United States Patent 9,687,495: Scope, Claims, Expiration, and Intranasal Benzodiazepine Patent Landscape

U.S. Patent No. 9,687,495 protects intranasal benzodiazepine products and administration methods that use methoxy-polyethylene glycol, or mPEG, as a formulation component. The broadest protection covers a nasal spray system containing a benzodiazepine formulation with mPEG having the structure CH3O-(CH2CH2O)n-H, where n is 1 to 25. The claims are particularly relevant to midazolam nasal spray products, including products using mPEG 350 or mPEG 550.

The patent has two independent claim categories:

A product-system claim covering a nasal spray device loaded with the formulation.
A method claim covering intranasal administration of the formulation to a mammal.

The patent does not require every formulation to contain midazolam, a specific device architecture, a particular dose, or a specific concentration. Those limitations appear only in dependent claims.

What does U.S. Patent 9,687,495 protect?

The patent protects the combination of an intranasal delivery platform and a liquid benzodiazepine formulation containing mPEG. Claim 1 is the principal product claim.

Claim 1: system claim

Claim 1 requires all of the following:

Required element	Scope
Nasal spray device	Any device meeting the claim's functional description
Liquid pharmaceutical composition	The composition must be formulated for intranasal administration
Benzodiazepine	A benzodiazepine, pharmaceutically acceptable salt, or combination
mPEG	Methoxy-polyethylene glycol of the specified formula
mPEG chain length	n must be 1 to 25

The claim uses "comprising." That term generally permits additional ingredients and additional device components. A competing product could therefore contain buffers, preservatives, surfactants, water, permeation enhancers, stabilizers, or other excipients without avoiding the claim, provided it still contains the required benzodiazepine and mPEG elements.

Claim 1 does not expressly require:

Midazolam;
A particular benzodiazepine concentration;
A particular mPEG concentration;
Water;
A specific pH;
A specific viscosity;
Single-dose packaging;
Multi-dose packaging;
A specified spray volume; or
A particular nasal applicator design.

Claim 15: method claim

Claim 15 covers administering to a mammalian intranasal mucosal membrane a liquid composition containing:

A therapeutically effective amount of a benzodiazepine or its pharmaceutically acceptable salt; and
mPEG with n from approximately 1 to approximately 25.

The method claim is materially broader than the product-system claims in one respect: it does not require use of a nasal spray device. Administration could potentially be performed through another intranasal delivery mechanism if the accused conduct satisfies the remaining limitations.

The method claim also does not expressly require a specific disease, seizure indication, rescue-treatment protocol, or patient population. Claim 17 narrows the mammal to a human.

How do the dependent claims narrow the patent's scope?

The dependent claims create several separate infringement positions around formulation composition, device configuration, and physical properties.

Claim	Limitation
2	Device contains a single-dose amount
3	Device contains a multi-dose amount
4	Benzodiazepine is midazolam or a salt
5	n is 2 to 15
6	n is 3 to 15
7	mPEG is mPEG 350, mPEG 550, or both
8	Benzodiazepine is approximately 0.001% to 20% w/v
9	mPEG is approximately 0.5% to 70% v/v
10	mPEG is 1% to 60% v/v
11	Composition contains water
12	Viscosity is 1.5 cP to 60 cP at 20°C
13	Viscosity is 5 cP to 25 cP at 20°C
14	pH is 4.5 to 8.5
16	Administration volume is 50 to 300 µL
17	Mammal is a human
18	n is 2 to 12

Claims 5 and 6 are nested restrictions of claim 1. Claims 12 and 13 are also nested viscosity ranges. A formulation with viscosity between 5 cP and 25 cP would fall within both claims if all other limitations are met.

Claim 7 is commercially important because it identifies mPEG 350 and mPEG 550 by name. A product using either material may present a straightforward claim-mapping issue if it also contains midazolam and is delivered intranasally.

What formulations are protected by U.S. Patent 9,687,495?

The protected formulation class is wider than a single commercial midazolam formulation.

Benzodiazepine scope

The independent claims cover the benzodiazepine genus. Claim 4 specifically identifies midazolam, but claim 1 is not limited to midazolam. Depending on the patent's specification and claim-construction record, the genus may encompass benzodiazepines such as:

Midazolam;
Diazepam;
Lorazepam;
Clonazepam;
Alprazolam;
Oxazepam; and
Other compounds meeting the ordinary meaning of benzodiazepine.

The independent claim requires a therapeutically effective amount but does not specify a therapeutic indication. A product using a different benzodiazepine could therefore implicate claim 1 or claim 15 without falling within claim 4.

mPEG scope

The claimed mPEG has the formula:

CH3-O-(CH2CH2O)n-H

The variable n ranges from 1 to 25 in the independent claims. The dependent claims narrow that range to:

2 to 15;
3 to 15; and
2 to 12.

mPEG 350 and mPEG 550 are expressly recited in claim 7. Because commercial mPEG materials can contain distributions of molecular weights and chain lengths, the composition of a particular excipient lot may become important in an infringement analysis. The relevant question is whether the material used in the product falls within the claimed chemical and molecular-weight scope, not merely whether the supplier labels it "mPEG."

Concentration, pH, viscosity, and volume

The patent creates additional protection around formulation performance parameters:

Benzodiazepine: approximately 0.001% to 20% w/v;
mPEG: approximately 0.5% to 70% v/v, or 1% to 60% v/v;
Viscosity: 1.5 cP to 60 cP, or 5 cP to 25 cP, at 20°C;
pH: 4.5 to 8.5; and
Administration volume: 50 µL to 300 µL.

These ranges can complicate design-around strategies. A product outside one dependent range may still fall within claim 1 or claim 15. Avoiding a dependent claim does not avoid the independent claim unless the formulation also removes or changes a required independent limitation.

How does the patent apply to midazolam nasal spray?

Midazolam nasal spray is the clearest commercial application of the patent. A product containing midazolam, mPEG 350 or mPEG 550, and a nasal spray device could potentially satisfy:

Claim 1, as a system;
Claim 4, as a midazolam-specific system;
Claim 7, if the mPEG is mPEG 350 or mPEG 550;
Claims 8 through 14, depending on composition data;
Claim 15, as an administration method;
Claim 16, if the delivered volume is 50 to 300 µL; and
Claim 17, when administered to a human.

A commercial product does not need to practice every dependent claim to infringe the patent. Infringement of claim 1 or claim 15 would be sufficient for liability if the claim is valid and enforceable.

The patent is therefore more significant for a midazolam nasal product than a patent limited to a specific brand name, seizure indication, or applicator. Its core combination is the active ingredient class plus the mPEG formulation vehicle plus intranasal delivery.

What is the FDA and Orange Book relevance of U.S. Patent 9,687,495?

Nayzilam, a midazolam nasal spray, was approved by the FDA in May 2019 under NDA 211321. The product is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern in patients with epilepsy six years of age and older (U.S. Food and Drug Administration, 2019).

U.S. Patent 9,687,495 is associated with the intranasal midazolam product patent estate and is relevant to Orange Book analysis. An Orange Book listing can require an abbreviated new drug application applicant to address the patent through:

A Paragraph III certification, accepting delayed approval until patent expiration;
A Paragraph IV certification, asserting that the patent is invalid, unenforceable, or not infringed; or
A statement that the patent is not relevant to the proposed generic product.

The regulatory significance depends on the patent's listing status, the NDA reference product, and any later patent listings covering the formulation, device, or method of use. The patent itself does not establish FDA exclusivity. Patent term and regulatory exclusivity are separate rights.

When does U.S. Patent 9,687,495 lose exclusivity?

The patent's expiration date must be calculated from the earliest effective nonprovisional or international filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable statutory changes. A provisional priority date does not itself determine the 20-year patent term.

The patent issued on June 27, 2017, as U.S. Patent No. 9,687,495 B2. Its practical exclusivity analysis should separate three dates:

Exclusivity component	Relevance
Patent term	Determines the ordinary enforceable life of the patent
FDA regulatory exclusivity	Determines when certain ANDA or 505(b)(2) submissions may be approved
Orange Book listing period	Determines whether an ANDA applicant must address the listed patent

For a generic applicant, the operative timing is not simply the patent's nominal expiration. A Paragraph IV filing can trigger litigation and a potential 30-month approval stay under the Hatch-Waxman Act. A first Paragraph IV applicant may also seek 180-day exclusivity if statutory conditions are satisfied.

Which companies are challenging the patent?

A complete challenge analysis requires review of:

USPTO Patent Center;
PACER and district-court dockets;
ANDA litigation filings;
FDA Paragraph IV notice activity;
PTAB proceedings; and
Orange Book updates.

The supplied claim text does not identify a Paragraph IV challenger, ANDA applicant, inter partes review, post-grant review, or federal litigation involving U.S. Patent 9,687,495. No challenger should be inferred solely from the existence of the patent or the approval of Nayzilam.

The absence of a known challenge in a limited record does not eliminate future generic litigation risk. A competitor could challenge the patent through an ANDA Paragraph IV certification, a declaratory-judgment action, or a validity challenge in a later infringement case.

What patent litigation affects intranasal midazolam?

The principal litigation questions for an intranasal midazolam competitor are likely to involve:

Whether the proposed formulation contains mPEG within the claimed n range.
Whether the commercial excipient qualifies as mPEG 350 or mPEG 550.
Whether the device and loaded composition form the claimed system.
Whether the method claim is infringed by the proposed label.
Whether the claims are enabled across the full benzodiazepine and mPEG genus.
Whether the viscosity, pH, concentration, and volume limitations are met.
Whether the patent is invalid for anticipation or obviousness over earlier intranasal benzodiazepine formulations.

The system claims may present proof issues because infringement requires the combination of the nasal device and the claimed composition. The method claims may present induced-infringement issues if a generic label instructs administration of a composition meeting the claimed limitations.

How strong is the patent estate?

The patent has moderate-to-strong blocking potential against products that use the same formulation strategy, but its strength depends on claim validity and the precise composition of the accused product.

Strengths

Claim 1 covers a broad benzodiazepine genus.
The mPEG chain-length range is broad.
The claims cover both the packaged system and the administration method.
Midazolam is expressly recited.
mPEG 350 and mPEG 550 are expressly recited.
The claims include common commercial parameters such as pH, viscosity, concentration, and spray volume.
The open-ended "comprising" language permits additional excipients.

Vulnerabilities

Broad genus claims may face written-description and enablement scrutiny.
Prior-art searches may identify earlier intranasal benzodiazepine compositions containing PEG derivatives.
The n-range may create analytical disputes for heterogeneous commercial mPEG materials.
Dependent claims with concentration and viscosity ranges may be vulnerable to routine-optimization arguments.
A competitor may design around the patent by using a different solubilizer, co-solvent, polymer, or delivery system.
The method claims may depend on the wording and scope of the proposed product label.

The strongest commercial claims are likely claims 1, 4, 7, 15, and 16 when the accused product uses midazolam, mPEG 350 or mPEG 550, a nasal device, and a 50-300 µL administration volume.

What generic launch scenarios exist?

Scenario 1: Paragraph III delay

A generic applicant certifies that it will not market until the patent expires. This avoids immediate patent litigation but postpones approval or commercial launch.

Scenario 2: Paragraph IV challenge

A generic applicant alleges that the patent is invalid, unenforceable, or not infringed. The NDA holder may sue within 45 days, potentially creating a 30-month FDA approval stay.

Scenario 3: Formulation design-around

A competitor uses a non-mPEG excipient or a different delivery vehicle. This could avoid the core claims if the product does not contain the claimed methoxy-polyethylene glycol.

Scenario 4: Different benzodiazepine

A product using another benzodiazepine would remain within the independent genus claims if it uses the claimed mPEG formulation. It would avoid the midazolam-specific dependent claim but not necessarily claims 1 or 15.

Scenario 5: Label-based method challenge

A generic label omits or changes the claimed administration instructions. That could reduce induced-infringement exposure for the method claims, although the system claims would remain relevant if the device and composition are sold together.

How does U.S. Patent 9,687,495 compare with other intranasal benzodiazepine patents?

The patent should be analyzed as one part of a layered estate:

Patent category	Typical subject matter	Relevance
Core formulation	Benzodiazepine plus mPEG or other excipient	Directly implicated by U.S. 9,687,495
Device	Spray pump, actuator, metering chamber, nozzle	Can create separate device barriers
Dosing	Single-dose or repeat-dose administration	May delay substitutable generic products
Method of use	Seizure rescue, cluster seizures, status epilepticus	Can affect label-based generic entry
Manufacturing	Mixing, filling, sterilization, container closure	Can create process or CMC barriers
Stability	Shelf-life and impurity control	Can limit practical design-around options
Regulatory exclusivity	NDA exclusivity and pediatric exclusivity	Independent of patent expiration

U.S. Patent 9,687,495 is strongest where the commercial product's formulation is substantially copied. It is less restrictive against a competitor that uses a different excipient system and a materially different intranasal delivery approach.

Does the patent protect manufacturing methods?

The supplied claims do not claim manufacturing steps. They claim a system, a composition contained in a device, and a method of intranasal administration. Manufacturing activity could still create infringement exposure if the manufacturing process produces or sells a system meeting claim 1, but the patent does not independently require:

A particular mixing sequence;
A filling process;
A sterilization method;
A container-closure system;
A manufacturing site; or
A specific quality-control test.

Manufacturing barriers may arise from other patents, trade secrets, supplier controls, regulatory comparability requirements, or device qualification rather than from the supplied claims.

What geographic coverage does the patent provide?

U.S. Patent 9,687,495 provides territorial protection in the United States. It does not directly block sales in Canada, Europe, Japan, China, or other markets. International protection would require separate national or regional patents in the corresponding patent family.

A global freedom-to-operate review should identify:

PCT applications;
National-stage filings;
Granted foreign counterparts;
Continuations and divisionals;
Patent-term adjustments;
Patent-term extensions;
Supplementary protection certificates; and
Local Orange Book or equivalent regulatory listings.

Key Takeaways

U.S. Patent 9,687,495 covers intranasal benzodiazepine systems and administration methods using mPEG.
Claim 1 is the central product claim and requires a nasal spray device plus a liquid benzodiazepine/mPEG composition.
Claim 15 covers intranasal administration without expressly requiring a spray device.
Midazolam is specifically claimed, but the independent claims cover a broader benzodiazepine genus.
mPEG 350 and mPEG 550 are expressly identified in claim 7.
The patent includes additional protection around drug concentration, mPEG concentration, viscosity, pH, and administration volume.
A product can avoid a dependent claim and still infringe an independent claim.
The patent is highly relevant to midazolam nasal spray products, including Nayzilam.
Generic entry may require a Paragraph III or Paragraph IV certification depending on Orange Book status and the proposed product.
The principal design-around path is replacement of mPEG with a formulation vehicle outside the claimed chemical scope.
Device, method-of-use, manufacturing, and stability patents may create additional barriers beyond this patent.

FAQs

Can a midazolam nasal spray avoid U.S. Patent 9,687,495 by using mPEG with a different molecular weight?

Potentially, but only if the material falls outside the claimed mPEG structure and the n ranges. A product outside claim 7 could still fall within claim 1 if its mPEG chain length remains within n=1 to 25.

Does using a multi-dose nasal spray avoid the patent?

No. Claim 3 expressly covers a multi-dose amount. Single-dose and multi-dose configurations are separately claimed.

Does the patent cover oral or injectable midazolam?

The supplied claims are directed to intranasal systems and intranasal administration. An oral or injectable midazolam product would not meet the intranasal delivery limitations of these claims.

Can a generic applicant challenge only the midazolam claim?

Yes. A challenger may target claim 4 specifically, but invalidating or avoiding claim 4 would not necessarily eliminate exposure under broader claims 1 or 15.

Is FDA approval blocked automatically until the patent expires?

No. Approval timing depends on the ANDA certification, any Paragraph IV litigation, the 30-month stay, regulatory exclusivities, and the final patent and court outcomes.

References

U.S. Patent No. 9,687,495 B2. (2017). Intranasal administration of benzodiazepines. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2019). Nayzilam (midazolam) nasal spray prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
United States Code, 35 U.S.C. §§ 154, 271, 282, 283, 284, 285.
United States Code, 21 U.S.C. § 355(j).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Ucb Inc	NAYZILAM	midazolam	SPRAY;NASAL	211321-001	May 17, 2019		RX	Yes	Yes	9,687,495	⤷ Start Trial	Y			ACUTE TREATMENT OF INTERMITTENT, STEREOTYPIC EPISODES OF FREQUENT SEIZURE ACTIVITY (I.E., SEIZURE CLUSTERS, ACUTE REPETITIVE SEIZURES) THAT ARE DISTINCT FROM A PATIENT'S USUAL SEIZURE PATTERN IN PATIENTS WITH EPILEPSY 12 YEARS OF AGE AND OLDER	⤷ 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

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Iceland	85932007	Jan 19, 2007

Details for Patent: 9,687,495

Which drugs does patent 9,687,495 protect, and when does it expire?

Summary for Patent: 9,687,495