U.S. Patent 5,212,199: Scope, Claim Construction, Expiration, and Transdermal Patent Landscape

U.S. Patent 5,212,199 covers transdermal delivery compositions and methods using sorbitan ester permeation enhancers, including sorbitan monooleate and sorbitan monolaurate. The claims extend to formulations containing a C1-C4 aliphatic alcohol and expressly identify pindolol as an active agent. The patent issued May 18, 1993 and, under the pre-Uruguay Round patent term applicable to the patent, expired May 18, 2010. It no longer creates a U.S. blocking right against generic products or competing transdermal formulations. [1, 2]

The patent remains relevant as prior art in disputes involving transdermal penetration enhancers, formulation obviousness, and freedom-to-operate analyses.

What does U.S. Patent 5,212,199 protect?

The patent protects two related categories:

Methods of enhancing skin penetration by applying an active agent and a specified sorbitan ester to intact skin.
Compositions containing the active agent and the specified sorbitan ester, with an optional lower aliphatic alcohol and inert vehicle.

The central technical feature is the use of a sorbitan ester as a permeation enhancer. The claims do not broadly cover every transdermal enhancer. They are limited by the structural and compositional requirements recited in the claims.

Claim group	Subject matter	Principal limitation
Claims 1-5	Transdermal application methods	Sorbitan ester enhancer
Claims 6-10	Transdermal application methods	Sorbitan ester plus C1-C4 alcohol
Claims 11-16	Transdermal compositions	Sorbitan ester enhancer
Claims 17-21	Transdermal compositions	Sorbitan ester plus C1-C4 alcohol

The claims use “consisting essentially of” for the sorbitan ester enhancer. That transitional phrase generally permits additional ingredients that do not materially affect the basic and novel characteristics of the claimed invention, while excluding ingredients that materially alter those characteristics. The legal effect depends on the specification, prosecution history, and the accused formulation. [3]

What chemical structures fall within the sorbitan ester claims?

The claimed enhancer is a sorbitan ester in which at least one ester substituent contains an aliphatic hydrocarbon chain. The claimed R' group may be:

Saturated;
Mono-unsaturated;
Di-unsaturated; or
Tri-unsaturated;

and may contain seven to 21 carbon atoms, with up to three hydroxyl groups.

The dependent claims narrow the carbon-chain range to 11-21 carbon atoms and require the remaining R2 and R3 positions to be hydroxyl groups. Claims 3, 8, 14, and 19 then identify specific compounds:

Sorbitan monooleate;
Sorbitan monolaurate; and
Mixtures of those compounds.

The principal commercial compounds are commonly associated with the surfactant excipients sold as Span 80, generally corresponding to sorbitan monooleate, and Span 20, generally corresponding to sorbitan monolaurate. Commercial excipient identity, purity, ester distribution, and manufacturing specifications would matter in an infringement analysis because commercial sorbitan products can contain related ester species.

How broad is the Markush definition?

The independent claims are materially broader than the named compounds. A formulation may potentially fall within the independent claims even if it does not use sorbitan monooleate or sorbitan monolaurate, provided the sorbitan ester satisfies the recited structural limitations.

The scope includes ester substituents with hydrocarbon chains from seven to 21 carbon atoms. Claims 2, 3, 7, 8, 13, 14, 18, and 19 narrow the scope to chains from 11 to 21 carbon atoms and require a monoester configuration with two hydroxyl groups remaining on the sorbitan moiety.

The independent claims do not require:

A particular patch or backing layer;
A reservoir or matrix system;
A specific drug concentration;
A particular application duration;
A specific skin site;
A particular therapeutic indication; or
A particular release-rate profile.

Those omissions make the claims potentially broad at the formulation and method level, although the patent is now expired.

Which claims cover pindolol transdermal delivery?

Claims 4, 15, and 21 specifically identify pindolol.

Claim	Category	Pindolol limitation
Claim 4	Method	Pindolol with the sorbitan ester enhancer
Claim 15	Composition	Pindolol with the sorbitan ester enhancer
Claim 21	Composition	Pindolol with the sorbitan ester and C1-C4 alcohol

Pindolol is a beta-adrenergic antagonist. The claims do not require that the active agent be limited to pindolol except in these dependent claims. The broader independent claims cover a “pharmacologically active agent,” subject to the other limitations.

The independent method claims require a “therapeutically effective amount” applied to intact skin. That limitation can create factual issues involving dose, intended therapeutic use, and whether the accused product is designed for pharmacologic transdermal delivery rather than topical treatment.

What formulations are protected by U.S. Patent 5,212,199?

Claims 5, 10, and 16 expressly require or permit a single pharmaceutical composition containing the active agent, enhancer, and pharmaceutically acceptable inert vehicle. Claims 10 and 17-21 cover the alcohol-containing formulation category.

Potentially relevant formulation elements include:

Pindolol or another pharmacologically active agent;
Sorbitan monooleate;
Sorbitan monolaurate;
A mixture of sorbitan monooleate and sorbitan monolaurate;
Ethanol;
n-Propanol;
Isopropanol;
t-Butanol; and
A pharmaceutically acceptable inert vehicle.

Claims 1 and 6 are drafted as application methods and can potentially reach separate application of the drug and enhancer. Claims 5 and 10 narrow the method to a single composition. Claims 11 and 17 are composition claims and do not require that the composition actually be applied, although the stated purpose is transdermal administration.

What does “single pharmaceutical composition” add?

The single-composition limitation narrows claims 5 and 10 compared with claims 1 and 6. A product that supplies the drug and enhancer from separate reservoirs, layers, or containers may not satisfy that limitation unless the components are legally considered part of one composition.

The inert-vehicle limitation is also relevant. A formulation containing only the active agent and enhancer may fall outside a claim requiring an inert vehicle, while a conventional solvent, carrier, gel base, adhesive, or excipient could potentially satisfy the vehicle requirement depending on the claim and specification.

What is the claim hierarchy?

The claim set has two main branches.

Sorbitan ester without specified alcohol

Claims 1-5 and 11-16 cover the sorbitan ester enhancer without expressly requiring a C1-C4 alcohol.

Claim 1 is the principal method claim.
Claims 2 and 3 narrow the sorbitan ester structure.
Claim 4 narrows the active agent to pindolol.
Claim 5 requires a single composition and inert vehicle.
Claim 11 is the principal composition claim.
Claims 12-14 further define the sorbitan ester.
Claim 15 narrows the active agent to pindolol.
Claim 16 adds an inert vehicle.

Sorbitan ester with C1-C4 alcohol

Claims 6-10 and 17-21 add a lower aliphatic alcohol.

Claim 9 identifies ethanol, n-propanol, isopropanol, t-butanol, and mixtures. The supplied text for claim 20 is incomplete after “selected from the group.” The issued patent text controls over an OCR or transcription error. Claims 7 and 8 appear to repeat the narrowing language of claims 2 and 3 but are stated in the supplied text as depending from claim 1 rather than claim 6. That dependency should be checked against the official issued patent and prosecution record before relying on the reproduced claim set in litigation.

When did U.S. Patent 5,212,199 expire?

U.S. Patent 5,212,199 issued on May 18, 1993. Because it was governed by the pre-Uruguay Round term rule, its basic term was 17 years from issuance. The patent therefore expired on May 18, 2010, absent an unusual terminal-disclaimer or other record-specific adjustment. The patent is not an active U.S. exclusionary right today. [1, 2]

Event	Date
U.S. patent issuance	May 18, 1993
Statutory term basis	17 years from issuance
Expected expiration	May 18, 2010
Current enforceability	Expired

The expiration eliminates current infringement exposure under this patent. It does not eliminate its value as prior art against later patent applications directed to sorbitan ester transdermal systems.

Does the patent have FDA Orange Book protection?

No Orange Book listing should be expected from this patent alone.

The Orange Book identifies patents submitted by sponsors for approved drug products, primarily drug substance, drug product, and certain method-of-use patents. U.S. Patent 5,212,199 is a broad transdermal formulation and delivery-platform patent. The supplied claims do not identify an FDA-approved product, NDA number, dosage form approval, or sponsor-submitted drug-product listing. [4]

The patent’s pindolol claims also do not establish Orange Book protection for pindolol products. A sponsor would need to submit a qualifying patent in connection with an approved NDA, and listing requirements would depend on the approved labeling and the patent’s relationship to the approved product.

Are there Paragraph IV challenges or generic-entry risks?

There is no current Paragraph IV barrier created by U.S. Patent 5,212,199 because the patent expired in 2010. A Paragraph IV certification is relevant when an ANDA applicant challenges a listed patent that has not expired or alleges that the patent will not be infringed. An expired patent cannot provide a current patent-based delay to approval or launch. [5]

The generic-entry analysis therefore shifts to:

Later patents covering a specific transdermal product;
Drug-specific formulation patents;
Patch construction and adhesive patents;
Manufacturing-process patents;
Device or applicator patents;
Method-of-use patents tied to approved labeling; and
Regulatory exclusivities independent of this patent.

For a pindolol transdermal product, the patent presents no current U.S. launch block. A product developer would still need to review the active patent family and product-specific estate surrounding the proposed dosage form.

How strong is the patent estate for the claimed technology?

The estate was relatively strong in breadth at the time of issuance because it combined:

A structural Markush definition for sorbitan esters;
Specific claims to monooleate and monolaurate;
Method claims;
Composition claims;
Optional alcohol-containing embodiments; and
Pindolol-specific dependent claims.

Its practical strength is now historical rather than exclusionary. The patent has expired, and the claims cannot support an injunction or damages claim for post-expiration conduct.

Strength factor	Assessment
Chemical breadth	Moderate to broad
Named-compound coverage	Clear for sorbitan monooleate and monolaurate
Product coverage	Broad at composition level
Method coverage	Broad, subject to application and skin-penetration limitations
Pindolol coverage	Express dependent claims
Current enforceability	None because expired
Prior-art significance	Potentially material
Biosimilar relevance	None

The “consisting essentially of” language could create litigation around whether other enhancers, solvents, surfactants, or excipients materially change the claimed invention. That issue would have mattered during the patent term but cannot create current infringement liability.

What manufacturing and intellectual-property barriers remain?

The patent does not prevent manufacture of sorbitan monooleate, sorbitan monolaurate, or related transdermal formulations today. Manufacturing barriers may still arise from:

Excipient quality specifications;
Residual solvents;
Ester composition and batch consistency;
Skin-irritation controls;
Adhesive compatibility;
Drug crystallization;
Content uniformity;
Permeation-rate control; and
Stability of the active agent in the vehicle.

Those are technical, regulatory, and quality barriers rather than barriers imposed by Patent 5,212,199.

Later patents may protect a particular manufacturing process, patch architecture, adhesive system, or formulation ratio. A freedom-to-operate review must therefore distinguish the expired platform patent from later, live patents.

What licensing deals or litigation affect this patent?

The supplied claims establish no licensing agreement, settlement agreement, Paragraph IV litigation, or active infringement case. Because the patent expired in 2010, any historical license or litigation would have no continuing exclusionary effect under the patent itself.

No biosimilar litigation is relevant. Pindolol is a small-molecule active agent, and the patent concerns transdermal delivery rather than a biologic or biosimilar reference product.

How does this patent compare with later transdermal patents?

Patent 5,212,199 is primarily an enhancer-composition patent. Later transdermal patents often focus on a narrower commercial implementation:

Patent category	Typical protected subject matter	Relationship to Patent 5,212,199
Enhancer patent	Chemical enhancer or enhancer class	Directly overlapping technical field
Patch patent	Matrix, reservoir, backing, or adhesive structure	Usually distinct structural coverage
Drug-specific patent	Particular active agent and dosage	May overlap only where the active agent is combined with the enhancer
Method-of-use patent	Treatment of a defined disease or patient group	Separate from general penetration enhancement
Manufacturing patent	Mixing, coating, drying, or lamination process	Potentially independent
Device patent	Applicator or delivery system	Usually independent
Regulatory exclusivity	FDA approval-based exclusivity	Separate from patent rights

The expired patent should be treated as foundational prior art, not as a current competitor-rights asset.

Key Takeaways

U.S. Patent 5,212,199 covers transdermal methods and compositions using specified sorbitan ester permeation enhancers.
Sorbitan monooleate and sorbitan monolaurate are expressly named in dependent claims.
The claims also cover sorbitan esters within a broader seven-to-21-carbon Markush definition.
Claims 6-10 and 17-21 add a C1-C4 aliphatic alcohol, including ethanol, n-propanol, isopropanol, and t-butanol.
Pindolol is expressly covered by claims 4, 15, and 21.
The patent issued May 18, 1993 and expired May 18, 2010.
It does not create a current Paragraph IV, Orange Book, generic-launch, or biosimilar barrier.
Its continuing value is as prior art and as a historical reference for transdermal enhancer technology.
The reproduced claim text contains apparent OCR or dependency defects, especially claim 20 and the dependencies of claims 7 and 8. The issued patent must control.

FAQs

Does Patent 5,212,199 cover sorbitan monooleate by itself?

No. The claims generally require sorbitan monooleate to be combined with a pharmacologically active agent in a transdermal method or composition. The patent does not claim sorbitan monooleate as an isolated chemical compound.

Can a formulation avoid the claims by replacing ethanol with propylene glycol?

Potentially, but claim scope must be assessed claim by claim. Propylene glycol is not one of the C1-C4 alcohols expressly identified in claim 9. It may also affect whether the formulation falls within the broader claims that do not require an alcohol.

Does the patent cover oral or injectable pindolol products?

No. The claims require transdermal administration or a composition for transdermal administration through intact skin. Oral and injectable pindolol products do not satisfy those limitations.

Could a later patent still block a sorbitan-based transdermal product?

Yes. A later, unexpired patent could cover a particular drug, concentration, patch design, adhesive, manufacturing process, or treatment method even though Patent 5,212,199 has expired.

Is a transdermal product using sorbitan monolaurate automatically free of patent risk?

No. It is free of current infringement exposure under Patent 5,212,199, but separate patents and regulatory requirements may apply to the commercial product.

References

U.S. Patent and Trademark Office. (1993). U.S. Patent No. 5,212,199.
35 U.S.C. § 154. Patent term provisions.
U.S. Patent and Trademark Office. (2024). Manual of Patent Examining Procedure § 2111.03: Transitional phrases.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application regulations, 21 C.F.R. § 314.101 and § 314.107.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	167384	⤷ Start Trial
Australia	656755	⤷ Start Trial
Australia	9141391	⤷ Start Trial
Canada	2098196	⤷ Start Trial
Germany	69129632	⤷ Start Trial
Denmark	0561983	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,212,199

Summary for Patent: 5,212,199