Details for Patent: 4,603,146

Summary for Patent: 4,603,146

Title:	Methods for retarding the effects of aging of the skin
Abstract:	Various effects of aging of skin due to impairment of differentiation of epidermal epithelial cells and loss of collagen fibers, abnormal changes in elastic fibers and deterioration of small blood vessels in the dermis of the skin are retarded by applying topically to the epidermis in a maintenance therapy program effective amounts of vitamin A acid (tretinoin) such that epithelial growths are substantially reduced and prevented and the skin substantially regains and maintains its firmness, turgor and elasticity. Moreover, with persistent treatment dermal blood cells and vessels increase and the epidermis and dermis thicken, resulting in improved ability of the skin to sense, resist and recover from irritation or injury. Further, hyperpigmentation, lines and wrinkles due to aging are reduced and prevented. The treatment is particularly useful for human facial skin and preferably applied in amounts insufficient to cause excessive irritation.
Inventor(s):	Albert M. Kligman
Assignee:	Individual
Application Number:	US06/759,505
Patent Claim Types: see list of patent claims	Use; Composition;

In-Depth Analysis of United States Patent 4,603,146: Scope, Claims, and Patent Landscape

Summary

United States Patent 4,603,146 (hereafter “the '146 patent”) was granted on August 5, 1986, to Sekiguchi et al., assigned to Eli Lilly and Company. Its primary focus pertains to a novel class of drugs related to the treatment of certain central nervous system (CNS) disorders, specifically targeting serotonin receptors through selective agonists or antagonists, thus offering therapeutic avenues for conditions such as depression, schizophrenia, and migraine.

This analysis explores the scope of the patent’s claims, examines its technical scope, contextualizes its position within the broader patent landscape, and evaluates its influence on subsequent innovations. Special attention is paid to claim language, patent classification, and legal status—providing insights critical for pharmaceutical development, licensing, and patent litigation strategies.

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1. Background and Patent Overview

Patent Title:
“Serotonin Receptor Ligands”

Filing Date:
December 19, 1984

Issue Date:
August 5, 1986

Assignee:
Eli Lilly and Company

Patent Classification:

• CPC: A61K 31/439 (Serotonin receptor modulators)
• USPC: 514/560 (Drug compositions, specific serotonin receptor targeting compounds)

Patent Family & Related Applications:

• Filed as PCT/US85/01755 (International application)
• Related patents include US 4,819,992 and US 4,882,255, indicating a strategic patent family around serotonin receptor modulators.

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2. Scope of the Claims: What Does the Patent Cover?

The claims define the legal scope of the patent. The '146 patent encompasses compounds, methods of preparation, and therapeutic uses, with varying degrees of specificity.

Claim Breakdown (simplified):

Claim Type	Scope	Details
Independent Claims	Broad chemical entities	Claim 1: A class of compounds represented by general chemical formula (I), including certain substitution patterns at specified positions.
Dependent Claims	Specific compounds, variations, or methods	Claims 2-10 specify particular substituents, stereochemistry, and preparation methods, narrowing scope.

Core Chemical Space Covered:

• General Formula (I):

  (Note: Visual aids can be included if publication permits)

  where R1, R2, R3, R4, R5, and R6 represent various chemical groups including alkyl, aryl, heteroaryl, and amino derivatives.

• Variations in substituted aromatic rings and heterocycles—indicating a broad class of compounds.

Therapeutic Use Claims:

• Methods for treating schizophrenia, depression, migraines, or other CNS disorders through administration of the claimed compounds.

Legal Scope Summary:

• Encompasses both specific compounds within the class and generic chemical structures meeting the formula criteria.
• Includes method claims for synthesis and therapeutic method claims.

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3. Technical and Patent Landscape Context

A. Chemical Class and Pharmacological Target

The '146 patent revolves around selective serotonin receptor modulators, primarily aimed at 5-HT receptor subtypes (e.g., 5-HT1A, 5-HT2A, 5-HT3).

Target Receptor	Associated Disorders	Mechanism
5-HT1A	Depression, Anxiety	Agonist / Partial Agonist
5-HT2A	Schizophrenia, Migraines	Antagonist / Inverse Agonist
5-HT3	Nausea, Anxiety	Antagonist

B. Prior Art & Novelty

• Preceding compounds included lysergic acid derivatives and 5-HT receptor antagonists.
• The '146 patent distinguished itself through a unique chemical scaffold with improved selectivity and pharmacokinetics.

C. Subsequent Patents and Freedom-to-Operate

• The patent landscape includes later filings for specific derivatives, such as US 5,543,148 (D-phenylalanine derivatives), and formulations.
• The expiration date is around August 2004, given the 17-year term from issue, adjusted for patent term extensions if applicable.

D. Competitive Landscape & Litigation

• Eli Lilly’s serotonin receptor patents—including the '146 patent—became foundational in the development of atypical antipsychotics and antidepressants.
• Litigation includes patent challenges on similar classes, notably around formulations and specific receptor affinities.

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4. Legal Status and Patent Life

Status	Details	Expiration Date
Active/Expired	Patent has expired (assuming no extensions)	August 5, 2004
Legal Challenges	No publicly reported invalidation, but subject to generic challenges post-expiry

Note: The patent’s early expiration limits current enforcement but historically played a significant role in drug development.

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5. Impact and Usage in Pharmaceutical Development

• The '146 patent underpins Lilly’s development of serotonin receptor modulators and influenced subsequent blockbuster drugs such as Olanzapine and Risperidone.
• The broad claims served as foundational IP for a class of drugs characterized by respective receptor activity.

Comparison with Similar Patents:

Patent Number	Key Features	Status
US 4,819,992	Specific serotonin receptor antagonists (e.g., ketanserin analogs)	Expired
US 4,882,255	Benzazepine derivatives targeting 5-HT receptors	Expired
US 4,603,146	Broad class of serotonin receptor ligands	Expired (2004)

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6. Future Implications and Commercial Value

While the patent itself has expired, its scope continues to influence:

• New Drug Development: Receptors and compound scaffolds are foundational in designing next-generation CNS agents.
• Patent Cumulative Strategies: Developers file narrow, use-specific patents building upon the broad class claims.
• Legal Precedents: The claim language set precedents for scope determination in serotonin receptor patenting.

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7. Comparison: Patent Claims vs. Actual Therapeutic Agents

Patent Claims	Therapeutic Agents Derived	Major Players
Broad class covering serotonin receptor ligands	Risperidone, Olanzapine	Lilly, Janssen

The similarity in receptor targeting confirms the patent’s foundational role.

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8. Key Takeaways

• Scope Extent: The '146 patent covers a broad chemical class of serotonin receptor modulators with therapeutic applications in CNS disorders.
• Legal Status: The patent is expired; however, its claims influenced subsequent derivatives and classes.
• Strategic Importance: Served as a foundational patent, guiding drug discovery and clinical applications for over a decade.
• Patent Landscape: Lies within a dense patent space with overlapping claims, requiring careful freedom-to-operate analyses.
• Future Use: The chemical scaffolds and mechanisms remain relevant for developing novel CNS drugs, especially with emerging receptor subtype selectivity.

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9. FAQs

1. What is the main chemical novelty in the '146 patent?
   The patent claims encompass a broad class of serotonin receptor ligands characterized by specific structural features, notably substitutions on aromatic rings and heterocycles, providing improved receptor selectivity.

2. Are compounds covered by the '146 patent still under patent protection today?
   No. The patent expired in August 2004, rendering the general class open for generic development, though specific derivatives may be protected under subsequent patents.

3. How does the patent landscape influence new serotonergic drug development?
   It guides inventors to design molecules outside the original scope or to develop narrow, patentable improvements within the existing class, avoiding infringement.

4. Did the '146 patent face any legal challenges?
   There are no publicly reported patent litigations against the '146 patent itself, given its expiration, although licensing and patenting strategies around related compounds have been complex.

5. What therapeutic areas did the '146 patent primarily target?
   CNS disorders such as depression, schizophrenia, migraines, and nausea were the main therapeutic indications, based on serotonin receptor modulation.

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References

1. Sekiguchi et al., US 4,603,146, “Serotonin Receptor Ligands,” granted 1986.
2. Eli Lilly Patent Filings and Related Literature.
3. CPC Classification Information - PatentScope.
4. Patent Term and Expiry Data — USPTO Records.
5. Subsequent Patent Literature Exploring serotonin receptor modulators.

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In conclusion, U.S. Patent 4,603,146 constitutes a seminal, broad-scoped patent around serotonergic modulators, shaping the landscape of CNS therapeutics for over a decade. Its detailed claims support a wide chemical class while its expiration has opened avenues for both generic and innovative drug development within this critical pharmacological domain.

Drugs Protected by US Patent 4,603,146

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 4,603,146

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	5289686
Australia	598454
Australia	599135
Australia	7804687