DCT
1:25-cv-00196
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; Latham & Watkins LLP; Morrison & Foerster LLP
- Case Identification: 1:25-cv-00196, D. Del., 02/18/2025
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Jazz Pharmaceuticals, Inc. is a Delaware corporation and therefore resides in the district.
- Core Dispute: Plaintiff alleges that Defendant’s XYWAV® oral solution, used for treating narcolepsy and idiopathic hypersomnia, infringes patents related to once-nightly, modified-release formulations of gamma-hydroxybutyrate (GHB) salts.
- Technical Context: The technology involves pharmaceutical formulations designed to provide therapeutic levels of GHB throughout the night with a single dose, avoiding the sleep disruption caused by the traditional twice-nightly dosing regimen.
- Key Procedural History: The complaint alleges a history of Defendant closely monitoring Plaintiff’s patent portfolio, citing deposition testimony from prior litigation between the parties. It further alleges that Defendant disclosed numerous related patents from Plaintiff’s portfolio in Information Disclosure Statements during the prosecution of its own patents, suggesting a basis for pre-suit knowledge of the patented technology.
Case Timeline
| Date | Event |
|---|---|
| 2016-07-22 | ’388 and ’389 Patents Priority Date |
| 2021-08-12 | Defendant's XYWAV product receives FDA approval |
| 2024-11-07 | Application for '389 Patent became public |
| 2024-11-14 | Application for '388 Patent became public |
| 2024-12-20 | Final claims and notice of allowance for '388 and '389 Patents became public |
| 2025-02-18 | U.S. Patent No. 12,226,388 Issued |
| 2025-02-18 | U.S. Patent No. 12,226,389 Issued |
| 2025-02-18 | 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"
The Invention Explained
- Problem Addressed: The patent’s background section describes the substantial inconvenience for narcolepsy patients of traditional sodium oxybate treatments (marketed as Xyrem®), which require a second dose taken 2.5 to 4 hours after bedtime, interrupting sleep (’388 Patent, col. 1:49-54). Previous attempts at once-nightly formulations suffered from significantly reduced bioavailability compared to the immediate-release, twice-nightly regimen (’388 Patent, col. 2:1-17).
- The Patented Solution: The invention is a method of treatment using a once-nightly modified-release formulation of GHB that approximates or exceeds the bioavailability of the twice-nightly immediate-release product (’388 Patent, col. 6:1-18). The formulation combines different pharmaceutically acceptable salts of GHB to achieve a specific pharmacokinetic profile that provides therapeutic effects throughout an eight-hour sleep period with a single dose (’388 Patent, col. 1:21-25; Abstract).
- Technical Importance: This approach sought to improve patient compliance and quality of life by eliminating the need for a disruptive middle-of-the-night dose while maintaining the therapeutic efficacy of established GHB treatments (’388 Patent, col. 1:49-54).
Key Claims at a Glance
- The complaint asserts independent Claim 1 (Compl. ¶15).
- Essential elements of Claim 1 include:
- Orally administering a single nighttime daily dose to a human.
- The dose comprises a first salt of gamma-hydroxybutyric acid and a second, different salt of gamma-hydroxybutyric acid.
- Both salts are selected from the group consisting of sodium, calcium, potassium, and magnesium salts of gamma-hydroxybutyric acid.
- The administration occurs only once nightly.
- 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 reserves the right to assert additional claims (Compl. ¶3).
U.S. Patent No. 12,226,389 - "Modified Release Gamma-Hydroxybutyrate Formulations Having Improved Pharmacokinetics"
The Invention Explained
- Problem Addressed: The patent addresses the same core problem as the ’388 Patent: the inconvenience and reduced bioavailability of prior once-nightly GHB formulations (’389 Patent, col. 1:49-54, col. 2:1-17).
- The Patented Solution: The invention is a method of treatment using a once-nightly formulation of mixed GHB salts that achieves a specific pharmacokinetic outcome related to food effect. The claimed method results in a mean reduction in the maximum plasma concentration (Cmax) of GHB by 33% when administered immediately after a high-fat meal, indicating a formulation designed to provide a more consistent and predictable therapeutic effect regardless of food intake (’389 Patent, Claim 1; Compl. ¶17).
- Technical Importance: Mitigating the "food effect"—where the presence of food alters drug absorption—is a significant goal in oral drug formulation, as it leads to more predictable dosing and reliable therapeutic outcomes for patients (’389 Patent, Abstract).
Key Claims at a Glance
- The complaint asserts independent Claim 1 (Compl. ¶17).
- Essential elements of Claim 1 include:
- Orally administering a single nighttime daily dose to a human.
- The dose comprises a first salt of gamma-hydroxybutyric acid and a second, different salt of gamma-hydroxybutyric acid.
- Both salts are selected from the group consisting of sodium, calcium, potassium, and magnesium salts of gamma-hydroxybutyric acid.
- The single nighttime 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.
- The administration occurs only once nightly.
- Administration immediately after a high-fat meal results in a mean reduction in Cmax of gamma-hydroxybutyrate by 33%.
- The complaint reserves the right to assert additional claims (Compl. ¶3).
III. The Accused Instrumentality
Product Identification
- The accused product is Defendant's XYWAV®, an oral solution (Compl. ¶18).
Functionality and Market Context
- XYWAV is described as an oral solution that is a mixture of calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate (gamma-hydroxybutyrate) (Compl. ¶19). It is approved for the treatment of idiopathic hypersomnia and for cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy (Compl. ¶¶21-22).
- The complaint cites XYWAV's Prescribing Information, which allegedly recommends both twice-nightly and once-nightly dosing regimens for adult patients (Compl. ¶28). The recommended once-nightly dosing allegedly involves initiating dosage at 3 g or less per night and titrating upwards in increments of up to 1.5 g per week, to a maximum of 6 g total nightly dose (Compl. ¶28).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
- 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 promotes and instructs patients and health care providers to orally administer its XYWAV product once nightly for treating idiopathic hypersomnia and narcolepsy. | ¶28, ¶42 | col. 7:42-50 |
| wherein said single nighttime daily dose comprises a first salt of gamma-hydroxybutyric acid and a second salt of gamma-hydroxybutyric acid, | XYWAV is a mixture of four different salts of gamma-hydroxybutyrate: calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate. | ¶19 | col. 8:55-60 |
| wherein the first salt is selected from the group consisting of a sodium salt..., a calcium salt..., a potassium salt..., and a magnesium salt of gamma-hydroxybutyric acid, | The salts in XYWAV (sodium, calcium, potassium, and magnesium oxybate) are all members of the claimed group. | ¶19 | col. 8:55-60 |
| wherein the second salt differs from the first salt and is selected from the group consisting of a sodium salt..., a calcium salt..., a potassium salt..., and a magnesium salt of gamma-hydroxybutyric acid, and, | XYWAV contains at least two different salts from the claimed group. | ¶19 | col. 8:55-60 |
| wherein the orally administering occurs only once nightly; and | The XYWAV Prescribing Information allegedly recommends a "once nightly regimen" for adult patients. | ¶28, ¶33 | col. 7:42-50 |
| 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." | ¶28, ¶41 | col. 8:48-54 |
- 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...comprising: orally administering a single nighttime daily dose to said human, | Defendant promotes and instructs users to orally administer XYWAV once nightly for treating idiopathic hypersomnia and narcolepsy. | ¶28, Count II ¶2 | col. 7:42-50 |
| wherein said single nighttime daily dose comprises a first salt...and a second salt of gamma-hydroxybutyric acid, | XYWAV is a mixture of four different salts of gamma-hydroxybutyrate. | ¶19 | col. 8:55-60 |
| wherein the first salt is selected from the group consisting of a sodium salt..., a calcium salt..., a potassium salt..., and a magnesium salt of gamma-hydroxybutyric acid, | The salts in XYWAV are all members of the claimed group. | ¶19 | col. 8:55-60 |
| wherein the second salt differs from the first salt and is selected from the group consisting of a sodium salt..., a calcium salt..., a potassium salt..., and a magnesium salt of gamma-hydroxybutyric acid, and, | XYWAV contains at least two different salts from the claimed group. | ¶19 | col. 8:55-60 |
| wherein the single nighttime daily 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, | The XYWAV labeling allegedly instructs once-nightly dosing at dosages of 3.0 g up to 6.0 g total nightly dose, which falls within the claimed range. | ¶20, ¶28 | col. 8:51-54 |
| wherein the orally administering occurs only once nightly and | The XYWAV Prescribing Information allegedly recommends a "once nightly regimen." | ¶28, ¶33 | col. 7:42-50 |
| wherein administration immediately after a high-fat meal results in a mean reduction in Cmax of gamma-hydroxybutyrate by 33%. | The complaint alleges that the XYWAV Prescribing Information explicitly states this pharmacokinetic property. | ¶29, Count II ¶2 | col. 10:1-12 |
- Identified Points of Contention:
- Scope Questions: The asserted claims are for methods of treatment. Infringement analysis may focus on whether Defendant’s instructions and marketing materials for XYWAV actively induce healthcare providers and patients to perform every step of the claimed methods, including the specific titration schedule of the ’388 Patent and the administration under conditions that produce the pharmacokinetic result of the ’389 Patent.
- Technical Questions: A key question for the ’389 Patent will be whether the statement in the XYWAV Prescribing Information regarding a "mean reduction in Cmax of GHD by 33%" after a high-fat meal is sufficient evidence that the accused method meets this claim limitation (Compl. ¶29). The litigation may explore the factual basis for this statement and whether it corresponds to the conditions under which the patented method is defined.
V. Key Claim Terms for Construction
The Term: "uptitrating...to effect" (’388 Patent, Claim 1)
Context and Importance: This term is central to the final step of the claimed method. The parties may dispute whether "to effect" requires achieving a specific, measurable clinical outcome in the patient, or if it is satisfied simply by following the prescribed titration schedule as instructed. Practitioners may focus on this term because its interpretation could determine whether merely following the label instructions constitutes infringement.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification describes a titration schedule as a way "to optimize reduction of daytime symptoms and minimize side effects," which could suggest that following the schedule itself is the intended meaning, regardless of the individual patient's outcome (’388 Patent, col. 1:62-65).
- Evidence for a Narrower Interpretation: The description of the ideal dose as one that provides "an effective eight hours of sleep" could support an argument that "to effect" requires achieving a specific therapeutic result (’388 Patent, col. 2:1-3).
The Term: "wherein administration immediately after a high-fat meal results in a mean reduction in Cmax of gamma-hydroxybutyrate by 33%" (’389 Patent, Claim 1)
Context and Importance: This result-oriented limitation defines the invention by a specific pharmacokinetic outcome rather than a structural or procedural step. Its construction will be critical. The dispute may center on whether this is a valid and enforceable limitation and what evidence is required to prove that the accused method achieves this precise numerical result.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification may describe this 33% reduction as a characteristic property of the novel formulation, suggesting that administering a formulation designed to have this property meets the limitation (’389 Patent, Abstract).
- Evidence for a Narrower Interpretation: The patent likely presents specific clinical trial data and conditions under which this 33% reduction was observed (’389 Patent, col. 10:1-12). A defendant may argue that infringement requires replicating those exact conditions, which may not be reflected in the instructions for the accused product.
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement of infringement under 35 U.S.C. § 271(b). The factual basis is Defendant's alleged marketing, selling, and distribution of XYWAV with its Prescribing Information, Medication Guide, and other promotional materials that allegedly instruct and encourage medical providers and patients to use XYWAV in a manner that directly practices the steps of the asserted claims (Compl. ¶¶43-44; Count II ¶¶4-5).
- Willful Infringement: The complaint alleges willful infringement based on Defendant's alleged pre-suit knowledge of the patents-in-suit. This allegation is supported by claims that Defendant has a "pattern and practice of closely monitoring" Plaintiff's patent portfolio, including citing related patents in its own patent prosecution filings and deposition testimony from prior litigation admitting to such monitoring (Compl. ¶¶34-37). The complaint further alleges that Defendant was aware of the specific claims of the patents-in-suit since at least December 20, 2024, based on the public disclosure of the allowed claims before the patents officially issued (Compl. ¶¶37, 39, 45; Count II ¶6).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of inducement: Can Plaintiff demonstrate that Defendant’s product labeling and marketing for XYWAV, particularly its instructions for once-nightly dosing and titration, show a specific intent to encourage users to perform every step of the patented methods, thereby infringing claims it allegedly knew about prior to their issuance?
- A central legal question will be the enforceability of a pharmacokinetic limitation: For the ’389 Patent, the case may turn on whether a claim limitation defined by a specific, numerical pharmacokinetic result ("a mean reduction in Cmax...by 33%") is valid and whether the allegation that this precise language appears in the accused product's label constitutes an admission of infringement.