DCT
1:24-cv-00830
Heron Therap Inc v. Azurity Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Heron Therapeutics, Inc. (Delaware)
- Defendant: Slayback Pharma LLC (Delaware) and Slayback Pharma India LLP (India)
- Plaintiff’s Counsel: Saul Ewing LLP; Paul Hastings LLP
- Case Identification: 1:24-cv-00830, D.N.J., 01/24/2024
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendant Slayback LLC’s principal place of business and commission of infringing acts within the district. For Defendant Slayback India, venue is based on its status as a non-U.S. resident and its alleged commission of infringing acts in the district.
- Core Dispute: Plaintiff alleges that Defendants’ submission of a New Drug Application to the U.S. Food and Drug Administration for a generic version of Plaintiff’s Cinvanti® product constitutes an act of infringement of ten patents related to emulsion formulations of the antiemetic drug aprepitant.
- Technical Context: The technology concerns stable, injectable oil-in-water emulsions for aprepitant, a poorly water-soluble compound, used for the prevention of chemotherapy-induced nausea and vomiting.
- Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' submission of New Drug Application No. 218754 with a Paragraph IV certification, asserting that the patents-in-suit are invalid and/or not infringed. Plaintiff states it received the corresponding notice letter on December 12, 2023, and filed this complaint within the statutory 45-day window, triggering a potential 30-month stay of regulatory approval for Defendants' product. The complaint notes related litigation involving the same plaintiff and overlapping patents against other generic drug manufacturers.
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® Product 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 |
| 2023-12-12 | Plaintiff Receives Slayback Notice Letter |
| 2024-01-24 | Complaint Filing Date |
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 challenge of creating a liquid formulation of the anti-nausea drug aprepitant suitable for intravenous administration (’229 Patent, col. 1:45-49). Aprepitant's poor water solubility makes such formulations difficult to create, and oral capsules are often unsuitable for patients already experiencing nausea and vomiting associated with chemotherapy ('229 Patent, col. 1:40-45).
- The Patented Solution: The invention is a stable oil-in-water emulsion that allows aprepitant to be administered intravenously ('229 Patent, Abstract). The formulation comprises an oil phase containing aprepitant, soybean oil, and an emulsifier (egg yolk lecithin), and an aqueous phase containing water, a tonicity agent, and a pH-adjusting agent, creating a physically and chemically stable injectable liquid ('229 Patent, col. 2:40-47). The stability of the emulsion, defined by maintaining a small droplet size and preventing drug crystallization over time, is a key aspect of the solution ('229 Patent, col. 2:2-34).
- Technical Importance: This technology provided a non-oral delivery route for aprepitant, offering a significant clinical benefit for patients undergoing highly emetogenic cancer therapy who cannot tolerate oral medications ('229 Patent, col. 1:40-49).
Key Claims at a Glance
- The complaint does not identify specific claims, asserting infringement of "one or more claims of the ’229 patent" (Compl. ¶49). Independent claim 1 is representative of the patent's composition claims.
- The essential elements of independent claim 1 include:
- 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. 9,808,465 - "Emulsion Formulations of Aprepitant," Issued November 7, 2017
The Invention Explained
- Problem Addressed: Similar to the ’229 patent, this patent addresses the need for a non-oral, injectable formulation of aprepitant for patients suffering from chemotherapy-induced nausea and vomiting (’465 Patent, col. 1:42-56).
- The Patented Solution: The invention is a method for preventing or treating emesis by administering a specific type of injectable, physically stable aprepitant emulsion ('465 Patent, Abstract). The claimed method requires an emulsion with defined components, including aprepitant, an emulsifier, an oil, an alcohol co-emulsifier, a tonicity modifier, a pH modifier, and water, with specific ratios between the emulsifier and aprepitant ('465 Patent, col. 2:38-47; Claim 1). The concept of "physical stability," defined with reference to USP standards and the absence of drug crystals, is central to the claimed method ('465 Patent, col. 8:5-22).
- Technical Importance: This patent protects the therapeutic application of the stable aprepitant emulsions, complementing the composition claims of related patents by covering the actual use of the formulation to treat patients ('465 Patent, col. 1:42-49).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims of the ’465 patent" (Compl. ¶58). Independent claim 1 is a representative method claim.
- The essential elements of independent claim 1 include:
- A method for preventing or treating a subject at risk of or suffering from emesis, comprising administering 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 does not explicitly reserve the right to assert dependent claims.
Multi-Patent Capsules
- 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 claims an injectable pharmaceutical emulsion containing a neurokinin-1 (NK-1) receptor antagonist (a class of drugs that includes aprepitant) (’742 Patent, Abstract). The claims define the emulsion by specific weight percentages of its components, including the emulsifier, oil, and a co-surfactant which is an alcohol ('742 Patent, Claim 1).
- Asserted Claims: Independent claim 1.
- Accused Features: Defendants' Proposed Slayback Product is alleged to meet the compositional elements of one or more claims of the ’742 patent (Compl. ¶67).
- U.S. Patent No. 9,974,793: "Emulsion Formulations of Aprepitant," issued May 22, 2018.
- Technology Synopsis: This patent claims a physically stable pharmaceutical composition comprising aprepitant, egg yolk lecithin, and soybean oil (’793 Patent, Abstract). The claims are defined by specific ratios of the emulsifier to aprepitant and the oil to aprepitant ('793 Patent, Claim 1).
- Asserted Claims: Independent claims 1 and 15.
- Accused Features: Defendants' Proposed Slayback Product is alleged to meet the compositional elements and specific component ratios of one or more claims of the ’793 patent (Compl. ¶76).
- U.S. Patent No. 9,974,794: "Emulsion Formulations of Aprepitant," issued May 22, 2018.
- Technology Synopsis: This patent claims an injectable pharmaceutical emulsion comprising specific weight percentages of aprepitant, egg yolk lecithin, and soybean oil, with a pH modifier of sodium oleate (’794 Patent, Abstract). The claims require a final emulsion pH between 7.5 and 9.0 ('794 Patent, Claim 1).
- Asserted Claims: Independent claims 1 and 8.
- Accused Features: The Proposed Slayback Product is alleged to contain the components at the concentrations and pH recited in one or more claims of the ’794 patent (Compl. ¶85).
- U.S. Patent No. 10,500,208: "Emulsion Formulations of Aprepitant," issued December 10, 2019.
- Technology Synopsis: This patent claims an injectable emulsion that requires physical stability and comprises aprepitant, an emulsifier, an oil, an alcohol co-emulsifier, a tonicity modifier, and a pH modifier (’208 Patent, Abstract). The claims specify particular ratios of emulsifier-to-aprepitant and oil-to-aprepitant ('208 Patent, Claim 1).
- Asserted Claims: Independent claim 1.
- Accused Features: The Proposed Slayback Product is alleged to be a physically stable emulsion meeting the component and ratio limitations of one or more claims of the ’208 patent (Compl. ¶94).
- 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 claims a method for treating emesis by administering an injectable, physically stable emulsion containing an NK-1 receptor antagonist (’850 Patent, Abstract). The claims define the required emulsion by specific component weight percentages and ratios, including a co-surfactant that is an alcohol ('850 Patent, Claim 1).
- Asserted Claims: Independent claim 1.
- Accused Features: The proposed labeling for the Proposed Slayback Product is alleged to instruct for its use in a manner that performs the claimed method of treatment (Compl. ¶103).
- U.S. Patent No. 10,953,018: "Emulsion Formulations of Aprepitant," issued March 23, 2021.
- Technology Synopsis: This patent claims a method for treating nausea and vomiting by administering a physically stable pharmaceutical composition comprising aprepitant (’018 Patent, Abstract). The claims define the required emulsion by specific ratios of emulsifier-to-aprepitant and oil-to-aprepitant ('018 Patent, Claim 1).
- Asserted Claims: Independent claim 1.
- Accused Features: The manufacture, use, or sale of the Proposed Slayback Product, and its proposed labeling, is alleged to constitute performance of the claimed method (Compl. ¶112).
- 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 claims an injectable emulsion comprising an NK-1 receptor antagonist, an emulsifier, an oil, a co-surfactant, a tonicity agent, a pH modifier, and water (’118 Patent, Abstract). The claims require specific ratios of the emulsifier to the antagonist ('118 Patent, Claim 1).
- Asserted Claims: Independent claim 1.
- Accused Features: The Proposed Slayback Product is alleged to meet the compositional and ratio limitations of one or more claims of the ’118 patent (Compl. ¶121).
- 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 claims a method for preventing post-operative nausea and vomiting by intravenously administering a specific injectable pharmaceutical emulsion (’800 Patent, Abstract). The claims recite specific weight percentages for egg lecithin, soybean oil, ethanol, sucrose, and sodium oleate, as well as a specific ratio of egg lecithin to aprepitant ('800 Patent, Claim 22).
- Asserted Claims: Independent claim 22.
- Accused Features: The Proposed Slayback Product is alleged to be a composition that will be used according to its label to perform the claimed method (Compl. ¶130).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is the "Proposed Slayback Product," an injectable emulsion containing 130mg/18mL (7.2 mg/mL) aprepitant, for which Defendants submitted New Drug Application ("NDA") No. 218754 to the FDA (Compl. ¶¶13, 18).
Functionality and Market Context
- The complaint alleges that the Proposed Slayback Product is a generic version of Plaintiff's Cinvanti® product (Compl. ¶¶4, 41). It is alleged to have the same active ingredient (aprepitant), the same or substantially the same indications, and the same or substantially the same proposed labeling as Cinvanti®, which is used for the prevention of acute and delayed nausea and vomiting associated with cancer chemotherapy (Compl. ¶¶38, 42). The complaint alleges on information and belief that the proposed product contains the same or equivalent ingredients in the same or equivalent amounts as the compositions claimed in the patents-in-suit (Compl. ¶41).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide a detailed element-by-element infringement analysis or claim chart exhibit. The infringement allegations are made on "information and belief" based on the theory that Defendants' product is a generic version of Plaintiff's Cinvanti® product, which Plaintiff asserts is an embodiment of the patents-in-suit (Compl. ¶¶39, 41, 49).
’229 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An injectable pharmaceutical emulsion comprising: | The Proposed Slayback Product is alleged to be an injectable emulsion formulation of aprepitant. | ¶¶18, 41 | col. 2:40-42 |
| 0.4 wt/wt % to 1.0 wt/wt % aprepitant | The complaint alleges that the Proposed Slayback Product has the same or equivalent ingredients in the same or equivalent amounts as the claimed compositions. | ¶41 | col. 23:13-14 |
| 13 wt/wt % to 15 wt/wt % egg yolk lecithin | The complaint alleges that the Proposed Slayback Product has the same or equivalent ingredients in the same or equivalent amounts as the claimed compositions. | ¶41 | col. 23:15-16 |
| 9 wt/wt % to 10 wt/wt % soybean oil | The complaint alleges that the Proposed Slayback Product has the same or equivalent ingredients in the same or equivalent amounts as the claimed compositions. | ¶41 | col. 23:17-18 |
| a pH modifier, wherein the pH modifier is sodium oleate | The complaint alleges that the Proposed Slayback Product has the same or equivalent ingredients in the same or equivalent amounts as the claimed compositions. | ¶41 | col. 23:19-20 |
| wherein the pH of the emulsion ranges from 7.5 to 9.0 | The complaint alleges that the Proposed Slayback Product has the same or equivalent ingredients and performs substantially the same function to achieve the same result as Cinvanti®. | ¶41 | col. 23:21-22 |
’465 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for preventing or treating ... emesis, comprising administering ... an injectable physically stable emulsion | The complaint alleges that Defendants' proposed labeling will direct the use of the Proposed Slayback Product for the same indications as Cinvanti®, which includes preventing emesis. | ¶42 | col. 1:13-18 |
| aprepitant | The Proposed Slayback Product is alleged to contain aprepitant as its active ingredient. | ¶¶18, 42 | col. 21:60 |
| 11 wt/wt % to 15 wt/wt % of an emulsifier | The complaint alleges that the Proposed Slayback Product has the same or equivalent ingredients in the same or equivalent amounts as the claimed compositions. | ¶41 | col. 21:61 |
| an oil; a co-emulsifier which is an alcohol; a tonicity modifier; a pH modifier; and water | The complaint alleges that the Proposed Slayback Product has the same or equivalent ingredients in the same or equivalent amounts as the claimed compositions. | ¶41 | col. 21:62-63 |
| wherein the ratio of emulsifier:aprepitant ranges from about 18:1 to 22:1 | The complaint alleges that the Proposed Slayback Product has the same or equivalent ingredients in the same or equivalent amounts as the claimed compositions. | ¶41 | col. 21:64-65 |
| wherein the pH of the emulsion ranges from about 7.5 to 9.0 | The complaint alleges that the Proposed Slayback Product has the same or equivalent ingredients and performs substantially the same function to achieve the same result as Cinvanti®. | ¶41 | col. 21:66-67 |
Identified Points of Contention
- Scope Questions: A central issue will be whether the specific components and concentrations in Defendants’ undisclosed formulation fall within the ranges claimed in the patents. For instance, does the term "egg yolk lecithin" as used in the ’229 patent read on the specific emulsifier used by Defendants, and is it present at "13 wt/wt % to 15 wt/wt %"?
- Technical Questions: An evidentiary question is whether Defendants' product is, in fact, "physically stable" under the definition provided in the '465 Patent, which requires meeting USP <729> criteria and showing no visible aprepitant crystals over a designated period ('465 Patent, col. 8:5-22). The complaint does not provide any test data for the accused product, making this a key factual dispute that will depend on discovery.
V. Key Claim Terms for Construction
The Term: "physically stable"
- Context and Importance: This term appears in method claims, such as claim 1 of the ’465 Patent. Practitioners may focus on this term because infringement depends not only on the composition administered but also on whether that composition possesses the claimed property of physical stability. The dispute may turn on whether Defendants' product meets the specific, multi-part definition of stability provided in the patent.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that "physically stable" should be given its plain and ordinary meaning in the context of pharmaceutical emulsions, potentially encompassing formulations that are stable by other metrics not explicitly recited.
- Evidence for a Narrower Interpretation: The specification provides a very explicit definition: an emulsion is "physically stable" if it meets the criteria under USP <729> for mean droplet size and large-diameter fat globules, and also shows "no visible aprepitant crystals upon storage" for a specified time ('465 Patent, col. 8:5-22). This detailed definition may support a narrower construction limited to emulsions that satisfy all of these specific criteria.
The Term: "emulsifier" and "egg yolk lecithin"
- Context and Importance: These terms are central to the composition claims, such as claim 1 of the ’229 Patent ("egg yolk lecithin") and claim 1 of the ’465 Patent ("emulsifier"). Infringement will depend entirely on the identity and source of the excipient used in the Proposed Slayback Product. A dispute could arise over whether an emulsifier derived from a different source or having a slightly different composition falls within the scope of the claims.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes "lecithin" as a class that includes not only egg-yolk derived lecithin but also those derived from soy and corn ('229 Patent, col. 9:43-50). A party could argue that in claims reciting the broader term "emulsifier," this disclosure supports a wide scope.
- Evidence for a Narrower Interpretation: For claims that specifically recite "egg yolk lecithin," the specificity of the language itself provides strong evidence for a narrow construction that excludes lecithins from other sources. The patentee's choice to claim the species ("egg yolk lecithin") rather than the genus ("lecithin" or "emulsifier") suggests a deliberate narrowing of scope.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendants will induce and contribute to infringement by selling the Proposed Slayback Product with proposed labeling that will instruct healthcare providers and patients to use the product in an infringing manner, specifically for the prevention of chemotherapy-induced nausea and vomiting (Compl. ¶¶42, 51, 60).
- Willful Infringement: Willfulness is alleged based on Defendants' pre-suit knowledge of the patents-in-suit (Compl. ¶¶55, 64). The complaint asserts this awareness stems from the Hatch-Waxman process, which requires a generic applicant to make a certification against patents listed in the FDA's Orange Book for the branded drug, and from providing notice of that certification to the patent holder (Compl. ¶¶39, 44).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: as the complaint is based on "information and belief," the case will turn on whether discovery reveals that the precise, undisclosed formulation of the Proposed Slayback Product—including the identity, concentration, and ratios of its excipients—literally meets every limitation of the asserted composition claims.
- A key legal question will be one of claim scope: can the term "physically stable" be construed narrowly to the patent’s explicit multi-part definition, and can terms like "egg yolk lecithin" be limited to their specific source? The outcome of claim construction will determine whether minor variations in Defendants' formulation, if any, are sufficient to place it outside the literal scope of the claims.
- A core issue for the method claims will be induced infringement: does the proposed label for the Slayback product, once produced, necessarily instruct medical professionals to administer the emulsion in a manner that performs all steps of the claimed methods for treating emesis, thereby creating liability for inducement?