DCT

1:25-cv-00829

Heron Therap Inc v. Qilu Pharmaceutical Co Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-00829, D. Del., 07/03/2025
  • Venue Allegations: Plaintiff alleges venue is proper because two defendants are not residents of the United States and have committed acts of infringement in the district, and the third defendant has also committed acts of infringement in the district. Plaintiff further alleges that all defendants have previously availed themselves of the court's jurisdiction in prior litigation.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s Cinvanti® injectable emulsion infringes thirteen patents related to emulsion formulations of the anti-emetic drug aprepitant and methods of their use.
  • Technical Context: The technology involves stable oil-in-water emulsion formulations designed to enable intravenous administration of aprepitant, a poorly water-soluble drug used to prevent chemotherapy-induced nausea and vomiting.
  • Key Procedural History: This is a Hatch-Waxman action filed under 35 U.S.C. § 271(e)(2) within the 45-day statutory window following Plaintiff’s receipt of Defendants' Paragraph IV Notice Letter. The notice letter asserted that the patents-in-suit are invalid and/or would not be infringed by the proposed generic product. The complaint notes for several patents that the notice letter did not set forth a separate opinion of noninfringement apart from assertions of obviousness.

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
2017-11-09 Plaintiff's Cinvanti® NDA Approved by FDA
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
2023-09-05 U.S. Patent No. 11,744,800 Issues
2024-10-15 U.S. Patent Nos. 12,115,254 and 12,115,255 Issue
2025-05-06 U.S. Patent No. 12,290,520 Issues
2025-06-10 Date of Defendants' Paragraph IV Notice Letter
2025-06-11 Plaintiff Receives Defendants' Notice Letter
2025-07-03 Complaint Filed

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

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

  • Patent Identification: U.S. Patent No. 10,500,208, "Emulsion Formulations of Aprepitant," issued December 10, 2019.

The Invention Explained

  • Problem Addressed: The patent describes the active ingredient aprepitant as a drug used to prevent nausea and vomiting associated with cancer chemotherapy (’208 Patent, col. 1:43-48). However, aprepitant has poor water solubility and permeability, which makes creating a stable liquid formulation for intravenous injection technically challenging (’208 Patent, col. 1:53-58). Intravenous emulsions must also maintain a very small and consistent droplet size over their shelf life to avoid causing capillary blockage or embolization in patients (’208 Patent, col. 1:59-65).
  • The Patented Solution: The invention is a stable, oil-in-water emulsion that allows for the intravenous delivery of aprepitant (’208 Patent, Abstract). The formulation places the poorly soluble aprepitant in an oil phase, which is then emulsified in an aqueous phase. The patent discloses that specific compositions—including an oil (e.g., soybean oil), an emulsifier (e.g., lecithin), a co-surfactant (e.g., alcohol), a tonicity agent, and a pH-adjusting agent—at particular ratios and concentrations, result in a formulation that is both physically and chemically stable for prolonged periods (’208 Patent, col. 2:41-49; col. 7:40-57).
  • Technical Importance: This technology provides a non-oral delivery method for an important anti-emetic, which is particularly useful for patients already suffering from the nausea and vomiting that can make oral administration difficult (’208 Patent, col. 1:48-53).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims; Claim 1 is a representative independent claim (Compl. ¶102; ’208 Patent, col. 21:58-22:11).
  • Claim 1 of the '208 Patent recites the following essential elements:
    • 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, but infringement is alleged as to "one or more claims" (Compl. ¶102).

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

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

The Invention Explained

  • Problem Addressed: This patent addresses the same technical challenge as the ’208 Patent: creating a stable, injectable formulation for a class of poorly water-soluble anti-emetic drugs (’850 Patent, col. 1:44-55). It broadens the scope from aprepitant specifically to the class of neurokinin-1 (NK-1) receptor antagonists, which are used to prevent chemotherapy-induced nausea and vomiting (CINV) ('850 Patent, col. 1:25-36).
  • The Patented Solution: The patent claims methods of treating emesis by administering a stable oil-in-water emulsion containing an NK-1 receptor antagonist ('850 Patent, Abstract). The claimed method requires an emulsion with specific components (an NK-1 antagonist, emulsifier, oil, co-surfactant, etc.) and compositional parameters, such as a high ratio of emulsifier to the active drug, which allegedly imparts enhanced stability ('850 Patent, col. 5:5-13, col. 33:5-10).
  • Technical Importance: The invention provides a method for administering an entire class of anti-emetic drugs via a non-oral route, which is a significant benefit for oncology patients who may be unable to tolerate oral medications ('850 Patent, col. 1:37-43).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims; Claim 1 is a representative independent claim (Compl. ¶112; ’850 Patent, col. 33:5-23).
  • Claim 1 of the '850 Patent recites the following essential elements:
    • A method for treating nausea and/or vomiting in a subject.
    • Comprising administering an injectable pharmaceutical emulsion.
    • The emulsion comprises: a neurokinase-1 (NK-1) receptor antagonist; 11 wt/wt % to 15 wt/wt % of an emulsifier; an oil; a co-surfactant which comprises an alcohol; a tonicity agent; a pH modifier; and water.
    • Wherein the pH of the emulsion ranges from about 7.5 to 9.0.
    • Wherein the ratio of the emulsifier to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt %).
  • The complaint alleges infringement of "one or more claims" of the ’850 Patent (Compl. ¶112).

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

  • Patent Identification: U.S. Patent No. 9,561,229, "Emulsion Formulations of Aprepitant," issued February 7, 2017 (Compl. ¶28).
  • Technology Synopsis: The patent describes stable oil-in-water emulsion formulations of aprepitant suitable for intravenous injection. The invention addresses the poor water solubility of aprepitant by incorporating it into an oil phase with specific excipients that ensure the emulsion remains stable with a small droplet size.
  • Asserted Claims: At least one independent claim (Compl. ¶52).
  • Accused Features: The complaint alleges that the composition of the Qilu Generic Product, which is an injectable emulsion of aprepitant, meets all the elements of one or more claims of the ’229 Patent (Compl. ¶52).

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

  • Patent Identification: U.S. Patent No. 9,808,465, "Emulsion Formulations of Aprepitant," issued November 7, 2017 (Compl. ¶29).
  • Technology Synopsis: This patent is directed to stable oil-in-water aprepitant emulsions for intravenous use. The technology focuses on achieving physical and chemical stability through specific ratios of components, including the emulsifier, oil, and aprepitant, and a defined pH range.
  • Asserted Claims: At least one independent claim (Compl. ¶62).
  • Accused Features: The complaint alleges that the Qilu Generic Product is a pharmaceutical composition that embodies the claimed elements of the ’465 Patent (Compl. ¶62).

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

  • Patent Identification: U.S. Patent No. 9,974,742, "Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof," issued May 22, 2018 (Compl. ¶30).
  • Technology Synopsis: This patent covers stable injectable emulsion formulations for the broader class of NK-1 receptor antagonists, not limited to aprepitant. The invention claims compositions that use an oil-in-water emulsion system to deliver these poorly soluble anti-emetic drugs intravenously.
  • Asserted Claims: At least one independent claim (Compl. ¶72).
  • Accused Features: The complaint alleges that the composition of the Qilu Generic Product, as an injectable emulsion containing the NK-1 receptor antagonist aprepitant, infringes the claims of the ’742 Patent (Compl. ¶72).

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

  • Patent Identification: U.S. Patent No. 9,974,793, "Emulsion Formulations of Aprepitant," issued May 22, 2018 (Compl. ¶31).
  • Technology Synopsis: This patent relates to specific, physically stable aprepitant emulsion compositions for intravenous administration. The claims define the invention by reciting specific components and their weight percentages, including aprepitant, egg yolk lecithin as the emulsifier, and soybean oil.
  • Asserted Claims: At least one independent claim (Compl. ¶82).
  • Accused Features: Plaintiff alleges that Defendants’ proposed generic aprepitant emulsion will have a composition that meets the limitations of the claims of the ’793 Patent (Compl. ¶82).

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

  • Patent Identification: U.S. Patent No. 9,974,794, "Emulsion Formulations of Aprepitant," issued May 22, 2018 (Compl. ¶32).
  • Technology Synopsis: This patent is directed to physically stable pharmaceutical compositions of aprepitant in an oil-in-water emulsion format. The invention is defined by specific ratios of the key components, such as the ratio of the emulsifier (egg yolk lecithin) to the active ingredient (aprepitant).
  • Asserted Claims: At least one independent claim (Compl. ¶92).
  • Accused Features: The complaint alleges that the Qilu Generic Product embodies the claimed elements of the ’794 Patent, including the specific ratios of its components (Compl. ¶92).

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

  • Patent Identification: U.S. Patent No. 10,953,018, "Emulsion Formulations of Aprepitant," issued March 23, 2021 (Compl. ¶35).
  • Technology Synopsis: This patent covers methods of treating nausea and vomiting by administering an injectable, physically stable aprepitant emulsion. The invention is defined by the specific composition of the emulsion being administered, including the weight percentages of its components and the ratios between them.
  • Asserted Claims: At least one independent claim (Compl. ¶122).
  • Accused Features: The complaint alleges that the manufacture, use, or sale of the Qilu Generic Product, particularly with its proposed labeling directing its use for preventing emesis, will infringe the method claims of the ’018 Patent (Compl. ¶¶122, 124).

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

  • Patent Identification: U.S. Patent No. 11,173,118, "Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof," issued November 16, 2021 (Compl. ¶36).
  • Technology Synopsis: This patent relates to injectable pharmaceutical emulsions containing an NK-1 receptor antagonist. The claims define the composition by specific weight percentages of the emulsifier and a particular ratio range of the emulsifier to the NK-1 receptor antagonist.
  • Asserted Claims: At least one independent claim (Compl. ¶132).
  • Accused Features: Plaintiff alleges that the Qilu Generic Product's formulation will fall within the claimed compositional parameters of the ’118 Patent (Compl. ¶132).

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

  • Patent Identification: U.S. Patent No. 11,744,800, "Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist," issued September 5, 2023 (Compl. ¶37).
  • Technology Synopsis: This patent claims methods of preventing post-operative nausea and vomiting by administering a specific injectable emulsion containing aprepitant. The method is defined by the specific formulation administered, including the weight percentages of its key components.
  • Asserted Claims: At least one independent claim (Compl. ¶142).
  • Accused Features: The complaint alleges that the use of the Qilu Generic Product as directed by its proposed labeling for preventing emesis will infringe the method claims of the ’800 Patent (Compl. ¶¶142, 144).

U.S. Patent No. 12,115,254 - "Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist"

  • Patent Identification: U.S. Patent No. 12,115,254, "Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist," issued October 15, 2024 (Compl. ¶38).
  • Technology Synopsis: This patent is directed to methods of treating nausea and vomiting by administering an injectable emulsion. The invention is characterized by the specific formulation being administered, including an NK-1 receptor antagonist and defined amounts of an emulsifier, oil, and other excipients.
  • Asserted Claims: At least one independent claim (Compl. ¶152).
  • Accused Features: Plaintiff alleges that the use of the Qilu Generic Product according to its proposed label will infringe the method claims of the ’254 Patent (Compl. ¶¶152, 154).

U.S. Patent No. 12,115,255 - "Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist"

  • Patent Identification: U.S. Patent No. 12,115,255, "Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist," issued October 15, 2024 (Compl. ¶39).
  • Technology Synopsis: This patent covers methods of treating emesis by administering an injectable pharmaceutical emulsion. The claims define the method by the specific composition being used, which includes aprepitant and a defined ratio of emulsifier to aprepitant.
  • Asserted Claims: At least one independent claim (Compl. ¶162).
  • Accused Features: The complaint alleges that the intended use of the Qilu Generic Product for treating emesis will infringe the claimed methods of the ’255 Patent (Compl. ¶¶162, 164).

U.S. Patent No. 12,290,520 - "Methods of Use of Emulsion Formulations of Aprepitant"

  • Patent Identification: U.S. Patent No. 12,290,520, "Methods of Use of Emulsion Formulations of Aprepitant," issued May 6, 2025 (Compl. ¶40).
  • Technology Synopsis: This patent is directed to methods of using specific injectable aprepitant emulsions. The invention is defined by the composition being administered, including particular weight percentages of aprepitant, egg lecithin, and soybean oil.
  • Asserted Claims: At least one independent claim (Compl. ¶172).
  • Accused Features: Plaintiff alleges that the directed use of the Qilu Generic Product for preventing nausea and vomiting will infringe the method claims of the ’520 Patent (Compl. ¶¶172, 174).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the "Qilu Generic Product," an injectable emulsion containing 130mg/18mL (7.2 mg/mL) of aprepitant, for which Defendants submitted ANDA No. 220608 to the FDA (Compl. ¶44).

Functionality and Market Context

  • The Qilu Generic Product is alleged to have the same active ingredient and the same or substantially the same indications and proposed labeling as Plaintiff’s branded drug, Cinvanti® (Compl. ¶45). Cinvanti® is used in combination with other antiemetic agents for the prevention of acute and delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy (Compl. ¶42). By filing an ANDA, Defendants seek to market a generic version of this product prior to the expiration of the patents-in-suit (Compl. ¶44).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain claim charts or detailed infringement theories beyond alleging that the Qilu Generic Product "meets or embodies all elements of one or more claims of each of the patents-in-suit" (Compl. ¶48). The infringement theory is premised on the Qilu Generic Product being a copy of Heron's Cinvanti® product with the same or substantially the same formulation and proposed label (Compl. ¶¶43, 45).

U.S. Patent No. 10,500,208 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An injectable emulsion comprising: aprepitant; The Qilu Generic Product is alleged to be an injectable emulsion containing aprepitant as the active ingredient. ¶¶44, 102 col. 1:43-45
11 wt/wt % to 15 wt/wt % of an emulsifier; The complaint alleges the Qilu Generic Product contains an emulsifier within this concentration range. ¶102 col. 7:61-63
an oil; The complaint alleges the Qilu Generic Product contains an oil as part of its emulsion formulation. ¶102 col. 7:58-60
a co-emulsifier which is an alcohol; The complaint alleges the Qilu Generic Product contains an alcohol co-emulsifier. ¶102 col. 8:13-15
a tonicity modifier; a pH modifier; and water; The complaint alleges the Qilu Generic Product contains these excipients as part of its aqueous phase. ¶102 col. 8:30-34
wherein the pH of the emulsion ranges from about 7.5 to 9.0, The complaint alleges the Qilu Generic Product is formulated to have a pH within this range. ¶102 col. 5:1-3
wherein the emulsion is physically stable. The complaint alleges the Qilu Generic Product is a physically stable emulsion as defined in the patent. ¶102 col. 8:7-22

U.S. Patent No. 10,624,850 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating nausea and/or vomiting in a subject at risk of or suffering from nausea and/or vomiting, the method comprising: administering to the subject an injectable pharmaceutical emulsion The Qilu Generic Product's proposed labeling is alleged to direct its use for treating nausea and vomiting, thereby inducing infringement of this method. ¶¶45, 114 col. 1:25-27
wherein the emulsion comprises: a neurokinase-1 (NK-1) receptor antagonist; The Qilu Generic Product contains aprepitant, which is an NK-1 receptor antagonist. ¶¶44, 112 col. 1:30-32
11 wt/wt % to 15 wt/wt % of an emulsifier; an oil; a co-surfactant which comprises an alcohol; a tonicity agent; a pH modifier; and water; The complaint alleges the Qilu Generic Product's formulation contains these components in the claimed amounts. ¶112 col. 5:5-13
wherein the pH of the emulsion ranges from about 7.5 to 9.0, The complaint alleges the Qilu Generic Product is formulated to have a pH within this range. ¶112 col. 5:15-17
wherein the ratio of the emulsifier to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt %). The complaint alleges the components of the Qilu Generic Product are present in this specific ratio. ¶112 col. 4:51-54

Identified Points of Contention

  • Scope Questions: A central issue may be the construction of "physically stable" (’208 Patent, col. 22:11). The patent provides a specific definition tied to USP standards and the absence of visible crystals (’208 Patent, col. 8:7-22). The dispute may turn on whether Defendants' product meets this precise definition of stability over its proposed shelf life. For the '850 Patent, the scope of "NK-1 receptor antagonist" may be relevant if Defendants argue certain properties of aprepitant distinguish it from the broader class in a way that impacts other claim elements ('850 Patent, col. 2:49-51).
  • Technical Questions: The primary technical questions will be evidentiary. The complaint does not provide the specific formulation of the Qilu Generic Product. A key question for the court will be whether the formulation disclosed in Defendants’ confidential ANDA filing meets every compositional and ratio limitation of the asserted claims, such as the "11 wt/wt % to 15 wt/wt % of an emulsifier" ('208 Patent, col. 21:59) and the "ratio of the emulsifier to the NK-1 receptor antagonist" from 18:1 to 22:1 ('850 Patent, col. 33:21-23).

V. Key Claim Terms for Construction

  • The Term: "an emulsifier"
  • Context and Importance: This term appears in the independent claims of numerous patents-in-suit, often with a required concentration range (e.g., "11 wt/wt % to 15 wt/wt %"). The identity and amount of the emulsifier is critical to the stability and droplet size of the claimed emulsion. The infringement analysis will depend heavily on whether the excipients in the Qilu Generic Product qualify as "an emulsifier" under the patents' definition and are present in the claimed amounts.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification defines "emulsifier" functionally as a compound that deters the separation of oil and aqueous phases and lists numerous examples beyond phospholipids, including propylene glycol esters and polyoxyethylene sorbitan fatty acid esters (’208 Patent, col. 10:56-65). This language may support a broad construction that is not limited to the specific lecithin used in the examples.
    • Evidence for a Narrower Interpretation: The detailed examples in the specification exclusively use "egg lecithin (LIPOID E 80)" as the emulsifier (’208 Patent, col. 16:8-9). A defendant may argue that the invention's success is uniquely tied to this specific type of emulsifier, suggesting that the claims should be construed more narrowly or challenged for lacking adequate written description for a broader scope.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges that Defendants will induce and contribute to infringement of the asserted method-of-use patents (Compl. ¶¶54, 74, 84, 104, 114, 124, 134, 144, 154, 164, 174). The basis for this allegation is that Defendants' proposed product labeling for the Qilu Generic Product will be the same or substantially the same as that for Cinvanti®, thereby instructing and encouraging physicians and patients to use the generic product in an infringing manner (Compl. ¶45).

Willful Infringement

  • The complaint does not explicitly use the word "willful." However, it alleges for each patent-in-suit that "Qilu was aware of the existence of the [asserted] patent" prior to the lawsuit, based on its Paragraph IV certification to the FDA (e.g., Compl. ¶¶59, 69, 79). This allegation of pre-suit knowledge of the patents and alleged infringement provides a potential basis for a later claim of willfulness.

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

  • A central issue will be one of evidentiary proof: does the specific formulation detailed in Defendants' confidential ANDA submission literally map onto every quantitative limitation of the asserted composition claims, particularly the weight percentages of the emulsifier, oil, and other excipients, as well as the ratios between them? The complaint's boilerplate allegations suggest Plaintiff may not yet have this information.
  • The case will also involve a significant validity dispute: can Defendants prove by clear and convincing evidence that the asserted claims, which rely on specific component concentrations and ratios for stability, are obvious in light of prior art related to pharmaceutical emulsions? The complaint's observation that Defendants' notice letter focused on obviousness over non-infringement for certain patents suggests this will be a primary defensive front.