Details for Patent: 5,016,652

Summary for Patent: 5,016,652

Title:	Method and apparatus for aiding in the reduction of incidence of tobacco smoking
Abstract:	A dermally applicable patch adapted for application to the skin of the user to enable a transdermal administration to the bloodstream of a user. The patch comprises an outer layer which is impermeable to the passage of nicotine and an inner layer which may operate as a rate controlling membrane to allow the passage of nicotine into the bloodstream of a user. An outer layer and an inner layer form a nicotine receiving area for receiving the nicotine to thereby allow the same to pass through the inner layer. In a preferred embodiment, the patch is highly effective in reducing the incidence of tobacco smoking by allowing transdermal nicotine migration into the bloodstream of a user at a rate sufficient to correspond to the nicotine level in the blood achieved by smoking.
Inventor(s):	Jed E. Rose, Murray E. Jarvik
Assignee:	University of California San Diego UCSD
Application Number:	US07/157,627
Patent Claim Types: see list of patent claims	Composition; Delivery;

United States Patent 5,016,652 (Nicotine Transdermal Patch): Scope, Claim Coverage, and U.S. Patent Landscape

Executive summary: U.S. Patent 5,016,652 claims a nicotine transdermal patch with (i) an outer nicotine-impermeable layer, (ii) an inner skin-contact porous layer (or rate controlling membrane) that enables transdermal nicotine migration to the bloodstream, (iii) a temporarily and releasably attached patch-to-skin interface, and (iv) a nicotine receiving area that releases nicotine through the inner layer. Dependent claims narrow into specific delivery targets (e.g., starting blood nicotine and maintenance nicotine ranges), and into formulation variants adding membranes, penetration enhancers, pH control agents, and nicotine antagonists (with hexamethonium named). The patent’s practical enforcement strength is concentrated on patch architectures with these structural elements and on formulation additives that are explicitly claimed.

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What exactly is claimed in U.S. Patent 5,016,652 for nicotine transdermal patches?

Core independent claim 1: What patch architecture is covered

Claim 1 is the structural backbone. It requires, in one patch:

1. Outer layer impermeable to nicotine
2. Inner layer placed against skin, porous enough to allow nicotine passage for transdermal administration to bloodstream
3. Means for temporarily and releasably attaching to the skin
4. Outer + inner layers form a “nicotine receiving area” that receives nicotine to allow it to pass through the inner layer

This is an architecture claim anchored to layer function, layer placement, and functional nicotine transport through the porous/inner layer.

Key dependent claim themes that expand scope from the architecture

Claim 2 (membrane in nicotine receiving area): adds a membrane in the nicotine receiving area “to receive and enable a release of the nicotine.”

• This tightens the release mechanism without changing the core outer/inner layer concept.

Claim 3 (rate controlling membrane as inner layer): specifies the inner layer is a rate controlling membrane controlling nicotine delivery rate.

Independent claim 4: “Smoking reduction” functional framing

Claim 4 recasts the invention as a patch “for aiding in reduction of incidence of tobacco smoking,” but still requires the same functional components:

• dermally applicable pad
• nicotine in the pad dispensed at a controlled rate
• applying means
• rate controlling membrane adjacent skin to migrate nicotine into bloodstream at a rate corresponding to blood nicotine “achieved by smoking”

This is essentially a delivery-rate target concept tied to smoking-replacement pharmacokinetics.

Delivery target narrowing claims 5–7

These are specific quantitative limitations:

• Claim 5: patch comprises at least 8 mg nicotine
• Claim 6: nicotine amount and delivery rate produce ~10 ng/mL blood nicotine at start of smoking reduction program
• Claim 7: patch configured to maintain ~50 to 250 µg nicotine in bloodstream

These claims are narrowest. They are the most vulnerable to design-around if a different nicotine load or different delivery rate/blood target is used.

Claims 8–9: explicit outer/inner nicotine receiving area variant

Claim 8 requires:

• outer nicotine-impermeable layer
• inner rate controlling membrane on skin
• outer+inner forming nicotine receiving area for receiving nicotine to pass through inner layer

Claim 10 adds the element that nicotine is received in admixture with a nicotine carrier for passage through the inner layer.

• “Carrier” can be a wide formulation concept, but the claim ties it to being in the receiving area.

Claims 11–13: agents controlling penetration and pH

Claim 11 adds an agent in nicotine receiving area to control penetration through skin (control mechanism for nicotine influx).

• Claim 12: agent increases skin permeability (increasing absorption rate)
• Claim 13: agent adjusts pH of nicotine to control delivery rate from patch

These claims are formulation additions that keep the patch architecture but add control mechanisms.

Claims 14–15: nicotine antagonists to reduce peripheral side effects

Claim 14 adds a nicotine antagonist in the nicotine receiving area to reduce peripheral side effects.
Claim 15: nicotine antagonist is hexamethonium.

This is the most distinctive dependent claim for commercial differentiation because it specifies a known antagonist.

Claim 16: penetration enhancer (genericized)

Claim 16 states the agent comprises a penetration enhancer. This maps onto a broad class of known excipients used for transdermal flux.

Claims 17–24: additional “smoking reduction” formulation and membrane release variants

Claims 17–24 parallel claims 4, 8, and 11–13 but in the “smoking reduction” framing and with additional dependent limitations:

• Claim 18: adds agent to control penetration
• Claim 19: agent increases skin permeability
• Claim 20: agent adjusts pH
• Claim 21: adds nicotine antagonist to reduce peripheral side effects
• Claim 22: antagonist is hexamethonium
• Claim 23: patch comprises ~1 to ~5 mg nicotine and agent is a penetration enhancer
• Claim 24: includes a membrane in nicotine receiving area to receive and enable nicotine release

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Which claim elements define infringement risk for products entering the nicotine patch market?

Element-by-element infringement mapping (high-value features)

For a nicotine transdermal patch to fall within the claim core, it must satisfy, at minimum:

• Outer nicotine-impermeable layer (or an equivalent that performs as impermeable to nicotine)
• Inner porous and skin-contact layer that enables nicotine passage to bloodstream
• Patch-to-skin releasable attachment means
• Nicotine receiving area formed by outer+inner layers
  Then, for dependent claim infringement risk, it must also include:
• Membrane in receiving area (claims 2, 24)
• Rate controlling membrane as inner layer (claims 3, 8)
• Nicotine load and blood nicotine targets (claims 5–7)
• Nicotine carrier admixture in receiving area (claim 10)
• Penetration control agent in receiving area (claims 11, 18) and/or
  • penetration enhancer (claim 16 and claim 23)
  • pH adjustment agent (claims 13 and 20)
• Nicotine antagonist to reduce peripheral side effects, specifically hexamethonium (claims 14–15, 21–22)

Design-around “pressure points”

1. Eliminate or change the “outer layer impermeable to nicotine” function
   • If a competitor’s system does not have a nicotine-impermeable backing and relies on different barrier/transport control architecture, it creates literal and doctrine-of-equivalents risk.
2. Change from a “nicotine receiving area formed by outer and inner layers”
   • If nicotine is held and released in a different structural compartment not defined by outer+inner interfaces as claimed, risk changes.
3. Avoid the claimed agent placements
   • The claims place agents “in the nicotine receiving area” (claims 11, 14, 18, 21). If penetration modifiers or antagonists are elsewhere (e.g., backing side, separate reservoir, different layer), claim construction may narrow.
4. Avoid hexamethonium specifically
   • Claims explicitly name hexamethonium as the antagonist in dependent claims 15 and 22. If a product uses a different antagonist, the dependent claim literals drop away.
5. Avoid quantitative nicotine load/delivery targets
   • Claims 5–7 are narrow and can be avoided by different dose and delivery kinetics, though independent claims may still capture a broader patch architecture.

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How strong is the patent estate around U.S. 5,016,652 for nicotine patch delivery mechanisms?

What this patent likely anchors

U.S. 5,016,652 is a foundation architecture patent for early nicotine patch concepts: backing as nicotine-impermeable, skin-contact porous/rate-control membrane, and an organized nicotine reservoir. The dependent claims cover common formulation strategies:

• transdermal flux enhancement
• pH-based modulation of nicotine delivery
• antagonist addition to reduce peripheral side effects
• explicit nicotine dose and pharmacokinetic targets
• membrane in the receiving area to manage release

Landscape implications

Even without enumerating every family member or related patent in the record provided, the claim scope strongly indicates the existence of adjacent U.S. patents likely targeting:

• alternative nicotine reservoir structures
• different rate-controlling membranes
• specific penetration enhancers and pH agents
• antagonist combinations
• nicotine dosage form variants (different patch sizes, loadings, and multi-layer release designs)

This matters commercially because nicotine patches are typically iterated by:

• backing materials and barrier performance
• membrane chemistry (rate controlling membrane)
• reservoir composition (carrier, polymer matrices)
• enhancers and acid/base/pH buffering systems
• dose targeting via membrane thickness and loading

A competitor can reduce exposure by changing at least one of the core architecture elements. A competitor with close structural similarity retains exposure even if the dose target differs, unless it also avoids independent claim features.

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What is the legal claim scope posture for nicotine patch “smoking reduction” claims?

Are the “smoking reduction” statements limiting?

Claims 4, 17, 18, 21, 23, 24 recite “a patch for aiding in the reduction of the incidence of tobacco smoking.” The operative technical limitations are still:

• nicotine content in a dermally applicable pad
• controlled-rate dispensability
• a rate controlling membrane adjacent skin
• migration into bloodstream corresponding to nicotine levels achieved by smoking

In practice, infringement analysis will focus on whether the patch is configured to produce the blood nicotine profile and uses the claimed structural components.

Dose and pharmacokinetic recitations

Claims 5–7 provide the strongest “factual” hook for enforcement. In disputes, the technical record typically centers on:

• nicotine load per patch
• membrane-controlled release rate
• in vivo blood nicotine concentration-time profile at program start and during use

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What formulations are protected by U.S. 5,016,652?

Carrier and nicotine admixture

Claim 10 explicitly protects nicotine in admixture with a nicotine carrier in the nicotine receiving area.

Penetration enhancers

• Claim 16: agent is a penetration enhancer
• Claim 23: specific subrange of nicotine content and enhancer presence
• Claims 12 and 19: permeability increased to thereby control absorption

pH adjustment

• Claim 13: adjusts pH of nicotine to control delivery rate
• Claim 20: same in the smoking reduction framed claims

Nicotine antagonists

• Claim 15 and 22: antagonist is hexamethonium
• Claim 14 and 21: antagonist as a class to reduce peripheral side effects (hexamethonium dependent)

Membrane release structures

• Claim 2 and 24: membrane in nicotine receiving area enabling nicotine release
• Claim 3 and 8: rate controlling membrane as inner layer

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What generic entry risks exist for nicotine transdermal patches under this claim set?

Why “generic” matters less than “formulation similarity”

Nicotine patches are often reformulated by changing:

• reservoir polymer/carrier system
• membrane type and thickness
• enhancers
• dose loading
• backing materials

Under 5,016,652, the highest risk sits with products that keep the same layer architecture and include agents positioned in the nicotine receiving area.

Risk tiers

• High risk: patches with nicotine-impermeable backing, porous/rate-controlling skin membrane, nicotine receiving area as defined, and formulation agents (pH modifier/penetration enhancer/antagonist) within the receiving area.
• Medium risk: patches that match architecture but change dose targets or remove pH/penetration enhancements.
• Lower risk: patches that differ materially from the layered architecture (especially backing impermeability) or place functional additives in different compartments.

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What patent expiration timelines and Orange Book status apply?

No complete Orange Book filing record, listed patents, or FDA product-specific data for nicotine transdermal patch products can be derived from the claim text alone. Without those identifiers, a complete exclusivity/expiration timeline cannot be produced from the information provided.

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Key Takeaways

• U.S. 5,016,652 is primarily a layered nicotine transdermal patch architecture patent: nicotine-impermeable outer layer, porous/rate-controlling inner membrane against skin, releasable attachment, and a nicotine receiving area formed by the layers.
• Dependent claim scope expands into release and delivery control (membranes, rate control), formulation modulation (penetration enhancers, pH control agents, nicotine carrier admixture), and side-effect management via hexamethonium-containing nicotine antagonist concepts.
• The narrowest commercially meaningful hooks are dose/loading and blood nicotine concentration targets (claims 5–7) and the specific antagonist identity (hexamethonium, claims 15 and 22).
• Design-around leverage is strongest by changing at least one of the core structural elements (outer impermeable layer, receiving area formation, inner porous/rate membrane role) and by relocating or eliminating dependent-claim additives.

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FAQs

1. Does U.S. 5,016,652 cover nicotine transdermal patches without a nicotine-impermeable outer layer?
   No, claims 1, 8, 10, 11, 14, and 24 all require an outer layer impermeable to nicotine.

2. What is the most specific dependent claim in terms of nicotine dosing?
   Claims 5–7 recite quantitative nicotine content and blood nicotine targets (about 10 ng/mL at program start and about 50 to 250 micrograms maintained).

3. Are penetration enhancers and pH modifiers protected only if they are in the nicotine receiving area?
   The claims place the agent in the nicotine receiving area (e.g., claims 11, 18, 14, 21), so location within the nicotine receiving area is a key limitation.

4. Is hexamethonium required for side-effect control claims to be covered?
   Hexamethonium is required for dependent coverage under claims 15 and 22; independent coverage for a nicotine antagonist concept exists in claims 14 and 21 (as a class), but the exact scope depends on how “nicotine antagonist” is construed.

5. What release-control mechanisms are claimed besides the rate controlling membrane?
   The patent also claims a membrane in the nicotine receiving area to enable nicotine release (claims 2 and 24).

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References (APA)

1. United States Patent 5,016,652, “Nicotine transdermal patch,” claims as provided in prompt.

Drugs Protected by US Patent 5,016,652

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 5,016,652

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	1283053
Mexico	9203535