Axsome Malta Ltd v. Alkem Laboratories Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Axsome Malta Ltd. (Malta) and Axsome Therapeutics, Inc. (Delaware)
  • Defendant: Alkem Laboratories Ltd. (India); Hikma Pharmaceuticals USA Inc. (Delaware); Sandoz Inc. (Colorado); and Unichem Laboratories Ltd. (India)
  • Plaintiff’s Counsel: Saul Ewing LLP
• Case Identification: 2:24-cv-04608, D.N.J., 04/05/2024
• Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey based on Defendants' systematic and continuous business contacts within the state, including the marketing and planned distribution of generic pharmaceutical products. For foreign defendants, venue is alleged to be proper in any judicial district.
• Core Dispute: Plaintiff alleges that Defendants' submission of Abbreviated New Drug Applications (ANDAs) to the FDA, seeking to market generic versions of Plaintiff's Sunosi® (solriamfetol) oral tablets, infringes thirteen U.S. patents covering methods of using the drug.
• Technical Context: The dispute centers on solriamfetol, a dopamine and norepinephrine reuptake inhibitor approved for improving wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea.
• Key Procedural History: This action under the Hatch-Waxman Act was triggered by Defendants sending Paragraph IV Certification Notice Letters to Plaintiff, stating their intent to market generic solriamfetol prior to the expiration of the patents listed in the FDA's Orange Book for Sunosi®. The complaint also references several other related patent infringement actions involving the same plaintiffs and some of the same patents and defendants.

Case Timeline

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

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, a drug used to treat conditions like excessive daytime sleepiness, to lactating subjects while minimizing potential adverse events in the breastfed infant due to drug exposure through breast milk (’666 Patent, col. 1:8-16). Pharmacokinetic challenges arise because solriamfetol is known to be detected in breast milk, presenting potential risks to the infant (’666 Patent, col. 5:15-19).
• The Patented Solution: The invention provides a specific method of use that reduces an infant's exposure to solriamfetol. The method involves orally administering a specific daily dose of solriamfetol to the mother and then feeding the infant breast milk only after a waiting period of at least about five hours, which corresponds to the drug's mean elimination half-life (’666 Patent, col. 2:42-59). This timing protocol is designed to ensure the concentration of the drug in the breast milk has decreased, thereby reducing the infant's total dose and the potential for adverse events like agitation or insomnia (’666 Patent, col. 2:25-28, col. 10:51-54).
• Technical Importance: The method provides a defined, data-supported protocol that may allow lactating women who require solriamfetol treatment to continue breastfeeding while managing and reducing the risk of drug exposure to their infants (’666 Patent, col. 5:15-24).

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶85).
• Essential elements of Claim 1 include:
  • A method of reducing exposure to solriamfetol in an infant fed breast milk obtained from a human subject treated with solriamfetol.
  • Orally administering 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.
• The complaint reserves the right to assert additional claims (Compl. ¶85).

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

The Invention Explained

• Problem Addressed: The patent addresses the same technical problem as the ’666 Patent: the need for a method to safely administer solriamfetol to lactating women while minimizing risk to the breastfed infant (’667 Patent, col. 1:12-16). It specifically focuses on reducing potential adverse events such as agitation, insomnia, anorexia, or reduced weight gain in the infant (’667 Patent, col. 2:25-28).
• The Patented Solution: The invention is a method of use nearly identical to that of the ’666 Patent, comprising the oral administration of solriamfetol followed by a waiting period of "at least about 5 hours" before breastfeeding (’667 Patent, col. 2:50-65). This timed-feeding approach is based on pharmacokinetic data showing the drug's concentration in breast milk decreases significantly after this interval, corresponding to its mean elimination half-life of approximately 5.0 hours (’667 Patent, col. 10:51-54).
• Technical Importance: This patent provides a specific method aimed at decreasing the potential for adverse events in the infant, offering a risk-mitigation strategy for lactating mothers who need solriamfetol therapy (’667 Patent, col. 2:25-28, col. 5:15-24).

Key Claims at a Glance

• The complaint asserts at least independent claim 1 (Compl. ¶94).
• Essential elements of Claim 1 include:
  • A method of treating excessive daytime sleepiness, attention deficit hyperactivity disorder, binge eating disorder, depression, or cognitive impairment in a lactating human mother.
  • Orally administering solriamfetol to the mother at a once-daily dose of about 150 mg.
  • Feeding the infant breast milk from the mother at least about 5 hours after administration.
  • Wherein the daily infant dose is reduced to about 0.3 mg or lower, and wherein the potential for adverse events in the infant is decreased.
• The complaint reserves the right to assert additional claims (Compl. ¶94).

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

• Patent Identification: U.S. Patent No. 11,779,554, "Methods of Administering Solriamfetol to Lactating Women," issued October 10, 2023.
• Technology Synopsis: This patent is directed to methods of reducing the risk of agitation in an infant fed breast milk from a mother treated with solriamfetol. The method involves administering a specific dose (e.g., about 150 mg) and waiting at least about 5 hours before breastfeeding, which is designed to reduce the infant's drug exposure to about 0.3 mg or lower (’554 Patent, Abstract; col. 1:8-16).
• Asserted Claims: At least independent claim 1 (Compl. ¶103).
• Accused Features: The proposed generic solriamfetol product and its intended method of use (Compl. ¶¶ 103, 105, 106).

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

• Patent Identification: U.S. Patent No. 11,793,776, "Methods of Administering Solriamfetol to Lactating Women," issued October 24, 2023.
• Technology Synopsis: This patent claims methods for improving wakefulness in a lactating woman by administering solriamfetol. The method includes the step of feeding the infant breast milk at least about 5 hours after drug administration to reduce the risk of adverse events in the infant, such as agitation (’776 Patent, Abstract; col. 2:24-28).
• Asserted Claims: At least independent claim 1 (Compl. ¶112).
• Accused Features: The proposed generic solriamfetol product and its intended method of use (Compl. ¶¶ 112, 114, 115).

Multi-Patent Capsule: U.S. Patent Nos. 11,839,598; 11,839,599; 11,850,226; 11,850,227; 11,850,228; and 11,857,528

• Patent Identification: This family of six patents, including the ’598 and ’599 patents, is titled "Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function," issued between December 12, 2023, and January 2, 2024.
• Technology Synopsis: These patents claim methods for safely administering solriamfetol to patients with moderate or severe renal impairment. The invention provides specific dose-escalation schemes and maximum daily dosages tailored to the patient's level of kidney function, which is necessary because the drug is primarily eliminated by the kidneys (’598 Patent, Abstract; col. 1:19-33). The methods are designed to increase tolerance and reduce adverse effects associated with higher drug exposure in these patients (’598 Patent, col. 2:57-65).
• Asserted Claims: At least independent claim 1 of each patent (Compl. ¶¶ 121, 130, 139, 148, 157, 166).
• Accused Features: The proposed generic solriamfetol product and its intended method of use, which would be prescribed to the full patient population, including those with renal impairment (Compl. ¶¶ 121-173).

Multi-Patent Capsule: U.S. Patent No. 11,865,098

• Patent Identification: U.S. Patent No. 11,865,098, "Methods and Compositions for Treating Excessive Sleepiness," issued January 9, 2024.
• Technology Synopsis: This patent is directed to methods of treating excessive daytime sleepiness by administering solriamfetol. The invention claims that these methods achieve a "normal" level of wakefulness as measured by standard objective (Maintenance of Wakefulness Test) and subjective (Epworth Sleepiness Scale) tests (’098 Patent, Abstract).
• Asserted Claims: At least independent claim 1 (Compl. ¶175).
• Accused Features: The proposed generic solriamfetol product and its intended use for treating excessive sleepiness (Compl. ¶¶ 175, 177, 178).

Multi-Patent Capsule: U.S. Patent Nos. 11,872,203 and 11,872,204

• Patent Identification: U.S. Patent Nos. 11,872,203 and 11,872,204, "Methods of Administering Solriamfetol to Lactating Women," issued January 16, 2024.
• Technology Synopsis: These patents are part of the same family as the '666 and '667 patents. They claim methods for treating excessive daytime sleepiness in lactating mothers by administering solriamfetol and waiting at least about 5 hours before breastfeeding, thereby reducing the risk of adverse events and/or reducing the volume of milk an infant ingests (’203 Patent, Abstract).
• Asserted Claims: At least independent claim 1 of each patent (Compl. ¶¶ 184, 193).
• Accused Features: The proposed generic solriamfetol product and its intended method of use (Compl. ¶¶ 184-200).

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are the proposed generic solriamfetol oral tablet drug products for which Defendants Alkem, Hikma, Sandoz, and Unichem seek FDA approval via their respective ANDAs (Nos. 218722, 218016, 218610, and 218761) (Compl. ¶1). The complaint refers to them individually, for example, as "Alkem's Proposed Product" (Compl. ¶29). No probative visual evidence provided in complaint.

Functionality and Market Context

• The proposed products are generic versions of Plaintiff's Sunosi® oral tablets, intended to be therapeutically equivalent for improving wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (Compl. ¶23). As this is a Hatch-Waxman action, the infringement allegation is predicated on the Defendants' act of filing an ANDA seeking approval to market these generic products for the patented uses prior to the expiration of the patents-in-suit (Compl. ¶¶ 64, 67, 85). The commercialization of these products would provide a lower-cost alternative to the branded Sunosi® drug (Compl. ¶29).

IV. Analysis of Infringement Allegations

The complaint does not contain claim charts or detailed factual allegations mapping product features to claim limitations. The infringement theory is an artificial one under 35 U.S.C. § 271(e)(2), where the filing of an ANDA for a patented use is itself an act of infringement. The allegations below are based on the premise that the proposed generic product's label will instruct users to perform the patented methods.

11,771,666 Infringement Allegations

11,771,667 Infringement Allegations

Identified Points of Contention

• Scope Questions: The central issue for the method-of-use patents will be one of induced infringement. The analysis will focus on whether the language in the Defendants' proposed drug labels will instruct or encourage prescribing physicians and lactating mothers to perform each step of the claimed methods. A key question is whether the label will explicitly direct a waiting period of "at least about 5 hours" before breastfeeding, or if it will merely present pharmacokinetic data and leave the decision to the physician's discretion.
• Technical Questions: A factual question for the court may be whether the final approved label for the generic products will be substantially the same as the current label for Sunosi®, which is the basis for the infringement allegation. Any differences between the proposed generic labels and the patented methods could create a non-infringement argument for the Defendants.

V. Key Claim Terms for Construction

• The Term: "at least about 5 hours"

  • Context and Importance: This temporal limitation is the core of the risk-mitigation strategy for the patents concerning lactating women. Its construction will determine whether a generic drug label that provides pharmacokinetic data but does not explicitly mandate a 5-hour waiting period can be found to induce infringement. Practitioners may focus on this term because the inclusion of "about" suggests a range, the scope of which will be disputed.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The repeated use of "about" in the claims and specification suggests the inventors did not intend the 5-hour mark to be a rigid, absolute cutoff (’666 Patent, col. 2:47, Claim 1).
    • Evidence for a Narrower Interpretation: The specification ties the 5-hour period directly to the measured mean elimination half-life of solriamfetol in breast milk, which was found to be "approximately 5.0 hours" (’666 Patent, col. 10:52-54). Defendants may argue that this data provides a specific, narrow technical anchor for the term, limiting the scope of "about" to values very close to 5.0 hours.

• The Term: "reducing exposure" / "decreasing the potential for adverse events"

  • Context and Importance: These phrases appear in the preambles or "wherein" clauses of the asserted method claims. A central dispute will be whether these clauses are merely statements of purpose or are actual, limiting steps of the claim that Plaintiff must prove are met.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation (Non-limiting): Plaintiff may argue this language simply states the intended result of practicing the preceding active steps (dosing and waiting), and that infringement is established by showing those steps are performed as instructed by the label, which will inherently achieve the stated purpose (’666 Patent, col. 2:36-49).
    • Evidence for a Narrower Interpretation (Limiting): Defendants may argue that this language imposes a separate, affirmative limitation on the claim, requiring Plaintiff to prove not only that the method is practiced, but that it actually results in a "reduction" or "decrease" in a legally and factually sufficient way. The patent abstract and summary are framed around this reduction, which may support its interpretation as an essential claim feature (’666 Patent, Abstract; col. 2:36-41).

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement against all Defendants for all asserted patents (e.g., Compl. ¶¶ 88, 89, 97, 98). The inducement allegation is based on the assertion that Defendants, with knowledge of the patents, will create and market a product with a label that encourages physicians and patients to perform the patented methods of use (Compl. ¶88). The contributory infringement allegation is based on the assertion that the proposed generic products are designed for an infringing use and lack a substantial non-infringing use (Compl. ¶89).
• Willful Infringement: While the complaint does not use the word "willful," it alleges that Defendants have knowledge of the patents-in-suit and know that their actions encourage infringement (e.g., Compl. ¶¶ 88, 97). These allegations of knowing and intentional infringement, stemming from the Paragraph IV certifications, could form the basis for a later claim of willful infringement.

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

• A core issue will be one of induced infringement: Will the language of the Defendants' final, FDA-approved labels be construed as actively encouraging or instructing clinicians and patients to perform all the steps of the asserted method claims? The outcome may depend on whether the labels mandate specific actions (e.g., "wait 5 hours before breastfeeding") versus merely providing clinical data for informational purposes.
• A second central question will be one of claim validity: Given that the patents were recently issued and cover methods of use for a known compound, the case will likely feature significant disputes over whether the claimed methods—such as adjusting dosage for renally impaired patients or advising a waiting period for lactating mothers based on pharmacokinetic data—are non-obvious under 35 U.S.C. § 103.
• A final key question will be one of claim construction: The scope of the asserted claims will depend heavily on the court's interpretation of terms such as "at least about 5 hours" and whether result-oriented clauses like "wherein the potential for adverse events...is decreased" are treated as affirmative claim limitations or simply statements of intended purpose.