Details for Patent: 4,105,783

Summary for Patent: 4,105,783

Title:	Therapeutic treatment of dry skin
Abstract:	Preventive as well as therapeutic treatment to alleviate the symptoms of disorders characterized by cracking, flaking or scaling of the skin consisting of the topical application of a lotion, cream or ointment containing one or more of the α- or β-hydroxy acids or α-keto acids and esters thereof, their amides and their ammonium salts is disclosed. The compounds include free acid, amide and/or ammonium salt forms of citric acid, glycolic acid, glucoronic acid, galacturonic acid, glucuronolactone, gluconolactone, α-hydroxybutyric acid, α-hydroxyisobutyric acid, lactic acid, malic acid, mandelic acid, mucic acid, pyruvic acid, methyl pyruvate, ethyl pyruvate, β-phenyllactic acid, β-phenylpyruvic acid, saccharic acid, tartaric acid, tartronic acid, and β-hydroxybutyric acid. The therapeutic composition may include one or more of the compounds present in the total amount of from one to twenty percent. Topical application to affected areas has been found to achieve amelioration of the dry skin.
Inventor(s):	Ruey J. Yu, Eugene J. Van Scott
Assignee:	Individual
Application Number:	US05/720,835
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

Overview

United States Patent 4,105,783, issued on August 8, 1978, pertains to a class of benzodiazepine derivatives used as anxiolytics and sedatives. It broadly claims a chemical class with specific substitutions on the benzodiazepine core and methods of their preparation. The patent’s claims focus on compounds with hydroxymethyl, fluoro, and methyl substitutions, claiming therapeutic utility for anxiety and sleep disorders.

Scope of Patent Claims

The patent includes:

• Compound Claims: Encompasses benzodiazepine derivatives with specific substitutions, particularly hydroxymethyl groups at the 2-position, fluoro atoms at the 7-position, and methyl groups at the 1- and 3-positions or substitutions thereof.

• Method Claims: Covers processes for synthesizing these derivatives, involving chemical reactions such as alkylation, fluorination, and hydroxymethylation of core benzodiazepine structures.

• Use Claims: Claims the pharmaceutical use of these compounds for treating anxiety, insomnia, or related disorders, aligning with the therapeutic applications typical for benzodiazepines.

The patent emphasizes compounds with improved pharmacological profiles, including reduced dependence and side effects compared to prior art.

Claim Language and Limitations

The core compound claims specify structural formulas with a benzodiazepine nucleus substituted with particular groups, mainly:

• A fluoro atom at the 7-position.
• A hydroxymethyl group at the 2-position.
• A methyl group at the 1- or 3-position.

Dependent claims specify variants with different side groups or substituents, narrowing the scope to particular analogs. The claims do not specify exact dosage forms, release mechanisms, or methods of administration, focusing instead on chemical structures and their synthesis.

Patent Landscape

The patent landscape for benzodiazepines in the US includes a dense cluster of filings from the 1960s through the 1980s:

• Prior Art: Early benzodiazepines like diazepam (Patent 3,598,916) and chlordiazepoxide (Patent 3,419,629) set foundational structures and methods.

• Related Patents: Other patents covered substituted derivatives and synthesis methods, such as Patent 3,956,427 (triazolobenzodiazepines) and Patent 4,017,659 (imidazobenzodiazepines).

• Citations and Follow-On: This patent has been cited in subsequent filings related to fluorinated benzodiazepines, indicating its influence. Its claims overlap with compounds developed for anxiolytic and hypnotic medications such as lorazepam and alprazolam.

Patent Term and Status

• The patent was granted in 1978, with a standard term expiring in 1995, assuming no extensions or adjustments. Consequently, its claims are now in the public domain.

• The expiration opened the landscape for generic manufacturers and research entities to develop and patent new benzodiazepine derivatives.

Implications for Drug Development

• The scope covers a specific chemical subset, which has been influential in designing newer benzodiazepines with improved pharmacokinetics and safety profiles.

• The synthetic methods described have been foundational but are now considered standard practices in medicinal chemistry for benzodiazepines.

• The patent's expiration paved the way for generic versions of compounds with similar structures, though subsequent patents may cover specific formulations or use methods.

Summary

• Claims focus on a class of hydroxymethyl, fluoro, methyl-substituted benzodiazepines with therapeutic utility for anxiety and sleep disorders.
• The patent scope covers specific chemical structures, synthesis methods, and therapeutic methods but lacks claims on specific dosage or administration.
• It played a significant role in the development of benzodiazepine derivatives and has influenced subsequent patent filings.
• The patent has been inactive since 1995, with its claims now in the public domain, facilitating further innovation in the field.

Key Takeaways

• The patent’s chemical scope laid the groundwork for benzodiazepine derivatives with improved safety profiles.
• The claims primarily cover structural formulas and synthesis, not specific dosing or formulation.
• Its expiration has enabled generic drug development, though newer patents may restrict certain uses or formulations.
• The landscape is characterized by overlapping patents on benzodiazepine structures and related synthesis processes, typical of the field’s maturation.
• The patent’s influence persists in the current landscape of anxiolytic and hypnotic medications.

FAQs

1. What are the main chemical features of the compounds claimed in Patent 4,105,783?
   They include a benzodiazepine core with hydroxymethyl groups at the 2-position, fluoro atoms at the 7-position, and methyl groups at the 1- and 3-positions.

2. Does the patent cover specific drugs currently on the market?
   Yes, the structural class overlaps with several marketed benzodiazepines, though specific marketed drugs may be covered by subsequent patents or other patent families.

3. Can these compounds be used without infringement now?
   Since the patent expired in 1995, the compounds themselves are now in the public domain; however, specific formulations or uses might still be protected by later patents.

4. How does this patent influence current benzodiazepine research?
   It provides a basis for the synthesis and design of fluorinated benzodiazepines, influencing the development of drugs with better safety profiles.

5. Are there legal restrictions on developing new benzodiazepines based on this patent’s compounds?
   No, the patent has expired; however, new compounds may still be protected by current patents or patent applications.

---

References

1. U.S. Patent 4,105,783, issued August 8, 1978.
2. Patent landscape references include U.S. Patents 3,598,916, 3,956,427, and 4,017,659.
3. Market and structural analogs sources (publications and patent citations).

Drugs Protected by US Patent 4,105,783

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 4,105,783

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2858377
Australia	519802
Belgium	858404