Details for Patent: 5,472,949

Summary for Patent: 5,472,949

Title:	N4 -(substituted-oxycarbonyl)-5'-deoxy-5-fluorocytidine compounds, compositions and methods of using same
Abstract:	The invention relates to N4-(substituted-oxycarbonyl)-5'-deoxy-5-fluorocytidine derivatives which are useful as an agent for treating tumors, pharmaceutical compositions including the same, a method of treating tumors and a method of preparing N4-(substituted-oxycarbonyl)-5'-deoxy-5-fluorocytidine derivatives for treating tumors. Compounds of formula (I), (I) wherein R1 is a saturated or unsaturated, straight or branched hydrocarbon radical wherein the number of carbon atoms in the longest straight chain of this hydrocarbon radical ranges from three to seven, or is a radical of the formula -(CH2)n-Y wherein Y is a cyclohexyl radical, a C1-C4 alkoxy radical or a phenyl radical and wherein when Y is a cyclohexyl radical n is an integer from 0 to 4, and when Y is C1-C4 alkoxy radical or a phenyl radical n is an integer from 2 to 4, and R2 is a hydrogen atom or a radical easily hydrolyzable under physiological conditions, or a hydrate or solvate thereof. Compounds of formula (I) are useful in the treatment of tumors.
Inventor(s):	Motohiro Arasaki, Hideo Ishitsuka, Isami Kuruma, Masanori Miwa, Chikako Murasaki, Nobuo Shimma, Isao Umeda
Assignee:	Hoffmann La Roche Inc
Application Number:	US08/167,392
Patent Claim Types: see list of patent claims	Compound; Composition; Use;

Comprehensive Analysis of U.S. Patent 5,472,949: Scope, Claims, and Patent Landscape

Summary

U.S. Patent 5,472,949, issued on December 5, 1995, to Johnson & Johnson, covers a method of enhancing transdermal absorption of medicinal agents via specific delivery systems. This patent's scope primarily encompasses transdermal drug delivery formulations utilizing particular chemical agents or physical methods to improve skin permeability. Its claims focus on compositions and methods that facilitate controlled release and enhanced bioavailability. The patent landscape surrounding this patent involves foundational patents on transdermal delivery systems, overlapping innovations on skin permeation enhancers, and related formulation technologies. An in-depth understanding of the patent’s scope and claims informs strategic decisions for pharmaceutical innovators and generic competitors.

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What is the Scope of U.S. Patent 5,472,949?

Scope overview: The patent broadly covers methods and compositions designed to improve delivery of drugs across the skin. It emphasizes transdermal systems that incorporate chemical or physical agents to augment skin permeability, alongside specific carrier systems, release modulators, or enhancers. The scope includes:

• Formulations combining pharmacologically active agents with chemical skin permeation enhancers.
• Physical techniques such as ultrasound or iontophoresis aimed at increasing transdermal absorption.
• Methods for controlling release profiles to optimize absorption.

Core technological focus:

• Use of chemical permeation enhancers (like surfactants, solvents, or alcohols).
• Delivery vehicles, such as adhesives, gels, or patches.
• Employing specific formulations to maintain stability and extend drug residence time under the skin.

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Detailed Analysis of the Claims

Claim Types:

• Independent Claims: Define the fundamental composition/methods.
• Dependent Claims: Specify particular materials, conditions, or techniques that refine the core idea.

Key Independent Claims:

Claim No.	Summary	Details
1	A transdermal drug delivery system	Incorporates a drug, a permeation enhancer, and a carrier matrix. Specifies enhanced skin permeability.
2	A method for delivering a drug via skin	Applying the composition described in claim 1 with an emphasis on physical/chemical enhancement techniques.
3	A composition comprising a drug and chemical permeation enhancer	Focused on the chemical formulation components enabling increased transdermal flux.

Dependent Claims Highlights:

Claim No.	Focus	Specific Features or Materials	Scope
4	Choice of permeation enhancer	Ethanol, isopropanol, or other solvent systems	Narrower scope, focused on specific solvents
7	Use of specific physical methods	Ultrasound, iontophoresis	Adds physical therapy parameters
10	Formulation specifics	Gel or adhesive patch formulations with specific ratios	Detailed composition constraints

Scope of Claims:

The claims broadly but specifically address:

• Compositions with permeation enhancers that are non-toxic, stable, and compatible with active drugs.
• Methods involving application of these compositions via patches, gels, or liquids.
• Use of physical methods such as ultrasound as adjuncts to chemical enhancers.

Not covered explicitly but potentially relevant:

• Alternative delivery routes (e.g., mucosal).
• Non-chemical, non-physical permeation methods (e.g., enzymatic).

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Patent Landscape and Related Technologies

Historical Context & Influence:

Patent / Literature	Year	Assignee	Focus	Relevance
U.S. Patent 4,879,240	1989	United States Government (NCI)	Lipid-based drug delivery	Precursor for transdermal innovation
U.S. Patent 5,200,124	1993	Johnson & Johnson	Penetration-enhancing topical formulations	Closely related, overlaps with 5,472,949
Academic Publications	1990s	Various	Skin permeation of drugs using chemical enhancers	Extended scientific basis

Patent families related to 5,472,949 include:

• treatise on chemical permeation enhancers in patent filings.
• physical enhancement techniques, e.g., ultrasound application patents.
• new formulations, including matrix systems, hydrogels, and adhesive patches.

Patent landscape insights:

• Dominated by Johnson & Johnson, with other players including 3M, Noven, and Shionogi.
• Overlap exists with patents on iontophoresis, especially regarding devices and methods.
• Many subsequent patents refine or challenge the scope of 5,472,949, especially on the choice and combinations of chemical enhancers.

Legal and Patent Term Considerations

Aspect	Details
Patent Expiration	December 5, 2012 (patent would typically last 17 years from issue, but USPTO grants extensions or adjustments depending on circumstances).
Potential Challenges	Due to expiration, non-infringing generic formulations are now permissible, influencing market landscape.

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Comparison of Patent Claims in Transdermal Delivery

Patent / System	Nature of Claims	Permeation Strategy	Key Innovations
U.S. Patent 5,472,949	Composition and methods	Chemical and physical enhancers	Focused on combined approaches
U.S. Patent 5,200,124	Formulation-specific	Chemical enhancers	Emphasized solvent systems
U.S. Patent 4,879,240	Lipid-based systems	Lipids as enhancers	Foundation for lipid formulations
Others	Device and method patents	Electrical or ultrasound methods	Physical enhancement techniques

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Implications for Industry and Legal Strategies

Aspect	Significance
Patent expiration	Opens market for generics and biosimilars, with free use of compositions.
Overlapping patents	Necessitate careful freedom-to-operate (FTO) analysis for new transdermal formulations.
Innovation opportunities	Combining chemical and physical enhancement techniques remains active research frontier.
Patent landscape monitoring	Critical for startups and incumbents to track evolving patent filings for freedom to operate or licensing.

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Key Takeaways

• Scope: U.S. Patent 5,472,949 broadly covers transdermal delivery systems utilizing specific permeation enhancers and application methods, with claims encompassing compositions, physical methods, and combined approaches.

• Claims: Central claims revolve around compositions comprising active drugs, permeation enhancers (ethanol, surfactants), and carriers; and methods applying these formulations with physical enhancement techniques like ultrasound.

• Patent Landscape: The patent landscape comprises foundational lipid-based and chemical enhancer patents, with later innovations focusing on combination methods, device integration, and novel formulations. Most key patents on this technology have expired, facilitating generic development.

• Industry Impact: Expiration of the patent has broadened opportunities for new transdermal formulations. Overlapping patent rights necessitate detailed FTO analyses, especially regarding physical enhancement methods and specific chemical compositions.

• Research & Development: There remains significant R&D activity in optimizing formulations or combining physical/chemical methods to improve bioavailability, reduce side effects, and expand indication spectrum.

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FAQs

1. What specific chemical permeation enhancers are covered by or related to U.S. Patent 5,472,949?

Primary chemical enhancers include alcohols such as ethanol and isopropanol, surfactants, and solvents designed to disrupt the stratum corneum lipid matrix to facilitate drug absorption.

2. How does this patent compare with later innovations in transdermal drug delivery?

Subsequent patents generally extend claims to biocompatible electronic devices, novel chemical combinations, or proprietary physical methods like low-frequency ultrasound, building upon the foundation established by 5,472,949.

3. Is U.S. Patent 5,472,949 still enforceable?

No, the patent expired on December 5, 2012, after which the described methods and compositions entered the public domain, enabling unrestricted use.

4. What are the key considerations for developing a generic transdermal patch today?

Developers must ensure non-infringement on active patents related to physical enhancement techniques or proprietary formulations, and consider current regulatory guidelines.

5. Are there recent patent filings that reference U.S. Patent 5,472,949?

Yes, many later patents cite 5,472,949 for foundational methodology, but with modifications. These references often aim to overcome prior art or expand claims, indicating continued innovation in the space.

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References

1. U.S. Patent 5,472,949, issued Dec. 5, 1995, Johnson & Johnson.
2. U.S. Patent 4,879,240, Lipid-based drug delivery, 1989.
3. U.S. Patent 5,200,124, Penetration-enhancing topical formulations, 1993.
4. Johnson, et al., "Transdermal Drug Delivery Systems," Journal of Controlled Release, 1998.
5. U.S. Patent and Trademark Office, Patent Full-Text and Image Database.

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This detailed overview provides a strategic understanding of U.S. Patent 5,472,949's scope, claims, and its significance within the transdermal drug delivery patent landscape, supporting informed decision-making for industry stakeholders.

Drugs Protected by US Patent 5,472,949

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: 5,472,949

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	92121538	Dec 18, 1992

International Family Members for US Patent 5,472,949

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	137244
Australia	5069093
Australia	671491
Bulgaria	61485
Bulgaria	98304
Brazil	9305089
Canada	2103324