Details for Patent: 10,973,814

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Which drugs does patent 10,973,814 protect, and when does it expire?

Patent 10,973,814 protects KLOXXADO and is included in one NDA.

This patent has fourteen patent family members in seven countries.

Summary for Patent: 10,973,814

Title:	Liquid naloxone spray
Abstract:	The invention provides stable liquid formulations containing naloxone, a pharmaceutically acceptable salt or a derivative thereof. The invention further provides methods for treating opioid overdose, opioid dependence, and congenital insensitivity to pain with anhidrosis by administering the liquid formulations of the present invention intranasally to a patient in need thereof. Further, the invention provides a method of treating opioid dependence, opioid overdose, and congenital insensitivity to pain with anhidrosis by administering intranasally the naloxone formulations of the present invention.
Inventor(s):	Kiran Amancha, Chandeshwari Chilampalli, Thrimoorthy Potta, Ningxin Yan, Venkat R. Goskonda
Assignee:	Hikma Pharmaceuticals USA Inc
Application Number:	US16/674,424
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,973,814
Patent Claim Types: see list of patent claims	Use; Formulation;

US Patent 10,973,814: Naloxone Spray Formulation Claims, Patent Scope, and Competitive Landscape

US Patent 10,973,814 protects specific high-concentration liquid naloxone spray formulations containing water, propylene glycol, ethanol, and edetate disodium dihydrate, while excluding buffers and isotonicity agents. Its method claims extend the formulation to opioid dependence, opioid overdose, and congenital insensitivity to pain with anhidrosis, with intranasal and sublingual administration pathways.

The patent’s commercial relevance depends on four limitations: the precise naloxone concentration, the water/propylene glycol/ethanol/edetate excipient profile, the absence of a buffer and isotonicity agent, and use in a liquid spray dosage form. A competing product that changes one of those elements may avoid literal infringement, although the doctrine of equivalents, prosecution history, and formulation-performance evidence remain relevant.

What does US Patent 10,973,814 cover?

The patent has three formulation claim groups:

Claim group	Active ingredient	Claimed concentration	Core excipients	Excluded components
Claim 1	Naloxone or pharmaceutically acceptable salt	About 7.5% w/w	About 66% water, 5% propylene glycol, 20% ethanol, 0.01% edetate disodium dihydrate	Isotonicity agent and buffer
Claim 5	Naloxone hydrochloride dihydrate	About 9% w/w	About 66% water, 5% propylene glycol, 20% ethanol, 0.01% edetate disodium dihydrate	Isotonicity agent and buffer
Claim 9	Naloxone hydrochloride	About 8% w/w	About 66% water, 5% propylene glycol, 20% ethanol, 0.01% edetate disodium dihydrate	Isotonicity agent and buffer

The claims are formulation-specific rather than molecule-specific. They do not cover naloxone generally, all nasal naloxone products, or every liquid naloxone spray.

The patent is identified as US 10,973,814 B2, issued by the United States Patent and Trademark Office. The controlling legal scope is the issued claim language, interpreted with the specification, prosecution history, and applicable Federal Circuit precedent. The claim text supplied for this analysis is the operative basis for the scope assessment. (USPTO, 2021; U.S. Patent No. 10,973,814, 2021)

How many independent claims does US 10,973,814 have?

The patent contains eight independent claims based on the supplied claim set:

• Claim 1: liquid spray formulation containing about 7.5% w/w naloxone or a pharmaceutically acceptable salt.
• Claim 2: opioid-dependence treatment using claim 1.
• Claim 3: opioid-overdose treatment using claim 1.
• Claim 5: liquid spray formulation containing about 9% w/w naloxone hydrochloride dihydrate.
• Claim 6: opioid-dependence treatment using claim 5.
• Claim 7: opioid-overdose treatment using claim 5.
• Claim 9: liquid spray formulation containing about 8% w/w naloxone hydrochloride.
• Claims 10 and 11: treatment of opioid dependence and opioid overdose using claim 9.

Although claims 2, 3, 6, 7, 10 and 11 are drafted as method claims, they incorporate the formulation limitations of claims 1, 5 or 9. Claims 4, 8 and 12 address congenital insensitivity to pain with anhidrosis.

The practical infringement risk is therefore concentrated in claims 1, 5 and 9. The method claims generally rise or fall with whether the accused product satisfies the relevant formulation claim and whether the claimed use and route are practiced.

What formulation limitations define the patent’s scope?

Liquid spray dosage form

Each independent formulation claim requires a liquid spray formulation. A dry powder, tablet, film, injectable solution, prefilled syringe, or solid oral dosage form would not literally meet this limitation.

A product supplied as a liquid but administered through a device other than a spray could create a noninfringement position, depending on whether the product is still characterized as a spray formulation and how the claims and specification define the term.

High naloxone loading

The claims require approximately:

• 7.5% w/w naloxone or salt under claim 1;
• 9% w/w naloxone hydrochloride dihydrate under claim 5; or
• 8% w/w naloxone hydrochloride under claim 9.

These concentrations are materially higher than the concentration commonly associated with standard 4 mg/0.1 mL naloxone nasal spray products. A product with a substantially lower concentration would have a strong literal noninfringement position against the concentration limitations, subject to the construction of “about.”

“About” creates a numerical boundary issue. The patent does not establish the permissible deviation in the claim text supplied. A court would ordinarily consider the specification, examples, prosecution record, measurement precision, formulation purpose, and technical understanding of the term. The phrase does not automatically cover every concentration near the stated value.

Water, propylene glycol, ethanol and edetate

The claimed excipient system is unusually specific:

• approximately 66% w/w water;
• approximately 5.0% w/w propylene glycol;
• approximately 20.0% w/w ethanol; and
• approximately 0.01% w/w edetate disodium dihydrate.

A formulation that replaces propylene glycol with glycerin, polyethylene glycol, or another cosolvent may avoid literal infringement. The same analysis applies to replacement of ethanol, omission of edetate, or use of a different chelating agent.

Because the claims use “comprising,” the listed components are required but additional ingredients may be present unless another claim limitation excludes them. The exclusion of isotonicity agents and buffers is express and narrows that otherwise open-ended transition.

No isotonicity agent and no buffer

This is a negative limitation. The claimed formulation must not contain an isotonicity agent or a buffer.

The limitation creates two questions:

1. Whether a particular excipient is an isotonicity agent or buffer under the patent’s technical meaning.
2. Whether an ingredient performs that function even if it is identified in the product documentation for another purpose.

Sodium chloride, dextrose, mannitol and similar excipients may be treated as isotonicity agents when included to adjust osmolality. Phosphate, citrate, acetate and borate systems may be treated as buffers when included to control pH. A formulation may face an infringement argument if it uses one of these materials, even if the manufacturer labels the ingredient a stabilizer or pH adjuster.

The negative limitation also gives generic developers a clear design-around pathway: use a buffered or isotonic formulation, provided the product does not otherwise fall within the asserted claims under an equivalents theory.

How do the 7.5%, 8% and 9% claims differ?

The three formulation claims protect closely related compositions but use different active-ingredient descriptions.

Issue	Claim 1	Claim 5	Claim 9
Active description	Naloxone or pharmaceutically acceptable salt	Naloxone hydrochloride dihydrate	Naloxone hydrochloride
Nominal strength	7.5% w/w	9% w/w	8% w/w
Salt specificity	Broad	Narrow	Intermediate
Excipient profile	Same	Same	Same
Buffer exclusion	Yes	Yes	Yes
Isotonicity-agent exclusion	Yes	Yes	Yes
Design-around sensitivity	Concentration and salt form	Hydrate and concentration	Concentration and salt form

Claim 1 is potentially the broadest formulation claim because it covers naloxone and pharmaceutically acceptable salts at about 7.5% w/w. Claims 5 and 9 are more chemically specific but cover different nominal loadings.

The distinctions between naloxone hydrochloride, naloxone hydrochloride dihydrate and active-moiety-equivalent concentrations can become important. A manufacturer cannot assume that a label expressed in milligrams of naloxone base avoids a claim expressed in weight percent of a salt. The analytical comparison must normalize the product composition to the claim’s stated chemical form and total formulation weight.

What methods of use does US 10,973,814 protect?

The method claims cover administration of the claimed formulations for three conditions.

Opioid overdose

The overdose claims are the most commercially relevant. They cover administration intranasally, sublingually, or through both routes. Combined intranasal and sublingual administration may occur simultaneously, sequentially or concomitantly.

A product used only for opioid overdose may still implicate the formulation claims even if the product label does not include the other claimed indications.

Opioid dependence

The claims also recite treatment of opioid dependence. This is broader than emergency overdose reversal and could affect a product promoted or clinically investigated for dependence treatment.

A method-of-use claim generally requires the claimed treatment to be performed. Manufacturer liability may depend on labeling, promotional conduct, instructions, clinical protocols and the relationship between the product’s approved uses and the claimed method.

Congenital insensitivity to pain with anhidrosis

Claims 4, 8 and 12 recite treatment of congenital insensitivity to pain with anhidrosis, a rare disorder involving impaired pain perception and abnormal sweating.

This indication appears commercially narrow. It still increases claim breadth because the formulation claims are incorporated into an additional therapeutic-use category. It may have more relevance to clinical development, orphan-disease research or patent licensing than to current naloxone emergency products.

Does the patent cover intranasal naloxone products such as Narcan or Kloxxado?

The patent does not automatically cover every intranasal naloxone product. The relevant question is whether a marketed product contains the claimed composition.

Commercial intranasal products commonly differ in at least one major parameter:

• lower or different naloxone concentration;
• different water and cosolvent ratios;
• use of a buffer;
• use of an isotonicity agent;
• different preservative or chelating system;
• different device and delivered volume;
• naloxone concentration stated per spray rather than by total formulation weight.

Narcan nasal spray, for example, has been marketed as a 4 mg dose in a 0.1 mL spray. Kloxxado has been marketed as an 8 mg dose in a 0.1 mL spray. Dose strength alone does not establish infringement because the patent claims use weight percentage of the total liquid formulation, not merely milligrams per actuation. The full qualitative and quantitative composition must be compared with the patent claims. (FDA, 2024a; FDA, 2024b)

What is the Orange Book status of US Patent 10,973,814?

A patent’s issuance does not establish that it is listed in the FDA’s Orange Book. Orange Book listing generally depends on the approved drug product, NDA holder, patent submission, FDA listing criteria and the relationship between the patent claims and the approved product. (FDA, 2024c)

US 10,973,814 should therefore be evaluated separately from the patent’s validity and enforceability:

Question	Relevance
Is the patent issued and unexpired?	Determines baseline legal term and potential enforcement
Is it listed in the Orange Book?	Determines whether it may support a listed-patent certification and potential statutory stay
Does the approved product practice the claims?	Determines commercial relevance
Does the patent claim the approved formulation or method?	Determines listing and infringement risk
Has the patent been disclaimed, expired or invalidated?	Determines enforceability

A Paragraph IV certification is relevant only if the patent is listed against the reference listed drug and the generic applicant relies on the applicable abbreviated pathway. An unlisted formulation patent may still be asserted in district court, but it generally does not create the same Orange Book litigation mechanism or automatic 30-month stay.

When does US Patent 10,973,814 lose exclusivity?

The patent’s expiration date cannot be determined from the claims alone. The statutory term requires the patent’s earliest effective nonprovisional filing date, applicable patent-term adjustment, patent-term extension, terminal disclaimer and any other term event.

For a post-June 8, 1995 utility patent, the baseline term is generally 20 years from the earliest effective U.S. nonprovisional filing date, subject to adjustment and extension. (35 U.S.C. §§ 154, 156; USPTO, 2024)

The relevant exclusivity dates should be separated:

Exclusivity type	Effect
Patent term	Blocks unauthorized practice of valid, enforceable claims
FDA new-drug exclusivity	Restricts certain abbreviated applications for a defined period
Orphan-drug exclusivity	Can restrict approval for the same indication for seven years
Pediatric exclusivity	Can add six months to certain regulatory exclusivities and listed patents
Orange Book listing	Affects certification obligations and potential litigation stay

The patent’s issue date, April 13, 2021, is not its expiration date. A reliable expiration analysis must use the USPTO patent record and any terminal disclaimer or PTA data associated with the patent. (USPTO, 2021)

Which companies challenge the patent or related naloxone patents?

The commercial naloxone market includes products and patent estates associated with several companies:

Company	Product or position	Relevance to US 10,973,814
Emergent BioSolutions	Narcan nasal spray	Major branded intranasal naloxone product; composition comparison required
Hikma Pharmaceuticals	Kloxxado nasal spray	High-dose intranasal competitor; concentration and excipient comparison required
Amphastar Pharmaceuticals	Naloxone products and generic activity	Potential generic and formulation competitor
Teva Pharmaceuticals	Generic naloxone products	Potential abbreviated-application participant
Sandoz and other generic manufacturers	Generic naloxone supply	Product-specific formulation and route analysis required
Opiant Pharmaceuticals	Naloxone nasal-delivery intellectual property and product development history	Relevant patent-family and licensing context

Public competition does not establish that any company has challenged US 10,973,814. A Paragraph IV challenge must be confirmed through FDA Orange Book records, ANDA litigation filings and district court dockets. The supplied claim information does not establish a filed Paragraph IV certification, inter partes review, post-grant review, district court invalidity action or settlement involving this patent.

What patent families are relevant to high-dose naloxone sprays?

The relevant landscape includes several overlapping patent categories:

Nasal-delivery patents

These patents may claim:

• intranasal administration of naloxone;
• spray devices and metering systems;
• delivered dose and plume characteristics;
• absorption-enhancing formulations;
• single-dose or unit-dose packaging.

They may create device or method-of-use risk even where a product avoids the specific composition claimed by US 10,973,814.

Formulation patents

Formulation patents may claim:

• naloxone concentration;
• pH;
• osmolality;
• preservatives;
• chelating agents;
• cosolvents;
• viscosity;
• stability;
• absence or presence of buffers.

US 10,973,814 fits primarily within this category.

Method-of-treatment patents

These patents may cover:

• overdose reversal;
• repeat dosing;
• treatment based on patient response;
• administration through multiple routes;
• opioid dependence;
• emergency community use.

The method claims in US 10,973,814 increase overlap with this category.

Device patents

A nasal spray product may require clearance of separate patents covering:

• actuator geometry;
• metering chambers;
• nozzle structure;
• dose uniformity;
• tamper resistance;
• packaging and assembly.

A formulation clearance opinion does not clear the delivery device.

How strong is the patent estate for US 10,973,814?

The patent has moderate formulation protection but limited breadth against all naloxone products.

Strengths

• Three separate nominal concentration positions: 7.5%, 8% and 9%.
• Coverage of naloxone and selected salt forms.
• Defined excipient combination.
• Express protection against formulations omitting buffers and isotonicity agents.
• Method claims covering overdose, dependence and a rare pain-insensitivity disorder.
• Intranasal and sublingual administration language.

Weaknesses

• The claims are composition-specific and may be designed around.
• “About” creates claim-construction uncertainty at the concentration boundaries.
• The excipient percentages are narrow.
• The negative limitations may be vulnerable to factual disputes over whether an ingredient is a buffer or isotonicity agent.
• The method claims depend on the accused product meeting the formulation limitations.
• The patent does not by itself cover all nasal naloxone products or all high-dose naloxone sprays.

The strongest enforcement scenario would involve a liquid spray with approximately the claimed naloxone loading and substantially identical water, propylene glycol, ethanol and edetate levels, without an intentional buffer or isotonicity agent.

What generic launch risks exist?

A generic or follow-on manufacturer faces four principal risks.

Formulation matching

A product copied closely enough to meet the claimed quantitative profile could face direct composition-claim infringement. This risk is highest for a product using the same excipient architecture and nominal strength.

Label-driven method claims

A label that instructs intranasal or sublingual use for opioid overdose or dependence could create method-claim exposure if the formulation falls within claims 1, 5 or 9.

Device and delivery patents

Avoiding US 10,973,814 does not clear patents covering spray hardware, packaging or nasal administration methods.

Regulatory timing

If the patent is listed against a reference product, a generic applicant may need to file a Paragraph IV certification or wait for patent expiry. If it is not listed, the applicant may face ordinary patent litigation without the same Orange Book-based stay.

What licensing deals affect the naloxone patent landscape?

The naloxone market has included licensing, acquisition and commercialization arrangements, particularly around intranasal delivery and Narcan-related intellectual property. Opiant’s naloxone nasal-spray assets became associated with Emergent BioSolutions through Emergent’s acquisition of Opiant Pharmaceuticals in 2023. (Emergent BioSolutions, 2023)

That transaction is relevant to ownership and enforcement analysis for Opiant-origin patent families. It does not establish that US 10,973,814 itself transferred unless the patent assignment record confirms the transfer. Ownership should be checked in the USPTO assignment database before any licensing, enforcement or freedom-to-operate conclusion.

What geographic coverage does US 10,973,814 provide?

US 10,973,814 provides protection only in the United States. Commercial launch in Canada, Europe, Japan, Australia or other jurisdictions requires review of corresponding national or regional family members.

A global clearance review should examine:

• international application and PCT records;
• European Patent Office family members;
• Canadian, Australian and Japanese counterparts;
• national-phase prosecution outcomes;
• granted claims and expiration dates;
• terminal disclaimers;
• divisional and continuation applications;
• ownership and recorded assignments.

A U.S. patent does not create foreign exclusivity, and a foreign counterpart may have materially different claims.

What manufacturing and intellectual-property barriers matter?

The formulation itself may be technically easy to reproduce, but commercial development requires control over:

• high-concentration naloxone solubility;
• chemical and physical stability;
• spray-dose uniformity;
• nozzle performance;
• microbial control;
• container-closure compatibility;
• ethanol and propylene glycol tolerance;
• edetate compatibility;
• nasal and sublingual tolerability;
• scale-up and fill-finish reproducibility.

The absence of a buffer and isotonicity agent may create a distinctive formulation profile. A design-around that adds a buffer or isotonicity agent may reduce patent risk but require new stability, tolerability and regulatory data.

Key Takeaways

• US 10,973,814 is a formulation-focused naloxone patent, not a patent on naloxone generally.
• The central protected composition contains high-concentration naloxone, water, propylene glycol, ethanol and edetate disodium dihydrate.
• Claims 1, 5 and 9 target approximately 7.5%, 9% and 8% w/w formulations.
• The absence of both a buffer and an isotonicity agent is a material limitation.
• The method claims cover opioid dependence, opioid overdose and congenital insensitivity to pain with anhidrosis.
• Narcan and Kloxxado cannot be assessed by dose strength alone. Full composition and total formulation weight must be compared.
• A Paragraph IV challenge, Orange Book listing or settlement cannot be inferred from patent issuance alone.
• The principal design-around options are changing concentration, salt or hydrate form, excipient ratios, chelating agent, buffer status or isotonicity profile.
• U.S. protection does not establish foreign patent coverage.
• Ownership, Orange Book status, term adjustment and litigation history require record-level verification before a launch or licensing decision.

FAQs

Does US 10,973,814 cover 8 mg naloxone nasal spray?

Not automatically. The claims are based on weight percentage of the total formulation, not the labeled milligrams per spray. An 8 mg spray may infringe only if its full formulation meets the applicable concentration, excipient and exclusion limitations.

Can adding sodium chloride avoid US 10,973,814?

It may create a literal noninfringement position if sodium chloride functions as an isotonicity agent and the product therefore contains an excluded component. The overall formulation and any equivalents theory would still require analysis.

Does the patent cover injectable naloxone?

The supplied claims require a liquid spray formulation and specified administration routes. A conventional injectable naloxone product would not ordinarily satisfy those limitations.

Can a generic use the same naloxone hydrochloride active ingredient?

Yes, use of the same active ingredient alone does not establish infringement. The generic must be compared against the claimed concentration, excipient composition, spray form, absence of buffer and absence of isotonicity agent.

Is congenital insensitivity to pain with anhidrosis a major commercial indication?

No. The indication is rare and is unlikely to drive the principal commercial value of the patent. Its importance is mainly that it broadens the claimed method-of-use coverage beyond overdose and dependence.

References

1. Emergent BioSolutions, Inc. (2023). Emergent BioSolutions completes acquisition of Opiant Pharmaceuticals.
2. U.S. Food and Drug Administration. (2024a). Narcan naloxone hydrochloride nasal spray prescribing information.
3. U.S. Food and Drug Administration. (2024b). Kloxxado naloxone hydrochloride nasal spray prescribing information.
4. U.S. Food and Drug Administration. (2024c). Approved drug products with therapeutic equivalence evaluations.
5. U.S. Patent No. 10,973,814. (2021). Naloxone formulations and methods of use thereof. United States Patent and Trademark Office.
6. United States Code, Title 35, §§ 154, 156.
7. United States Patent and Trademark Office. (2024). Patent term adjustment and patent term extension guidance.

Drugs Protected by US Patent 10,973,814

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	10,973,814		Y			USE OF NALOXONE FOR THE EMERGENCY TREATMENT OF KNOWN OR SUSPECTED OPIOID OVERDOSE, AS MANIFESTED BY RESPIRATORY AND/OR CENTRAL NERVOUS SYSTEM DEPRESSION, FOR ADULT AND PEDIATRIC PATIENTS

International Family Members for US Patent 10,973,814

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2017312811
Canada	2954370
Canada	3033897
China	109922805
European Patent Office	3177146