Scope and claims review and US patent landscape for U.S. Patent 6,818,226 (non-occlusive volatile-vehicle transdermal systems with touch-dry time)
U.S. Patent 6,818,226 claims a non-occlusive percutaneous/transdermal drug delivery system built around (1) a volatile liquid vehicle that evaporates after application, (2) a low-toxicity dermal penetration enhancer (including specific long-chain alkyl para-aminobenzoate/cinnamate/methoxycinnamate/salicylate esters) that forms a reservoir/depot within skin/mucosa as the volatile evaporates, and (3) a performance requirement that the treated area is touch-dry within 3 minutes (or narrower dependent claims: within 1 minute). The patent’s claim architecture mixes device/system structural elements with functional aftermath (reservoir formation) and rapid-dry kinetics (touch-dry time), creating enforceability opportunities against “volatile-enhancer depot-forming” topical/transdermal products, but also litigation risk if accused products do not meet those exact kinetic or enhancer-adaptation constraints.
What is US Patent 6,818,226 claiming: non-occlusive volatile transdermal depots and touch-dry requirements?
Independent claim 1 is the core scope. It is not limited to a single drug and is drafted to read on multiple therapeutic payloads via broad “physiologically active agent or prodrug” language. It also is not limited to a specific formulation carrier beyond requiring a volatile liquid vehicle and a penetration enhancer with defined properties.
Claim 1 scope in plain technical terms
Claim 1 recites a system comprising:
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Non-occlusive percutaneous or transdermal delivery system
- Implies the system is not designed to occlude skin/mucosa (a common design lever to reduce transepidermal hydration and alter penetration).
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Therapeutically effective amount of at least one physiologically active agent or prodrug
- Intended to cover broad drug classes and specific examples in dependent claims.
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Dermal penetration enhancer present at 10 to 10,000 wt % based on weight of the active
- This is a major quantitative anchor: the enhancer mass relative to active must fall inside a wide but defined ratio.
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At least one volatile liquid present in an amount to act as vehicle for the active and penetration enhancer
- Volatility is central to the claimed mechanism.
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Penetration enhancer functional adaptation (A) and tolerability (B)
- (A) is “adapted to transport” the active across skin/mucosa when the volatile evaporates to form a reservoir/depot mixture of enhancer + active within the surface/membrane.
- (B) low toxicity and tolerated by skin/mucosa.
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Kinetics/performance
- After application, the area becomes touch-dry within 3 minutes of application.
Key claim-interpretation pressure points
- “Non-occlusive”: accused products designed with occlusive films/patches, gels with non-volatile components, or polymer membranes may fall outside the limitation.
- “Touch-dry within 3 minutes”: a measurable endpoint; enforcement turns on test conditions and product-specific drying behavior.
- “Adapted… when volatile evaporates… to form a reservoir/depot”: includes both mechanism and structural outcome. If an accused product uses an enhancer that primarily partitions without forming a reservoir/depot after evaporation, or if it does not rely on evaporation to trigger the deposition, claim 1 narrows.
- Enhancer ratio (10–10,000 wt % based on active): many commercial transdermal products use lower enhancer-to-drug ratios. A ratio mismatch is a direct validity/enforceability risk.
Which penetration enhancers are explicitly covered (and how do dependent claims narrow the estate)?
Dependent claims 2, 6, 7, 8, and 5 create a layered enhancer scope.
What exact enhancer chemistries are named? (Dependent claims 2, 7, 8)
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Claim 2: esters selected from:
- C8 to C18 alkyl para-aminobenzoate
- C8 to C18 alkyl dimethyl-para-aminobenzoate
- C8 to C18 alkyl cinnamate
- C8 to C18 alkyl methoxycinnamate
- C8 to C18 alkyl salicylate
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Claim 7: long-chain alkyl analogs of the same families (para-aminobenzoate, dimethyl-para-aminobenzoate, cinnamate, methoxycinnamate, salicylate).
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Claim 8: specific exemplars:
- octyl dimethyl-para-aminobenzoate
- octyl para-methoxycinnamate
- octyl salicylate
Practical effect: these dependent claims carve out the most commercially common “sunscreen-like” penetration enhancers (octyl salicylate and UV filter families), increasing the plausibility that many topical/transdermal products could land within the enhancer structural definitions if the rest of claim 1 (volatile + non-occlusive + touch-dry + depot mechanism) is met.
What general formula enhancer is claimed? (Dependent claim 6)
Claim 6 recites an ester of formula (I), defining:
- R1: hydrogen, lower alkyl, lower alkoxy, halide, hydroxy, or NR3R4
- R2: long chain alkyl
- R3/R4: hydrogen or lower alkyl, or together form a 5- or 6-membered heterocycle with nitrogen
- n: 0 or 1
- q: 1 or 2
This formula-driven dependent claim gives broader coverage than the named octyl exemplars while remaining chemically tethered to the same ester architecture.
Skin tolerance and sunscreen framing (Dependent claim 5)
Claim 5: penetration enhancer is “a safe skin tolerant sunscreen.”
Interpretation pressure: “safe skin tolerant” is an additional limitation that can be argued via formulation safety profiles, ingredient selection rationale, or regulatory status for sunscreen use.
How fast must the formulation dry: what do dependent claims 4 and 3 do to enforceability?
Touch-dry time narrowing
- Claim 1: touch-dry within 3 minutes
- Claim 4: touch-dry within 1 minute
Enforcement impact: accused products that are fast-drying may still avoid Claim 4 yet still potentially infringe Claim 1. Conversely, slower products are more vulnerable on Claim 4 but could still infringe Claim 1 if they dry within 3 minutes under relevant testing conditions.
Supersaturation limitation (Dependent claim 3)
Claim 3 excludes systems “supersaturated with respect to the physiologically active agent.”
Commercial impact: many transdermal approaches use supersaturation to drive thermodynamic activity. A supersaturation-based competitor can attempt non-infringement using this dependent limitation, assuming claim 3 becomes part of asserted claim sets.
Is the volatile vehicle limited: what do ethanol/isopropanol dependencies imply?
- Claim 9: volatile liquid is ethanol or isopropanol.
This is a specific limitation that narrows if asserted, but it signals the patent’s practical formulation space: alcohol-driven evaporation and “dry touch” performance.
Claim 1 itself only requires at least one volatile liquid acting as vehicle; it is not restricted to ethanol/isopropanol in claim 1, but claim 9 narrows.
What forms of administration are covered: aerosol/spray and shroud mechanics?
Administration mode (Dependent claims 12-13, 21)
- Claim 12: applied by aerosol spray
- Claim 13: fixed or variable metered dose aerosol
- Claim 21: aerosol/spray with a shroud that keeps actuator nozzle at a predetermined height above application site
Infringement map: products marketed as metered-dose aerosol sprays with designed nozzle spacing align closely. Non-aerosol topical gels/solutions may argue outside these dependent claims, but still could infringe claim 1 if claim 1 does not require aerosol.
What drugs are listed: does the patent claim a broad drug class or specific actives?
Claim 10 and 11 include long enumerations of possible physiologically active agents (and prodrugs), including:
- steroid and hormone derivatives (testosterone, estradiol, ethinylestradiol, progesterone, norethisterone acetate)
- anti-inflammatories (ibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac)
- opioids (fentanyl, buprenorphine)
- antiemetics/antagonists (scopolamine, prochlorperazine, metoclopramide, ondansetron)
- cancer and endocrine modulators (tamoxifen, exemestane, finasteride, turostende, LY191704, MK-306, cyproterone acetate, mazindol)
- CNS agents (alprazolam, melatonin, tacrine, fluphenazine, haloperidol)
- dermal/neuro effects (minoxidil and prodrugs)
- cardiovascular and respiratory (amlodipine, nitrendipine, salbutamol, terbutaline, salmeterol)
- antivirals/prodrugs (lipophilic pro-drugs of acyclovir)
- anticoagulant (low molecular weight heparin, enoxaparin)
- other specific agents (sumatriptan, primaquine, pilocarpine, prostacylcin)
Legal meaning: these lists expand the patent’s written description support and may reduce arguments that “physiologically active agent” is narrow. They also provide a roadmap to likely infringement targets in endocrine, pain, respiratory, and CNS categories.
What methods are claimed: administration and treatment method coverage
Method-of-administration (Claim 15)
A method of administering a systemic or local active by applying an effective amount of the system of claim 1 to dermal surface or mucosal membrane.
Method-of-treatment (Claim 16-18)
- Claim 16: method for treating a disease/condition in an animal by administering therapeutically effective amount using claim 1 system.
- Claim 17: enumerated disease/condition list including:
- testosterone deficient hypogonadal men
- postmenopausal female hormone replacement
- androgen replacement for females lacking libido
- soft tissue injury
- narcotic withdrawal
- severe post-operative pain
- estrogen dependent breast cancer
- prostatic enlargement and prostatic cancer
- alopecia
- anxiety disorder, male impotence
- Raynaud’s syndrome, varicose veins
- sleep disorder
- herpes virus infection
- deep vein thrombosis
- migraine, high blood pressure, malaria
- Claim 18: for motion sickness, acne, jetlag, asthma and nocturnal asthma
- Claim 19: animal is human
Contraception and diagnosis (Claims 22-23)
- Claim 22: male contraception or female contraception
- Claim 23: diagnosis of cystic fibrosis
Litigation practical note: claims 15-23 are method claims. In a US context, enforcing these method claims against third parties can turn on evidence of use/administration (consumer/clinic handling) and whether the accused activity includes applying the patented system to dermal/mucosal sites.
How strong is the “patent scope” versus typical transdermal design-arounds?
Design-arounds likely relevant to this claim set
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Occlusive or semi-occlusive formulations
- If a product uses occluding films, patches, or polymer membranes, it can challenge the “non-occlusive” limitation.
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Non-evaporative vehicles
- If the system uses non-volatile solvents or sustained release gels without relying on evaporation to trigger depot formation, it can challenge the “when volatile liquid evaporates… reservoir/depot” mechanism.
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Slow drying
- If touch-dry time exceeds 3 minutes in relevant conditions, it can challenge Claim 1.
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Supersaturation
- If the formulation is deliberately supersaturated to drive activity, it can avoid Claim 3 if asserted; even if Claim 1 is asserted alone, supersaturation strategies may still create factual disputes on how the system functions after application.
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Enhancer class mismatch
- If the penetration enhancer is not in the claimed low-toxicity, depot-forming class, and is not an ester of the specified families, the strongest dependent-claim paths narrow. Claim 1 still covers “at least one dermal penetration enhancer” that matches functional/tolerability criteria, so complete escape usually requires more than chemistry substitution; the depot and evaporation mechanism must not match.
What does the patent landscape look like around this concept (US non-occlusive volatile transdermal depot systems)?
A complete US “landscape” requires the patent’s full bibliographic record (publication numbers, priority dates, assignee) and an examination of forward citations, family members, and US continuations. Those data are not present in the provided material. Without them, any attempt to list specific neighboring patents, litigation outcomes, or Orange Book listings would be incomplete and potentially incorrect.
Therefore, the analysis below focuses on claim-structure-driven landscape implications that govern how competitors search, design, and litigate around this patent concept.
Which companies and products are most likely to implicate this estate concept, based on claim design?
Even without enumerating specific accused products, the claim’s technical constraints identify the competitor set:
- Topical alcohol-based delivery sprays that achieve “touch-dry” quickly
- Transdermal or dermal delivery formulations using:
- alkyl para-aminobenzoate esters
- alkyl cinnamate/methoxycinnamate
- alkyl salicylate, including octyl salicylate
- Systems marketed as non-occlusive
- Products designed to create skin/mucosal depots after evaporation rather than continuous permeation from a film
Because dependent claim 8 explicitly includes common UV filters, companies working with UV-filter esters as penetration enhancers face a higher probability of being within the claim chemistry space, leaving factual issues to test-driven parameters (touch-dry time, occlusion status, enhancer-to-drug ratio, and depot formation mechanism).
How does the “touch-dry” limit affect freedom-to-operate (FTO) and litigation strategy?
FTO testing and evidence generation
- Expect heavy reliance on formulation characterization and surface dryness kinetics.
- A manufacturer can reduce risk by:
- demonstrating dry time outside the claimed window under standardized test conditions
- altering the composition to ensure the enhancer-to-active ratio falls outside 10–10,000 wt %
- using vehicles and compositions where no reservoir/depot of enhancer+active persists after evaporation in the claimed manner
Litigation evidentiary leverage
- “Touch-dry within X minutes” often becomes the factual battleground.
- Claims 1 and 4 allow either “within 3 minutes” or “within 1 minute” theories. A defendant may attack both via testing or via argument that “touch-dry” is not met by their product as used.
What would a generic or follow-on product need to do to enter without infringing this patent?
Because this is a device/system and method patent with broad drug coverage, a “generic” entrant would usually need to address multiple elements simultaneously:
- avoid non-occlusive volatile evaporation depot architecture (or change one element so the claim fails)
- adjust enhancer choice and loading relative to active
- ensure drying endpoint exceeds claimed touch-dry limits
- if using alcohol or similar volatile vehicles, prevent formation of the claimed reservoir/depot
If the follow-on uses different delivery mechanisms (e.g., passive diffusion from non-volatile gel, patches with polymer reservoirs, or iontophoretic methods), it may avoid the combination limitations in claim 1.
Key Takeaways
- Independent claim 1 is broad in payload and enhancer type but narrow on architecture: non-occlusive system + volatile vehicle + low-toxicity penetration enhancer that drives depot formation upon evaporation + touch-dry within 3 minutes.
- Dependent claims tighten scope on:
- specific enhancer chemistries (C8–C18 alkyl ester families; octyl dimethyl-PABA; octyl p-methoxycinnamate; octyl salicylate)
- faster drying (touch-dry within 1 minute)
- avoidance of supersaturation (dependent claim 3)
- volatile liquid identity (ethanol/isopropanol)
- aerosol delivery mechanics (including metered dose and shroud)
- Enforceability and FTO risk typically hinge on testable formulation performance (dry time), quantitative composition (enhancer-to-active ratio), and mechanistic evidence (depot formation as volatile evaporates).
FAQs
1. Does claim 1 require a specific drug active ingredient?
No. It requires at least one “physiologically active agent or prodrug,” with many examples in dependent claims.
2. What is the single most litigated numeric limitation in this claim set?
The post-application touch-dry time: within 3 minutes (and potentially within 1 minute under claim 4).
3. If a product uses octyl salicylate as a penetration enhancer, is it automatically within claim scope?
No. It also must be a non-occlusive volatile-vehicle system that drives reservoir/depot formation upon evaporation and meets the touch-dry time and enhancer-to-active ratio constraints.
4. Can a supersaturated transdermal formulation avoid infringement?
It can target non-infringement of dependent claim 3 if asserted, since claim 3 excludes supersaturated systems.
5. Are method claims in this patent limited to humans?
No. Claims 15-18 broadly cover animals; claim 19 specifies human as a dependent limitation.
References (APA)
- U.S. Patent 6,818,226. (n.d.). Non-occlusive percutaneous or transdermal drug delivery system with volatile vehicle and penetration enhancer forming depot; touch-dry within specified time.
