DCT
1:24-cv-00043
Heron Therap Inc v. Mylan Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Heron Therapeutics, Inc. (Delaware)
- Defendant: Mylan Pharmaceuticals Inc. (West Virginia)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Paul, Hastings LLP
- Case Identification: 1:24-cv-00043, D. Del., 01/11/2024
- Venue Allegations: Plaintiff Heron alleges venue is proper in the District of Delaware because Defendant Mylan has committed acts of infringement in the district, intends to market and sell its generic product in the state, is registered to do business in Delaware, and has appointed an agent for service of process in Delaware.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff’s Aponvie® injectable emulsion product constitutes an act of infringement of ten U.S. patents covering formulations of the drug aprepitant.
- Technical Context: The patents relate to stable oil-in-water emulsion formulations for intravenous administration of aprepitant, a drug used to prevent nausea and vomiting, particularly in postoperative settings.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff’s receipt on December 18, 2023, of a Paragraph IV Certification Notice Letter from Defendant, dated December 15, 2023. The letter notified Plaintiff of Defendant's filing of ANDA No. 218851 with the U.S. Food and Drug Administration, which seeks approval to market a generic aprepitant product. 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, & 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 | FDA approves Plaintiff's Aponvie® New Drug Application |
| 2023-09-05 | U.S. Patent No. 11,744,800 Issues |
| 2023-12-15 | Defendant sends Paragraph IV Certification Notice Letter |
| 2023-12-18 | Plaintiff receives Defendant’s Notice Letter |
| 2024-01-11 | Complaint for Patent Infringement Filed |
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 for preventing nausea and vomiting, as an injectable liquid. Aprepitant has poor water solubility and permeability, making it difficult to create a formulation suitable for intravenous administration, which is desirable for patients already experiencing nausea. (’229 Patent, col. 1:45-58).
- The Patented Solution: The invention is a stable oil-in-water emulsion that allows aprepitant to be administered intravenously. The solution involves creating a formulation with specific components—including an oil, an emulsifier, a co-emulsifier, and pH modifiers—at particular concentrations and ratios to ensure the emulsion is both physically and chemically stable, with a small droplet size to prevent blockages in capillaries. (’229 Patent, Abstract; col. 2:3-31).
- Technical Importance: This technology provides a non-oral delivery method for an important anti-emetic drug, which is particularly useful for patients undergoing chemotherapy or in a post-operative setting where oral administration is difficult. (’229 Patent, col. 1:45-54).
Key Claims at a Glance
- The complaint does not identify specific asserted claims but alleges infringement of "one or more claims" of the ’229 Patent (Compl. ¶29). Independent claim 1 is representative of the patent's composition claims.
- Essential Elements of Independent Claim 1:
- 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.
U.S. Patent No. 9,808,465 - "Emulsion Formulations of Aprepitant"
The Invention Explained
- Problem Addressed: The patent addresses the same technical problem as the ’229 Patent: the difficulty of creating a stable, injectable formulation of the poorly soluble anti-emetic drug aprepitant. (’465 Patent, col. 1:45-58).
- The Patented Solution: The invention is a method of preventing or treating emesis by administering a stable, injectable oil-in-water aprepitant emulsion. The stability of the emulsion is a key aspect, defined by criteria under USP <729> regarding droplet size and the absence of visible drug crystals over time. (’465 Patent, Abstract; col. 8:8-23).
- Technical Importance: This patent protects the method of using the formulated aprepitant emulsion, extending protection beyond the composition itself to its clinical application for preventing nausea and vomiting. (’465 Patent, col. 1:45-50).
Key Claims at a Glance
- The complaint does not identify specific asserted claims but alleges infringement of "one or more claims" of the ’465 Patent (Compl. ¶39). Independent claim 1 is representative of the patent's method claims.
- Essential Elements of Independent Claim 1:
- A method for preventing or treating a subject at risk of or suffering from emesis, comprising administering a composition that is an injectable physically stable emulsion, the 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 ratio of emulsifier to aprepitant is from about 18:1 to 22:1, and the pH is from about 7.5 to 9.0.
- The complaint reserves the right to assert additional claims.
U.S. Patent No. 9,974,742 - "Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof"
- Patent Identification: "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 suitable for intravenous administration. It is directed more broadly to neurokinin-1 (NK-1) receptor antagonists, a class of drugs that includes aprepitant, for the treatment of emesis. (’742 Patent, Abstract).
- Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶49).
- Accused Features: The accused feature is the proposed Mylan Generic Product, an injectable aprepitant emulsion (Compl. ¶21, 49).
U.S. Patent No. 9,974,793 - "Emulsion Formulations of Aprepitant"
- Patent Identification: "Emulsion Formulations of Aprepitant," issued May 22, 2018.
- Technology Synopsis: This patent describes specific stable oil-in-water emulsion formulations of aprepitant for parenteral administration. The claims focus on particular ratios and components to achieve a physically stable injectable liquid. (’793 Patent, Abstract).
- Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶59).
- Accused Features: The accused feature is the proposed Mylan Generic Product, an injectable aprepitant emulsion (Compl. ¶21, 59).
U.S. Patent No. 9,974,794 - "Emulsion Formulations of Aprepitant"
- Patent Identification: "Emulsion Formulations of Aprepitant," issued May 22, 2018.
- Technology Synopsis: This patent also describes stable oil-in-water emulsion formulations of aprepitant for intravenous administration. The claims cover specific formulations defined by their components and physical properties, such as pH and component ratios. (’794 Patent, Abstract).
- Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶69).
- Accused Features: The accused feature is the proposed Mylan Generic Product, an injectable aprepitant emulsion (Compl. ¶21, 69).
U.S. Patent No. 10,500,208 - "Emulsion Formulations of Aprepitant"
- Patent Identification: "Emulsion Formulations of Aprepitant," issued December 10, 2019.
- Technology Synopsis: This patent covers novel, stable oil-in-water pharmaceutical formulations of aprepitant suitable for parenteral administration. The invention also includes formulations containing both aprepitant and dexamethasone, another anti-emetic drug. (’208 Patent, Abstract).
- Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶79).
- Accused Features: The accused feature is the proposed Mylan Generic Product, an injectable aprepitant emulsion (Compl. ¶21, 79).
U.S. Patent No. 10,624,850 - "Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof"
- Patent Identification: "Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof," issued April 21, 2020.
- Technology Synopsis: This patent is directed to stable oil-in-water emulsion formulations of NK-1 receptor antagonists generally, and also includes formulations containing both an NK-1 receptor antagonist and dexamethasone sodium phosphate. The technology is for non-oral treatment of emesis. (’850 Patent, Abstract).
- Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶89).
- Accused Features: The accused feature is the proposed Mylan Generic Product, an injectable aprepitant emulsion (Compl. ¶21, 89).
U.S. Patent No. 10,953,018 - "Emulsion Formulations of Aprepitant"
- Patent Identification: "Emulsion Formulations of Aprepitant," issued March 23, 2021.
- Technology Synopsis: The patent discloses stable oil-in-water emulsion formulations of aprepitant, including those combined with dexamethasone sodium phosphate, for intravenous administration to treat emesis. (’018 Patent, Abstract).
- Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶99).
- Accused Features: The accused feature is the proposed Mylan Generic Product, an injectable aprepitant emulsion (Compl. ¶21, 99).
U.S. Patent No. 11,173,118 - "Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof"
- Patent Identification: "Emulsion Formulations of an NK-1 Receptor Antagonist and Uses Thereof," issued November 16, 2021.
- Technology Synopsis: This patent covers stable oil-in-water emulsion formulations of NK-1 receptor antagonists, including those combined with dexamethasone, for non-oral treatment of emesis. (’118 Patent, Abstract).
- Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶109).
- Accused Features: The accused feature is the proposed Mylan Generic Product, an injectable aprepitant emulsion (Compl. ¶21, 109).
U.S. Patent No. 11,744,800 - "Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist"
- Patent Identification: "Methods of Use of Emulsion Formulations of an NK-1 Receptor Antagonist," issued September 5, 2023.
- Technology Synopsis: This patent covers methods of using the disclosed stable oil-in-water emulsion formulations of NK-1 receptor antagonists for treating emesis, particularly in subjects undergoing highly emetogenic cancer chemotherapy. (’800 Patent, Abstract).
- Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶119).
- Accused Features: The accused feature is the proposed Mylan Generic Product, an injectable aprepitant emulsion, and its intended use for preventing nausea and vomiting (Compl. ¶21-22, 119).
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is identified as "the Mylan Generic Product," which is an injectable emulsion containing 32mg/4.4mL (7.2 mg/mL) of the active ingredient aprepitant (Compl. ¶21). This product is the subject of Mylan's ANDA No. 218851 submitted to the FDA (Compl. ¶21).
- Functionality and Market Context: The complaint alleges that the Mylan Generic Product has the same active ingredient and the same or substantially the same indications as Plaintiff's branded drug, Aponvie® (Compl. ¶22). Aponvie® is indicated for the prevention of postoperative nausea and vomiting in adults (Compl. ¶19). The Mylan Generic Product is intended for commercial manufacture, use, and sale in the United States upon receiving FDA approval (Compl. ¶21). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide a claim chart or specific factual allegations mapping elements of the asserted claims to the accused product. The analysis below is based on the representative independent claims selected in Section II and the general allegations in the complaint.
U.S. Patent No. 9,561,229 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An injectable pharmaceutical emulsion comprising: | The complaint alleges Mylan's Generic Product is an injectable emulsion containing aprepitant. | ¶21 | col. 2:42-49 |
| 0.4 wt/wt % to 1.0 wt/wt % aprepitant; | The complaint alleges the Mylan Generic Product meets all elements of one or more claims. | ¶29 | col. 14:3-8 |
| 13 wt/wt % to 15 wt/wt % egg yolk lecithin; | The complaint alleges the Mylan Generic Product meets all elements of one or more claims. | ¶29 | col. 14:9-16 |
| 9 wt/wt % to 10 wt/wt % soybean oil; and | The complaint alleges the Mylan Generic Product meets all elements of one or more claims. | ¶29 | col. 11:1-2 |
| a pH modifier, wherein the pH modifier is sodium oleate; | The complaint alleges the Mylan Generic Product meets all elements of one or more claims. | ¶29 | col. 12:60-64 |
| wherein the pH of the emulsion ranges from 7.5 to 9.0. | The complaint alleges the Mylan Generic Product meets all elements of one or more claims. | ¶29 | col. 12:1-3 |
U.S. Patent No. 9,808,465 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for preventing or treating ... emesis, comprising administering a composition | The Mylan Generic Product is alleged to have the same indications as Aponvie®, which is used to prevent nausea and vomiting. Mylan's proposed label allegedly directs this use. | ¶22 | col. 1:45-50 |
| which is an injectable physically stable emulsion | The complaint alleges Mylan's Generic Product is an injectable emulsion. | ¶21 | col. 8:8-23 |
| comprising: aprepitant; | The Mylan Generic Product contains aprepitant as its active ingredient. | ¶21 | col. 1:26-43 |
| 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; | The complaint alleges the Mylan Generic Product meets all elements of one or more claims. | ¶39 | col. 13:60-65 |
| wherein the ratio of emulsifier:aprepitant ranges from about 18:1 to 22:1, and | The complaint alleges the Mylan Generic Product meets all elements of one or more claims. | ¶39 | col. 17:1-3 |
| wherein the pH of the emulsion ranges from about 7.5 to 9.0. | The complaint alleges the Mylan Generic Product meets all elements of one or more claims. | ¶39 | col. 17:18-20 |
- Identified Points of Contention:
- Factual Questions: The primary point of contention will be factual: does the precise formulation of the Mylan Generic Product, including the identity and weight percentages of all excipients, fall within the ranges specified in the asserted claims? The complaint does not provide these details. Mylan’s Paragraph IV letter, by asserting non-infringement, suggests a factual mismatch between its formulation and the patent claims (Compl. ¶23).
- Scope Questions: A potential dispute may arise over the definition of claim terms such as "physically stable." Infringement of method claims like Claim 1 of the ’465 Patent will depend on whether Mylan's product meets the patent's specific criteria for stability, which is defined functionally with reference to USP standards and the absence of crystallization (’465 Patent, col. 8:8-23).
V. Key Claim Terms for Construction
The Term: "emulsifier"
Context and Importance: This term is central to the composition claims (e.g., Claim 1 of the ’229 Patent) and method claims (e.g., Claim 1 of the ’465 Patent). The specific type (e.g., egg yolk lecithin) and amount of the emulsifier are critical for creating the stable emulsion that is the core of the invention. Practitioners may focus on this term because a non-infringement defense could be based on an argument that the substance used in the Mylan product is chemically different or does not function as the claimed "emulsifier" in the context of the patent.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a general definition of an "emulsifier" as a compound that "deters the separation of the injectable emulsion into individual oil and aqueous phases" and lists numerous suitable examples beyond lecithin, such as propylene glycol esters and polyoxyethylene sorbitan fatty acid esters (’229 Patent, col. 8:56-col. 9:4).
- Evidence for a Narrower Interpretation: The claims themselves, such as Claim 1 of the ’229 Patent, explicitly recite "egg yolk lecithin," suggesting a narrower scope for that specific claim. Further, the specification emphasizes that "naturally occurring lecithin" is an exemplary type of phospholipid emulsifier (’229 Patent, col. 9:28-41).
The Term: "physically stable"
Context and Importance: This term appears in method claims, such as Claim 1 of the ’465 Patent, and represents a required functional property of the administered emulsion. Infringement will depend on whether the Mylan product exhibits this characteristic. Practitioners may focus on this term because it links infringement to the performance and characteristics of the accused product over time, which will be a matter of factual evidence and testing.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The complaint does not provide sufficient detail for analysis of this element.
- Evidence for a Narrower Interpretation: The specification provides a specific, multi-part definition for "physically stable." It requires that the emulsion meet the criteria under USP <729> (defining limits for mean droplet size and the population of large-diameter fat globules) and also show "no visible aprepitant crystals upon storage at 5° C. or room temperature for a designated time period." (’465 Patent, col. 8:8-23). This explicit definition provides a clear, albeit narrow, benchmark for infringement.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Mylan will induce infringement of method claims by virtue of its proposed product labeling, which will allegedly instruct healthcare professionals to administer the generic product for the patented indications (Compl. ¶¶ 22, 31). It also alleges contributory infringement, although the factual basis is not detailed (Compl. ¶31).
- Willful Infringement: Willfulness allegations are based on Mylan's alleged pre-suit knowledge of the patents-in-suit. The complaint asserts that Mylan was aware of the patents and knew that the submission of its ANDA and the certification constituted an act of infringement (Compl. ¶¶ 36, 46, 56, 66, 76, 86, 96, 106, 116, 126).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of compositional identity: does the precise formulation of the Mylan Generic Product—specifically its excipients, their weight percentages, pH, and component ratios—literally fall within the ranges claimed by Heron’s patents, or does it occupy a non-infringing space outside those parameters?
- A key evidentiary question will be one of validity: as suggested by Mylan’s Paragraph IV certification, are the claimed emulsion formulations obvious over prior art? The complaint repeatedly notes that Mylan's notice letter focused on obviousness, suggesting this will be a primary defense and a focal point of the litigation (Compl. ¶¶ 32, 42, 52).