DCT

2:24-cv-09209

Axsome Malta Ltd v. Alkem Laboratories Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:24-cv-09209, D.N.J., 09/16/2024
  • Venue Allegations: Venue is alleged based on the U.S. corporate defendants having principal places of business or established physical locations in New Jersey, and on the foreign corporate defendants being subject to jurisdiction in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of Abbreviated New Drug Applications (ANDAs) to market generic versions of Axsome's Sunosi® (solriamfetol) oral tablets infringes seven U.S. patents relating to specific formulations and methods of use.
  • Technical Context: The technology concerns formulations of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, and methods of administering it to improve wakefulness, particularly for patient subpopulations such as those with impaired renal function or lactating women.
  • Key Procedural History: The litigation was triggered by Defendants sending Paragraph IV Certification notice letters to Axsome, stating their belief that Axsome's Orange Book-listed patents for Sunosi® are invalid, unenforceable, or will not be infringed by their proposed generic products. The complaint also references other related, consolidated actions involving the same parties and patents.

Case Timeline

Date Event
2016-09-06 U.S. Patent No. 11,998,639 Priority Date
2020-03-19 U.S. Patent Nos. 11,969,404; 11,986,454; 11,986,455 Priority Date
2022-12-30 U.S. Patent Nos. 12,005,036; 12,036,194; 12,064,411 Priority Date
2023-08-01 Hikma sends First Notice Letter to Axsome (earliest date)
2023-08-10 Aurobindo sends First Notice Letter to Axsome (earliest date)
2023-08-11 Alkem sends First Notice Letter to Axsome (earliest date)
2023-08-15 Hetero sends First Notice Letter to Axsome (earliest date)
2024-04-30 U.S. Patent No. 11,969,404 Issues
2024-05-21 U.S. Patent No. 11,986,454 Issues
2024-05-21 U.S. Patent No. 11,986,455 Issues
2024-06-04 U.S. Patent No. 11,998,639 Issues
2024-06-11 U.S. Patent No. 12,005,036 Issues
2024-07-16 U.S. Patent No. 12,036,194 Issues
2024-08-20 U.S. Patent No. 12,064,411 Issues
2024-09-16 Complaint Filing Date

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," issued April 30, 2024 (’404 Patent)

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of safely administering solriamfetol (APC-HCl), a drug eliminated through the kidneys, to patients with impaired renal function. Standard doses in such patients could lead to higher drug exposure and exacerbated dose-dependent adverse effects, but a safe and effective adjusted dosage was not known. (’404 Patent, col. 2:31-54).
  • The Patented Solution: The invention provides specific, optimized dosing regimens for patients with moderate or severe renal impairment. It teaches a dose escalation scheme for moderately impaired patients (e.g., starting at 37.5 mg and increasing to 75 mg after at least five days) and a maximum daily dose for severely impaired patients (e.g., 37.5 mg), based on pharmacokinetic data modeling drug exposure against renal function. (’404 Patent, Abstract; col. 3:20-41).
  • Technical Importance: This approach allows for the therapeutic use of solriamfetol in patient populations that might otherwise be excluded or be at higher risk of adverse effects, by tailoring the dosage to their specific physiological state. (’404 Patent, col. 2:55-65).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1. (Compl. ¶¶ 136, 199).
  • Essential elements of claim 1 include:
    • A method of treating a human subject with [R]-2-amino-3-phenylpropylcarbamate (APC) who has a history of bipolar disorders.
    • Determining if the patient has moderate or severe renal impairment based on estimated glomerular filtration rate (eGFR).
    • If the patient has moderate renal impairment (eGFR of about 30 to 59 mL/min/1.73 m²), providing a first daily dose of 37.5 mg APC for at least 5 days, followed by a second daily dose of 75 mg APC, with a maximum dose not exceeding 75 mg APC.
    • If the patient has severe renal impairment (eGFR of about 15 to 29 mL/min/1.73 m²), providing a daily dose of 37.5 mg APC, with a maximum dose not exceeding 37.5 mg APC.
  • The complaint reserves the right to assert additional claims. (Compl. ¶¶ 136, 199).

U.S. Patent No. 11,986,454 - "Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function," issued May 21, 2024 (’454 Patent)

The Invention Explained

  • Problem Addressed: This patent, a continuation of the family that includes the ’404 patent, addresses the same technical problem: determining a safe and effective dosing regimen for solriamfetol in patients with impaired renal function to avoid heightened exposure and adverse effects. (’454 Patent, col. 2:37-54).
  • The Patented Solution: The patent claims methods for treating excessive daytime sleepiness by first selecting a patient who does not have end-stage renal disease and then administering specific, tiered dosing regimens based on whether the patient's renal impairment is moderate or severe. The claimed dosing schedules are designed to manage drug exposure based on pharmacokinetic findings. (’454 Patent, Abstract; col. 3:20-41).
  • Technical Importance: The invention provides a structured, data-driven method for physicians to treat excessive daytime sleepiness in renally impaired patients, a group for whom dosing of renally-cleared drugs presents a significant clinical challenge. (’454 Patent, col. 2:55-65).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1. (Compl. ¶¶ 145, 208).
  • Essential elements of claim 1 include:
    • A method of treating excessive daytime sleepiness.
    • Selecting a subject who does not have end-stage renal disease.
    • Determining the subject's eGFR.
    • For subjects with moderate renal impairment (eGFR of about 30 to 59 mL/min/1.73 m²), providing a first daily dose of 37.5 mg APC for at least 5 days, followed by a second daily dose of 75 mg APC, with a maximum dose not exceeding 75 mg APC.
    • For subjects with severe renal impairment (eGFR of about 15 to 29 mL/min/1.73 m²), providing a daily dose equivalent to 37.5 mg APC, with a maximum dose not exceeding 37.5 mg APC.
  • The complaint reserves the right to assert additional claims. (Compl. ¶¶ 145, 208).

Multi-Patent Capsule: U.S. Patent No. 11,986,455

  • Patent Identification: U.S. Patent No. 11986455, "Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function," issued May 21, 2024 (’455 Patent). (Compl. ¶ 15).
  • Technology Synopsis: This patent covers methods of treating excessive daytime sleepiness by administering solriamfetol. It claims a comprehensive method that includes specific dosing regimens for patients with mild, moderate, or severe renal impairment, creating a tiered therapeutic approach based on kidney function. (Compl. ¶¶ 15, 154, 217).
  • Asserted Claims: At least independent claim 12 is asserted. (Compl. ¶¶ 154, 217).
  • Accused Features: Defendants' proposed generic products are accused of infringement because their labels will allegedly instruct medical professionals and patients to follow the patented dosing regimens based on renal function. (Compl. ¶¶ 91, 98, 156-158, 219-221).

Multi-Patent Capsule: U.S. Patent No. 11,998,639

  • Patent Identification: U.S. Patent No. 11998639, "Formulations of (R)-2-Amino-Phenylpropyl Carbamate," issued June 4, 2024 (’639 Patent). (Compl. ¶ 16).
  • Technology Synopsis: This patent claims specific oral pharmaceutical formulations of solriamfetol designed for immediate release. The claims recite a composition with a high concentration of the active ingredient (90-98%), a small amount of binder (1-5%), and a small amount of lubricant (0.1-2%), which is formulated to dissolve quickly and does not contain a disintegrant. (’639 Patent, Claim 1).
  • Asserted Claims: At least independent claims 1 and 16 are asserted. (Compl. ¶¶ 163, 226).
  • Accused Features: The physical composition of Defendants' proposed generic solriamfetol tablets are accused of infringing the patent's formulation claims. (Compl. ¶¶ 91, 98, 165-167, 228-230).

Multi-Patent Capsule: U.S. Patent Nos. 12,005,036, 12,036,194, and 12,064,411

  • Patent Identification: U.S. Patent Nos. 12005036 (’036 Patent), 12036194 (’194 Patent), and 12064411 (’411 Patent), all titled "Methods of Administering Solriamfetol to Lactating Women," issued June 11, July 16, and August 20, 2024, respectively. (Compl. ¶¶ 17-19).
  • Technology Synopsis: These patents cover methods for reducing an infant's exposure to solriamfetol from breast milk. The invention involves having the nursing mother wait a specific period of time (e.g., at least 5 hours) after taking her dose before feeding the infant breast milk, thereby avoiding the peak concentration of the drug in the milk. (Compl. ¶¶ 17-19, 100, 109, 118, 127, 172, 181, 190, 235, 244, 253).
  • Asserted Claims: At least independent claim 1 of each patent is asserted. (Compl. ¶¶ 100, 109, 118, 127, 172, 181, 190, 235, 244, 253).
  • Accused Features: Defendants' proposed product labels are accused of infringement because they will allegedly instruct lactating mothers on methods of using solriamfetol that will directly track the patented methods for minimizing infant exposure. (Compl. ¶¶ 91, 98, 102-104, 111-113, etc.).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are the generic solriamfetol oral tablet drug products for which Alkem Laboratories Ltd., Aurobindo Pharma USA, Inc. et al., Hetero USA Inc. et al., and Hikma Pharmaceuticals USA Inc. have filed Abbreviated New Drug Applications Nos. 218722, 218725, 218654, and 218016, respectively. (Compl. ¶ 1).
  • Functionality and Market Context: The proposed products are generic versions 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). The complaint alleges that upon FDA approval, Defendants will manufacture, market, and sell these generic products in the United States prior to the expiration of the patents-in-suit. (Compl. ¶¶ 76, 85, 91, 98). The complaint does not provide specific technical details of the Defendants' proposed products beyond identifying them as generic equivalents of Sunosi®.

IV. Analysis of Infringement Allegations

The complaint does not contain or append claim charts. The infringement theory is articulated through narrative allegations that the submission of an ANDA is a statutory act of infringement under 35 U.S.C. § 271(e)(2) and that the eventual commercialization of the proposed generic products will constitute direct infringement (§ 271(a)), induced infringement (§ 271(b)), and contributory infringement (§ 271(c)). (Compl. ¶¶ 100-104, 109-113).

For the method-of-use patents (e.g., ’404 and ’454 Patents), the central allegation is that the product labeling for the Defendants' generic drugs will instruct physicians and patients to administer the drug in a manner that practices the claimed methods, such as adjusting dosage based on the patient's level of renal impairment. For the formulation patent (’639 Patent), the allegation is that the physical composition of the Defendants' generic tablets will meet the limitations of the patent's claims.

No probative visual evidence provided in complaint.

  • Identified Points of Contention:
    • Scope Questions: A central question for the method claims will be whether the language on the Defendants’ proposed drug labels instructs or encourages the performance of every step of the claimed methods. For example, does a label that provides physicians with dosing information for renally impaired patients rise to the level of actively inducing infringement of a claim that requires a specific multi-day titration schedule (e.g., "a first oral daily dose...from day one to day n₁, and a second oral daily dose...starting on day n₂")?
    • Technical Questions: For the formulation patent (’639 Patent), a key technical question will be whether the Defendants' generic products, which must be bioequivalent to Sunosi®, will necessarily be formulated with the specific percentages of active ingredient, binder, and lubricant recited in the claims.

V. Key Claim Terms for Construction

  • The Term: "about"

    • Context and Importance: This term appears in the eGFR ranges that define patient populations in the asserted method claims (e.g., "eGFR of about 30 mL/min/1.73 m² to about 59 mL/min/1.73 m²"). (’454 Patent, claim 1). The scope of "about" will determine the breadth of the patient populations covered by the claims and will be critical to both infringement and validity analyses. Practitioners may focus on this term because its construction could either capture or exclude standard clinical thresholds for defining renal impairment.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent does not explicitly define "about," which may support giving the term its ordinary meaning of "approximately" or "close to," allowing for reasonable variation based on the precision of clinical measurements. The specification's reliance on pharmacokinetic modeling and simulations across patient groups, rather than just rigid cutoffs, could also support a broader reading. (’454 Patent, col. 38:45-55).
      • Evidence for a Narrower Interpretation: The specification explicitly references the FDA's guidance for defining renal impairment categories with precise numerical ranges (e.g., "Moderate: eGFR 30-59 mL/min/1.73 m²"). (’454 Patent, col. 13:1-2). A party could argue that "about" should be construed narrowly to mean the recited number and its standard clinical equivalents, effectively limiting the term to the specific boundaries of the established clinical definitions.

  • The Term: "providing ... a first oral daily dose ... from day one to day n₁ ... and a second oral daily dose ... starting on day n₂"

    • Context and Importance: This language from claim 1 of the ’454 Patent defines a specific, multi-stage dose escalation regimen over a period of at least five days. The construction of this entire phrase will be central to determining whether a generic drug label that offers dosing guidelines, but gives a physician discretion in titration timing, induces infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent describes the invention as providing a "dose escalation scheme" to "minimize adverse effects." (’454 Patent, col. 2:57-60). A plaintiff may argue that any label that recommends starting at the lower dose and escalating to the higher dose for moderately impaired patients teaches the core of this claimed method, even if it does not use the exact "day n₁/day n₂" language.
      • Evidence for a Narrower Interpretation: The claim language is highly specific, requiring a first dosing period of "n₁" days where n₁ is at least 5, followed by a second dosing period starting on day "n₂+1". A defendant may argue that this creates a precise, mandatory schedule and that a label merely suggesting that a dose "may be increased" after some time does not meet this specific temporal limitation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement against all defendants for all asserted patents. (Compl. ¶¶ 103-104, 112-113, etc.). The allegations are based on Defendants' knowledge of the patents-in-suit and the assertion that their proposed product labeling will instruct users to perform the patented methods. The complaint further alleges the proposed products lack substantial non-infringing uses. (Compl. ¶¶ 104, 113).
  • Willful Infringement: While the term "willful" is not used, the complaint alleges for each count that the case is "an exceptional one" and requests attorneys' fees under 35 U.S.C. § 285. (Compl. ¶¶ 107, 116, etc.). This allegation is predicated on the Defendants' knowledge of the patents, established by their filing of Paragraph IV certifications.

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

  • A core issue will be one of validity over clinical practice: Can method claims reciting specific dosing regimens, which were developed from pharmacokinetic studies, withstand obviousness challenges based on the general knowledge that drug dosages should be adjusted for patients with renal impairment? The case may turn on whether the specific titration schedules and dosage caps claimed in the patents would have been obvious to try with a reasonable expectation of success.
  • A second central question will be one of induced infringement via labeling: Assuming the claims are valid, does the language in the Defendants’ proposed generic drug labels rise to the level of actively encouraging or instructing physicians and patients to perform every step of the claimed methods? The dispute will likely focus on whether providing dosage information and suggesting possible titration constitutes inducement of claims that recite precise, multi-day schedules.
  • For the formulation patent, a key evidentiary question will be one of compositional identity: Will discovery show that the Defendants' ANDA products, in seeking to be bioequivalent to the branded drug, are necessarily formulated with the specific high-concentration, low-excipient ratios required by the ’639 patent claims?