DCT

1:25-cv-00357

Heron Therap Inc v. Qilu Pharmaceutical Co Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-00357, D. Del., 03/21/2025
  • Venue Allegations: Plaintiff alleges venue is proper because the Defendants have committed or will commit acts of infringement in the district and, as foreign entities, may be sued in any judicial district. For the domestic defendant, venue is alleged based on acts of infringement committed in the district.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's Aponvie® product constitutes infringement of thirteen patents related to stable, injectable emulsion formulations of the antiemetic drug aprepitant.
  • Technical Context: The technology concerns pharmaceutical oil-in-water emulsions designed to intravenously deliver poorly soluble drugs like aprepitant, which is used to prevent nausea and vomiting, particularly that induced by chemotherapy.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of a Paragraph IV certification notice letter from Defendants on February 7, 2025. This notice letter informed Plaintiff of Defendants' ANDA filing seeking approval to market a generic aprepitant emulsion and asserted that the patents-in-suit are invalid and/or would not be infringed. The complaint was filed within the 45-day statutory window.

Case Timeline

Date Event
2014-09-19 Priority Date for all 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
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
2022-09-16 Plaintiff's Aponvie® NDA Approved by FDA
2023-09-05 U.S. Patent No. 11,744,800 Issues
2024-01-23 U.S. Patent No. 11,878,074 Issues
2024-10-15 U.S. Patent Nos. 12,115,254 and 12,115,255 Issue
2025-02-07 Plaintiff Receives Defendants' Paragraph IV Notice Letter
2025-03-21 Complaint Filed

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

U.S. Patent No. 9,561,229 - Emulsion Formulations of Aprepitant, issued February 7, 2017

The Invention Explained

  • Problem Addressed: The patent addresses the difficulty of administering aprepitant, a drug for preventing chemotherapy-induced nausea and vomiting (CINV). Aprepitant is poorly soluble in water and, at the time of the invention, was only available as an oral capsule, which is problematic for patients already experiencing nausea (’208 Patent, col. 1:45-58).
  • The Patented Solution: The invention is a stable, oil-in-water emulsion formulation suitable for intravenous administration. This formulation suspends the poorly soluble aprepitant in an oil phase, which is then emulsified in an aqueous phase, creating a stable liquid that can be injected, bypassing the challenges of oral delivery and poor solubility (’208 Patent, col. 2:32-36, col. 7:41-50).
  • Technical Importance: This technology provided a method for non-oral administration of an important anti-emetic drug, offering a critical alternative for patients unable to tolerate oral medications due to severe nausea (’208 Patent, col. 1:45-50).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’229 patent (Compl. ¶52). 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 reserves the right to assert additional claims, including dependent claims (Compl. ¶52).

U.S. Patent No. 9,808,465 - Emulsion Formulations of Aprepitant, issued November 7, 2017

The Invention Explained

  • Problem Addressed: Similar to the ’229 Patent, this patent targets the challenge of creating a stable, injectable liquid formulation for aprepitant, a drug with poor water solubility that is used to treat CINV (’208 Patent, col. 1:45-58).
  • The Patented Solution: The invention provides a stable oil-in-water emulsion that allows aprepitant to be administered intravenously. The claims define specific ratios and components, such as the emulsifier, oil, a co-emulsifier (alcohol), and a tonicity modifier, to ensure the emulsion is physically stable and suitable for injection (’208 Patent, Abstract; col. 2:41-50).
  • Technical Importance: This formulation offers a practical solution for administering aprepitant to patients for whom oral dosage forms are not viable, thereby improving treatment options for CINV (’208 Patent, col. 1:45-50).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’465 patent (Compl. ¶62). Independent claim 1 is representative:
    • A method for preventing or treating a subject at risk of or suffering from emesis, comprising administering to the subject a composition comprising an injectable physically stable emulsion wherein the emulsion comprises:
    • 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 ratio of emulsifier:aprepitant ranges from about 18:1 to 22:1, and
    • wherein the pH of the emulsion ranges from about 7.5 to 9.0.
  • The complaint reserves the right to assert additional claims (Compl. ¶62).

Multi-Patent Capsule: U.S. Patent No. 9,974,742 - Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof, issued May 22, 2018

  • Technology Synopsis: This patent describes stable oil-in-water emulsion formulations of a neurokinin-1 (NK-1) receptor antagonist, such as aprepitant, suitable for intravenous administration. The formulations are designed to overcome the poor solubility of the active agent and provide a non-oral treatment for emesis (Compl. ¶30; ’850 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of one or more claims, including claims 1-7, 9-14, and 16-21 (Compl. ¶¶72, 75).
  • Accused Features: The entirety of the "Qilu Generic Product" is accused of infringing the patent's claims directed to pharmaceutical emulsions (Compl. ¶72).

Multi-Patent Capsule: U.S. Patent No. 9,974,793 - Emulsion Formulations of Aprepitant, issued May 22, 2018

  • Technology Synopsis: This patent covers physically stable, injectable oil-in-water emulsions of aprepitant. The invention specifies particular weight percentages and ratios of components like egg yolk lecithin and soybean oil to achieve a formulation with a pH suitable for intravenous use (Compl. ¶31; ’208 Patent, col. 2:51-60).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶82).
  • Accused Features: Defendants' ANDA product, alleged to be a generic equivalent of Aponvie®, is accused of infringing the claimed formulation (Compl. ¶82).

Multi-Patent Capsule: U.S. Patent No. 9,974,794 - Emulsion Formulations of Aprepitant, issued May 22, 2018

  • Technology Synopsis: This patent relates to stable, injectable pharmaceutical compositions of aprepitant formulated as an oil-in-water emulsion. The claims focus on specific component ratios, such as the ratio of emulsifier to aprepitant and oil to aprepitant, to ensure physical stability (Compl. ¶32; ’208 Patent, col. 3:30-44).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶92).
  • Accused Features: The "Qilu Generic Product" is accused of embodying the claimed emulsion composition (Compl. ¶92).

Multi-Patent Capsule: U.S. Patent No. 10,500,208 - Emulsion Formulations of Aprepitant, issued December 10, 2019

  • Technology Synopsis: This patent claims injectable oil-in-water emulsions containing aprepitant, an emulsifier, an oil, a co-emulsifier, and a tonicity modifier. The claims define a physically stable emulsion with a specific pH range suitable for parenteral administration to treat emesis (Compl. ¶33; ’208 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶102).
  • Accused Features: The formulation of Defendants' ANDA product is accused of infringing the patent (Compl. ¶102).

Multi-Patent Capsule: U.S. Patent No. 10,624,850 - Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof, issued April 21, 2020

  • Technology Synopsis: This patent is directed to methods of treating nausea and vomiting by administering an injectable emulsion of an NK-1 receptor antagonist. The invention specifies ratios of emulsifier to the active agent and requires the emulsion to be physically stable (Compl. ¶34; ’850 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of claims 1-7 and 9-16 (Compl. ¶¶112, 115).
  • Accused Features: The proposed use of the "Qilu Generic Product," as directed by its labeling, is accused of infringing the claimed methods of treatment (Compl. ¶112).

Multi-Patent Capsule: U.S. Patent No. 10,953,018 - Emulsion Formulations of Aprepitant, issued March 23, 2021

  • Technology Synopsis: This patent claims methods of treating nausea and vomiting by administering a physically stable injectable emulsion of aprepitant with specific component ratios. The claims recite ratios of emulsifier-to-aprepitant and oil-to-aprepitant (Compl. ¶35; ’018 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶122).
  • Accused Features: The intended use of the "Qilu Generic Product" for treating nausea and vomiting is accused of infringing the claimed methods (Compl. ¶122).

Multi-Patent Capsule: U.S. Patent No. 11,173,118 - Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof, issued November 16, 2021

  • Technology Synopsis: This patent describes an injectable emulsion containing an NK-1 receptor antagonist, an emulsifier, an oil, and other excipients. The claims focus on specific weight percentages of the components to achieve a stable formulation for treating emesis (Compl. ¶36; ’118 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of claims 1-9 and 11-18 (Compl. ¶¶132, 135).
  • Accused Features: The composition of the "Qilu Generic Product" is accused of infringing the patent's formulation claims (Compl. ¶132).

Multi-Patent Capsule: U.S. Patent No. 11,744,800 - Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist, issued September 5, 2023

  • Technology Synopsis: This patent covers methods of preventing post-operative nausea and vomiting by administering an injectable aprepitant emulsion with specific component ratios. The claims require particular weight percentages for egg lecithin, soybean oil, and other excipients (Compl. ¶37; ’800 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶142).
  • Accused Features: The intended use of the "Qilu Generic Product" for post-operative nausea and vomiting is accused of infringing the claimed methods (Compl. ¶142).

Multi-Patent Capsule: U.S. Patent No. 11,878,074 - Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist, issued January 23, 2024

  • Technology Synopsis: This patent claims methods for preventing post-operative nausea and vomiting by administering an injectable emulsion containing aprepitant. The claims specify component ratios, including the ratio of egg lecithin to aprepitant (Compl. ¶38; ’074 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of claims 1-6 and 8-13 (Compl. ¶¶152, 155).
  • Accused Features: Defendants' proposed marketing of their generic product for preventing post-operative nausea and vomiting is accused of infringing the claimed methods (Compl. ¶152).

Multi-Patent Capsule: U.S. Patent No. 12,115,254 - Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist, issued October 15, 2024

  • Technology Synopsis: The patent relates to methods of using injectable emulsions of NK-1 receptor antagonists to treat emesis. The claims recite specific ratios and concentrations of components within the emulsion (Compl. ¶39; ’254 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶162).
  • Accused Features: The intended and directed use of the "Qilu Generic Product" is accused of infringing the claimed methods (Compl. ¶162).

Multi-Patent Capsule: U.S. Patent No. 12,115,255 - Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist, issued October 15, 2024

  • Technology Synopsis: This patent covers methods of using injectable emulsions of aprepitant for treating nausea and vomiting. The claims focus on the ratios of emulsifier and oil to aprepitant within the formulation (Compl. ¶40; ’255 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶172).
  • Accused Features: The "Qilu Generic Product," when used as directed by its proposed label, is accused of infringing the claimed methods (Compl. ¶172).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the "Qilu Generic Product," an injectable emulsion containing 32mg/4.4mL (7.2 mg/mL) of aprepitant, for which Defendants submitted ANDA No. 220259 to the FDA (Compl. ¶44).

Functionality and Market Context

The Qilu Generic Product is alleged to be a generic version of Heron's branded Aponvie® injectable emulsion (Compl. ¶¶44, 45). The complaint alleges that by filing the ANDA, Qilu certified that its product has the same active ingredient as Aponvie®, the same or substantially the same indications, and substantially the same proposed labeling (Compl. ¶45). Aponvie® is indicated for the prevention of postoperative nausea and vomiting in adults (Compl. ¶42). The product is intended for commercial manufacture, use, and sale in the United States upon receiving FDA approval, positioning it as a direct competitor to Aponvie® (Compl. ¶44).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that by submitting ANDA No. 220259, Defendants have committed an act of infringement under 35 U.S.C. § 271(e)(2) and that the future commercial manufacture, use, or sale of the Qilu Generic Product will constitute direct infringement under § 271(a) and/or indirect infringement under §§ 271(b) and (c) (Compl. ¶¶51, 54, 61, 64). As an ANDA action involving a generic equivalent, the core of the infringement allegation is that the Qilu product is a copy of the patented Aponvie® product and will be used in the same patented manner.

'229 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An injectable pharmaceutical emulsion comprising: The Qilu Generic Product is an injectable emulsion containing aprepitant. ¶44 '208 Patent, col. 7:41-45
0.4 wt/wt % to 1.0 wt/wt % aprepitant; The Qilu Generic Product allegedly contains aprepitant within the claimed concentration range. ¶¶44, 52 '208 Patent, col. 13:5-8
13 wt/wt % to 15 wt/wt % egg yolk lecithin; The Qilu Generic Product allegedly contains egg yolk lecithin as an emulsifier within the claimed concentration range. ¶52 '208 Patent, col. 11:3-4
9 wt/wt % to 10 wt/wt % soybean oil; and The Qilu Generic Product allegedly contains soybean oil within the claimed concentration range. ¶52 '208 Patent, col. 11:60-65
a pH modifier, wherein the pH modifier is sodium oleate; The Qilu Generic Product allegedly contains sodium oleate as a pH modifier. ¶52 '208 Patent, col. 12:60-63
wherein the pH of the emulsion ranges from 7.5 to 9.0. The Qilu Generic Product allegedly has a final pH within the claimed range. ¶52 '208 Patent, col. 5:1-4

'465 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for preventing or treating a subject at risk of or suffering from emesis, comprising administering to the subject a composition comprising an injectable physically stable emulsion wherein the emulsion comprises: The Qilu Generic Product is intended for preventing emesis and its proposed labeling allegedly directs its administration for this purpose. ¶¶42, 45, 62 '208 Patent, col. 15:46-51
aprepitant; The Qilu Generic Product contains aprepitant as the active ingredient. ¶44 '208 Patent, col. 7:27-31
11 wt/wt % to 15 wt/wt % of an emulsifier; The product allegedly contains an emulsifier within the claimed concentration range. ¶62 '208 Patent, col. 7:62-65
an oil; a co-emulsifier which is an alcohol; a tonicity modifier; a pH modifier; and water; The product is an oil-in-water emulsion alleged to contain these required excipients. ¶¶44, 62 '208 Patent, col. 11:1-25
wherein the ratio of emulsifier:aprepitant ranges from about 18:1 to 22:1, and The product allegedly contains an emulsifier and aprepitant in a ratio that falls within the claimed range. ¶62 '208 Patent, col. 3:39-44
wherein the pH of the emulsion ranges from about 7.5 to 9.0. The Qilu Generic Product allegedly has a final pH within the claimed range. ¶62 '208 Patent, col. 5:1-4

Identified Points of Contention

  • Validity Questions: The complaint notes that for several patents, Qilu's Paragraph IV letter "did not set forth an opinion of noninfringement... separate and apart from any assertions of obviousness" (Compl. ¶¶55, 65, 75, 85, 95, 105). This suggests that the primary point of contention will be Defendants' challenge to the validity of the patents on grounds such as obviousness, rather than a dispute over whether the generic product's formulation literally meets the claim limitations.
  • Scope Questions: A potential dispute may arise over the construction of functional limitations. For instance, in claims requiring the emulsion to be "physically stable," a point of contention could be whether Defendants' product meets the specific definition of that term as provided in the patent specifications over its entire proposed shelf-life (’208 Patent, col. 8:7-22).

V. Key Claim Terms for Construction

The Term: "physically stable"

  • Context and Importance: This term appears in many independent claims (e.g., ’465 Patent, cl. 1) and is a critical performance limitation. Practitioners may focus on this term because infringement requires the accused product to meet this standard. The dispute will likely center on whether Qilu's product satisfies every element of the patent's specific definition of stability throughout its proposed commercial shelf life.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The plain and ordinary meaning of "physically stable" might suggest a general lack of separation or degradation. A party could argue that minor, transient changes do not render an emulsion unstable.
    • Evidence for a Narrower Interpretation: The specification provides an explicit and limiting definition: the emulsion must meet the criteria under USP <729> for globule size and have no visible aprepitant crystals upon storage for a designated time period (’208 Patent, col. 8:7-22). This detailed definition provides strong evidence for a narrow construction that requires satisfaction of both conditions.

The Term: "emulsifier"

  • Context and Importance: The type and amount of emulsifier are central to the composition claims (e.g., ’229 Patent, cl. 1 requires "13 wt/wt % to 15 wt/wt % egg yolk lecithin"). The dispute could turn on whether the specific substance used by Qilu is technically "egg yolk lecithin" as understood in the art and whether its concentration, accounting for manufacturing variances, falls within the claimed range.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes emulsifiers generally as compounds that deter separation and lists various types, including phospholipids (’208 Patent, col. 10:56-64).
    • Evidence for a Narrower Interpretation: The claims themselves narrow the term to specific substances (e.g., "egg yolk lecithin") and concentrations. The specification further describes preferred emulsifiers as naturally occurring phospholipids like lecithin derived from eggs or soy beans, providing context for a narrow definition tied to these specific sources and compositions (’208 Patent, col. 9:28-40).

VI. Other Allegations

Indirect Infringement

The complaint alleges inducement of infringement for the method patents. The basis for this allegation is that Defendants' proposed product labeling will instruct and encourage physicians and other healthcare providers to administer the Qilu Generic Product in a manner that directly infringes the patented methods of treating emesis (Compl. ¶¶45, 54, 57).

Willful Infringement

The complaint alleges that Defendants were aware of the existence of the patents-in-suit prior to the filing of the lawsuit, as evidenced by their Paragraph IV certification (Compl. ¶¶59, 69, 79). This pre-suit knowledge is the basis for the allegation that the act of infringement via the ANDA submission was willful.

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

  • A central issue will be one of patent validity: given that infringement appears to be based on the allegation that the accused product is a bioequivalent copy, the case will likely turn on whether the claimed formulations and methods would have been obvious to a person of ordinary skill in the art at the time of the invention. The court will need to analyze the prior art concerning oil-in-water emulsions and the specific challenges of formulating aprepitant.
  • A key legal question will be one of definitional compliance: can Defendants successfully argue that their generic product avoids infringement by not meeting the patents' specific, multi-part definition of "physically stable" over the product's entire shelf life? This will require a detailed factual analysis of the stability data for the Qilu Generic Product measured against the precise claim construction adopted by the court.