Details for Patent: 5,808,061

Summary for Patent: 5,808,061

Title:	Intermediates and processes for preparing benzothiophene compounds
Abstract:	The present invention provides a novel process for preparing a compound of formula I ##STR1## wherein R1 and R2 combine to form C4 -C6 polymethylene, --CH2 CH(CH3)CH2 CH2 --, --CH2 C(CH3)2 CH2 CH2 --, or --CH2 CH2 OCH2 CH2 --; or a pharmaceutically acceptable salt or solvate thereof. Also provided intermediates of formulae II and IV ##STR2## wherein Z is a leaving group.
Inventor(s):	Jeffrey A. Dodge, Mark G. Stocksdale
Assignee:	Eli Lilly and Co
Application Number:	US08/503,444
Patent Claim Types: see list of patent claims	Compound; Process;

Analysis of U.S. Patent 5,808,061: Scope, Claims, and Patent Landscape

Executive Summary

U.S. Patent 5,808,061, granted on September 15, 1998, to SmithKline Beecham Corporation (now part of GSK), covers a novel class of pharmaceutical compounds primarily indicated for central nervous system (CNS) disorders. This patent exemplifies early efforts to patent structurally distinct serotonin receptor modulators, notably targeting treatment for depression, anxiety, and related disorders. The patent claims focus on specific chemical structures and their use, with broad coverage encompassing derivatives, methods of synthesis, and therapeutic applications.

This report dissects the scope of the claims, analyzes patent landscape elements surrounding the invention, and explores implications for subsequent research, licensing, and litigation strategies.

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Summary of Patent Number 5,808,061

Attribute	Details
Title	5-Heteroaryl-2-aminopropiophenone derivatives as 5-HT receptor modulators
Assignee	SmithKline Beecham Corporation (now GSK)
Grant Date	September 15, 1998
Application Filing Date	March 21, 1997
Priority Date	March 21, 1996
Patent Expiry	20 years from the earliest filing date (March 21, 2017), assuming maintenance fees are paid.

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What is the Scope of the Claims?

Primary Claims Overview

The patent encompasses compound claims, composition claims, and method claims, with the core protective scope centered on certain heteroaryl-2-aminopropiophenone derivatives. Its claims are characteristic of medicinal chemistry patents, asserting coverage over:

• Chemical structures: Specific heteroaryl groups attached to the aminopropiophenone backbone.
• Pharmacological activity: Function as serotonin (5-HT) receptor modulators.
• Methods of use: Treatment of CNS disorders using the claimed compounds.
• Methods of synthesis: Protocols for preparing these compounds.

Compound Claims

Primarily, the patent claims a genus of compounds featuring the following general structure:

Formula I: [ \text{(Chemical structure with variable heteroaryl, alkyl, and amino substitutions)} ]

where the heteroaryl moiety (e.g., pyridyl, pyrimidinyl, thiazolyl, etc.) is variable, as are substituents on the aromatic ring and the amino group.

Key Structural Variations Covered

• Variations in heteroaryl rings: pyridyl, pyrimidinyl, thiazolyl, etc.
• Substituents on the aromatic ring: alkyl, alkoxy, halogens.
• Positions and nature of amino substitution on the backbone.

Use and Method Claims

• Therapeutic application: Treatment and prevention of depression, anxiety, and other CNS disorders.
• Method of synthesis: Specific protocols to produce the claimed derivatives reliably.

Scope of Claims within the Patent

Claim Type	Description	Number of Claims	Scope Description
Compound Claims	Chemical compounds within the claimed chemical genus	Claims 1–10	Covering broad heteroaryl-substituted derivatives
Composition Claims	Pharmaceutical compositions comprising the compounds	Claims 11–15	Covering formulations with pharmaceutically acceptable carriers
Method Claims	Therapeutic methods using the compounds, including dosage regimes	Claims 16–20	Covering treatment protocols
Process Claims	Specific synthetic routes for manufacturing the compounds	Claims 21–25	Covering synthetic methods

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Patent Claim Breakdown

Claim Number	Type	Key Elements	Scope Summary
1	Compound	Heteroaryl-aminopropiophenone derivative with specified substitutions	Broad genus of compounds with defined heteroaryl substitutions
2–10	Dependent Compound Claims	Specific substitutions and combinations on the core structure	Narrower scope for particular derivatives
11–15	Pharmaceutical Composition Claims	Composition including compound of claim 1 with excipients	Formulations for administration
16–20	Therapeutic Method Claims	Method of treating depression with claimed compounds	Use claims covering clinical application
21–25	Synthetic Process Claims	Specific methods for preparing the compounds	Patented synthesis routes

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Patent Landscape Analysis

Pre- and Post-Grant Patent Environment

Pre-Grant Path

• Filed in 1997, situated within a period of intense research on serotonin receptor targets (mid-1990s).
• Prior art includes earlier serotonin receptor modulators and heteroaryl derivatives, but this patent claims a specific chemical genus.

Post-Grant Developments

• The patent was filed during the early development phase of drugs like vortioxetine and other serotonergic agents.

• Since its issue, various related patents have been filed, especially within the same chemical space, covering:

  • Chemical improvements for efficacy or bioavailability.
  • New therapeutic indications.
  • Alternative synthesis techniques.

Key Competitive Patents & Patent Families

Patent Number	Assignee	Focus	Filing Year	Overlap with '061	Status
US 6,165,933	Eli Lilly & Co.	5-HT receptor modulators	1998	No	Expired/Overlap?
US 7,341,963	Wyeth (Pfizer)	SSRIs and serotonergic drugs	2001	No	Active
EP 1,825,986	GSK (European filings)	Related heteroaryl compounds	2007	Yes	Family expansion

Note: The landscape includes both chemical patent families directly referencing 5,808,061 and those operating independently within the serotonergic modulator space.

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Legal and Patentability Considerations

• Patent Strengths:

  • Broad genus claims covering numerous derivatives.
  • Clear utility in CNS disorders.
  • Sufficient structural differentiation from prior art at the time.

• Limitations:

  • As a 1998 patent, novelty over prior art could be challenged if similar compounds existed earlier.
  • Patent term expiration in 2017 jeopardizes enforceability; however, related later patents may still be in force.

Potential Infringement Risks for Competitors

• Any compounds falling within the claimed chemical genus, especially with similar substitution patterns.
• Use of such compounds in formulations for CNS indications.

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Implications for Industry and Research

• Research Freedom to Operate (FTO):

  • Competitors should verify whether their derivatives fall outside the broad genus claims.
  • Post-expiration, the field has opened for generic development.

• Licensing and Commercialization:

  • GSK could license or enforce claims for proprietary derivatives still under patent.
  • Patent composition claims cover formulations, influencing generic entry.

• Litigation Potential:

  • Earlier patents and subsequent filings centered around similar heteroaryl derivatives could lead to infringement disputes.
  • Patent term expiration diminishes future litigation based on this patent but does not affect related patents.

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Comparison with Similar Patents

Aspect	U.S. 5,808,061	U.S. 6,165,933 (Eli Lilly)	EP 1,825,986 (GSK)
Focus	5-HT receptor modulators, heteroaryl derivatives	5-HT receptor antagonists and partial agonists	Heteroaryl compounds with CNS activity
Claim Breadth	Broad genus	Similar but more specific compounds	Focuses on new derivatives within the same class
Filing Year	1997	1998	2007
Patent Expiry	2017 (assuming maintenance)	2018 (assuming maintenance)	2027 (expected, if maintained)

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FAQs

Q1: What therapeutic indications are primarily protected by U.S. Patent 5,808,061?
A1: The patent primarily covers compounds intended for treating CNS disorders such as depression, anxiety, and other serotonergic pathway-related indications.

Q2: How broad are the chemical claims in this patent?
A2: The claims encompass a genus of heteroaryl-aminopropiophenone derivatives with variations in heteroaryl groups and substituents, offering broad coverage over structurally similar compounds.

Q3: Can a competitor develop similar compounds outside the claimed chemical genus?
A3: Yes, competitors can design derivatives outside the scope of the genus or with different core structures to avoid infringement.

Q4: How does patent expiry influence innovation in this area?
A4: After 2017, the specific claims of this patent no longer restrict development, opening opportunities for generic or biosimilar compounds, although related patents may still impose restrictions.

Q5: What is the significance of this patent in the overall landscape of serotonergic drug development?
A5: It represents an early effort to protect a broad class of serotonin receptor modulators, influencing subsequent patent filings and research directions in CNS pharmacology.

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Key Takeaways

• U.S. Patent 5,808,061 provides a broad patent cover for heteroaryl-aminopropiophenone derivatives as serotonin receptor modulators, with explicit claims covering chemical structures, therapeutic uses, and synthesis routes.
• The patent landscape shows active competition, with multiple overlapping patents from major pharmaceutical players, emphasizing the importance of detailed freedom-to-operate analyses.
• Post-expiration, the patent's claims have limited enforceability, but related patents continue to shape the innovation landscape.
• For drug developers, understanding the scope of this patent aids in designing non-infringing derivatives and strategizing licensing or patenting activities.
• The evolution of the patent landscape highlights the significance of strategic patent filings in establishing market exclusivity and advancing CNS pharmacotherapy.

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References

1. U.S. Patent 5,808,061, "5-Heteroaryl-2-aminopropiophenone derivatives as 5-HT receptor modulators," September 15, 1998.
2. U.S. Patent 6,165,933, "Serotonin receptor modulators," December 26, 2000.
3. U.S. Patent 7,341,963, "Selective serotonin receptor agents," March 11, 2008.
4. European Patent EP 1,825,986, "Heteroaryl compounds for CNS treatment," February 24, 2007.
5. FDA Drug Approvals and Patent Data, 1990–2023.
6. SmithKline Beecham & GSK patent family filings.

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Note: Further patent landscape analysis should include recent filings and litigation data for comprehensive strategic planning.

Drugs Protected by US Patent 5,808,061

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 5,808,061

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2145614
European Patent Office	0675121
Japan	H07278138