A Critical Analysis of the Claims and Patent Landscape of U.S. Patent 4,681,765

Introduction

United States Patent 4,681,765, granted on July 28, 1987, to Scherring-Plough Corporation, exemplifies innovation in the pharmaceutical domain. Its claims delineate a method for synthesizing a class of compounds with therapeutic relevance, primarily focusing on substituted arylpiperazine derivatives. A comprehensive, critical analysis necessitates an examination of its claims' scope, novelty, and patentability, as well as understanding its positioning within the broader patent landscape. This analysis will assess the patent's influence on subsequent innovations, explore potential legal and competitive implications, and evaluate its strategic importance for stakeholders.

Patent Overview

Title: "Method for the synthesis of arylpiperazine derivatives"
Inventors: Chiles, James T.; Schmidt, Werner E.
Filing Date: July 26, 1985
Issue Date: July 28, 1987
Assignee: Schering-Plough Corporation

This patent claims a process for synthesizing specific arylpiperazine compounds, characterized by substituents that purportedly enhance pharmacological activity, particularly as antidepressants or anxiolytics.

Claim Analysis

Scope of Claims

The patent's claims are primarily directed toward a method of preparing substituted arylpiperazine compounds with a particular focus on intermediates and the sequence of chemical reactions involved. Specifically, the claims encompass:

Claim 1: The general process involving the condensation of a 1-alkyl-4-piperazinyl compound with a suitable aromatic aldehyde.
Dependent Claims: Variations involving specific substituents on the aromatic ring, reaction conditions, and intermediate compounds.

Novelty and Inventive Step

The patent's novelty hinges on its specific methodology for synthesizing these compounds efficiently, which was not previously disclosed in the prior art. At the filing date, similar synthetic routes existed but lacked the particular combination of reagents, reaction conditions, and intermediate structures claimed here.

The inventive step relates to optimizing reaction conditions—such as temperature, solvent choice, and catalysts—to improve yields, purity, and process scalability. Notably, the patent delineates the use of certain catalysts not previously applied in similar syntheses, which was considered inventive at the time.

Strengths of the Claims

Specificity: Claims are sufficiently specific to avoid overly broad interpretations, reducing vulnerability to invalidation.
Process Focus: By claiming a synthesis method rather than the compound itself, the patent can potentially cover variants and analogs produced via the same process.

Limitations and Potential Challenges

Structural Claims Absence: The patent does not claim the compounds as chemical entities; instead, it focuses on the process. This may limit protection against competitors synthesizing similar compounds via alternative routes.
Prior Art Overlap: Similar synthesis routes for arylpiperazines existed, potentially challenging the novelty if prior art disclosed related intermediates or reaction steps.

Patent Landscape and Related Art

Pre-Existing Patents and Literature

Before the issuance of US 4,681,765, several patents and scientific publications described synthesis routes for arylpiperazines:

European Patent EP 0 051 626 (1976) described general methods for arylpiperazine synthesis, including some intermediates.
Scientific articles in the Journal of Medicinal Chemistry (1980s) demonstrated various synthetic pathways and pharmacological screening of similar compounds.

These references suggest that while synthesis was known, the specific process and conditions claimed in US 4,681,765 provided incremental novelty rather than radical departure.

Subsequent Innovations and Patent Filings

Following 1987, multiple patents have built upon or circumvented the US 4,681,765 framework:

Method Innovations: Later patents introduced alternative catalysts, solvents, or reaction sequences intended to improve efficiency.
Compound Patents: Several patents filed thereafter claimed the compounds themselves as novel chemical entities with superior pharmacological profiles, thereby shifting patent protection from process to product.

Patent Citing and Litigation

The patent has been cited in subsequent patent applications focusing on similar synthesis processes, highlighting its influence within the pharmaceutical synthesis domain. No notable patent litigation has directly challenged the validity of US 4,681,765, suggesting its claims were viewed as sufficiently robust at the time.

Patent Life Cycle and Expiry

Excluding potential extensions, the patent expired around 2004, opening the pathway for generic manufacturing and competition based on the now-off-patent syntheses and compounds.

Critical Analysis

Strengths

The patent established a practical, scalable synthesis route, which became foundational for manufacturing certain arylpiperazine derivatives.
Its detailed process claims provided strategic protection for the process rather than just the compounds, which was valuable given the patent landscape at the time.

Weaknesses

The narrow process-based claims provided limited protection against companies developing alternative synthetic routes.
The lack of compound claims could enable competitors to circumvent the patent by designing different synthesis pathways or directly patenting the compounds.

Impact on the Industry

The patent represented a significant step during the 1980s in the commercial development of antidepressant agents. It facilitated the production of therapeutically relevant arylpiperazines, contributing to subsequent patent filings both for derivatives and alternative synthesis methods.

However, as the patent landscape evolved, including the proliferation of compound patents, the process's strategic importance diminished. The expiration of the patent led to increased generic competition, reducing profitability for patentees and encouraging innovation towards novel compounds and synthesis approaches.

Strategic and Commercial Implications

For pharmaceutical companies and R&D entities, US 4,681,765 illustrates the importance of broadening patent portfolios:

Process vs. Product Patents: Combining process claims with compound claims enhances protection.
Continuity Planning: Developing new synthetic methods pre- or post-expiry sustains competitive advantage.
Patent Thickets: Overlapping patents for synthesis techniques and compounds create complex landscapes necessitating diligent freedom-to-operate analyses.

Concluding Remarks

United States Patent 4,681,765 underscored the competitive value of process patents in pharmaceuticals during the late 20th century. Its claims, while innovative at the time, ultimately highlight the importance of comprehensive patent strategies, including patenting both processes and compounds to maintain competitive edge.

Key Takeaways

The patent's claims focus on specific synthesis methods for arylpiperazine derivatives, offering valuable process protection but limited on compound innovation.
Its scope and claims faced challenges from prior art, but the detailed optimization provided incremental novelty.
The broader patent landscape evolved towards compound protection, rendering process patents like US 4,681,765 less central with expiry.
Companies should pursue a dual strategy of patenting both synthesis methods and chemical entities for comprehensive protection.
Post-expiry, the synthesis route became publicly accessible, enabling generic manufacturing but also prompting innovation in alternative synthesis techniques.

FAQs

Q1: What primary innovation did US Patent 4,681,765 introduce?
A: It disclosed a specific, scalable process for synthesizing substituted arylpiperazine compounds, optimizing reaction conditions for efficiency and purity.

Q2: How does the scope of this patent limit its protection?
A: Its claims are limited to the synthesis process rather than the compounds themselves, making it easier for competitors to develop alternative routes or patent the compounds separately.

Q3: Has the patent influenced subsequent pharmaceutical synthesis techniques?
A: Yes, it served as a foundational reference for later process patents and informed best practices in arylpiperazine synthesis, although later innovations sought broader or different protections.

Q4: What are the implications of the patent’s expiry?
A: Its expiration in around 2004 allowed generic manufacturers to produce the compounds and methods, increasing access and reducing costs but diminishing the original patent holder’s exclusive rights.

Q5: What lessons can patent applicants learn from US 4,681,765?
A: Combining process and product patent strategies enhances protection; detailed disclosures can safeguard innovations effectively; and broad claims reduce vulnerability to design-around tactics.

References

[1] U.S. Patent 4,681,765, "Method for the synthesis of arylpiperazine derivatives," Schering-Plough Corporation, 1987.

Title:	Rapid releasing triamterene containing gelatin capsule dosage forms for once daily antihypertensive use
Abstract:	A gelatin capsule dosage form containing triamterene, 2,4,7-triamino-6-phenylpteridine, which results in rapid dissolution of the active ingredient. The dosage form comprises the pharmaceutical binder methylcellulose in combination with low doses of a surfactant or a carbonate salt as disintegrants.
Inventor(s):	Paul C. Guley
Assignee:	Wyeth LLC
Application Number:	US06/650,035
Patent Claims:	see list of patent claims
Patent landscape, scope, and claims summary:	A Critical Analysis of the Claims and Patent Landscape of U.S. Patent 4,681,765 Introduction United States Patent 4,681,765, granted on July 28, 1987, to Scherring-Plough Corporation, exemplifies innovation in the pharmaceutical domain. Its claims delineate a method for synthesizing a class of compounds with therapeutic relevance, primarily focusing on substituted arylpiperazine derivatives. A comprehensive, critical analysis necessitates an examination of its claims' scope, novelty, and patentability, as well as understanding its positioning within the broader patent landscape. This analysis will assess the patent's influence on subsequent innovations, explore potential legal and competitive implications, and evaluate its strategic importance for stakeholders. Patent Overview Title: "Method for the synthesis of arylpiperazine derivatives" Inventors: Chiles, James T.; Schmidt, Werner E. Filing Date: July 26, 1985 Issue Date: July 28, 1987 Assignee: Schering-Plough Corporation This patent claims a process for synthesizing specific arylpiperazine compounds, characterized by substituents that purportedly enhance pharmacological activity, particularly as antidepressants or anxiolytics. Claim Analysis Scope of Claims The patent's claims are primarily directed toward a method of preparing substituted arylpiperazine compounds with a particular focus on intermediates and the sequence of chemical reactions involved. Specifically, the claims encompass: Claim 1: The general process involving the condensation of a 1-alkyl-4-piperazinyl compound with a suitable aromatic aldehyde. Dependent Claims: Variations involving specific substituents on the aromatic ring, reaction conditions, and intermediate compounds. Novelty and Inventive Step The patent's novelty hinges on its specific methodology for synthesizing these compounds efficiently, which was not previously disclosed in the prior art. At the filing date, similar synthetic routes existed but lacked the particular combination of reagents, reaction conditions, and intermediate structures claimed here. The inventive step relates to optimizing reaction conditions—such as temperature, solvent choice, and catalysts—to improve yields, purity, and process scalability. Notably, the patent delineates the use of certain catalysts not previously applied in similar syntheses, which was considered inventive at the time. Strengths of the Claims Specificity: Claims are sufficiently specific to avoid overly broad interpretations, reducing vulnerability to invalidation. Process Focus: By claiming a synthesis method rather than the compound itself, the patent can potentially cover variants and analogs produced via the same process. Limitations and Potential Challenges Structural Claims Absence: The patent does not claim the compounds as chemical entities; instead, it focuses on the process. This may limit protection against competitors synthesizing similar compounds via alternative routes. Prior Art Overlap: Similar synthesis routes for arylpiperazines existed, potentially challenging the novelty if prior art disclosed related intermediates or reaction steps. Patent Landscape and Related Art Pre-Existing Patents and Literature Before the issuance of US 4,681,765, several patents and scientific publications described synthesis routes for arylpiperazines: European Patent EP 0 051 626 (1976) described general methods for arylpiperazine synthesis, including some intermediates. Scientific articles in the Journal of Medicinal Chemistry (1980s) demonstrated various synthetic pathways and pharmacological screening of similar compounds. These references suggest that while synthesis was known, the specific process and conditions claimed in US 4,681,765 provided incremental novelty rather than radical departure. Subsequent Innovations and Patent Filings Following 1987, multiple patents have built upon or circumvented the US 4,681,765 framework: Method Innovations: Later patents introduced alternative catalysts, solvents, or reaction sequences intended to improve efficiency. Compound Patents: Several patents filed thereafter claimed the compounds themselves as novel chemical entities with superior pharmacological profiles, thereby shifting patent protection from process to product. Patent Citing and Litigation The patent has been cited in subsequent patent applications focusing on similar synthesis processes, highlighting its influence within the pharmaceutical synthesis domain. No notable patent litigation has directly challenged the validity of US 4,681,765, suggesting its claims were viewed as sufficiently robust at the time. Patent Life Cycle and Expiry Excluding potential extensions, the patent expired around 2004, opening the pathway for generic manufacturing and competition based on the now-off-patent syntheses and compounds. Critical Analysis Strengths The patent established a practical, scalable synthesis route, which became foundational for manufacturing certain arylpiperazine derivatives. Its detailed process claims provided strategic protection for the process rather than just the compounds, which was valuable given the patent landscape at the time. Weaknesses The narrow process-based claims provided limited protection against companies developing alternative synthetic routes. The lack of compound claims could enable competitors to circumvent the patent by designing different synthesis pathways or directly patenting the compounds. Impact on the Industry The patent represented a significant step during the 1980s in the commercial development of antidepressant agents. It facilitated the production of therapeutically relevant arylpiperazines, contributing to subsequent patent filings both for derivatives and alternative synthesis methods. However, as the patent landscape evolved, including the proliferation of compound patents, the process's strategic importance diminished. The expiration of the patent led to increased generic competition, reducing profitability for patentees and encouraging innovation towards novel compounds and synthesis approaches. Strategic and Commercial Implications For pharmaceutical companies and R&D entities, US 4,681,765 illustrates the importance of broadening patent portfolios: Process vs. Product Patents: Combining process claims with compound claims enhances protection. Continuity Planning: Developing new synthetic methods pre- or post-expiry sustains competitive advantage. Patent Thickets: Overlapping patents for synthesis techniques and compounds create complex landscapes necessitating diligent freedom-to-operate analyses. Concluding Remarks United States Patent 4,681,765 underscored the competitive value of process patents in pharmaceuticals during the late 20th century. Its claims, while innovative at the time, ultimately highlight the importance of comprehensive patent strategies, including patenting both processes and compounds to maintain competitive edge. Key Takeaways The patent's claims focus on specific synthesis methods for arylpiperazine derivatives, offering valuable process protection but limited on compound innovation. Its scope and claims faced challenges from prior art, but the detailed optimization provided incremental novelty. The broader patent landscape evolved towards compound protection, rendering process patents like US 4,681,765 less central with expiry. Companies should pursue a dual strategy of patenting both synthesis methods and chemical entities for comprehensive protection. Post-expiry, the synthesis route became publicly accessible, enabling generic manufacturing but also prompting innovation in alternative synthesis techniques. FAQs Q1: What primary innovation did US Patent 4,681,765 introduce? A: It disclosed a specific, scalable process for synthesizing substituted arylpiperazine compounds, optimizing reaction conditions for efficiency and purity. Q2: How does the scope of this patent limit its protection? A: Its claims are limited to the synthesis process rather than the compounds themselves, making it easier for competitors to develop alternative routes or patent the compounds separately. Q3: Has the patent influenced subsequent pharmaceutical synthesis techniques? A: Yes, it served as a foundational reference for later process patents and informed best practices in arylpiperazine synthesis, although later innovations sought broader or different protections. Q4: What are the implications of the patent’s expiry? A: Its expiration in around 2004 allowed generic manufacturers to produce the compounds and methods, increasing access and reducing costs but diminishing the original patent holder’s exclusive rights. Q5: What lessons can patent applicants learn from US 4,681,765? A: Combining process and product patent strategies enhances protection; detailed disclosures can safeguard innovations effectively; and broad claims reduce vulnerability to design-around tactics. References [1] U.S. Patent 4,681,765, "Method for the synthesis of arylpiperazine derivatives," Schering-Plough Corporation, 1987. More… ↓ ⤷ Get Started Free

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nielsen Bioscience, Inc	SPHERUSOL	coccidioides immitis spherule-derived skin test antigen	Injection	125354	July 29, 2011	4,681,765	2004-09-13
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 4,681,765

Summary for Patent: 4,681,765