US Patent 5,482,931: Claim Scope, Desmopressin Formulation Coverage, Expiration and Patent Landscape

US Patent 5,482,931 covers preserved, buffered, osmotically controlled aqueous compositions containing oxytocin-family or vasopressin-family peptides. Its commercial center of gravity is nasal desmopressin, particularly formulations using citrate, disodium hydrogen phosphate, benzalkonium chloride and sodium chloride. Claim 18 is the most product-specific claim. The patent issued on January 9, 1996, and its enforceable term has expired under the 20-year term applicable to modern US applications, absent an unusual term adjustment or extension. The patent therefore does not currently block generic or reformulated desmopressin products.

What does US Patent 5,482,931 cover?

The patent covers stable aqueous peptide compositions containing four functional elements:

A biologically active peptide.
A buffering agent.
A quaternary amine preservative or disinfectant.
An osmotic pressure-controlling agent.

The principal peptide genus includes:

Oxytocin.
Vasopressin.
Oxytocin analogs.
Oxytocin derivatives.
Vasopressin analogs.
Vasopressin derivatives.

The claims identify terlipressin, atosiban, carbetocin, triptorelin and desmopressin as specific peptide embodiments. The claimed compositions can be administered orally, parenterally or nasally, although the most commercially relevant claims are directed to nasal administration.

The patent is a formulation patent. It does not claim the underlying desmopressin molecule, oxytocin molecule or vasopressin molecule. Its technical focus is stabilization of aqueous peptide products at room temperature through pH control, antimicrobial preservation and osmotic adjustment.

What is the claim structure of US 5,482,931?

Independent claim 1: broad peptide composition

Claim 1 covers a stable aqueous composition "consisting essentially of" the four listed components. The claim is broad in several respects:

It covers multiple peptide families.
It does not limit the composition to nasal use.
It does not require a specific buffer.
It does not require benzalkonium chloride specifically.
It does not recite numerical concentration ranges.
It permits additional ingredients that do not materially alter the basic and novel characteristics of the composition.

The phrase "consisting essentially of" is important. It is narrower than "comprising," because additional ingredients can be excluded if they materially affect the claimed stability or formulation characteristics. It is broader than "consisting of," because incidental excipients and compatible ingredients may remain within the claim.

Claims 2 and 3: named peptide embodiments

Claim 2 identifies terlipressin, atosiban, carbetocin and triptorelin. Claim 3 identifies desmopressin as a vasopressin analog.

These claims reduce the breadth of claim 1 by specifying the peptide, but they do not independently impose a concentration, route of administration or exact excipient system.

Claims 4 through 7: buffer and pH limitations

Claims 4 and 5 require a pH range of 4.0 to 6.0, with claim 5 narrowing the target to approximately pH 5.0.

Claims 6 and 7 cover:

Citrate buffer.
Phosphate buffer.
Citrate-phosphate mixtures.
Specific citrate, phosphate and sodium-ion ratios.

Claim 7 recites a molar ratio of citrate, phosphate and sodium ions from approximately 1:3:3 to approximately 1:1:2.

The buffer claims create a technical boundary around formulations that maintain peptide stability in a mildly acidic aqueous environment. A competing product using a different buffer, such as acetate or histidine, may avoid these dependent claims but could still implicate claim 1 if the broader elements are satisfied.

Claim 8: benzalkonium chloride

Claim 8 identifies the quaternary amine preservative as benzalkonium chloride, using a structure in which:

R1 and R2 are methyl groups.
R3 is benzyl.
R4 is a C8 to C18 alkyl group.

Benzalkonium chloride is typically a mixture of homologues rather than a single molecular species. The claim reflects that commercial composition by defining the variable alkyl chain range.

Claims 9 and 10: route of administration

Claims 9 and 10 specify oral and parenteral administration. These claims are less commercially central than the nasal claims because the patent's detailed formulation and product-specific coverage focuses on nasal delivery.

Claim 11: nasal composition

Claim 11 covers an aqueous composition for nasal administration containing:

The specified peptide genus.
A buffering agent.
A quaternary amine preservative or disinfectant.
An osmotic pressure-controlling agent.

The claim also requires that the composition maintain the active component in a functionally stable condition over extended periods and at room temperature.

This functional language can create evidentiary issues in litigation. A patentee would generally need to establish that the accused composition meets the stability requirement, either through testing, product specifications, stability data or an appropriate technical inference.

Claims 12 through 17: nasal formulation subclaims

Claims 12 through 17 narrow claim 11 through:

Desmopressin.
pH 4.0 to 6.0.
Approximately pH 5.0.
Citrate or phosphate buffering.
Citrate and phosphate mixtures.
Specific sodium and buffer ratios.
Benzalkonium chloride.

These claims are more vulnerable to design-around strategies than claim 11 because a competitor can alter the peptide, buffer, preservative or pH while maintaining nasal delivery.

Claim 18: most specific desmopressin formulation

Claim 18 covers a stable aqueous nasal composition containing:

Component	Claimed amount
Desmopressin acetate	0.025 mg to 1.5 mg
Citric acid	1.35 mg to 1.75 mg
Disodium hydrogen phosphate	2.25 mg to 2.65 mg
Benzalkonium chloride	0.05 mg to 0.20 mg
Sodium chloride	Amount sufficient to produce plasma-comparable osmotic pressure

Claim 18 is the clearest product-style claim. It targets a defined excipient platform rather than the full Markush genus.

The numerical ranges are written as open interval limitations within a composition claim. An accused product would generally need to satisfy each recited range, either literally or under an applicable doctrine of equivalents. The sodium chloride limitation is functional: the amount depends on the total formulation and the resulting osmotic pressure.

Claims 19 through 22: overlapping osmotic-control functions

Claims 19 through 22 clarify that:

The buffer may also control osmotic pressure.
The buffer together with sodium chloride may control osmotic pressure.

These claims address potential ambiguity over whether the osmotic pressure-controlling agent must be a separate excipient. They broaden the functional role of the buffer and reduce the force of an argument that the formulation lacks a distinct tonicity component.

What patents protect desmopressin nasal formulations?

US Patent 5,482,931 protects a formulation architecture rather than the desmopressin active ingredient itself. Its principal coverage has four layers:

Layer	Coverage
Peptide genus	Oxytocin, vasopressin, analogs and derivatives
Nasal composition	Buffered, preserved, osmotically controlled aqueous peptide formulation
Excipient system	Citrate, phosphate, citrate-phosphate, benzalkonium chloride and sodium chloride
Product-specific formulation	Defined ranges for desmopressin acetate, citric acid, disodium hydrogen phosphate, benzalkonium chloride and sodium chloride

The most commercially relevant combination is desmopressin plus an acidic citrate-phosphate buffer and benzalkonium chloride. A product that uses desmopressin but substitutes a different preservative or buffer may avoid the narrower claims while requiring analysis under the broader claims.

When did US Patent 5,482,931 expire?

The patent issued January 9, 1996. US utility patents filed after June 8, 1995 generally receive a term ending 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and terminal-disclaimer rules. Earlier applications were governed by a 17-year term from issuance.

The patent's term was therefore expected to end no later than the early 2010s under the applicable filing and priority structure. The patent is not a current enforceable barrier to generic entry.

Event	Date or status
Patent	US 5,482,931
Issue date	January 9, 1996
Technology	Stable aqueous peptide compositions
Primary commercial relevance	Nasal desmopressin formulations
Current term	Expired
Current blocking effect	None from this patent alone

Patent expiration does not invalidate the technical disclosure. It removes the right to exclude others from practicing the claimed invention in the United States.

What is the Orange Book status of US Patent 5,482,931?

US Patent 5,482,931 should not be treated as a current Orange Book barrier merely because it concerns a formulation used in an approved drug.

Orange Book listing depends on FDA listing by the NDA holder and the statutory categories for patents that claim the drug substance, drug product or an approved method of use. A formulation patent can be listed if it meets FDA listing requirements, but an expired patent does not create a current exclusivity period.

For desmopressin products, the relevant FDA products have included nasal sprays, nasal solutions, tablets and other dosage forms. The applicable patent estate differs by product and NDA. A patent associated with one desmopressin NDA does not automatically apply to every desmopressin product.

The practical status of US 5,482,931 is:

It is not a live patent exclusion right.
It cannot independently support a current Paragraph IV litigation strategy.
It does not prevent an ANDA applicant from relying on the expired disclosure.
Any Orange Book listing would have no remaining blocking term after expiration.

Are there Paragraph IV challenges involving this patent?

No current Paragraph IV challenge can produce a live commercial dispute based solely on US Patent 5,482,931 because the patent has expired.

Historically, an ANDA applicant could have challenged the patent by certifying that:

The patent was invalid.
The patent was unenforceable.
The proposed generic would not infringe.
The patent had expired.

For an expired patent, an applicant ordinarily would not need to delay launch based on that patent. The 30-month stay mechanism under Hatch-Waxman applies to a timely infringement action involving a listed patent and does not convert an expired patent into a continuing exclusion right. The relevant statutory framework is in 21 U.S.C. § 355(j) and 35 U.S.C. § 271(e).

How strong is the patent estate for the claimed formulation?

Historical strength

The patent had meaningful historical scope because claim 1 and claim 11 covered a broad combination of:

Peptide active ingredient.
Buffer.
Quaternary amine preservative.
Osmotic control.

The claims also included specific desmopressin and benzalkonium chloride embodiments. A product closely matching the disclosed formulation could have presented infringement risk during the patent term.

Current strength

The current enforceability strength is zero because the patent has expired. The relevant commercial question is no longer whether the claims are valid, but whether later patents cover:

A specific desmopressin product.
A nasal spray device.
A pump or metered-dose delivery system.
A particular concentration.
A manufacturing process.
A preservative-free formulation.
A new indication.
A method of reducing adverse effects.
A stability profile or storage condition.

Patent expiration also removes the ability to assert claim 18 against a current generic product, even if the generic product exactly matches the claimed concentration ranges.

What design-around options exist for a desmopressin nasal product?

During the original patent term, potential design-around paths included:

Design-around strategy	Potential claim impact
Use a non-quaternary preservative	Could avoid claims requiring a quaternary amine
Use a preservative-free package	Could avoid preservative limitations
Use acetate, lactate or histidine buffer	Could avoid citrate/phosphate subclaims
Change pH outside 4.0 to 6.0	Could avoid pH-dependent claims, subject to product stability
Use a different osmotic system	Could avoid the specific sodium chloride and buffer relationships
Use a nonaqueous or reconstituted product	Could avoid aqueous-composition claims
Alter excipient concentrations	Could avoid claim 18's numerical ranges
Use a different delivery device	Could avoid device claims in later patents, but not necessarily composition claims

Because the patent is expired, these strategies are now relevant mainly to freedom-to-operate analysis against later patents, not against US 5,482,931.

Does the patent create biosimilar risk?

No conventional biosimilar risk arises from US Patent 5,482,931.

Desmopressin is a chemically defined peptide and is generally pursued through abbreviated drug pathways rather than the biologics-license-application biosimilar pathway applicable to therapeutic proteins and other biological products. The patent does not claim a biologic manufacturing cell line, protein sequence, host cell, biologic process or biosimilar reference product.

The competitive risk is therefore primarily generic and formulation-based:

ANDA products.
505(b)(2) products.
Alternative nasal delivery systems.
Oral or sublingual desmopressin products.
New formulations with different preservatives or excipients.

Which companies are relevant to the desmopressin competitive landscape?

Ferring Pharmaceuticals has been the principal commercial company associated with branded desmopressin products, including DDAVP and related products. Other market participants have included generic manufacturers and specialty pharmaceutical companies pursuing nasal, oral tablet, orally disintegrating tablet and other dosage forms.

The patent's formulation scope does not establish that every product sold by Ferring or a generic manufacturer infringed the claims. Product-by-product analysis requires comparison of:

Active ingredient form.
Concentration.
Buffer identity.
Preservative identity.
Osmolality.
Route.
Dosage form.
Manufacturing process.
NDA or ANDA labeling.

What litigation and settlement issues affect this patent?

No current litigation or settlement rights arise from an expired patent unless a dispute concerns historical conduct, damages, ownership, inventorship or contract rights.

The main historical litigation questions would have been:

Whether a competing nasal composition contained a covered peptide.
Whether the composition contained a quaternary amine preservative.
Whether the buffer met the claimed identity or pH limitations.
Whether the product was osmotically controlled within the claim scope.
Whether claim 18's concentration ranges were met.
Whether the "consisting essentially of" language excluded additional excipients.
Whether the patent was valid in view of earlier stabilized peptide formulations.
Whether the patent's functional stability limitations were satisfied.

No settlement can revive an expired patent. A settlement involving this patent could affect only past liability, launch timing during the historical term, licensing payments, or related patents that remained unexpired.

What manufacturing and intellectual-property barriers remain?

The expired patent does not remove practical manufacturing barriers. A current developer may still face:

Peptide degradation in aqueous solution.
Adsorption to containers or delivery components.
Preservative compatibility problems.
Pump-dose variability.
Microbial-control requirements.
Osmolality and nasal tolerability constraints.
Sterility or microbial-limit specifications.
Extractables and leachables concerns.
Device and formulation compatibility.
Stability testing under FDA requirements.

These are regulatory and technical barriers, not continuing rights under US 5,482,931. Later patents may protect particular pumps, containers, spray patterns, compositions, manufacturing controls or clinical uses.

How does US 5,482,931 compare with later formulation patents?

US 5,482,931 is broad at the composition-genus level and relatively narrow at the product-specific level. Later patents commonly divide the technology into more focused categories:

Patent category	Typical protected subject matter
Composition patent	Active ingredient and excipient ranges
Device patent	Nasal pump, actuator, metering chamber or spray profile
Method-of-use patent	Treatment of nocturia, diabetes insipidus or bleeding disorders
Manufacturing patent	Peptide purification, filling or stabilization
Packaging patent	Container closure, moisture control or preservative compatibility
Reformulation patent	Preservative-free, low-dose or alternative-route product

A freedom-to-operate review for a modern desmopressin nasal product should therefore search beyond the expired formulation patent. The relevant live estate may sit in device, method-of-use or manufacturing patents rather than in the original composition claims.

Key Takeaways

US Patent 5,482,931 claims stable aqueous formulations of oxytocin-family and vasopressin-family peptides.
Desmopressin is expressly covered in dependent claims.
The most important product-specific claim is claim 18, covering defined ranges of desmopressin acetate, citric acid, disodium hydrogen phosphate, benzalkonium chloride and sodium chloride.
Claims 11 through 17 focus on nasal administration and citrate-phosphate-buffered compositions.
The patent is a formulation patent, not a basic desmopressin compound patent.
The patent has expired and does not currently block generic entry.
No current Paragraph IV risk arises from this patent alone.
No biosimilar pathway issue arises from this patent.
Current freedom-to-operate risk must be assessed against later patents covering delivery devices, reformulations, manufacturing processes and methods of use.
The expired patent remains relevant as prior art and as a technical disclosure, but not as an enforceable US exclusion right.

FAQs

Does US Patent 5,482,931 cover all desmopressin products?

No. It covers specified aqueous compositions and, in some claims, nasal compositions containing particular formulation elements. It does not cover every desmopressin dosage form or route.

Can a generic desmopressin product use the formulation disclosed in claim 18?

Yes, from the perspective of US 5,482,931, because the patent has expired. Later patents, regulatory requirements and product-specific rights must be reviewed separately.

Does benzalkonium chloride make a desmopressin product infringe?

No. Benzalkonium chloride is only one element of the relevant claims. Infringement would require satisfaction of all limitations of an applicable claim, including the peptide, aqueous composition, buffering and osmotic-control requirements.

Are claims 19 through 22 separate protection for sodium chloride?

No. Those claims clarify how osmotic pressure may be controlled. They do not create a standalone sodium chloride monopoly.

Is US Patent 5,482,931 relevant to oral desmopressin tablets?

Only indirectly. Claims 1, 9 and related composition claims include oral administration, but the patent's detailed commercial focus is aqueous peptide formulations, particularly nasal desmopressin. Oral tablets may fall outside the claim scope based on composition, dosage form or excipient differences.

References

United States Patent and Trademark Office. (1996). Stable aqueous compositions of biologically active peptides (U.S. Patent No. 5,482,931).
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
21 U.S.C. § 355. (2024). Applications for FDA approval of new drugs.
35 U.S.C. § 154. (2024). Contents and term of patents; provisional rights.
35 U.S.C. § 271(e). (2024). Infringement of patents in regulated drug submissions.
U.S. Food and Drug Administration. (2024). Nasal spray and inhalation solution, suspension, and spray drug products: Chemistry, manufacturing, and controls documentation.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	210462	⤷ Start Trial
Canada	2166296	⤷ Start Trial
China	1109558	⤷ Start Trial
China	1126440	⤷ Start Trial
Czech Republic	283186	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,482,931

Summary for Patent: 5,482,931