Axsome Malta Ltd v. Unichem Laboratories Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Axsome Malta Ltd. (Malta) and Axsome Therapeutics, Inc. (Delaware)
  • Defendant: Unichem Laboratories Ltd. (India)
  • Plaintiff’s Counsel: Saul Ewing LLP
• Case Identification: 2:23-cv-23255, D.N.J., 12/20/2023
• Venue Allegations: Plaintiff alleges venue is proper because Defendant is a foreign company and has conducted systematic and continuous business in the district, including marketing pharmaceutical products. The complaint also notes that Defendant has previously consented to personal jurisdiction in the District of New Jersey in other ANDA litigation.
• Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's Sunosi® (solriamfetol) oral tablets infringes five patents related to methods of using solriamfetol to treat sleep-wake disorders and to administer the drug to lactating women.
• Technical Context: The dispute concerns solriamfetol, a dopamine and norepinephrine reuptake inhibitor (DNRI) approved to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea.
• Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendant’s submission of an ANDA with a Paragraph IV certification, alleging that Plaintiff’s patents are invalid and/or will not be infringed by the proposed generic product. Defendant provided notice of its certification to Plaintiff in two letters, dated August 9, 2023, and November 7, 2023.

Case Timeline

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

U.S. Patent No. 11,753,368 - "Treatment of Sleep-Wake Disorders"

The Invention Explained

• Problem Addressed: The patent addresses Excessive Daytime Sleepiness (EDS), a debilitating condition that can arise from disorders like narcolepsy or sleep apnea. It notes that existing treatments, such as CNS stimulants, may have significant side effects or require high doses to be effective (’368 Patent, col. 1:41-52; col. 4:54-67).
• The Patented Solution: The invention claims a method for treating sleep-wake disorders by administering a phenylalkylamino carbamate compound, specifically the (R)-enantiomer known as solriamfetol. The patent describes this compound as having an "activating or energizing effect" that increases active wakefulness at the expense of time spent in sleep, based on animal studies (’368 Patent, Abstract; col. 6:50-61).
• Technical Importance: The invention provides a method of using a specific chemical entity to address the significant clinical need for effective EDS treatments that may possess a distinct mechanism of action from traditional stimulants (’368 Patent, col. 6:52-56).

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶28, 30-32).
• Claim 1 recites essential elements for:
  • A method of treating a sleep-wake disorder in a subject
  • Comprising administration of a therapeutically effective amount of a compound of Formula (I) or its salt/ester, where the compound is identified as solriamfetol
  • Wherein the cause of the disorder is chosen from a specific list including narcolepsy, obstructive sleep apnea, insufficient nocturnal sleep, Parkinson's disease, and others
• The complaint does not explicitly reserve the right to assert dependent claims but makes general allegations of infringement of "one or more claims" (Compl. ¶30).

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

The Invention Explained

• Problem Addressed: The patent addresses the challenge of administering solriamfetol to a lactating subject. It recognizes that the drug may be present in breast milk, creating a risk of adverse events for the nursing infant, and that solriamfetol concentrations in breast milk can be higher than in plasma (’666 Patent, col. 1:20-32; col. 5:15-18).
• The Patented Solution: The patent discloses a method to reduce an infant's exposure to solriamfetol by timing the feeding schedule relative to the mother's dose. The proposed solution is to feed the infant "at least about 5 hours after administering the solriamfetol to the subject," a timeframe based on the drug's pharmacokinetic profile and mean elimination half-life, which decreases the potential for adverse events in the infant (’666 Patent, Abstract; col. 7:31-35). Figure 1 illustrates the time course of solriamfetol concentration in plasma versus breast milk, providing the scientific basis for the claimed delay (’666 Patent, Fig. 1).
• Technical Importance: This invention provides a specific, data-driven dosing and feeding regimen intended to enhance the safety profile for the particular patient population of breastfeeding mothers who require treatment for EDS.

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶37, 39-41).
• Claim 1 recites essential elements for:
  • A method of reducing exposure to solriamfetol in an infant fed breast milk from a human subject treated with the drug
  • Comprising orally administering solriamfetol at a once-daily dose of about 150 mg
  • And feeding the infant breast milk at least about 5 hours after administration
  • Wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or lower
• The complaint makes general allegations of infringement of "one or more claims" (Compl. ¶39).

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

• Technology Synopsis: Similar to the ’666 Patent, this patent addresses the safe administration of solriamfetol to breastfeeding mothers. It discloses a method of timed feeding relative to drug administration to decrease the potential for adverse events in the nursing infant, such as agitation, insomnia, anorexia, or reduced weight gain (’667 Patent, Abstract; col. 2:4-8).
• Asserted Claims: At least independent claim 1 is asserted (Compl. ¶46, 48-50).
• Accused Features: The accused features are the instructions and indications for use in Defendant's proposed generic product label, which Plaintiff alleges will induce infringement of the claimed methods (Compl. ¶46, 49).

U.S. Patent No. 11,779,554 (’554 Patent) - "Methods of Administering Solriamfetol to Lactating Women"

• Technology Synopsis: This patent is also directed to methods for safely administering solriamfetol to lactating women to reduce infant exposure and risk of adverse events. The claims focus on specific dosages (e.g., 75 mg) and the resulting reduction in the risk of agitation in the infant (’554 Patent, col. 24:49-61).
• Asserted Claims: At least independent claims 1 and 10 are asserted (Compl. ¶55, 57-59).
• Accused Features: Plaintiff alleges that Defendant's submission of an ANDA for its proposed generic product, which will be marketed for the same indications as Sunosi®, infringes the claimed methods (Compl. ¶55, 58).

U.S. Patent No. 11,793,776 (’776 Patent) - "Methods of Administering Solriamfetol to Lactating Women"

• Technology Synopsis: This patent continues the theme of safe administration of solriamfetol to breastfeeding mothers. It claims methods of treating various disorders (e.g., excessive daytime sleepiness) in a postpartum human subject by administering specific doses of solriamfetol and timing infant feeding to occur at least 5 hours later, thereby reducing the infant's drug exposure (’776 Patent, col. 23:41-55).
• Asserted Claims: At least independent claim 1 is asserted (Compl. ¶64, 66-68).
• Accused Features: The accused features are the anticipated instructions for use on the label of Defendant's generic solriamfetol product (Compl. ¶64, 67).

III. The Accused Instrumentality

Product Identification

• Defendant Unichem’s proposed generic solriamfetol oral tablets, for which it seeks FDA approval via ANDA No. 218761 ("Unichem's Proposed Product") (Compl. ¶1, 18).

Functionality and Market Context

• As an ANDA case, the infringement is predicated on the act of filing the application to market a generic drug prior to patent expiry (Compl. ¶22). The relevant functionality is that which will be described on the proposed product's label. The complaint alleges that Unichem seeks approval to market its generic product for the same indications as Axsome’s Sunosi®, namely "to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea" (Compl. ¶12). Upon approval, Unichem would compete directly with Axsome's branded Sunosi® product (Compl. ¶23).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint does not contain or reference a claim chart exhibit. The infringement theory in an ANDA case is that the defendant's proposed product label will instruct physicians and patients to use the generic drug in a manner that directly infringes the asserted method claims, thereby making the defendant liable for induced infringement. The following tables summarize this theory based on the complaint's allegations.

11753368 Infringement Allegations

11771666 Infringement Allegations

• Identified Points of Contention:
  • Scope Questions (’368 Patent): A potential dispute may arise over the scope of "sleep-wake disorder." While the core indications of narcolepsy and obstructive sleep apnea are central, the claim includes a broad list of other conditions (e.g., "chronic pain," "urinary incontinence"). A central question for the court could be whether the patent provides adequate written description and enablement for this full scope, or if the term should be construed more narrowly in light of the specification's primary focus on EDS.
  • Technical & Legal Questions (Lactation Patents): For the ’666, ’667, ’554, and ’776 patents, the central dispute will likely concern induced infringement. The key question will be evidentiary: What specific language does Unichem's proposed product label contain, and is that language sufficient to demonstrate that Unichem possessed the specific intent to encourage medical providers and patients to perform the patented method, including the specific step of waiting "at least about 5 hours" before breastfeeding?

V. Key Claim Terms for Construction

• The Term: "sleep-wake disorder" (’368 Patent, Claim 1)

  • Context and Importance: This term's construction is critical to the scope of the ’368 Patent. Claim 1 defines the term by providing a long list of exemplary conditions. Defendant may argue that the term should be limited to primary sleep disorders like narcolepsy and idiopathic hypersomnia, which are the focus of the patent's background, potentially carving out some of the listed secondary causes from the claim's scope.
  • Evidence for a Broader Interpretation: The claim language itself provides the broadest support, stating the cause of the disorder "is chosen from the group consisting of..." and then explicitly listing numerous conditions, including those not typically considered primary sleep disorders (’368 Patent, col. 31:11-32:14).
  • Evidence for a Narrower Interpretation: The patent’s "Description of Related Art" section focuses almost exclusively on EDS and narcolepsy (’368 Patent, col. 1:41-4:67). This focus could be cited to argue that a person of ordinary skill in the art would understand the invention to be directed primarily at these core conditions.

• The Term: "feeding the infant breast milk... at least about 5 hours after administering" (’666 Patent, Claim 1)

  • Context and Importance: This term defines the central, active step of the claimed method in the lactation patents. Its construction will be critical for the induced infringement analysis. Practitioners may focus on this term because infringement turns on whether the defendant's label instructs or encourages this specific, timed action.
  • Evidence for a Broader Interpretation: The use of the word "about" suggests the 5-hour mark is not a rigid cutoff and could encompass a range of times reasonably close to five hours, which may be supported by language in the specification describing the pharmacokinetic principles (’666 Patent, col. 7:31-35).
  • Evidence for a Narrower Interpretation: The specification ties the 5-hour period to the drug's mean elimination half-life, which it identifies as approximately 5.0 hours (’666 Patent, col. 10:50-54). This data could be used to argue that "about 5 hours" is a technically significant milestone and that substantial deviations would fall outside the claim.

VI. Other Allegations

• Indirect Infringement: This is the foundation of the case. The complaint alleges that Unichem will induce infringement by marketing its generic product with a label that will instruct and encourage physicians and patients to practice the patented methods of treatment (Compl. ¶31, 40, 49, 58, 67). It also alleges contributory infringement, stating that Unichem's product is designed for an infringing use and lacks a substantial non-infringing use (Compl. ¶32, 41, 50, 59, 68).
• Willful Infringement: The complaint does not use the word "willful." However, it alleges that Unichem acted with knowledge of the patents-in-suit, as evidenced by its Paragraph IV certifications and notice letters sent to Axsome (Compl. ¶26, 31, 40). The complaint requests a finding that the case is "exceptional" and seeks an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶35, 44, 53, 62, 71).

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

• A primary issue will be one of validity: can the broad method claims of the ’368 Patent, which cover the use of solriamfetol for a wide range of conditions causing sleep-wake disturbances, withstand challenges of obviousness and/or lack of written description, given the prior art context for solriamfetol and its known effects on wakefulness?
• A central question will be one of induced infringement: does the specific language of Unichem's proposed generic drug label contain sufficient instruction or encouragement to prove that Unichem possessed the requisite intent for medical professionals and lactating mothers to perform the specific, timed feeding methods claimed in the ’666, ’667, ’554, and ’776 patents?