Details for Patent: 12,115,142

Which drugs does patent 12,115,142 protect, and when does it expire?

Patent 12,115,142 protects LUMRYZ and is included in one NDA.

This patent has thirty-eight patent family members in ten countries.

Summary for Patent: 12,115,142

Title:	Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
Abstract:	Modified release formulations of gamma-hydroxybutyrate having improved dissolution and pharmacokinetic properties are provided, and therapeutic uses thereof.
Inventor(s):	Jordan Dubow, Hervé Guillard, Claire Mégret, Jean-François DUBUISSON
Assignee:	Flamel Ireland Ltd
Application Number:	US18/537,318
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,115,142
Patent Claim Types: see list of patent claims	Use; Formulation; Compound; Delivery;

US Patent 12,115,142: Scope, Claim Analysis, and Sodium Oxybate Patent Landscape

US Patent 12,115,142 claims once-nightly oral gamma-hydroxybutyrate formulations for narcolepsy that combine an immediate-release dose with a modified-release dose. The core technical limitations are a pH-triggered methacrylic-acid-polymer coating, a hydrophobic compound with a melting point of at least 40°C, defined polymer-to-hydrophobe ratios, specified immediate-release and modified-release particle proportions, and pharmacokinetic performance at selected sodium oxybate-equivalent doses.

The claims are composition claims, not method-of-treatment claims. They target the formulation architecture associated with once-nightly sodium oxybate products, particularly formulations designed to maintain exposure over an eight-hour sleep period.

What technology does US Patent 12,115,142 protect?

The patent protects a multipart oral formulation containing:

1. An immediate-release gamma-hydroxybutyrate component.
2. A modified-release gamma-hydroxybutyrate component.
3. An acidifying agent.
4. A pH-sensitive polymer system.
5. A hydrophobic compound with a melting point of at least 40°C.
6. A total gamma-hydroxybutyrate dose equivalent to 3.0 to 12 g of sodium oxybate.
7. A dosage design intended for one oral administration per night.

The claims are directed to a controlled-release sodium oxybate platform rather than to gamma-hydroxybutyrate as a molecule. The commercially relevant distinction is the release profile: an initial release intended to support sleep onset, followed by delayed release intended to sustain exposure without a second nighttime administration.

Core formulation architecture

Element	Claim requirement
Active ingredient	Gamma-hydroxybutyrate
Therapeutic use	Narcolepsy or a symptom of narcolepsy
Administration	Oral, once nightly
Immediate-release phase	Required
Modified-release phase	Required
Acidifying agent	Required
Hydrophobic compound	Melting point at least 40°C
pH-sensitive polymer	Polymer carrying free carboxylic groups
Sodium oxybate-equivalent dose	3.0 to 12 g
Modified-release trigger	pH 5.5 to 6.97 in certain claims
Release-particle ratio	Defined ranges in claims 13-30
Pharmacokinetic limitations	AUC8h/AUCinf values in claims 9-11

The independent claims are claims 1 and 7. Claims 2-6 narrow claim 1. Claims 8-30 narrow claim 7.

What are the independent claims in US Patent 12,115,142?

Claim 1: formulation defined by excipient ratio and release design

Claim 1 requires a formulation with an immediate-release portion and a modified-release portion. The modified-release portion must contain:

• Gamma-hydroxybutyrate;
• A polymer carrying free carboxylic groups;
• A hydrophobic compound having a melting point of at least 40°C; and
• A hydrophobic-compound-to-polymer weight ratio of 0.6 to 2.5.

The formulation must also contain an acidifying agent and be designed for once-nightly oral administration. The total active amount must correspond to 3.0 to 12 g of sodium oxybate.

The claim does not require a specific polymer identity, a specific hydrophobic excipient, a specific particle size, or a capsule or sachet dosage form. Its breadth comes from the functional formulation combination and the ratio limitation.

Claim 7: coating, particle ratio, and release composition

Claim 7 is more structurally detailed. It requires:

• An immediate-release portion containing gamma-hydroxybutyrate;
• A modified-release portion containing gamma-hydroxybutyrate and a coating;
• A methacrylic acid copolymer with free carboxylic groups;
• A pH trigger from 5.5 to 6.97;
• A hydrophobic compound with a melting point of at least 40°C;
• A hydrophobic-compound-to-polymer ratio of 0.4 to 4;
• Coating representing 10% to 50% of particle weight;
• Immediate-release-to-modified-release gamma-hydroxybutyrate ratio of 10/90 to 65/35;
• An acidifying agent; and
• A total dose equivalent to 3.0 to 12 g of sodium oxybate.

Claim 7 is likely the principal composition claim for an accused multiparticulate product. It contains more limitations than claim 1 but also uses broader ratio boundaries for the hydrophobic compound and polymer.

How do dependent claims 2 through 6 narrow the patent scope?

Claims 2-6 narrow claim 1 as follows:

Claim	Added limitation
2	Hydrophobic compound/polymer ratio of 0.6 to 2.33
3	Ratio of about 1.5
4	pH-triggered release from 5.5 to 6.97
5	pH-triggered release from 6.5 to 6.97
6	Hydrogenated vegetable oil

Claim 3 is a narrow formulation-ratio claim. It may be commercially important if the marketed formulation uses a hydrophobe-to-polymer ratio near 1.5. Claims 4 and 5 focus on dissolution behavior rather than merely ingredient identity. Claim 5 is narrower because it requires the release trigger to fall within the 6.5 to 6.97 range.

Claim 6 adds hydrogenated vegetable oil. This limitation can capture a formulation using hydrogenated vegetable oil as a coating or matrix component, but it also creates a straightforward design-around route if the product achieves the same release profile with a different hydrophobic compound.

What formulation features are protected by claims 7 through 30?

Claims 8-30 divide into four groups: excipient composition, pharmacokinetics, particle architecture, and immediate-release particle percentages.

Excipient limitation

Claim 8 adds hydrogenated vegetable oil to the coating. This claim is narrower than claim 7 and depends on the coating containing the specified methacrylic acid copolymer and hydrophobic compound.

Pharmacokinetic limitations

Claims 9-11 require specific AUC8h/AUCinf ratios:

Claim	Sodium oxybate-equivalent dose	AUC8h/AUCinf
9	4.5 g	0.83
10	6.0 g	0.93
11	7.5 g	0.89

These claims are composition claims that include pharmacokinetic performance limitations. The enforceability of such limitations would depend on how the ratios are measured, the study conditions, the sampling schedule, and whether the claimed value is construed as an exact value or a value subject to ordinary analytical variation.

The claims could be difficult to assess from a public product label alone. They may require formulation testing and a pharmacokinetic study using the claimed dose.

Particle architecture

Claim 12 requires:

• Immediate-release particles containing gamma-hydroxybutyrate; and
• Modified-release particles containing gamma-hydroxybutyrate and the coating.

This limitation is narrower than a formulation in which the immediate-release and modified-release phases are blended in a nonparticulate matrix. A product using discrete multiparticulates would be more directly exposed to claim 12 and its dependent claims.

Immediate-release particle percentage ranges

Claims 13-30 define overlapping ranges for the weight percentage of immediate-release particles relative to the combined weight of immediate-release and modified-release particles.

Claims	Immediate-release particle percentage
13	7.2% to 58.2%
14	11.0% to 52.9%
15	14.9% to 47.8%
16	18.9% to 47.8%
17	23.1% to 47.8%
18	27.4% to 47.8%
19	31.8% to 47.8%
20	31.8% to 52.9%
21	36.4% to 47.8%
22	5.9% to 63.2%
23	9.1% to 58.1%
24	12.4% to 53.1%
25	19.9% to 53.1%
26	19.6% to 53.1%
27	23.4% to 53.1%
28	27.4% to 53.1%
29	27.4% to 58.1%
30	31.7% to 53.1%

The ranges overlap heavily. This creates a tiered fallback structure. If a formulation falls outside a narrower range, it may still fall within a broader dependent range. Claims 22-30 are especially important because they cover wider particle-percentage windows than many claims 13-21.

How broad is the patent’s practical infringement scope?

The practical scope is strongest against a product that uses all of the following:

• Sodium oxybate or another gamma-hydroxybutyrate formulation;
• A single nighttime administration;
• Separate immediate-release and modified-release fractions;
• Coated modified-release particles;
• A methacrylic acid copolymer;
• A hydrophobic, higher-melting-point coating component;
• An acidifying agent;
• A sodium oxybate-equivalent dose within 3.0 to 12 g; and
• Immediate-release and modified-release portions in the claimed proportions.

A product does not necessarily avoid the patent merely by changing the brand name, capsule size, package configuration, or total dose within the claimed range. The relevant inquiry is whether the formulation contains each required limitation.

Highest-risk design profile

The highest-risk product would be a once-nightly multiparticulate sodium oxybate product with an enteric or pH-sensitive methacrylic acid copolymer coating and a hydrophobic excipient such as a hydrogenated lipid or wax.

Lower-risk design profiles

Potentially lower-risk configurations include:

• A twice-nightly formulation;
• A formulation using only immediate release;
• A formulation using a non-pH-triggered extended-release matrix;
• A formulation using a polymer without free carboxylic groups;
• A formulation using a hydrophobic compound with a melting point below 40°C;
• A formulation with no acidifying agent;
• A formulation outside the claimed dose range;
• A monolithic matrix rather than separate immediate-release and modified-release particles; or
• A modified-release system triggered by a mechanism other than the claimed pH range.

These are design-around concepts, not conclusions that a particular product is noninfringing. A modified formulation could still implicate other patents or the doctrine of equivalents.

How does US Patent 12,115,142 compare with earlier sodium oxybate products?

Xyrem

Xyrem is an immediate-release sodium oxybate product historically administered in two nighttime doses. Its formulation and dosing architecture differ from the once-nightly immediate-plus-modified-release structure targeted by US 12,115,142.

Xyrem’s principal commercial patent exposure has historically involved Jazz Pharmaceuticals’ sodium oxybate patents, including patents directed to dosing, safety controls, and formulation or delivery technology. A standard two-dose immediate-release product would not, based solely on the supplied claims, satisfy the once-nightly limitation in claims 1 and 7.

Xywav

Xywav is a lower-sodium oxybate product containing calcium, magnesium, potassium, and sodium oxybates. Its reduced-sodium composition distinguishes it chemically from a conventional sodium oxybate formulation, although the claims of US 12,115,142 are written to gamma-hydroxybutyrate and sodium oxybate-equivalent dosage rather than simply to sodium oxybate as the only salt.

Whether Xywav falls within the claims would depend on its release architecture, excipients, coating composition, pH-trigger behavior, and once-nightly administration. A product can contain gamma-hydroxybutyrate equivalents without using sodium oxybate as its only salt.

Lumryz

Lumryz is the most direct commercial comparator because it is designed for once-nightly sodium oxybate administration. Its commercial formulation uses immediate-release and extended-release components intended to maintain overnight exposure.

The supplied claims closely track the technical attributes that distinguish a once-nightly controlled-release oxybate formulation from a conventional two-dose product. A marketed product matching the claimed methacrylic-acid coating, hydrophobic component, acidifying agent, particle architecture, and percentage ranges would face the most material exposure.

What is the likely patent landscape for once-nightly sodium oxybate?

The landscape contains several distinct patent categories.

Patent category	Typical protected subject matter	Relevance to US 12,115,142
Active ingredient and salt patents	Gamma-hydroxybutyrate or oxybate salts	Usually historical or limited because the molecule is old
Immediate-release formulations	Liquid or powder sodium oxybate formulations	Less directly aligned with once-nightly release
Modified-release formulations	Coated particles, matrices, multiparticulates	Directly relevant
Dosing patents	Once-nightly or split-dose administration	May create separate method-of-treatment exposure
Abuse-deterrence and safety systems	Restricted distribution, monitoring, dosing controls	Commercially important but technically distinct
Low-sodium oxybate	Mixed oxybate salts	Relevant to Xywav-type products
Manufacturing patents	Particle manufacture, coating, blending, encapsulation	Can create supply-chain barriers
Regulatory exclusivity	New-drug, orphan-drug, or pediatric exclusivity	Separate from patent rights

US 12,115,142 is most significant within the modified-release formulation and manufacturing interface. Its limitations can be tested through product composition, coating analysis, dissolution testing, particle-weight calculations, and pharmacokinetic data.

What patent litigation and Paragraph IV risks affect this market?

A generic applicant seeking approval for a product referencing a listed sodium oxybate product could challenge Orange Book-listed patents through a Paragraph IV certification. The patent-specific risk depends on whether US 12,115,142 is listed against the relevant reference product and whether the generic product includes the claimed formulation characteristics.

A Paragraph IV challenge would typically raise one or more of:

• Noninfringement;
• Invalidity for anticipation;
• Obviousness;
• Lack of written description;
• Lack of enablement;
• Indefiniteness, particularly for ratio, pH, coating-weight, and pharmacokinetic limitations; or
• Improper patent listing, where applicable.

The statutory litigation framework can trigger a 30-month stay of FDA approval if the patent holder files an infringement action within the applicable period following notice of the Paragraph IV certification. The exact regulatory effect depends on the reference product, listing status, certification timing, and litigation posture. [1]

Likely technical attack points

The most contestable limitations may include:

1. The meaning of “designed to be administered orally only once nightly.”
2. The test method for determining pH-triggered release.
3. The identity and melting point of the hydrophobic compound.
4. The calculation of coating weight as a percentage of particle weight.
5. The basis for the immediate-release particle percentage.
6. The precision and reproducibility of AUC8h/AUCinf values.
7. Whether the claimed ranges were adequately supported across the full breadth of the claims.

The extensive overlapping ranges in claims 13-30 provide numerous fallback positions but may also invite written-description and obviousness scrutiny if the specification does not demonstrate representative support across those ranges.

How strong is the patent estate represented by US 12,115,142?

Strengths

The patent has several commercially meaningful strengths:

• It combines formulation composition and release-performance limitations.
• It targets a once-nightly product architecture.
• It includes both broad independent claims and narrower ratio, pH, particle, and pharmacokinetic claims.
• It covers multiple hydrophobic compounds rather than a single named excipient.
• The overlapping dependent claims create alternative infringement theories.
• Claims 9-11 may capture dose-specific pharmacokinetic targets that are difficult to avoid while preserving the same overnight exposure profile.

Vulnerabilities

The principal vulnerabilities are:

• The field of controlled-release pharmaceutical coatings is mature.
• Methacrylic acid copolymers and hydrophobic coating agents are established excipient technologies.
• The claims rely heavily on numerical ranges that may be attacked as obvious optimizations.
• Some limitations require specialized testing and may create factual disputes.
• A competitor could potentially alter the release mechanism, polymer chemistry, particle format, or dosing schedule.
• The patent does not, from the supplied claims, claim every once-nightly gamma-hydroxybutyrate formulation.

The estate’s commercial strength therefore depends on whether the patent is paired with continuation patents, method-of-use patents, manufacturing patents, and Orange Book-listed claims covering the marketed product.

What manufacturing and IP barriers does the patent create?

A competing manufacturer would need to control several variables:

• Active loading of gamma-hydroxybutyrate;
• Immediate-release particle proportion;
• Modified-release coating composition;
• Polymer-to-hydrophobe ratio;
• Coating weight;
• pH-triggered dissolution;
• Acidifying-agent selection;
• Particle blending and content uniformity;
• Dose-specific pharmacokinetics; and
• Stability and moisture control.

A design-around that changes one variable may affect the product’s overnight exposure, dose proportionality, manufacturability, or regulatory comparability. This makes the patent commercially relevant even where literal claim avoidance is technically possible.

What geographic coverage does US Patent 12,115,142 provide?

US Patent 12,115,142 provides rights in the United States only. Parallel protection would require corresponding patents in other jurisdictions. International risk should be assessed separately across:

• European Patent Office jurisdictions;
• Canada;
• Japan;
• South Korea;
• Australia;
• China; and
• Other markets where once-nightly oxybate products may be commercialized.

Patent term, prosecution history, claim scope, opposition status, and supplementary protection mechanisms can differ by country. A US noninfringement position would not establish freedom to operate elsewhere.

What is the generic launch risk?

A generic launch strategy could take three forms:

1. Full formulation challenge. The applicant develops a once-nightly multiparticulate product and challenges the patent through Paragraph IV.
2. Design-around product. The applicant uses a different release mechanism, polymer, hydrophobe, dosing schedule, or particle architecture.
3. Delayed or limited launch. The applicant waits for patent expiry or resolves the dispute through settlement.

The first strategy offers the closest product performance but creates the greatest infringement exposure. The second reduces patent risk but increases development and regulatory risk. The third limits litigation cost but delays market entry.

For a product that closely copies the claimed architecture, claims 1 and 7 create the principal risk. Claims 9-11 and 13-30 may provide additional enforcement positions if testing confirms the claimed pharmacokinetic or particle-percentage limitations.

Key Takeaways

• US Patent 12,115,142 targets once-nightly oral gamma-hydroxybutyrate formulations for narcolepsy.
• Claims 1 and 7 are the principal independent composition claims.
• The central technical combination is immediate release plus modified release, a pH-sensitive polymer, a high-melting hydrophobic compound, an acidifying agent, and a 3.0-12 g sodium oxybate-equivalent dose.
• Claim 7 is particularly relevant to coated multiparticulate products.
• Claims 9-11 add dose-specific AUC8h/AUCinf limitations.
• Claims 13-30 create overlapping coverage for immediate-release particle percentages.
• Lumryz-type once-nightly formulations are the closest commercial comparator.
• Conventional twice-nightly immediate-release sodium oxybate products are less directly aligned with the supplied claims.
• Generic risk will depend on the accused product’s coating chemistry, release testing, particle architecture, dose, and regulatory certification.
• The patent is strongest against a close copy of the claimed multiparticulate controlled-release architecture and weaker against products using a different release mechanism or nonparticulate structure.

FAQs About US Patent 12,115,142

Does US Patent 12,115,142 cover sodium oxybate itself?

No. The supplied claims cover pharmaceutical formulations containing gamma-hydroxybutyrate with specified immediate-release and modified-release characteristics. They do not claim sodium oxybate as a standalone chemical compound.

Does the patent cover a twice-nightly sodium oxybate product?

The claims require a formulation designed to be administered orally only once nightly. A conventional twice-nightly product would not satisfy that express limitation based on the supplied claim language.

Can a competitor avoid the patent by removing the methacrylic acid copolymer?

Claims 7 and its dependents expressly require a methacrylic acid copolymer carrying free carboxylic groups. Claim 1 is broader in polymer wording but still requires a polymer carrying free carboxylic groups. Removing that polymer could materially reduce literal infringement risk.

Are the AUC limitations required for every claim?

No. The AUC8h/AUCinf limitations appear only in claims 9-11. Claims 1-8 and 12-30 do not require those specific pharmacokinetic ratios.

Does the patent cover low-sodium mixed oxybate products?

The answer depends on whether the product contains gamma-hydroxybutyrate in the claimed formulation architecture and satisfies the other limitations. The claims are not expressly limited to a formulation containing sodium oxybate as the only oxybate salt.

Sources

1. U.S. Food and Drug Administration. (n.d.). Hatch-Waxman Amendments and patent certification procedures. FDA.
2. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation. USPTO.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
4. U.S. Patent No. 12,115,142, claims 1-30.

Drugs Protected by US Patent 12,115,142

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Avadel Cns	LUMRYZ	sodium oxybate	FOR SUSPENSION, EXTENDED RELEASE;ORAL	214755-001	May 1, 2023		RX	Yes	Yes	12,115,142		Y
Avadel Cns	LUMRYZ	sodium oxybate	FOR SUSPENSION, EXTENDED RELEASE;ORAL	214755-002	May 1, 2023		RX	Yes	No	12,115,142		Y
Avadel Cns	LUMRYZ	sodium oxybate	FOR SUSPENSION, EXTENDED RELEASE;ORAL	214755-003	May 1, 2023		RX	Yes	No	12,115,142		Y
Avadel Cns	LUMRYZ	sodium oxybate	FOR SUSPENSION, EXTENDED RELEASE;ORAL	214755-004	May 1, 2023		RX	Yes	No	12,115,142		Y

International Family Members for US Patent 12,115,142

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	109376
Australia	2017300845
Australia	2020231916
Australia	2023203055
Australia	2025201830