Details for Patent: 6,939,559

Summary for Patent: 6,939,559

Title:	Pharmaceutical composition for application to mucosa
Abstract:	The present invention provides a pharmaceutical composition for application to the mucosa to be used in drug therapy comprising a water-insoluble and/or water-low soluble substance, a medicament, and an aqueous medium, and having an osmotic pressure of less than 290 mOsm. This composition is superior over conventional pharmaceutical compositions for application to the mucosa, due to efficient and high permeability to the blood at the mucosa. The present invention further provides a pharmaceutical composition for application to the mucosa comprising a hemostatic agent and a medicament. This composition is superior over conventional pharmaceutical compositions for application to the mucosa, due to permeability and retentivity at the mucosa.
Inventor(s):	Yoshihisa Nishibe, Wataru Kinoshita, Hiroyuki Kawabe
Assignee:	Teijin Pharma Ltd
Application Number:	US09/446,276
Patent Claim Types: see list of patent claims	Composition; Compound;

United States Patent 6,939,559: Claim Scope, Patent Strength, Exclusivity and Competitive Landscape

US Patent 6,939,559 protects low-osmotic pharmaceutical compositions for mucosal administration, with particular coverage for aqueous nasal formulations containing poorly water-soluble materials, hemostatic agents, medicaments, polymers, surfactants and specified excipients. Claim 2 is the broadest independent claim because it does not require an aqueous vehicle, a low osmotic pressure, or a poorly soluble substance. The patent is a formulation patent, not an active-ingredient patent, and its commercial relevance depends on whether a marketed or development-stage product practices the required combination of composition and use limitations.

What does US Patent 6,939,559 claim?

The patent has three independent claims:

Claim	Core subject matter	Principal limitations
1	Aqueous mucosal pharmaceutical composition	Poorly soluble or water-insoluble substance, medicament, osmotic pressure of 72 mOsm or less
2	Mucosal pharmaceutical composition	Hemostatic agent and medicament
3	Aqueous mucosal pharmaceutical composition	Hemostatic agent, poorly soluble or water-insoluble substance, medicament, osmotic pressure of 72 mOsm or less

All three claims use the open-ended term “comprising.” Additional ingredients therefore generally do not avoid infringement if every required element is present.

Claim 1 is directed to a low-osmotic aqueous formulation containing a poorly soluble or insoluble component and a medicament. Claim 3 adds a hemostatic agent. Claim 2 is structurally different and potentially broader because it requires only a mucosa-directed composition containing a hemostatic agent and a medicament.

The claims are not limited to a particular active ingredient. They can reach formulations containing water-soluble or liposoluble drugs, as specified by claims 24 and 25, provided the applicable independent-claim limitations are satisfied.

How broad is the independent-claim coverage?

Claim 1: low-osmotic aqueous mucosal formulations

Claim 1 requires all of the following:

1. An aqueous pharmaceutical composition.
2. Application to a mucosa.
3. At least one water-insoluble or low-water-solubility substance.
4. At least one medicament.
5. Osmotic pressure of 72 mOsm or less.

The low-osmotic limitation is central. An aqueous mucosal formulation containing a poorly soluble excipient and a medicament would fall outside claim 1 if its osmotic pressure exceeds 72 mOsm.

The claim does not expressly require nasal administration. The mucosa could include nasal, oral, ophthalmic, vaginal, rectal or other mucosal tissue, subject to the specification and claim-construction record.

Claim 2: hemostatic-agent combinations

Claim 2 requires:

• A pharmaceutical composition for application to a mucosa;
• At least one hemostatic agent; and
• At least one medicament.

Claim 2 does not expressly require:

• An aqueous formulation;
• An osmotic pressure of 72 mOsm or less;
• A poorly soluble or insoluble substance;
• Nasal administration; or
• Any particular hemostatic agent.

This makes claim 2 the principal litigation risk for a mucosal product combining a hemostatic agent with another therapeutic agent. The scope may depend heavily on whether the accused composition is objectively intended for mucosal use and whether the second component qualifies as a “medicament.”

Claim 3: combined low-osmotic hemostatic formulation

Claim 3 combines the limitations of claims 1 and 2. It requires an aqueous mucosal formulation containing:

• A hemostatic agent;
• A poorly soluble or low-water-solubility substance;
• A medicament; and
• Osmotic pressure of 72 mOsm or less.

Claim 3 is narrower than claim 2 but may be commercially significant for nasal formulations designed to control bleeding while delivering an active drug.

What formulations are protected by the dependent claims?

The dependent claims create several technical subgroups.

Claims	Protected feature
4	Osmotic pressure of 60 mOsm or less
5	Osmotic pressure of 30 mOsm or less
6	Osmotic pressure of 10 mOsm or less
7-11	Osmotic-pressure-controlling agent, including salt, sodium chloride, water-soluble sugar and glucose
12-15	Cellulose or particulate insoluble material dispersed in an aqueous medium
16-21	Water-soluble polymers and crystalline cellulose-carmellose sodium
22-23	Surfactant, specifically polysorbate 80
24-25	Water-soluble or liposoluble medicament
26	Nasal mucosa
27	Specified hemostatic agents
28-29	Nasal formulations containing antiallergic, antihistamine, anticholinergic, steroid, vaccine or gene-therapy agents

Claims 4 through 6 establish progressively lower osmotic-pressure thresholds. A formulation at 10 mOsm or less would generally satisfy the broader 72, 60 and 30 mOsm limitations if the other claim elements are met.

Claims 7 through 11 cover control of osmotic pressure with salts or sugars. Sodium chloride and glucose are expressly identified. The claims do not require that the controlling agent lower osmotic pressure; they cover compositions “further comprising” the agent. The specification and prosecution history would be important in determining whether the agent must be present in an amount selected to achieve the claimed osmotic range.

Claims 12 through 15 focus on insoluble or poorly soluble particulate materials. Claim 13 narrows the cellulose to crystalline cellulose. Claims 14 and 15 distinguish the presence and dispersion of solid particles in an aqueous medium.

Claim 21 is commercially relevant because it covers the combination identified as crystalline cellulose and carmellose sodium. This type of excipient system can provide suspension, viscosity, deposition and residence-time properties in nasal formulations.

Claims 16 through 20 cover water-soluble polymers, including:

• Sodium carboxymethyl cellulose;
• Xanthan gum;
• Hydroxypropyl methyl cellulose;
• Alginic acid;
• Polyethylene glycol;
• Pectin;
• Guar gum;
• Gum arabic; and
• Other listed polymers.

Claim 23 specifically covers polysorbate 80. A product using an alternative surfactant could avoid that dependent claim but would remain exposed to the broader claims if the independent limitations are met.

Which hemostatic agents fall within the patent?

Claim 27 expressly identifies the following hemostatic agents:

• Tranexamic acid;
• Epsilon-aminocaproic acid;
• Carbazochrome;
• Carbazochrome sulfonate;
• Carbazochrome sodium sulfonate;
• Phytonadione;
• Etamsylate;
• Monoethanolamine oleate;
• Thrombin;
• Hemocoagulase; and
• Adrenochrome monoaminoguanidine mesilate.

The listing narrows claim 27 to the specified agents or their claim-construction equivalents. It does not necessarily limit claim 2 or claim 3 to this list. A different hemostatic agent could still implicate an independent claim if it satisfies the broader term “hemostatic agent.”

The patent therefore has two distinct hemostatic coverage levels:

1. Generic hemostatic-agent coverage in claims 2 and 3.
2. Express compound-level coverage in claim 27.

What is the scope of the nasal steroid claims?

Claims 26, 28 and 29 create a nasal-product subgroup.

Claim 26 limits the mucosa to nasal mucosa. Claim 28 covers a nasal composition containing a hemostatic agent and an additional agent selected from antiallergic agents, antihistamines, anticholinergics, steroids, vaccines and gene-therapy substances. Claim 29 narrows the additional agent to a steroid.

A nasal steroid product would not infringe claim 29 merely because it is a nasal steroid. The formulation would also need to satisfy the limitations inherited from claim 3, including:

• Aqueous composition;
• Hemostatic agent;
• Poorly soluble or low-solubility substance;
• Medicament; and
• Osmotic pressure of 72 mOsm or less.

This inherited-limitation structure materially narrows claim 29. A conventional isotonic nasal steroid spray without a hemostatic agent would generally fall outside claim 29 as written.

How strong is the patent estate?

The patent appears to have a focused formulation estate rather than broad protection over a therapeutic molecule. Its commercial strength depends on formulation details that are often difficult to establish from public product labeling alone.

Strengths

• Claim 2 does not require an aqueous vehicle or low osmotic pressure.
• Claims 1 and 3 use a quantitative osmotic-pressure threshold.
• The claims cover both water-soluble and liposoluble medicaments.
• Claim 26 reaches nasal administration.
• The dependent claims identify commercially common excipients, including sodium carboxymethyl cellulose, xanthan gum, hydroxypropyl methyl cellulose, crystalline cellulose and polysorbate 80.
• The claims cover combinations of hemostatic and therapeutic agents rather than a single active ingredient.

Weaknesses and potential validity pressure points

The principal validity and enforcement issues are likely to concern claim construction, written description, enablement, indefiniteness and anticipation or obviousness.

Issue	Potential pressure point
“Low water soluble”	The claims do not state a numerical solubility threshold
“Application to the mucosa”	The required degree of product-use intent may be disputed
“Osmotic pressure”	Measurement method, temperature, concentration and test conditions may matter
“Medicament”	The term may require construction in the context of the specification
Broad claim 2	Prior art may disclose mucosal combinations of hemostatic and therapeutic agents
Polymer and cellulose limitations	Known suspension and mucoadhesive excipients may support obviousness arguments
Low osmotic pressure	Prior art on isotonic or hypotonic mucosal delivery may be relevant
Markush hemostatic list	Individual compounds may have separate prior-art histories

The strongest infringement case would usually involve a product with a documented formulation matching the claimed osmotic pressure and excipient profile. The strongest validity challenge would likely combine earlier mucosal delivery art, known hemostatic formulations and routine excipient-selection evidence.

When did US Patent 6,939,559 lose exclusivity?

US Patent 6,939,559 was granted on September 6, 2005. The grant date does not determine the patent’s expiration date. Under 35 U.S.C. §154, the ordinary term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and terminal-disclaimer rules.[1]

The patent’s enforceable term therefore cannot be calculated from the claims or grant number alone. A complete term determination requires the USPTO continuity data, earliest effective filing date, patent-term adjustment and any terminal-disclaimer record. Patent expiration, maintenance-fee status and reexamination history must be verified in the USPTO patent file before relying on the patent for a current freedom-to-operate conclusion.

What is the Orange Book status of US Patent 6,939,559?

US Patent 6,939,559 is not, by its claim structure, an active-ingredient patent. It covers a general mucosal formulation platform and does not identify a specific approved drug product in the supplied claims.

The FDA Orange Book lists patents submitted by sponsors for approved drug products, including drug-substance, drug-product and method-of-use patents when the statutory listing requirements are met.[2] A formulation patent may be Orange Book-listed only if it is associated with a particular approved product and satisfies FDA listing rules. The patent number alone does not establish Orange Book listing.

The patent should therefore be treated as a potential formulation patent, not automatically as an Orange Book-listed barrier to an ANDA.

Do Paragraph IV challenges or generic-entry risks exist?

A Paragraph IV challenge is relevant only if the patent is listed in the Orange Book for a reference-listed drug and an ANDA applicant certifies that the patent is invalid, unenforceable or will not be infringed.[3]

For this patent, generic-entry analysis should distinguish three scenarios:

Scenario	Principal risk
Product does not use a hemostatic agent	Claims 2, 3 and 27 may be avoided; claims 1 and dependent claims may remain relevant
Product uses a hemostatic agent but is not aqueous or low-osmotic	Claim 2 may remain relevant; claims 1 and 3 may be avoided
Product uses low-osmotic aqueous suspension with listed polymers or cellulose	Multiple claim layers may be implicated

A generic nasal product could pursue a non-infringing formulation by changing one or more of the following:

• Omit the hemostatic agent;
• Use a formulation with osmotic pressure above 72 mOsm;
• Replace the claimed insoluble particulate system;
• Use a different polymer or surfactant;
• Use a nonaqueous dosage form; or
• Avoid a nasal indication where the claim requires nasal mucosa.

These design-around strategies require product-specific formulation data. Substitution of one excipient alone may not avoid claim 1 or claim 3 if the replacement remains a water-insoluble or low-solubility substance.

Are biosimilars relevant to this patent?

Biosimilar risk is generally low because the claims do not target a biologic molecule or a biologic manufacturing process. The patent covers mucosal pharmaceutical compositions and can theoretically include a vaccine or gene-therapy medicament under claim 28, but that does not convert the patent into a biosimilar patent.

The more relevant competitors are:

• Generic nasal sprays;
• Branded nasal formulations;
• Compounded mucosal products;
• Combination hemostatic-delivery products; and
• Developers using alternative mucoadhesive suspension systems.

For biologics, the relevant regulatory pathway would be under the Public Health Service Act rather than a conventional small-molecule ANDA. The patent’s formulation claims could still be asserted against a biologic delivery product if the product satisfies every limitation, but that is a secondary risk category.[4]

What patent landscape surrounds the claimed technology?

The surrounding landscape can be divided into five technical clusters.

Low-osmotic mucosal delivery

Relevant prior art includes hypotonic, isotonic and low-osmotic nasal formulations intended to reduce irritation, improve mucosal compatibility or enhance residence time. The quantitative thresholds of 72, 60, 30 and 10 mOsm are the patent’s principal differentiators within this cluster.

Insoluble-particle suspension systems

This cluster includes crystalline cellulose, microcrystalline cellulose, cellulose derivatives and other suspended solids used to stabilize poorly soluble medicaments. The key competitive question is whether the product contains a qualifying insoluble or low-solubility substance as a solid particle in an aqueous medium.

Mucoadhesive polymers

Sodium carboxymethyl cellulose, xanthan gum and hydroxypropyl methyl cellulose are established pharmaceutical excipients. Their presence may support a claim only when combined with the inherited limitations of the relevant independent claim. The use of a known polymer is not, by itself, enough to establish infringement of the full combination.

Hemostatic mucosal products

Tranexamic acid, aminocaproic acid, carbazochrome and related agents form the hemostatic subfield. A product combining one of these agents with another medicament for mucosal administration faces the greatest exposure under claim 2.

Nasal therapeutic combinations

Claims 28 and 29 are directed to combinations involving antiallergic agents, antihistamines, anticholinergics, steroids, vaccines and gene-therapy materials. The claims are most relevant where the nasal product also contains a hemostatic agent and satisfies the low-osmotic aqueous requirements inherited from claim 3.

What litigation and licensing issues affect the patent?

The supplied claim set does not establish any litigation, settlement, licensing transaction, covenant not to sue, terminal disclaimer or ownership transfer. Those matters are separate from claim scope and must be established from USPTO assignment records, PACER, district-court dockets, PTAB records and commercial licensing disclosures.

For transaction diligence, the key legal checks are:

1. Confirm current ownership and recorded assignments.
2. Confirm maintenance-fee payment history.
3. Confirm patent-term adjustment and any terminal disclaimer.
4. Search district-court and PTAB proceedings.
5. Search Orange Book listings associated with any relevant approved product.
6. Compare the target formulation against claims 1, 2, 3, 21, 23, 27 and 29.
7. Review prosecution history for amendments affecting “osmotic pressure,” “low water soluble,” “medicament” and “hemostatic agent.”

Key Takeaways

• Claim 2 is the broadest independent claim because it requires only a mucosal composition containing a hemostatic agent and a medicament.
• Claims 1 and 3 are narrower and depend on an aqueous vehicle, poorly soluble material and osmotic pressure of 72 mOsm or less.
• Claims 4 through 6 create increasingly restrictive low-osmotic ranges.
• Claims 12 through 23 protect specific cellulose, polymer and surfactant architectures.
• Claims 26 through 29 focus on nasal formulations, including nasal steroid combinations.
• The patent is a formulation patent, not an active-ingredient patent.
• Biosimilar risk is limited; generic and branded formulation competition is more relevant.
• Orange Book listing cannot be inferred from the patent number or claims.
• Patent expiration cannot be determined from the claims alone because the statutory term depends on the earliest effective filing date and any patent-term adjustments.
• The most material freedom-to-operate variables are the presence of a hemostatic agent, osmotic pressure, aqueous status, insoluble particulate system and nasal-use designation.

FAQs About US Patent 6,939,559

Does a nasal steroid spray automatically infringe US Patent 6,939,559?

No. Claim 29 also requires the inherited limitations of claim 3, including a hemostatic agent, an aqueous formulation, a poorly soluble or insoluble substance and osmotic pressure of 72 mOsm or less.

Can a product avoid the patent by using a different polymer?

Possibly, but changing the polymer does not necessarily avoid claims 1, 2 or 3. Those claims do not require a particular polymer. A different polymer may avoid claims 16 through 20 while leaving the independent claims in force.

Is tranexamic acid specifically covered?

Yes. Claim 27 expressly identifies tranexamic acid, but the product must also satisfy the limitations inherited from claim 3.

Does claim 2 require low osmotic pressure?

No. Claim 2 does not expressly require an aqueous composition or any osmotic-pressure threshold.

Is US Patent 6,939,559 a patent on a specific drug?

No. The claims cover pharmaceutical compositions for mucosal application and do not limit the invention to one active pharmaceutical ingredient.

References

1. United States Code, 35 U.S.C. §154. (2024). Patent term.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
3. U.S. Food and Drug Administration. (2024). ANDA submissions: Patent certifications and Paragraph IV procedures.
4. United States Code, 42 U.S.C. §262. (2024). Licensure of biological products and biosimilar biological products.
5. United States Patent and Trademark Office. (2005). U.S. Patent No. 6,939,559, Pharmaceutical composition for application to mucosa.

Drugs Protected by US Patent 6,939,559

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

Foreign Priority and PCT Information for Patent: 6,939,559

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	10-110887	Apr 21, 1998
Japan	10-110888	Apr 21, 1998

PCT Information
PCT Filed	April 21, 1999	PCT Application Number:	PCT/JP99/02126
PCT Publication Date:	October 28, 1999	PCT Publication Number:	WO99/53899

International Family Members for US Patent 6,939,559

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	336986
Australia	3534399
Australia	757772
Bulgaria	104020
Bulgaria	64919
Brazil	9906372
Brazil	PI9906372