DCT

2:23-cv-20354

Axsome Malta Ltd v. Alkem Laboratories Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-20354, D.N.J., 09/13/2023
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendants conduct substantial business in the district, some maintain established places of business there, and the district will be a destination for the allegedly infringing generic products. For foreign-domiciled defendants, venue is alleged as proper in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of Abbreviated New Drug Applications (ANDAs) seeking to market generic versions of Plaintiff's Sunosi® (solriamfetol) oral tablets constitutes an act of infringement of thirteen U.S. patents covering solriamfetol compositions and methods of treating excessive sleepiness.
  • Technical Context: The technology concerns pharmaceutical compositions of solriamfetol and methods for its use in treating excessive daytime sleepiness associated with conditions such as narcolepsy and obstructive sleep apnea.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendants' service of Paragraph IV certification notice letters, which advised Plaintiff that Defendants were seeking FDA approval for their generic products and believe the patents-in-suit are invalid, unenforceable, and/or will not be infringed. The complaint does not mention any prior litigation or post-grant validity challenges involving the patents-in-suit.

Case Timeline

Date Event
2005-06-08 Priority Date for ’715, ’806, ’917, ’517 Patents
2013-05-14 ’715 Patent Issued
2014-11-04 ’806 Patent Issued
2016-09-06 Priority Date for ’151, ’609, ’597, ’354 Patents
2017-03-28 ’917 Patent Issued
2017-06-02 Priority Date for ’754, ’976, ’779, ’133, ’232 Patents
2019-02-05 ’151 Patent Issued
2019-07-16 ’517 Patent Issued
2019-12-24 ’609 Patent Issued
2021-02-09 ’754 Patent Issued
2021-03-09 ’133 Patent Issued
2021-03-30 ’976 Patent Issued
2021-11-02 ’779 Patent Issued
2022-09-13 ’597 Patent Issued
2023-01-24 ’354 Patent Issued
2023-05-16 ’232 Patent Issued
2023-08-01 Earliest Alleged Date of Hikma's Notice Letter
2023-08-09 Earliest Alleged Date of Unichem's Notice Letter
2023-08-10 Earliest Alleged Date of Aurobindo's Notice Letter
2023-08-11 Earliest Alleged Date of Alkem's Notice Letter
2023-08-15 Earliest Alleged Date of Hetero's Notice Letter
2023-08-15 Earliest Alleged Date of Sandoz's Notice Letter
2023-09-13 Complaint Filing Date

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

U.S. Patent No. 8,440,715 - "Treatment of Sleep-wake Disorders"

The Invention Explained

  • Problem Addressed: The patent's background section describes Excessive Daytime Sleepiness (EDS) as a primary complaint in sleep clinics that can be "debilitating and even life threatening," with narcolepsy identified as a common cause (’715 Patent, col. 1:40-51, col. 2:2-4).
  • The Patented Solution: The invention provides a method for treating EDS and related sleep-wake disorders by administering a therapeutically effective amount of a specific class of compounds, namely phenylalkylamino carbamates represented by Formula (I) (’715 Patent, Abstract; col. 4:21-44). The core compound, (R)-2-amino-3-phenylpropyl carbamate, is identified as having "novel and unique pharmacological properties" that increase wakefulness (’715 Patent, col. 5:20-30, col. 6:50-67).
  • Technical Importance: This approach provided a method of using a specific carbamate compound to treat EDS, a condition for which existing CNS stimulants could have "very dangerous side effects" when used at the high doses necessary to restore normal alertness (’715 Patent, col. 3:56-62).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶118).
  • The essential elements of Claim 1 are:
    • A method of increasing wakefulness or alertness in a subject.
    • Administering to the subject an effective amount of a compound of Formula (Ia) or a pharmaceutically acceptable salt thereof.
    • The subject has a condition selected from a list that includes, among others, a central nervous system (CNS) pathologic abnormality, narcolepsy, or obstructive sleep apnea.
  • The complaint does not explicitly reserve the right to assert dependent claims but makes general allegations of infringement of "one or more claims" (Compl. ¶118).

U.S. Patent No. 8,877,806 - "Treatment of Sleep-wake Disorders"

The Invention Explained

  • Problem Addressed: Similar to the ’715 Patent, this patent addresses Excessive Daytime Sleepiness (EDS) as a debilitating condition, citing narcolepsy as a primary example and noting the shortcomings of existing treatments (’806 Patent, col. 1:43-52, col. 3:55-62).
  • The Patented Solution: The invention claims a method of treating EDS by administering a therapeutically effective amount of an enantiomer of a specific phenylalkylamino carbamate compound, Formula (I), where that enantiomer is "substantially free of other enantiomers" (’806 Patent, Abstract; col. 4:45-51). The specification identifies the (R)-enantiomer, also named O-carbamoyl-(D)-phenylalaninol, as having activating effects that increase wakefulness (’806 Patent, col. 7:1-15).
  • Technical Importance: This patent refined the therapeutic approach by focusing on an enantiomerically pure form of the compound, which can offer a better therapeutic profile compared to a racemic mixture.

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 against Defendant Unichem (Compl. ¶640).
  • The essential elements of Claim 1 are:
    • A method of increasing wakefulness or alertness in a subject.
    • Administering to the subject an effective amount of an enantiomer of Formula (Ia) that is "substantially free of other enantiomers," or a salt thereof.
    • The subject has a condition selected from a list that includes, among others, a CNS pathologic abnormality, narcolepsy, or obstructive sleep apnea.
  • The complaint generally alleges infringement of "one or more claims" of the patent (Compl. ¶640).

U.S. Patent No. 9,604,917 - "Treatment of Sleep-wake Disorders"

  • Technology Synopsis: A continuation of the applications leading to the ’715 and ’806 patents, this patent also claims methods for treating Excessive Daytime Sleepiness (EDS) by administering a therapeutically effective amount of the enantiomer of (R)-2-amino-3-phenylpropyl carbamate (’917 Patent, Abstract). The patent asserts the compound is effective for EDS regardless of the underlying etiology (’917 Patent, col. 7:1-4).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶648).
  • Accused Features: The complaint alleges that the proposed generic solriamfetol products, intended for treating EDS, will infringe (Compl. ¶648-649).

U.S. Patent No. 10,351,517 - "Treatment of Sleep-wake Disorders"

  • Technology Synopsis: This patent also relates to methods of treating EDS by administering (R)-2-amino-3-phenylpropyl carbamate. It specifically claims methods of increasing wakefulness in subjects with conditions such as narcolepsy or obstructive sleep apnea (’517 Patent, Abstract).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶657).
  • Accused Features: The complaint alleges that the proposed generic solriamfetol products, intended for treating EDS, will infringe (Compl. ¶657-658).

U.S. Patent No. 10,195,151 - "Formulations of (R)-2-amino-3-phenylpropyl carbamate"

  • Technology Synopsis: This patent shifts focus from methods of use to specific pharmaceutical compositions. It claims an immediate-release compressed oral tablet formulation containing a high percentage (90-98% by weight) of (R)-2-amino-3-phenylpropyl carbamate (APC), a binder, and a lubricant, characterized by rapid dissolution (’151 Patent, Abstract; col. 7:42-55).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶127).
  • Accused Features: The complaint alleges that the proposed generic solriamfetol oral tablet products embody the claimed formulation (Compl. ¶127).

U.S. Patent No. 10,512,609 - "Formulations of (R)-2-amino-3-phenylpropyl carbamate"

  • Technology Synopsis: This patent is related to the ’151 patent and also claims specific immediate-release oral dosage forms of (R)-2-amino-3-phenylpropyl carbamate. The claims define the formulation by its components and their weight percentages, including the active ingredient (90-98%), a binder, and a lubricant (’609 Patent, Abstract).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶136).
  • Accused Features: The complaint alleges that the proposed generic solriamfetol oral tablet products embody the claimed formulation (Compl. ¶136).

U.S. Patent No. 11,439,597 - "Formulations of (R)-2-amino-3-phenylpropyl carbamate"

  • Technology Synopsis: This patent is also in the same family as the ’151 and ’609 patents and claims specific oral pharmaceutical formulations. The claims are directed to solid formulations containing a high concentration of an APC salt (75 mg), specific binders, and lubricants, which release the drug quickly after administration (’597 Patent, Abstract; col. 18:1-24).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶145).
  • Accused Features: The complaint alleges that the proposed generic solriamfetol oral tablet products embody the claimed formulation (Compl. ¶145).

U.S. Patent No. 10,912,754 - "Methods and Compositions for Treating Excessive Sleepiness"

  • Technology Synopsis: This patent claims methods of treating excessive sleepiness by administering solriamfetol in an amount sufficient to achieve a "normal" level of wakefulness. Normalcy is defined by achieving a specific score (e.g., ≤10) on the Epworth Sleepiness Scale (ESS) or a significant improvement (e.g., ≥5 minutes) on the Maintenance of Wakefulness Test (MWT) (’754 Patent, col. 2:1-16).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶154).
  • Accused Features: The complaint alleges that the proposed generic products, by being bioequivalent to Sunosi®, will achieve the claimed clinical outcomes when administered according to their labels (Compl. ¶154).

U.S. Patent No. 10,959,976 - "Methods and Compositions for Treating Excessive Sleepiness"

  • Technology Synopsis: Related to the ’754 patent, this patent also claims methods of treating EDS in patients with obstructive sleep apnea or narcolepsy by administering solriamfetol. The claims are tied to achieving specific clinical results, such as improving ESS or MWT scores by a defined amount or to a specific level (’976 Patent, Abstract).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶163).
  • Accused Features: The complaint alleges that administration of the proposed generic products according to their labels will practice the claimed methods and achieve the specified clinical results (Compl. ¶163).

U.S. Patent No. 11,160,779 - "Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function"

  • Technology Synopsis: This patent claims specific methods for administering solriamfetol to patients with moderate or severe renal impairment. The invention is a dose escalation regimen tailored to the patient's level of renal function, as measured by estimated glomerular filtration rate (eGFR), to reduce toxicity (’779 Patent, Abstract; col. 4:45-53).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶172).
  • Accused Features: The complaint alleges that the proposed generic product labels will instruct for dosing in renally impaired patients in a way that infringes the claimed methods (Compl. ¶172).

U.S. Patent No. 10,940,133 - "Methods of Providing Solriamfetol Therapy to Subjects with Impaired Renal Function"

  • Technology Synopsis: Similar to the ’779 patent, this patent claims methods for dosing solriamfetol in patients with impaired renal function. The claims specify dose escalation schemes for patients with moderate renal impairment, involving an initial dose followed by an increased dose after a set number of days (’133 Patent, Abstract; col. 3:6-21).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶181).
  • Accused Features: The complaint alleges infringement based on the expectation that the generic product labels will contain instructions for dosing renally impaired patients that align with the claimed regimens (Compl. ¶181).

U.S. Patent No. 11,560,354 - "Compositions comprising (R)-2-amino-3-phenylpropyl carbamate and uses thereof"

  • Technology Synopsis: This patent discloses a newly identified solvate form (a hemihydrate) of (R)-2-amino-3-phenylpropyl carbamate hydrochloride. It also claims compositions containing this form and methods of using it to treat disorders like narcolepsy and cataplexy (’354 Patent, Abstract).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶190).
  • Accused Features: The complaint alleges that the proposed generic products, which comprise solriamfetol, infringe the claims (Compl. ¶190).

U.S. Patent No. 11,648,232 - "Methods and Compositions for Treating Excessive Sleepiness"

  • Technology Synopsis: This patent is in the family of the ’754 and ’976 patents. It claims methods for improving or treating excessive sleepiness by administering solriamfetol to achieve specified improvements in clinical measures like the Epworth Sleepiness Scale score (’232 Patent, Abstract; col. 37:1-14).
  • Asserted Claims: At least independent claim 1 is asserted (Compl. ¶199).
  • Accused Features: The complaint alleges that use of the proposed generic products as directed by their labels will infringe the claimed methods (Compl. ¶199).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are the generic solriamfetol oral tablet drug products for which each Defendant has filed an Abbreviated New Drug Application (ANDA) with the FDA (Compl. ¶1, 33, 42, 51, 65, 74, 83).
  • Functionality and Market Context: The complaint alleges that the Defendants' proposed products are generic versions of Plaintiff's Sunosi® (solriamfetol) oral tablets (Compl. ¶1, 27). 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, 27). The Defendants seek FDA approval to commercially manufacture, market, and sell these generic versions prior to the expiration of the patents-in-suit, which are listed in the FDA's "Orange Book" with respect to Sunosi® (Compl. ¶1, 28). The act of filing the ANDAs seeking such approval is the statutory basis for the infringement claims under 35 U.S.C. § 271(e)(2) (Compl. ¶118).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain or reference any claim charts or provide a detailed, element-by-element infringement analysis. Instead, it asserts infringement based on the statutory framework of the Hatch-Waxman Act, where the filing of an ANDA is a technical act of infringement (Compl. ¶118, 127). The narrative infringement theory is that the Defendants' proposed generic products contain the same active ingredient (solriamfetol), are formulated as oral tablets, and will be prescribed for the same indications as Plaintiff's branded Sunosi® product (Compl. ¶1, 27). Therefore, the commercial manufacture, use, or sale of the generic products would directly infringe the composition claims, and their prescribed use would induce infringement of the method-of-use claims.

  • Identified Points of Contention: The complaint itself does not detail specific points of contention, as it presents only the Plaintiff's allegations. However, the nature of this ANDA litigation suggests that the primary disputes will arise from the Defendants' non-infringement and invalidity arguments, as outlined in their Paragraph IV notice letters (Compl. ¶89, 94, 99, 104, 109, 114).
    • Scope Questions: For the method patents (e.g., ’715, ’806), a question may arise as to whether the instructions on the generic products' proposed labels will direct users to perform every step of the claimed methods. For the formulation patents (e.g., ’151), a potential dispute is whether the excipients, manufacturing processes, and resulting dissolution profiles of the generic products fall within the literal scope of the claims.
    • Technical Questions: A central technical question for the formulation patents (e.g., ’151, ’609, ’597) will be whether the specific compositions of the generic tablets—including the identity and percentage of binders and lubricants—meet the claim limitations. For the method claims tied to clinical outcomes (e.g., ’754, ’976), a question for the court may be how infringement is demonstrated in an ANDA context where the generic product's efficacy is established through bioequivalence rather than independent clinical trials mirroring the patent's data.

V. Key Claim Terms for Construction

  • The Term: "an effective amount" (from Claim 1 of the ’715 Patent)

  • Context and Importance: This term is fundamental to all asserted method claims, as it defines the required dosage. Its construction will be critical for determining infringement. Practitioners may focus on this term because Defendants could argue that their proposed dosage, while bioequivalent to the branded product, does not meet a specific definition of "effective" required by the patent, or that the term is indefinite for failing to specify a result.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification of the related ’806 Patent defines "therapeutically effective amount" broadly as that which "imparts a modulating effect...including improvement in the condition of the subject" (’806 Patent, col. 9:22-34). This suggests the term should be read broadly to cover any amount that provides a clinical benefit.
    • Evidence for a Narrower Interpretation: The ’806 Patent also provides specific dosage ranges, such as "about 0.01 mg/kg/dose to about 150 mg/kg/dose" (’806 Patent, col. 20:20-22). A party could argue that "effective amount" should be construed in light of these more specific disclosures.

  • The Term: "substantially free of other enantiomers" (from Claim 1 of the ’806 Patent)

  • Context and Importance: This term defines the required enantiomeric purity of the active ingredient. The accused products contain solriamfetol, which is the (R)-enantiomer. The dispute will likely center on the specific percentage of purity required to be "substantially free."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The ’806 Patent specification states, "In preferred embodiments, the compound includes at least about 90% by weight of a preferred enantiomer" (’806 Patent, col. 14:23-25). This language could support an interpretation that any purity level of 90% or greater meets the limitation.
    • Evidence for a Narrower Interpretation: The same section of the specification continues, "In other embodiments of the invention, the compound includes at least about 99% by weight of a preferred enantiomer" (’806 Patent, col. 14:25-27). A party could argue that this represents the truly inventive purity level and that "substantially free" should be construed more narrowly to mean at least 99% purity.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all asserted patents. Inducement is based on the allegation that Defendants' proposed product labeling will instruct physicians and patients to administer the generic drugs in a manner that infringes the method claims (Compl. ¶121, 130). Contributory infringement is based on the allegation that the generic products are designed for an infringing use and lack a substantial non-infringing use (Compl. ¶122, 131).
  • Willful Infringement: The complaint does not explicitly allege willful infringement. However, for each patent and defendant, it requests a judgment that the case is "exceptional" and an award of attorneys' fees pursuant to 35 U.S.C. § 285 (Compl. ¶125). The factual basis for this appears to be the Defendants' pre-suit knowledge of the patents, evidenced by their Paragraph IV notice letters (Compl. ¶88, 93, 98, 103, 108, 113).

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

  • A central issue will be one of validity: given that the core compound, a phenylalaninol derivative, was known in the art, will the defendants be able to demonstrate by clear and convincing evidence that the specific method-of-use and formulation claims asserted by the plaintiff were obvious to a person of ordinary skill at the time of the inventions?
  • A key question of claim scope will arise for the formulation patents (e.g., ’151, ’609): can the specific combination of active pharmaceutical ingredient percentage, binder type, and lubricant type claimed in the patents be read to cover the formulations disclosed in the Defendants' confidential ANDA filings, or do differences in excipients or manufacturing place the generic products outside the claims' literal scope?
  • An evidentiary question of infringement will be presented by the method claims tied to clinical outcomes (e.g., ’754, ’976): what level of proof is required to show that a generic product, approved on the basis of bioequivalence, will induce infringement of claims that require achieving a "normal" level of wakefulness or specific improvements on clinical scales like the Epworth Sleepiness Scale?