Details for Patent: 6,344,211

Summary for Patent: 6,344,211

Title:	Transdermal absorption of active substances from subcooled melts
Abstract:	A pharmaceutical product for the release of medicinal agents to the skin having absorption-increasing auxiliary agents is characterized in that the auxiliary material forms subcooled melts.
Inventor(s):	Thomas Hille
Assignee:	Purdue Pharma LP
Application Number:	US09/716,442
Patent Claim Types: see list of patent claims	Use;

United States Patent 6,344,211 (Transdermal Therapeutic System Release Methods): Scope, Claim Coverage, and US Patent Landscape

Executive summary: US Patent 6,344,211 claims a method of releasing pharmaceutical agents (local and/or systemic) from a layered transdermal therapeutic system, where an “auxiliary agent” that increases penetration has a melting point above room temperature and is processed by melting, cooling to form a “subcooled melt” at room temperature, then applying the resulting system to skin. The claim set is medium-specific on process steps and on auxiliary-agent physical state (subcooled melt) and melting-point condition, while it is broad on the pharmaceutical active class (local effect categories; systemic effect categories) and includes narrow dependent claim hooks that specify buprenorphine base combined with particular auxiliary agents (levulic acid; glutaric acid monomethyl ester; dodecanol). The landscape is likely dominated by: (i) transdermal penetration-enhancer formulation IP, (ii) layered transdermal structures, and (iii) processing approaches for penetration enhancers and/or other matrix components that generate amorphous, metastable, or supercooled/subcooled states. The specific “subcooled melt by cooling it down to room temperature” limitation will be the key differentiator for validity and infringement defenses.

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Scope of US Patent 6,344,211: What exactly is claimed in the release method?

Core claim concept (Claim 1): A two-step process tied to a transdermal therapeutic system with a layered structure that contains:

• at least one pharmaceutical agent for topical or systemic effect, and
• at least one penetration-increasing auxiliary agent with melting point above room temperature,

where the auxiliary agent is processed by:

• Step (a): melting the auxiliary agent, then cooling to room temperature to form a subcooled melt, and
• Step (b): applying the resulting transdermal therapeutic system to skin.

Featured-snippet answer: Claim 1 covers making and using a layered transdermal system where a high-melting penetration enhancer is converted into a subcooled melt at room temperature, then the system is applied to deliver local and/or systemic drug via topical exposure.

What “transdermal therapeutic system having a layered structure” implies

The claim language does not enumerate the layers, but it requires:

• a transdermal therapeutic system that is layered; and
• the listed pharmaceutical agent(s) and auxiliary agent(s) are present in that system.

In practical infringement mapping, “layered” is usually interpreted broadly, covering multi-layer patches, laminates, reservoirs, adhesive layers, backing layers, rate-controlling membranes, and skin-contact layers, as long as the accused product has distinct functional layers.

What the auxiliary-agent limitations require

Claim 1 imposes three auxiliary-agent constraints:

1. Penetration role: auxiliary agent increases penetration of the pharmaceutical agents.
2. Melting point constraint: auxiliary agent has melting point above room temperature.
3. Processing state constraint: the auxiliary agent is melted, then cooled to room temperature to form a “subcooled melt.”

The last element is the most technically load-bearing for both infringement and patentability.

Why “subcooled melt” is the likely claim choke point

“Subcooled melt” is not defined in the claim text you provided. It is likely intended to capture a metastable, supercooled, or amorphous state formed by controlled cooling that avoids crystallization at temperatures down to room temperature. This matters because many prior transdermal penetration-enhancer disclosures rely on:

• dissolving actives into solvents,
• incorporating penetration enhancers as liquids/low-melting components,
• amorphous dispersions or glass-formers,
• or plasticizers,

but may not specifically require:

• a melting step,
• cooling to room temperature,
• and attainment of a metastable “subcooled” state.

Any design-around that uses the same auxiliary agent but avoids creating a subcooled melt at room temperature is a credible noninfringement vector.

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How broad are Claim 1’s “local effect” and “systemic effect” drug categories?

Local effect drug class (Claim 2)

Claim 2 limits the “local effect” pharmaceutical agent to a member selected from:

• antiperspirants
• fungicides
• bactericides
• bacteriostatics

This is still broad across many actives used in topical antimicrobial and anti-sweating products.

Coverage impact: If an accused transdermal patch delivers an antimicrobial/antifungal agent using a penetration-enhancer processed via the subcooled-melt method, Claim 2 strengthens the asserted claim path for topical actives.

Systemic effect drug class (Claim 3)

Claim 3 provides a wide list of systemic-effect categories, including:

• antibiotics
• hormones
• antipyretics
• antidiabetic agents
• coronary vasodilators
• cardioactive glycosides
• analgesics
• spasmolytics
• antihypertensives
• psychotropic drugs
• migraine analgesics
• corticosteroids
• contraceptives
• antirheumatics
• anticholinergics
• sympathicolytics
• sympathicomimetics
• vasodilators
• anticoagulants
• antiarrhythmics

This claim is structurally a “choose-one-from-list” limitation, but the list is extensive.

Systemic effect narrowed exemplars (Claim 4)

Claim 4 further narrows systemic effect to:

• buprenorphine base
• pilocarpine base
• ephedrine base

Buprenorphine base and specific auxiliary agents (Claims 5-6)

• Claim 5: pharmaceutical agent is buprenorphine base and auxiliary agent is selected from:
  • levulic acid
  • glutaric acid monomethyl ester
  • dodecanol
• Claim 6: pharmaceutical agent is buprenorphine base and auxiliary agent is levulic acid.

These dependent claims create the most targeted commercial hooks. If a product uses buprenorphine base in transdermal therapy with levulic-acid-type penetration enhancement and processes that auxiliary via the subcooled-melt method, Claims 5 and 6 are the most directly relevant.

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What is the independent claim structure: does Claim 1 require both local and systemic delivery?

Claim 1 states “topical or systemic effect.” It does not require both simultaneously. The structure indicates:

• the pharmaceutical agent(s) can be selected for local effect, systemic effect, or both, as long as the system and method match the transdermal layered system and auxiliary-agent processing steps.

So, for infringement analysis, the key question is whether the method releases a pharmaceutical agent to achieve topical and/or systemic effect, not that both are present.

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Infringement theory mapping: how would an accused manufacturer practice the claimed steps?

A practical infringement checklist for Claim 1:

1. The accused process prepares a layered transdermal therapeutic system.
2. That system includes:
   • at least one pharmaceutical agent intended to produce a topical or systemic effect, and
   • at least one auxiliary agent that increases penetration and has melting point above room temperature.
3. The auxiliary agent is:
   • melted, then
   • cooled down to room temperature to form a subcooled melt.
4. The system prepared using that processing is applied to skin of a patient.

Process-and-use claim: Because the claim is a method that includes an “applying” step on skin, infringement theories commonly hinge on:

• whether the act of “applying” is attributable to the defendant (patient use after manufacturing can be litigated as direct infringement in some contexts), and/or
• whether there is induced infringement of the “use” step.

Design-around points:

• Avoid creating a “subcooled melt” at room temperature (e.g., crystallize, keep at higher temperature, use different state-control approach).
• Use an auxiliary agent that does not have melting point above room temperature.
• Employ an auxiliary agent with penetration enhancement but without the specific melt-to-subcooled-melt processing step.

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What formulations and delivery systems are within “layered structure” coverage?

While Claim 1 does not specify layer types, the combination of “layered transdermal therapeutic system” and penetration enhancer processing suggests coverage of:

• multi-layer adhesive patches (backing, drug reservoir or matrix, adhesive/penetration layer),
• laminate systems with distinct skin-contact layers,
• systems with rate-controlling membranes,
• and layered reservoir/matrix hybrids.

If the patent office prosecuted the family with “layered” embodiments such as adhesive layers and drug layers, those will inform claim construction. Absent that history in your prompt, the safe read is: any transdermal “patch-like” or “system-like” structure with distinct layers.

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Patent landscape for US 6,344,211: What other US patents likely overlap on key limitations?

With only the claim text provided, the landscape can be mapped by limitation-based technology clusters rather than by listing uncertain citation sets. The largest overlap risk areas are:

1) Penetration enhancer chemistry and physical-state processing

High overlap targets:

• subcooled melt / supercooled liquid / metastable penetration enhancer processing,
• glass-formers and amorphous excipients that remain metastable at room temperature,
• controlled cooling to avoid crystallization,
• eutectic formation and solidification control.

Why it matters: Claim 1 is not just about having a penetration enhancer with high melting point. It is about processing that enhancer into a subcooled melt at room temperature.

2) Transdermal layered systems with penetration enhancement

Many US transdermal patents cover layered patches and penetration enhancers:

• limonene-like terpenes,
• fatty alcohols,
• organic acids,
• surfactant-type enhancers,
• solvents and co-solvents,
• polymer matrices that improve permeation.

Overlap arises if the prior art also uses melting and controlled cooling to maintain metastable states, or if it explicitly describes melting high-melting agents and casting/solidifying in ways that could be argued to form subcooled melts.

3) Buprenorphine base transdermal delivery with penetration enhancers

Claims 5-6 create a narrower but commercially salient slice:

• buprenorphine base (systemic opioid delivery),
• auxiliary agent = levulic acid.

Landscape overlap is expected with buprenorphine transdermal systems that:

• use levulic acid or structurally related acids,
• or use fatty alcohols or ester compounds similar to the listed glutaric acid monomethyl ester / dodecanol.

4) Method-of-use and patient treatment patents

Because Claim 1 includes application to skin, there will be adjacent patent families involving:

• methods of treating pain/opioid disorders with transdermal buprenorphine,
• methods using transdermal patches containing specific excipients/penetration enhancers.

Those may not replicate the subcooled-melt processing step, but can overlap on the systemic therapeutic effect portion.

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Which claim elements drive patentability and validity challenges?

A strength/weakness assessment by limitation:

Potential vulnerability: “subcooled melt” claim scope

If prior art describes:

• melting and cooling of high-melting components,
• forming amorphous dispersions by cooling,
• or “supercooled” or “amorphous” mixtures at room temperature, then examiners or challengers may argue that “subcooled melt” is not meaningfully novel, depending on how the prior art operationally implements the process.

Potential strengthening: specific combination of features

Novelty and nonobviousness arguments are more likely when a challenger lacks prior art that combines:

• layered transdermal system,
• penetration enhancer with melting point above room temperature,
• and melting + cooling to form a subcooled melt at room temperature,
• applied to deliver the claimed topical/systemic effect.

Dependent Claims 5-6 further strengthen the estate against broad transdermal generic penetration-enhancer art by anchoring to:

• buprenorphine base,
• and specific auxiliary agents (especially levulic acid).

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Commercial and enforcement implications: where the patent bites hardest

Buprenorphine + levulic acid transdermal

If a commercial buprenorphine transdermal platform uses levulic acid as a penetration enhancer and uses a melt-to-subcooled-melt processing step before patch formation, it fits Claims 5-6 most tightly.

Other systemic agents (pilocarpine, ephedrine)

The broader Claim 4 list suggests additional enforcement pathways, but without the dependent auxiliary-agent specificity, the patent’s leverage depends heavily on proving the subcooled-melt processing step for the specific auxiliary-agent used.

Local effect categories

Antiperspirant and antimicrobial/fungicidal transdermal systems can be within Claim 2, but again, infringement hinges on the auxiliary-agent melting and subcooled-melt steps.

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Key design-around strategies tied to Claim 1

1. Different thermal history: Use a penetration enhancer with melting point above room temperature but avoid a subcooled melt state at room temperature (e.g., crystallize or lock in a different physical form).
2. Different penetration enhancer melting point profile: Use an auxiliary agent whose melting point is not above room temperature.
3. Omit the “subcooled melt” formation step: If the enhancer is processed as a solution, emulsion, or incorporated in a way that does not include “melted then cooled to form subcooled melt at room temperature,” then Claim 1 is weakened.
4. Process sequencing change: If manufacturing is modified so that the subcooled-melt auxiliary is not part of the transdermal therapeutic system “as prepared,” it can challenge step attribution.

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What is the scope of Claim 2-6 compared with Claim 1? (independent vs dependent narrowing)

• Claim 1 is the broad base: method + transdermal layered system + auxiliary agent melt/subcooled melt at room temperature + application to skin.
• Claim 2 narrows local-effect actives to the listed topical functional categories.
• Claim 3 narrows systemic-effect actives to the listed systemic categories.
• Claim 4 narrows systemic-effect actives to buprenorphine base, pilocarpine base, ephedrine base.
• Claim 5 narrows to buprenorphine base plus specific auxiliary agents.
• Claim 6 is the tightest: buprenorphine base + levulic acid.

For enforcement, the tight claims are most useful when the accused product uses those specific combinations and when manufacturing records can tie the process to subcooled-melt formation.

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Key Takeaways

• US 6,344,211 Claim 1 is a layered transdermal system release method that requires a high-melting penetration enhancer processed into a subcooled melt at room temperature, followed by application to skin.
• The independent claim is broad on which pharmaceutical agents produce topical/systemic effects, but narrow on auxiliary-agent processing state and thermal history.
• Dependent claims create the most enforceable commercial anchor for buprenorphine base paired with levulic acid (Claim 6).
• The most credible freedom-to-operate risks concentrate in transdermal buprenorphine/penetration-enhancer systems using levulic acid and in any platform that uses melt-to-subcooled-melt processing rather than crystallizing or keeping the enhancer in another physical state.
• Design-arounds that change the enhancer’s physical-state outcome at room temperature are most aligned with Claim 1’s novelty focus.

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FAQs

1. What does “subcooled melt” likely mean for infringement of US 6,344,211?
   The term is the pivotal limitation. Infringement turns on whether the auxiliary agent is processed by melting and controlled cooling to room temperature to achieve a metastable subcooled state rather than a crystallized or otherwise different solid form.

2. Can US 6,344,211 cover topical-only transdermal patches?
   Yes. Claim 1 expressly covers “topical or systemic effect,” and Claim 2 targets local-effect categories like antiperspirants and antimicrobial/fungicidal actives.

3. Which claims most directly target buprenorphine transdermal formulations?
   Claims 4-6. Claim 6 is the narrowest: buprenorphine base with levulic acid as the penetration-increasing auxiliary agent.

4. How does the melting point condition affect claim scope?
   The auxiliary agent must have a melting point above room temperature. If an accused formulation uses a penetration enhancer with a melting point below room temperature or uses only low-melting components, it can fall outside Claim 1.

5. What manufacturing evidence is typically most relevant for these thermal-history limitations?
   Process validation data that identifies the melting and cooling profile down to room temperature, plus characterization showing metastable “subcooled melt” formation (or an equivalent physical-state outcome) for the auxiliary agent in the finished transdermal system.

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References

1. US Patent 6,344,211. United States Patent and Trademark Office. (Claim text provided in prompt).

Drugs Protected by US Patent 6,344,211

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 6,344,211

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	44 46 600	Dec 24, 1994

International Family Members for US Patent 6,344,211

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	172640
Australia	4387196
Germany	4446600
Germany	59504097