Detailed Analysis of the Scope and Claims of United States Patent 4,957,924
Introduction
United States Patent 4,957,924, titled "Therapeutic valine esters of acyclovir and pharmaceutically acceptable salts thereof," is a significant patent in the field of antiviral medications. This patent, filed in 1988 and granted in 1990, addresses the limitations of the antiviral drug acyclovir by introducing valine esters that enhance its bioavailability and solubility.
Background of Acyclovir
Acyclovir, known chemically as 9-(2-hydroxyethoxymethyl)guanine, is a potent antiviral agent particularly effective against herpes viruses, including HSV-1 and HSV-2[1].
However, acyclovir has two major drawbacks: it is poorly soluble in water and has low bioavailability when administered orally, requiring large doses to achieve therapeutic levels.
Invention Overview
The patent introduces a new ester of acyclovir, specifically the valine ester, which is characterized by a side-chain branching adjacent to the α-carbon atom. This ester, named 2-(2-amino-1,6-dihydro-6-oxo-9H(purin-9-yl)methoxy)ethyl L-valinate, shows improved water solubility and enhanced bioavailability compared to the parent compound acyclovir and other amino acid esters like glycine and alanine esters[1].
Claims of the Patent
The patent claims include:
- Compound Claims: The patent claims the valine ester of acyclovir and its pharmaceutically acceptable salts. The compound is defined by the formula where R1 represents a group of formula --CH[CH₃]₂[1].
- Method of Preparation: The patent describes methods for preparing the valine ester of acyclovir, including esterification processes.
- Pharmaceutical Formulations: The patent covers pharmaceutical formulations that include the valine ester of acyclovir, either alone or in combination with other therapeutic agents, such as zidovudine for treating HIV infections[1].
- Therapeutic Uses: The claims extend to the use of these compounds for treating viral infections, particularly herpes virus infections.
Scope of the Patent
The scope of the patent is broad and includes:
- Chemical Entities: The valine ester of acyclovir and its pharmaceutically acceptable salts.
- Pharmaceutical Preparations: Various formulations suitable for human and veterinary use, including oral, parenteral, and topical preparations.
- Therapeutic Applications: Treatment of herpes virus infections and potentially other viral infections when used in combination with other antiviral agents[1].
Patent Landscape
Related Patents
- European Patent Specification No. 99493: This patent describes glycine and alanine esters of acyclovir but does not include the valine ester, which is a unique aspect of the U.S. Patent 4,957,924[1].
- Other Antiviral Patents: Patents related to zidovudine and other antiviral agents that can be used in combination with the valine ester of acyclovir.
Patent Term and Extensions
The original patent term would have expired based on the standard 17-year term from the grant date. However, patents can be extended under certain conditions, such as regulatory reviews by the FDA, as outlined in 35 U.S.C. 156(e)(1)[2].
Competitive Landscape
The introduction of valacyclovir, a prodrug of acyclovir, which is also an ester but with a different amino acid (L-valine), has been a significant development in the antiviral field. Valacyclovir has improved bioavailability compared to acyclovir, similar to the valine ester described in this patent[5].
Impact and Significance
The patent has had a significant impact on the development of antiviral therapies:
- Improved Bioavailability: The valine ester of acyclovir addresses the poor bioavailability of the parent compound, making it more effective in treating viral infections.
- Enhanced Solubility: The improved water solubility of the valine ester facilitates the formulation of aqueous pharmaceutical preparations.
- Combination Therapies: The patent's inclusion of combination therapies with other antiviral agents like zidovudine has expanded treatment options for complex viral infections.
Current Status and Future Directions
Expiration and Extensions
The patent has expired, given its grant date and the standard patent term. Any extensions would have been based on regulatory reviews and approvals[2].
Continued Relevance
Despite the expiration, the concepts and compounds described in this patent remain relevant in antiviral research and development. The use of esterification to improve drug properties is a common strategy in pharmaceutical development.
Key Takeaways
- The U.S. Patent 4,957,924 introduces the valine ester of acyclovir, improving its bioavailability and solubility.
- The patent covers the compound, its preparation, pharmaceutical formulations, and therapeutic uses.
- The scope includes chemical entities, pharmaceutical preparations, and therapeutic applications.
- The patent landscape involves related patents on other amino acid esters and antiviral agents.
- The impact includes improved bioavailability, enhanced solubility, and expanded treatment options.
FAQs
What is the main innovation of U.S. Patent 4,957,924?
The main innovation is the introduction of the valine ester of acyclovir, which improves the bioavailability and water solubility of acyclovir.
How does the valine ester of acyclovir differ from other amino acid esters?
The valine ester has a side-chain branching adjacent to the α-carbon atom, which is not present in glycine and alanine esters, and it shows improved bioavailability compared to these esters[1].
What are the therapeutic applications of the valine ester of acyclovir?
The valine ester is used to treat herpes virus infections and can be used in combination with other antiviral agents like zidovudine for treating HIV infections[1].
Has the patent been extended under any regulatory provisions?
Patents can be extended under 35 U.S.C. 156(e)(1) if they undergo certain regulatory reviews, but specific details for this patent are not provided[2].
What is the current status of the patent?
The patent has expired given its grant date and the standard patent term.
Cited Sources
- US4957924A - Therapeutic valine esters of acyclovir and pharmaceutically acceptable salts thereof.
- Extension Under 35 U.S.C. 156(e)(1) - OG Date: 29 July 2003.
- Patent Analytics | Intellectual Property Law.
- U.S. Patent Number 4,957,924 : Articles :: Law360.
- US20190023706A1 - Process for the preparation of Valacyclovir.
