United States Patent 8,809,322: Scope, Claim Construction, and Intranasal Midazolam Patent Landscape

US Patent 8,809,322 protects liquid intranasal midazolam compositions containing methoxy-polyethylene glycol, or mPEG, within a defined molecular-weight range. The independent claim is composition-based and uses “comprising,” creating an open formulation scope. The patent does not claim every intranasal midazolam product. A potentially infringing product must contain midazolam or a permitted salt, an mPEG meeting the claimed structural range, and a liquid formulation intended for intranasal administration.

The strongest claim elements are the combination of intranasal liquid delivery, midazolam, and methoxy-PEG with an ethylene oxide chain corresponding to n=2 to 12. The dependent claims narrow the formulation by adding water, PEG 200-400, propylene glycol, specific mPEG grades, or specified midazolam concentration ranges. The claims do not require a particular device, spray volume, pH, preservative, buffer, indication, or clinical outcome. (U.S. Patent No. 8,809,322, 2014)

What does United States Patent 8,809,322 cover?

The patent covers a liquid pharmaceutical composition for intranasal administration containing two mandatory components:

A therapeutically effective amount of midazolam, a pharmaceutically acceptable midazolam salt, or both.
Methoxy-polyethylene glycol having the formula H3C-O-(CH2CH2O)n-H, where n is 2 to 12.

The independent claim is not limited to a particular concentration, dosage, disease, patient group, nasal device, or formulation volume. The claim is also not limited to midazolam hydrochloride, although that is the clinically common salt form.

Claim 1 construction

Claim element	Scope
“A liquid pharmaceutical composition”	Requires a liquid composition, not a dry powder, tablet, capsule, implant, or neat solid
“Formulated for intranasal administration”	Requires formulation suitability or intended use for nasal delivery
“Therapeutically effective amount”	Requires an amount capable of producing a therapeutic effect; the claim does not define one fixed dose
“Midazolam, a pharmaceutically acceptable salt thereof or combinations thereof”	Covers free midazolam, acceptable salts such as midazolam hydrochloride, or mixtures
“A methoxy-polyethylene glycol”	Requires an mPEG species or composition within the claimed structural definition
“n is a number in the range of 2 to 12”	Defines the ethylene oxide repeat-unit range for the claimed mPEG

The claim uses “comprising.” That term generally permits additional ingredients unless they eliminate a required claim element or otherwise alter the claimed composition. A formulation can therefore contain water, buffers, tonicity agents, preservatives, surfactants, additional glycols, flavoring agents, or other excipients without avoiding claim 1 solely because those ingredients are present.

How do claims 2 through 10 narrow the patent scope?

Claims 2 through 10 create narrower fallback positions but do not expand claim 1.

Claim	Additional limitation	Commercial significance
1	mPEG with n=2-12	Broadest composition claim
2	n=3-10	Excludes mPEG species corresponding to n=2 or n=11-12
3	Water	Covers aqueous compositions
4	mPEG 350	Targets a named mPEG grade
5	mPEG 550	Targets a higher-molecular-weight mPEG grade
6	PEG 200, 300, or 400	Covers combinations of mPEG with conventional PEG
7	Propylene glycol	Covers mPEG/propylene-glycol systems
8	Midazolam at about 0.0001% to about 50% w/v	Extremely broad concentration range
9	Midazolam at about 0.001% to about 20% w/v	Narrower concentration range
10	Therapeutic agent is midazolam	Excludes a formulation relying only on a salt or combination under the claim’s wording

Claims 4 and 5: mPEG 350 and mPEG 550

Commercial mPEG products are commonly identified by approximate average molecular weight. The claimed chemical formula is based on an integer or numerical range for n, while commercial mPEG 350 and mPEG 550 may contain molecular-weight distributions rather than one uniform molecular species.

That creates a claim-construction issue. A product labeled mPEG 350 or mPEG 550 may need to be assessed by its actual composition, average molecular weight, molecular-weight distribution, and the applicable interpretation of “comprises.” A commercial grade should not be treated as automatically outside the claim merely because its label uses an average molecular weight.

Claims 8 and 9: concentration limitations

The concentration range in claim 8 runs from approximately 0.0001% to 50% w/v. Claim 9 narrows that range to approximately 0.001% to 20% w/v.

For a 0.1 mL nasal spray, the claim 9 range corresponds approximately to:

Concentration	Midazolam amount per 0.1 mL
0.001% w/v	0.001 mg
0.1% w/v	0.1 mg
1% w/v	1 mg
5% w/v	5 mg
20% w/v	20 mg

The calculation assumes the concentration is expressed as grams per 100 mL and the delivered volume is exactly 0.1 mL. The claims themselves do not impose a spray volume.

What formulation design-around options exist?

A formulation that omits mPEG is the clearest design-around route because mPEG is a required element of claim 1 and every dependent claim. A formulation containing midazolam in water, saline, propylene glycol, PEG 200-400, or another vehicle may avoid these claims if it contains no qualifying mPEG.

Potential design-around variables include:

Using a non-methoxylated PEG rather than mPEG.
Using a nasal formulation with no PEG-type excipient.
Using a solid, powder, gel, or other non-liquid formulation, subject to the scope of other patent claims.
Using an active ingredient other than midazolam.
Using a route other than intranasal administration.
Using an mPEG outside the claimed molecular range, subject to equivalence and other patent rights.
Using a formulation in which the relevant mPEG is not present in the finished pharmaceutical composition.

The fifth and sixth approaches require care. Changing the route or excipient can avoid literal infringement of this claim set while remaining exposed to other patents covering intranasal midazolam, spray devices, dosing regimens, pH control, permeation enhancement, or manufacturing processes.

What patents protect intranasal midazolam beyond Patent 8,809,322?

The relevant landscape is broader than the mPEG formulation claims. Intranasal midazolam products can be protected by several patent families:

Formulation patents

These may claim:

Midazolam concentration and dose volume
Aqueous or nonaqueous nasal formulations
pH ranges
Osmolality or tonicity
Buffers and stabilizers
Preservative-free formulations
Solubilizers and permeation enhancers
Specific excipient ratios
Chemical stability during storage

Patent 8,809,322 is concentrated on the mPEG excipient platform. It does not, on the face of the supplied claims, require a particular pH, buffer, tonicity profile, or device.

Method-of-use patents

Other patents may claim:

Treating seizure clusters
Rescue treatment for acute repetitive seizures
Treating status epilepticus
Administering a specified dose at specified intervals
Redosing after a defined period
Use in adults, adolescents, or pediatric patients
Administration during impaired consciousness or seizure activity

A company may avoid the composition claims in Patent 8,809,322 yet face method-of-use exposure if it promotes the product for a patented indication or dosing regimen.

Device and delivery-system patents

Nasal delivery patents may cover:

Single-use nasal spray actuators
Metered-dose pumps
Spray plume geometry
Dose uniformity
Priming and actuation mechanisms
Unit-dose containers
Container-closure systems
Device and formulation combinations

Patent 8,809,322 does not require a specific nasal spray device. A product using a different device may still infringe separate device claims.

Manufacturing and process patents

Manufacturing claims can cover:

Dissolution and mixing order
Control of mPEG molecular-weight distribution
Midazolam salt formation
Filtration and aseptic processing
Filling into unit-dose nasal containers
Stability-control procedures
Packaging and storage conditions

These rights can create manufacturing and supply-chain barriers even when a finished formulation avoids the composition claims.

How strong is the patent estate based on the supplied claims?

The claim estate has meaningful breadth but a clear technical boundary.

Strength factor	Assessment
Independent claim breadth	Broad within liquid intranasal midazolam/mPEG formulations
Open-ended language	“Comprising” permits additional ingredients
Active-ingredient coverage	Covers midazolam and pharmaceutically acceptable salts
Excipient limitation	Narrower because qualifying mPEG is mandatory
Device coverage	None apparent from the supplied claims
Method-of-use coverage	None apparent
Concentration coverage	Broad, with claims 8 and 9 providing fallback ranges
Manufacturing coverage	None apparent
Design-around potential	Moderate to high if mPEG can be removed or replaced
Litigation leverage	Strongest against products that publicly identify mPEG 350 or mPEG 550

The patent is strongest when a competitor’s label, formulation dossier, product specification, or manufacturing records identify mPEG 350, mPEG 550, or another mPEG falling within the claimed range. It is weaker against products using only water, saline, conventional PEG, propylene glycol, or alternative solubilizers without qualifying mPEG.

What is the infringement analysis for a competing intranasal midazolam product?

A product-by-product analysis should map the following elements:

Question	Relevance
Is the finished product liquid?	Required by claim 1
Is it intended or formulated for intranasal administration?	Required by claim 1
Does it contain midazolam or an acceptable salt?	Required by claim 1
Does it contain mPEG?	Required by claim 1
Does the mPEG fall within n=2-12?	Determines literal scope of claim 1
Is water present?	Relevant to claim 3
Is the mPEG identified as 350 or 550?	Relevant to claims 4 and 5
Is PEG 200, 300, or 400 present?	Relevant to claim 6
Is propylene glycol present?	Relevant to claim 7
Is midazolam within the stated concentration range?	Relevant to claims 8 and 9
Is the therapeutic agent specifically midazolam?	Relevant to claim 10

The presence of an ingredient in a manufacturing intermediate may not establish infringement if that ingredient is absent from the finished product. Conversely, a low concentration of mPEG may still matter because the supplied claims do not impose a minimum mPEG concentration.

What is the FDA and Orange Book relevance?

Midazolam is an established small-molecule active ingredient. Intranasal midazolam products are regulated through the FDA drug-approval framework, not the biosimilar pathway. A follow-on applicant would generally evaluate an abbreviated new drug application, a suitability petition where applicable, or a full or hybrid regulatory route depending on the reference product and formulation.

FDA regulatory approval and patent clearance are separate questions. FDA approval does not eliminate infringement risk, and patent expiry does not guarantee regulatory substitutability.

For an Orange Book-listed reference product, the relevant patent analysis would distinguish:

Listed formulation patents
Listed method-of-use patents
Regulatory exclusivity
Paragraph IV certifications
Carve-outs or statements under section viii
Any pediatric or other statutory extension
Patent-term adjustment or extension

A patent may be relevant to a product commercially without being listed in the Orange Book, particularly where it covers manufacturing, a broader platform, a device, or a method that is not eligible for listing.

When does Patent 8,809,322 lose exclusivity?

The patent’s precise expiration date cannot be determined from the claims alone. U.S. patent term generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable patent-term extension. (35 U.S.C. § 154)

The issue date was August 19, 2014. The issue date does not control expiration. A reliable term calculation requires the patent’s priority chain, filing dates, continuity data, terminal-disclaimer status, patent-term adjustment, and any patent-term extension recorded by the USPTO. A patent can also cease to be enforceable before its nominal expiration through disclaimer, invalidation, expiration for failure to pay maintenance fees, or other legal events.

Which companies could challenge the patent?

A generic or competing sponsor would typically assess:

Paragraph IV certification if the patent is listed against the relevant reference product
Declaratory-judgment options if listing or litigation conditions are met
Invalidity based on anticipation or obviousness
Written-description and enablement challenges
Claim-construction disputes over mPEG molecular weight and the meaning of n
Noninfringement based on the absence of mPEG or use of a nonqualifying PEG
Regulatory carve-outs for method-of-use claims, if applicable

The supplied claim set presents potential validity issues around the breadth of the mPEG range, the relationship between a defined n value and commercial mPEG mixtures, and whether the claimed combination would have been obvious from prior intranasal midazolam and PEG formulations. Those issues require a prior-art and prosecution-history review rather than claim text alone.

How does this patent compare with conventional intranasal midazolam products?

A conventional aqueous intranasal midazolam product containing midazolam hydrochloride, water, sodium chloride, and acid or buffer but no mPEG would not appear to meet claim 1 as written. The absence of mPEG would be a missing mandatory element.

Product architecture	Apparent exposure under supplied claims
Midazolam + mPEG 350 + water	High
Midazolam + mPEG 550 + water	High
Midazolam + mPEG + propylene glycol	High; claim 7 may apply
Midazolam + mPEG + PEG 400	High; claim 6 may apply
Midazolam + water + saline, no mPEG	Low under this claim set
Midazolam + PEG 400, no mPEG	Lower under this claim set
Midazolam powder for nasal delivery	Low under claim 1’s liquid limitation
Non-midazolam nasal benzodiazepine	Outside the active-agent limitation

Key Takeaways

US 8,809,322 is a composition patent focused on liquid intranasal midazolam containing qualifying mPEG.
Claim 1 is open-ended because it uses “comprising.”
mPEG is the central required element and the clearest design-around target.
Claims 4 and 5 specifically target mPEG 350 and mPEG 550.
Claims 6 and 7 create narrower protection for combinations with PEG 200-400 or propylene glycol.
Claims 8 and 9 cover unusually broad midazolam concentration ranges.
The supplied claims do not cover a specific nasal device, indication, dosing regimen, pH, or manufacturing process.
A standard aqueous intranasal midazolam formulation without mPEG appears outside the literal scope of the supplied claims.
Patent expiry, Orange Book listing, Paragraph IV risk, litigation status, and ownership require the patent’s complete public prosecution and regulatory record.

FAQs

Does US 8,809,322 cover midazolam nasal spray without PEG?

Not on the supplied claim language. Claim 1 requires methoxy-polyethylene glycol. A midazolam nasal spray containing water, saline, buffer, or another excipient but no qualifying mPEG would lack a required claim element.

Is PEG 400 the same as methoxy-PEG?

No. PEG 400 is generally polyethylene glycol, while the claimed excipient is methoxy-polyethylene glycol with one terminal methoxy group. PEG 400 alone does not necessarily satisfy the mPEG limitation, although claim 6 addresses PEG 200, 300, or 400 when used in addition to mPEG.

Does midazolam hydrochloride fall within the patent?

Yes, claim 1 expressly covers a pharmaceutically acceptable salt of midazolam. Midazolam hydrochloride would generally fall within that active-agent category if the other claim elements are present.

Can a formulation avoid the patent by using mPEG outside n=2 to 12?

That may avoid literal infringement of claim 1, but the result depends on the actual molecular composition and any doctrine-of-equivalents analysis. Commercial mPEG grades can contain molecular-weight distributions, so the product’s technical specification is material.

Is this a biosimilar patent issue?

No. Midazolam is a small-molecule drug. A follow-on intranasal midazolam product would generally raise generic-drug and Hatch-Waxman issues, not biosimilar approval under the Public Health Service Act.

References

U.S. Patent No. 8,809,322. (2014). United States Patent and Trademark Office.

35 U.S.C. § 154. Patent term.

Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

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	8,809,322	⤷ 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

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

Details for Patent: 8,809,322

Which drugs does patent 8,809,322 protect, and when does it expire?

Summary for Patent: 8,809,322