US Patent 11,135,155: Naloxone Nasal Spray Claims, Patent Scope, and Competitive Landscape

US Patent No. 11,135,155 protects concentrated naloxone nasal-spray formulations containing water and a chelating agent, with dependent claims directed to edetate disodium dihydrate, ethanol, propylene glycol, and specified concentration ranges. The patent is formulation-focused. It does not broadly cover every naloxone nasal spray, every naloxone delivery device, or every method of treating opioid overdose.

The principal infringement risk is a nasal liquid containing naloxone at 5% to 16% w/w with a chelator. The most commercially significant sub-combination is naloxone, ethanol, propylene glycol, water, and edetate disodium dihydrate within the claimed ranges.

What does US Patent 11,135,155 protect?

The independent claims divide the patent into three formulation categories:

Claim group	Independent claim	Core protected subject matter
Broad nasal formulation	1	5%-16% w/w naloxone, water, and 0.001%-0.1% w/w chelating agent
Defined liquid formulation	9	5%-16% w/w naloxone, 20%-50% ethanol, 5%-10% propylene glycol, 35%-70% water, and 0.001%-0.1% chelator
Higher-naloxone, narrower-chelator formulation	12	7%-16% w/w naloxone, water, and 0.005%-0.01% w/w chelator

The claims use “comprising.” That open-ended transition generally permits additional ingredients, provided the accused formulation still contains every required claimed element.

Claim 1: broadest practical scope

Claim 1 requires:

A nasal spray formulation;
5%-16% w/w naloxone or a pharmaceutically acceptable salt;
Water; and
0.001%-0.1% w/w of a chelating agent.

The claim does not require ethanol, propylene glycol, a specific pH, a particular spray device, a specified dose per actuation, a preservative, or a particular particle-size distribution.

The claim therefore reaches formulations that omit ethanol and propylene glycol if they retain the required naloxone, water, and chelator concentrations.

Claim 9: defined solvent system

Claim 9 is narrower than claim 1 because it requires all of the following:

5%-16% w/w naloxone or salt;
20%-50% w/w ethanol;
5%-10% w/w propylene glycol;
35%-70% w/w water; and
0.001%-0.1% w/w chelating agent.

A formulation may fall within claim 9 even if it contains other excipients, because the claim is open-ended. The total listed ranges do not need to add to 100%; other ingredients can occupy the balance.

Claim 12: higher active concentration and narrower chelator range

Claim 12 requires:

7%-16% w/w naloxone or salt;
Water; and
0.005%-0.01% w/w chelating agent.

This claim is narrower than claim 1 in two ways. It raises the minimum naloxone concentration from 5% to 7% and narrows the chelator range from 0.001%-0.1% to 0.005%-0.01%.

How do the dependent claims narrow the patent?

The dependent claims create overlapping fallback positions rather than separate inventions.

Claims	Limitation
2, 11, 13	Chelator is edetate disodium dihydrate
3, 17	Ethanol and propylene glycol are present
4, 18	Ethanol is 2%-50%; propylene glycol is 5%-10%
5	Ethanol is 20%-50%
6	Naloxone is 7%-16%
7	Water is 20%-95%
8	Water is 30%-85%
10	Chelator is 0.005%-0.01%
14	Water is 10%-90%
15	Water is 20%-90%
16	Water is 35%-85%
19	Water is 10%-95%

Claims 7, 14, 15, and 19 have broad water ranges that overlap substantially. For example, a formulation containing 40% water satisfies each of those claims if the independent claim requirements are also met.

What formulations are protected by US 11,135,155?

High-risk formulation profile

A formulation has the clearest exposure when it contains:

Naloxone hydrochloride or another pharmaceutically acceptable naloxone salt;
Naloxone at 7%-16% w/w;
Water at 35%-70% w/w;
Ethanol at 20%-50% w/w;
Propylene glycol at 5%-10% w/w; and
Edetate disodium dihydrate at 0.005%-0.01% w/w.

That formulation would likely read on claim 9 and one or more of claims 10-11. It may also read on claim 1, claim 2, claim 3, claim 4, claim 5, claim 6, and claim 12, depending on the exact concentrations.

Representative claim chart

Formulation characteristic	Claim 1	Claim 9	Claim 12
Naloxone 5%-16%	Required	Required	No, minimum is 7%
Naloxone 7%-16%	Optional dependent limitation	Optional by overlap	Required
Water	Required	Required at 35%-70%	Required
Chelator 0.001%-0.1%	Required	Required	No, requires 0.005%-0.01%
Ethanol	Not required	Required	Not required
Propylene glycol	Not required	Required	Not required
Edetate disodium dihydrate	Dependent claim	Dependent claim	Dependent claim

Formulations outside the literal concentration ranges

A formulation containing 4% w/w naloxone would not literally satisfy claims 1, 9, or 12 because each independent claim begins at 5% or 7%. A formulation containing no chelating agent would not satisfy the independent claims.

Literal non-infringement does not automatically eliminate litigation risk. A patentee could assert the doctrine of equivalents, although prosecution history, claim amendments, prior-art arguments, and the importance of the numerical ranges would control that analysis. Numerical concentration limitations often create substantial prosecution-history and ensnarement constraints.

What is the patent’s technical scope?

The patent is directed to formulation chemistry rather than delivery hardware. Its claims do not expressly require:

A specific nasal actuator;
A metered dose;
A particular spray plume;
A defined droplet-size distribution;
A preservative;
A particular pH;
A particular osmolality;
A specific container-closure system;
A particular manufacturing process; or
A clinical indication.

The use of a nasal spray limitation remains important. A non-nasal dosage form would not satisfy the claims as written. A liquid formulation supplied in a device capable of nasal administration presents a stronger infringement case than an oral, injectable, or ophthalmic product.

The claims also cover naloxone salts, not only naloxone base. The salt language expands coverage across pharmaceutically acceptable salt forms, subject to claim construction and the specification’s disclosure.

How strong is the patent estate for US 11,135,155?

The patent’s commercial strength depends on three issues: whether a marketed product falls within the high-concentration ranges, whether the patent is listed against a relevant FDA-approved product, and whether earlier disclosures anticipate or render obvious the claimed formulation.

Strengths

The independent claims cover the active formulation combination rather than only a narrow excipient recipe.
The claims contain overlapping concentration ranges, creating multiple infringement theories.
Edetate disodium dihydrate provides a specific dependent-claim fallback.
Claim 9 captures a defined solvent system using ethanol and propylene glycol.
The open “comprising” language leaves room for additional excipients.

Weaknesses

The claims require unusually high naloxone concentrations relative to several marketed naloxone nasal sprays.
The use of water and chelators in pharmaceutical formulations may be vulnerable to prior-art combination arguments.
The claims do not require a demonstrated clinical or pharmacokinetic result.
The broad independent claims could face written-description, enablement, anticipation, or obviousness attacks across the full concentration ranges.
The patent does not itself establish exclusivity over all naloxone nasal delivery systems.

When does US Patent 11,135,155 lose exclusivity?

US Patent 11,135,155 issued on October 5, 2021.[1] The ordinary US patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and other statutory adjustments.[2]

Public family records associate the patent with the naloxone nasal-formulation patent family and an expiration period in the mid-2030s. The controlling expiration date is the term shown in USPTO Patent Center and any applicable Orange Book listing. The issue date alone does not determine the expiration date.

Exclusivity timeline

Event	Date or status
Patent issued	October 5, 2021
Ordinary patent term	20 years from applicable earliest nonprovisional filing
Expected family-level expiration period	Mid-2030s
FDA new-drug exclusivity	Separate from patent term
Pediatric exclusivity	Separate six-month extension where granted
Generic entry	Controlled by applicable patents, regulatory exclusivity, litigation, and settlement terms

Patent exclusivity and FDA regulatory exclusivity are separate rights. FDA approval of an ANDA or 505(b)(2) application can be blocked by regulatory exclusivity even after a patent expires. Conversely, patent rights can delay entry after FDA exclusivity ends.

What is the Orange Book status of US 11,135,155?

An Orange Book listing must be evaluated against a specific reference-listed drug and NDA. A patent is not automatically an Orange Book patent merely because it covers a drug formulation.

For a nasal naloxone product, the key questions are:

Whether the patent is listed against the relevant NDA;
Whether the listing identifies the drug substance, drug product, or method of use;
Whether the listed patent claims the approved formulation;
Whether the NDA holder submitted the patent information within the FDA listing framework; and
Whether the patent remains active and relevant to an ANDA applicant.

FDA regulations limit the types of patents that may be listed in the Orange Book.[3] A formulation patent generally must claim the approved drug product or a method of using the approved product. A patent directed solely to a research formulation that is not the approved product may not provide an effective Orange Book barrier.

The patent’s practical Hatch-Waxman value therefore depends on its listing status against the specific naloxone NDA, not merely on its issued claims.

What Paragraph IV challenges could target this patent?

A generic or 505(b)(2) applicant could file a Paragraph IV certification if the patent is listed in the Orange Book and the applicant asserts that the patent is invalid, unenforceable, or not infringed.[4]

Likely challenge theories include:

Non-infringement

An applicant could design around one or more required ranges by:

Using less than 5% w/w naloxone;
Using more than 16% w/w naloxone;
Omitting a chelating agent;
Using a non-chelating stabilizer;
Eliminating ethanol or propylene glycol;
Holding ethanol below 20% for claim 9; or
Using propylene glycol below 5% or above 10%.

A design-around must be assessed against all claims, including claims 1 and 12, not only claim 9.

Anticipation

An invalidity challenger would search earlier naloxone nasal formulations disclosing:

Concentrated naloxone;
Water-based nasal liquids;
EDTA or another chelator;
Ethanol and propylene glycol; and
The claimed overlapping numerical ranges.

A single prior-art reference must disclose every element of the challenged claim.

Obviousness

The most significant validity issue is likely obviousness. A challenger could argue that a skilled formulator would have combined known naloxone nasal delivery, water, ethanol, propylene glycol, and EDTA to improve solubility, stability, or manufacturability.

The patent holder would likely rely on unexpected stability, improved concentration capability, improved nasal absorption, or other formulation performance data. The strength of that defense depends on comparative examples tied to the full claim scope.

Written description and enablement

The broad ranges in claims 1 and 12 could be tested against the specification’s working examples. If the specification provides only a small number of compositions, a challenger may argue that the claims cover undue experimentation across the full concentration ranges and across multiple naloxone salts and chelators.

What litigation and settlement risks affect the patent?

The supplied record does not establish a complete litigation docket, settlement history, or current assignee status for US 11,135,155. Those matters must be determined from USPTO assignment records, PACER, district-court dockets, the Federal Circuit docket, and FDA patent-listing records.

The relevant litigation triggers are:

A Paragraph IV notice identifying the patent;
A 45-day infringement action by the NDA holder or patent owner;
A 30-month FDA approval stay under the Hatch-Waxman framework;
A claim-construction dispute over “nasal spray formulation,” “about,” w/w concentration, or pharmaceutically acceptable salt;
A settlement permitting an agreed generic launch date; and
A possible authorized-generic or license arrangement.

Settlement agreements involving controlled-substance products may also attract FTC review, especially where payment, supply restrictions, delayed entry, or market-allocation provisions are alleged.[5]

Which companies are challenging naloxone nasal-spray patents?

The competitive field includes branded naloxone developers, generic manufacturers, nonprofit or public-interest developers, and companies developing alternative opioid-antagonist products.

Relevant commercial categories include:

Category	Examples
Branded naloxone nasal spray	Emergent BioSolutions and other NDA holders
Generic naloxone nasal spray	Teva and other ANDA applicants
Alternative high-dose products	Developers of concentrated naloxone nasal sprays
Public-interest products	Government-supported or nonprofit-backed naloxone programs
Competing opioid antagonists	Developers of nalmefene nasal spray

A company can challenge the patent through Paragraph IV, an inter partes review petition, a district-court declaratory-judgment action, or a design-around product. The existence of a competing product does not establish that it practices the claims.

Does the patent create biosimilar risk?

No conventional biosimilar risk exists. Naloxone is a small-molecule active pharmaceutical ingredient, not a biologic. The relevant regulatory pathways are generally an ANDA under section 505(j) or a 505(b)(2) application under the Federal Food, Drug, and Cosmetic Act.[6]

A follow-on product may still face:

Orange Book patent litigation;
Formulation differences requiring a 505(b)(2) application;
Device or combination-product requirements;
Clinical bridging requirements;
Controlled-substance manufacturing controls; and
FDA requirements for nasal-spray performance and human-factors validation.

What manufacturing and IP barriers exist?

The patent does not claim a manufacturing process, but formulation development may create practical barriers. A competitor must control:

High-concentration naloxone solubility;
Chemical stability;
Chelator compatibility;
Ethanol and propylene glycol tolerance;
Nasal mucosal tolerability;
Spray-device compatibility;
Container-closure extractables and leachables;
Dose uniformity; and
Long-term stability.

These technical constraints can make a literal design-around commercially unattractive even if it avoids the patent. Separate patents may cover the spray device, actuator, container, manufacturing process, dosing regimen, or clinical use.

How does US 11,135,155 compare with typical naloxone nasal-spray patents?

US 11,135,155 is narrower in subject matter than a platform patent covering all intranasal naloxone delivery. It is broader than a claim limited to one exact composition because its independent claims use concentration ranges and open-ended “comprising” language.

Patent characteristic	US 11,135,155
Active ingredient	Naloxone or pharmaceutically acceptable salt
Dosage form	Nasal spray or liquid spray
Primary protection	Formulation composition
Device protection	None apparent from supplied claims
Method-of-use protection	None apparent from supplied claims
Manufacturing protection	None apparent from supplied claims
Key excipient	Chelating agent, particularly edetate disodium dihydrate
Solvent system	Optional broadly; required in claim 9
Biosimilar relevance	None
Main competitor pathway	ANDA or 505(b)(2)

What generic launch scenarios exist?

Scenario 1: product falls outside all claimed ranges

A generic sponsor could launch after satisfying FDA requirements if its formulation avoids every independent claim and no separate patent blocks approval.

Scenario 2: Paragraph IV challenge

The sponsor could certify that the patent is invalid, unenforceable, or not infringed. Litigation could produce a 30-month stay, an early settlement, or an invalidity/non-infringement judgment.

Scenario 3: licensed or authorized entry

The patent owner or NDA holder could license the formulation technology, supply an authorized generic, or agree to a future entry date.

Scenario 4: 505(b)(2) alternative formulation

A sponsor could develop a different naloxone nasal formulation and rely on bridging studies rather than seeking exact ANDA sameness. This route may avoid claim 9 but still implicate claims 1 or 12.

Key Takeaways

US 11,135,155 is a formulation patent for concentrated naloxone nasal sprays.
Claims 1, 9, and 12 are the principal infringement targets.
The highest-risk composition contains 7%-16% w/w naloxone, ethanol, propylene glycol, water, and edetate disodium dihydrate.
The patent does not, based on the supplied claims, cover all naloxone nasal sprays, spray devices, methods of treating overdose, or manufacturing processes.
Its main validity risks are prior-art formulation disclosures, obviousness, written description, and enablement across broad concentration ranges.
It is relevant to ANDA and 505(b)(2) strategies, not biosimilar litigation.
Orange Book significance depends on listing against the specific approved naloxone product.
Generic entry could occur through design-around, Paragraph IV litigation, settlement, licensing, or a later 505(b)(2) product.

Frequently Asked Questions

Is 4% w/w naloxone covered by US 11,135,155?

No. The independent claims begin at 5% w/w for claims 1 and 9, and at 7% w/w for claim 12. A 4% formulation would not literally meet those concentration limitations.

Does a formulation without EDTA avoid the patent?

Not necessarily. Claims 1, 9, and 12 cover a “chelating agent” generally. EDTA is required only by dependent claims 2, 11, and 13. Another chelating agent could still fall within an independent claim.

Does removing ethanol avoid infringement?

It may avoid claim 9 and its dependent claims, but it would not necessarily avoid claim 1 or claim 12, which do not require ethanol.

Is Narcan automatically covered by US 11,135,155?

No. Coverage depends on the marketed product’s exact composition, including naloxone concentration, chelator concentration, and the applicable claim construction. Product branding alone does not establish infringement.

Can a generic launch before the patent expires?

Yes, potentially, through a successful Paragraph IV challenge, a design-around formulation, a license or settlement, an authorized-generic arrangement, or a regulatory pathway that is not blocked by the patent. Separate Orange Book-listed patents and regulatory exclusivities must also be cleared.

References

United States Patent and Trademark Office. (2021). United States Patent No. 11,135,155, Naloxone nasal formulations.
United States Code, 35 U.S.C. §§ 154, 156, 163.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
United States Code, 21 U.S.C. § 355(j); 21 C.F.R. § 314.101.
Federal Trade Commission. (2013). Authorized generic drugs: Short-term effects and long-term impact.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application and 505(b)(2) drug approval pathways.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Hikma	KLOXXADO	naloxone hydrochloride	SPRAY;NASAL	212045-001	Apr 29, 2021		RX	Yes	Yes	11,135,155	⤷ 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
Australia	2017312811	⤷ Start Trial
Canada	2954370	⤷ Start Trial
Canada	3033897	⤷ Start Trial
China	109922805	⤷ Start Trial
European Patent Office	3177146	⤷ Start Trial
European Patent Office	3500261	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 11,135,155