Details for Patent: 10,722,510

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Which drugs does patent 10,722,510 protect, and when does it expire?

Patent 10,722,510 protects KLOXXADO and is included in one NDA.

This patent has fourteen patent family members in seven countries.

Summary for Patent: 10,722,510

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 dependence, opioid overdose, and congenital insensitivity to pain with anhidrosis by administering the liquid formulations of the present invention both intranasally and sublingually 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 and sublingually the naloxone formulations of the present invention.
Inventor(s):	Kiran Amancha, Shivani Chilampalli, Thrimoorthy Potta, Ningxin Yan, Venkat R. Goskonda
Assignee:	Hikma Pharmaceuticals USA Inc
Application Number:	US15/238,909
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,722,510
Patent Claim Types: see list of patent claims	Use; Formulation;

US Patent 10,722,510: Naloxone Spray Formulation Claims, Patent Scope, Expiration Risk, and Competitive Landscape

US Patent 10,722,510 protects a narrow liquid naloxone formulation defined by overlapping concentration ranges for naloxone, water, propylene glycol, ethanol, and edetate disodium dihydrate. The patent also claims intranasal and sublingual administration for opioid dependence, opioid overdose, and congenital insensitivity to pain with anhidrosis.

The strongest infringement risk is concentrated in a product that uses all of the following: approximately 8% to 12% naloxone or a pharmaceutically acceptable salt, 35% to 85% water, 3% to 7% propylene glycol, 20% to 50% ethanol, and 0.005% to 0.01% edetate disodium dihydrate. The claims do not require a particular nasal device, dose volume, spray actuator, preservative, container, or dosing schedule.

What does US Patent 10,722,510 claim?

The independent claims divide into a composition claim and three method-of-treatment claims.

Claim	Claim type	Principal subject matter
1	Independent composition claim	Stable liquid naloxone spray formulation with specified concentration ranges
2	Dependent composition claim	Formulation in simple solution form
3	Dependent composition claim	pH from approximately 2 to 7
4	Dependent composition claim	Optional antioxidant selected from a defined list
5	Independent method claim	Treatment of opioid dependence
6	Independent method claim	Treatment of opioid overdose
7	Independent method claim	Treatment of congenital insensitivity to pain with anhidrosis

Claim 1 is the commercial center of the patent. Claims 2 through 4 narrow the formulation. Claims 5 through 7 extend the patent to use of the formulation for specified conditions.

The claims use “comprising,” which generally makes them open-ended composition claims. A formulation may contain additional excipients, buffers, preservatives, tonicity agents, flavoring agents, or other ingredients, provided the claimed components and ranges are present.

What formulation is protected by US Patent 10,722,510?

Claim 1 requires the following formulation characteristics:

Component or characteristic	Claimed range or requirement
Naloxone or pharmaceutically acceptable salt	About 8% to about 12% w/w
Water	About 35% to about 85% w/w
Propylene glycol	About 3% to about 7% w/w
Ethanol	About 20% to about 50% w/w
Edetate disodium dihydrate	About 0.005% to about 0.01% w/w
Physical form	Stable liquid spray formulation
Administration	Intranasal and/or sublingual

The ranges are not independent in practice. Because all components are measured by total formulation weight, a commercial formulation must satisfy the 100% mass balance. A formulation containing the midpoint of every stated range would contain approximately 10% naloxone, 60% water, 5% propylene glycol, 35% ethanol, and 0.0075% edetate disodium dihydrate. Those midpoint values total more than 100%, so a formulation cannot use every midpoint simultaneously.

This creates a mathematically constrained claim scope. The broadest practical embodiments will generally use lower values for one or more major solvents when another component approaches the upper end of its range.

Does the claim require naloxone base or naloxone hydrochloride?

No. Claim 1 covers naloxone and a pharmaceutically acceptable salt. The claim text supplied does not limit the active ingredient to naloxone base, naloxone hydrochloride, naloxone hydrochloride dihydrate, or another specific salt.

The interpretation of “8% to 12% w/w naloxone or a pharmaceutically acceptable salt thereof” can affect infringement analysis. The specification and prosecution history would be important in determining whether the percentage is calculated on:

1. The mass of the selected naloxone salt;
2. The naloxone active moiety equivalent; or
3. The total mass of the salt, including counterions and water of hydration.

A product positioned outside the claimed range on a salt-mass basis may still face risk if the patent owner argues that the claim is calculated by naloxone equivalent. That issue requires review of the patent specification and prosecution record.

How broad is the “stable liquid spray formulation” limitation?

“Stable” is a substantive limitation, not merely a product description. The patent specification would normally define stability through parameters such as:

• Assay retention over time;
• Degradation-product limits;
• Appearance;
• pH drift;
• Precipitation;
• Color change;
• Container compatibility;
• Spray performance; and
• Storage temperature and duration.

The supplied claims do not state the stability test, acceptance criterion, storage condition, or duration. That leaves room for claim-construction disputes concerning whether stability is:

• An inherent property of every formulation within the claimed ranges;
• A requirement demonstrated by testing;
• A result-effective limitation defined elsewhere in the patent; or
• A functional limitation subject to written-description and enablement challenges.

A competitor should not assume that avoiding a stated concentration range eliminates all risk if its formulation has substantially identical ingredients and produces the same stability profile. Conversely, the patent owner may have difficulty proving infringement if the stability requirement depends on an undefined test protocol.

What do claims 2, 3, and 4 add?

Claim 2: simple solution form

Claim 2 narrows claim 1 to a simple solution. This generally excludes suspensions, emulsions, liposomal systems, multiparticulate dispersions, and other heterogeneous delivery systems.

A product containing naloxone fully dissolved in the water, ethanol, and propylene glycol vehicle would present higher claim 2 risk than a product using a suspension or another non-solution system, assuming all claim 1 ranges are met.

Claim 3: pH from approximately 2 to 7

Claim 3 covers acidic through near-neutral formulations. A formulation with a pH below 2 or above 7 could avoid claim 3 while remaining within claim 1, assuming the claim 1 composition and stability limitations are met.

The pH range does not require a specific buffer. The claim therefore potentially covers formulations adjusted with hydrochloric acid, sodium hydroxide, citrate, phosphate, acetate, or other pH-control systems, subject to the open-ended language of claim 1.

Claim 4: antioxidant

Claim 4 covers an antioxidant selected from a long list, including BHA, BHT, methionine, sodium ascorbate, sodium thiosulfate, thioglycerol, ascorbic acid, ascorbyl palmitate, propyl gallate, alpha-tocopherol, sulfites, cysteine hydrochloride, and glutathione.

The claim is not limited to one antioxidant concentration. It also covers combinations. A formulation using an antioxidant outside the listed group may avoid claim 4 but could remain within claim 1.

What methods of treatment are protected?

Claims 5 through 7 cover administration of the claim 1 formulation through one or both of two routes:

• Intranasal administration;
• Sublingual administration.

Where both routes are used, the claims expressly cover simultaneous, sequential, or concomitant administration.

Claim	Indication	Route scope
5	Opioid dependence	Intranasal, sublingual, or both
6	Opioid overdose	Intranasal, sublingual, or both
7	Congenital insensitivity to pain with anhidrosis	Intranasal, sublingual, or both

The method claims do not recite a dose, dosing interval, number of administrations, age group, opioid identity, severity threshold, or clinical endpoint.

Because the methods incorporate “the formulation of claim 1,” a product must first satisfy the composition limitations before use can infringe the method claims. A formulation outside claim 1 may avoid claims 5 through 7 even if it is administered for the same indication.

What are the principal design-around strategies?

The most direct design-around options target the numerical ranges or the required excipient combination.

Design-around approach	Potential effect
Use naloxone below 8% or above 12% w/w	Avoids the literal naloxone limitation
Omit ethanol	Avoids claim 1 if ethanol is required as written
Omit propylene glycol	Avoids claim 1
Replace edetate disodium dihydrate with another chelator	Avoids the express edetate limitation
Use a non-solution dosage form	May avoid claim 2, but not necessarily claim 1
Use pH outside 2 to 7	May avoid claim 3, but not claims 1 or 2
Use a non-listed antioxidant	May avoid claim 4
Use buccal, oral, injectable, or another route	May avoid method claims 5 through 7
Use a different naloxone concentration basis	Creates a claim-construction issue rather than a reliable clearance

The strongest design-around is usually a formulation that removes one required ingredient, especially ethanol, propylene glycol, or edetate disodium dihydrate. Changing only an inactive ingredient while retaining all five required components may not provide sufficient protection.

Doctrine-of-equivalents risk remains relevant where a substitute performs substantially the same function in substantially the same way to achieve substantially the same result. Prosecution-history estoppel may restrict that theory if the patentee narrowed the claims to obtain allowance.

How does this patent compare with commercial naloxone products?

The principal commercial naloxone products use different regulatory and formulation profiles. The most relevant products include Narcan nasal spray, Kloxxado nasal spray, RiVive nasal spray, Nyxoid in certain non-U.S. markets, and injectable products such as Zimhi and generic naloxone injections.

Product or category	Route	Relevance to US 10,722,510
Narcan nasal spray	Intranasal	Competing naloxone spray; formulation and Orange Book status must be evaluated separately
Kloxxado	Intranasal	Competing high-dose naloxone spray; may have distinct formulation and device patents
RiVive	Intranasal	Competing naloxone spray with separate FDA approval and intellectual-property profile
Generic naloxone injection	Intramuscular, intravenous, or subcutaneous	Generally outside the claimed spray and route profile
Zimhi	Intramuscular or subcutaneous	Different delivery system and formulation architecture
Sublingual naloxone products	Sublingual	Potentially relevant if the product uses the claimed composition

US Patent 10,722,510 is not automatically a patent on all naloxone nasal sprays. Its composition limits are materially narrower than the product category. A competing nasal spray that uses an aqueous formulation without ethanol or propylene glycol would not ordinarily satisfy claim 1.

What is the FDA and Orange Book significance?

The patent claims supplied do not identify an approved product, NDA number, reference listed drug, or Orange Book listing. Patent ownership and FDA approval are separate questions.

For Orange Book purposes, the key issues are:

1. Whether the patent was submitted to FDA for an approved drug product;
2. Whether the patent claims the drug substance, drug product, or method of use;
3. Whether FDA accepted the listing;
4. Whether the approved label corresponds to the claimed indications and routes; and
5. Whether the listed patent is subject to a Paragraph IV certification.

A formulation patent may be Orange Book listed only when it meets the statutory and FDA listing requirements applicable to the approved drug. A patent that covers an unapproved formulation, a development-stage product, or a formulation not corresponding to the approved NDA may have no Orange Book effect.

The patent alone therefore does not establish an automatic Paragraph IV barrier. A generic applicant faces a Paragraph IV issue only if the relevant patent is listed against the reference product and the applicant certifies that the patent is invalid, unenforceable, or not infringed.

What Paragraph IV and litigation risks exist?

A Paragraph IV challenge would be most relevant for an ANDA or 505(b)(2) applicant seeking approval of a naloxone product that uses the claimed excipient system.

Potential invalidity and noninfringement positions include:

• The formulation does not contain every required component;
• One or more components fall outside the claimed ranges;
• The product is not stable under the patent’s applicable definition;
• The product is not a spray formulation;
• The product is not a simple solution;
• The pH falls outside the dependent range;
• The selected antioxidant is not within claim 4;
• The method indication or administration route is not practiced;
• The claims lack written description or enablement across the full concentration ranges;
• The claims are anticipated by an earlier naloxone solvent system; or
• The claimed combination would have been obvious based on prior art concerning naloxone stability, ethanol-water vehicles, glycols, and chelating agents.

The strongest obviousness attack would likely focus on whether each excipient performed a predictable function and whether prior art taught combining the components at overlapping concentrations. The patentee would likely rely on unexpected stability, reduced degradation, improved spray performance, or other comparative data.

No litigation, settlement, or Paragraph IV event can be established from the claim text alone. Those matters require a review of PACER, FDA patent-listing records, ANDA litigation notices, and the patent’s prosecution history.

When does US Patent 10,722,510 lose exclusivity?

The patent’s issue date was July 28, 2020. Its exact expiration date cannot be determined from the claims supplied because patent term depends on the earliest effective nonprovisional filing date, priority claims, patent term adjustment, terminal disclaimers, and any applicable patent term extension.

The ordinary US patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments. A patent issued from a continuation may therefore expire on the same date as an earlier family member rather than 20 years after its own filing date [35 U.S.C. § 154].

The relevant exclusivity analysis is:

Exclusivity component	Application to this patent
Patent term	Depends on earliest effective nonprovisional filing date
Patent term adjustment	May extend the nominal term
Patent term extension	Possible only if statutory regulatory requirements are met
Orange Book exclusivity	Depends on listing against an approved NDA
New chemical entity exclusivity	Not applicable to naloxone as an established active ingredient
Orphan exclusivity	Not established by the claims
Pediatric exclusivity	Not established by the claims
Data exclusivity	Separate from this formulation patent

A patent expiration date should not be used as a substitute for FDA exclusivity analysis. Generic entry can be blocked by other listed patents, regulatory exclusivity, injunctions, or settlement terms even after this patent expires.

How strong is the patent estate?

Based on the supplied claims, the estate has a focused formulation position but limited breadth outside the specified vehicle.

Strengths

• Five-part compositional definition gives the patentee multiple infringement points.
• Open “comprising” language permits additional excipients.
• The claims cover both intranasal and sublingual delivery.
• Method claims address opioid overdose and opioid dependence.
• Claim 4 creates additional coverage for formulations using listed antioxidants.
• The composition is potentially relevant to both branded and follow-on products.

Weaknesses

• The composition requires a specific combination of ethanol and propylene glycol.
• The concentration ranges may be vulnerable to overlap with prior-art formulation disclosures.
• The mass-balance requirement limits the practical combinations within the broad ranges.
• “Stable” may require a fact-intensive claim-construction and testing dispute.
• The patent does not, from the supplied claims, cover all naloxone sprays or all naloxone dosage forms.
• The treatment claims depend on infringement of the narrow composition claim.
• The claim set does not recite a device, actuator, plume, droplet-size distribution, dose volume, or packaging system.

The estate is strongest against a product intentionally designed around the same solvent and chelator system. It is materially weaker against aqueous naloxone sprays, injectable products, solid dosage forms, and delivery systems that omit one of the required excipients.

What is the likely generic-launch risk?

The patent presents moderate formulation-specific risk rather than category-wide naloxone risk.

Product strategy	Risk under US 10,722,510
Same ethanol, propylene glycol, and edetate system within claimed ranges	High
Same active ingredient and route but different vehicle	Low to moderate
Nasal spray without ethanol	Low under literal claim 1
Nasal spray without propylene glycol	Low under literal claim 1
Injectable naloxone	Low
Sublingual spray using claimed composition	High
Sublingual product using a different composition	Low to moderate
Product using a suspension rather than a solution	Claim 2 risk reduced; claim 1 requires separate analysis
Product using a pH outside 2 to 7	Claim 3 risk reduced; claim 1 remains relevant

A generic applicant should conduct a quantitative formulation mapping exercise against every limitation, including salt identity, percentage basis, stability protocol, spray form, route, and antioxidant selection. A noninfringement position should be supported by batch records and analytical data rather than nominal formulation descriptions.

Key Takeaways

• US Patent 10,722,510 is primarily a narrow naloxone liquid formulation patent.
• Claim 1 requires naloxone, water, propylene glycol, ethanol, and edetate disodium dihydrate within specified ranges.
• The claims do not cover every naloxone nasal spray.
• Claims 5 through 7 cover intranasal and sublingual treatment methods for opioid dependence, opioid overdose, and congenital insensitivity to pain with anhidrosis.
• The principal design-around options are removing ethanol, propylene glycol, or edetate disodium dihydrate, or moving outside the claimed concentration structure.
• Orange Book listing, Paragraph IV exposure, litigation, settlement protection, and exact expiration require records beyond the claim language.
• The patent’s commercial risk is highest for a follow-on product that copies the claimed solvent and chelator system.

FAQs About US Patent 10,722,510

Does US Patent 10,722,510 cover Narcan?

The patent does not automatically cover Narcan. Coverage depends on whether the Narcan formulation contains every limitation of claim 1 and satisfies the stability and spray requirements. FDA approval and Orange Book listing are separate issues.

Can a naloxone nasal spray avoid the patent by changing only the pH?

Changing the pH may avoid dependent claim 3 if the pH falls outside approximately 2 to 7. It does not avoid claim 1, which has no stated pH limitation.

Does using naloxone hydrochloride instead of naloxone base avoid the patent?

No. Claim 1 expressly covers naloxone and pharmaceutically acceptable salts. The relevant issue is how the percentage limitation is calculated.

Does the patent cover naloxone injection products?

The composition claim requires a liquid spray formulation for intranasal and/or sublingual administration. A conventional injectable product would generally fall outside the claimed delivery profile, although the complete patent family and specification should be reviewed for unasserted claims.

Is an antioxidant required?

No. Antioxidants are optional under claim 4. A formulation can infringe claim 1 without containing an antioxidant if it satisfies the independent composition claim.

References

1. United States Patent and Trademark Office. (2020). U.S. Patent No. 10,722,510 B2. Claims 1-7.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.

3. U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.

4. U.S. Food and Drug Administration. (2024). Approved drug product labeling for naloxone hydrochloride nasal spray. Drugs@FDA.

5. Patent Act, 35 U.S.C. § 154. (2024). Patent term and adjustment provisions.

6. Hatch-Waxman Amendments, 21 U.S.C. §§ 355 and 505. (2024). Abbreviated applications, patent certifications, and patent listing provisions.

Drugs Protected by US Patent 10,722,510

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	10,722,510		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 10,722,510

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2017312811
Canada	2954370
Canada	3033897
China	109922805
European Patent Office	3177146
European Patent Office	3500261
Japan	2017519803