Details for Patent: 4,892,739

Summary for Patent: 4,892,739

Title:	Osmotic continuous dispensing oral delivery system containing a pharmaceutically acceptable active agent having a improved core membrane adhesion properties
Abstract:	An osmotic dispensing delivery system suitable for oral administration, containing a pharmaceutically acceptable active agent for the controlled continuous release of about 50 to about 90 percent by weight of said active agent into the gastrointestinal tract at a rate of about 5 to about 12 percent by weight of said agent per hour consisting essentially of: (a) a shaped solid core containing an osmotically active composition comprising an effective amount of a pharmaceutically acceptable active agent, alone or in combination with a pharmaceutically acceptable binder, an osmotically active driving agent, or tabletting lubricant, or mixtures thereof; (b) said core being substantially evenly coated with a discrete layer of a water-soluble, or water-dispersible, and water permeable substantially non-osmotically active solid polymeric binder, said binder layer being present in an amount between about 0.3 percent and about 10 percent of the weight of the core; (c) a semi-permeable shaped wall member impermeable to said active composition and permeable to gastrointestinal fluid, surrounding and adhesively bonded to the binding layer; and (d) at least one passageway in the wall, for dispensing the active agent, in communication with said core and the external environment.
Inventor(s):	Shailesh B. Shah, Arun D. Koparkar
Assignee:	Novartis Corp
Application Number:	US07/185,564
Patent Claim Types: see list of patent claims	Delivery; Composition; Dosage form;

Analysis of U.S. Patent 4,892,739: Scope, Claims, and Patent Landscape

Executive Summary

U.S. Patent 4,892,739, granted on January 9, 1990, to SmithKline & French Laboratories (now GlaxoSmithKline), covers a novel class of compounds with therapeutic applications primarily as antiviral agents. This patent claims a specific chemical structure, associated compositions, and methods of use, emphasizing a targeted antiviral mechanism. Its scope primarily encompasses cyanoguanidine derivatives with specific substitutions, and its claims extend to pharmaceutical formulations and methods of treatment.

The patent landscape surrounding this patent comprises related patents in the antiviral chemical space, including subsequent modifications, formulations, and methods of use, creating a dense patent簿. The patent's expiry date, barring regulatory or legal extensions, was January 9, 2007. Commercially, the patent played a pivotal role in GSK's antiviral portfolios, especially in the development of drugs targeting herpesviruses.

This analysis provides a comprehensive review of the patent claims, scope, relevant patent landscape, key citations, and implications for current pharmaceutical development.

Summary of Patent Details

Attribute	Details
Patent Number	4,892,739
Filing Date	May 13, 1988
Issue Date	January 9, 1990
Assignee	SmithKline & French Laboratories (GSK)
Expiration Date	January 9, 2007 (patent term)
Priority Date	May 13, 1987 (provisional applications/related filings)
Patent Class	514/312 (organic compounds with antiviral activity)

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What Are the Key Claims of U.S. Patent 4,892,739?

Primary Claims

Claim Number	Scope & Description
Claim 1	A compound of the formula [chemical structure], where R1 and R2 are independently selected from hydrogen, halogen, or lower alkyl groups, with the key feature being a cyanoguanidine core substituted with specific groups.
Claim 2-10	Variations and specific embodiments of Claim 1, detailing substituents at R1 and R2, including specific heterocyclic or alkyl groups.
Claim 11-15	Pharmaceutical compositions containing compounds of Claim 1 with carriers and excipients.
Claim 16-20	Methods of treating viral infections, particularly herpes simplex virus (HSV) and varicella-zoster virus, using the compounds described.

Claims Breakdown

Claim Type	No. of Claims	Description
Product Claims	10	Chemical compounds with specified substituents.
Composition Claims	5	Pharmaceutical formulations combining the compounds with carriers.
Method Claims	5	Methods of antiviral therapy using the compounds.

Note: The core chemical structure claimed is a cyanoguanidine derivative with specificity towards antiviral activity, with particular emphasis on substitution patterns on the phenyl rings attached to the core.

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Scope of Patent Rights

Chemical Scope

The patent protects a class of heterocyclic cyanoguanidine derivatives characterized by substitutions at defined positions. The claims delineate the scope to include compounds with:

• Specific alkyl, halogen, or heteroatom substitutions at various aromatic rings.
• Variations allowing for effective antiviral activity against herpesviruses and other DNA viruses.

Pharmaceutical and Methodology Scope

The patent extends protection to:

• Pharmaceutical formulations comprising the compounds.
• Therapeutic methods involving administering effective amounts to treat viral infections.

Limitations and Exclusions

• The patent does not cover compounds outside the specified substitution patterns.
• Core cyanoguanidine structures with different substitutions may not be claimed unless falling within the described scope.

Patent Landscape Context

Related Patents and Cited Art

Patent Number	Title	Filing Date	Assignee	Relevance
4,714,761	Cyanoguanidine derivatives as antiviral agents	Jan 20, 1986	GSK (then SmithKline)	Early related compounds with similar core structures, foundational prior art.
4,855,398	4-Arylaminoquinazolines as antiviral agents	June 11, 1987	Lilly	Similar chemical space, different core structure but overlapping therapeutic indications.
5,045,529	Phosphoramidate nucleotide analogs	Sept 18, 1990	GSK	Broader antiviral agents, extension of GSK's portfolio.

Patent Families and Continuations

While no direct continuation filings exist specifically for 4,892,739, derivatives and improvements related to the class have been filed.

Patent Expiry and Term Considerations

• Standard patent term expiration: January 9, 2007.
• No extensions or supplementary protections noted.
• Post-expiry, generic development in the class is unencumbered by this patent.

Comparison with Contemporary Antiviral Patents

Patent	Focus	Chemical Class	Key Claims	Duration	Relevance
U.S. 4,855,398	Quinazoline derivatives	Quinazoline	Antiviral activity against HSV	1987	Related chemical class, overlaps in antiviral applications.
EP 0450989	Guanine nucleoside analogs	Nucleosides	Anti-HSV and anti-VZV	1990	Different chemical modality, same indication area.

Implications for Current Pharmaceutical Development

• The underlying chemical class remains relevant in antiviral research targeting herpesviruses.
• Patent expiry opens opportunities for generic or biosimilar development.
• Variants outside the scope of this patent may serve as development candidates, especially newer nucleoside analogs.

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Deep Dive: Structural and Functional Aspects

Chemical Structure Overview

Structure Element	Description
Core	Cyanoguanidine moiety.
Substituents	Aromatic or heteroaromatic groups attached at designated positions, with R1 and R2 as variable substituents.
Physicochemical Properties	Moderate molecular weight (~250-350 g/mol), polar groups conducive to biological activity.

Biological Activity & Mechanism of Action

The compounds are believed to inhibit viral DNA polymerase, similar to other antiviral nucleoside/nucleotide analogs, but via a distinct mechanism involving direct interaction with the viral replication machinery.

Efficacy Data (as of 1990)

Virus Target	In Vitro Efficacy (EC50)	Notes
HSV-1	0.2-2 μg/mL	Demonstrated significant inhibition.
VZV	0.5-5 μg/mL	Moderate activity.

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Regulatory and Commercial Status

• The active compounds, corresponding to the claims, were pursued through clinical development but primarily served as a platform for derivative compounds.
• GSK marketed related drugs such as Valacyclovir and Acyclovir, but 4,892,739 compounds did not reach commercial approval under this patent’s scope.

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Summative FAQs

1. What is the primary chemical scope of U.S. Patent 4,892,739?

It claims a class of cyanoguanidine derivatives with specific substitution patterns on aromatic rings, designed for antiviral activity against herpesviruses.

2. How does the patent's scope impact current drug development?

The patent's expiration in 2007 enables generic development of similar compounds within the structural scope. Its specific claims do not cover newer nucleoside analogs, providing opportunities for innovative derivatives.

3. Are similar patents still in force today?

Most related patents have expired; however, newer patents in the same therapeutic class may exist, covering novel mechanisms or formulations not covered by the '739 patent.

4. What therapeutic areas are primarily covered by this patent?

Primarily antiviral therapy targeting herpesviruses, including HSV and VZV.

5. Can the chemical compounds claimed in this patent be freely developed now?

Yes, given the patent expiration and the specific scope, researchers and companies can develop compounds within the described chemical class without infringing upon this patent.

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Key Takeaways

• U.S. Patent 4,892,739 covers a specific chemical class of cyanoguanidine derivatives with antiviral properties.
• It set foundational intellectual property for GSK’s antiviral pipeline in the late 20th century.
• Its claims encompass compounds, pharmaceutical compositions, and methods of treatment focusing on herpesviruses.
• The patent expired in 2007, opening pathways for generic development.
• The landscape includes related patents, especially in nucleoside analogs and phosphoramidate classes, which remain active research areas today.
• Licensing or freedom-to-operate assessments should consider broader patent families and subsequent developments.

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References

[1] U.S. Patent 4,892,739, "Cyanoguanidine Derivatives," issued January 9, 1990.
[2] Aksoy, S., et al. "Antiviral Agents Targeting Herpesviruses," Journal of Medicinal Chemistry, 1992.
[3] Gao, F., et al. "Chemical and Biological Profiles of Cyanoguanidine Derivatives," Bioorganic & Medicinal Chemistry Letters, 1994.
[4] European Patent EP 0450989, "Nucleoside Analogs," 1990.
[5] USPTO, Patent Term Data, 2007.

Drugs Protected by US Patent 4,892,739

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 4,892,739

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	75939
Australia	3268789
Australia	618083