Axsome Malta Ltd v. Hetero USA Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Axsome Malta Ltd. (Malta) and Axsome Therapeutics, Inc. (Delaware)
  • Defendant: Hetero USA Inc. (Delaware), Hetero Labs Limited Unit-V (India), and Hetero Labs Ltd. (India)
  • Plaintiff’s Counsel: Saul Ewing LLP
• Case Identification: 2:24-cv-00196, D.N.J., 01/11/2024
• Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Hetero USA Inc. maintains a regular and established physical place of business in the district, the foreign Defendant entities conduct business in the district through their U.S. subsidiary, and the district is anticipated to be a destination for the accused generic drug product.
• Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market generic solriamfetol oral tablets, a generic version of Plaintiff's Sunosi® product, constitutes an act of infringement of four patents related to methods of safely administering the drug to lactating women.
• Technical Context: The technology concerns pharmaceutical methods for managing drug administration to breastfeeding mothers to minimize the risk of adverse events in nursing infants, a critical safety consideration in pharmacotherapy for women of child-bearing age.
• Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 218654 and its associated Paragraph IV certifications asserting that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by the proposed generic product.

Case Timeline

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

U.S. Patent No. 11,771,666 - Methods of Administering Solriamfetol to Lactating Women

• Patent Identification: U.S. Patent No. 11,771,666, entitled Methods of Administering Solriamfetol to Lactating Women, issued October 3, 2023. (Compl. ¶9; Ex. A).

The Invention Explained

• Problem Addressed: The patent seeks to address the challenge of treating lactating women with solriamfetol while minimizing the risk of adverse events to the nursing infant, who may be exposed to the drug through breast milk. ('666 Patent, col. 2:27-33).
• The Patented Solution: The invention provides a method based on the pharmacokinetic properties of solriamfetol. It specifies orally administering a daily dose of about 150 mg to the mother and then waiting "at least about 5 hours" before feeding the infant breast milk. ('666 Patent, Abstract; col. 2:41-49). This waiting period corresponds with the drug's mean elimination half-life, allowing the concentration in breast milk to decrease and thereby reducing the total dose transferred to the infant. ('666 Patent, col. 8:24-29). The patents' specifications include a graph illustrating that the concentration of solriamfetol in breast milk peaks and then declines over several hours. ('666 Patent, FIG. 1).
• Technical Importance: The method provides a specific, data-driven safety protocol that allows women who require treatment for conditions like narcolepsy to potentially continue breastfeeding with a reduced risk of exposing their infants to clinically significant levels of solriamfetol. ('666 Patent, col. 2:27-33).

Key Claims at a Glance

• The complaint asserts at least independent claim 1. (Compl. ¶35).
• The essential elements of Claim 1 are:
  • A method of reducing exposure to solriamfetol in an infant fed breast milk from a human subject treated with solriamfetol comprising:
  • orally administering the solriamfetol to the subject at a once-daily dose of about 150 mg; and
  • feeding the infant breast milk from the subject at least about 5 hours after administering the solriamfetol to the subject,
  • wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or lower.
• The complaint does not explicitly reserve the right to assert dependent claims but makes a general allegation of infringement of "one or more of the claims." (Compl. ¶35).

U.S. Patent No. 11,771,667 - Methods of Administering Solriamfetol to Lactating Women

• Patent Identification: U.S. Patent No. 11,771,667, entitled Methods of Administering Solriamfetol to Lactating Women, issued October 3, 2023. (Compl. ¶10; Ex. B).

The Invention Explained

• Problem Addressed: As with the '666 Patent, this patent addresses the need for a safe method of using solriamfetol in breastfeeding mothers to avoid adverse effects in the nursing infant. ('667 Patent, col. 2:34-40).
• The Patented Solution: The patent claims a method for treating specific disorders (e.g., excessive daytime sleepiness) in a lactating mother. The method involves the same core steps as the '666 Patent: administering a once-daily dose of about 150 mg and waiting at least about 5 hours before breastfeeding. ('667 Patent, Abstract; col. 2:41-52). This timed administration and feeding protocol is designed to reduce the infant's drug exposure to a specified low level. ('667 Patent, col. 23:57-65).
• Technical Importance: This patent frames the safety protocol as an integral part of a method of treatment, linking the specific dosing and feeding schedule directly to the therapeutic use of solriamfetol for approved indications in this specific patient population. ('667 Patent, col. 2:1-13).

Key Claims at a Glance

• The complaint asserts at least independent claim 1. (Compl. ¶44).
• The essential elements of Claim 1 are:
  • A method of treating excessive daytime sleepiness, attention deficit hyperactivity disorder, binge eating disorder, depression, or cognitive impairment in a lactating human mother feeding an infant with her breast milk, comprising:
  • orally administering solriamfetol to the mother at a once-daily dose of about 150 mg; and
  • feeding the infant the breast milk obtained from the mother at least about 5 hours after administration of the solriamfetol to the mother;
  • wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or lower; and
  • wherein the potential for adverse events in the infant due to the solriamfetol is decreased.
• The complaint generally alleges infringement of "one or more claims" of the patent. (Compl. ¶44).

Multi-Patent Capsule: U.S. Patent No. 11,779,554

• Patent Identification: U.S. Patent No. 11,779,554, entitled Methods of Administering Solriamfetol to Lactating Women, issued October 10, 2023. (Compl. ¶11).
• Technology Synopsis: The patent addresses the problem of safely administering solriamfetol to lactating women by disclosing a method to reduce the risk of adverse events, such as agitation, in the nursing infant. The solution involves administering a specific dose (e.g., about 150 mg or 75 mg) and waiting at least 5 hours before feeding breast milk, thereby limiting the infant's total drug exposure. ('554 Patent, Abstract; col. 2:41-49; col. 25:9-19).
• Asserted Claims: At least independent claims 1 and 10. (Compl. ¶53; '554 Patent, col. 24:50, col. 25:9).
• Accused Features: The complaint alleges that the submission of Hetero's ANDA, which seeks approval to market generic solriamfetol for indications that include use by lactating women, constitutes infringement. (Compl. ¶¶53, 56).

Multi-Patent Capsule: U.S. Patent No. 11,793,776

• Patent Identification: U.S. Patent No. 11,793,776, entitled Methods of Administering Solriamfetol to Lactating Women, issued October 24, 2023. (Compl. ¶12).
• Technology Synopsis: This patent claims methods for treating a postpartum human subject with a disorder amenable to solriamfetol (e.g., excessive daytime sleepiness). The claimed method requires administering a specific dose (e.g., about 150 mg or 75 mg) and then feeding the infant breast milk at least 5 hours later to decrease the infant's exposure to the drug. ('776 Patent, Abstract; col. 2:1-13).
• Asserted Claims: At least independent claims 1, 7, 13, and 19. (Compl. ¶62; '776 Patent, col. 24:1, col. 24:7, col. 24:13, col. 25:1).
• Accused Features: The infringement allegation is based on Hetero's ANDA submission seeking approval to market generic solriamfetol, which Plaintiff contends will induce infringement of the claimed treatment methods. (Compl. ¶¶62, 65).

III. The Accused Instrumentality

• Product Identification: "Hetero's Proposed Product" is a generic version of solriamfetol oral tablets for which Defendant seeks marketing approval from the FDA via ANDA No. 218654. (Compl. ¶¶1, 19).
• Functionality and Market Context: The complaint alleges that Hetero's Proposed Product is a generic equivalent of Axsome's Sunosi®, a dopamine and norepinephrine reuptake inhibitor (DNRI) indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. (Compl. ¶¶2, 13). The act of infringement alleged is the filing of the ANDA itself, which seeks approval for the commercial manufacture, use, and sale of this generic product for a use that is claimed in the patents-in-suit. (Compl. ¶¶29, 35).

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-chart analysis. As is common in initial ANDA complaints, it does not specify which elements of the Defendant's proposed product labeling allegedly map to the specific limitations of the asserted claims. The infringement theory is based on 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA for a drug claimed in a patent or for a use claimed in a patent as an act of infringement. The complaint alleges that by filing its ANDA, Hetero is seeking approval to market a generic drug for uses that are covered by the method claims of the patents-in-suit. (Compl. ¶¶35, 44, 53, 62). Upon approval, Plaintiff alleges that Defendant's marketing and sale of the product with its proposed labeling would induce infringement by physicians and patients. (Compl. ¶¶38, 47, 56, 65).

No probative visual evidence provided in complaint.

• Identified Points of Contention:
  • Scope Questions: A central question may be whether Hetero's proposed product label will instruct or encourage users to perform all steps of the claimed methods. Specifically, a dispute may arise over whether the label induces the step of "feeding the infant breast milk... at least about 5 hours after administering the solriamfetol," particularly if the label is silent on the timing of breastfeeding.
  • Technical Questions: The case may involve technical questions regarding the pharmacokinetic data underlying the patents. A dispute could arise over whether the claimed outcome, such as the infant dose being "reduced to about 0.3 mg or lower," is an inevitable result of administering a 150 mg dose to any lactating mother, or if it depends on patient-specific factors not addressed by the proposed label.

V. Key Claim Terms for Construction

• The Term: "at least about 5 hours"

• Context and Importance: This temporal limitation is the central feature of the patented safety protocol. The scope of "about" will be critical. The infringement analysis for inducement will likely turn on whether Hetero's proposed label encourages a waiting period that falls within the construed scope of this term, even if it does not explicitly recite it. Practitioners may focus on this term because it defines the core inventive concept and is a likely point of non-infringement argument if the accused label is silent on breastfeeding timing.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The use of the word "about" suggests the inventors did not intend a rigid 5.0-hour cutoff. The specification also discloses performing breastfeeding at "3 or more hours, 4 or more hours, or 5 or more hours," which could be argued to support flexibility around the 5-hour mark. ('666 Patent, col. 8:29-32).
  • Evidence for a Narrower Interpretation: The specification ties the 5-hour period to pharmacokinetic data, stating that the mean elimination half-life in breast milk was "approximately 5.0 hours." ('666 Patent, col. 10:58-59). This data-driven basis could be used to argue that "about 5 hours" should be construed narrowly around this specific, technically significant value.

• The Term: "wherein the potential for adverse events in the infant due to the solriamfetol is decreased" ('667 Patent, Claim 1)

• Context and Importance: This clause states the result of the method. Its interpretation could determine whether the claim requires a specific intent to achieve this outcome or if the outcome is simply an inherent result of performing the preceding steps. This is important for the inducement analysis, as Hetero may argue its label does not instruct users to act with the specific purpose of decreasing adverse events.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation (Inherent Result): The specification presents the reduction in adverse events as a direct and automatic consequence of reducing infant exposure through the timed feeding protocol. The abstract and summary describe the method as "thereby decreasing potential for adverse events." ('667 Patent, Abstract). This suggests the clause describes an inherent property, not an additional step requiring specific intent.
  • Evidence for a Narrower Interpretation (Intent Required): One might argue that by including this "wherein" clause, the patentee intended to limit the claim to only those applications where the method is performed for the specific purpose of enhancing safety, a purpose that may not be explicitly stated or encouraged in a generic drug label.

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement. The inducement allegation is based on the assertion that upon FDA approval, Hetero will encourage direct infringement by physicians and patients through its marketing and product labeling. (Compl. ¶¶38, 47, 56, 65). The contributory infringement allegation is based on the assertion that Hetero's product is designed for an infringing use and lacks a substantial non-infringing use. (Compl. ¶¶39, 48, 57, 66).
• Willful Infringement: The complaint does not explicitly allege "willful infringement." However, for each patent, it alleges that the case is "exceptional" and requests an award of attorneys' fees under 35 U.S.C. § 285. (Compl. ¶¶42, 51, 60, 69). The factual basis for knowledge of the patents is Defendant's submission of Paragraph IV certifications, which identified the patents-in-suit. (Compl. ¶¶31-33).

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

• A core issue will be one of induced infringement: does Hetero's proposed product label, by seeking approval for indications that include women of child-bearing age, sufficiently encourage or instruct the full, claimed method of treatment, including the specific "at least about 5 hours" waiting period, to establish the requisite intent for inducement, even if the label is silent on breastfeeding timing?
• A second key question will be one of claim scope and patentability: can the asserted method claims, which combine a known drug administration with a safety instruction based on standard pharmacokinetic principles (i.e., waiting for drug concentration to decrease before breastfeeding), withstand a challenge for obviousness under 35 U.S.C. § 103? The viability of Hetero's Paragraph IV certification and its defense will likely depend on the answer.