Details for Patent: 8,518,442

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Summary for Patent: 8,518,442

Title:	Prolonged release bioadhesive therapeutic systems
Abstract:	The present invention concerns a prolonged release bioadhesive mucosal therapeutic system containing at least one active principle, with an active principle dissolution test of more than 70% over 8 hours and to a method for its preparation. Said bioadhesive therapeutic system comprises quantities of natural proteins representing at least 50% by weight of active principle and at least 20% by weight of said tablet, between 10% and 20% of a hydrophilic polymer, and compression excipients, and comprising between 4% and 10% of an alkali metal alkylsulphate to reinforce the local availability of active principle and between 0.1% and 1% of a monohydrate sugar.
Inventor(s):	Jean-Marc Aiache, Dominique Costantini, Christine Chaumont
Assignee:	Vectans Pharma
Application Number:	US12/830,090
Patent Claim Types: see list of patent claims	Composition; Compound; Dosage form;

US Patent 8,518,442: Scope, Claims, Exclusivity and Patent Landscape for Miconazole Bioadhesive Tablets

US Patent 8,518,442 protects a prolonged-release, mucoadhesive antifungal tablet centered on four formulation elements: an azole antifungal, natural proteins, a hydrophilic polymer, and an alkali metal alkylsulfate. The commercially relevant embodiment is a 50 mg miconazole buccal tablet containing milk protein concentrate, methylhydroxypropylcellulose, sodium lauryl sulfate, and conventional compression excipients.

The patent is closely associated with the Oravig formulation for treatment of oropharyngeal candidiasis. Its strongest practical coverage is directed to a specific composition window rather than to miconazole generally. A competing product would need to avoid at least one material limitation, concentration range, dosage form, or claimed combination to reduce literal infringement risk.

What does US Patent 8,518,442 protect?

The patent protects a prolonged-release bioadhesive therapeutic system comprising:

Required element	Independent claim 1 requirement
Antifungal	Broad-spectrum azole
Natural proteins	At least 50% by weight of the antifungal agent and at least 20% by weight of the system
Hydrophilic polymer	10% to 20%
Compression excipients	Required
Alkali metal alkylsulfate	3.5% to 10%
Release platform	Prolonged-release bioadhesive system

Claim 1 is composition-focused. It does not require a particular disease, patient population, administration schedule, manufacturing process, or clinical outcome. Claims 2 through 28 narrow the system into a mucoadhesive tablet, predominantly using sodium lauryl sulfate, miconazole, milk protein concentrate, methylhydroxypropylcellulose, corn starch, lactose monohydrate, and magnesium stearate.

The commercial center of gravity is claims 17 through 28. Those claims combine:

• miconazole;
• milk protein concentrate;
• methylhydroxypropylcellulose or Metolose;
• sodium lauryl sulfate;
• specified miconazole dose ranges;
• specified milk protein concentration ranges;
• specified sodium lauryl sulfate ranges; and
• optional corn starch, lactose monohydrate, and magnesium stearate.

How broad is independent claim 1?

Claim 1 has broad drug-class coverage but narrow formulation architecture.

The azole limitation includes the following compounds under claim 11:

• miconazole;
• clotrimazole;
• ketoconazole;
• fluconazole;
• itraconazole;
• isoconazole;
• econazole;
• saperconazole;
• genaconazole;
• terconazole;
• butoconazole;
• tioconazole;
• oxiconazole;
• bifonazole;
• fenticonazole;
• omoconazole;
• sertaconazole; and
• sulconazole.

The claim does not require miconazole. A product using another listed azole could fall within the claim if all other structural and quantitative requirements are met.

The protein limitation is important. The natural protein must represent at least 20% by weight of the entire bioadhesive system. It must also equal at least 50% of the antifungal agent's weight. For a 50 mg miconazole tablet, the minimum protein amount under the first ratio is 25 mg, although the 20% total-system requirement may impose a higher absolute amount depending on tablet weight.

The polymer limitation requires 10% to 20% hydrophilic polymer. A formulation with 9.9% or 20.1% polymer may present a literal infringement distinction, subject to claim construction and equivalents analysis.

The surfactant limitation requires 3.5% to 10% of an alkali metal alkylsulfate. Claim 3 identifies sodium lauryl sulfate and sodium diethyl sulfosuccinate. Claim 4 narrows the material to sodium lauryl sulfate.

Which dependent claims create the main commercial coverage?

Claims 17 through 24 provide the most important formulation-specific protection.

Claim	Principal limitation
17	Miconazole, milk protein concentrate, methylhydroxypropylcellulose or Metolose, and sodium lauryl sulfate
18	Miconazole dose of 10 to 150 mg per tablet
19	Miconazole dose of 25 to 75 mg per tablet
20	Miconazole dose of 50 mg per tablet
21	Milk protein concentrate at 15% to 50%
22	Milk protein concentrate at 20% to 30%
23	Sodium lauryl sulfate at 4% to 10%
24	Sodium lauryl sulfate at 4% to 6%
25	Corn starch
26	0.1% to 1% monohydrate sugar
27	Lactose monohydrate
28	Magnesium stearate

A 50 mg miconazole buccal tablet containing 20% to 30% milk protein concentrate, 4% to 6% sodium lauryl sulfate, and 10% to 20% methylhydroxypropylcellulose would sit close to the center of the claim set.

Claims 20, 22, and 24 are particularly important because they align the dose and excipient windows with the likely commercial formulation. Claims 25 through 28 add conventional excipient combinations and may be easier to design around, but they provide additional fallback positions if the broader composition claims are narrowed or invalidated.

What formulations are protected by US Patent 8,518,442?

The patent protects more than a simple miconazole tablet. It covers a functional formulation platform in which the protein, polymer, and surfactant jointly support adhesion, hydration, prolonged release, and local delivery.

Protected formulation features

The claimed formulation may include:

1. A broad-spectrum azole antifungal.
2. Natural proteins, including milk protein concentrate.
3. A hydrophilic cellulose polymer.
4. Sodium lauryl sulfate or another claimed alkali metal alkylsulfate.
5. Compression excipients such as corn starch.
6. Optional lactose monohydrate.
7. Optional magnesium stearate.
8. A second active ingredient, including a polyene antifungal, analgesic, anesthetic, salivation agent, antiseptic, antibiotic, anti-inflammatory, salivary substitute, or thalidomide.

Claim 7 expands the system to combination therapy. Claim 8 narrows the second active ingredient to a polyene at 10 to 100 mg per tablet. Claim 14 narrows the polyene to 20 to 90 mg. Claim 9 adds an anesthetic and/or salivation agent at 0.1% to 10%.

The second-agent claims may be commercially relevant for oral candidiasis products combining miconazole with another local therapeutic. They also create additional invalidity and enablement questions because the claim covers a wide range of second agents with different physicochemical properties.

When does US Patent 8,518,442 lose exclusivity?

The patent issued on August 27, 2013, as US Patent No. 8,518,442 B2. Its term is generally calculated from the relevant US or international nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and maintenance-fee status. Public patent records associate the patent with a priority chain dating to the mid-2000s and a nominal expiration in the mid-2020s.

Event	Date or status
Patent number	US 8,518,442 B2
Grant date	August 27, 2013
Technology	Prolonged-release bioadhesive antifungal system
Principal commercial product	Oravig, miconazole 50 mg buccal tablet
Nominal term	Approximately 20 years from the applicable earliest nonprovisional filing date
Expected ordinary expiry	Approximately 2026, subject to official term calculation
Patent-term extension	No extension is established from the supplied record
Regulatory exclusivity	Separate from patent term and dependent on the NDA record

The legally operative expiration date should be taken from the USPTO Patent Center term calculation and the FDA Orange Book listing. Patent expiration does not automatically eliminate regulatory exclusivity, unlisted patent rights, trade secrets, or design-around barriers.

What is the Orange Book status of US Patent 8,518,442?

Oravig is an FDA-approved 50 mg miconazole buccal tablet for treatment of oropharyngeal candidiasis. The product was approved under NDA 022282. FDA labeling describes placement of the tablet on the upper gum, where it adheres and releases miconazole locally over an extended period.[2]

A patent covering the drug product or approved formulation may be listed in the Orange Book if it meets FDA listing requirements. The relevant Orange Book issues are:

• whether US 8,518,442 is listed against NDA 022282;
• whether an FDA use code is assigned;
• whether the listing covers the product, formulation, or method of use;
• whether the listed patent has expired; and
• whether the NDA holder has submitted a patent declaration or delisting notice.

The claims supplied here are formulation claims. They do not contain a conventional method-of-treatment limitation. If the patent is listed against Oravig, its principal Hatch-Waxman relevance would be the product or formulation certification rather than a method-of-use certification.

How do Paragraph IV challenges apply?

An ANDA applicant seeking approval for a generic miconazole buccal tablet would need to address any Orange Book-listed patent associated with Oravig. The applicant could use:

• Paragraph I, if no patent information is listed;
• Paragraph II, if the patent has expired;
• Paragraph III, if approval is sought after the patent expiration date; or
• Paragraph IV, if the applicant asserts that the patent is invalid, unenforceable, or not infringed.

A Paragraph IV notice can trigger litigation if the patent owner or NDA holder files suit within 45 days. A timely suit can create a 30-month stay of FDA approval, subject to statutory exceptions and court action.[3]

For this patent, a Paragraph IV strategy would likely focus on one or more of the following:

Noninfringement

A proposed product could avoid literal infringement by using:

• less than 20% natural protein;
• a non-natural or synthetic bioadhesive;
• a hydrophilic polymer concentration outside 10% to 20%;
• a surfactant other than an alkali metal alkylsulfate;
• sodium lauryl sulfate outside the relevant dependent-claim ranges;
• a non-azole antifungal;
• a non-mucoadhesive dosage form; or
• a different release mechanism.

Invalidity

Potential invalidity theories would include:

• anticipation by an earlier mucoadhesive antifungal tablet;
• obviousness based on combining miconazole, milk proteins, cellulose polymers, and surfactants;
• indefiniteness concerning terms such as "natural proteins," "broad spectrum azole family," or "prolonged release";
• written-description challenges to the broad list of azoles and second agents; and
• enablement challenges based on the breadth of the formulation and combination-agent claims.

The quantitative limitations may help the patent against generic prior art, but they also create potential obviousness arguments if the prior art discloses overlapping ranges or routine optimization of excipient levels.

Which companies are challenging US Patent 8,518,442?

No specific Paragraph IV challenger, ANDA number, or federal infringement action is established by the claim information supplied. A reliable challenger analysis requires current FDA Orange Book data, FDA Paragraph IV notice records, PACER litigation records, and USPTO status data.

The relevant commercial parties have included:

Entity	Role
BioAlliance Pharma	Originator associated with the formulation technology
Strativa Pharmaceuticals	Commercial sponsor associated with Oravig in FDA product materials
Par Pharmaceutical	Commercial and regulatory organization associated with Strativa
Generic manufacturers	Potential ANDA applicants for a miconazole buccal product

The absence of a confirmed challenger in the supplied record should not be treated as proof that no confidential or subsequently filed challenge exists.

How strong is the patent estate?

US 8,518,442 has moderate-to-strong product protection for a formulation that tracks the claimed excipient architecture, but weaker protection against broad product substitution.

Strengths

• The claims use multiple quantitative limitations.
• Claims 17 through 24 target a commercially coherent miconazole formulation.
• The protein, polymer, and surfactant combination may distinguish ordinary miconazole oral dosage forms.
• The 50 mg dose is specifically claimed.
• The patent covers both broad azole alternatives and a narrower miconazole embodiment.

Vulnerabilities

• The core ingredients are conventional pharmaceutical excipients.
• The broad azole list may create written-description and enablement issues.
• The ranges may be attacked through overlapping prior-art disclosures.
• A competitor can potentially alter the protein source, polymer level, surfactant, or release platform.
• The patent does not protect miconazole as an active ingredient generally.
• It does not independently control all oral or buccal miconazole dosage forms.

The most defensible commercial position is therefore formulation-specific. The patent is materially stronger against a close Oravig copy than against a substantially redesigned local miconazole product.

What generic launch risks exist?

Generic launch risk depends on whether an ANDA applicant copies the claimed formulation or pursues a design-around.

Generic strategy	Risk under US 8,518,442
Exact 50 mg miconazole buccal tablet with claimed excipients	High
Same dose but no milk protein concentrate	Reduced, subject to claim 1 and equivalents
Same ingredients with polymer outside 10% to 20%	Reduced
Same ingredients with SLS outside 3.5% to 10%	Reduced
Miconazole lozenge without claimed mucoadhesion	Lower
Non-azole antifungal	Low under the supplied claims
Different bioadhesive protein or synthetic polymer	Potentially lower
Compounded or non-ANDA product	Separate regulatory and infringement analysis

The most practical design-around routes are substitution of the natural protein component, use of a different mucoadhesive polymer system, or removal of the claimed alkali metal alkylsulfate. Each route must be tested against the full claim language and the doctrine of equivalents.

Does the patent create biosimilar risk?

No meaningful biosimilar risk exists. Miconazole is a small-molecule antifungal, not a biologic. The relevant competitive pathway is an ANDA for a generic drug, not a 351(k) biosimilar application.

The principal regulatory and IP issues are:

• pharmaceutical equivalence;
• bioequivalence or other FDA requirements for the buccal dosage form;
• formulation similarity;
• Orange Book patent certifications;
• Paragraph IV litigation; and
• possible differences in local adhesion and release performance.

What manufacturing and trade-secret barriers remain after patent expiry?

Patent expiry would remove the enforceable exclusionary rights of the patent, but it would not necessarily eliminate manufacturing barriers. A competitor may still need to solve:

• uniform distribution of miconazole in a protein-rich matrix;
• control of tablet adhesion to oral mucosa;
• reproducible prolonged release;
• compression behavior of milk protein concentrate;
• surfactant compatibility;
• moisture and stability control;
• taste masking; and
• scale-up of the tablet compression process.

Those barriers may be protected by manufacturing know-how, process parameters, analytical methods, trademarks, or regulatory data even when the formulation patent is no longer enforceable.

How does US Patent 8,518,442 compare with a conventional miconazole product?

Attribute	US 8,518,442 formulation	Conventional miconazole oral product
Dosage form	Mucoadhesive tablet	Tablet, lozenge, cream, or other form
Release	Prolonged	May be immediate or non-bioadhesive
Local adhesion	Required in dependent claims	Not necessarily present
Protein matrix	Natural protein at defined levels	Not required
Hydrophilic polymer	10% to 20% in claim 1	Not required
SLS or related surfactant	3.5% to 10% in claim 1	Not required
Dose specifically claimed	50 mg in claim 13 and claim 20	Dose varies
Regulatory pathway	FDA-approved buccal product and generic ANDA analysis	Product-specific

Key Takeaways

• US Patent 8,518,442 is a formulation patent for prolonged-release, bioadhesive antifungal systems.
• The most commercially important claims cover a 50 mg miconazole mucoadhesive tablet.
• The core limitations are natural protein, hydrophilic polymer, alkali metal alkylsulfate, and compression excipients.
• Milk protein concentrate, methylhydroxypropylcellulose, sodium lauryl sulfate, corn starch, lactose monohydrate, and magnesium stearate are expressly addressed in dependent claims.
• The patent does not broadly claim miconazole or all miconazole dosage forms.
• Generic risk is highest for an Oravig-like formulation and lower for a redesigned dosage form.
• Biosimilar analysis is not applicable because miconazole is a small molecule.
• The nominal patent term reaches approximately 2026, subject to the official USPTO term calculation and any applicable adjustments.
• Paragraph IV exposure depends on current Orange Book listing status and the filing of an ANDA directed to the claimed buccal formulation.
• Formulation know-how and manufacturing controls may remain commercially relevant after patent expiry.

Frequently Asked Questions

Is US Patent 8,518,442 a method-of-use patent?

No. The supplied claims are directed primarily to a bioadhesive therapeutic system and its formulation components. They do not recite a conventional therapeutic treatment method.

Does the patent cover all 50 mg miconazole tablets?

No. It covers 50 mg miconazole tablets only when the claimed formulation and dosage-form limitations are also satisfied, including the relevant protein, polymer, surfactant, and bioadhesive requirements.

Can a generic avoid the patent by changing sodium lauryl sulfate?

Potentially. Replacing sodium lauryl sulfate with a material outside the claimed alkali metal alkylsulfate limitation may reduce literal infringement risk, but the full claim set and equivalents analysis remain relevant.

Is milk protein concentrate mandatory for every claim?

No. It is required by narrower claims such as claims 15, 17, and 21 through 24, but claim 1 covers natural proteins more broadly.

Is an FDA-approved generic miconazole buccal tablet automatically substitutable for Oravig?

No. FDA substitutability depends on the approved ANDA, dosage-form equivalence, labeling, pharmaceutical equivalence, and Orange Book rating. Patent clearance is a separate question.

References

1. United States Patent and Trademark Office. (2013). US Patent No. 8,518,442 B2: Prolonged release bioadhesive therapeutic system.
2. U.S. Food and Drug Administration. (2010). Oravig (miconazole) buccal tablets, 50 mg: Prescribing information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
4. United States Code, 21 U.S.C. § 355(j). (2024). Abbreviated applications for new drugs.

Drugs Protected by US Patent 8,518,442

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: 8,518,442

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
France	01 09811	Jul 23, 2001

International Family Members for US Patent 8,518,442

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	373464
Austria	411003
Canada	2455633
China	101524337
China	1547464
Cyprus	1107828