Axsome Malta Ltd v. Alkem Laboratories Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Axsome Malta Ltd. (Republic of Malta) and Axsome Therapeutics, Inc. (Delaware)
  • Defendant: Alkem Laboratories Ltd. (India)
  • Plaintiff’s Counsel: Saul Ewing LLP
• Case Identification: 2:24-cv-10617, D.N.J., 11/20/2024
• Venue Allegations: Plaintiff alleges venue is proper because Defendant is a foreign company, conducts systematic and continuous business in New Jersey, and will market the accused generic product in the district.
• 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) drug product constitutes an act of infringement of a patent covering methods of administering the drug to lactating women.
• Technical Context: The technology involves a specific dosing and administration regimen for the wakefulness-promoting agent solriamfetol, designed to minimize an infant's exposure to the drug via breast milk.
• Key Procedural History: This action arises under the Hatch-Waxman Act following Defendant's Paragraph IV certification asserting non-infringement and/or invalidity of the patent-in-suit. The complaint notes this is the fourth in a series of notice letters from Defendant concerning its ANDA and references a related, consolidated action between the parties (Civil Action No. 23-20354), suggesting an ongoing dispute over the patent portfolio protecting the Sunosi® drug product.

Case Timeline

Date	Event
2022-12-30	'126 Patent Priority Date
2023-08-11	Alkem's First Paragraph IV Notice Letter Sent (No earlier than)
2024-03-29	Alkem's Second Paragraph IV Notice Letter Sent (No earlier than)
2024-06-26	Alkem's Third Paragraph IV Notice Letter Sent (No earlier than)
2024-09-17	U.S. Patent No. 12,090,126 Issued
2024-10-15	Alkem's Fourth Paragraph IV Notice Letter Sent (No earlier than)
2024-11-20	Complaint Filed

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

U.S. Patent No. 12,090,126 - "Methods of Administering Solriamfetol to Lactating Women"

The Invention Explained

• Problem Addressed: The drug solriamfetol, used to treat excessive daytime sleepiness (EDS), was known from nonclinical studies to be present in breast milk at concentrations higher than in blood plasma (Compl. ¶8; ’126 Patent, col. 7:26-29). This creates a challenge for safely administering the drug to lactating mothers who wish to breastfeed, as it is desirable to minimize infant exposure and potential adverse effects (’126 Patent, col. 7:29-33).
• The Patented Solution: The patent discloses a method of administering solriamfetol that is timed to reduce infant exposure. The method involves giving a specific oral dose to the mother and then instructing her to wait a minimum period of time (e.g., at least 3.5 or 5 hours) before breastfeeding (’126 Patent, col. 2:56-63). This waiting period is based on pharmacokinetic studies, illustrated in figures such as Figure 1, which show that the concentration of solriamfetol in breast milk peaks relatively quickly (median Tmax of 1.1 hours) and then declines, allowing the mother to breastfeed after the peak has passed (’126 Patent, col. 2:20-28, Fig. 1).
• Technical Importance: This dosing regimen provides a potential protocol for lactating mothers with conditions like narcolepsy to use solriamfetol while mitigating risks to their infants, thereby allowing them to receive needed therapy without necessarily ceasing breastfeeding (’126 Patent, col. 15:6-9).

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 1 (Compl. ¶28).
• The essential elements of independent claim 1 are:
  • A method of treating excessive daytime sleepiness in a lactating human mother with an infant at risk, who wishes to breastfeed.
  • Determining the mother's Epworth Sleepiness Scale (ESS) total score and whether she experiences sleep attacks while caring for the infant.
  • Providing the mother (if her ESS score is 15 or greater and she has sleep attacks) a specific starting dose of solriamfetol (37.5 mg for OSA or 75 mg for narcolepsy), with potential dose doubling.
  • Feeding the infant breast milk obtained from the mother "at least about 3.5 hours after administration" of the drug.
  • The method is further characterized by pharmacokinetic parameters, including a median breast milk Tmax of approximately 1.1 hours and a specified daily infant dose.
• The complaint does not explicitly reserve the right to assert dependent claims, but the allegation of infringing "one or more claims" leaves this possibility open (Compl. ¶28).

III. The Accused Instrumentality

Product Identification

Alkem's proposed generic solriamfetol oral tablets, for which it seeks FDA approval via ANDA No. 218722 ("Alkem's Proposed Product") (Compl. ¶1).

Functionality and Market Context

• The complaint alleges that Alkem's Proposed Product is a generic version of Axsome's Sunosi®, a dopamine and norepinephrine reuptake inhibitor indicated to improve wakefulness in adults with excessive daytime sleepiness from narcolepsy or obstructive sleep apnea (Compl. ¶2, 8).
• The infringement theory is predicated on the future marketing of this generic product. The complaint alleges that upon approval, Alkem will make, use, sell, and import the product, and that the product's use in accordance with its labeling will infringe the ’126 Patent (Compl. ¶¶21, 30-32).
• The complaint references Figure 1 from the ’126 Patent, which depicts the time course of mean solriamfetol concentration in breast milk and plasma, as foundational to the patented method that Alkem's product will allegedly infringe (’126 Patent, Fig. 1).

IV. Analysis of Infringement Allegations

The complaint pleads infringement under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA as a statutory act of infringement if the proposed generic product would infringe a patent upon commercialization. The core theory is that Alkem's proposed product label will instruct or encourage physicians and patients to practice the patented method. The complaint does not contain a detailed claim chart or the proposed product label.

’126 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method of treating excessive daytime sleepiness in a lactating human mother...	The proposed generic product's labeling will allegedly instruct its use for treating excessive daytime sleepiness in the relevant patient population.	¶28, ¶31	col. 30:41-45
a) determining the Epworth Sleepiness Scale (ESS) total score of the mother and if the mother experiences sleep attacks while caring for the infant,	Alkem's proposed label will allegedly instruct or encourage physicians to perform these diagnostic and assessment steps before prescribing the generic product.	¶31	col. 30:46-49
b) providing the mother having an ESS total score of 15 or greater and who experiences sleep attacks... a starting dose of solriamfetol...	Alkem's proposed label will allegedly instruct physicians to prescribe, and patients to take, specific doses of the generic product based on these diagnostic criteria.	¶31	col. 30:50-55
c) feeding the infant breast milk obtained from the lactating mother at least about 3.5 hours after administration of the solriamfetol...	Alkem's proposed label will allegedly instruct or encourage mothers to delay breastfeeding for at least about 3.5 hours post-dose to avoid peak drug concentrations in breast milk.	¶31	col. 30:4-7

Identified Points of Contention

• Scope Questions: Claim 1 recites both diagnostic steps (e.g., determining an ESS score) likely performed by a physician, and administration/feeding steps performed by the patient. This raises the question of whether infringement can be found when the steps are "divided" between multiple actors and, if so, whether the complaint contains sufficient factual allegations to support a theory of joint enterprise or direction and control.
• Technical Questions: The central evidentiary question will be whether Alkem's proposed product label instructs or encourages the performance of all the specific limitations of Claim 1. This includes not only the general indication but also the specific diagnostic criteria (ESS ≥ 15, sleep attacks), the particular starting doses, and the explicit instruction to wait "at least about 3.5 hours" before breastfeeding. A mismatch between the label's instructions and any single claim element could present a barrier to proving induced infringement.

V. Key Claim Terms for Construction

The Term: "determining the Epworth Sleepiness Scale (ESS) total score"

Context and Importance: This term recites an active, diagnostic step. Its construction is critical because infringement will depend on whether a physician's standard diagnostic evaluation can be said to meet this limitation, or if a more formal, documented procedure is required. Practitioners may focus on this term because it is a potential point of failure for a divided infringement theory if the patient is the only direct infringer.

Intrinsic Evidence for Interpretation:

• Evidence for a Broader Interpretation: A party might argue that a physician's standard assessment of a patient's daytime sleepiness, which would cover the factors in the ESS, is sufficient to meet the "determining" limitation, even without a formal, scored test.
• Evidence for a Narrower Interpretation: The specification describes the ESS as a "subjective sleepiness test that is well known in the art" and details its specific scoring ranges (0-10 normal, 13-15 moderate, 16+ severe), suggesting "determining" requires the administration of the formal questionnaire and calculation of a numerical score as described (’126 Patent, col. 15:10-24).

The Term: "at least about 3.5 hours"

Context and Importance: This phrase defines the crucial waiting period that forms the basis of the patented solution. The scope of "about" will be central to the infringement analysis, as it defines the boundary of infringing conduct.

Intrinsic Evidence for Interpretation:

• Evidence for a Broader Interpretation: The specification repeatedly uses flexible language, such as "at least about 2 hours (e.g., at least about 3, 4, or 5 hours)" when describing the waiting period, which may support a construction where "about 3.5 hours" encompasses a range of times that achieves the goal of avoiding peak concentration (’126 Patent, col. 2:56-60).
• Evidence for a Narrower Interpretation: The claim links the waiting period to specific pharmacokinetic data, including a median Tmax of "approximately 1.1 hour" (’126 Patent, col. 30:7-10). A party could argue that "about" should be narrowly construed to a range scientifically justified by the patent's disclosed pharmacokinetic profile for avoiding this peak.

VI. Other Allegations

Indirect Infringement

The complaint alleges that upon approval, Alkem will induce infringement by encouraging acts of direct infringement through its product labeling and marketing (Compl. ¶31). It also alleges contributory infringement, stating that Alkem knows its product is designed for an infringing use and that it lacks a substantial non-infringing use (Compl. ¶32). The allegation that the product lacks a substantial non-infringing use may be contested, as solriamfetol is indicated for patient populations beyond lactating women; however, Plaintiff's argument may be that for the specific sub-population of lactating women, there is no substantial non-infringing method of use.

Willful Infringement

The complaint does not use the term "willful infringement." However, it alleges that Alkem will act with "knowledge of the '126 patent and knowledge that its acts are encouraging infringement" (Compl. ¶31) and pleads that the case is "exceptional" and warrants an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶35). These allegations lay a foundation for a potential future argument of willfulness or egregious conduct.

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

• A core issue will be one of induced infringement by label: will Alkem’s proposed generic label contain instructions that specifically direct or encourage users to perform every step of the asserted method claim, including the precise diagnostic prerequisites (e.g., ESS score ≥ 15) and the timed administration/feeding regimen? The absence of the proposed label in the complaint leaves this as the central, unresolved factual question.
• A second key question will be one of divided infringement: can Axsome establish infringement when the claimed method requires diagnostic steps performed by a physician and administration/feeding steps performed by the patient? The viability of the infringement claim may depend on whether the actions of the physician and patient can be attributed to a single actor or if Axsome can prove the elements required to hold Alkem liable for inducing infringement across multiple actors.
• Finally, a likely battleground will be validity based on obviousness: given that solriamfetol, the ESS diagnostic test, and the general principle of timing drug administration around breastfeeding to avoid peak milk concentrations were all known, a critical question for the court will be whether it was obvious to a person of ordinary skill to combine these elements to arrive at the specific method claimed in the ’126 patent.