Details for Patent: 5,976,573

Summary for Patent: 5,976,573

Title:	Aqueous-based pharmaceutical composition
Abstract:	An aqueous pharmaceutical composition which is capable of being sprayed into the nasal cavity of an individual and which comprises: (A) a pharmaceutically effective amount of solid particles of medicament which is effective in treating a bodily condition by virtue of its being present on the mucosal surfaces of the nasal cavity; and (B) a suspending agent in an amount effective to maintain said particles dispersed uniformly in the composition and to impart to the composition the following thixotropic properties: (i) the viscosity of the position in unsheared form is relatively high, with the composition being in gel-like form; (ii) as the composition is subjected to shear (shaken) in preparation for spraying, the viscosity of the composition becomes relatively low and such that the composition in the form of a mist flows readily into the nasal passages for deposit on the mucosal surfaces of the nasal cavity; and (iii) in deposited form on the mucosal surfaces, the viscosity of the composition is relatively high and such that it resists being cleared from the mucosal surfaces by the inherent mucocillary forces which are present in the nasal cavity, a method of use of the composition and a method for preparation of the composition, including in preferred form the use of anti-inflammatory steroid, for example, triamcinolone acetonide, and an odorless form of the composition.
Inventor(s):	Soo-Il Kim
Assignee:	Aventis Pharmaceuticals Inc
Application Number:	US08/678,465
Patent Claim Types: see list of patent claims	Use; Composition;

United States Drug Patent 5,976,573: Claim Scope, Expiration, Orange Book Status, and Competitive Patent Landscape

U.S. Patent No. 5,976,573 protects a thixotropic aqueous nasal suspension of triamcinolone acetonide, related manufacturing processes, and methods for treating allergic rhinitis. Its core technical concept is a sprayable suspension that becomes less viscous when shaken, deposits triamcinolone acetonide on nasal and sinus mucosa, and regains higher viscosity after deposition to resist mucociliary clearance.

The patent is no longer an active barrier to U.S. generic entry. Its relevant patent term expired in approximately late 2016, subject to the exact patent-term-adjustment calculation recorded by the USPTO. The claims remain useful for historical freedom-to-operate analysis, product characterization, and comparison with later nasal-spray patents, but they do not currently provide enforceable exclusion against a lawful triamcinolone acetonide nasal-spray product.

What does U.S. Patent 5,976,573 protect?

The patent protects four related subject-matter groups:

Claim group	Claims	Protected subject matter
Composition claims	1-10	Aqueous, propellant-free triamcinolone acetonide nasal suspensions with thixotropic behavior
Product-by-process claims	11-14	A final pharmaceutical product made by combining two suspensions in a specified bottom-introduction sequence
Manufacturing method claims	15-20	Processes for preparing the suspension, including excipient segregation and controlled combination
Treatment and administration claims	21-35	Spraying the composition for allergic rhinitis, specified doses, deposition sites, retention periods, particle sizes, and viscosity ranges

The patent is directed to a suspension rather than a solution. The triamcinolone acetonide must be present as solid particles. A formulation that dissolves the active ingredient completely would generally fall outside the central composition limitations, although other patents could apply.

The claims also require nasal delivery. Oral, ophthalmic, dermal, injectable, or pulmonary products are outside the express scope of the principal claims unless they satisfy the specific limitations of a particular claim.

What are the broadest composition claims in Patent 5,976,573?

Claim 1 is the broadest independent composition claim. It requires:

1. An aqueous pharmaceutical composition;
2. Solid particles of triamcinolone acetonide;
3. A pharmaceutically effective amount of the active ingredient;
4. A suspending agent;
5. Three functional rheological conditions:
   • high viscosity while unsheared;
   • lower viscosity after shaking for spray delivery; and
   • high viscosity after deposition on nasal mucosa to resist clearance.

Claim 1 does not require the specific excipient combination recited in claim 5. It also does not state the quantitative viscosity ranges, benzalkonium chloride, EDTA, dextrose, or Polysorbate 80 limitations found in narrower claims.

The principal infringement question under claim 1 would be whether the accused product has the required thixotropic behavior, not merely whether it contains triamcinolone acetonide and is delivered through a nasal spray.

How does claim 5 narrow the formulation scope?

Claim 5 is the most technically detailed independent composition claim. It requires all of the following:

Limitation	Claimed range or requirement
Water	At least about 85 wt.%
Triamcinolone acetonide	About 0.001 to about 2 wt.%
Suspending agent	About 1 to about 5 wt.%
Suspending-agent composition	About 85-95 wt.% microcrystalline cellulose and 5-15 wt.% sodium carboxymethylcellulose
Unsheared viscosity	About 400-800 centipoise
Shaken viscosity	About 50-200 centipoise
Antimicrobial	About 0.004-0.02 wt.% quaternary ammonium compound
Chelating agent	About 0.01-0.5 wt.%
Product characteristics	Odorless, propellant-free, pH about 4.5-7.5

Claim 5 is materially narrower than claim 1. A competing product could avoid claim 5 by using a different suspending system, omitting the specified quaternary ammonium concentration, falling outside the stated viscosity ranges, or using a nonaqueous or substantially different delivery system. Such a product could still face claim 1 or later patent claims depending on its actual formulation and rheology.

What formulations are protected by the dependent claims?

Claims 2-10 add formulation and particle limitations:

• Claims 2 and 3 require microcrystalline cellulose, sodium carboxymethylcellulose, and a chelating agent, specifically disodium EDTA in claim 3.
• Claim 4 adds dextrose.
• Claims 6 and 22 specify benzalkonium chloride and disodium EDTA.
• Claims 7 and 8 add a wetting or dispersing agent, specifically Polysorbate 80.
• Claim 9 adds dextrose.
• Claim 10 requires triamcinolone acetonide particles with an average size of about 1-20 microns.

The excipient combination is commercially significant because it resembles the formulation architecture historically associated with Nasacort AQ: triamcinolone acetonide suspension, microcrystalline cellulose and sodium carboxymethylcellulose as rheology modifiers, benzalkonium chloride as preservative, EDTA as chelating agent, Polysorbate 80 as wetting agent, dextrose as an isotonicity-adjusting excipient, and purified water. The FDA-approved labeling should be used to confirm the exact marketed formulation and strength. [Sanofi-Aventis U.S. LLC, 2010]

The claims do not cover every nasal triamcinolone product automatically. A product must satisfy the applicable claim elements, including particle form, excipient ranges, pH, viscosity, concentration, or manufacturing sequence.

How do the manufacturing claims operate?

Claims 11-20 target preparation rather than only the final composition.

The process requires two separate suspensions:

• Suspension A contains triamcinolone acetonide particles and a dispersing agent.
• Suspension B contains the thixotropic suspending system.

The suspensions are combined by introducing one suspension into the bottom of the other. Claims 12, 13, and 18 narrow the process by requiring suspension A to be introduced into the bottom of suspension B, with claim 13 specifying pumping.

Claim 14 adds a process architecture in which:

• the aqueous quaternary ammonium solution is added to suspension A; and
• an isotonicity agent and chelating agent are added to suspension B before combination.

Claims 15-20 are method claims and therefore focus on the steps performed by a manufacturer. A finished product could contain the same ingredients without infringing a process claim if it was not made by the claimed sequence. In practice, proving process infringement can require batch records, manufacturing instructions, validation documents, deposition testimony, or analytical evidence.

Claims 11-14 also raise product-by-process issues. The language "a product ... prepared by a process comprising" ties the claim to a product made by the stated process, but infringement analysis would depend on the governing construction and whether the accused product has the required structural and compositional characteristics.

What methods of treatment are protected?

Claims 21-35 protect administration of the composition for allergic rhinitis.

Claim 21 requires:

• applying the claim 5 composition;
• spraying a dose into each nasal cavity;
• depositing effective quantities on specified nasal and sinus regions; and
• retaining effective amounts for at least about one hour.

The listed anatomical areas include the anterior nose, frontal sinus, maxillary sinuses, and mucosal surfaces overlying the turbinates and conchae. Claims 29 and 30 specify seasonal and perennial allergic rhinitis.

Claims 25-28 add dosing and delivery restrictions:

Claim	Limitation
25	About 200-450 micrograms of medicament per nasal cavity dose
26	Once-daily application with about 100-130 micrograms per nasal cavity
27	Precompression pump
28	Specific excipient combination, including triamcinolone acetonide, cellulose system, Polysorbate 80, EDTA, benzalkonium chloride, dextrose, and purified water

Claims 31-33 contain regional deposition and retention limitations:

• at least about 47% retained in the frontal cavity after two hours;
• at least about 23% retained in the inferior concha region after two hours; and
• at least about 6% retained in the superior concha region after two hours.

These limitations are difficult to assess from ordinary product labeling alone. They may require deposition studies, imaging, radiolabeling, pharmacokinetic analysis, or comparable experimental evidence.

Claim 35 requires unsheared viscosity of about 400-1,000 centipoise and shaken viscosity of about 50-200 centipoise. It is broader on the unsheared viscosity range than claim 5 but retains the central rheological concept.

When did Patent 5,976,573 lose exclusivity?

Patent 5,976,573 was issued on November 2, 1999. Its term was governed by the Uruguay Round Agreements Act, which generally provides a 20-year term measured from the earliest effective nonprovisional filing date, with possible patent-term adjustment and other statutory modifications. [U.S. Patent and Trademark Office, n.d.-a]

Public patent records and historical Orange Book information place the patent’s effective expiration in approximately late 2016. The patent is therefore expired as of 2026. No patent-term extension can be assumed from the patent number alone. Patent-term extension under 35 U.S.C. § 156 is product-specific and must be confirmed in the USPTO and FDA records.

Exclusivity timeline

Event	Date or period
Patent issued	November 2, 1999
Nasacort AQ U.S. approval	1996, based on FDA product history
Expected patent expiration	Approximately late 2016
Current status	Expired
Current FDA exclusivity barrier	None attributable to this patent
Current Paragraph IV significance	Historical or moot for this patent

The patent’s expiration does not eliminate other possible barriers, including later patents, regulatory exclusivity, device patents, trade secrets, or patents covering different corticosteroid formulations.

What is the Orange Book status of Patent 5,976,573?

The patent was associated with the U.S. regulatory and commercial history of triamcinolone acetonide nasal spray products, including Nasacort AQ. The FDA Orange Book is the relevant source for determining whether a patent was submitted for a particular approved NDA and whether it remains listed. [U.S. Food and Drug Administration, n.d.-a]

A historical listing does not mean that the patent remains enforceable. An expired patent may remain visible in historical Orange Book records or patent databases while no longer blocking approval or launch.

For a current ANDA analysis, the operative questions are:

1. Whether the reference NDA remains listed in the active Orange Book;
2. Whether Patent 5,976,573 remains listed against the specific NDA;
3. Whether any listed patent has expired;
4. Whether newer formulation, device, or method-of-use patents are listed; and
5. Whether the ANDA applicant must make a Paragraph IV certification or may file a Paragraph III certification.

For an expired patent, a Paragraph IV challenge is generally no longer needed to clear that patent. A generic applicant would not obtain a meaningful launch advantage by challenging an already expired patent.

Which companies have challenged triamcinolone acetonide nasal-spray patents?

The U.S. market has included generic triamcinolone acetonide nasal sprays and an OTC version of Nasacort marketed as Nasacort Allergy 24HR. FDA approved OTC Nasacort Allergy 24HR in 2013, moving the product from prescription to nonprescription status. [U.S. Food and Drug Administration, 2013]

Because Patent 5,976,573 expired around 2016, any ANDA or OTC switch activity occurring after expiration would not require a live Paragraph IV dispute over this patent. A company may still have challenged the patent before expiration, but the patent number alone does not establish the identity of a challenger, the certification date, the litigation outcome, or a settlement term. Those facts must be taken from FDA Paragraph IV notices and federal court dockets.

No current biosimilar risk applies. Triamcinolone acetonide is a chemically synthesized small molecule, not a biologic. Competition proceeds through the ANDA pathway, OTC monograph pathway, or, for a materially different product, a 505(b)(2) application. [FDA, n.d.-b]

What patent litigation and settlement issues affect the patent?

The main historical litigation risk would have involved an ANDA applicant proposing a triamcinolone acetonide nasal suspension before expiration. Potential causes of action could include:

• direct infringement of composition claims;
• infringement of manufacturing claims under 35 U.S.C. § 271(e)(2);
• induced or contributory infringement theories for method-of-use claims;
• invalidity based on anticipation or obviousness;
• written-description or enablement challenges to functional rheology and deposition limitations.

The strongest litigation issues would likely have been claim construction and proof of the rheological limitations. Terms such as "thixotropic," "relatively high," "relatively low," "uniformly dispersed," and "pharmaceutically effective amount" require technical and factual interpretation. Claims 5 and 35 are more measurable because they recite viscosity ranges, but testing conditions remain important. Viscosity can vary with temperature, shear rate, spindle geometry, rest time, and instrument method.

The provided claim set does not identify a settlement agreement. A settlement would require confirmation from court filings, FDA correspondence, or a public company disclosure. Patent expiration now limits the commercial value of any historical settlement.

How strong was the patent estate?

The patent was technically focused but commercially important during its term.

Strengths

• Claim 1 captured the central formulation concept without requiring every named excipient.
• Claim 5 provided a detailed composition claim closely aligned with a commercial formulation.
• Claims 15-20 created manufacturing-process coverage.
• Claims 21-35 added treatment, dosing, deposition, and retention claims.
• The combination of composition, process, and use claims created several potential infringement theories.

Vulnerabilities

• Functional rheology limitations may be difficult to construe and prove.
• Quantitative viscosity claims depend on testing methodology.
• Deposition and retention claims require specialized evidence.
• Broad claims may face prior-art challenges involving nasal suspensions, cellulose thickeners, preservatives, and corticosteroids.
• A design-around using a different suspending polymer, dissolved active ingredient, alternative preservative, or different pump could avoid narrower claims.
• Method claims are difficult to enforce against manufacturers when labeling omits the claimed use or when the product has multiple uses.

The estate’s current strength is effectively zero as an exclusionary right because the patent has expired. Its historical strength was greater for a product that reproduced the same formulation and rheological profile.

How does Nasacort compare with competing nasal corticosteroids?

Product	Active ingredient	Dosage form	Generic or biosimilar pathway	Patent risk relative to Patent 5,976,573
Nasacort AQ / Nasacort Allergy 24HR	Triamcinolone acetonide	Aqueous nasal suspension	ANDA or OTC pathway	Patent 5,976,573 expired
Flonase	Fluticasone propionate	Nasal spray	ANDA or OTC pathway	Separate active ingredient and patent estate
Nasonex	Mometasone furoate	Nasal spray	ANDA pathway	Separate active ingredient and formulation claims
Rhinocort	Budesonide	Nasal spray	ANDA or OTC pathway	Separate active ingredient and formulation claims
Dymista	Fluticasone propionate plus azelastine	Combination nasal spray	ANDA or 505(b)(2), depending on product	Separate combination and device estate

Patent 5,976,573 does not cover fluticasone, mometasone, budesonide, or combination products merely because they are nasal corticosteroid sprays. Its active-ingredient limitation is triamcinolone acetonide.

What generic launch risks remain?

The expired patent creates no current blocking risk by itself. Current launch analysis should focus on:

1. Other unexpired patents listed against the reference NDA;
2. Pump and actuator patents;
3. Later formulation patents;
4. Preservative-free or single-dose delivery systems;
5. Manufacturing know-how and process trade secrets;
6. FDA product-specific bioequivalence requirements;
7. OTC monograph compliance, labeling, and manufacturing requirements;
8. Trademark and trade-dress restrictions.

A generic triamcinolone acetonide nasal spray that uses a different formulation may avoid the expired patent but still need to demonstrate pharmaceutical equivalence, bioequivalence, spray-pattern comparability, droplet-size distribution, delivered-dose uniformity, and microbiological quality under FDA requirements.

What geographic coverage did the patent have?

U.S. Patent 5,976,573 provided protection only in the United States. Corresponding foreign applications may have existed, but the U.S. patent number does not establish the status of foreign counterparts.

For international freedom-to-operate analysis, the relevant jurisdictions include:

• European Patent Convention states;
• Canada;
• Japan;
• Australia;
• China;
• South Korea;
• Brazil;
• Mexico.

Foreign patent terms, prosecution outcomes, supplementary protection certificates, and national-phase claims must be reviewed separately. Expiration of the U.S. patent does not establish expiration of foreign family members.

Key Takeaways

• Patent 5,976,573 covers an aqueous, thixotropic triamcinolone acetonide nasal suspension.
• Claim 1 targets the core rheological concept: high viscosity at rest, lower viscosity after shaking, and high viscosity after nasal deposition.
• Claim 5 is the principal narrow formulation claim and requires cellulose-based suspension agents, defined viscosity ranges, preservative, chelator, water, pH, and concentration limits.
• Claims 11-20 cover two-stage suspension preparation and bottom-introduction manufacturing steps.
• Claims 21-35 cover allergic-rhinitis treatment, dosing, spray-device use, anatomical deposition, and retention.
• The patent issued November 2, 1999 and expired approximately in late 2016.
• It is no longer a current U.S. exclusivity barrier.
• Triamcinolone acetonide is a small molecule, so biosimilar analysis is inapplicable.
• Current generic risk depends on later patents, device rights, regulatory requirements, and manufacturing barriers rather than Patent 5,976,573.

FAQs

Does Patent 5,976,573 cover all triamcinolone acetonide nasal sprays?

No. The claims require specific features, including solid triamcinolone acetonide particles, aqueous suspension, suspending agents, and, for narrower claims, defined excipients, viscosity, pH, concentration, and spray or dosing characteristics.

Can a generic use microcrystalline cellulose and sodium carboxymethylcellulose after the patent expired?

Yes. Patent expiration removes the patent-based exclusion. The generic must still satisfy FDA requirements and avoid any other unexpired patents.

Is a triamcinolone acetonide solution covered by these claims?

Generally, no. The claims repeatedly require the medicament to be present as solid particles. A fully dissolved triamcinolone formulation would not satisfy that limitation, although other patents or regulatory requirements could apply.

Does Patent 5,976,573 protect the Nasacort trademark?

No. The patent protects claimed technology. Nasacort is a trademark and is governed by separate trademark rights.

Are the deposition percentages in claims 31-33 commercially important today?

They have limited current exclusionary value because the patent has expired. Historically, they could have increased enforcement complexity by requiring evidence of regional nasal or sinus deposition and two-hour retention.

References

1. U.S. Patent No. 5,976,573. (1999). Aqueous pharmaceutical composition containing triamcinolone acetonide. U.S. Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2013). FDA approves first over-the-counter nasal spray to treat allergies. https://www.fda.gov

3. U.S. Food and Drug Administration. (n.d.-a). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/

4. U.S. Food and Drug Administration. (n.d.-b). Abbreviated new drug application process. https://www.fda.gov

5. Sanofi-Aventis U.S. LLC. (2010). Nasacort AQ prescribing information. U.S. Food and Drug Administration labeling database.

6. U.S. Patent and Trademark Office. (n.d.-a). Patent term adjustment. https://www.uspto.gov

7. U.S. Patent and Trademark Office. (n.d.-b). Patent Center. https://patentcenter.uspto.gov

Drugs Protected by US Patent 5,976,573

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 5,976,573

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	1045
African Regional IP Organization (ARIPO)	9901495
Austria	250432
Australia	3647197
Australia	737506
Bulgaria	103127
Bulgaria	64585