DCT
1:25-cv-00221
Avadel CNS Pharma LLC v. Jazz Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Avadel CNS Pharmaceuticals, LLC (Delaware) and Flamel Ireland Limited (Ireland)
- Defendant: Jazz Pharmaceuticals, Inc. (Delaware) and Jazz Pharmaceuticals Ireland Limited (Ireland)
- Plaintiff’s Counsel: McCarter & English, LLP
- Case Identification: 1:25-cv-00221, D. Del., 02/25/2025
- Venue Allegations: Venue is alleged to be proper as to Jazz Pharmaceuticals, Inc. because it is a Delaware corporation and as to Jazz Pharmaceuticals Ireland Limited because it is not a resident of the United States.
- Core Dispute: Plaintiff alleges that Defendant’s XYWAV® product infringes two patents related to once-nightly treatment methods using mixed-salt formulations of gamma-hydroxybutyrate.
- Technical Context: The technology concerns modified-release pharmaceutical formulations for treating sleep disorders like narcolepsy, aiming to provide a therapeutic effect throughout the night with a single bedtime dose.
- Key Procedural History: The complaint alleges that Defendant has a history of monitoring Plaintiff’s patent portfolio, citing testimony from prior litigation and Information Disclosure Statements filed during Defendant's own patent prosecutions that referenced Plaintiff's patents. Plaintiff also alleges it sent Defendant a notice letter on the day the patents-in-suit issued.
Case Timeline
| Date | Event |
|---|---|
| 2016-07-22 | Earliest Priority Date for '388 and '389 Patents |
| 2021-08-12 | XYWAV® receives FDA approval for Idiopathic Hypersomnia |
| 2024-11-07 | Application for '389 Patent becomes public |
| 2024-11-14 | Application for '388 Patent becomes public |
| 2024-12-20 | Final claims for '388 and '389 Patents become public |
| 2025-02-18 | '388 and '389 Patents Issue |
| 2025-02-18 | Plaintiff sends notice letter to Defendant |
| 2025-02-25 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 12,226,388 - "Modified Release Gamma-Hydroxybutyrate Formulations Having Improved Pharmacokinetics"
- Issued: February 18, 2025
The Invention Explained
- Problem Addressed: The patent's background section describes the "substantial inconvenience" for narcolepsy patients of existing treatments like Xyrem®, which require a second dose to be taken 2.5 to 4 hours after bedtime, thereby interrupting sleep (’388 Patent, col. 1:47-53). A further drawback noted is the high sodium intake associated with such treatments (’388 Patent, col. 2:38-46).
- The Patented Solution: The invention is a modified-release formulation of gamma-hydroxybutyrate (GHB) that is designed for once-nightly administration (’388 Patent, Abstract). The patent describes discovering a relationship between a specific in vitro dissolution profile and in vivo absorption that allows a once-nightly dose to approximate the bioavailability of a twice-nightly immediate-release product, solving the prior art problem of reduced bioavailability in once-nightly formulations (’388 Patent, col. 6:49-65).
- Technical Importance: This approach seeks to improve patient quality of life and compliance by providing a full night of therapeutic effect from a single dose, eliminating the need to wake up to take a second dose (’388 Patent, col. 1:51-53).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶15).
- The essential elements of Claim 1 are:
- A method of treating a disorder treatable with a pharmaceutically acceptable salt of gamma-hydroxybutyrate in a human subject in need thereof,
- The method comprising orally administering a single nighttime daily dose to said human,
- Wherein the dose comprises a first salt and a second, different salt of gamma-hydroxybutyric acid, with each salt selected from the group of sodium, calcium, potassium, or magnesium salts,
- Wherein the oral administration occurs only once nightly, and
- The method further comprises uptitrating the single nighttime daily dose in increments equivalent to about 1.5 g of sodium oxybate per night at weekly intervals to effect.
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 12,226,389 - "Modified Release Gamma-Hydroxybutyrate Formulations Having Improved Pharmacokinetics"
- Issued: February 18, 2025
The Invention Explained
- Problem Addressed: The patent addresses the same problems as the ’388 Patent: the inconvenience of twice-nightly dosing for GHB treatments and the reduced bioavailability of previous once-nightly formulations (’389 Patent, col. 1:47-61).
- The Patented Solution: The invention is a once-nightly, modified-release GHB formulation that achieves a specific pharmacokinetic profile, particularly concerning its interaction with food (’389 Patent, Abstract). The patent claims a method of treatment where administration after a high-fat meal results in a specific, defined reduction in the maximum plasma concentration (Cmax) of the drug, which provides a predictable therapeutic profile (’389 Patent, col. 5:24-26).
- Technical Importance: By defining and claiming a specific pharmacokinetic food-effect profile, the invention aims to provide a reliable and predictable therapeutic outcome for a once-nightly dose, a challenge for prior modified-release formulations.
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶17).
- The essential elements of Claim 1 are:
- A method of treating a disorder treatable with a pharmaceutically acceptable salt of gamma-hydroxybutyrate in a human subject in need thereof,
- The method comprising orally administering a single nighttime daily dose to said human,
- Wherein the dose comprises a first salt and a second, different salt of gamma-hydroxybutyric acid, with each salt selected from the group of sodium, calcium, potassium, or magnesium salts,
- Wherein the dose comprises an amount of salts equivalent to 1.5 g, 3.0 g, 4.5 g, 6.0 g, 7.5 g, or 9.0 g of sodium oxybate,
- Wherein the oral administration occurs only once nightly, and
- Wherein administration immediately after a high-fat meal results in a mean reduction in Cmax of gamma-hydroxybutyrate by 33%.
- The complaint does not explicitly reserve the right to assert dependent claims.
III. The Accused Instrumentality
Product Identification
- The accused product is Defendant's XYWAV® oral solution (Compl. ¶18).
Functionality and Market Context
- XYWAV® is an oral solution containing a mixture of calcium, magnesium, potassium, and sodium salts of gamma-hydroxybutyrate (Compl. ¶19). It is approved by the FDA for the treatment of idiopathic hypersomnia and for cataplexy or excessive daytime sleepiness in patients with narcolepsy (Compl. ¶¶21-22).
- The complaint alleges that the approved labeling for XYWAV® provides instructions for a "once nightly regimen" for adult patients with idiopathic hypersomnia (Compl. ¶28). The labeling allegedly recommends initiating dosage at 3 g or less per night and titrating "to effect in increments of up to 1.5 g per night per week, up to 6 g total nightly dose" (Compl. ¶28). The complaint also quotes the XYWAV® Prescribing Information as stating that administration after a high-fat meal resulted in a 33% reduction in the Cmax of gamma-hydroxybutyrate (Compl. ¶29).
- The complaint alleges Defendant markets XYWAV® for treating symptoms including excessive daytime sleepiness and promotes its use via its website and promotional materials (Compl. ¶¶30-31).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
12,226,388 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a disorder treatable with a pharmaceutically acceptable salt of gamma-hydroxybutyrate in a human subject in need thereof, the method comprising: orally administering a single nighttime daily dose to said human, | Defendant allegedly encourages, instructs, and/or promotes the administration of XYWAV® "once-nightly orally" to treat disorders like idiopathic hypersomnia. | ¶28, 43 | col. 8:5-6 |
| wherein said single nighttime daily dose comprises a first salt of gamma-hydroxybutyric acid and a second salt of gamma-hydroxybutyric acid... wherein the second salt differs from the first salt... | The XYWAV® product is a mixture of four different salts of gamma-hydroxybutyrate: calcium, magnesium, potassium, and sodium oxybate. | ¶19 | col. 8:1-4 |
| wherein the orally administering occurs only once nightly; and | The XYWAV® Prescribing Information allegedly instructs on a "once nightly regimen in adults." | ¶28 | col. 8:11-12 |
| uptitrating the single nighttime daily dose in increments equivalent to about 1.5 g of sodium oxybate per night at weekly intervals to effect. | The XYWAV® Prescribing Information allegedly recommends titration "in increments of up to 1.5 g per night per week, up to 6 g total nightly dose." | ¶28 | col. 8:12-15 |
12,226,389 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a disorder treatable with a pharmaceutically acceptable salt of gamma-hydroxybutyrate in a human subject in need thereof, the method comprising: orally administering a single nighttime daily dose to said human, | Defendant allegedly encourages, instructs, and/or promotes the administration of XYWAV® "once-nightly orally" to treat disorders like idiopathic hypersomnia. | ¶27-28 | col. 5:10-12 |
| wherein said single nighttime daily dose comprises a first salt of gamma-hydroxybutyric acid and a second salt of gamma-hydroxybutyric acid... wherein the second salt differs from the first salt... | The XYWAV® product is a mixture of four different salts of gamma-hydroxybutyrate: calcium, magnesium, potassium, and sodium oxybate. | ¶19 | col. 5:15-20 |
| wherein the single nighttime daily dose comprises an amount of salts of gamma-hydroxybutyric acid equivalent to 1.5 g, 3.0 g, 4.5 g, 6.0 g, 7.5 g, or 9.0 g of sodium oxybate, | The XYWAV® labeling allegedly instructs that a dose of XYWAV® is equivalent to the same gram-for-gram dose of sodium oxybate, and recommends once-nightly dosages within the claimed range (e.g., up to 6.0 g). | ¶20, 28 | col. 5:21-23 |
| wherein administration immediately after a high-fat meal results in a mean reduction in Cmax of gamma-hydroxybutyrate by 33%. | The complaint quotes the XYWAV® Prescribing Information as stating that administration after a high-fat meal "resulted in a mean reduction in Cmax of GHD by 33%." GHD is alleged to be gamma-hydroxybutyrate. | ¶29 | col. 5:24-26 |
- Identified Points of Contention:
- Scope Questions: A central question for the court will be whether Defendant’s actions rise to the level of active inducement. The infringement theory depends on third parties (healthcare providers and patients) performing the claimed methods based on Defendant's instructions. The dispute may focus on whether the product label's descriptions of a once-nightly regimen and its pharmacokinetic properties constitute specific instructions and encouragement to infringe, or merely statements of clinical findings.
- Technical Questions: For the ’389 Patent, a key factual question will be whether the accused method of administering XYWAV® actually results in the claimed pharmacokinetic profile ("mean reduction in Cmax... by 33%"). While the complaint quotes the product label stating this exact figure, Defendant may contest whether this clinical trial result is a guaranteed outcome of the method or if the "GHD" (gamma-hydroxybutyrate derivative) measured in its studies is identical to the "gamma-hydroxybutyrate" defined by the claim.
V. Key Claim Terms for Construction
The Term: "uptitrating ... to effect" (’388 Patent, Claim 1)
Context and Importance: This term is central to defining the claimed therapeutic process. Infringement of this step requires not just adjusting a dose, but doing so for a particular purpose ("to effect"). Practitioners may focus on this term because Defendant could argue that its titration instructions are merely safety guidelines for dose escalation rather than a required step for achieving the therapeutic "effect" as claimed.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification describes titration as a process "to optimize reduction of daytime symptoms and minimize side effects," suggesting "to effect" relates to achieving a general optimal therapeutic outcome (’388 Patent, col. 1:39-41).
- Evidence for a Narrower Interpretation: The claim specifies "weekly intervals," which links the "uptitrating" action to a specific cadence. Defendant may argue that any deviation from strict weekly intervals falls outside the claim, narrowing the scope of what constitutes an infringing act.
The Term: "a mean reduction in Cmax of gamma-hydroxybutyrate by 33%" (’389 Patent, Claim 1)
Context and Importance: This is a functional, result-oriented limitation that defines the invention by a specific pharmacokinetic outcome. Its construction is critical because infringement hinges on proving that the accused method produces this exact numerical result. Practitioners may focus on this term because disputes often arise over how to prove a specific "mean" value is met and whether the conditions under which the accused product is tested align with those underlying the patent.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Plaintiff may argue that this term describes an inherent property of the claimed multi-salt formulation when administered according to the method, and that Defendant's own product label admission of a 33% reduction is dispositive evidence (’389 Patent, col. 5:24-26).
- Evidence for a Narrower Interpretation: Defendant may argue that "mean reduction" requires a specific statistical methodology and patient population that must match the context of the patent. The term "by 33%" is precise, and Defendant could argue that its product's actual mean reduction, if re-tested, is statistically distinguishable from exactly 33%, or that the "GHD" on its label is a technically distinct compound from the claimed "gamma-hydroxybutyrate."
VI. Other Allegations
- Indirect Infringement: The complaint's theory is centered on induced infringement under 35 U.S.C. § 271(b). It alleges that Defendant, through its product labeling, prescribing information, medication guides, and marketing materials, actively encourages and instructs healthcare providers to prescribe and patients to use XYWAV® in a manner that directly practices the steps of the asserted method claims (Compl. ¶¶44-45, 53-54).
- Willful Infringement: The willfulness allegation is based on both pre- and post-issuance knowledge. The complaint alleges pre-issuance knowledge based on Defendant’s established "pattern and practice of closely monitoring" Plaintiff's patent filings, citing testimony from prior litigation and Defendant's own Information Disclosure Statements that listed related patents from the same family (Compl. ¶¶34, 37). It alleges actual notice as of the patents' issue date, February 18, 2025, via a formal notice letter sent by Plaintiff’s counsel (Compl. ¶40). Continued infringement after this date is alleged to be willful (Compl. ¶¶48, 56).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of inducement: does the XYWAV® label, by describing the clinical outcomes and administration protocols for a once-nightly regimen, constitute active encouragement to perform the patented methods sufficient to establish specific intent, or does it merely report clinical findings without instructing infringement?
- A key evidentiary question will be one of functional performance: for the ’389 Patent, can Plaintiff prove that the administration of XYWAV® as instructed on its label necessarily results in the precise "mean reduction in Cmax ... by 33%" required by the claim, and is the "GHD" measured by Defendant technically and legally equivalent to the claimed "gamma-hydroxybutyrate"?
- The dispute over willfulness will likely turn on the adequacy of pre-suit investigation: given the extensive litigation history and alleged monitoring of Plaintiff’s intellectual property, what steps, if any, did Defendant take to form an objectively reasonable belief of non-infringement or invalidity prior to receiving the notice letter on the date the patents issued?