Axsome Malta Ltd v. Sandoz Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Axsome Malta Ltd. (Malta) and Axsome Therapeutics, Inc. (Delaware)
  • Defendant: Sandoz Inc. (Delaware)
  • Plaintiff’s Counsel: Saul Ewing LLP
• Case Identification: 2:24-cv-00860, D.N.J., 02/14/2024
• Venue Allegations: Venue is based on Defendant Sandoz Inc.'s principal place of business being located in Princeton, New Jersey, within 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) oral tablets constitutes an act of patent infringement.
• Technical Context: The patents relate to specific methods of administering solriamfetol, a treatment for excessive daytime sleepiness, to particular patient populations to enhance safety and efficacy.
• Key Procedural History: The action was triggered by a Paragraph IV Certification notice letter sent by Sandoz to Axsome no earlier than January 12, 2024, alleging that the nine patents-in-suit are invalid and/or will not be infringed by its proposed generic product.

Case Timeline

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

No probative visual evidence provided in complaint.

U.S. Patent No. 11,771,666 - “Methods of Administering Solriamfetol to Lactating Women,” Issued October 3, 2023 (’666 Patent)

The Invention Explained

• Problem Addressed: The patent addresses the challenge of administering solriamfetol to lactating subjects while minimizing potential adverse events in infants fed with their breast milk ( Compl. ¶7; ’666 Patent, col. 1:26-32). Pre-clinical studies indicated that solriamfetol could be present in breast milk at concentrations higher than in plasma, creating a potential safety risk for the nursing infant (’666 Patent, col. 5:15-22).
• The Patented Solution: The invention provides a method that specifies a dosage of solriamfetol and a minimum time interval between drug administration and breastfeeding. This method is designed to reduce the infant's exposure by ensuring breastfeeding occurs after the drug concentration in the mother's system has decreased significantly, based on the drug's pharmacokinetic profile, which shows a mean elimination half-life of approximately 5 hours (’666 Patent, col. 10:56-60; col. 17:56-61).
• Technical Importance: This approach provides a protocol for lactating individuals requiring treatment for conditions like narcolepsy to continue therapy while managing the risk of drug exposure to their infants.

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶34).
• Claim 1 requires:
  • A method of reducing exposure to solriamfetol in an infant fed breast milk obtained from a human subject treated with solriamfetol.
  • Orally administering the solriamfetol to the subject at a once-daily dose of about 150 mg.
  • Feeding the infant breast milk from the subject at least about 5 hours after administering the solriamfetol.
  • Wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or lower.

U.S. Patent No. 11,771,667 - “Methods of Administering Solriamfetol to Lactating Women,” Issued October 3, 2023 (’667 Patent)

The Invention Explained

• Problem Addressed: The patent addresses the same technical problem as the ’666 Patent: the safe administration of solriamfetol to lactating subjects to treat certain disorders while protecting the nursing infant from adverse events due to drug exposure through breast milk (’667 Patent, col. 1:26-32).
• The Patented Solution: The invention is a method of treatment for specific disorders (e.g., excessive daytime sleepiness) that integrates the same timed-feeding protocol described in the ’666 Patent. The method claims not only the administration steps but also the resulting decrease in potential adverse events for the infant (’667 Patent, Abstract; col. 6:1-13).
• Technical Importance: This method provides a therapeutic regimen that allows for the continued treatment of the lactating mother's underlying condition while managing infant safety.

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶43).
• Claim 1 requires:
  • 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.
  • Orally administering solriamfetol to the mother at a once-daily dose of about 150 mg.
  • Feeding the infant the breast milk obtained from the mother at least about 5 hours after administration.
  • Wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or lower.
  • Wherein the potential for adverse events in the infant due to the solriamfetol is decreased.

Multi-Patent Capsule: U.S. Patent Nos. 11,779,554 and 11,793,776

• Patent Identification: ’554 Patent, “Methods of Administering Solriamfetol to Lactating Women,” Issued Oct. 10, 2023; ’776 Patent, “Methods of Administering Solriamfetol to Lactating Women,” Issued Oct. 24, 2023.
• Technology Synopsis: These patents, similar to the ’666 and ’667 Patents, claim methods for safely administering solriamfetol to lactating women by specifying dosages and a time-delayed feeding schedule to minimize infant drug exposure (Compl. ¶9-10). The claims appear to cover different dosages or specific outcomes compared to the lead patents.
• Asserted Claims: At least Claim 1 of each patent (Compl. ¶52, ¶61).
• Accused Features: Sandoz’s submission of its ANDA for a generic version of Sunosi® is alleged to infringe (Compl. ¶52, ¶61).

Multi-Patent Capsule: U.S. Patent Nos. 11,839,598; 11,839,599; 11,850,226; 11,850,227; and 11,850,228

• Patent Identification: ’598, ’599, ’226, ’227, and ’228 Patents, all titled “Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function,” issued between December 12, 2023 and December 26, 2023.
• Technology Synopsis: These patents address the problem that solriamfetol is primarily eliminated by the kidneys, necessitating modified dosing for patients with impaired renal function to avoid adverse effects from drug accumulation (’598 Patent, col. 16:39-54). The solution is a set of specific dosing regimens, including starting doses and dose escalation schedules, tailored to different levels of renal impairment (e.g., mild, moderate, severe) (’598 Patent, col. 16:56-62; col. 17:1-15).
• Asserted Claims: At least Claim 1 of each patent (Compl. ¶70, ¶79, ¶88, ¶97, ¶106).
• Accused Features: Sandoz’s submission of its ANDA is alleged to infringe by seeking approval for a product whose label will presumably instruct for use in patients with impaired renal function (Compl. ¶70, ¶79, ¶88, ¶97, ¶106).

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is "Sandoz's Proposed Product," which are generic solriamfetol oral tablets for which Sandoz seeks FDA approval via ANDA No. 218610 (Compl. ¶1, ¶28).

Functionality and Market Context

• The proposed generic product is intended to be a bioequivalent version of Axsome's Sunosi® oral tablets (Compl. ¶1). 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. ¶2, ¶16). The complaint alleges that upon FDA approval, Sandoz will manufacture, market, and sell this generic product in the United States (Compl. ¶29).

IV. Analysis of Infringement Allegations

The complaint does not contain claim charts or detailed infringement allegations beyond asserting that the filing of ANDA No. 218610 infringes at least claim 1 of each patent-in-suit. The following analysis is based on the asserted claims and the understanding that the proposed generic product's label must substantially mirror the approved label for Sunosi®.

’666 Patent Infringement Allegations

’667 Patent Infringement Allegations

Identified Points of Contention

• Scope Questions: A central question for the method claims will be whether the act of submitting an ANDA for a generic drug, whose label will necessarily contain instructions for use, constitutes inducement of infringement. The dispute may focus on whether the instructions in Sandoz's proposed label actively encourage, rather than merely inform of risks, the specific steps of the patented methods.
• Technical Questions: For claims that recite a specific outcome (e.g., "daily infant dose... is reduced to about 0.3 mg or lower"), a point of contention will be whether Axsome can prove that following the instructions for Sandoz's product will necessarily and inevitably lead to this result. This raises evidentiary questions about the pharmacokinetic properties of the proposed generic product.

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for analysis of specific claim terms. However, based on the asserted claims, certain terms may become central to the dispute.

The Term: "at least about 5 hours"

• Context and Importance: This term defines the critical waiting period in the methods for treating lactating women. The construction of "about" will determine the scope of infringement, particularly whether a slightly different time period recommended on a generic label could avoid infringement.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification repeatedly uses "about," suggesting the patentee did not intend to be limited to a precise 5.0-hour figure. The rationale is tied to the drug's mean elimination half-life, which is described as "approximately 5.0 hours," further supporting a range rather than a strict cutoff (’666 Patent, col. 10:59-60).
  • Evidence for a Narrower Interpretation: A defendant may argue that the term should be construed more narrowly in light of the specific clinical trial data presented in the patent, which forms the basis for the 5-hour recommendation (’666 Patent, Table 1).

The Term: "wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or lower"

• Context and Importance: This is a result-oriented limitation. Practitioners may focus on this term because its enforceability could be challenged on grounds of indefiniteness under 35 U.S.C. § 112. The dispute will turn on whether one of ordinary skill in the art could determine if this result is achieved when the method is performed.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation (supporting enforceability): The patent provides clinical data showing that a 150 mg maternal dose results in an estimated daily infant dose of 0.59 mg over 24 hours, and that the drug concentration is significantly lower after 5 hours, which may provide an objective standard for determining if the claimed result is met (’666 Patent, col. 10:59-64).
  • Evidence for a Narrower Interpretation (challenging enforceability): A defendant could argue that the actual infant dose can vary significantly based on maternal metabolism, feeding frequency, and milk volume, making the "0.3 mg or lower" threshold difficult to verify consistently and thus potentially indefinite.

VI. Other Allegations

Indirect Infringement

• The complaint alleges that Sandoz will induce infringement under § 271(b) because, upon information and belief, Sandoz will intentionally encourage direct infringement by physicians and patients through its product labeling and instructions (Compl. ¶37, ¶46). It also alleges contributory infringement under § 271(c), stating that Sandoz knows its product is designed for an infringing use and lacks a substantial non-infringing use (Compl. ¶38, ¶47).

Willful Infringement

• The complaint does not explicitly use the word "willful" but alleges that the case is "exceptional" and seeks attorneys' fees under 35 U.S.C. § 285 (Compl. ¶41). It does not plead specific facts to support a claim of willful infringement, such as pre-suit knowledge of the patents combined with egregious conduct.

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

• A core issue will be one of inducement: Will the instructions, warnings, and dosage recommendations in Sandoz’s proposed product label be found to actively encourage physicians and patients to perform the specific, patented methods of administration for lactating women and patients with impaired renal function, thereby satisfying the intent requirement for induced infringement?
• A key legal question will be one of enforceability and proof: For claims that require a specific clinical outcome (e.g., reducing an infant’s daily dose to "about 0.3 mg or lower"), can Axsome meet the evidentiary burden of proving that use of Sandoz's proposed generic will necessarily achieve this result, and will the court find such result-oriented limitations to be definite and enforceable under 35 U.S.C. § 112?