United States Patent 12,337,061: Scope, Claim Architecture, and US Patent Landscape for Diazepam Vitamin E Nasal Spray for Acute Recurrent Seizure Activity
Executive summary. US Patent 12,337,061 is a US-method-of-treatment patent that claims nasal spray administration of diazepam in a specific excipient system anchored by vitamin E (USP), dodecyl maltoside (including n-dodecyl-β-D-maltoside forms), benzyl alcohol, and ethanol (including dehydrated ethanol), delivered as a tightly constrained metered volume (100 µL, with ±5% alternatives across dependent claim sets). The claims tie clinical effect to pharmacokinetic performance, especially absolute bioavailability (core windows of 96–97% in Claim 1; 92.5–107.5% in broader variants), and additional PK/PD metrics (Cmax, Tmax, half-life, and AUC). The patent’s practical enforceability concentrates on US prescribing/administering behavior for intermittent/stereotypic increased seizure bouts distinct from other patient seizures, using the claimed nasal dosing regimen and solution composition. The landscape risk for generic entry is driven by whether competitors can design around (i) the excipient package and/or (ii) PK/bioavailability targets and/or (iii) the specific “single spray” vs “single + second nostril spray” regimen. The strongest infringement theories track medical-use administration plus dose-formulation conformity rather than manufacturing per se.
What does US Patent 12,337,061 claim: nasal diazepam excipient-defined method of treatment for intermittent stereotypic seizure bouts?
Short answer: It claims treating intermittent and stereotypic episodes of increased seizure activity in epilepsy patients by administering nasal diazepam via a stable 100 µL metered spray (and in many claim branches, a 100 µL spray to each nostril), using a defined excipient formulation and delivering exposure comparable to IV diazepam, with defined bioavailability, PK metrics, and a clinical outcome set.
Claim scope essentials (what must be present for coverage)
Across the claim set, the independent-method claim elements repeatedly converge on:
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Patient phenotype/endpoint framing
- “Bouts of intermittent and stereotypic episodes of increased seizure activity in an epilepsy patient”
- “Distinguishable from other seizures suffered by the patient”
- Treatment results in one or more of: reduction in severity, reduced probability of repeat seizure, increased interval to next seizure, reduced seizure frequency, combinations.
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Route and device modality
- Nasal administration
- Single metered spray of 100 µL to a nostril (Claim 1 branch)
- Or two sprays of 100 µL each to both nostrils (Claim 5/33/… branch).
- Dependent claims explicitly require “single metered spray.”
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Formulation composition and stability
- Vitamin E (USP): 14.47 mg (or ±5% variants)
- Diazepam: 10 mg (or ±5% variants; note multiple independent claim variants with diazepam at 7.5 mg or 5 mg in the formulation)
- Dodecyl maltoside: 0.25 mg (or ±5%)
- including n-dodecyl-B-D-maltoside / n-dodecyl-β-D-maltoside dependent positions
- Benzyl alcohol: 0.50 mg (or 10.50 mg with the ±5% branches as written)
- Ethanol (including dehydrated ethanol dependent variants)
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Pharmacokinetic performance tying nasal to IV
- Bioavailability windows
- Claim 1: administering a single 100 µL spray achieves 96% to 97% of bioavailability of an equivalent IV diazepam dose.
- Claim 21 and most ±5% branches: achieves 92.5% to 107.5% of IV equivalent bioavailability.
- Claim 32 and Claim 42: “absolute bioavailability is 96% to 97%.”
- Additional PK metrics in dependent form:
- AUC0-∞: 7338 hours·ng/mL (Claim 15/16/28)
- Cmax: 272 ng/mL (Claim 17/18/29)
- Tmax: 1.5 hours (Claim 19/20/30)
- Half-life: about 49.2 hours (Claim 31/41)
- Dependent claim language also includes treatment onset/maintenance:
- “treatment in less than about 5 minutes” (claims under Claim 1/21/33 branches)
- “treatment over about 24 hours.”
Core enabling constraints that shape enforceability
This patent’s enforceability is less about the general idea of nasal diazepam and more about meeting a formula-and-exposure fingerprint:
- Excipients are not generic: vitamin E USP plus a maltoside surfactant plus benzyl alcohol in ethanol.
- Coverage can be avoided by shifting beyond the claimed formulation, volume, or PK target windows (depending on how strictly an adjudicator treats “about” and percent ranges).
- The “distinguishable from other seizures” limitation narrows the method to patient seizures clinically characterized as such, but it is still a practical medical-use lever because it is embedded into the claim text.
How many claims and what is the claim architecture of US Patent 12,337,061?
Short answer: The claim set is a lattice built from a few independent-method compositions (single-nostril; two-nostril), then layered dependent claims that progressively lock in stability, dosing time, PK metrics, and specific ingredient forms (e.g., dehydrated ethanol; specific maltoside stereochemical naming).
High-level mapping of claim branches
Based on the text provided, the independent-method cores include:
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Single nostril, fixed excipient amounts (Claim 1)
- 100 µL single spray
- vitamin E 14.47 mg, diazepam 10 mg, dodecyl maltoside 0.25 mg, benzyl alcohol 0.50 mg, ethanol sufficient quantity
- bioavailability 96–97% vs IV
- clinical effect set
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Two nostril, fixed excipient amounts (Claim 5)
- 100 µL single spray to each nostril (two total sprays)
- same composition and bioavailability 96–97% vs IV
- clinical effect set
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Single nostril, ±5% formulation variability (Claim 21)
- 100 µL ±5% to a nostril
- vitamin E 14.47 mg ±5%, diazepam 10 mg, dodecyl maltoside 0.25 mg ±5%, benzyl alcohol 10.50 mg +/−5% as written, ethanol sufficient quantity
- bioavailability 92.5–107.5% vs IV
- clinical effect set
- dependent: stability, <5 min treatment, ~24 hr treatment, metered spray requirement, dehydrated ethanol, maltoside naming, AUC/Cmax/Tmax, half-life, absolute bioavailability 96–97%
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Two nostril, ±5% formulation variability (Claim 33)
- 100 µL ±5% to first nostril + second nostril, each 100 µL ±5%
- same ±5% scaffold and bioavailability 92.5–107.5% vs IV
- dependent: stability, <5 min treatment, ~24 hr treatment, metered spray, dehydrated ethanol, maltoside naming, Tmax/half-life/absolute bioavailability
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Independent variants with different diazepam amounts (Claims 43 and 53)
- Claim 43: two sprays (±5% scaffold) with diazepam 7.5 mg
- Claim 53: single spray (fixed-style scaffold) with diazepam 5 mg
- Both retain the same overall excipient and nasal stabilization framing and the same “92.5% to 107.5%” bioavailability language as written.
Dependent claim clusters (what each “locks in”)
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Stability
- “stable at 25° C. and 60% relative humidity for at least 3 months” (Claims 2/6/22/34/44/54)
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Time to effect and duration
- “less than about 5 minutes” (Claims 3/7/23/35/45/55)
- “over about 24 hours” (Claims 4/8/24/36/46/56)
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Dosing modality
- “single metered spray” (Claims 9/10/25/26? and Claim 37/47 as written)
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Ingredient specificity
- Ethanol = dehydrated ethanol (Claims 11/12/26/38/48/58)
- Dodecyl maltoside = n-dodecyl-B-D-maltoside / n-dodecyl-β-D-maltoside (Claims 13/14/27/39/49/59)
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PK fingerprint
- AUC0-∞ 7338 hours·ng/mL (Claims 15/16/28)
- Cmax 272 ng/mL (Claims 17/18/29)
- Tmax 1.5 hours (Claims 19/20/30, and Claim 40/50)
- half-life about 49.2 hours (Claims 31/41)
- absolute bioavailability 96–97% (Claim 32/42)
What are the key claim limitations that competitors must avoid to design around US 12,337,061?
Short answer: Competitors have the primary design-around axes of (1) excipient system and/or (2) dose volume/spray regimen and/or (3) bioavailability/PK targets, and second-order axes of (4) stability and (5) specific maltoside naming/sourcing.
1) Excipient package design-around
The claimed formulation is not merely “diazepam nasal spray.” The coverage binds:
- Vitamin E USP at 14.47 mg (or ±5%)
- Dodecyl maltoside at 0.25 mg (or ±5%), specifically including n-dodecyl-B-D-maltoside / n-dodecyl-β-D-maltoside naming in dependent claims
- Benzyl alcohol at a specific mass (as written; fixed branch includes 0.50 mg, ±5% branches show 10.50 mg with the provided claim text)
- Ethanol, including dehydrated ethanol
Most enforceable theory for infringement generally follows “same drug, same route, same formula system, same dosing.”
2) Bioavailability equivalence to IV
The patent includes explicit bioavailability constraints:
- Claim 1: 96–97%
- Claim 21/33 branches: 92.5–107.5%
- Other dependent claims reaffirm absolute bioavailability 96–97%.
This creates a measurable infringement lever. If a competitor can show different systemic exposure relative to IV equivalent diazepam doses under the claimed test conditions, it may avoid the bioavailability-limited limitations.
3) Nasal dosing regimen and volume
The method is tied to:
- 100 µL single spray to a nostril
- or 100 µL + 100 µL across both nostrils
- in some branches with ±5% volume allowance
- plus “single metered spray.”
Switching to a different device volume (or non-metered droplet administration) creates a potential design-around point, depending on whether “+/−5%” and doctrine-of-equivalents arguments apply.
4) Stability and handling
Dependent claims add stability at 25° C. and 60% RH for at least 3 months. A product designed for different shelf-life stress conditions may avoid those dependent limitations, though the independent composition limits remain unless the stability is treated as required.
5) PK fingerprint secondary
AUC0-∞ 7338 hours·ng/mL, Cmax 272 ng/mL, Tmax 1.5 hours, half-life 49.2 hours appear in dependent form in the text provided. For infringement, the competitor must satisfy the particular dependent limitations only if those dependent claims are asserted.
What does the patent landscape look like for US nasal diazepam products treating acute intermittent seizure bouts?
Short answer: Without the full external patent list and Orange Book/FDA product history, the only reliable landscape elements that can be derived from the provided text are the likely competitive risk categories: product-method overlap with nasal diazepam for acute seizure clusters, formulation patents covering excipient systems for bioavailability, and regulatory-entry strategies that attempt to change exposure metrics or excipient selection.
Landscape buckets relevant to litigation or licensing
Even with only the provided claim text, US litigation and licensing for this technology class typically turns on:
- Formulation/excipient patents (vitamin E and surfactant package to drive nasal absorption and IV-like exposure)
- Device and dosing regimen (metered spray volume and single vs bilateral dosing)
- Method-of-treatment patents (acute seizure bout definitions and endpoints)
- PK-based constraints (bioavailability equivalence windows and PK parameter locking)
- Stability and manufacturing conditions (shelf-life and humidity/temperature robustness)
Practical infringement risk for “generic-like” nasal diazepam
A true “copy” strategy is unlikely to succeed without matching:
- vitamin E USP amount,
- maltoside type,
- benzyl alcohol amount,
- ethanol type,
- metered volume, and
- systemic exposure targets.
A “different formulation but same dose” strategy can still trigger method-of-treatment infringement if the administration and exposure constraints align. A “different route” strategy (rectal, buccal, intranasal with different volume) is more likely to change whether the claim is met.
When does US 12,337,061 lose exclusivity or become challengeable via Paragraph IV?
Short answer: This cannot be computed from the claim text alone.
What formulations or dosing variations are explicitly covered by US 12,337,061?
Short answer: The patent covers a narrow set of nasal formulations and regimens with quantified diazepam and excipient masses, including both single-nostril and bilateral nostril dosing, plus explicit constraints on ethanol type and maltoside naming in dependent claims.
Formulation/dose variants present in the claim text
Biosimilar risk
This is a small-molecule diazepam formulation method patent; biosimilar pathways are not the relevant analog. The landscape is generic/small-molecule formulation.
How strong is the patent estate for US nasal diazepam methods: what in the claims drives enforceability?
Short answer: Enforceability is driven by high specificity: defined formulation masses, defined route and volume, and defined bioavailability/PK parameters. Those features reduce the space for generic substitutes that change only inactive ingredients or device volume.
Claim features that increase litigation leverage
- Objective measurable endpoints
- bioavailability percent vs IV,
- AUC/Cmax/Tmax/half-life.
- Concrete dosing details
- 100 µL metered spray,
- single vs bilateral nostril regimen.
- Tightly bound excipient identities
- vitamin E USP,
- dodecyl maltoside with stereochemical naming.
- Safety/effect framing tied to treatment outcomes
- severity/probability/frequency/interval outcomes.
Claim features that can be litigated as limiting
- “Distinguishable from other seizures suffered by the patient” is a clinical characterization. It can become a limitation for proof of patient phenotype and treatment context.
- The “approximately” and ±5% language creates interpretive room about what is “within” a limitation.
Key takeaways
- US Patent 12,337,061 is a method-of-treatment patent covering nasal administration of diazepam with a specific excipient system (vitamin E USP, dodecyl maltoside, benzyl alcohol, ethanol including dehydrated ethanol) and defined systemic exposure to match IV-like bioavailability.
- The claim set is structured around single-nostril (100 µL) and bilateral nostril (100 µL + 100 µL) regimens, plus ±5% formulation variance branches and explicit PK windows (including absolute bioavailability 96–97% and broader 92.5–107.5% ranges).
- Design-around opportunities concentrate on changing excipient composition, metered volume/regimen, and/or bioavailability/PK profile.
- The enforceability center of gravity is on administration + formulation + exposure, not merely “intranasal diazepam.”
FAQs
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Does US 12,337,061 require metered spraying rather than other intranasal dosing methods?
Yes. Dependent claims explicitly require the 100 µL to be administered as a “single metered spray.”
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Is bilateral (two-nostril) dosing required for infringement, or is single-nostril administration sufficient?
Single-nostril independent claims exist (Claim 1 and Claim 21; plus Claim 53 as written). Bilateral dosing is claimed in other independent branches (Claim 5, Claim 33, Claim 43).
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Which pharmacokinetic parameters are explicitly recited in dependent limitations?
The provided text includes AUC0-∞ 7338 hours·ng/mL, Cmax 272 ng/mL, Tmax 1.5 hours, and half-life about 49.2 hours, plus absolute bioavailability 96–97% and broader bioavailability equivalence ranges.
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Are specific excipient identities (maltoside form and ethanol type) treated as limitations?
Yes. Dependent claims recite dehydrated ethanol and specific naming for dodecyl maltoside stereochemical forms.
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Is the therapeutic use limited to seizure clusters that are “distinguishable from other seizures” in the same patient?
Yes. The independent-method claim language includes that distinction, which functions as a limitation on the claimed method.
References
- (Not provided in the prompt: no external bibliographic sources, USPTO record, FDA label/Orange Book entries, or litigation docket references were included.)
