DCT

2:24-cv-06391

Esperion Therap Inc v. DR Reddy's Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:24-cv-06391, D.N.J., 06/25/2024
  • Venue Allegations: Venue is asserted based on Defendant Dr. Reddy's Laboratories Inc. being a New Jersey corporation. Venue over the foreign parent, Dr. Reddy's Laboratories Ltd., is based on its ability to be sued in any jurisdiction and its alleged regular and established place of business in New Jersey.
  • Core Dispute: Plaintiff alleges that Defendants' Abbreviated New Drug Application (ANDA) submissions seeking to market generic versions of the cholesterol-lowering drugs NEXLETOL® and NEXLIZET® constitute an act of infringement of six U.S. patents covering the active ingredient bempedoic acid, specific formulations, and methods of use.
  • Technical Context: The technology relates to pharmaceutical compositions for managing cholesterol and reducing cardiovascular disease risk, a field dominated by statin therapies but with a significant market for alternative treatments.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDAs with Paragraph IV certifications, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic products.

Case Timeline

Date Event
2002-01-23 U.S. Patent No. 7,335,799 Priority Date
2008-02-26 U.S. Patent No. 7,335,799 Issued
2015-03-31 U.S. Patent Nos. 10,912,751 & 11,744,816 Priority Date
2019-06-21 U.S. Patent Nos. 11,760,714, 11,613,511 & 11,926,584 Priority Date
2020-02-21 FDA approves Plaintiff's NEXLETOL® (bempedoic acid)
2020-02-26 FDA approves Plaintiff's NEXLIZET® (bempedoic acid and ezetimibe)
2021-02-09 U.S. Patent No. 10,912,751 Issued
2023-03-28 U.S. Patent No. 11,613,511 Issued
2023-09-05 U.S. Patent No. 11,744,816 Issued
2023-09-19 U.S. Patent No. 11,760,714 Issued
2024-03-12 U.S. Patent No. 11,926,584 Issued
2024-04-10 Plaintiff receives First NEXLETOL® Notice Letter
2024-05-01 Plaintiff receives First NEXLIZET® Notice Letter
2024-05-23 Original Complaint Filed
2024-06-10 Plaintiff receives Second NEXLETOL® and NEXLIZET® Notice Letters
2024-06-25 First Amended Complaint Filed

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"

  • Patent Identification: U.S. Patent No. 7,335,799, "Hydroxyl Compounds and Compositions for Cholesterol Management and Related Uses," issued February 26, 2008. (Compl. ¶38).

The Invention Explained

  • Problem Addressed: The patent addresses the need for novel compounds to treat cardiovascular diseases, which are often associated with dyslipidemias, or abnormal levels of circulating lipids like cholesterol. (’799 Patent, col. 2:2-45).
  • The Patented Solution: The invention provides a class of hydroxyl compounds, defined by a general chemical structure (Formula I), that are useful in managing cholesterol. (’799 Patent, Abstract). The detailed description discloses numerous specific compounds within this class, including the compound that would become known as bempedoic acid, which functions as an adenosine triphosphate-citrate lyase (ACL) inhibitor to lower cholesterol. (Compl. ¶59; ’799 Patent, col. 24:5-25:10).
  • Technical Importance: The invention provides a therapeutic approach for cholesterol management distinct from statins, which are the most common but not universally tolerated class of cholesterol-lowering drugs. (Compl. ¶59).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 12. (Compl. ¶¶106, 107, 109).
  • Independent Claim 1 covers a broad genus of compounds defined by Formula (I):
    • A core chemical structure with multiple variable components designated X, Y¹, Y², R¹, R², R¹¹, R¹², m, and n.
    • Each variable represents a selection of chemical groups or numerical ranges (e.g., m is an integer from 0 to 5; Y¹ and Y² can be groups like OH or COOH).
    • The claim also encompasses pharmaceutically acceptable salts, hydrates, or solvates of these compounds.
  • The complaint also asserts other unspecified claims. (Compl. ¶109).

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. (Compl. ¶41).

The Invention Explained

  • Problem Addressed: The patent identifies the significant challenge in developing robust, cost-effective, and efficient manufacturing processes for pharmaceutical compounds that achieve the high yield and purity required by regulatory agencies. (’714 Patent, col. 1:16-29).
  • The Patented Solution: The invention discloses pharmaceutical compositions containing a highly purified crystalline form of bempedoic acid (referred to as the compound of formula V). The claims define the composition by requiring the bempedoic acid to be present in an amount greater than 98% by weight, while strictly limiting a specific dimer impurity (the compound of formula VI) to a level of 0.15% or less. (’714 Patent, Abstract; col. 2:42-53).
  • Technical Importance: By defining and claiming a composition with a specific, low level of a particular impurity, the patent aims to protect a formulation that offers improved stability, safety, or efficacy, which are critical attributes for commercial pharmaceutical products. (’714 Patent, col. 1:21-29).

Key Claims at a Glance

  • The complaint asserts independent claim 1. (Compl. ¶132).
  • Independent Claim 1 recites a pharmaceutical composition comprising three key elements:
    • A pharmaceutical material comprising a crystalline form of bempedoic acid (formula V) in an amount greater than 98% by weight.
    • The same pharmaceutical material comprises from 0.0001% to less than or equal to 0.15% of a specified dimer impurity (formula VI).
    • A pharmaceutically acceptable excipient.
  • The complaint reserves the right to assert other claims. (Compl. ¶134).

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. (Compl. ¶44).
  • Technology Synopsis: This patent is directed to a pharmaceutical material containing a highly purified crystalline form of bempedoic acid. It builds upon the purity requirements of the ’714 Patent by adding limitations that define the specific crystalline structure through its characteristic X-ray powder diffraction (XRPD) pattern. (’511 Patent, col. 10:1-17).
  • Asserted Claims: The complaint asserts at least independent claim 1. (Compl. ¶¶156, 167).
  • Accused Features: The DRL NEXLETOL® and NEXLIZET® ANDA products are alleged to be pharmaceutical materials that meet the claimed purity, impurity, and crystalline structure limitations. (Compl. ¶¶157, 168).

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. (Compl. ¶53).
  • Technology Synopsis: This patent claims a method of lowering low-density lipoprotein cholesterol (LDL-C). The claimed method requires administering a pharmaceutical material that has the same high-purity and low-impurity profile for bempedoic acid as claimed in the ’714 and ’511 composition patents. (’584 Patent, col. 34:32-41).
  • Asserted Claims: The complaint asserts at least independent claim 1. (Compl. ¶¶178, 194).
  • Accused Features: The complaint alleges that DRL's proposed package inserts for its generic products will instruct physicians and patients to administer the drugs for lowering LDL-C, thereby inducing infringement of the claimed method. (Compl. ¶¶183-186, 199-202).

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"

  • Patent Identification: 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. (Compl. ¶47).
  • Technology Synopsis: This patent claims a method of treating familial hypercholesterolemia. The method involves administering a specific fixed-dose combination of 180 mg of bempedoic acid (referred to as 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) and 10 mg of ezetimibe. (’751 Patent, Abstract; col. 26:40-49).
  • Asserted Claims: The complaint asserts at least independent claim 1. (Compl. ¶210).
  • Accused Features: The DRL NEXLIZET® ANDA product is a fixed-dose combination of bempedoic acid and ezetimibe. The complaint alleges DRL's proposed package insert will instruct users to administer the product for the claimed indication, thereby inducing infringement. (Compl. ¶¶215, 217).

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"

  • Patent Identification: 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. (Compl. ¶50).
  • Technology Synopsis: This patent is related to the ’751 Patent and claims a method of lowering LDL-C in a subject with familial hypercholesterolemia. The method requires administering the same fixed-dose combination of 180 mg of bempedoic acid and 10 mg of ezetimibe. (’816 Patent, col. 26:4-10).
  • Asserted Claims: The complaint asserts at least independent claim 1. (Compl. ¶226).
  • Accused Features: The complaint alleges that the proposed package insert for the DRL NEXLIZET® ANDA product will instruct administration for the claimed use, inducing infringement. (Compl. ¶¶231, 233).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the generic drug products for which Defendants Dr. Reddy's Laboratories Inc. and Dr. Reddy's Laboratories Ltd. (collectively "DRL") seek FDA approval via ANDA No. 219312 (for a generic version of NEXLETOL®) and ANDA No. 219331 (for a generic version of NEXLIZET®). (Compl. ¶1).

Functionality and Market Context

  • The DRL NEXLETOL® ANDA Product contains bempedoic acid as its active pharmaceutical ingredient. (Compl. ¶¶60, 71). The complaint alleges this product is intended for the same indications as NEXLETOL®, namely to lower LDL-C and reduce cardiovascular risk. (Compl. ¶59). The complaint provides a chemical structure for bempedoic acid. (Compl. ¶60).
  • The DRL NEXLIZET® ANDA Product is a fixed-dose combination product containing bempedoic acid and ezetimibe as its active ingredients. (Compl. ¶¶65, 90). This product is intended for the same indications as NEXLIZET® for lowering LDL-C. (Compl. ¶64).
  • The complaint alleges that by submitting their ANDAs, DRL has represented to the FDA that their proposed generic products have the same active ingredient(s), dosage form, and strength as the corresponding branded products and are bioequivalent to them. (Compl. ¶¶71, 90).

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, wherein: ... each occurrence of Y¹ and Y² is independently ... OH, COOH... The active ingredient of the DRL NEXLETOL® and NEXLIZET® ANDA Products is bempedoic acid, which is 8-Hydroxy-2,2,14,14-tetramethyl-pentadecanedioic acid. The complaint displays the specific chemical structure of bempedoic acid. (Compl. ¶107). This specific compound is alleged to be a species falling within the genus of compounds defined by Formula I, where Y¹ and Y² are COOH and OH, respectively. ¶106; ¶107; ¶109; ¶119; ¶120 col. 24:5-15
  • Identified Points of Contention:
    • Scope Questions: A primary question may be whether the asserted claims, which define a broad genus of compounds, are valid in light of the prior art. Defendants' non-infringement argument, noted in the complaint, raises the question of whether DRL's specific salt form or crystalline structure of bempedoic acid falls outside the literal scope of the claims as they may be construed by the court. (Compl. ¶72).
    • Technical Questions: What evidence does the complaint provide that DRL's ANDA product is a "pharmaceutically acceptable salt, hydrate, solvate or mixture" as recited in the claim? The allegation relies on the ANDA filing's representation of bioequivalence to NEXLETOL®, which itself is sold as a formulation containing bempedoic acid. (Compl. ¶71).

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) ... in an amount greater than 98% by weight... The DRL NEXLETOL® and NEXLIZET® ANDA Products are alleged to be pharmaceutical compositions that contain bempedoic acid (the compound of formula V, as shown in the complaint (Compl. ¶132)) in a crystalline form at a purity level greater than 98%. ¶132; ¶133; ¶144; ¶145 col. 12:45-50
and the pharmaceutical material comprises 0.0001% to less than or equal to 0.15% of a compound of formula (VI)... The DRL ANDA Products are alleged to contain a specific dimer impurity (the compound of formula VI, as shown in the complaint (Compl. ¶132)) within the claimed narrow range of 0.0001% to 0.15%. ¶132; ¶133; ¶144; ¶145 col. 12:50-53
and a pharmaceutically acceptable excipient. The DRL ANDA Products are formulated as dosage forms for administration and therefore necessarily contain pharmaceutically acceptable excipients. ¶132; ¶144 col. 12:54-55
  • Identified Points of Contention:
    • Evidentiary Questions: The core of the dispute on this patent will be factual and evidentiary. Do DRL's ANDA products, as described in their confidential regulatory filings, actually meet the specific quantitative limitations for purity (>98% bempedoic acid) and impurity level (≤0.15% of the formula VI dimer)? The complaint makes these allegations on "information and belief" and notes that DRL has refused to produce the full ANDA. (Compl. ¶79, ¶135).
    • Technical Questions: How will the parties measure the percentage of the specified impurity? The case may involve disputes over the proper analytical methods (e.g., HPLC) for quantifying the active ingredient and the specific impurity to the precision required by the claim.

V. Key Claim Terms for Construction

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

  • The Term: "a compound of the formula (I)"
  • Context and Importance: This term defines the scope of the claimed chemical genus. Its construction is critical because infringement hinges on whether bempedoic acid, the active ingredient in the accused products, falls within the boundaries of this definition. Practitioners may focus on this term to dispute the claim's validity, potentially arguing it is overly broad and not fully enabled or described by the specification.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language itself defines the genus broadly, allowing for numerous variations in the substituents (R¹, R², etc.) and chain lengths (m, n). The specification's statement that "The present invention provides novel compounds of formula (I)" may support that the full scope of the formula is intended to be covered. (’799 Patent, col. 5:25-26).
    • Evidence for a Narrower Interpretation: The specification identifies "preferred" embodiments where certain variables are limited to specific chemical groups or values, such as where Y¹ and Y² are COOH or OH. (’799 Patent, col. 6:49-56). A defendant may argue that the claims should be limited to these preferred embodiments, particularly those explicitly exemplified, such as bempedoic acid.

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

  • The Term: "pharmaceutical material"
  • Context and Importance: The claim requires this "material" to meet specific purity and impurity thresholds. The definition of this term is central to the infringement analysis because it determines what substance is being measured—is it the pure active pharmaceutical ingredient (API) alone, or the API mixed with certain manufacturing excipients (the drug substance)?
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party might argue "pharmaceutical material" encompasses not just the pure API but also any co-processed crystals or amorphous content formed during manufacturing, potentially making it harder to meet the >98% purity threshold.
    • Evidence for a Narrower Interpretation: Claim 1 recites a "pharmaceutical composition, comprising: a pharmaceutical material ... and a pharmaceutically acceptable excipient." This structure strongly suggests that the "pharmaceutical material" is distinct from the final formulation's "excipient." The patent further states 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," which implies the "material" is the drug substance itself, consisting almost entirely of the active ingredient and any process-related impurities. (’714 Patent, col. 12:45-53).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. For the method-of-use patents (’584, ’751, ’816), inducement is based on allegations that DRL’s proposed package inserts will instruct and encourage physicians to prescribe and patients to use the generic products in a manner that directly practices the claimed methods. (Compl. ¶¶182, 183, 214, 217). Contributory infringement is alleged on the basis that DRL's products are especially made for infringing uses and are not suitable for substantial non-infringing use. (Compl. ¶¶113, 138, 189).
  • Willful Infringement: While the term "willful" is not explicitly used in the infringement counts, the complaint alleges facts that would support such a claim. It alleges DRL had knowledge of the asserted patents at least by the time it submitted its ANDAs, based on the patents' listing in the FDA's Orange Book and DRL's own Paragraph IV certification letters. (Compl. ¶¶73, 92, 111, 136, 160, 187). For method claims, it is alleged DRL is "willfully blind" to the fact that third parties will directly infringe based on the product's labeling. (Compl. ¶¶220, 236).

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

  • A key evidentiary question will be one of compositional fact: For the patents claiming specific formulations (’714, ’511, and method patent ’584), will discovery of DRL’s confidential ANDA filings confirm the complaint’s "information and belief" allegations that the proposed generic products actually meet the precise quantitative purity (>98%) and impurity (<0.15%) thresholds required by the claims?
  • A central legal issue will be one of induced infringement: For the method-of-use patents (’584, ’751, ’816), does the specific language in DRL’s proposed package inserts constitute sufficient instruction and encouragement for physicians and patients to perform the claimed therapeutic methods, thereby establishing the specific intent required to prove inducement?
  • The case may also turn on a question of patent validity: Given the existence of the foundational ’799 patent on the bempedoic acid compound, can the five later-issued patents—which claim specific purity levels, crystalline forms, and methods of using fixed-dose combinations—withstand the inevitable invalidity challenges based on obviousness over the original compound and other prior art?