US Patent 11,065,224: Claim Scope, Exclusivity, Litigation Risk, and Sodium Oxybate Patent Landscape

US Patent No. 11,065,224 covers once-nightly controlled-release gamma-hydroxybutyrate compositions that produce defined pharmacokinetic and dissolution profiles. The patent is directed to the formulation performance of Avadel Pharmaceuticals’ Lumryz, formerly FT218, rather than to sodium oxybate as a chemical compound.

The strongest commercial protection arises from claim 1, which requires a single nighttime administration, at least six hours of sleep induction, and specified plasma concentration-time behavior at sodium oxybate-equivalent doses. Claims 2 through 37 add dissolution-profile limitations. Claims 7 through 14 add pharmacokinetic limitations based on eight-hour plasma concentrations and median Tmax. Claim 38 extends the sleep-duration limitation from six to eight hours.

The patent is materially different from patents protecting Xyrem or Xywav. It targets the once-nightly extended-release delivery profile that distinguishes Lumryz from conventional sodium oxybate products requiring multiple nighttime doses.

What drug and formulation does US Patent 11,065,224 protect?

US 11,065,224 protects pharmaceutical compositions that release gamma-hydroxybutyrate, the active moiety of sodium oxybate, according to defined in vivo and in vitro performance characteristics.

The patent does not broadly claim:

gamma-hydroxybutyrate as a molecule;
every sodium oxybate formulation;
every extended-release oxybate formulation;
every once-nightly treatment method; or
every product capable of inducing sleep.

Instead, infringement depends on whether the accused composition satisfies the claim’s combined structural and performance requirements.

The claimed product must be:

A pharmaceutical composition that releases gamma-hydroxybutyrate into human blood.
Designed for administration only once per night.
Effective to induce sleep for at least six consecutive hours under claim 1, or eight hours under claim 38.
Bioequivalent to specified plasma concentration-time curves at stated sodium oxybate-equivalent doses.
In dependent claims, within specified dissolution or pharmacokinetic ranges.

The claims are therefore product claims defined partly by function and measurable performance. They can reach a formulation even if the formulation’s excipients, manufacturing process, tablet design, or dosage form differ from the disclosed examples, provided the resulting product meets the claimed performance limitations.

How many claims does US 11,065,224 contain?

The patent contains 38 claims based on the claim set provided. Claim 1 is the sole independent claim. Claims 2 through 38 depend directly from claim 1.

Claim group	Subject matter	Commercial relevance
Claim 1	Once-nightly GHB composition with specified PK behavior and six-hour sleep effect	Principal product claim
Claims 2-6	Dissolution-profile alternatives tied to Figures 7, 8, 20, 21, 25-28	Formulation-performance protection
Claims 7-12	Eight-hour mean plasma concentration ranges, or C8h	PK fallback protection
Claims 13-14	Median Tmax ranges after evening administration	Absorption-rate protection
Claims 15-37	Additional dissolution profiles tied to Figures 29-89	Extensive dependent-claim coverage
Claim 38	At least eight consecutive hours of sleep	Higher sleep-duration limitation

The dependent claims are not independent alternatives to claim 1. An accused product must first satisfy every limitation of claim 1 and then satisfy the additional limitation of the relevant dependent claim.

What is the scope of claim 1?

Claim 1 is broad in formulation identity but narrow in required performance.

The claim uses alternative pharmacokinetic pathways. A composition can satisfy claim 1 if, at the specified sodium oxybate-equivalent dose and meal timing, its plasma concentration-time curve is bioequivalent to the curve in Figure 12, Figure 13, or Figure 90 for the corresponding dose.

Those alternatives cover different dose sets:

Figure	Dose equivalents expressly identified in claim 1
Figure 12	4.5 g or 6.0 g sodium oxybate
Figure 13	4.5 g, 6.0 g, or 7.5 g sodium oxybate
Figure 90	4.5 g, 7.5 g, or 9.0 g sodium oxybate

The claim also requires administration approximately two hours after a standardized evening meal for the Figure 12 pathway. The precise interpretation of “bioequivalent,” “standardized evening meal,” and “approximately two hours” would be central in litigation.

Why the claim is commercially important

Conventional Xyrem treatment generally involves two nighttime doses. Lumryz was approved as an extended-release sodium oxybate product administered once at bedtime. The claim is directed to that commercial distinction.

A competing product could use a different:

polymer system;
matrix or multiparticulate architecture;
capsule or tablet format;
excipient combination;
manufacturing process; or
release-control mechanism.

It could still fall within claim 1 if its plasma profile and sleep effect satisfy the claim. Conversely, a product with a similar formulation concept may avoid infringement if it does not meet the specified PK bioequivalence requirements.

What do the dissolution claims protect?

Claims 2 through 6 and 15 through 37 protect compositions by reference to dissolution profiles shown in patent figures. These claims are unusually dependent on graphical performance data rather than on a simple numerical release schedule.

The claims cover:

bioequivalence to specific dissolution curves;
dissolution behavior between minimum and maximum curves;
paired dissolution profiles for different test conditions; and
multiple formulation-performance windows spanning Figures 7 through 89.

The claim set expressly reaches profiles associated with Figures 7, 8, 20, 21, 25 through 32, 34, 35, 37 through 40, 42 through 50, 53, 55, 56, 58, 59, 61, 62, 64 through 66, 68, 70, 71, 74, 75, 77, 78, 80, 81, 84, 85, and 88 through 90.

How dissolution claims would be tested

A litigation or ANDA comparison would likely examine:

dissolution medium;
pH;
apparatus and agitation speed;
temperature;
sampling intervals;
dosage strength;
number of units tested;
statistical comparison method; and
whether the patent’s “bioequivalent” or minimum-maximum boundaries are met.

A generic applicant could challenge whether the figures provide sufficiently definite boundaries for claim enforcement. The patentee would argue that the figures, specification, analytical methods, and examples establish reproducible performance criteria.

Dissolution claims can be valuable against a formulation that has a different excipient composition but releases sodium oxybate through substantially the same profile. They also create design-around pressure because a competing product may seek a clinically acceptable PK profile outside the claimed dissolution ranges.

What pharmacokinetic ranges are protected?

Claims 7 through 12 define the composition by mean plasma gamma-hydroxybutyrate concentration eight hours after dosing.

Claim	Sodium oxybate-equivalent dose	Claimed mean C8h
7	4.5 g	4.7 to 9.0 microgram/mL
8	4.5 g	3.5 to 4.7 microgram/mL
9	6.0 g	6.3 to 16.7 microgram/mL
10	6.0 g	7.3 to 15.4 microgram/mL
11	7.5 g	13.0 to 40.3 microgram/mL
12	7.5 g	24.7 to 37.2 microgram/mL

The overlapping endpoints in claims 7 and 8, and in claims 9 and 10, create potential claim-construction issues. A result exactly at 4.7 microgram/mL, for example, appears within both stated ranges. Such overlap generally increases the number of claim pathways available to the patentee, although enforceability depends on the full claim language and prosecution history.

The C8h claims are particularly relevant to distinguishing once-nightly extended-release products from immediate-release or shorter-duration formulations. A product that produces an acceptable initial exposure but falls below the claimed eight-hour concentration range may avoid these claims while potentially remaining within claim 1 or a dissolution claim.

What do the Tmax claims protect?

Claims 13 and 14 require a median Tmax within specified ranges after one administration approximately two hours after a standardized evening meal.

Claim	Median Tmax range
13	1.25 to 3.25 hours
14	0.5 to 3.25 hours

Claim 14 is broader than claim 13 because it extends the lower boundary to 0.5 hour. These claims target the absorption timing of the formulation rather than only total exposure.

Tmax claims can be difficult to enforce because median values depend on:

study population;
sampling schedule;
food conditions;
dose strength;
analytical method;
handling of tied or censored observations; and
statistical treatment of individual Tmax values.

A generic or competing product might produce a similar area under the curve but a different median Tmax. That could support a noninfringement position under claims 13 and 14 while leaving other claims at issue.

What is the patent expiration date?

The patent’s nominal expiration is determined by the earliest effective nonprovisional filing date in its priority chain, subject to patent-term adjustment and any applicable terminal disclaimer. The patent issued on June 15, 2021. Public patent records associate the patent family with a December 2016 filing and an expiration in the 2036 period, subject to the official USPTO term calculation.[1]

The exact enforceable expiration date should be taken from the USPTO patent-term data and the Orange Book listing for the relevant approved product. Patent-term adjustment can extend the ordinary 20-year term. Patent-term extension under 35 U.S.C. § 156 is a separate issue and requires a qualifying regulatory application.

Exclusivity timeline

Event	Date
US Patent 11,065,224 issued	June 15, 2021
Lumryz approved by FDA under NDA 214755	May 1, 2023
Patent protection	Generally extends into the 2036 period, subject to USPTO term calculations
FDA new chemical entity exclusivity for Lumryz	Not applicable as a new active ingredient
FDA orphan-drug exclusivity	Not the principal exclusivity mechanism for Lumryz
Generic entry timing	Controlled by patent certifications, litigation, settlement terms, and any applicable regulatory exclusivity

Lumryz contains sodium oxybate, an already approved active ingredient. Its principal commercial protection is therefore formulation patent protection and regulatory approval, not new chemical entity exclusivity.

What is the Orange Book status of US 11,065,224?

The patent is associated with the Lumryz regulatory patent estate and should be assessed through the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book.[2]

An Orange Book listing can support a Paragraph IV certification against an ANDA applicant. The listing does not establish validity or infringement. It gives the NDA holder a statutory mechanism to bring an infringement action after receiving a Paragraph IV notice.

The relevant Orange Book analysis should distinguish:

the patent number listed for Lumryz;
the approved dosage form and strengths;
the use code, if any;
the patent expiration date recorded by FDA; and
whether the patent is listed as a drug substance, drug product, formulation, or method-of-use patent.

Because US 11,065,224 is directed principally to the formulation’s PK and dissolution performance, it is best characterized as a drug-product or formulation patent rather than a basic compound patent.

What Paragraph IV challenges could target this patent?

An ANDA applicant could challenge US 11,065,224 through a Paragraph IV certification asserting that the patent is:

invalid;
unenforceable; or
not infringed.

The most plausible technical defenses would involve the following issues.

Claim indefiniteness

The accused applicant could challenge terms such as:

“bioequivalent”;
“approximately two hours”;
“designed to be administered only once per night”;
“effective to induce sleep”;
“standardized evening meal”; and
graphical dissolution boundaries.

The defense would argue that a skilled person cannot determine claim scope with reasonable certainty. The patentee would rely on the specification, disclosed study protocols, statistical methods, and examples.

Written description and enablement

The claims cover broad performance-defined compositions. A challenger could argue that the specification does not support the full breadth of all compositions capable of meeting the claimed plasma and dissolution profiles, particularly if the claims encompass formulation architectures not specifically exemplified.

The response would be that the invention is defined by measurable product performance and that the specification teaches formulation development, testing, and optimization across the claimed ranges.

Obviousness

An obviousness challenge would likely combine:

immediate-release sodium oxybate products;
known controlled-release delivery technologies;
prior pharmacokinetic studies;
food-effect data; and
conventional dissolution and formulation optimization.

The patentee would emphasize the once-nightly clinical target, the required exposure over at least six or eight hours, the food-conditioned PK profile, and any unexpected clinical or pharmacokinetic results.

Infringement and product-by-process issues

An ANDA applicant may argue that its formulation does not meet the claimed plasma profile or dissolution range, even if it has the same active ingredient and once-nightly dosing schedule. The patent holder may request samples, manufacturing information, dissolution data, bioequivalence reports, and, in litigation, testing under the ANDA’s proposed conditions.

Which companies are challenging Lumryz or competing with its patent estate?

The primary competitive group includes:

Company	Product or asset	Patent relevance
Avadel Pharmaceuticals	Lumryz, once-nightly sodium oxybate	Patent owner and NDA holder associated with the FT218 formulation
Jazz Pharmaceuticals	Xyrem and Xywav	Competing oxybate products with separate patent estates
Generic manufacturers	Potential ANDA sodium oxybate entrants	May challenge Orange Book-listed Lumryz patents through Paragraph IV
Specialty pharmaceutical developers	Potential controlled-release oxybate programs	Could face formulation, PK, dissolution, and method-of-use barriers

Xyrem is an immediate-release sodium oxybate product requiring divided nighttime dosing. Xywav is a mixed-salt oxybate product with lower sodium content and separate formulation characteristics. Lumryz competes through once-nightly administration rather than through a new active moiety.

No biosimilar pathway applies. Sodium oxybate is a small-molecule active ingredient, and a competing product would generally use an ANDA, 505(b)(2) application, or full NDA pathway rather than a biosimilar application under the Public Health Service Act.

How does US 11,065,224 compare with Xyrem and Xywav patent protection?

Issue	Lumryz and US 11,065,224	Xyrem	Xywav
Active ingredient	Sodium oxybate	Sodium oxybate	Mixed oxybate salts
Dosing concept	Once nightly	Divided nighttime dosing	Divided nighttime dosing
Main technical distinction	Extended-release PK and dissolution profile	Immediate-release oxybate delivery and use	Lower-sodium oxybate composition
Principal regulatory strategy	NDA 214755	NDA 21-196	NDA 212690
Biosimilar pathway	Not applicable	Not applicable	Not applicable
Key patent risk	Formulation-performance claims	Use, formulation, and abuse-deterrence claims	Composition and formulation claims
Generic design-around	Must avoid claimed PK and dissolution windows	Can target different salt, formulation, or use claims	Must address mixed-salt composition and formulation claims

US 11,065,224 is narrower than a compound patent but potentially harder to design around than a claim limited to a particular excipient list. The competitor must avoid the claimed performance window, not merely substitute one inactive ingredient.

How strong is the patent estate?

The patent is commercially meaningful but its strength is mixed across claim categories.

Strength factor	Assessment
Product differentiation	Strong. The claims track the once-nightly extended-release concept.
Breadth of formulation identity	Strong. The claims do not require one narrowly specified excipient formula.
Dependence on measured performance	Mixed. PK and dissolution testing creates objective infringement evidence but also creates claim-construction disputes.
Claim redundancy	Strong. Multiple dissolution and PK alternatives create fallback positions.
Validity exposure	Mixed. Broad graph-based and bioequivalence-defined claims may face definiteness, written-description, enablement, or obviousness challenges.
Design-around feasibility	Moderate. A competitor could target a different PK or dissolution profile, but clinical requirements constrain formulation choices.
Regulatory leverage	Strong if listed in the Orange Book and accompanied by a valid use or product listing.
Small-molecule generic exposure	Meaningful. ANDA applicants can directly challenge the listed claims through Paragraph IV.

The estate is strongest when the commercial product’s clinical and dissolution data fall squarely within the disclosed profiles. It is weaker if the claims depend on ambiguous figure boundaries or if the marketed product’s approved specifications do not map cleanly to the claimed ranges.

What manufacturing and intellectual-property barriers affect generic entry?

A generic entrant would face more than an active-ingredient replication exercise. Relevant barriers include:

reproducing a once-nightly release profile;
controlling early and late plasma exposure;
meeting dose-specific C8h ranges;
maintaining performance after food administration;
matching multiple dissolution conditions;
demonstrating bioequivalence to an extended-release reference product;
avoiding dose dumping;
establishing manufacturing consistency; and
addressing any device, packaging, risk-management, or controlled-substance requirements.

Sodium oxybate also presents safety and diversion concerns. FDA-approved oxybate products are subject to restricted distribution and risk-management controls. These controls do not independently extend patent term, but they can increase commercial launch complexity.[3][4]

What litigation and settlement issues should investors monitor?

The principal litigation triggers are:

A Paragraph IV certification against an Orange Book-listed Lumryz patent.
A 45-day infringement action by the NDA holder.
A 30-month ANDA stay under the Hatch-Waxman framework, subject to statutory exceptions.
Claim-construction rulings concerning “bioequivalent,” figure-defined dissolution, and food timing.
Expert disputes over PK variability and statistical equivalence.
Settlement agreements setting an authorized-generic or licensed-entry date.
Regulatory changes affecting the reference product’s labeling or approved dosage strengths.

A settlement could permit entry before patent expiration while preserving the patent’s nominal term. Public settlement terms may disclose an agreed launch date but not the full economics, supply arrangements, or authorized-generic provisions.

What revenue exposure is tied to this patent?

The patent is relevant to Lumryz revenue rather than to the entire oxybate market. Its exposure depends on:

Lumryz prescription growth;
payer coverage;
conversion from Xyrem and Xywav;
the approved dose distribution;
the timing of ANDA filings;
litigation outcomes;
settlement economics; and
the number of additional patents protecting Lumryz.

A successful generic challenge to US 11,065,224 would not necessarily eliminate every barrier to entry. Other Orange Book-listed patents, nonlisted patents, regulatory exclusivities, controlled-distribution requirements, and manufacturing know-how could continue to affect launch timing.

Conversely, a generic applicant that avoids this patent may still face other formulation or method-of-use claims. Portfolio-level analysis is therefore more important than treating US 11,065,224 as the sole barrier.

Key Takeaways

US 11,065,224 is a formulation-performance patent for once-nightly gamma-hydroxybutyrate delivery.
Claim 1 requires a single nighttime administration, at least six hours of sleep induction, and defined plasma concentration-time behavior.
Claims 2 through 37 protect multiple dissolution-profile alternatives.
Claims 7 through 12 protect dose-specific eight-hour plasma concentration ranges.
Claims 13 and 14 protect median Tmax ranges after evening administration.
Claim 38 raises the sleep-duration requirement to at least eight consecutive hours.
The patent does not claim sodium oxybate as a chemical compound.
The patent is relevant to Lumryz and its FT218 once-nightly formulation.
Generic applicants would likely use a Paragraph IV certification if the patent is listed in the Orange Book.
The principal validity risks concern claim definiteness, written description, enablement, obviousness, and the interpretation of figure-defined performance limits.
Biosimilar litigation is not relevant because sodium oxybate is a small-molecule product.
Patent protection is associated with the 2036 period, subject to the official USPTO patent-term calculation and any adjustment.

FAQs About US Patent 11,065,224

Does US 11,065,224 cover Xyrem?

No. The claims are directed to compositions with once-nightly extended-release performance. Xyrem is an immediate-release sodium oxybate product generally administered in divided nighttime doses.

Can a generic avoid US 11,065,224 by using different excipients?

Not necessarily. A different excipient system may still infringe if the resulting product satisfies the claimed PK, dissolution, dosing, and sleep-duration limitations.

Is US 11,065,224 a method-of-use patent?

The claims provided are composition claims, not conventional method-of-treatment claims. They define the composition partly through its intended administration and biological performance.

Does the patent protect all once-nightly sodium oxybate products?

No. A competing once-nightly product must satisfy the specific claim limitations, including the relevant plasma profile, dissolution profile, or pharmacokinetic range.

Does FDA approval of Lumryz create patent exclusivity until 2036?

No. FDA approval and patent rights are separate. FDA approval establishes regulatory authorization. Patent exclusivity depends on validity, enforceability, listed patent status, and the expiration date calculated under the patent statute.

References

United States Patent and Trademark Office. (2021). United States Patent No. 11,065,224: Controlled release formulations of gamma-hydroxybutyrate. https://patents.google.com/patent/US11065224B2/en
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm
U.S. Food and Drug Administration. (2023). FDA approves new once-nightly drug for treatment of idiopathic hypersomnia and narcolepsy. https://www.fda.gov/news-events/press-announcements
U.S. Food and Drug Administration. (2023). Lumryz prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/214755s000lbl.pdf
United States Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov/patents/laws/patent-term-calculator

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

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

Details for Patent: 11,065,224

Which drugs does patent 11,065,224 protect, and when does it expire?

Summary for Patent: 11,065,224