United States Patent 4,782,047: scope, claim architecture, and US landscape

US Patent 4,782,047 is directed to an aqueous intranasal anti-inflammatory steroid formulation that is “substantially non-stinging,” with specific excipient ratios to achieve preservability, stability, and tolerability, and to method claims for treating nasal mucosal inflammation by administering that formulation.

What is the core invention in the claims?

Across the independent claims, the invention is a single formulation “box” defined by:

Drug substance: an anti-inflammatory steroid (with dependent fall-backs to flunisolide hemihydrate at ~0.025% w/v).
Vehicle / solubilization / wetting:
- Propylene glycol: about 2% to 10% w/v
- PEG 400: about 10% to 25% w/v
- Polysorbate 20: about 1% to 4% w/v
Preservation / stabilization system:
- “Effective amount of preservative”
- “Effective amount of antioxidant”
- “Effective amount of stabilizer”
pH system: “pH buffering agent sufficient” to adjust resulting solution to about 3.5 to 7 (method and formulation claims).
Tolerability target: “stable, effectively preservable, substantially non-stinging” aqueous formulation suitable for intranasal administration.

This structure matters for the landscape because most later design-arounds in intranasal steroid products tend to alter one of four things: (1) preservative (including using non-preserved versions), (2) pH, (3) cosolvent/surfactant ratios, or (4) steriod identity/dose form. Claim language here makes those levers central.

What do the independent claims cover (claim 1 and claim 9), and what is the effective claim “center of gravity”?

Claim 1 (formulation scope)

Claim 1 covers a formulation meeting all of the following concurrently:

Quantitative ranges (must all be satisfied):

Anti-inflammatory steroid: 0.01% to 0.05% (w/v)
Propylene glycol: 2% to 10% (w/v)
PEG 400: 10% to 25% (w/v)
Polysorbate 20: 1% to 4% (w/v)
pH: 3.5 to 7 (via buffering agent)

Qualitative elements (must be present but not pinned to specific chemistry in claim 1):

Effective preservative amount
Effective antioxidant amount
Effective stabilizer amount
Water
pH buffering agent sufficient to set pH within the band

Tolerability descriptor (functional/goal language):

“stable, effectively preservable, substantially non-stinging”

Claim 9 (method scope)

Claim 9 tracks claim 1 but in a treatment posture:

Treating inflammation of nasal mucosa without stinging by intranasally administering the claim-1 type formulation.

Practical effect: if a product infringes claim 1, it can also infringe claim 9 for the corresponding therapeutic use, unless the product-labeling/use context is carved out in practice. With composition-defined method claims, “labeling” often becomes the battleground rather than pharmacology.

Claim “center of gravity”

Although claim 1 is range-based, dependent claim 2 and claim 8 give a high-precision “working example”:

Flunisolide hemihydrate 0.0255% (w/v)
Propylene glycol 5.0%
PEG 400 20.0%
Polysorbate 20 2.50%
Benzalkonium chloride 0.07% (w/v) (claim 2)
Benzalkonium chloride 0.035% (w/v) (claim 8)
Disodium EDTA 0.01%
BHT 0.01%
Citric acid 0.005%
Trisodium citrate dihydrate 0.00765% (claim 2)
Sorbitol 2.86% (claim 2)
Purified water q.s.
pH about 5.3 (claim 2) or about 5.2 (claim 8)

This pair of near-identical compositions anchors the expected infringement analysis because many accused products are likely to cluster around commercially adopted concentrations and pH values rather than drift within the broad bands in claim 1.

How do the dependent claims narrow scope (and which variables become design-around targets)?

Excipient concentration bands that tighten claim 1

Claim 3 tightens the “effective amount” triad by adding:
- Preservative: 0.02% to 0.08% (w/v)
- Antioxidant: 0.001% to 0.05% (w/v)
- Stabilizer: 0.005% to 0.05% (w/v)

This converts qualitative “effective amount” language into quantitative ranges. If a product uses preservatives outside those bands, it may avoid claim 1 even if it hits the cosolvent/polysorbate ranges.

Steroid identity and dose precision

Claim 4: anti-inflammatory steroid is flunisolide at ~0.025% (w/v).

Specific preservative / stabilizer / antioxidant selection

Claim 5:
- Preservative = benzalkonium chloride
- Stabilizer = disodium EDTA
- Antioxidant = BHT

This trio is a second-order gate. Many intranasal steroid competitors use different antioxidants (or omit BHT), different chelators, or different preservatives (including alternatives to benzalkonium chloride), so claim 5 is a key map for design-around.

Additional osmotic/tolerability component

Claim 6 adds sorbitol 0.001% to 5% (w/v).

Buffer system chemistry

Claim 7 requires buffer comprising:
- citric acid 0.001% to 0.05% (w/v)
- sodium citrate dihydrate 0.001% to 0.05% (w/v)

Notably, claim 2 uses “Trisodium citrate dihydrate,” while claim 7 specifies sodium citrate dihydrate. In infringement, chemical identity and salt form can matter in practice when comparing compositions and analytical reports.

What do the example composition claims (2 and 8) cover exactly?

Claim 2 (one embodiment, pH ~5.3)

A concrete flunisolide aqueous formulation meeting:

Flunisolide hemihydrate 0.0255%
Propylene glycol 5.0%
PEG 400 20.0%
Polysorbate 20 2.50%
Benzalkonium chloride (50%) 0.07%
Disodium EDTA 0.01%
BHT 0.01%
Citric acid 0.005%
Trisodium citrate dihydrate 0.00765%
Sorbitol (70%) 2.86%
Purified water q.s. to 100%
pH adjusted to 5.3

Claim 8 (near-duplicate embodiment, pH ~5.2)

A concrete flunisolide formulation:

Flunisolide hemihydrate 0.025%
Propylene glycol 5%
PEG 400 20%
Polysorbate 20 2.50%
Benzalkonium chloride 0.035%
Disodium EDTA 0.01%
BHT 0.01%
Citric acid 0.005%
Sodium citrate dihydrate 0.00765%
Sorbitol 2.00%
Water to 100%
pH adjusted to 5.2

Landscape implication: a product that keeps the same solubilizer/surfactant/cosolvent triad (propylene glycol 5%, PEG 400 20%, polysorbate 20 2.5%) but changes preservative concentration from 0.035% or 0.07% becomes a direct question of claim-range compliance and dependent claim capture.

What is the “stinging” limitation doing to scope?

“Substantially non-stinging” is not a numeric parameter in the claims. In practice, it functions as a functional outcome limitation tied to formulation attributes that include:

preservative selection and level (benzalkonium chloride often drives irritation in intranasal products),
surfactant and cosolvent loading (propylene glycol and polysorbate can influence mucosal contact effects),
pH (acidic pH can increase irritation),
osmoticants and buffering agents.

From a patent-landscape standpoint, “stinging” usually does not give clean technical bounds; instead, it raises the evidentiary bar. Still, the claim requires “stable, effectively preservable” and then locks excipient and pH bands, which keeps the scope tethered to formulation chemistry rather than purely pharmacodynamic outcomes.

How would a competitor design around this patent (where the claims are most brittle)?

The highest-impact design-around vectors are the ones that change claim-defined numeric bands:

1) Alter or omit benzalkonium chloride and/or move preservative concentration outside claim 3

Claim 3 sets preservative at 0.02% to 0.08%.
Dependent claims (5) specify benzalkonium chloride and claims 2/8 give explicit values.

A competitor that uses:

a different preservative system (not benzalkonium chloride), or
benzalkonium chloride at <0.02% or >0.08%, or
no preservative (where product and claim construction allow) creates a direct mismatch with claim 3 (and claim 5 if it persists).

2) Change the pH band

Claim 1 requires pH 3.5 to 7.
Embodiments center around pH 5.2 to 5.3.

Moving below 3.5 is less common because stability and tolerability often degrade, but moving outside the band removes claim 1 coverage.

3) Change propylene glycol, PEG 400, or polysorbate 20 concentrations

Propylene glycol: 2% to 10%
PEG 400: 10% to 25%
Polysorbate 20: 1% to 4%

Any reformulation that breaks at least one of these ranges avoids claim 1 outright, even if the preservative/antioxidant/stabilizer are present.

4) Replace the antioxidant and/or chelator

Dependent claim 5 locks:
- Antioxidant = BHT
- Stabilizer = disodium EDTA

A product using different antioxidants (or EDTA substitutes) avoids claim 5 and related method dependencies, but it may still fall within claim 1 if “effective amount” is present and the excipient ranges are satisfied. So the most robust design-around often combines antioxidant/chelator changes with cosolvent/surfactant shifts.

US patent landscape: what this claim set likely does in a freedom-to-operate context

Without external bibliographic verification in this prompt, the safest landscape analysis is structural: identify how this patent’s claim set partitions the intranasal flunisolide formulation space.

A) Segment the “formulation space” by excipient triad

This patent claims a specific functional solubilization/wetting architecture:

propylene glycol + PEG 400 + polysorbate 20 in the specified bands

That triad creates a “core region.” Products that keep the triad and the pH band have higher exposure, even if preservative/antioxidant/stabilizer are changed.

B) Segment by preservative architecture

It also targets a benzalkonium chloride plus EDTA plus BHT architecture (in dependent claims) with explicit concentration ranges.

So landscape risk tends to split into:

High risk: products using benzalkonium chloride in 0.02% to 0.08% range and matching EDTA/BHT presence and pH band.
Medium risk: products matching excipient triad and pH but using a different preservative or lacking EDTA/BHT at those effective ranges.
Lower risk: products breaking the triad ranges or pH band.

C) Segment by flunisolide dosing concentration

Claim 1 allows steroid dose 0.01% to 0.05%. Dependent claims narrow to flunisolide ~0.025%. So landscape risk for other intranasal steroids (beclomethasone, budesonide, fluticasone) is structurally lower because claim 1 limits “an anti-inflammatory steroid” but explicitly ties dependent embodiments to flunisolide; still, claim 1 could read on other anti-inflammatory steroids if they fit the dose and the same excipient/pH scaffolding. In practice, most competitive products cluster by molecule identity and dose, which shapes risk.

D) Method claims convert formulation infringement into use infringement

Claim 9 and claim 15 tie the formulation to treatment without stinging. For FTO, if a product contains the claimed formulation but the clinical use differs, method claims can still be implicated if the therapeutic labeling aligns with “inflammation of the nasal mucosa.”

Key claim-to-landscape mapping table

Claim element	Numeric coverage in this patent	Highest leverage for design-around	Why it matters for landscape
Steroid concentration	0.01% to 0.05% (w/v) (claim 1)	Change steroid concentration outside band	Avoids claim 1 base scaffold
Propylene glycol	2% to 10% (w/v)	Shift propylene glycol	Breaks core vehicle range
PEG 400	10% to 25% (w/v)	Shift PEG 400	Breaks core solubilization range
Polysorbate 20	1% to 4% (w/v)	Shift polysorbate 20	Breaks wetting/surfactant range
Preservative	0.02% to 0.08% (claim 3); benzalkonium chloride (claim 5)	Change preservative system or move concentration outside range	Cuts claim 3 and dependent capture
Antioxidant	0.001% to 0.05% (claim 3); BHT (claim 5)	Replace BHT or move dose outside band	Avoids dependent capture, may still affect claim 1
Stabilizer	0.005% to 0.05% (claim 3); disodium EDTA (claim 5)	Replace EDTA or move dose	Avoids dependent capture
pH	3.5 to 7 (claim 1)	Shift pH outside band	Removes claim 1 entirely
“Non-stinging”	Functional	Hard to “engineer out” without changing excipient/pH	Outcome tied to claimed composition choices

Key Takeaways

US 4,782,047 claims a specific aqueous intranasal steroid formulation defined by excipient triad ranges (propylene glycol, PEG 400, polysorbate 20), a steroid dose band, and a broad but bounded pH range (3.5 to 7).
Dependent claims transform qualitative preservative/antioxidant/stabilizer language into quantitative bands (claim 3) and then lock specific chemistries (benzalkonium chloride, disodium EDTA, BHT) in claim 5.
The patent’s concrete embodiments (claims 2 and 8) cluster around a flunisolide concentration near 0.025% and a midrange excipient package (propylene glycol ~5%, PEG 400 20%, polysorbate 20 2.5%), with pH ~5.2 to 5.3. That clustering concentrates infringement risk on products that track this package.
For freedom-to-operate, the highest-value design-around levers are: change one of the excipient triad concentrations to exit claim 1 ranges, shift pH out of 3.5 to 7, or replace benzalkonium chloride (and/or move preservative level outside claim 3’s 0.02% to 0.08% band).

FAQs

1) Does claim 1 require benzalkonium chloride specifically?

No. Claim 1 requires an “effective amount of preservative,” while benzalkonium chloride is specified in dependent claim 5.

2) What numeric ranges control the formulation more than the “non-stinging” term?

Claim 1’s excipient and pH ranges drive the compositional boundaries. “Substantially non-stinging” is a functional outcome descriptor with no separate numeric test in the claim text.

3) If a product matches the excipient triad and pH band, can it still avoid infringement by changing antioxidant/stabilizer?

It can avoid dependent claims tied to BHT and disodium EDTA, but it may still face claim 1 infringement if it uses “effective amounts” of antioxidant and stabilizer and meets all other claim 1 ranges.

4) How do claims 9 and 15 interact with a product that infringes the composition claims?

Claims 9 and 15 are method claims: they cover treating nasal mucosal inflammation without stinging by administering the claimed formulation. If a product contains the formulation, the remaining question is whether its therapeutic use fits the claimed method.

5) Which elements are most likely to be changed in generic or follow-on formulations to reduce exposure?

Preservative system (benzalkonium chloride vs alternatives), pH buffering design, and the propylene glycol / PEG 400 / polysorbate 20 concentrations that define the claim 1 excipient triad.

References

[1] United States Patent 4,782,047.

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Details for Patent: 4,782,047

Summary for Patent: 4,782,047