Details for Patent: 3,641,152

Summary for Patent: 3,641,152

Title:	3 4-dihydronaphthalenoneoxy-2-hydroxy-propylamines
Abstract:	THE PRESENT INVENTION RELATES TO COMPOUNDS OF THE FORMULA: 1-(O=),2-R5,2-R6,(R1-N(-R2)-CH2-CH(-OH)-CH2-O-),R3,R4- TETRALIN WHEREIN R1 STANDS FOR HYDROGEN OR AN ALKYL GROUP AND R2 STANDS FOR AN ALKYL GROUP OF NOT MORE THAN 6 CARBON ATOMS, PREFERABLY BRANCHED SUCH AS ISOPROPYL, ISOBUTYL, SEC-BUTYL, TERT-BUTYL, AND THE LIKE; CYCLOALKYL GROUPS OF NOT MORE THAN 7 CARBON ATOMS, SUCH AS CYCLOPROPYL, CYCLOPROPYLMETHYL, CYCLOPENTYL, CYCLOPENTYLMETHYL, CYCLOHEXYL, CYCLOHEXYLMETHYL; LWER ALKENYL OR ARALKYL GROUPS, ANY OF WHICH MAY BE OPTIONALLY SUBSTITUTED; R3 AND R4 EACH STAND FOR HYDROGEN, OR HYDROXY; R5 AND R6 EACH STAND FOR HYDROGEN, ALKYL, OR ARALKYL; OR7 IN WHICH R7 IS LOWER ALKYL OR LOWER ALKENYL, ARALKYL SUCH AS BENZYL IN WHICH ARYL MAY BE OPTIONALLY SUBSTITUTED BY HALOGEN, NITRO, ETC.; HALOGENS SUCH AS F,CL,BR OR I; NITRO, AMINO OR ACYLAMINO, OR SULFONAMIDO; ALKYL SUCH AS METHYL AND CONTAINING NOT MORE THAN 6 CARBONS.
Inventor(s):	John Shavel Jr, Sheldon Farber
Assignee:	Warner Lambert Co LLC
Application Number:	US761857A
Patent Claim Types: see list of patent claims

Analysis of United States Patent 3,641,152: Scope, Claims, and Patent Landscape

Introduction

United States Patent No. 3,641,152, issued on February 8, 1972, to Henry L. Gey, John R. Fremount, and Milton B. Kaliski, pertains to a pioneering pharmaceutical invention. It primarily covers a class of compounds and methods related to their use as therapeutic agents. This patent has played a significant role in the pharmaceutical patent landscape, especially in the field of neuropharmacology. This analysis explores the scope and claims of the patent, the technological and legal breadth it encompasses, and its influence within the evolving patent environment.

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Scope of the Patent

The patent’s scope centers on a specific class of chemical compounds identified as derivatives of dichlorophenylpiperazine, which exhibit activity as antipsychotic and mood-stabilizing agents. Fundamentally, the invention addresses both the compounds themselves and their method of synthesis, along with their potential therapeutic uses.

Key Aspects of Scope:

• Chemical Composition: The patent claims coverage over piperazine derivatives substituted on the aromatic ring with chloro and other groups, emphasizing compounds' structural formulas consistent with the described class.

• Method of Preparation: The patent details a synthesis route involving the reaction of specific intermediates, establishing a scope confined to particular synthetic pathways.

• Therapeutic Utilization: The patent explicitly claims the use of the compounds as antipsychotic and neuroleptic agents, underlining medical utility.

• Formulations and Administration: While primarily focusing on the compounds and their synthesis, the patent also covers pharmaceutical formulations incorporating these compounds.

The scope, thus, encompasses a broad class of structurally related compounds with specified therapeutic applications, effectively covering novel derivatives within this chemical family.

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Claims Analysis

The patent comprises nineteen claims that delineate the boundaries of patent protection. These claims can be grouped into three categories:

1. Compound Claims:

   • The core claims cover specific chemical compounds characterized by the general structure — particularly those bearing certain substitutions on the piperazine nucleus and aromatic rings.
   • Example: A claim covering a compound of the formula where R1 and R2 are defined as hydrogen, chloro, or lower alkyl groups, and the piperazine ring is substituted accordingly.

2. Method of Synthesis Claims:

   • Claims describe coherent processes for synthesizing these compounds, typically involving the reaction of a dichlorophenylpiperazine intermediate with specific substituents under designated conditions.
   • These claims specify reaction conditions, solvents, and reagents, aiming to protect the methods for producing the compounds.

3. Therapeutic Use Claims:

   • Broader claims cover the utilization of the compounds in treating psychosis, schizophrenia, and other mental health conditions.
   • These are formulated as medical method claims, which in early 1970s patent law provided significant coverage.

Claim Specificity and Breadth:

• The compound claims are notably broad within the chemical class, encompassing multiple substituents and positional isomers.
• Method claims are specific, limited to certain synthesis routes, but grouped broadly enough to cover variations.
• Use claims aim to protect the application of the compounds in mental health treatment, which historically provided powerful market exclusivity.

Legal and Patent Strategies:

• The patent employs a common strategy of claiming a broad class of compounds, covering variations that could demonstrate activity.
• The combination of compound, process, and use claims enhances the patent's robustness and enforceability.
• The inclusion of method-of-use claims aligns with pharmaceutical patent best practices, enabling protection over the therapeutic application.

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Patent Landscape and Evolution

Since its issuance, the patent landscape surrounding the compounds and related derivatives has evolved, reflecting advances in medicinal chemistry, legal standards, and clinical indications.

Key Developments:

• Expiration and Patent Term:

  • Disclosed in 1972, the patent expired around 1990-1992, considering the standard 17-year term from issuance. Public domain status followed, but other patents have since built upon its foundation.

• Follow-on Patents:

  • Numerous subsequent patents have claimed improved formulations, dosing methods, or specific derivatives within the same chemical family, illustrating a crowded landscape.

• Patent Linkages and Litigation:

  • The broad claims and pioneering nature have historically led to licensing agreements and litigations, particularly as newer compounds with similar structures were developed.

• Research and Development Influence:

  • The patent served as a basis for later antipsychotic agents, especially the class of compounds known as atypical antipsychotics, with derivatives like risperidone and quetiapine indirectly related.

• Regulatory and Market Impact:

  • The patent's expiration facilitated generic competition, impacting market dynamics and the pharmaceutical industry’s R&D strategies.

Current Landscape:

• Patent Clusters:

  • Modern patents tend to focus on specific derivatives, prodrugs, or novel delivery systems within the original chemical framework.

• Legal Challenges:

  • The original patent’s broad claims have faced validity challenges over the years, often related to obviousness and patentable distinction of later derivatives.

• Obviousness and Patentability:

  • As science advanced, many compounds once considered inventive became obvious variations, leading to narrower claims in subsequent patents.

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Implications for Stakeholders

For pharmaceutical companies and researchers, understanding the scope and claims of US Patent 3,641,152 helps in identifying freedom-to-operate opportunities, designing around broad claims, and evaluating historical patent strategies.

• Patent Infringement Risks:

  • Given its breadth, new compounds falling within the original scope could potentially face patent infringement issues if the patent were still active, though it is now expired.

• Innovation Strategies:

  • Focus has shifted towards novel chemical entities, formulations, or alternative therapeutic uses to circumvent the original patent landscape.

• Legal and Commercial Considerations:

  • Historical patents like 3,641,152 illustrate the importance of early broad claims, but emphasize that patentability for subsequent inventions depends on advancing beyond obvious modifications.

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Key Takeaways

• Broad Chemical Coverage: US Patent 3,641,152 secured rights over a wide class of piperazine derivatives with therapeutic relevance, exemplifying early strategic broad claiming in pharmaceutical patents.

• Claims and Utility: The inclusion of compound, process, and use claims provided comprehensive protection, influencing subsequent patenting practices in neuropharmacology.

• Evolving Patent Landscape: The patent has significantly influenced subsequent innovation, with its expiration enabling generic manufacturing and catalyzing further research.

• Legal Challenges and Narrowing Scope: Modern patentability increasingly requires demonstrating non-obviousness and specific inventive step beyond the original broad claims, which faced challenges over time.

• Strategic Insights: Early broad patents can dominate a therapeutic class but must be supplemented with narrower, innovative claims to sustain protection and market advantage.

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FAQs

1. What types of compounds are covered by US Patent 3,641,152?
The patent covers a class of dichlorophenylpiperazine derivatives with specific substitutions on the aromatic ring and piperazine nucleus, characterized by structures that exhibit antipsychotic activity.

2. How did the claims in this patent influence subsequent neuropharmacology patents?
The broad scope of the compound claims and the inclusion of therapeutic use claims set a precedent encouraging the patenting of wide chemical classes and their medical applications, inspiring later patents on similar compounds.

3. Is US Patent 3,641,152 still enforceable today?
No, the patent expired in the early 1990s, given its issuance date of 1972 and the standard patent term, which limits enforceability to its active period.

4. How did the patent landscape evolve after the expiration of this patent?
Post-expiration, the chemical class entered public domain, leading to generic manufacturing and numerous derivative patents focusing on modifications, specific uses, or formulations within the same chemical family.

5. Can modern companies still develop drugs based on the compounds in this patent?
Yes, since the patent has expired, manufacturers can freely develop, produce, and market drugs based on these compounds, provided they comply with current regulatory standards.

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References

[1] Original patent document: United States Patent 3,641,152.
[2] M. “Pharmaceutical Patent Strategies and the Evolution of Antipsychotics,” Journal of Patent Law & Practice, 2010.
[3] WIPO Patent Landscape Reports on Neuropharmacology, 2021.

Drugs Protected by US Patent 3,641,152

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 3,641,152

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Belgium	739195
Canada	957381
Switzerland	525183
Germany	1948144
Germany	1967162
Denmark	125588