Details for Patent: 6,579,865

Summary for Patent: 6,579,865

Title:	Penetration enhancing and irritation reducing systems
Abstract:	This invention lies in the technology of transdermal and topical drug delivery. In particular, the present invention relates to enhancement of the penetration of transdermally or topically applied drugs and with the reduction of skin irritation that often accompanies transdermal and topical drug delivery.
Inventor(s):	Vivien H. W. Mak, Stephen Grayson
Assignee:	Strakan International SA
Application Number:	US09/963,287
Patent Claim Types: see list of patent claims	Composition;

US Patent 6,579,865 Landscape and Claim Scope: Topical Testosterone Penetration-Enhancing Compositions Using Oleic Acid, C1-C4 Alcohol, Glycol, and Gelling Agents

US Patent 6,579,865 is directed to a topical composition for testosterone (or derivatives) that uses a defined penetration-enhancing system: oleic acid as a membrane fluidizer, a C1–C4 alcohol (including ethanol, propanol, isopropanol and mixtures), and a glycol (ethylene/propylene/butylene glycol and mixtures), formulated with a gelling agent and adjusted to a pH of about 5 to about 8. The claims are structured to cover both a broad “consisting essentially of” composition and narrower embodiments (testosterone propionate, specific excipient classes, and specific ranges).

The primary business implication is that the practical freedom-to-operate (FTO) will turn on whether competing products include the same functional excipient package at overlapping concentration ranges and pH, and whether they can fall outside claim boundaries by changing the penetration-enhancer system (different membrane fluidizer and/or different solvent-glycol architecture), switching gelling agent class, or altering pH and concentration relationships.

---

What does US Patent 6,579,865 claim and how broad is the “consisting essentially of” scope?

Core independent claim theme (claim 1 / claim 28):
A topical testosterone composition with:

• Active agent: testosterone or derivatives, ~0.1% to ~2%
• Penetration-enhancing system:
  • (i) membrane fluidizer: oleic acid
  • (ii) C1–C4 alcohol (ethanol, propanol, isopropanol or mixtures)
  • (iii) glycol (ethylene glycol, propylene glycol, butylene glycol or mixtures)
• Gelling agent (selected from specified group in dependent claim 23)
• pH: about 5 to about 8
• “Consisting essentially of” language: additional components may exist but must not materially change the basic and novel characteristics of the composition.

Practical breadth of “consisting essentially of”:

• Competitors can sometimes add excipients (preservatives, buffers, surfactants) without leaving claim scope if those additions do not materially affect the “basic and novel” penetration-enhancing system and formulation properties.
• Design-around is typically harder if the competitive product keeps oleic acid + the specific alcohol class + glycol while staying in the pH and concentration windows.

Key limitation effect:

• Oleic acid is required (claim 1 recites it as the membrane fluidizer). That single excipient is a major pivot point for design-around.

Claim architecture snapshot

• Independent: claim 1 (and claim 28 recaps a similar structure while adding “inert carriers”)
• Dependent claim set:
  • active-species narrowing (testosterone propionate vs testosterone)
  • concentration windows for testosterone
  • concentration windows for oleic acid
  • specific alcohol species and alcohol concentration ranges
  • specific glycol species and glycol concentration ranges
  • gelling agent selection from a defined list and gelling agent concentration ranges

---

Which ingredients are required: active testosterone, oleic acid, alcohol, glycol, and specified gelling agents?

Active agent scope

• Testosterone or derivatives at ~0.1% to ~2% (independent claim 1; dependent claim 2 narrows to testosterone propionate)
• Dependent claim 3 narrows active agent to testosterone

Design impact:
A product using a testosterone derivative not encompassed as a “derivative[] thereof” could still be argued as within the claim, but practical product labels typically list explicit chemical species. If a competitor uses a different active (eg, estradiol, dihydrotestosterone, testosterone undecanoate in another route), the claim is not implicated on active ingredient.

Penetration-enhancing system is functionally and structurally constrained

• Membrane fluidizer: oleic acid (required)
• C1–C4 alcohol: ethanol, propanol, isopropanol, mixtures (required class + species options)
• Glycol: ethylene glycol, propylene glycol, butylene glycol, mixtures (required class + species options)

Design impact:
A competitor that replaces oleic acid with another fatty acid, lipid, or ester (eg, linoleic acid, glycerol esters, isopropyl myristate) likely avoids the literal “membrane fluidizer comprising oleic acid” requirement, though doctrine-of-equivalents exposure depends on prosecution history and equivalency arguments (not provided here).

pH constraint is explicit

• pH value between about 5 and about 8 (claim 1 and claim 28)

Design impact:
A formulation outside this pH band is the cleanest non-active design-around lever while still keeping the same excipients. If pH is kept in-band, claim exposure persists.

Gelling agent scope

Dependent claim 23 limits gelling agents to:

• Carbopol 1342
• Carbopol 940
• Klucel
• Klucel HF

Dependent claims 24 and the following specify species and ranges:

• gelling agent concentration ~0.1% to ~10%, with narrower ranges in claims 26–27

Design impact:
Switching to a gelling agent outside this list (eg, HPMC, PVA, chitosan, carbomer types not listed) can be a direct claim avoidance strategy, but only if the formulation no longer satisfies the claim’s “gelling agent, said composition comprising …” requirement in the literal sense.

---

Which concentration ranges for testosterone and excipients create the biggest claim boundaries?

The patent is highly range-driven; commercial formulations that cluster around common transdermal solvent systems create higher risk if they overlap these numeric boundaries.

Testosterone concentration (active agent)

• claim 1: ~0.1% to ~2%
• claim 4: ~1% to ~2% (subset)

Oleic acid concentration

• claim 5: ~0.1% to ~10%
• claim 6: ~0.1% to ~5% (subset)

C1–C4 alcohol concentration

• claim 12: ~5% to ~65%
• claim 13: ~10% to ~40%
• claim 14: ~25% to ~35%

Glycol concentration

• claim 21: ~25% to ~55%
• claim 22: ~30% to ~40%

Gelling agent concentration

• claim 25: ~0.1% to ~10%
• claim 26: ~0.1% to ~5%
• claim 27: ~1% to ~3%

Boundary implication:
Even if a competitor uses oleic acid + the same alcohol and glycol classes, the claim may still be avoided by moving concentrations outside these bands (especially the “middle” ranges that match typical solvent systems), but this must be balanced against product performance constraints and pH requirements.

---

What specific alcohols and glycols are explicitly covered?

Alcohols (claims 7–14)

Covered alcohols:

• Ethanol
• Propanol
• Isopropanol
• Mixtures of ethanol and isopropanol (claim 11) All within the C1–C4 alcohol class and within the applicable concentration ranges.

Glycols (claims 15–22)

Covered glycols:

• Ethylene glycol
• Propylene glycol
• Butylene glycol
• Mixtures (ethylene + butylene; propylene + butylene) All within the applicable glycol concentration ranges.

Formulation diligence point:
If a competitor uses a glycol-like penetration enhancer (eg, glycerol) rather than a glycol as defined (ethylene/propylene/butylene glycols), it may avoid the “glycol” literal requirement.

---

How do the dependent claims expand coverage: testosterone propionate, ethanol vs isopropanol, and specific carbomers?

Testosterone propionate (claim 2)

• If the product uses testosterone propionate as the active, it lands squarely in claim 2.

Testosterone as active (claim 3)

• If active is testosterone itself, claim 3 applies.

Gelling agent sub-species (claim 24)

• If gelling agent is Carbopol 1342, claim 24 applies.

Narrower solvent system variants

• Alcohol species selection (claims 8–11)
• Alcohol concentration subset (claims 13–14)
• Glycol species selection (claims 16–20)
• Glycol concentration subset (claims 22)

Overall: the dependent claims do not broaden claim scope beyond claim 1; they increase likelihood of literal match depending on the competitor’s specific formulation.

---

What is the patent’s claim “coverage map” for design-around decisions?

The claim can be decomposed into five gatekeepers. A product avoids literal infringement if it fails at least one required gatekeeper.

Gatekeeper 1: Active

• Testosterone or “derivatives thereof”
• If active is not testosterone nor a derivative, low risk from this patent.

Gatekeeper 2: Membrane fluidizer

• Must include oleic acid
• Replacing oleic acid is the cleanest design-around lever.

Gatekeeper 3: Alcohol class and identity

• Must include C1–C4 alcohol
• If a competitor uses a non-C1–C4 alcohol solvent system or uses no alcohol of that class, risk falls.

Gatekeeper 4: Glycol identity

• Must include ethylene/propylene/butylene glycol or mixtures
• Using glycerol or other humectants outside the glycol set can reduce risk.

Gatekeeper 5: pH band and gelling agent

• Must have pH 5–8
• Must include a gelling agent among: Carbopol 1342, Carbopol 940, Klucel, Klucel HF

If all five gates match: exposure is high, especially if concentrations overlap.

---

What other patents typically surround this chemistry space, and how would they compete with US 6,579,865?

This specific patent claims a particular solvent architecture and pH/gelling agent scaffold. In the broader transdermal testosterone space, competing patent estates commonly fall into one or more clusters:

1. Alternative penetration enhancers (different fatty acids/esters/surfactants or terpene-like systems)
2. Alternative solvent-glycol architectures (different humectants/penetration enhancers)
3. Alternative polymer systems (gelling agents, matrix formers, tackifiers)
4. Different testosterone forms and salt/ester variants tied to penetration performance
5. Manufacturing and process patents (mixing order, pH adjustment steps, gel preparation methods)

However, no patent-number-level landscape can be produced from the information provided here. A credible freedom-to-operate conclusion depends on identifying the full US patent family, continuations/divisionals, and relevant later-filed competitors’ patents, which require external bibliographic and litigation records that are not included in the prompt.

Given the constraint, the landscape below is limited to claim-structure-driven competitive risk logic rather than a numbered set of specific patents.

---

What claim elements drive infringement analysis in a litigation or licensing review?

Literal infringement checklist (practical order)

1. Does the product contain testosterone or a “derivative thereof” at 0.1%–2%?
2. Does it contain oleic acid as a membrane fluidizer?
3. Does it include a C1–C4 alcohol (ethanol/propanol/isopropanol/mixtures) at overlapping concentration?
4. Does it include ethylene/propylene/butylene glycol at overlapping concentration?
5. Is the formulation pH 5–8?
6. Does it use a gelling agent from the enumerated list at overlapping concentration?

“Consisting essentially of” impact

• If the product includes extra excipients, infringement still hinges on whether those additives materially change the claimed penetration-enhancing characteristics.

Equivalents exposure

• If oleic acid is replaced with a substantially similar membrane fluidizer, the risk becomes an equivalents inquiry, but that depends on prosecution history and claim interpretation. Those records are not part of the prompt.

---

How does claim 28 affect the scope: inert carriers and composition structure?

Claim 28 recites a composition with:

• testosterone (0.1%–2%)
• penetration-enhancing system: oleic acid + C1–C4 alcohol + glycol
• gelling agent
• d) inert carriers
• pH 5–8

This is consistent with claim 1’s structure but explicitly addresses inert carriers. For infringement analysis, that can matter if an accused product argues it has an “inert carrier” structure that still fits. Practically, most topicals contain carriers anyway, so claim 28 reinforces that excipient variability is not a clear escape route.

---

Key takeaways

• US 6,579,865 is tightly centered on a topical testosterone formulation using a defined penetration system: oleic acid + C1–C4 alcohol + specified glycols with pH 5–8 and a listed gelling agent set (Carbopol 1342/940, Klucel/Klucel HF).
• The claim’s strongest design-around levers are:
  1. Remove or replace oleic acid (membrane fluidizer requirement)
  2. Use a non-enumerated gelling agent
  3. Move formulation pH outside 5–8
  4. Change glycol identity away from ethylene/propylene/butylene glycols
  5. Move excipient concentrations outside the numeric ranges
• The dependent claims mainly increase literal match probability; they do not broaden beyond the independent claim scaffold.

---

FAQs

1) Does US 6,579,865 cover testosterone propionate specifically?

Yes. Claim 2 narrows claim 1 where the active agent is testosterone propionate.

2) What gelling agents are enumerated in US 6,579,865?

Carbopol 1342, Carbopol 940, Klucel, and Klucel HF (claim 23).

3) Are ethanol and isopropanol both covered alcohol options?

Yes. Ethanol, propanol, isopropanol and mixtures are covered (claims 7–11).

4) Is the pH requirement part of the independent claim limitations?

Yes. Claim 1 requires a pH value between about 5 and about 8.

5) What excipient concentration ranges are most likely to determine infringement risk?

Most numeric limits are concentrated in: testosterone (0.1%–2%), oleic acid (0.1%–10%), alcohol (5%–65%), glycol (25%–55%), gelling agent (0.1%–10%), plus narrower subranges in dependent claims.

---

References (APA)

No citable sources are included in the provided prompt.

Drugs Protected by US Patent 6,579,865

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 6,579,865

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	418988
Australia	1313299
Australia	747041
Brazil	9814014
Canada	2309688
China	1172674