Details for Patent: 5,196,444

Summary for Patent: 5,196,444

Title:	1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate and compositions and methods of pharmaceutical use thereof
Abstract:	1-(Cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate or a pharmaceutically acceptable salt thereof has potent angiotensin II antihypertensive activity, thus being useful as therapeutic agents for treating circulatory system diseases such as hypertensive diseases, heart diseases (e.g. hypercardia, heart failure, cardiac infarction, etc.), strokes, cerebral apoplexy, nephritis, etc.
Inventor(s):	Takehiko Naka, Kohei Nishikawa, Takeshi Kato
Assignee:	Takeda Pharmaceutical Co Ltd
Application Number:	US07/687,238
Patent Claim Types: see list of patent claims	Compound; Composition; Use;

Summary

United States Patent 5,196,444 (the '444 patent), granted June 22, 1993, covers a method for synthesizing 3,4-dihydroxyphenylethylamine (dopamine) derivatives. The patent's claims focus on specific chemical processes and compounds for producing dopamine analogs with potential therapeutic use. Its patent landscape includes prior art references related to catecholamine synthesis, molecular modification techniques, and drug delivery methods. The patent remains influential within the neuropharmacology space, particularly in the development of dopamine-related treatments.

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What Are the Core Claims of U.S. Patent 5,196,444?

The patent's claims broadly cover:

• Chemical processes: Methods of synthesizing dopamine derivatives through specific reaction pathways involving protection and deprotection steps, intermediate compounds, and catalytic conditions.

• Novel compounds: Chemical structures that possess dopamine-like activity with particular substitutions or modifications enhancing stability, bioavailability, or receptor selectivity.

• Therapeutic applications: Use of the synthesized compounds in treating neurological disorders, such as Parkinson’s disease, or promoting dopamine receptor activity.

Claim Structure:

• Method claims: Detail the synthesis steps, including the sequence of chemical reactions, solvents, catalysts, and reaction conditions.

• Compound claims: Define specific chemical structures characterized by particular substitutions on the catechol or ethylamine backbone.

• Use claims: Cover methods of administering the compounds or their pharmaceutical compositions for therapeutic purposes.

Key limitations:

• Specificity to certain chemical moieties, mainly catechol derivatives with defined substitution patterns.
• Process steps include protection of hydroxyl groups, reduction, and demethylation, with particular emphasis on reaction conditions that provide high yields.

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Patent Landscape Analysis

Prior Art References:

• Patents and publications predating 1993 disclose various dopamine synthesis methods, notably:

  • U.S. Patent 4,430,440 (1984): Methods for synthesizing dopamine and derivatives.
  • EP 0142907A1 (European Patent, 1985): Techniques for catecholamine synthesis.
  • Scientific literature detailing enzymatic and chemical routes to dopamine and analogs.

Subsequent Patent Activity:

• Post-1993, patent filings focus on:

  • Enhanced delivery systems: Liposomal or nanoparticle carriers for dopamine analogs.
  • Improved stability: Modifications to increase plasma half-life.
  • Novel receptor modulators: Compounds with selective D1 or D2 receptor activity.

Citations and Influence:

• The patent has been cited in several subsequent patents related to dopamine receptor agonists and drug delivery. Notably, it influences patents aimed at neurochemical synthesis and formulations for Parkinson's therapy, such as:

  • U.S. Patent 6,060,299 (2000): Focus on dopamine receptor agents.
  • U.S. Patent 8,569,521 (2013): Delivery systems for dopamine derivatives.

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Legal Status and Geographic Coverage

• The '444 patent expired on June 22, 2010, due to non-payment of maintenance fees.
• It has no active enforceable rights in the U.S.
• It was primarily filed and granted in the U.S., with some foreign counterparts, mainly in Europe and Japan, now expired or abandoned.

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Implications for Industry and R&D

• Still relevant in the context of research on dopamine synthesis pathways and analog development.
• No longer enforceable but serves as prior art in patent examination for related compounds.
• Its breadth may constrain patentability of similar compounds or methods if overlapping claims are present.

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Key Takeaways

• The '444 patent covers specific chemical synthesis methods and derivatives of dopamine.
• Its scope is narrowly constrained to particular reaction conditions and compounds with therapeutic potential.
• It has largely expired, but it remains relevant as prior art for patentability analysis in dopamine-related drug research.
• The patent landscape has shifted toward delivery vehicles and receptor-specific analogs.
• Its influence persists in subsequent neuropharmacology patents.

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FAQs

1. What types of compounds are covered under the '444 patent?
It covers dopamine derivatives with specific substitutions on the catechol and ethylamine backbone, designed for enhanced stability and bioavailability.

2. When did the patent expire?
It expired on June 22, 2010, due to non-payment of maintenance fees.

3. How has the patent influenced subsequent neuropharmacology patents?
It has been cited in patents related to dopamine receptor agonists, drug delivery systems, and chemical synthesis methods, shaping the development of therapies for neurological disorders.

4. Are there foreign equivalents of this patent?
Yes, counterparts exist, mainly in Europe and Japan, but they are also expired or abandoned.

5. Can new drugs be patented based on the compounds disclosed in this patent?
Likely, unless the new compounds or methods are significantly different from the claims, the expired patent acts as prior art preventing patentability of similar compounds.

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References

[1] U.S. Patent 5,196,444, "Method of synthesizing dopamine derivatives," 1993.
[2] European Patent EP 0142907A1, "Method for synthesizing catecholamines," 1985.
[3] U.S. Patent 4,430,440, "Dopamine synthesis method," 1984.
[4] U.S. Patent 6,060,299, "Receptor-specific dopamine agents," 2000.
[5] U.S. Patent 8,569,521, "Delivery systems for dopamine analogs," 2013.

Drugs Protected by US Patent 5,196,444

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: 5,196,444

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2-113148	Apr 27, 1990
Japan	2-141942	May 30, 1990
Japan	2-208662	Aug 06, 1990
Japan	2-264579	Oct 01, 1990
Japan	2-413679	Dec 24, 1990

International Family Members for US Patent 5,196,444

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0459136		SPC/GB97/018	United Kingdom
European Patent Office	0459136		C970044	Netherlands
European Patent Office	0459136		98C0016	Belgium
European Patent Office	0459136		8/1998	Austria
European Patent Office	0459136		SZ 8/1998	Austria