US Patent 6,335,031: Rivastigmine Formulation, Transdermal, and Stabilization Patent Analysis

US Patent 6,335,031 protects stabilized pharmaceutical compositions containing rivastigmine, also identified in the patent as (S)-N-ethyl-3-{(1-dimethylamino)ethyl}-N-methyl-phenyl-carbamate. Its principal inventive concept is the use of a low concentration of antioxidant to reduce degradation of rivastigmine, particularly in polymer-based transdermal systems.

The patent covers three related claim groups:

Oral or other pharmaceutical compositions containing rivastigmine and antioxidant.
Transdermal devices containing a rivastigmine-polymer matrix, antioxidant, adhesive, backing layer and release liner.
Methods of stabilizing rivastigmine by combining it with an effective amount of antioxidant.

The patent was granted on January 1, 2002, and its ordinary US patent term expired in approximately April 2018, based on the April 30, 1998 international filing date and the patent’s priority chain. It therefore does not presently block generic or alternative rivastigmine products in the United States, subject to any unusual terminal-disclaimer, patent-term-adjustment or litigation-specific issue not reflected in the supplied claim set. (U.S. Patent No. 6,335,031, 2002)

What drug does US Patent 6,335,031 protect?

The claimed active ingredient is rivastigmine, specifically the S-enantiomer:

Patent designation	Modern pharmaceutical name
Compound A	Rivastigmine
Chemical class	Carbamate acetylcholinesterase inhibitor
Principal branded product	Exelon
Major dosage forms	Capsules, oral solution and transdermal patch
Original innovator	Novartis and predecessor Sandoz entities

Rivastigmine is approved for the treatment of mild-to-moderate dementia associated with Alzheimer’s disease and mild-to-moderate dementia associated with Parkinson’s disease. The FDA-approved transdermal system delivers rivastigmine through the skin over an extended period. (FDA, 2024a)

US Patent 6,335,031 does not broadly claim rivastigmine as a chemical compound. Its scope is directed to formulations and stabilization technology. The core compound itself was protected by separate compound patents and related pharmaceutical patent families.

What are the main claim categories in US Patent 6,335,031?

The claims fall into four practical categories.

Antioxidant-stabilized pharmaceutical compositions

Claim 1 is the broadest composition claim. It requires:

A therapeutically effective amount of rivastigmine, in free-base or acid-addition-salt form.
Approximately 0.01% to 0.5% antioxidant by weight.
A diluent or carrier.

The claim does not require a transdermal system. A tablet, capsule, liquid, matrix, suspension or other pharmaceutical composition could potentially fall within its literal scope if it satisfies the listed elements.

Claim 2 narrows claim 1 by requiring rivastigmine at 1% to 40% by weight.

Claims 3 and 4 limit the antioxidant to specified compounds. The listed antioxidants include:

Tocopherol and tocopherol esters.
Ascorbic acid.
Ascorbyl palmitate.
Butylhydroxytoluene.
Butylhydroxyanisole.
Propyl gallate.

Claim 5 narrows the formulation to tocopherol at 0.1% by weight.

Polymer matrix formulation

Claim 6 is the most commercially specific composition claim. It requires the following approximate composition:

Component	Claimed amount
Rivastigmine free base	20% to 40%
Polymethacrylate	10% to 30%
Acrylate copolymer	40% to 60%
Alpha-tocopherol	0.05% to 0.3%
Total composition	100%

This claim is directed to a polymeric matrix suitable for controlled drug delivery. It is materially narrower than claim 1 because it requires defined polymer classes, high rivastigmine loading and alpha-tocopherol.

The claim does not expressly require a backing layer, adhesive layer or release liner. Those features are addressed in the transdermal-device claims.

Transdermal devices

Claims 7 through 9 cover a transdermal device containing the claim 1 composition. The device includes:

A substrate.
The pharmaceutical composition.
An adhesive layer.
A release liner that releasably contacts the adhesive layer.

Claim 11 is a more detailed device claim. It requires:

A backing layer.
A layer containing therapeutically effective rivastigmine.
An antioxidant effective to stabilize rivastigmine in a polymer matrix.
A release liner.
A discrete adhesive layer between the rivastigmine-containing polymer matrix and the release liner.

The distinction between claims 7 to 9 and claim 11 is important. Claims 7 to 9 incorporate the composition by reference, while claim 11 specifies a multilayer patch architecture.

Stabilization methods

Claims 15 through 20 cover methods of stabilizing rivastigmine. The method consists of forming a composition by combining rivastigmine with an amount of antioxidant effective to prevent or reduce degradation.

The dependent method claims specify:

The listed antioxidant classes.
Alpha-tocopherol or ascorbyl palmitate.
Antioxidant concentration of approximately 0.01% to 0.5%.
Alpha-tocopherol at 0.1%.
Optional silicone oil.

These method claims are formulation-process claims. They do not claim administration of rivastigmine to a patient or treatment of dementia.

How broad is claim 1 of US Patent 6,335,031?

Claim 1 is broad in dosage-form terms but narrow in active-ingredient terms.

A potentially infringing product would need to contain all of the following:

Rivastigmine in the claimed stereochemical form.
An antioxidant.
Antioxidant concentration of approximately 0.01% to 0.5% by total composition weight.
A carrier or diluent.
A therapeutically effective amount of rivastigmine.

The claim could potentially reach an oral formulation or a transdermal matrix. It is not limited to a particular antioxidant, polymer, adhesive or delivery route.

The principal design-around options would have included:

Omitting antioxidant.
Using an antioxidant concentration outside the claimed range.
Substituting a stabilizer that does not fall within the claim’s antioxidant construction.
Using a formulation that lacks a diluent or carrier, although this route would raise pharmaceutical-formulation and claim-construction issues.
Using a different active ingredient or stereochemical composition.

The practical importance of these design-around strategies is historical because the patent has expired.

What formulations are protected by claims 3 through 6?

Claims 3 through 6 protect increasingly narrow formulations.

Claim	Scope
3	Claim 1 composition using one of several listed antioxidants
4	Claim 3 narrowed to alpha-tocopherol or ascorbyl palmitate
5	Tocopherol at 0.1% by weight
6	Rivastigmine-polymer matrix with specified polymer and antioxidant ranges

Claim 6 is the strongest formulation claim from a technical specificity perspective. It identifies both the active-loading range and the polymer system. A competing patch using a different polymer matrix, a different antioxidant, or a materially different composition could avoid literal infringement of claim 6 while still requiring analysis under the broader claims.

The patent’s formulation concept is consistent with the known stability challenges of rivastigmine. Rivastigmine can undergo degradation in certain formulation environments, and antioxidants can reduce oxidative or related degradation pathways. The patent therefore links chemical stabilization to transdermal matrix design.

What is the scope of the transdermal-device claims?

Claims 7 to 9 and 11 to 14 target patch construction rather than only chemical composition.

A covered patch would generally include:

A rivastigmine-containing polymer layer.
An antioxidant in the drug matrix.
A backing or substrate.
A separate adhesive component.
A release liner before application.

Claim 11 requires a discrete adhesive layer positioned between the drug-containing polymer matrix and the release liner. This limitation distinguishes the claimed device from systems in which the drug is incorporated directly into the adhesive.

The claims therefore address two different patch designs:

A drug-in-polymer matrix with a separate adhesive layer.
A composition supported by a substrate, with adhesive and release-liner components.

Claim dependency and drafting issues

The supplied text identifies claims 12, 13 and 14 as depending on “claim 1,” even though those claims describe transdermal-device subject matter. That dependency appears internally inconsistent. If the issued patent contains the same language, the issue would require review of the certified patent document and prosecution history.

The likely intended dependencies may have been claim 11 or another transdermal-device claim. The distinction matters because:

A claim dependent on claim 1 would inherit composition limitations.
A claim dependent on claim 11 would inherit device-architecture limitations.
A claim depending on the wrong statutory category could create claim-construction and enforceability issues.

The analysis should therefore use the issued patent text, not an informal claim transcription, for litigation or freedom-to-operate conclusions.

How does silicone oil affect the patent scope?

Claims 10, 12 and 20 add silicone oil.

Silicone oil can function as a formulation or processing component in a transdermal system. Depending on the formulation, it may affect adhesive properties, drug release, matrix flexibility or skin contact.

Claim 10 adds silicone oil to the claim 1 pharmaceutical composition. Claim 20 adds it to the stabilization method. The supplied wording for claim 12 again identifies a dependency problem because it refers to “claim 1” while describing a transdermal device.

Silicone oil is not required by the broadest claim 1, claim 7 or claim 11. It is an additional limitation. A product that does not contain silicone oil could still have been evaluated under the broader composition or device claims during the patent term.

When did US Patent 6,335,031 lose exclusivity?

The patent’s ordinary term expired in approximately April 2018.

Event	Date
International filing and relevant priority period	April 30, 1998
US patent grant	January 1, 2002
Expected ordinary patent-term endpoint	Approximately April 30, 2018
Current status	Expired by term

The patent was not a current barrier to US generic entry after expiration. Patent expiration is separate from FDA regulatory exclusivity. FDA approval exclusivity, if applicable to a specific product or supplement, would not extend the life of an expired formulation patent.

What was the Orange Book status of US Patent 6,335,031?

The Orange Book question must be separated by product and dosage form.

The FDA Orange Book lists patents submitted by sponsors for approved drug products. A patent may be listed for a capsule, oral solution or transdermal patch only if the sponsor submitted it in connection with that approved product and the FDA accepted the listing under its patent-listing standards. The existence of a patent covering rivastigmine generally does not establish that the patent was listed against every Exelon dosage form.

The relevant Orange Book analysis requires checking:

Exelon capsules.
Exelon oral solution.
Exelon transdermal system.
Any authorized generic or supplemental approval.
Patent delisting or expiration entries.
Listed use codes for method-of-use patents.

Because US Patent 6,335,031 is expired, any historical Orange Book listing would have no current exclusionary effect. The FDA Orange Book remains the controlling source for product-specific listing and Paragraph IV status. (FDA, 2024b)

Were there Paragraph IV challenges to this patent?

A Paragraph IV certification challenges the validity, enforceability or infringement of an Orange Book-listed patent in connection with an ANDA.

For US Patent 6,335,031, the commercial significance of any Paragraph IV challenge was limited by the patent’s 2018 expiration. Generic applicants could have certified that the patent was expired or would expire before commercial launch. A Paragraph IV certification may have been relevant before expiration if the patent was listed against the relevant Exelon product.

The supplied information does not establish a specific ANDA number, certification date, notice letter, district-court complaint or settlement involving this patent. No litigation conclusion should be attributed to the patent without matching the patent number to FDA listing records and PACER or court docket evidence.

Which companies challenged rivastigmine exclusivity?

The competitive field includes:

Novartis, through the Exelon franchise.
Generic manufacturers of rivastigmine capsules and oral solution.
Generic manufacturers of rivastigmine transdermal systems.
Contract manufacturers and suppliers of acrylic or methacrylate patch matrices.
Potential developers of alternative transdermal delivery systems.

Generic competition has focused on both oral rivastigmine and transdermal rivastigmine. The commercial barriers differ by product:

Product	Primary barriers
Capsules	Bioequivalence, content uniformity and manufacturing scale
Oral solution	Dose uniformity, stability and container-closure performance
Transdermal patch	Adhesion, delivery rate, skin irritation, residual drug and IVRT or related performance testing
Alternative patch	Clinical or comparative-performance requirements, depending on FDA pathway

For a transdermal generic, expiration of US Patent 6,335,031 removed one formulation barrier but did not eliminate regulatory development risk.

How strong was the patent estate?

The estate was technically meaningful during its term but not comprehensive.

Strengths

Claim 1 covered a broad antioxidant concentration range.
The claim applied to more than one dosage form.
The patent linked the antioxidant to stabilization of rivastigmine.
Claim 6 targeted a commercially relevant polymer-matrix formulation.
The transdermal claims addressed patch architecture, not only drug chemistry.
Method claims created an additional infringement theory based on manufacturing or formulation operations.

Limitations

The patent did not broadly claim rivastigmine as a molecule.
The antioxidant range was a potential design-around point.
Claims 3 to 6 depended on specific antioxidant or polymer choices.
Transdermal-device claims included structural limitations that could be avoided by different patch architecture.
The apparent dependency errors in claims 12 to 14 could complicate enforcement.
Expiration eliminated present-term exclusivity.

The overall estate was strongest against a rivastigmine patch using the claimed antioxidant range and polymer-matrix structure. It was weaker against alternative formulations that used different stabilizers, different polymer systems or different adhesive configurations.

What manufacturing and IP barriers remain after expiration?

Patent expiration does not remove technical barriers. A competing manufacturer still must address:

Rivastigmine degradation during manufacturing and storage.
Homogeneous distribution of low-level antioxidant.
Polymer compatibility.
Drug release through the skin.
Adhesion over the labeled wear period.
Skin irritation and sensitization.
Residual drug after patch removal.
Packaging and moisture or oxygen control.
Batch-to-batch content uniformity.
Scale-up of solvent casting or coating operations.
FDA product-specific bioequivalence and performance requirements.

These barriers can support trade-secret protection even after patent expiration. Manufacturing parameters, coating conditions, drying profiles, antioxidant incorporation methods and adhesive selection may remain confidential know-how.

How does US Patent 6,335,031 compare with the broader rivastigmine patent landscape?

Patent category	Subject matter	Current commercial relevance
Compound patents	Rivastigmine molecule and stereochemistry	Expired
Formulation patents	Antioxidant-stabilized compositions	Expired
Transdermal patents	Polymer matrix, adhesive and patch architecture	Expired or subject to separate patent-family review
Method-of-use patents	Treatment of dementia with rivastigmine	Product- and listing-specific
Manufacturing patents	Coating, matrix formation and processing	Requires separate family analysis
Regulatory exclusivity	FDA approval-based exclusivity	Separate from patent term

US Patent 6,335,031 should not be treated as the complete Exelon patent estate. A freedom-to-operate review must separately identify patents directed to the active ingredient, patch construction, dose strengths, treatment indications, manufacturing processes and any later-filed continuation or divisional applications.

What generic launch risks existed for rivastigmine patches?

Before expiration, the principal launch risks were:

Patent certification risk under the ANDA pathway.
Potential infringement allegations based on the antioxidant formulation.
Equivalence risk involving drug release and adhesion.
FDA review risk for transdermal performance.
Commercial risk from limited dementia-patch volume and incumbent brand recognition.

After expiration, the patent-specific launch risk from US Patent 6,335,031 is no longer material. The remaining risks are regulatory, technical, manufacturing and commercial.

Key Takeaways

US Patent 6,335,031 covers antioxidant-stabilized rivastigmine formulations and transdermal systems.
Claim 1 is the broadest composition claim and requires rivastigmine, antioxidant, carrier or diluent, and antioxidant concentration of approximately 0.01% to 0.5%.
Claim 6 is the principal narrow polymer-matrix claim, requiring rivastigmine, polymethacrylate, acrylate copolymer and alpha-tocopherol within specified ranges.
Claims 7 to 14 address transdermal-device architecture, including backing layers, adhesive layers and release liners.
Claims 15 to 20 cover methods of stabilizing rivastigmine.
The patent’s ordinary US term expired in approximately April 2018.
The patent no longer creates a current US exclusivity barrier for generic rivastigmine products.
Its historical commercial relevance was greatest for rivastigmine transdermal patches using antioxidant-containing polymer matrices.
Claims 12 to 14, as supplied, contain apparent dependency inconsistencies that should be checked against the issued patent document before litigation or validity analysis.
Separate patents and regulatory requirements may still affect a specific rivastigmine product.

FAQs About US Patent 6,335,031 and Rivastigmine

Does US Patent 6,335,031 cover Exelon?

It covers formulation and transdermal-system technology applicable to rivastigmine products, including technology associated with the Exelon franchise. It does not broadly claim the Exelon brand or rivastigmine as a chemical compound.

Can a generic rivastigmine patch launch after this patent expired?

Yes. Expiration of the patent removed this patent-based barrier, although the generic must still satisfy FDA requirements for transdermal equivalence, adhesion, drug release, stability and safety.

Does the patent cover alpha-tocopherol in rivastigmine patches?

Yes. Claims 4, 5, 6, 14, 17 and 19 identify alpha-tocopherol or tocopherol as a claimed antioxidant, subject to the other limitations of the applicable claim.

Does the patent cover rivastigmine capsules?

Potentially, under the broad composition claims, if the formulation includes the required antioxidant concentration and carrier or diluent. The transdermal-device claims do not cover an ordinary capsule.

Is a method of stabilizing rivastigmine the same as a method of treating dementia?

No. Claims 15 to 20 concern formulation stabilization. They do not claim administering rivastigmine to treat Alzheimer’s disease or Parkinson’s disease dementia.

References

Food and Drug Administration. (2024a). Exelon (rivastigmine transdermal system) prescribing information. U.S. Department of Health and Human Services.

Food and Drug Administration. (2024b). Approved drug products with therapeutic equivalence evaluations, Orange Book. U.S. Department of Health and Human Services.

U.S. Patent No. 6,335,031. (2002). Pharmaceutical compositions comprising a carbamate. U.S. Patent and Trademark Office.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	9800526	Jan 12, 1998

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	223711	⤷ Start Trial
Australia	2278599	⤷ Start Trial
Australia	745661	⤷ Start Trial
Brazil	9906920	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,335,031

Summary for Patent: 6,335,031