inc. (Delaware); MSN Laboratories Private Limited (India); APICHEM Laboratories Private Limited (India)
- Plaintiff’s Counsel: Walsh Pizzi Oreilly Falanga LLP
- Case Identification: 2:24-cv-06386, D.N.J., 05/23/2024
- Venue Allegations: Venue is alleged as proper in the District of New Jersey because Defendant MSN Pharmaceuticals Inc. has its principal place of business in the district. Venue over the foreign defendants, MSN Laboratories and APICHEM, is asserted on the basis that they are not residents of the United States and may be sued in any judicial district.
- Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) seeking to market a generic version of Plaintiff's NEXLETOL® product infringes patents related to high-purity crystalline compositions of the active ingredient, 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).
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' notification to Plaintiff, via a Paragraph IV certification letter, of their filing of ANDA No. 219437. In the letter, Defendants asserted that the patents-in-suit are invalid, unenforceable, or will not be infringed by their proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2019-06-21 | Patent Priority Date ('714 and '511 Patents) |
| 2020-02-21 | FDA Approval of NEXLETOL® (bempedoic acid) |
| 2023-03-28 | '511 Patent Issued |
| 2023-09-19 | '714 Patent Issued |
| 2024-04-09 | Date of Defendants' Notice Letter |
| 2024-04-10 | Earliest date Plaintiff received Notice Letter |
| 2024-05-23 | Complaint Filing Date |
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.
The Invention Explained
- Problem Addressed: The patent's background section identifies the "significant challenge" of developing robust, cost-effective, and efficient manufacturing methods for pharmaceutical compounds that achieve the desired yield and purity required by regulatory agencies ('714 Patent, col. 1:15-29).
- The Patented Solution: The invention provides methods for producing high-purity bempedoic acid, as well as the compositions resulting from such methods ('714 Patent, Abstract). The asserted claims are directed not to the method itself, but to a pharmaceutical composition defined by a high level of purity for bempedoic acid and a strictly controlled low level of a specific "diol" impurity ('714 Patent, col. 83:11-25).
- Technical Importance: For orally administered drugs, ensuring high purity and minimizing specific process-related impurities is critical for product safety, stability, and compliance with regulatory standards.
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶64).
- Claim 1 requires:
- A pharmaceutical material comprising a crystalline form of bempedoic acid (formula V).
- The material must contain bempedoic acid in an amount greater than 98% by weight.
- The material must also contain from 0.0001% to no more than 0.15% of a specific diol impurity (formula VI).
- The composition must further include a pharmaceutically acceptable excipient.
- The complaint does not explicitly reserve the right to assert dependent claims.
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.
The Invention Explained
- Problem Addressed: The patent addresses the same challenge as its counterpart: the need for manufacturing processes that yield high-purity bempedoic acid suitable for use as an active pharmaceutical ingredient ('511 Patent, col. 1:21-29).
- The Patented Solution: This patent claims a specific crystalline form, or polymorph, of bempedoic acid, which is defined by a characteristic pattern of peaks in an X-ray powder diffraction (XRPD) analysis ('511 Patent, col. 9:18-42). The claims couple this specific solid-state form with high purity requirements, including a purity of greater than 99.0% for bempedoic acid and the same upper limit of 0.15% for the diol impurity as the ’714 Patent ('511 Patent, col. 82:48-67).
- Technical Importance: The specific crystalline form of a drug substance can significantly impact its physical properties, such as stability, dissolution rate, and bioavailability, making polymorphic control a critical aspect of pharmaceutical manufacturing.
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶76).
- Claim 1 requires:
- A pharmaceutical material comprising a crystalline form of bempedoic acid (formula V).
- The material must contain bempedoic acid in an amount greater than 99.0% by weight.
- The material must contain from 0.0001% to no more than 0.15% of the diol impurity (formula VI).
- The crystalline form must exhibit an XRPD pattern with peaks at six specific diffraction 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).
- The complaint does not explicitly reserve the right to assert dependent claims.
III. The Accused Instrumentality
Product Identification
The accused instrumentality is the "MSN ANDA Product," a generic version of NEXLETOL® for which Defendants seek FDA approval via ANDA No. 219437 (Compl. ¶¶1, 55).
Functionality and Market Context
- The MSN ANDA Product contains bempedoic acid as its active pharmaceutical ingredient (Compl. ¶57). Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor indicated for lowering LDL-C in adults with primary hyperlipidemia and for reducing cardiovascular risk (Compl. ¶51).
- The complaint alleges that by submitting the ANDA, Defendants have represented to the FDA that their product has the same active ingredient, dosage form, and strength as NEXLETOL® and is bioequivalent to it (Compl. ¶57). The complaint further alleges that Defendants intend to engage in the commercial manufacture, use, and sale of the product promptly upon receiving FDA approval (Compl. ¶56). The complaint includes a diagram of the chemical structure of bempedoic acid, the active ingredient in both the brand-name and accused generic products (Compl. ¶52).
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) | The complaint alleges that the MSN ANDA Product is a pharmaceutical composition that contains bempedoic acid, the compound of formula (V), as its active ingredient. The complaint provides the chemical structure for formula (V). | ¶¶57, 64 | col. 83:11-25 |
| wherein the pharmaceutical material comprises the compound of formula (V) ... in an amount greater than 98% by weight | Based on information and belief, the complaint alleges the MSN ANDA Product will contain bempedoic acid at a purity level meeting this limitation. | ¶67 | col. 83:15-18 |
| and the pharmaceutical material comprises 0.0001 % to less than or equal to 0.15% of a compound of formula (VI) | Based on information and belief, the complaint alleges the MSN ANDA Product will contain the diol impurity of formula (VI) within the claimed range. The complaint provides the chemical structure for formula (VI). | ¶¶64, 67 | col. 83:19-23 |
| and a pharmaceutically acceptable excipient | The complaint alleges the MSN ANDA Product is a pharmaceutical dosage form that necessarily contains pharmaceutically acceptable excipients. | ¶57 | col. 83:24-25 |
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) | The complaint alleges the MSN ANDA Product is a pharmaceutical composition containing a crystalline form of bempedoic acid, the compound of formula (V). | ¶¶57, 76 | col. 82:48-52 |
| wherein the pharmaceutical material comprises the compound of formula (V) ... in an amount greater than 99.0% by weight | Based on information and belief, the complaint alleges the MSN ANDA Product will contain bempedoic acid at a purity level of greater than 99.0%. | ¶79 | col. 82:53-56 |
| the pharmaceutical material comprises 0.0001 % to less than or equal to 0.15% of a compound of formula (VI) | Based on information and belief, the complaint alleges the MSN ANDA Product will contain the diol impurity of formula (VI) within the claimed range. | ¶76 | col. 82:57-60 |
| and the crystalline form of the compound of formula (V) exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (20): 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 | Based on information and belief, the complaint alleges the crystalline form of bempedoic acid in the MSN ANDA Product will exhibit the specific XRPD peaks recited in the claim. | ¶76 | col. 82:61-67 |
Identified Points of Contention
- Factual Questions: The core of the dispute appears to be factual. Defendants have asserted non-infringement in their notice letter (Compl. ¶58). This raises the question of what evidence the parties will present regarding the precise characteristics of the proposed MSN ANDA Product. The dispute may center on whether Defendants' product meets the specific purity thresholds (>98% for the ’714 Patent; >99% for the ’511 Patent) and the diol impurity limits (<0.15%) required by the claims.
- Technical Questions: For the ’511 Patent, a key technical question is whether the crystalline form of bempedoic acid in the MSN ANDA product is the same polymorph claimed in the patent. The infringement analysis will depend on a comparison of the XRPD pattern of Defendants' product with the six specific peaks recited in claim 1.
V. Key Claim Terms for Construction
The Term: "pharmaceutical material"
- Context and Importance: This term appears in both asserted claims and provides the basis for the weight percentage calculations for both purity and impurity levels. Its definition is critical to determining whether the accused product meets these quantitative limitations. Practitioners may focus on whether this term refers only to the bempedoic acid active pharmaceutical ingredient (API) itself, or if it could also encompass the API mixed with certain manufacturing aids or stabilizers prior to final formulation with excipients.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim language recites "a pharmaceutical material comprising a crystalline form of the compound of formula (V)," which may suggest the material can contain other components besides bempedoic acid ('511 Patent, col. 82:49-50).
- Evidence for a Narrower Interpretation: The claims distinguish between the "pharmaceutical material" and the "pharmaceutically acceptable excipient," suggesting they are distinct components ('714 Patent, col. 83:12, 24). The patent abstract describes making a "pharmaceutical material comprising a purified amount of" bempedoic acid, which could be interpreted as referring to the bulk drug substance itself ('511 Patent, Abstract).
The Term: "crystalline form ... exhibits an X-ray powder diffraction pattern comprising peaks at..."
- Context and Importance: This term is central to the infringement analysis for the ’511 Patent. The word "comprising" suggests an open-ended list, meaning the accused product would infringe if its XRPD pattern includes the six recited peaks, even if it also contains additional peaks. The dispute will likely focus on whether Defendants can prove their product utilizes a different polymorph that lacks one or more of the required peaks.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The standard legal definition of "comprising" is inclusive. The claim does not state "consisting of" or "consisting essentially of" the listed peaks.
- Evidence for a Narrower Interpretation: Defendants may argue that the specification, by providing a single, detailed characterization of one crystalline form (e.g., ’511 Patent, Table 1, col. 16), implicitly defines a specific polymorph. They could argue that this context limits the scope of "crystalline form" to the specific polymorph disclosed in the patent's examples, rather than any form that happens to share those six peaks.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon approval, Defendants will induce infringement by marketing the ANDA product and encouraging its prescription by doctors and use by patients (Compl. ¶¶69, 81). It also alleges contributory infringement on the basis that the product is especially made for use in an infringing manner and is not a staple article suitable for substantial noninfringing use (Compl. ¶¶70, 82).
- Willful Infringement: While not pleaded as a separate count, the complaint establishes a basis for potential willfulness by alleging Defendants had knowledge of the asserted patents. This knowledge is alleged to stem from the patents' listing in the FDA's Orange Book and from their identification in Defendants' own Paragraph IV Notice Letter (Compl. ¶¶68, 80).
VII. Analyst’s Conclusion: Key Questions for the Case
The complaint frames a dispute that will likely depend on the resolution of two central evidentiary questions:
- A core issue will be one of quantitative compliance: Does the bempedoic acid in Defendants' proposed generic product, as described in their ANDA and as would be commercially manufactured, actually meet the specific numerical thresholds for purity (>98% or >99%) and impurity (<0.15% of the diol compound) required by the asserted claims?
- A key question for the ’511 patent will be one of polymorphic identity: Does the crystalline active ingredient in the MSN ANDA Product exhibit the specific six-peak X-ray diffraction signature of the claimed polymorph, or have Defendants developed a formulation using a distinct, non-infringing crystalline form of bempedoic acid?