Details for Patent: 5,004,610

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Summary for Patent: 5,004,610

Title:	Subsaturated nicotine transdermal therapeutic system
Abstract:	Rate controlled transdermal nicotine delivery systems are disclosed which utilize an in-line adhesive to maintain the systems on the skin. The initial equilibrated concentration of nicotine in the nicotine reservoir and the adhesive is below saturation, preferably at a thermodynamic activity no greater than 0.50, and the reservoir comprises the nicotine dissolved in a material with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of nicotine in the reservoir is sufficient to prevent the activity of the nicotine in the reservoir from decreasing by more than about 75% and preferably no more than about 25% during the predetermined period of administration; and the thickness of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and, preferably at least 75% of the initial equilibrated nicotine loading is in the reservoir layer.
Inventor(s):	James L. Osborne, Melinda Nelson, David J. Enscore, Su I. Yum, Robert M. Gale
Assignee:	Alza Corp
Application Number:	US07/537,672
Patent Claim Types: see list of patent claims	Use; Device;

United States Patent 5,004,610: Scope, Claims, Expiration, and Nicotine Patch Patent Landscape

US Patent 5,004,610 covers reservoir-type transdermal nicotine patches designed to maintain a substantially stable nicotine driving force over at least eight hours. Its core combination is a subsaturated nicotine reservoir, a nicotine-permeable and solvent-blocking rate-control membrane, an adhesive layer, and a removable release liner. The strongest claims narrow the technology to ethylene vinyl acetate, high-density polyethylene, specified nicotine loadings, activity ranges, and steady-state flux.

The patent issued April 2, 1991, and its pre-Uruguay Round Agreements Act term was 17 years from issuance. On that basis, US 5,004,610 expired April 2, 2008. It no longer presents an enforceable US patent barrier to nicotine patches, generic nicotine transdermal systems, or competing cessation products.

What invention does US Patent 5,004,610 protect?

The patent protects a controlled-release nicotine patch architecture rather than nicotine administration generally. The invention addresses a formulation and delivery problem: nicotine concentration and thermodynamic activity can decline as nicotine leaves the patch, causing declining flux during the administration period.

The broadest independent claim requires all of the following:

Claim element	Requirement
Product	Medical device for transdermal nicotine administration
Administration period	At least about eight hours
Delivery rate	About 250 to 4,000 micrograms per hour for a substantial portion of the period
Reservoir	Nicotine dissolved in a solvent at less than saturation
Reservoir loading	Sufficient initial loading to limit concentration decline to no more than 75%
Rate-control layer	Nicotine-permeable and substantially solvent-impermeable
Adhesive	Positioned between the rate-control layer and skin
Liner	Removable release liner on the adhesive

The claim therefore requires a multilayer patch with an in-line adhesive arrangement. A nicotine-containing adhesive-only product would not literally satisfy claim 1 unless the adhesive operates as the claimed reservoir or the product otherwise contains each required layer and function.

How many independent claims does the patent contain?

US 5,004,610 has three independent claims: claims 1, 9, and 18.

Claim 1: Functional reservoir and delivery claim

Claim 1 is the broadest independent claim. It does not limit the reservoir polymer to EVA or specify a particular membrane polymer. Its principal limitations are functional:

• subsaturated nicotine;
• sustained delivery for at least eight hours;
• delivery of 250 to 4,000 micrograms per hour;
• reservoir concentration decline of no more than 75%;
• a membrane that passes nicotine but substantially blocks solvent.

Claim 1 could potentially read on several polymeric reservoir systems if they meet the claimed thermodynamic and transport properties.

Claim 9: EVA reservoir and in-line adhesive claim

Claim 9 narrows the reservoir to nicotine dissolved in an ethylene vinyl acetate copolymer. It also limits the rate-control layer to:

• low-density polyethylene;
• high-density polyethylene; or
• an ethylene vinyl acetate copolymer.

The claim retains the broad delivery range and eight-hour minimum but uses thermodynamic activity, rather than only concentration, as the key stability parameter.

Claim 18: Defined composition and HDPE membrane claim

Claim 18 is the most composition-specific independent claim. It requires:

• 5 to 40 weight percent nicotine;
• 60 to 95 weight percent EVA;
• EVA vinyl acetate content of approximately 28% to 40%;
• an HDPE rate-control membrane;
• sufficient loading for 250 to 4,000 micrograms per hour;
• an activity decline of no more than 75%;
• an adhesive and release liner.

This claim is narrower in materials and composition but potentially stronger against products using the specified EVA and HDPE configuration.

What dependent claim limitations matter most?

The dependent claims establish several narrower protection zones.

Claims	Added limitation
2, 10	Initial nicotine thermodynamic activity no greater than about 0.50
3	Adhesive has high nicotine solubility
4, 11	At least 50% of initial nicotine loading is in the reservoir
5, 13, 14	Activity decline no greater than 25%
6, 12	At least 75% of initial nicotine loading is in the reservoir
7	Rate-control layer is substantially solvent-impermeable
8, 15, 16	Initial activity in reservoir and adhesive is about 0.20 to 0.40
17	EVA has approximately 40% vinyl acetate
19	Nicotine loading is approximately 5 mg/cm²
20	At least 50% of initial loading is in the reservoir
21	Administration period is approximately 24 hours
22-29	Steady-state flux is approximately 30 to 120 micrograms/cm² per hour

The activity limitations are important because they address the chemical driving force for nicotine transport. Claims 5, 13, and 14 are substantially narrower than claims requiring only a 75% maximum decline. A product maintaining activity within 25% would fall within a more demanding subset of the claimed performance profile.

What technical elements define the patent’s scope?

Subsat­urated nicotine reservoir

The reservoir must contain nicotine below saturation. This limitation distinguishes the claimed system from a saturated reservoir designed to maintain constant activity through excess undissolved drug.

The patent instead relies on sufficient initial dissolved nicotine loading and controlled transport to keep concentration or activity from declining beyond the stated threshold.

Thermodynamic activity

Thermodynamic activity is a central technical variable in claims 2, 5, 8, 10, 13, 14, 15, and 16. The claims specify either:

• initial activity no greater than 0.50;
• initial activity of approximately 0.20 to 0.40; or
• activity decline of no more than 25% or 75%.

Activity is not identical to weight percent loading. A formulation with a particular nicotine concentration may have different activity depending on the polymer, solvent environment, temperature, and interactions between nicotine and EVA.

Solvent-blocking membrane

The membrane must be permeable to nicotine while substantially impermeable to the reservoir solvent. This creates a selective transport barrier. The claim language is directed to preventing solvent migration from materially altering the reservoir or adhesive system while allowing nicotine to pass toward the skin.

Claims 9 and 18 identify specific membrane materials. Claim 18 requires HDPE, making it particularly relevant to freedom-to-operate reviews involving HDPE-controlled patches.

In-line adhesive

The adhesive is positioned in the migration path between the rate-control layer and the skin. This differs from systems in which adhesive is placed only around the patch perimeter.

Claims 3 and 9 emphasize adhesive behavior, including high nicotine solubility in claim 3. The adhesive is therefore part of the delivery system and not merely a mechanical attachment component.

Flux and delivery rate

The patent uses two related but distinct performance metrics:

• total delivery rate: 250 to 4,000 micrograms per hour;
• steady-state flux: 30 to 120 micrograms/cm² per hour.

The claims do not identify a single patch surface area. A product may meet the total-rate limitation while failing the flux limitation, or vice versa, depending on area and measured transport performance.

What formulations are protected by US 5,004,610?

The most specifically protected formulation is the combination in claim 18:

Component	Claimed range or material
Nicotine	5 to 40 weight percent
EVA	60 to 95 weight percent
EVA vinyl acetate	Approximately 28% to 40%
Membrane	HDPE
Delivery period	At least about eight hours
Nicotine rate	250 to 4,000 micrograms per hour
Nicotine activity decline	No more than 75%
Adhesive	Required
Release liner	Required

Claim 19 adds approximately 5 mg/cm² nicotine loading. Claim 21 adds a 24-hour administration period. Claims 20 and 22-29 add reservoir-loading and flux limitations.

A formulation outside the 5% to 40% nicotine range or using a non-HDPE membrane could avoid literal infringement of claim 18, but it could still require analysis against claims 1 or 9. The independent claims overlap functionally, but they are not interchangeable. A product that fails the EVA limitation of claim 9 may still raise questions under claim 1 if it satisfies the broader reservoir and membrane requirements.

When did US Patent 5,004,610 lose exclusivity?

US 5,004,610 lost enforceable US patent exclusivity in 2008.

Event	Date or period
Patent issued	April 2, 1991
Statutory term applicable to an early-1990s patent	17 years from issuance
Expected ordinary expiration	April 2, 2008
Current status	Expired
Present infringement risk	No enforceable US patent risk from this patent

The patent predates the effective application of the modern 20-year-from-earliest-effective-filing-date term under the Uruguay Round Agreements Act. Its ordinary term therefore ran from issuance rather than from the earliest priority filing date, subject to any applicable term adjustment, disclaimer, or other prosecution-specific event reflected in the official file history. Public patent databases identify the patent as expired.

What is the Orange Book status of US 5,004,610?

US 5,004,610 is not a currently enforceable Orange Book barrier. The patent expired in 2008, and an expired patent cannot block FDA approval or commercial launch through present patent enforcement.

Nicotine patches are approved small-molecule drug products generally regulated through the NDA and ANDA pathways. They are not biologics and do not create biosimilar substitution issues. FDA product approval, labeling, manufacturing controls, and bioequivalence remain separate from the expired patent rights. The FDA Orange Book identifies approved drug products and certain patent and exclusivity information, but it does not revive expired patents.[2]

Historical Orange Book listing status should not be confused with present legal effect. Even if the patent was associated with an approved nicotine patch during its term, the listing would not extend the patent beyond its statutory expiration.

Which companies challenged or could have challenged this patent?

A Paragraph IV challenge would have been relevant only while the patent was listed and unexpired. Paragraph IV certification allows an ANDA applicant to assert that a listed patent is invalid, unenforceable, or not infringed. After expiration, an applicant generally has no commercial need to defeat the patent through Paragraph IV litigation because the patent no longer blocks launch.[3]

The patent record and claims provided do not establish a specific Paragraph IV challenger, settlement, or final judgment. No current Paragraph IV risk remains against US 5,004,610.

The likely commercial parties associated with the broader nicotine patch market included Alza Corporation and later product companies marketing Nicoderm, Habitrol, generic nicotine transdermal systems, and other cessation products. Product marketing rights, manufacturing arrangements, and patent ownership should be distinguished. A patent assignment does not itself prove a commercial license, and no license agreement should be inferred solely from the claim set.

What patent litigation affects US 5,004,610?

The patent is expired, so litigation based solely on its present enforceability is no longer commercially material. Any historical litigation would require review of the district-court docket, Federal Circuit decisions, prosecution history, and assignment records.

The principal legal issues that would have mattered during the patent term were:

1. Whether a competing patch had a separate nicotine reservoir and in-line adhesive.
2. Whether nicotine was dissolved below saturation.
3. Whether the reservoir maintained concentration or activity within the claimed decline limits.
4. Whether the membrane was substantially impermeable to the reservoir solvent.
5. Whether the measured delivery rate or flux fell within the claimed ranges.
6. Whether the accused product used the specified EVA and HDPE materials.

The functional limitations could have created proof issues. Infringement analysis would likely require formulation data, membrane permeability data, loading measurements, activity calculations, patch area, and in-use release testing.

How strong was the patent estate for nicotine patches?

The individual patent was technically meaningful but commercially narrow in several respects.

Strength factor	Assessment
Core concept	Strongly defined multilayer reservoir-patch architecture
Breadth	Claim 1 is materially broader than claims 9 and 18
Materials coverage	Focused on EVA and polyethylene systems
Functional limitations	Potentially difficult to assess without testing
Product relevance	High for reservoir patches with in-line adhesive
Relevance to drug-in-adhesive patches	More limited
Current enforceability	None because the patent expired
Biosimilar relevance	None
Generic launch impact today	No blocking effect

The patent did not claim every transdermal nicotine product. It focused on a specific delivery architecture and the use of reservoir loading, selective membranes, and thermodynamic activity to maintain nicotine release.

A modern drug-in-adhesive patch with nicotine dissolved directly in an adhesive matrix could fall outside important structural limitations, particularly the separate reservoir and rate-control membrane requirements. A reservoir patch using EVA and HDPE would have been closer to the center of the patent’s technical scope.

How does this patent compare with competing nicotine patch patents?

US 5,004,610 should be compared with earlier and later nicotine delivery patents covering different architectures.

Technology category	Typical distinction from US 5,004,610
Reservoir patch	Separate drug reservoir and membrane, closest to the patent
Drug-in-adhesive patch	Nicotine incorporated into adhesive, potentially outside separate-reservoir claims
Matrix patch	Drug dispersed through polymer matrix, with release controlled by matrix properties
Membrane-controlled system	Uses a dedicated rate-control membrane, directly relevant
Oral nicotine replacement	Gum, lozenge, inhaler, or spray, outside transdermal device claims
Later formulation patents	May focus on adhesive chemistry, skin adhesion, crystallization, or nicotine stability

Earlier nicotine-transdermal patents, including US 4,597,961, established foundational concepts for transdermal nicotine delivery. Later patents addressed adhesive matrices, permeation enhancement, multilayer construction, and commercial patch manufacturing. The relevant competitive landscape therefore consisted of overlapping but distinct patent families rather than a single blocking patent.[4]

What generic entry risks exist?

There is no current generic entry risk created by US 5,004,610 because the patent expired.

During its term, the principal design-around options would have included:

• using a drug-in-adhesive configuration without a separate reservoir;
• using a saturated or supersaturated nicotine system;
• selecting a membrane that did not substantially block solvent;
• using a non-EVA reservoir;
• using a membrane other than the specified polyethylene or EVA materials;
• altering the loading, activity, flux, or administration period;
• using a different adhesive arrangement.

These changes would not automatically eliminate risk under every claim. Claim 1 is broad enough that a non-EVA design could still require analysis if it retained the claimed functional structure.

What manufacturing and IP barriers did the patent create?

The patent’s manufacturing limitations centered on controlling several variables simultaneously:

• nicotine concentration in the reservoir;
• EVA vinyl acetate content;
• membrane thickness and permeability;
• adhesive nicotine solubility;
• total patch loading;
• reservoir-to-adhesive loading distribution;
• nicotine flux over time;
• solvent migration.

Commercial implementation would require reproducible laminate construction and validated release testing. Claims 11, 12, 20, and related claims make layer thickness commercially relevant because thickness determines how much of the initial nicotine loading resides in the reservoir.

The manufacturing know-how could remain valuable after patent expiration, but it would be trade-secret or process know-how rather than enforceable exclusivity under US 5,004,610.

What is the geographic coverage of the patent?

US 5,004,610 provided rights only in the United States. It did not independently block products in Europe, Canada, Japan, or other markets. International protection would require separate national or regional patent applications.

The commercial patent landscape for nicotine patches would therefore require a family-by-family review across:

• United States;
• European Patent Office jurisdictions;
• Canada;
• Japan;
• Australia;
• major manufacturing jurisdictions.

Expiration of the US patent did not determine the status of corresponding foreign patents, although most related rights from the same early filing period would also be expected to have expired by the 2000s or early 2010s under ordinary patent terms.

Key Takeaways

• US 5,004,610 covers a multilayer transdermal nicotine patch with a subsaturated reservoir, selective rate-control membrane, in-line adhesive, and release liner.
• Claims 1, 9, and 18 are the three independent claims.
• Claim 1 is the broadest functional claim.
• Claim 9 requires an EVA reservoir and an LDPE, HDPE, or EVA membrane.
• Claim 18 requires 5% to 40% nicotine, 28% to 40% vinyl acetate EVA, and an HDPE membrane.
• Dependent claims add activity, loading, flux, nicotine concentration, and 24-hour-use limitations.
• The patent issued April 2, 1991, and expired on or about April 2, 2008 under the applicable pre-URAA term.
• It has no current blocking effect on generic nicotine patches or FDA ANDA approval.
• Paragraph IV challenges and patent litigation are no longer commercially necessary for this patent.
• Biosimilar analysis is irrelevant because nicotine is a small-molecule drug.
• Current freedom-to-operate analysis should focus on later, unexpired patents covering drug-in-adhesive systems, adhesive chemistry, permeation enhancement, manufacturing, and commercial patch designs.

FAQs

Does US 5,004,610 cover all nicotine patches?

No. It focuses on a reservoir-based patch with a nicotine-permeable, solvent-blocking membrane and an in-line adhesive. Drug-in-adhesive and matrix patches may fall outside its structural limitations.

Can a company still sue for infringement of US 5,004,610?

No current infringement action can be based on an expired patent. The patent’s enforceable US term ended in 2008.

Does a 24-hour nicotine patch necessarily infringe the patent?

No. Claim 21 narrows claim 18 to an approximately 24-hour administration period, but a 24-hour patch must also satisfy the other limitations of the applicable independent and dependent claim.

Is an EVA nicotine reservoir covered if it uses a non-HDPE membrane?

It may fall outside claim 18, which requires HDPE, but it could still require analysis under claim 9 if the membrane is LDPE, HDPE, or EVA and the other limitations are met. Claim 1 is broader as to membrane material.

Does the patent cover nicotine gum, lozenges, inhalers, or oral sprays?

No. The claims are directed to a transdermal medical device with a reservoir, rate-control layer, adhesive, and release liner.

References

1. United States Patent and Trademark Office. (1991). Transdermal nicotine delivery device, U.S. Patent No. 5,004,610.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
3. U.S. Food and Drug Administration. (2024). ANDA submissions: Patent certification and the Paragraph IV process.
4. United States Patent and Trademark Office. (1986). Transdermal administration of nicotine, U.S. Patent No. 4,597,961.

Drugs Protected by US Patent 5,004,610

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 5,004,610

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	161734
Australia	3852189
Australia	3913695
Australia	4491193