United States Drug Patent 4,906,463: Claim Scope, Expiration, and Transdermal Patent Landscape

United States Patent 4,906,463 covers polymer-based, nonaqueous transdermal or transmucosal compositions using selected fatty acid esters or fatty alcohol ethers as permeation enhancers. The most commercially specific claims focus on propylene glycol monolaurate used with estradiol or fentanyl. The patent issued on March 6, 1990 and, absent patent-term adjustment or extension, expired on March 6, 2007 under the pre-URAA 17-year term from grant. Its U.S. claims no longer create an enforceable exclusivity barrier.

What does United States Patent 4,906,463 cover?

The patent claims a drug-delivery composition containing four required elements:

A drug.
A polymer.
A nonaqueous formulation.
A permeation-enhancing fatty acid ester or fatty alcohol ether derived from a C2 to C4 alkanediol.

The fatty-acid or fatty-alcohol portion must contain approximately 8 to 22 carbon atoms. The claims extend to transdermal and transmucosal administration and include both composition and method-of-use protection.[1]

The central technical concept is the use of a lipophilic enhancer incorporated into a polymeric delivery system. The enhancer is intended to increase transport of the drug through skin or a mucosal membrane while remaining in a substantially nonaqueous polymer formulation.

What chemical classes fall within the claimed enhancer?

The independent claims identify two principal classes:

Claimed class	Structural requirement	Representative scope
Fatty acid ester of a C2-C4 alkanediol	Ester formed between an alkanediol and a C8-C22 fatty acid	Propylene glycol laurate
Fatty alcohol ether of a C2-C4 alkanediol	Ether formed between an alkanediol and a C8-C22 fatty alcohol	C8-C22 fatty alcohol ether of ethylene glycol, propylene glycol, or butylene glycol

Claim 6 narrows the ester and ether categories to monoesters and monoethers. Claim 7 separately recites a fatty acid monoester of propylene glycol. Claim 8 narrows that category to propylene glycol monolaurate.

The claim language does not cover every permeation enhancer. A formulation using ethanol, oleic acid, isopropyl myristate, a surfactant, or a different glycol ester would not fall within the claims merely because it improves skin permeation. The enhancer must satisfy the claimed structural and carbon-chain limitations.

How do the claims of U.S. Patent 4,906,463 differ?

Claims 1 through 6: broad composition and device claims

Claim 1 is the principal composition claim. It requires a nonaqueous mixture of:

A polymer;
A drug; and
A permeation-enhancing fatty acid ester or fatty alcohol ether meeting the C2-C4 alkanediol and C8-C22 chain limitations.

Claim 2 limits the composition to a solid-state transdermal drug-delivery device.

Claim 3 limits the drug to estradiol or fentanyl. This is commercially important because both drugs were established transdermal products, but claim 3 remains subject to every limitation in claims 1 and 2.

Claim 4 requires a laminated composite with:

A reservoir layer; and
A pressure-sensitive adhesive layer.

Claim 5 requires the drug and enhancer to be primarily in the reservoir layer. A product that places the active ingredient primarily in the adhesive layer may avoid literal infringement of this limitation, although the full claim set and equivalents would still require analysis.

Claims 7 through 9: propylene glycol monoester claims

Claim 7 is narrower in chemical scope than claim 1 but removes the express requirement that the alkanediol be any C2-C4 member. It specifically requires a fatty acid monoester of propylene glycol.

Claim 8 identifies propylene glycol monolaurate. Lauric acid has 12 carbon atoms, placing the compound within the claimed C8-C22 range.

Claim 9 further limits the drug to estradiol or fentanyl. This is the most commercially targeted composition subgroup in the patent.

Claims 10 through 12: method claims

Claim 10 covers a method of enhancing drug permeation by coadministering the claimed enhancer from a nonaqueous polymer mixture.

Claim 11 limits the drug to estradiol or fentanyl.

Claim 12 is the narrowest method claim. It requires:

Skin administration;
Estradiol or fentanyl;
Propylene glycol monolaurate;
A nonaqueous mixture;
A polymer; and
The selected drug.

A method claim generally requires performance of the claimed administration steps. Merely manufacturing or selling a composition may implicate a composition claim without independently practicing the method claim.

What is the patent expiration date for U.S. Patent 4,906,463?

U.S. Patent 4,906,463 issued on March 6, 1990.[1] For a patent subject to the pre-URAA term regime, the ordinary term was 17 years from issuance. The resulting base expiration date was March 6, 2007.[2]

Event	Date
Patent issued	March 6, 1990
Standard pre-URAA term	17 years from issue
Base expiration	March 6, 2007
Current U.S. enforceability	Expired

A patent-term extension under 35 U.S.C. § 156 would require an eligible regulatory product and a qualifying application. No current Orange Book or FDA record establishes a term extension for this patent. Patent-term adjustment under modern § 154 rules generally does not alter the analysis for a patent issued in 1990.

The expired status means that a new U.S. product meeting the historical claim limitations would not face infringement liability from this patent. Expiration does not invalidate the patent’s historical relevance as prior art.

What is the Orange Book status of U.S. Patent 4,906,463?

U.S. Patent 4,906,463 is not a current source of Orange Book exclusivity. The Orange Book lists patents and exclusivity associated with approved drug products, not every patent that may relate technically to a drug-delivery platform.[3]

The patent’s claims are platform-oriented. They do not identify a single FDA-approved product, New Drug Application, dosage strength, or labeled indication. That structure reduces the likelihood that the patent would function as a product-specific Orange Book barrier.

For a listed drug, a generic applicant’s Paragraph IV certification could historically have challenged a listed patent. Once the patent expired in 2007, it ceased to present a current Paragraph IV launch obstacle. A generic applicant would instead evaluate any later-expiring patents covering the active ingredient, dosage form, formulation, delivery system, or method of use.

How strong is the patent estate for estradiol and fentanyl transdermal products?

The patent was technically significant at the formulation level but is weak as a current exclusivity asset because its only identified U.S. patent term has ended.

Estradiol patches

Estradiol transdermal products have historically included reservoir and matrix patch technologies. Commercial products have been protected through combinations of:

Drug-delivery system patents;
Adhesive and matrix patents;
Controlled-release patents;
Manufacturing patents;
Method-of-treatment patents; and
Regulatory exclusivity attached to particular approvals.

U.S. Patent 4,906,463 would reach an estradiol product only if the product used the claimed enhancer, polymer, nonaqueous formulation, and, for narrower claims, the required reservoir and adhesive architecture. The presence of estradiol alone is insufficient.

Fentanyl patches

Fentanyl delivery systems have relied on reservoir patches, matrix patches, pressure-sensitive adhesives, rate-controlling membranes, and abuse-deterrence technologies. The patent’s fentanyl claims are limited to formulations using the specified enhancer classes.

A fentanyl patch using a different enhancer system, a substantially different architecture, or no claimed fatty ester or fatty alcohol ether would require separate analysis. The patent does not claim fentanyl transdermal delivery generally.

What generic entry risks existed before expiration?

Before March 6, 2007, a generic or follow-on transdermal manufacturer could have faced several risks:

Risk	Relevance to Patent 4,906,463
Literal composition infringement	Required the claimed polymer, drug, nonaqueous mixture, and enhancer
Device infringement	Applied to solid-state devices and, in narrower claims, laminated reservoir/adhesive systems
Method infringement	Applied to administration of the claimed enhancer-containing formulation
Doctrine of equivalents	Could address insubstantial structural substitutions, subject to prosecution history and claim limits
Validity challenge	Potential grounds included anticipation, obviousness, enablement, written description, and indefiniteness
FDA listing risk	Depended on whether the patent was listed for a specific approved product
Manufacturing risk	Could arise where the same enhancer-polymer mixture was used during commercial production

After expiration, the patent no longer creates a generic-launch risk in the United States. Later patents can still create blocking positions even when an earlier platform patent has expired.

Were Paragraph IV challenges or patent litigation material to this patent?

The patent’s expiration eliminates any current Paragraph IV challenge directed solely to U.S. Patent 4,906,463. A Paragraph IV certification is relevant only when a listed patent remains unexpired or otherwise affects the ANDA applicant’s certification position.[4]

The patent number alone does not establish that a specific estradiol or fentanyl product was covered by the patent, listed in the Orange Book, or involved in litigation. Patent litigation would require a product-specific record showing:

The asserted claims;
The accused product;
The relevant FDA listing;
The filing date;
The court and docket;
Any preliminary injunction or settlement; and
The final disposition.

No current enforcement action can be based on the expired U.S. rights in this patent. Any historical settlement involving a product or related patent would not revive the expired patent term.

What patent landscape surrounds transdermal permeation enhancers?

The surrounding landscape generally divides into five patent groups.

Formulation patents

These cover the combination of a drug, polymer, adhesive, solvent, enhancer, stabilizer, or crystallization inhibitor. U.S. Patent 4,906,463 belongs primarily to this category.

Device and architecture patents

These cover reservoirs, membranes, adhesive matrices, multilayer patches, backing layers, and rate-control structures. Claim 4 of the patent reaches one laminated reservoir-and-adhesive configuration.

Method-of-use patents

These cover treatment of a disease or administration of a drug through skin or mucosa. Claims 10 through 12 are formulation-linked permeation-enhancement method claims rather than broad therapeutic indication claims.

Manufacturing patents

These may cover mixing, coating, drying, laminating, cutting, packaging, or controlling residual solvent and drug crystallization. They can create practical barriers after a core composition patent expires.

Product-specific patents

These are directed to a particular commercial patch, dosage strength, adhesive system, release profile, or approved use. They are more likely than a historical platform patent to appear in an Orange Book patent listing.

Does U.S. Patent 4,906,463 create biosimilar risk?

No. Estradiol and fentanyl are small-molecule active ingredients, not biologic products. Biosimilar pathways under the Biologics Price Competition and Innovation Act do not apply to these products.[5]

The relevant competitive pathways are:

ANDA approval for a qualifying generic;
Section 505(b)(2) approval for a reformulated or differently delivered product;
A new NDA for a materially novel transdermal system; and
State and federal controlled-substance requirements for fentanyl products.

Fentanyl products face additional manufacturing, diversion-control, labeling, and risk-management considerations that are separate from this patent.

How does this patent compare with later transdermal patent estates?

Attribute	U.S. Patent 4,906,463	Later product-specific estates
Primary focus	Permeation-enhancer composition	Commercial patch, release profile, adhesive, or indication
Key chemical limitation	C2-C4 alkanediol ester or ether with C8-C22 fatty portion	Often a defined polymer, adhesive, solvent, or drug concentration
Drug specificity	Estradiol or fentanyl in dependent claims	Often one approved active ingredient
Device coverage	Includes reservoir and pressure-sensitive adhesive configuration	May cover matrix, multilayer, membrane, or microneedle systems
U.S. status	Expired March 6, 2007	Depends on each patent’s filing and term dates
Current launch impact	None from this patent alone	Potentially material if unexpired and enforceable

The key diligence issue is claim overlap, not product-label similarity. A modern patch may deliver the same drug and use the same route while avoiding this patent through a different enhancer, polymer, layer arrangement, or manufacturing process.

What geographic coverage remains?

The patent provides rights only in the United States. Any international family members would require separate country-by-country review. Foreign patents may have:

Different claims;
Different priority dates;
Different term calculations;
Different prosecution amendments;
Different legal status; and
Different litigation or opposition histories.

Expiration of the U.S. patent does not establish expiration of a corresponding European, Canadian, Japanese, or other foreign patent. A global freedom-to-operate analysis must identify each family member and check national registers.

Key Takeaways

U.S. Patent 4,906,463 covers nonaqueous polymeric transdermal or transmucosal formulations using specified fatty acid esters or fatty alcohol ethers.
Propylene glycol monolaurate is the most specific enhancer identified in the claims.
Estradiol and fentanyl are expressly recited in dependent composition and method claims.
The patent reaches both formulations and selected device architectures, including reservoir and pressure-sensitive adhesive systems.
The patent issued March 6, 1990 and ordinarily expired March 6, 2007.
It is not a current U.S. exclusivity barrier, Orange Book barrier, or Paragraph IV obstacle.
The patent does not cover all estradiol or fentanyl patches.
Current risk must be assessed against later formulation, device, manufacturing, method-of-use, and product-specific patents.
No biosimilar pathway applies because estradiol and fentanyl are small molecules.
Foreign family members, if any, require separate national-status analysis.

Frequently Asked Questions

Can a company sell a propylene glycol monolaurate transdermal patch today?

In the United States, U.S. Patent 4,906,463 alone does not prevent sale because its patent term expired in 2007. Other unexpired patents, FDA requirements, controlled-substance rules, and product-specific rights may still apply.

Does the patent cover a fentanyl patch with any fatty-acid enhancer?

No. The enhancer must satisfy the claimed structural limitations. The formulation must also include the required polymer, drug, and nonaqueous mixture.

Would an adhesive matrix patch infringe claims 1 and 7?

Potentially, if it contains the claimed drug, polymer, nonaqueous mixture, and qualifying fatty acid ester or fatty alcohol ether. Claims 1 and 7 are not limited to the laminated reservoir structure in claim 4.

Does patent expiration eliminate FDA approval requirements?

No. Patent expiration affects exclusivity only. A transdermal estradiol or fentanyl product still requires the applicable FDA approval pathway, manufacturing controls, labeling, and postmarket obligations.

Can the expired patent be used against a later product outside the United States?

No, not as a U.S. patent right. A corresponding foreign patent could have a separate term and enforceability status, but that requires confirmation in the relevant national patent register.

References

U.S. Patent No. 4,906,463. (1990). Pharmaceutical compositions and methods for transdermal or transmucosal drug administration. United States Patent and Trademark Office.
35 U.S.C. § 154. (2024). Patent term and adjustment. United States Code.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Patent certifications and the 30-month stay. FDA.
Biologics Price Competition and Innovation Act of 2009, Pub. L. No. 111-148, §§ 7001-7003, 124 Stat. 119.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	119019	⤷ Start Trial
Austria	124256	⤷ Start Trial
Austria	87202	⤷ Start Trial
Australia	3853089	⤷ Start Trial
Australia	5784590	⤷ Start Trial
Australia	601528	⤷ Start Trial
Australia	633500	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,906,463

Summary for Patent: 4,906,463