DCT

2:24-cv-04002

Axsome Malta Ltd v. Aurobindo Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:24-cv-04002, D.N.J., 03/19/2024
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Aurobindo Pharma USA, Inc. maintains a regular and established place of business in the district, and Defendant Aurobindo Pharma Limited has purposefully availed itself of the district through its U.S. subsidiary and has consented to personal jurisdiction in the court through prior litigation.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's Sunosi® (solriamfetol) oral tablets infringes eight U.S. patents covering methods of administering the drug.
  • Technical Context: The technology concerns pharmaceutical methods for safely administering solriamfetol, a dopamine and norepinephrine reuptake inhibitor, to treat excessive daytime sleepiness in specific patient populations, such as those with impaired renal function or who are lactating.
  • Key Procedural History: The litigation was triggered by Defendant's submission of ANDA No. 218725 and its associated Paragraph IV Certifications, which allege that the patents-in-suit are invalid and/or will not be infringed by the proposed generic product. Plaintiff received a series of notice letters from Defendant regarding these certifications between August 2023 and February 2024, establishing a justiciable controversy under the Hatch-Waxman Act.

Case Timeline

Date Event
2017-06-02 Earliest Priority Date for ’098 Patent
2020-03-19 Earliest Priority Date for ’598, ’226, ’227, ’228, ’528 Patents
2022-10-28 Earliest Priority Date for ’203, ’204 Patents
2023-08-10 Aurobindo's First Paragraph IV Notice Letter Sent
2023-12-08 Aurobindo's Second Paragraph IV Notice Letter Sent
2023-12-12 ’598 Patent Issued
2023-12-26 ’226, ’227, ’228 Patents Issued
2024-01-02 ’528 Patent Issued
2024-01-09 ’098 Patent Issued
2024-01-16 ’203, ’204 Patents Issued
2024-02-13 Aurobindo's Third Paragraph IV Notice Letter Sent
2024-02-27 Aurobindo's Fourth Paragraph IV Notice Letter Sent
2024-03-19 Complaint Filed

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

U.S. Patent No. 11,839,598 - Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function

The Invention Explained

  • Problem Addressed: The patent describes that solriamfetol is primarily eliminated from the body via renal excretion, meaning patients with impaired kidney function would be expected to have higher, potentially unsafe, exposure to the drug (U.S. 11,839,598 B2, col. 2:40-54). The most common adverse effects associated with the drug are dose-dependent and can interfere with daily activities (U.S. 11,839,598 B2, col. 2:32-39).
  • The Patented Solution: The patent claims to solve this problem by providing specific, optimized dosing regimens tailored to a patient's level of renal impairment. For subjects with moderate renal impairment, it discloses a dose-escalation scheme starting at a low initial dose and increasing to a maximum dose only after at least five days to allow for tolerance development (U.S. 11,839,598 B2, col. 3:1-10). For subjects with severe renal impairment, it provides a fixed, low maximum daily dose (U.S. 11,839,598 B2, col. 3:10-14).
  • Technical Importance: The claimed methods provide a way to safely administer the therapeutic agent to a specific patient sub-population that would otherwise be at high risk for dose-dependent adverse effects (U.S. 11,839,598 B2, col. 2:56-62).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶39).
  • Essential elements of claim 1:
    • A method of reducing toxicity due to solriamfetol ([R]-2-amino-3-phenylpropylcarbamate or APC) administration in a subject having moderate or severe renal impairment.
    • For a subject with moderate renal impairment (eGFR of about 30 mL/min/1.73 m² to about 59 mL/min/1.73 m²), providing a first oral daily dose equivalent to 37.5 mg APC from day one to day n₁, and a second oral daily dose equivalent to 75 mg APC starting on day n₂, where n₁ is an integer equal to or greater than 5.
    • For a subject with severe renal impairment (eGFR of about 15 mL/min/1.73 m² to about 29 mL/min/1.73 m²), providing an oral daily dose equivalent to 37.5 mg APC.
  • The complaint reserves the right to assert additional claims (Compl. ¶39).

U.S. Patent No. 11,850,226 - Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function

The Invention Explained

  • Problem Addressed: The patent addresses the same technical problem as the ’598 Patent: the need for adjusted dosing of renally-excreted solriamfetol in patients with impaired kidney function to avoid dose-dependent adverse effects (U.S. 11,850,226 B2, col. 2:32-54). This patent specifically addresses the problem in patients aged 65 years or over (U.S. 11,850,226 B2, Claim 1).
  • The Patented Solution: The invention provides a method of improving wakefulness in elderly patients by first determining the patient's level of renal function and then administering solriamfetol according to specific, multi-step dosing schedules corresponding to mild, moderate, or severe renal impairment, while avoiding its use in patients with end-stage renal disease (U.S. 11,850,226 B2, col. 3:56-4:15).
  • Technical Importance: The method provides specific guidance for safely dosing an at-risk patient population (elderly patients with renal impairment), thereby allowing them to receive the therapeutic benefit of the drug while minimizing the risk of adverse events (U.S. 11,850,226 B2, col. 2:56-62).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶48).
  • Essential elements of claim 1:
    • A method of improving wakefulness in a patient aged 65 years or over with excessive daytime sleepiness.
    • (a) Determining the renal status (eGFR) of the patient.
    • (b) Providing a first oral daily dose of 37.5 mg, a second dose of 75 mg after at least 3 days, and a third dose of 150 mg after at least 3 days for patients with mild or no renal impairment.
    • (c) Providing a first oral daily dose of 37.5 mg and a second dose of 75 mg after at least 5 days for patients with moderate renal impairment.
    • (d) Providing an oral daily dose of 37.5 mg for patients with severe renal impairment.
    • (e) Avoiding use of the drug when the patient has end-stage renal disease.
  • The complaint reserves the right to assert additional claims (Compl. ¶48).

U.S. Patent No. 11,850,227 - Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function

  • Technology Synopsis: This patent claims methods of treating excessive daytime sleepiness in patients with renal impairment. It specifies distinct dosing regimens for patients with mild, moderate, or severe renal impairment, based on their estimated glomerular filtration rate (eGFR), while proscribing use in patients with end-stage renal disease (U.S. 11,850,227 B2, Abstract; Claim 12).
  • Asserted Claims: At least independent claim 12 (Compl. ¶57).
  • Accused Features: The submission of ANDA No. 218725 for a generic version of solriamfetol, which Plaintiff alleges will be labeled with instructions that direct the infringing methods of administration (Compl. ¶57).

U.S. Patent No. 11,850,228 - Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function

  • Technology Synopsis: This patent claims methods of treating excessive daytime sleepiness in subjects with no, mild, moderate, or severe renal impairment. It requires selecting a subject who has not been treated with a monoamine oxidase inhibitor within the preceding 14 days and then administering solriamfetol according to specific dosing regimens tailored to the subject's level of renal function (U.S. 11,850,228 B2, Abstract; Claim 12).
  • Asserted Claims: At least independent claim 12 (Compl. ¶66).
  • Accused Features: The submission of ANDA No. 218725 for a generic version of solriamfetol, which Plaintiff alleges will be labeled with instructions that direct the infringing methods of administration (Compl. ¶66).

U.S. Patent No. 11,857,528 - Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function

  • Technology Synopsis: This patent claims methods of treating excessive daytime sleepiness by administering solriamfetol according to specific dosing regimens based on the subject's level of renal impairment. The claims define the appropriate dosing based on whether the resulting drug exposure (AUC) exceeds certain multiples of the exposure in a subject without renal impairment (U.S. 11,857,528 B1, Abstract; Claim 1).
  • Asserted Claims: At least independent claim 1 (Compl. ¶75).
  • Accused Features: The submission of ANDA No. 218725 for a generic version of solriamfetol, which Plaintiff alleges will be labeled with instructions that direct the infringing methods of administration (Compl. ¶75).

U.S. Patent No. 11,865,098 - Methods and Compositions for Treating Excessive Sleepiness

  • Technology Synopsis: This patent is directed to methods of treating excessive daytime sleepiness by administering solriamfetol at least 9 hours before the subject's bedtime. The patent states this timing minimizes insomnia (U.S. 11,865,098 B1, Abstract; Claim 14). The claims cover specific therapeutic amounts of the drug.
  • Asserted Claims: At least independent claim 1 (Compl. ¶84).
  • Accused Features: The submission of ANDA No. 218725 for a generic version of solriamfetol, which Plaintiff alleges will be labeled with instructions that direct the infringing methods of administration (Compl. ¶84).

U.S. Patent No. 11,872,203 - Methods of Administering Solriamfetol to Lactating Women

  • Technology Synopsis: This patent addresses the problem of administering solriamfetol to a breastfeeding subject while minimizing risk to the infant. The claimed solution involves feeding the infant breast milk at least 5 hours after the subject takes the drug, which is alleged to reduce the infant's exposure and decrease the potential for adverse events (U.S. 11,872,203 B1, Abstract; Claim 1).
  • Asserted Claims: At least independent claim 1 (Compl. ¶93).
  • Accused Features: The submission of ANDA No. 218725 for a generic version of solriamfetol, which Plaintiff alleges will be labeled with instructions that direct the infringing methods of administration (Compl. ¶93).

U.S. Patent No. 11,872,204 - Methods of Administering Solriamfetol to Lactating Women

  • Technology Synopsis: Similar to the '203 patent, this patent claims methods for reducing the risk of adverse events in an infant fed breast milk from a subject treated with solriamfetol. The method involves administering a specific daily dose (e.g., about 150 mg) and feeding the infant at least 5 hours later, resulting in a specified daily infant dose of 0.3 mg or lower (U.S. 11,872,204 B1, Abstract; Claim 1).
  • Asserted Claims: At least independent claim 1 (Compl. ¶102).
  • Accused Features: The submission of ANDA No. 218725 for a generic version of solriamfetol, which Plaintiff alleges will be labeled with instructions that direct the infringing methods of administration (Compl. ¶102).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Aurobindo’s Proposed Product," a generic version of solriamfetol oral tablets for which Defendant Aurobindo submitted Abbreviated New Drug Application (ANDA) No. 218725 to the FDA for marketing approval (Compl. ¶¶ 1, 31).

Functionality and Market Context

The complaint alleges that Aurobindo seeks approval to market a generic version of Axsome's Sunosi® drug product, which is a dopamine and norepinephrine reuptake inhibitor (DNRI) indicated to improve wakefulness in patients with excessive daytime sleepiness (Compl. ¶¶ 1-2, 16). The act of infringement alleged under 35 U.S.C. § 271(e)(2) is the submission of the ANDA itself. The infringement theory is prospective, based on the allegation that following FDA approval, Aurobindo will manufacture and sell its generic product with a label that instructs physicians and patients to use it in ways that practice the methods claimed in the patents-in-suit (Compl. ¶¶ 32, 42, 51).

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-chart analysis. The infringement allegations for each patent are pleaded conclusorily, stating that the submission of ANDA No. 218725 constitutes infringement of at least claim 1 of each patent-in-suit under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶¶ 39, 48, 57, 66, 75, 84, 93, 102). The central infringement theory is that Aurobindo is seeking FDA approval for a drug whose proposed labeling will instruct users to perform the patented methods of administration, which will constitute induced infringement upon approval and launch.

No probative visual evidence provided in complaint.

Identified Points of Contention

  • Scope Questions: A central dispute will likely concern the specific language of Aurobindo's proposed product label. The question for the court will be whether the label's instructions will necessarily lead a user or prescriber to practice every limitation of the asserted method claims. For example, for Claim 1 of the ’598 Patent, does the proposed label instruct the specific dose-escalation timing of waiting "at least" five days for moderately impaired patients, or does it provide more general guidance that might fall outside the claim scope?
  • Technical Questions: A key question will be whether following the instructions on Aurobindo's proposed label would inevitably result in the claimed "reducing toxicity" (recited in the preamble of Claim 1 of the ’598 Patent). Aurobindo may argue that this is a therapeutic outcome that is not guaranteed or that its label makes no such claim, while Axsome may argue it is an inherent result of following the patented dosing regimen.

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for analysis of specific claim term disputes. However, based on the asserted claims, practitioners may anticipate disputes over the following terms:

"reducing toxicity" (’598 Patent, Claim 1)

  • Context and Importance: This term appears in the preamble of the claim. Its construction is critical because if the court deems it a limiting claim element, Axsome would need to prove that Aurobindo's proposed label instructs a method that necessarily "reduces toxicity." Practitioners may focus on this term because Aurobindo could argue that its generic product is merely bioequivalent to Sunosi® and makes no separate claims about toxicity reduction, or that the term is indefinite.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification links the patented dosing schemes directly to minimizing "adverse effects" that are "dose-dependent," suggesting that following the claimed steps inherently achieves the purpose of reducing toxicity (U.S. 11,839,598 B2, col. 2:32-39; col. 2:56-62).
    • Evidence for a Narrower Interpretation: The patent does not provide a quantitative definition or baseline for what constitutes "reducing toxicity." A defendant could argue this lack of specificity renders the term indefinite or requires a specific, measurable reduction in adverse events that is not guaranteed by simply following the dosing steps.

"an integer equal to or greater than 5" (’598 Patent, Claim 1)

  • Context and Importance: This term defines the minimum waiting period (n₁) before escalating a dose in moderately impaired patients. This precise numerical limitation will be a focal point of the infringement analysis. If Aurobindo's proposed label instructs a waiting period of less than five days, or provides ambiguous guidance (e.g., "titrate as tolerated"), it may support a non-infringement argument.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification also mentions waiting "at least seven days" as an embodiment, framing the "at least five days" as a minimum threshold, which could support reading the term to cover any instructed waiting period of five days or more (U.S. 11,839,598 B2, col. 3:6-7).
    • Evidence for a Narrower Interpretation: The claim language is precise and mathematical ("an integer equal to or greater than 5"). This suggests a strict interpretation. A defendant would argue that any instruction for a period less than a full five days, or language that gives a physician discretion to escalate sooner, would not meet this limitation.

VI. Other Allegations

Indirect Infringement

The complaint alleges both induced and contributory infringement for each of the eight patents-in-suit. The basis for these allegations is that Aurobindo, by submitting its ANDA, knows that its proposed generic product is designed for uses that infringe the patents-in-suit and that its proposed product label will intentionally encourage and instruct physicians and patients to perform the claimed methods (e.g., Compl. ¶¶ 42-43, 51-52).

Willful Infringement

The complaint does not explicitly allege willful infringement. However, for each count, it alleges the case is "an exceptional one" and seeks an award of attorneys' fees under 35 U.S.C. § 285 (e.g., Compl. ¶ 46). The complaint establishes Aurobindo's knowledge of the patents-in-suit through its recitation of the multiple Paragraph IV notice letters sent to Axsome (Compl. ¶¶ 34-37).

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

  • A core issue will be one of label-based infringement: will the specific instructions in Aurobindo's proposed product label be found to direct physicians and patients to perform each and every step of the asserted method claims? The case will likely involve a meticulous comparison of the label's text against the precise dosing schedules, patient populations, and timings recited in the claims.
  • A key question for the defense will likely be one of patent validity: can Aurobindo prove by clear and convincing evidence that the claimed methods—which involve specific dose adjustments for distinct patient subpopulations—were obvious to a person of ordinary skill in the art at the time of the invention? This may involve arguing that such adjustments represent routine clinical practice for a renally-cleared drug, rather than a non-obvious, patentable discovery.