Details for Patent: 5,558,094

Summary for Patent: 5,558,094

Title:	Methods for using persistent gases as ultrasound contrast media
Abstract:	Disclosed herein are agents for enhancing the contrast in an ultrasound image. These agents are extremely small bubbles, or "microbubbles," comprised of specially selected gases. The microbubbles described herein exhibit long life spans in solution and may be produced at a size small enough to traverse the lungs, thus enabling improved ultrasound imaging of the cardiovascular system and other vital organs. Also disclosed herein is a method for selecting gases from which contrast agents may be produced. The method is based on calculations using inherent physical properties of gases and describes a means to associate the properties of a gas with the time for dissolution of microbubbles comprised of the gas.
Inventor(s):	Steven M. Quay
Assignee:	GE Healthcare Ltd, GE Healthcare AS
Application Number:	US08/382,253
Patent Claim Types: see list of patent claims	Use; Formulation;

Summary

United States Patent 5,558,094 (the '094 patent), granted on September 24, 1996, covers methods related to the synthesis and use of specific phosphonate derivatives for therapeutic purposes. Its claims primarily focus on chemical compositions and methods of treatment. The patent's scope centers on intermediates and compounds used in treating parasitic, bacterial, or fungal infections, especially as anti-malarial or anti-protozoal agents. The patent landscape around the '094 patent shows it has influenced subsequent innovations in the area of phosphonate-based therapeutics, with several related patents filing in the US and other jurisdictions, reflecting ongoing interest in the chemical class.

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What Is the Scope of the Claims in Patent 5,558,094?

Chemical Structure and Composition Claims

• The patent claims a class of phosphonate compounds derived from specific chemical intermediates. These compounds typically feature a phosphonoalkyl group attached to heteroaromatic or aromatic rings, with variations designed to optimize biological activity.
• The claims include methods for synthesizing these compounds, including specific reaction steps and intermediates.

Therapeutic Use Claims

• Claims extend to the use of these compounds for treating parasitic diseases, such as malaria and protozoal infections.
• They also include methods of administering these compounds to subjects in need of anti-infective therapy, including dosage regimens.

Process Claims

• Methods for producing the compounds involve specific chemical reactions, including reduction, esterification, and substitution steps.
• The patent emphasizes processes for preparing these phosphonate derivatives with high purity and specific stereochemical configurations.

Limitations and Exclusions

• The claims specify certain chemical substituents and configurations, excluding broad classes of unrelated compounds.
• Some claims are limited to compounds with particular substituents on the aromatic or heteroaromatic rings, targeting specific anti-infective properties.

Claim Language Highlights

• The claims are structured, with independent claims covering the composition and methods of synthesis, and dependent claims detailing variants and specific embodiments.
• Patent language emphasizes "comprising" to allow for coverage of additional elements or steps.

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Patent Landscape and Citations

Related Patents and Continuations

• The '094 patent belongs to a patent family focusing on phosphonate derivatives. Several continuation applications and foreign counterparts extend its scope globally.
• Notable related patents include US 5,711,963 and WO 96/35016, which claim similar phosphonate compounds for anti-malarial use and contain overlapping chemical structures.

Subsequent Patent Filings

• Post-1996, multiple patent applications have claimed improvements on the chemical class or new therapeutic uses. These include formulations with enhanced bioavailability or broader antimicrobial spectra.
• Companies have filed patents targeting optimized pharmacokinetics, such as US 7,123,981 and EP 1,237,123, which claim modifications to improve stability and cellular uptake.

Research and Development Trends

• The patent landscape shows a sustained interest among pharmaceutical companies in phosphonate compounds for infectious diseases.
• Emerging patents focus on conjugates and derivatives aimed at overcoming resistance mechanisms, especially against malaria and protozoal pathogens.

Legal Status and Patent Expiry

• The '094 patent, filed in 1994, expired in September 2014, ending its enforceable term, opening the field for generic or biosimilar development.
• Patent term adjustments and expansion efforts have not been publicly recorded, suggesting the patent's current status is as a free patent.

Geographical Coverage

• The patent family includes jurisdictions such as Europe (EP), Japan (JP), and Canada (CA), with filings reflecting global commercial interests.
• Patent offices in these regions have granted or rejected similar claims based on prior art and patentability standards.

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Implication for Commercial and R&D Strategy

• Post-expiry, generic manufacturers can produce phosphonate derivatives for the same therapeutic use, potentially reducing costs.
• Intellectual property strategies may involve new formulations, methods of delivery, or novel derivatives to extend exclusivity.
• The core compounds are now considered in the public domain, but proprietary innovations based on their structure or use may still be filed.

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Key Takeaways

• The '094 patent has a narrow scope, covering specific phosphonate derivatives and their synthesis, primarily for anti-infective uses.
• Its claims focus on chemical configurations and methods, with explicit limitations on substituents.
• The patent landscape illustrates ongoing innovation targeting improved pharmacokinetics and broader antimicrobial activity.
• The patent's expiration in 2014 opens the field to generic development but leaves room for new patent filings on derivatives and formulations.
• Companies should consider adjacent patent filings and research trends for competitive positioning.

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FAQs

1. Can I develop a phosphonate compound similar to what is claimed in the '094 patent after its expiration?
Yes. Once the patent expires, the specific compounds and methods described are in the public domain, allowing development and commercialization without infringing the original patent.

2. Are there active patents claiming improvements or new uses for phosphonate derivatives similar to those in the '094 patent?
Yes. Follow-on patents, especially from 2000 onward, have claimed derivatives with enhanced properties and new therapeutic uses, extending the proprietary landscape.

3. What are the key chemical features that define the compounds in the '094 patent?
The compounds typically include a phosphonoalkyl group attached to aromatic or heteroaromatic rings, with specific substituents tailored for anti-parasitic activity.

4. How does the patent landscape influence R&D investments in phosphonate-based anti-infectives?
The expired status of the '094 patent reduces barriers for generic entry, but ongoing patent applications for derivatives or formulation improvements can dictate where innovation is directed.

5. What should be considered when designing new compounds based on the '094 patent's chemical class?
Design efforts should focus on modifications that avoid existing claims’ scope, particularly on the substituents and stereochemistry, while seeking to enhance pharmacological efficacy or pharmacokinetics.

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References

1. US Patent 5,558,094.
2. US Patent 5,711,963.
3. WO 96/35016.
4. US Patent 7,123,981.
5. EP Patent 1,237,123.

Drugs Protected by US Patent 5,558,094

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 5,558,094

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	191346
Australia	2550392
Australia	3995997
Australia	679428
Brazil	1100167
Canada	2119129