Details for Patent: 5,919,479

Summary for Patent: 5,919,479

Title:	Noninvasive dermal anesthetics
Abstract:	An apparatus, product formulation, and method for improved dermal permeation of pharmaceuticals wherein the apparatus includes a thin drug formulation reservoir and a heat-generating chamber separated by a first non-permeable wall, wherein the reservoir and chamber are formed in or supported by a housing. The drug formulation reservoir houses or is capable of housing a predetermined amount of a formulation containing pharmaceutically-active agent(s). The heat-generating/temperature-regulating chamber includes a medium for generating controlled heat, preferably a chemical composition made of carbon, iron, water and/or salt which is activated upon contact with air (oxygen). The function of the heat-generating/temperature-regulating element is to heat the user's skin, rapidly bring the skin temperature to a desired and elevated narrow range and keep it in this range for sufficient time to obtain more rapid, enhanced and less variable dermal absorption of selected pharmaceutically-active agents and to obtain improved clinical effects. Structure for controlling the generation of heat is also disclosed. The apparatus may optionally include a spacing or standoff structure which spans the drug formulation reservoir between the non-permeable wall and the user's skin surface for maintaining a predetermined thickness of the drug formulation on the user's skin surface. Also, a novel product formulation which can be used with the apparatus which uses high percentage of eutectic mixture of local anesthetics to reduce the overall degradation rate of the local anesthetic compound(s) in formulations which are subject to hydrolysis.
Inventor(s):	Jie Zhang, Hao Zhang
Assignee:	NUVO RESEARCH AMERICA Inc , Nuvo Research Inc
Application Number:	US08/819,880
Patent Claim Types: see list of patent claims	Formulation; Compound;

United States Patent 5,919,479: Scope, Claims, Expiration, and Topical Anesthetic Patent Landscape

U.S. Patent No. 5,919,479 covers topical dermal anesthetic emulsions containing a eutectic mixture of tetracaine and lidocaine at a concentration of at least about 12% by weight. The broadest claim requires an oil-in-water or related emulsion in which the oil phase is the tetracaine-lidocaine eutectic mixture. Dependent claims add gelation, thickening, pH control, permeation enhancers, and temperature-responsive behavior.

The patent is expired. Its commercial importance was concentrated in topical anesthetic products using approximately equal amounts of tetracaine and lidocaine, including formulations related to the product concepts later commercialized as Pliaglis and Synera. The patent does not currently create a blocking U.S. right for generic creams, gels, patches, or other products.

What does U.S. Patent 5,919,479 protect?

The patent protects a specific formulation architecture rather than tetracaine, lidocaine, or topical anesthesia generally.

The core elements are:

1. A formulation intended to provide dermal anesthesia.
2. An emulsion containing an oil phase and an aqueous phase.
3. An oil phase composed of a eutectic mixture of tetracaine and lidocaine.
4. A eutectic-mixture concentration of about 12% or greater by weight.

The claim set then narrows the formulation by adding physical, chemical, or performance characteristics:

Claim	Principal limitation	Scope
1	Emulsion; tetracaine-lidocaine eutectic in oil phase; at least about 12% by weight	Broad independent formulation claim
2	Emulsion is substantially non-flowable and cohesive at ambient temperature	Thickened or semi-solid products
3	pH regulators, coloring agents, permeation enhancers, or combinations	Additive-containing formulations
4	Tetracaine-to-lidocaine ratio between 1:0.5 and 1:1.5	Approximately balanced anesthetic ratio
5	Approximately 1:1 tetracaine-to-lidocaine ratio	Narrower equal-weight formulation
6	Eutectic mixture exceeds about 18% by weight	Higher-loading products
7	Emulsifier, gelling agent, or thickening agent	Structured emulsions
8	Emulsion is gelled	Gelled formulation
9	Gelled emulsion rapidly melts or substantially softens above about 30°C	Temperature-softening product
10	Gelled emulsion does not melt or substantially soften at about 30°C	Temperature-stable product
11	Gelled emulsion softens or melts at about 30°C	Independent temperature-responsive claim
12	Gelled emulsion remains stable at about 30°C	Independent temperature-stable claim

The specification’s stated objectives are reduced anesthetic degradation and improved noninvasive dermal anesthesia. Those objectives help explain the invention but do not replace the structural limitations in the claims. A product must satisfy the required formulation elements, not merely produce topical anesthesia.

How broad is claim 1 of U.S. Patent 5,919,479?

Claim 1 is the principal scope-defining claim. It is broad in formulation design but narrow in active-ingredient selection and physical arrangement.

A formulation would generally need to satisfy all of the following to fall within the literal scope:

• It must be an emulsion.
• The emulsion must have both an oil phase and an aqueous phase.
• The oil phase must contain, or be constituted by, a eutectic mixture of tetracaine and lidocaine.
• The eutectic mixture must comprise about 12% or more of the total formulation by weight.

The claim does not expressly require:

• A particular commercial dosage form.
• A specific pH.
• A particular emulsifier.
• A particular permeation enhancer.
• A particular container or delivery system.
• A specific treatment indication.
• A particular application time.
• A specific ratio within claim 1 itself, although claims 4 and 5 narrow the ratio.

The phrase "about 12%" introduces a numerical boundary that would require technical and legal construction. A formulation containing 12%, 13%, or 14% of the eutectic mixture would present a materially greater literal-infringement risk than a formulation containing 10% or 11%. The precise boundary would depend on the intrinsic evidence, prosecution history, analytical measurement method, and any applicable tolerance for the term "about."

What does the eutectic-mixture limitation require?

A eutectic mixture is not merely a physical blend of tetracaine and lidocaine. It is a mixture having a depressed melting point relative to the individual components, typically produced at or near a composition that permits the anesthetics to form a liquid or low-melting phase.

Claims 4 and 5 indicate that the preferred composition is approximately equal parts tetracaine and lidocaine by weight:

• Claim 4 covers a ratio from 1:0.5 to 1:1.5.
• Claim 5 narrows the ratio to substantially 1:1.
• Claim 1 does not expressly recite a ratio, but the eutectic-mixture requirement may impose a practical compositional limitation through the patent’s technical disclosure.

A formulation containing lidocaine alone, tetracaine alone, or a non-eutectic combination of the two anesthetics would not satisfy the central limitation as written. A product with the two drugs in separate phases would also present a substantial non-infringement argument unless the separate phases nevertheless constituted the claimed eutectic oil phase under the relevant claim construction.

How do claims 2 through 12 narrow the patent?

Claims 2 through 10 depend from claim 1 and therefore retain every limitation of claim 1. They do not provide alternative routes around the emulsion and eutectic-mixture requirements.

Claims 2, 7, and 8 address formulation structure. They target products that are thickened or gelled rather than freely flowing liquids. Claim 2 requires a formulation that is substantially non-flowable and cohesive at ambient temperature. Claim 8 requires a gelled emulsion.

Claims 9 and 11 cover formulations that soften or melt when heated to approximately 30°C. Claims 10 and 12 cover the opposite behavior: the formulation does not melt or significantly soften at approximately 30°C.

Claims 9 and 10 are alternative dependent limitations. A single formulation may not ordinarily satisfy both unless the terms are interpreted through different test conditions or temperature ranges. Claims 11 and 12 are independent claims that repeat most of the same limitations but expressly place the thermal behavior in the independent claim.

The claim structure creates two technical product categories:

Product category	Relevant claims	Commercial implication
Semi-solid or cohesive emulsion	1, 2, 7, 8	Creams, gels, and structured topical products
Heat-softening gelled emulsion	9, 11	Products that become easier to spread or remove near skin temperature
Heat-stable gelled emulsion	10, 12	Products designed to retain structure at approximately 30°C
High-loading anesthetic emulsion	6	Formulations containing more than about 18% eutectic mixture

What formulations are protected by the patent?

The strongest product fit is a topical cream or gel containing approximately equal weights of lidocaine and tetracaine, with the combined eutectic phase representing at least about 12% of the formulation.

A 7% lidocaine and 7% tetracaine formulation contains approximately 14% total anesthetic, assuming the two active ingredients form the claimed eutectic mixture. That concentration is above the claim 1 threshold but below the more than 18% threshold in claim 6.

Potentially relevant formulation types include:

• Peelable topical anesthetic creams.
• Gelled emulsions.
• Semi-solid dermal anesthetic preparations.
• Emulsions containing permeation enhancers.
• Formulations with pH modifiers and stabilizers.
• Temperature-responsive topical anesthetic products.
• Products using approximately 1:1 tetracaine and lidocaine.

The claims do not expressly require a peelable film. A peelable film may satisfy the claims if it is technically an emulsion with the claimed oil phase and concentration.

When did U.S. Patent 5,919,479 lose exclusivity?

U.S. Patent 5,919,479 issued on July 6, 1999. Because it was filed under the post-1995 patent-term regime, its nominal term was generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and other statutory adjustments.[1]

The patent’s enforceable term therefore ended in approximately 2016 or 2017. It is expired and cannot support a new U.S. infringement action based on conduct occurring after expiration.

The expiration analysis is separate from FDA regulatory exclusivity. Even when the patent was in force, an approved product could have had additional FDA exclusivity. Conversely, the expiration of this patent did not automatically remove other patents covering a commercial product, delivery device, manufacturing process, or separate formulation.

What is the Orange Book status of U.S. Patent 5,919,479?

U.S. Patent 5,919,479 is not, by itself, a current Orange Book barrier.

The Orange Book lists patents submitted for approved drug products under Section 505 of the Federal Food, Drug, and Cosmetic Act. Listing depends on the NDA holder’s submission and FDA’s administrative treatment of the patent. A patent covering a formulation concept may be absent from the Orange Book, may have been listed for a particular NDA, or may have expired while remaining historically visible in product records.[2]

The patent does not create a current 30-month stay risk for an ANDA applicant solely because it once covered a topical anesthetic concept. A Paragraph IV certification would be relevant only if the patent were listed for the reference product and remained unexpired. For an expired patent, the practical certification and litigation consequences are materially different from those associated with an active Orange Book patent.

Which companies and products are most relevant to this patent landscape?

The relevant competitive landscape includes two-part topical anesthetic systems containing lidocaine and tetracaine.

Pliaglis

Pliaglis is a topical anesthetic cream containing lidocaine and tetracaine. The product uses a peelable formulation that dries on the skin and can be removed after application. Its commercial formulation is commonly described as 7% lidocaine and 7% tetracaine, or approximately 14% combined active ingredient.[3]

That concentration falls within the numerical range of claim 1 if the active ingredients are present as the claimed eutectic mixture. Commercial protection for Pliaglis, however, depended on the full patent estate associated with the product, not solely on U.S. Patent 5,919,479.

Synera

Synera is a topical anesthetic patch that delivers lidocaine and tetracaine through a heat-activated or drug-in-adhesive delivery system. It is a different dosage form from a cream or gel, but its active-ingredient combination is relevant to the same technical field.[4]

A patch product would not infringe claim 1 merely because it contains tetracaine and lidocaine. It would need to meet the claim’s emulsion and oil-phase requirements. Device and adhesive-layer patents may create separate intellectual-property issues.

EMLA

EMLA contains lidocaine and prilocaine, not tetracaine. It is therefore outside the specific active-ingredient combination required by Patent 5,919,479.[5] EMLA remains a relevant comparator for topical anesthetic formulation, regulatory, and generic competition analysis, but it is not a direct active-ingredient match.

How does this patent compare with competing topical anesthetic patents?

Patent concept	Active ingredients	Core dosage form	Relationship to 5,919,479
U.S. 5,919,479	Tetracaine plus lidocaine	Emulsion or gelled emulsion	Directly claims the eutectic formulation architecture
Pliaglis-related estate	Tetracaine plus lidocaine	Peelable cream	May overlap technically but depends on separate product claims
Synera-related estate	Tetracaine plus lidocaine	Patch or delivery system	Active-ingredient overlap; emulsion limitation may not be met
EMLA-related estate	Lidocaine plus prilocaine	Cream	Different active-ingredient combination
Lidocaine-only products	Lidocaine	Cream, gel, patch, ointment	Outside the tetracaine-lidocaine requirement

The patent’s principal distinction is the combination of a eutectic tetracaine-lidocaine phase with an emulsion containing an aqueous phase. A competitor can reduce literal overlap by using a different active ingredient, a non-emulsion dosage form, a non-eutectic mixture, or a concentration below the claimed threshold. Each design-around must be evaluated against the full patent estate and the doctrine of equivalents.

What Paragraph IV challenges and litigation affected this patent?

The principal litigation risk associated with this patent is historical, not current. The patent expired approximately eight years ago, so it no longer presents a live patent-term barrier to generic or follow-on formulation development.

Paragraph IV activity for topical tetracaine-lidocaine products would more likely have focused on patents listed for specific reference products, including product-specific formulation, peel-film, delivery-device, or manufacturing patents. A Paragraph IV challenge to another patent does not establish invalidity or noninfringement of U.S. Patent 5,919,479.

No current litigation based solely on U.S. Patent 5,919,479 can maintain an ordinary prospective exclusion right after expiration. Historical cases, if any, must be distinguished from current launch risk because the patent’s term has ended. Current exposure would arise from other unexpired patents, trade secrets, trademarks, regulatory exclusivity, or product-specific rights.

How strong was the patent estate?

The patent was technically meaningful but commercially narrow.

Strengths

• It claimed the central active-ingredient combination.
• It covered both liquid and structured emulsion embodiments.
• It included concentration, ratio, gelation, and thermal-response limitations.
• Claims 11 and 12 provided independent protection for two thermal-behavior categories.
• A commercial product containing approximately 7% lidocaine and 7% tetracaine could fall above the 12% threshold.

Weaknesses

• The claims are limited to an emulsion with an oil phase and aqueous phase.
• The eutectic-mixture requirement creates a technical proof issue.
• The "about 12%" and "about 30°C" limitations can generate claim-construction disputes.
• The claims do not broadly cover every topical tetracaine-lidocaine product.
• The claims do not cover lidocaine-prilocaine products.
• The patent does not provide current exclusivity because its term has expired.

The formulation claims could have been challenged on written-description, enablement, indefiniteness, anticipation, or obviousness grounds depending on the prior art and prosecution history. The most vulnerable issues would likely have involved the meaning of "eutectic mixture," the boundaries of "about," and whether the specification enabled the claimed range of formulations without undue experimentation.

What generic entry risks exist for tetracaine-lidocaine products?

For a new U.S. product, Patent 5,919,479 presents no current patent-expiry delay. The remaining risks are product-specific.

A generic or follow-on applicant should assess:

1. Active Orange Book patents for the selected reference product.
2. Formulation patents covering peelability, drying, film formation, or stability.
3. Device patents for patches, applicators, or heat activation.
4. Method-of-use patents covering dermal anesthesia procedures.
5. Manufacturing patents involving emulsification, particle size, or phase control.
6. FDA pathway classification, including NDA, ANDA, or 505(b)(2).
7. Demonstration of equivalent local anesthetic delivery and clinical performance.
8. Controlled-substance, pharmacovigilance, and local-anesthetic safety requirements.

For a cream containing approximately 14% combined lidocaine and tetracaine, the expired patent is unlikely to be the principal launch obstacle. The main regulatory issue is whether the product can rely on an approved reference product or must proceed through a 505(b)(2) or NDA pathway.

What manufacturing and geographic barriers remain?

The patent’s territorial scope was limited to the United States. It did not independently block manufacture, sale, or use outside the United States. Foreign equivalents would require separate national or regional analysis.

Manufacturing complexity can remain important even after patent expiry. A stable tetracaine-lidocaine eutectic emulsion may require control of:

• Active-ingredient ratios.
• Phase inversion and emulsification conditions.
• Particle or droplet size.
• pH.
• Water activity.
• Preservative compatibility.
• Anesthetic degradation products.
• Gel strength and spreadability.
• Temperature sensitivity.
• Packaging and storage conditions.

Those process parameters may be protected by separate patents or trade secrets. They may also affect FDA comparability, stability data, and batch-release specifications.

Key Takeaways

• U.S. Patent 5,919,479 claims emulsions containing a tetracaine-lidocaine eutectic mixture at about 12% or greater by weight.
• Claims 4 and 5 focus on approximately equal tetracaine and lidocaine ratios.
• Claims 2, 7, and 8 cover thickened or gelled emulsions.
• Claims 9 through 12 divide products by whether they soften or remain stable at approximately 30°C.
• A 7% lidocaine/7% tetracaine formulation contains approximately 14% combined anesthetic and may fit the numerical threshold of claim 1.
• The patent’s nominal term ended in approximately 2016 or 2017, and the patent is expired.
• It does not create a current U.S. Orange Book or Paragraph IV barrier by itself.
• Pliaglis is the closest commercial formulation comparator.
• Synera is relevant to the same active ingredients but uses a patch-based delivery system.
• EMLA is not a direct overlap because it contains prilocaine instead of tetracaine.
• Current launch risk depends on other formulation, device, manufacturing, method-of-use, regulatory, and trademark rights.

FAQs

Does Patent 5,919,479 cover Pliaglis?

Pliaglis is technically relevant because it contains lidocaine and tetracaine at approximately 7% each. Its approximately 14% combined active concentration is above the patent’s about 12% threshold. Whether a particular Pliaglis formulation met every limitation depended on its emulsion structure, eutectic phase, and prosecution history. The patent is now expired.

Can a company launch a tetracaine-lidocaine cream without a Paragraph IV challenge?

Yes, with respect to Patent 5,919,479 because it is expired. A Paragraph IV certification may still be required for other unexpired patents listed for the selected reference product.

Does the patent cover a lidocaine-tetracaine patch?

Not automatically. Claim 1 requires an emulsion with an oil phase and an aqueous phase. A patch would fall within the claim only if its drug-containing layer satisfies those formulation limitations. Separate patch or adhesive patents may apply.

Does a 10% lidocaine-tetracaine formulation avoid the patent?

It would be below the express about 12% threshold, creating a strong literal noninfringement position. The complete formulation would still need review against other claims, other patents, and any doctrine-of-equivalents argument.

Are foreign patents based on U.S. Patent 5,919,479 still enforceable?

The U.S. patent’s expiration does not determine foreign rights. Each foreign counterpart requires a separate review of filing dates, national-phase status, patent-term adjustments, maintenance fees, and expiration dates.

References

1. United States Patent and Trademark Office. (2024). Patent term calculator and patent term provisions. https://www.uspto.gov/patents/laws/patent-term-calculator
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
3. Galderma Laboratories, L.P. (2023). Pliaglis prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov
4. ZARS Pharma, Inc. (2023). Synera prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov
5. AstraZeneca Pharmaceuticals LP. (2023). EMLA prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov
6. United States Patent and Trademark Office. (1999). U.S. Patent No. 5,919,479. https://patents.google.com/patent/US5919479A en

Drugs Protected by US Patent 5,919,479

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 5,919,479

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	320233
Austria	489949
Australia	2002336585
Australia	5924199
Australia	6406299
Australia	6638696