DCT

1:23-cv-01015

Heron Therap Inc v. Mylan Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-01015, D. Del., 01/12/2024
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendant has committed, and will commit, acts of patent infringement in the district.
  • Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff's Cinvanti® injectable emulsion constitutes infringement of ten patents related to emulsion formulations of the antiemetic drug aprepitant.
  • Technical Context: The technology concerns stable, injectable oil-in-water emulsion formulations of aprepitant, a drug used to prevent nausea and vomiting caused by cancer chemotherapy, providing an alternative for patients who may have difficulty with oral administration.
  • Key Procedural History: This is a Hatch-Waxman action initiated after Plaintiff received a Paragraph IV Certification Notice Letter from Defendant on August 4, 2023, asserting that the patents-in-suit are invalid and/or would not be infringed by Defendant's proposed generic product. The complaint notes that the most recently issued patent, U.S. Patent No. 11,744,800, had not yet issued at the time Mylan sent its notice letter.

Case Timeline

Date Event
2013-01-22 U.S. Patent No. 9,561,229 Priority Date
2014-09-19 Priority Date for all other patents-in-suit
2017-02-07 U.S. Patent No. 9,561,229 Issues
2017-11-07 U.S. Patent No. 9,808,465 Issues
2017-11-09 Plaintiff's Cinvanti® NDA Approved
2018-05-22 U.S. Patent Nos. 9,974,742, 9,974,793, and 9,974,794 Issue
2019-12-10 U.S. Patent No. 10,500,208 Issues
2020-04-21 U.S. Patent No. 10,624,850 Issues
2021-03-23 U.S. Patent No. 10,953,018 Issues
2021-11-16 U.S. Patent No. 11,173,118 Issues
2023-08-04 Plaintiff receives Defendant's ANDA Notification Letter
2023-09-05 U.S. Patent No. 11,744,800 Issues
2024-01-12 Amended Complaint Filing Date

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 9,561,229 - Emulsion Formulations of Aprepitant

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of formulating aprepitant, a drug used to prevent chemotherapy-induced nausea, for intravenous administration. Aprepitant is poorly soluble in water, making liquid formulations difficult to create, particularly for patients who cannot take oral capsules due to nausea. (’229 Patent, col. 1:47-56).
  • The Patented Solution: The invention is a stable, oil-in-water emulsion that allows aprepitant to be dissolved in an "oil phase" which is then dispersed in an "aqueous phase" to create a formulation suitable for injection. The solution focuses on specific ratios and types of components—including an oil (e.g., soybean oil), an emulsifier (e.g., egg yolk lecithin), a co-surfactant, a tonicity agent, and a pH-adjusting agent—to ensure the emulsion remains physically and chemically stable for its shelf life. (’229 Patent, Abstract; col. 2:40-49).
  • Technical Importance: This approach provides a non-oral delivery method for a critical anti-nausea medication, enhancing its bioavailability and making it accessible to patients experiencing emesis during chemotherapy. (’229 Patent, col. 1:52-59).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" without specifying which ones (Compl. ¶29). Independent claim 1 is representative:
  • An injectable pharmaceutical emulsion comprising:
    • 0.4 wt/wt % to 1.0 wt/wt % aprepitant;
    • 13 wt/wt % to 15 wt/wt % egg yolk lecithin;
    • 9 wt/wt % to 10 wt/wt % soybean oil; and
    • a pH modifier, wherein the pH modifier is sodium oleate;
    • wherein the pH of the emulsion ranges from 7.5 to 9.0.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 10,500,208 - Emulsion Formulations of Aprepitant

The Invention Explained

  • Problem Addressed: The patent describes the difficulty in creating liquid formulations of aprepitant due to its poor solubility and permeability. Intravenous emulsions must have very small, stable droplet sizes to avoid causing capillary blockage and embolization when administered. (’208 Patent, col. 1:52-61).
  • The Patented Solution: The invention is an injectable oil-in-water emulsion characterized by specific components and ratios that ensure its physical stability over time. The solution comprises aprepitant, an emulsifier, an oil, a co-emulsifier (alcohol), a tonicity modifier, a pH modifier, and water, with a pH range of about 7.5 to 9.0. (’208 Patent, Abstract; col. 17:55-col. 18:0). The patent defines "physically stable" with reference to criteria under USP <729> and the absence of visible aprepitant crystals upon storage. (’208 Patent, col. 8:8-22).
  • Technical Importance: The claimed formulation provides a specific recipe for a stable, injectable aprepitant emulsion that is safe for intravenous use and can be readily manufactured. (’208 Patent, col. 2:32-37).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" without specifying which ones (Compl. ¶79). Independent claim 1 is representative:
  • An injectable emulsion comprising:
    • aprepitant;
    • 11 wt/wt % to 15 wt/wt % of an emulsifier;
    • an oil;
    • a co-emulsifier which is an alcohol;
    • a tonicity modifier;
    • a pH modifier; and
    • water;
    • wherein the pH of the emulsion ranges from about 7.5 to 9.0,
    • wherein the emulsion is physically stable.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,808,465 - Emulsion Formulations of Aprepitant

  • Technology Synopsis: This patent relates to methods of preventing or treating emesis in a subject by administering a physically stable, injectable emulsion containing aprepitant. The claims focus on the therapeutic application of formulations with specific component ratios, such as the ratio of oil to aprepitant and the ratio of emulsifier to oil. (’465 Patent, Abstract; claim 1).
  • Asserted Claims: The complaint alleges infringement of one or more claims without further specification (Compl. ¶39).
  • Accused Features: The accused feature is Defendant's filing of ANDA No. 216976 for its generic aprepitant injectable emulsion (Compl. ¶38).

U.S. Patent No. 9,974,742 - Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof

  • Technology Synopsis: This patent covers injectable pharmaceutical emulsions containing a neurokinin-1 (NK-1) receptor antagonist (a class of drugs that includes aprepitant) and specific combinations of excipients. The claims are directed to the composition itself, defined by its components and their specific weight percentages and ratios, and a pH range of 7.5 to 9.0. (’742 Patent, Abstract; claim 1).
  • Asserted Claims: The complaint alleges infringement of one or more claims without further specification (Compl. ¶49).
  • Accused Features: The accused feature is Defendant's filing of ANDA No. 216976 for its generic aprepitant injectable emulsion (Compl. ¶48).

U.S. Patent No. 9,974,793 - Emulsion Formulations of Aprepitant

  • Technology Synopsis: This patent claims physically stable pharmaceutical compositions comprising aprepitant, an emulsifier, an oil, and water, characterized by specific ratios of emulsifier-to-aprepitant and oil-to-aprepitant. It also claims compositions with specific weight percentages of aprepitant and egg yolk lecithin. (’793 Patent, Abstract; claim 1).
  • Asserted Claims: The complaint alleges infringement of one or more claims without further specification (Compl. ¶59).
  • Accused Features: The accused feature is Defendant's filing of ANDA No. 216976 for its generic aprepitant injectable emulsion (Compl. ¶58).

U.S. Patent No. 9,974,794 - Emulsion Formulations of Aprepitant

  • Technology Synopsis: This patent relates to physically stable pharmaceutical compositions suitable for intravenous administration. The claims are directed to an emulsion comprising aprepitant, egg yolk lecithin, soybean oil, a sodium oleate pH modifier, and specific ranges for sucrose and ethanol. (’794 Patent, Abstract; claim 8).
  • Asserted Claims: The complaint alleges infringement of one or more claims without further specification (Compl. ¶69).
  • Accused Features: The accused feature is Defendant's filing of ANDA No. 216976 for its generic aprepitant injectable emulsion (Compl. ¶68).

U.S. Patent No. 10,624,850 - Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof

  • Technology Synopsis: This patent claims methods for treating nausea and vomiting by administering an injectable emulsion containing an NK-1 receptor antagonist. The claims specify the pH of the emulsion and the ratios of emulsifier to the antagonist, defining the therapeutic method. (’850 Patent, Abstract; claim 1).
  • Asserted Claims: The complaint alleges infringement of one or more claims without further specification (Compl. ¶89).
  • Accused Features: The accused feature is Defendant's filing of ANDA No. 216976 for its generic aprepitant injectable emulsion (Compl. ¶88).

U.S. Patent No. 10,953,018 - Emulsion Formulations of Aprepitant

  • Technology Synopsis: This patent covers methods of treating nausea and vomiting with a physically stable emulsion comprising aprepitant. The claims define the method by the specific ratios of emulsifier-to-aprepitant and oil-to-aprepitant in the administered composition. (’018 Patent, Abstract; claim 1).
  • Asserted Claims: The complaint alleges infringement of one or more claims without further specification (Compl. ¶99).
  • Accused Features: The accused feature is Defendant's filing of ANDA No. 216976 for its generic aprepitant injectable emulsion (Compl. ¶98).

U.S. Patent No. 11,173,118 - Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof

  • Technology Synopsis: This patent is directed to an injectable pharmaceutical emulsion composition containing an NK-1 receptor antagonist. The claims require specific ratios of emulsifier to the antagonist and define the composition by its constituent parts, including an oil, co-surfactant, and aqueous phase. (’118 Patent, Abstract; claim 1).
  • Asserted Claims: The complaint alleges infringement of one or more claims without further specification (Compl. ¶109).
  • Accused Features: The accused feature is Defendant's filing of ANDA No. 216976 for its generic aprepitant injectable emulsion (Compl. ¶108).

U.S. Patent No. 11,744,800 - Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist

  • Technology Synopsis: This patent claims methods for preventing post-operative nausea and vomiting by administering an injectable pharmaceutical emulsion. The claims define the emulsion by its components and their specific weight percentages, including egg lecithin, soybean oil, ethanol, sucrose, and sodium oleate. (’800 Patent, Abstract; claim 22).
  • Asserted Claims: The complaint alleges infringement of one or more claims without further specification (Compl. ¶119).
  • Accused Features: The accused feature is Defendant's filing of ANDA No. 216976 for its generic aprepitant injectable emulsion (Compl. ¶118).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the generic drug product that is the subject of Mylan's ANDA No. 216976, identified as an “injectable emulsion containing 130mg/18mL (7.2 mg/mL) aprepitant” (“the Mylan Generic Product”) (Compl. ¶21).

Functionality and Market Context

The complaint alleges that by filing its ANDA, Mylan has certified to the FDA that its generic product has the same active ingredient, the same or substantially the same indications, and the same or substantially the same proposed labeling as Heron's branded product, Cinvanti® (Compl. ¶22). Cinvanti® is used in adults for the prevention of acute and delayed nausea and vomiting associated with various types of emetogenic cancer chemotherapy (Compl. ¶19). The Mylan Generic Product is therefore intended to be a direct generic substitute for Cinvanti®. No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges infringement in general terms, asserting that Mylan's submission of ANDA No. 216976 constituted an act of infringement under 35 U.S.C. § 271(e)(2)(A) and that the proposed generic product "meets or embodies all elements of one or more claims" of each patent-in-suit (Compl. ¶¶ 28-29, 38-39, 48-49, 58-59, 68-69, 78-79, 88-89, 98-99, 108-109, 118-119). It does not provide a detailed, element-by-element mapping of the accused product's features to the specific limitations of any asserted claims. Therefore, a claim chart summary cannot be constructed from the complaint's allegations.

  • Identified Points of Contention: Given the nature of ANDA litigation, the dispute will likely center on whether the specific formulation of the Mylan Generic Product falls within the scope of the asserted claims. Key questions may include:
    • Scope Questions: Do the specific weight percentages and component ratios of the excipients in Mylan's formulation meet the ranges required by claims such as claim 1 of the ’229 Patent?
    • Technical Questions: Does Mylan's formulation achieve "physical stability" as that term is defined and used within the ’208 Patent specification, which sets specific criteria regarding droplet size and the absence of crystallization over time? The factual evidence regarding the stability and composition of Mylan's product, once produced in discovery, will be central to the infringement analysis.

V. Key Claim Terms for Construction

  • The Term: "physically stable" (’208 Patent, claim 1).

  • Context and Importance: The definition of this term is critical because it is a required limitation in several independent claims across the patent family. Infringement will depend on whether Mylan’s product meets the patent's specific criteria for stability. Practitioners may focus on this term because the patent provides an explicit definition, creating a potential battleground for claim construction and infringement analysis.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent states that "physically stable" emulsions "will meet the criteria under USP <729>," which defines universal limits for droplet size and percentage of large-diameter fat globules. A party could argue that any formulation meeting these public, industry-standard criteria is "physically stable." (’208 Patent, col. 8:8-14).
    • Evidence for a Narrower Interpretation: The same passage adds a second requirement: "physically stable emulsions will have no visible aprepitant crystals upon storage at 5° C. or room temperature for a designated time period." A party could argue this creates a two-part test, and that a formulation is only "physically stable" if it both meets USP <729> criteria and remains free of visible crystals for a specific duration (e.g., "at least 1 week, 2 weeks, 4 weeks, 1 month," etc.). (’208 Patent, col. 8:14-22).

  • The Term: "emulsifier" (’229 Patent, claim 1; ’208 Patent, claim 1).

  • Context and Importance: The patents claim specific weight percentages and ratios of an "emulsifier." The classification of certain ingredients in Mylan's formulation as either an "emulsifier" or another type of excipient (e.g., a co-surfactant) could determine whether the claimed concentration ranges are met.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification provides a broad functional definition: an emulsifier "refers to a compound that deters the separation of the injectable emulsion into individual oil and aqueous phases." It also provides a long list of suitable emulsifiers, including phospholipids like lecithin as well as propylene glycol esters and polyoxyethylene sorbitan fatty acid esters. (’208 Patent, col. 8:56-65).
    • Evidence for a Narrower Interpretation: The preferred embodiments and examples consistently use phospholipids, specifically egg yolk lecithin, as the primary emulsifier. A party might argue that in the context of the invention, the term "emulsifier" should be construed to mean a primary emulsifying agent like a phospholipid, distinct from other components like alcohols which are separately claimed as "co-emulsifiers." (’208 Patent, col. 17:55-col. 18:0; ’229 Patent, col. 15:8-10).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that if Mylan commercially manufactures and sells its generic product, it will induce and/or contribute to the infringement of the patents-in-suit (Compl. ¶¶ 31, 41, 51, 61, 71, 81, 91, 101, 111, 121). This allegation is based on the premise that Mylan’s proposed labeling will instruct medical professionals and patients to use the product in an infringing manner.
  • Willful Infringement: While the word "willful" is not used, the complaint alleges for each patent that "Mylan was aware of the existence of the [asserted] patent and was aware that the filing of ANDA No. 216976 and the certification with respect to the [asserted] patent constituted an act of infringement of that patent" (Compl. ¶¶ 36, 46, 56, 66, 76, 86, 96, 106, 116). These allegations of pre-suit knowledge of the patents and the alleged infringement form the basis for a potential claim of willfulness.

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

The resolution of this case will likely depend on the answers to two central questions:

  • A core issue will be one of compositional identity: Does the precise formulation of Mylan’s generic product—specifically, its list of ingredients and their exact weight percentages and ratios—fall within the numerical ranges defined by the asserted patent claims? The case may turn on highly technical, fact-intensive comparisons between the accused product and the claimed invention.
  • A key legal question will be one of claim scope: How will the court construe key terms such as "physically stable"? The outcome could depend on whether the court adopts the patent's specific, multi-part definition or a broader, industry-standard meaning, which would directly impact the infringement analysis.