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-08365, D.N.J., 08/08/2024
• Venue Allegations: Plaintiff alleges venue is proper because Defendant is a foreign company and conducts business in the District of New Jersey, where its proposed generic product will be marketed.
• Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market generic solriamfetol oral tablets infringes five patents covering formulations and methods of using Plaintiff's branded drug, Sunosi®.
• Technical Context: The technology concerns pharmaceutical formulations and specific dosing methods for solriamfetol, a dopamine and norepinephrine reuptake inhibitor used to improve wakefulness in adults with excessive daytime sleepiness.
• Key Procedural History: This action was triggered by Defendant’s Paragraph IV certifications asserting that the patents-in-suit are invalid and/or not infringed by its proposed generic product. The complaint notes a related, consolidated action between the same parties, suggesting a history of litigation over the Sunosi® product.

Case Timeline

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

U.S. Patent No. 11,969,404 - "Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function"

The Invention Explained

• Problem Addressed: The patent describes that solriamfetol (also referred to as APC-HCl) is eliminated from the body primarily through renal excretion, meaning patients with impaired kidney function would be expected to have higher, potentially unsafe, exposure to the drug (ʼ404 Patent, col. 2:40-50). Prior to the invention, it was reportedly unknown what specific dosing regimen would be safe and effective for this patient population (ʼ404 Patent, col. 2:50-54).
• The Patented Solution: The invention provides specific, adjusted dosing regimens for solriamfetol based on a patient's level of renal impairment, as measured by their estimated glomerular filtration rate (eGFR) (ʼ404 Patent, Abstract). The patent teaches tailored dose escalation schemes for patients with moderate renal impairment and a specific maximum daily dose for patients with severe renal impairment, intended to minimize adverse effects while providing therapeutic benefit (ʼ404 Patent, col. 3:1-19).
• Technical Importance: This dosing methodology enables the safe administration of solriamfetol to a specific patient sub-population that might otherwise be excluded from treatment due to the risk of adverse effects associated with high drug exposure (ʼ404 Patent, col. 2:55-65).

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶31).
• Essential elements of independent claim 1:
  • A method of treating a human subject with [R]-2-amino-3-phenylpropylcarbamate (APC) who has a history of bipolar disorders.
  • The method involves determining if the patient has moderate or severe renal impairment based on eGFR.
  • If the patient has moderate renal impairment (eGFR of ~30-59 mL/min/1.73 m²), the method requires providing a first daily dose (equivalent to 37.5 mg APC) for at least five days, followed by a second, higher daily dose (equivalent to 75 mg APC), with a maximum dose not exceeding 75 mg APC.
  • If the patient has severe renal impairment (eGFR of ~15-29 mL/min/1.73 m²), the method requires providing a daily dose equivalent to 37.5 mg APC, with the dose not exceeding that amount.
• The complaint does not explicitly reserve the right to assert dependent claims but makes general allegations of infringement of "one or more of the claims" (Compl. ¶31).

U.S. Patent No. 11,986,454 - "Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function"

The Invention Explained

• Problem Addressed: As with the ʼ404 Patent, this patent addresses the unmet need for a safe and effective dosing protocol for solriamfetol in patients with impaired renal function, who are at risk of increased drug exposure and associated adverse effects (ʼ454 Patent, col. 2:40-54).
• The Patented Solution: The invention provides specific dosing instructions tailored to different levels of renal impairment to minimize adverse effects (ʼ454 Patent, Abstract). For patients with moderate renal impairment, it prescribes a specific multi-day dose escalation regimen, while for patients with severe renal impairment, it sets a maximum daily dose (ʼ454 Patent, col. 3:1-19).
• Technical Importance: The claimed methods provide a defined protocol that allows clinicians to safely prescribe a wake-promoting agent to patients with compromised kidney function, expanding the drug's utility (ʼ454 Patent, col. 2:55-65).

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶40).
• Essential elements of independent claim 1:
  • A method of treating excessive daytime sleepiness in a subject.
  • The method requires selecting a subject who does not have end-stage renal disease and determining their eGFR.
  • For a subject with moderate renal impairment (eGFR of ~30-59 mL/min/1.73 m²), the method specifies a first daily dose (equivalent to 37.5 mg APC) for at least five days, followed by a second daily dose (equivalent to 75 mg APC), with a maximum daily dose not to exceed 75 mg APC.
  • For a subject with severe renal impairment (eGFR of ~15-29 mL/min/1.73 m²), the method specifies a maximum daily dose equivalent to 37.5 mg APC.
• The complaint generally alleges infringement of "one or more claims" of the patent (Compl. ¶40).

U.S. Patent No. 11,986,455 - "Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function"

• Technology Synopsis: The patent claims methods for safely administering solriamfetol to patients with impaired renal function. It discloses specific dose-escalation regimens for patients with moderate renal impairment and maximum daily doses for those with severe renal impairment, based on the patient's kidney function (eGFR), to mitigate adverse effects from increased drug exposure (Compl. ¶9; ʼ455 Patent, Abstract).
• Asserted Claims: At least independent claim 1 (Compl. ¶49).
• Accused Features: The complaint alleges that the instructions for use in Defendant's proposed product label will induce infringement of the claimed dosing methods for patients with renal impairment (Compl. ¶51-53).

U.S. Patent No. 11,998,639 - "Formulations of (R)-2-Amino-Phenylpropyl Carbamate"

• Technology Synopsis: This patent relates to a specific solid oral formulation of solriamfetol designed for immediate release. The invention addresses the technical challenge of creating a tablet with a high drug load that dissolves quickly and consistently across different pH environments, which is notable given the drug's pH-dependent solubility. The claimed solution is a formulation comprising 90-98% solriamfetol salt, 1-5% hydroxypropyl cellulose as a binder, and 0.1-2% magnesium stearate as a lubricant, and which notably lacks a disintegrant (Compl. ¶10; ʼ639 Patent, Abstract, claim 1).
• Asserted Claims: At least independent claim 1 (Compl. ¶58).
• Accused Features: The complaint alleges that Defendant's proposed generic solriamfetol tablet itself—its physical composition and performance characteristics—will infringe the claimed formulation (Compl. ¶58, ¶60).

U.S. Patent No. 12,005,036 - "Methods of Administering Solriamfetol to Lactating Women"

• Technology Synopsis: The patent addresses the problem of minimizing drug exposure to an infant through breast milk when the mother is treated with solriamfetol. The invention is a method wherein the nursing mother waits a specified period of time (e.g., at least 3.5 hours) after taking her dose before feeding the infant breast milk. This delay is designed to bypass the peak concentration of the drug in breast milk, thereby reducing the total dose transferred to the infant (Compl. ¶11; ʼ036 Patent, Abstract).
• Asserted Claims: At least independent claim 1 (Compl. ¶67).
• Accused Features: The complaint alleges that the labeling for Defendant's generic product will instruct lactating women on administration timing in a way that will induce infringement of the claimed method (Compl. ¶69-71).

III. The Accused Instrumentality

• Product Identification: Alkem’s proposed generic solriamfetol oral tablets, for which it seeks FDA approval under ANDA No. 218722 ("Alkem's Proposed Product") (Compl. ¶1, ¶18).
• Functionality and Market Context:
  • Alkem's Proposed Product is a generic version of Axsome's Sunosi® oral tablets, intended to be a therapeutic equivalent (Compl. ¶1, ¶13). Sunosi® is 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. ¶12).
  • The complaint alleges Alkem seeks to commercially manufacture, use, sell, and import its generic product prior to the expiration of the patents-in-suit (Compl. ¶1).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-chart analysis of infringement. It makes general allegations that Alkem’s submission of its ANDA constitutes an act of infringement under 35 U.S.C. § 271(e)(2)(A) and that the future commercialization of the proposed product will constitute direct, induced, and contributory infringement under 35 U.S.C. § 271(a), (b), and (c) (Compl. ¶31-35, ¶40-44). The complaint does not include Alkem’s proposed product label or details of its formulation.

The central infringement theory for the method-of-use patents (’404, ’454, ’455, and ’036 Patents) is one of induced infringement. Plaintiff alleges that the label for Alkem’s Proposed Product will instruct or encourage physicians and patients to administer the drug in a manner that practices the steps of the asserted method claims, such as the specific dosing regimens for renally impaired patients (Compl. ¶34, ¶43). For the formulation patent (’639 Patent), the infringement theory is direct infringement, alleging that Alkem’s tablet itself will contain the claimed ingredients in the claimed amounts and exhibit the claimed dissolution properties (Compl. ¶60).

• Identified Points of Contention:
  • Scope Questions: A primary question for the ’404 Patent will be whether the preamble phrase "a history of bipolar disorders" is a limitation of claim 1. If the court finds it is limiting, a dispute may arise as to whether Alkem's proposed label specifically instructs use in this patient population or if it can be "carved out" to avoid infringement.
  • Technical Questions: For the ʼ639 Patent, a key factual question will be whether Alkem's formulation literally meets the claimed weight percentages of the active pharmaceutical ingredient, binder, and lubricant, and whether it exhibits a "substantially identical" dissolution rate across the three specified pH levels. For the method patents, a technical and legal question is whether Alkem's proposed label directs, encourages, or merely informs clinicians about dosing in specific populations, which will be central to the question of inducement.

V. Key Claim Terms for Construction

• The Term: "a history of bipolar disorders" (from the preamble of claim 1 of the ʼ404 Patent).
• Context and Importance: Practitioners may focus on this term because its interpretation could be dispositive of infringement for the ʼ404 Patent. If the court construes this preamble phrase as a necessary limitation of the claim, the defendant could potentially avoid infringement by carving out any mention of this patient population from its proposed product label.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation (Non-Limiting): A party might argue that the body of the claim is a self-contained method for dosing renally impaired patients and that the preamble merely states an intended, but not required, patient characteristic. The specification discusses the application of solriamfetol for a wide variety of disorders, not just bipolar disorder (ʼ404 Patent, col. 8:26-51).
  • Evidence for a Narrower Interpretation (Limiting): A party could argue that the phrase provides essential context and defines a specific patient population to which the claimed method applies, distinguishing it from the prior art. The patent repeatedly mentions bipolar disorder as a condition treatable with APC (ʼ404 Patent, col. 8:37, col. 9:35), suggesting the inventors may have considered this context important.
• The Term: "providing to a subject... a first oral daily dose... and a second oral daily dose" (from claim 1 of the ʼ404 and ʼ454 Patents).
• Context and Importance: This term is critical because it defines the active steps of the claimed method. In an ANDA case, the dispute will center on whether the defendant's proposed label will inevitably cause or encourage doctors to perform these specific, sequential steps for the specified patient population, thereby inducing infringement.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: A party might argue that "providing" should be construed broadly to cover the entire act of making the drug available with instructions for the claimed dosing regimen. The specification describes this regimen as the "patented solution" for managing toxicity in renally impaired patients (ʼ454 Patent, col. 3:1-19).
  • Evidence for a Narrower Interpretation: A party could argue that infringement requires the label to explicitly instruct the two-step dose escalation over the specified time period (n₁ ≥ 5 days). If the label offers physicians discretion or alternative schedules that fall outside the claim's specific temporal requirements, it may not meet the standard for inducing infringement.

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement for all five patents-in-suit. The basis for inducement is the allegation that Alkem's proposed product labeling will instruct medical professionals and patients to use the generic drug in a way that infringes the claimed methods (e.g., Compl. ¶34, ¶43). The basis for contributory infringement is the allegation that Alkem's product is designed for an infringing use and lacks a substantial non-infringing use (e.g., Compl. ¶35, ¶44).
• Willful Infringement: While the complaint does not use the word "willful," for each count it alleges the case is "exceptional" and seeks attorneys' fees under 35 U.S.C. § 285 (e.g., Compl. ¶38, ¶47). This claim is predicated on Alkem’s alleged knowledge of the patents, evidenced by its sending of Paragraph IV Notice Letters to Axsome (Compl. ¶27-29).

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

• A core issue will be one of inducement: Does Alkem's proposed product label, which is not yet available in the record, contain instructions that are specific enough to encourage or direct medical professionals to perform all the steps of the claimed methods of use (’404, ’454, ’455, and ’036 patents), or does it provide sufficient discretion to practice non-infringing alternatives?
• A key question of claim scope will arise for the ’404 patent: Is the preamble phrase "a history of bipolar disorders" a substantive limitation of the claim, and if so, can Alkem avoid infringement through a "skinny label" that carves out this indication?
• A central evidentiary question for the ’639 patent will be a direct comparison of Alkem's ANDA product to the claim limitations: Does the accused generic tablet contain the same components in the same proportions and exhibit the same pH-independent dissolution profile as required by the claims, constituting literal infringement?