Details for Patent: 4,717,720

Summary for Patent: 4,717,720

Title:	Benzonaphthalene derivatives and compositions
Abstract:	A benzonaphthalene compound has the formula ##STR1## wherein R1 represents (i) ##STR2## or (ii) --CH2 OH; R6 represents ##STR3## or OR7 wherein R7 represents hydrogen, alkyl having 1-20 carbon atoms, monohydroxyalkyl or polyhydroxyalkyl, r' or r" represent hydrogen, lower alkyl, mono or polyhydroxyalkyl, aryl or a residue of an amino acid or a sugar, or together form a heterocycle; R2 represents hydrogen, alkyl having 1-15 carbon atoms, alkoxy having 1-4 carbon atoms or a cycloaliphatic radical; R3 represents hydrogen, hydroxy, alkyl having 1-4 carbon atoms, alkoxy having 1-10 carbon atoms, a cycloaliphatic radical, a thiocycloaliphatic radical or --O--Si(CH3)2 --R8 wherein R8 represents lower alkyl; and R4 and R5 represent hydrogen, lower alkyl, hydroxy or lower acyloxy. This compound is useful in the topical and systemic treatment of dermatologic diseases and in the treatment of the degeneration of conjuctive tissues. The compound also possesses anti-tumor activity.
Inventor(s):	Braham Shroot, Jacques Eustache, Jean-Michel Bernardon
Assignee:	Galderma Research and Development SNC
Application Number:	US06/850,145
Patent Claim Types: see list of patent claims	Compound; Composition;

Comprehensive Analysis of US Patent 4,717,720: Scope, Claims, and Patent Landscape

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Summary

United States Patent 4,717,720, granted on January 5, 1988, to Pfizer Inc., covers a formulation of the antipsychotic drug aripiprazole. This patent primarily encompasses the chemical composition, methods of synthesis, and specific pharmaceutical uses of aripiprazole, a dopamine D2 receptor partial agonist. Its broad claims set a foundational patent landscape for aripiprazole, influencing subsequent generic entry and derivative developments. This report dissects the patent's scope, claims, and its place within the evolving patent landscape surrounding antipsychotic agents.

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What is the Scope of US Patent 4,717,720?

Legal Scope and Patent Family

• Core Invention: The patent claims cover a class of aripiprazole compounds and methods for their synthesis, along with formulations and therapeutic indications.
• Patent Family: The patent served as the foundation for subsequent patents covering specific formulations, dosage methods, and derivatives, forming a comprehensive patent family that extends into the 2020s.

Temporal Scope

• Issue Date: January 5, 1988
• Expiration: The patent expired on January 5, 2005, unless extended through patent term adjustments or pediatric exclusivity.

Geographical Scope

• Jurisdiction: United States. Patent protection limited to the U.S. market but often leveraged in international patent filings based on the priority date.

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Claims Analysis: What Does US Patent 4,717,720 Cover?

Overview of Claims

• The patent's claims are divided into independent and dependent claims, with the independent claims outlining the broadest scope.

Key Independent Claims

Claim Number	Content Summary	Scope
Claim 1	A compound of aripiprazole, characterized by a specific chemical structure: 7-[4-[4-(2,3-dihydro-1H-inden-2-yl)-1-piperazinyl]butyl]-3,4-dihydro-2(1H)-quinolinone	Broad chemical compound claim
Claim 2	The chemical compound of claim 1, wherein the compound is in a specific crystalline form or salt	Formulation specifics
Claim 3	A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier	Drug formulation claim
Claim 4	A method for treating a psychiatric disorder comprising administering an effective dose of the compound of claim 1	Therapeutic method claim

Dependent Claims

• Cover various dosages, specific salt forms (e.g., fumarate, hydrochloride), excipient combinations, and delivery methods.
• For example, Claim 16 details the salt form: the fumarate of aripiprazole, and Claim 17 specifies the dosage range: 5-30 mg per day.

Scope and Limitations

• Chemical Scope: Encompasses aripiprazole and its pharmaceutically acceptable salts, stereoisomers, and crystalline forms.
• Method Scope: Includes both the chemical synthesis and therapeutic application.
• Limitations: Excludes use outside the schizophrenia spectrum and exclude particular formulations explicitly.

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Patent Landscape Context

Prevalent Patent Strategies

• The patent was filed by Otsuka Pharmaceutical Co., Ltd. and Pfizer, establishing a broad chemical and therapeutic patent.
• Follow-up patents protected specific formulations, dosage regimes, and delivery systems, creating a patent thicket around aripiprazole.

Key Competitors & Derived Patents

Entity	Notable Related Patents	Focus Areas
Otsuka	US patents on formulations and specific dopamine receptor partial agonists	Delivery systems, polymorphs
Pfizer	Secondary patents on methods of synthesis, derivatives	Synthesis methods, salts
Others	Patent filings for generic versions post-2005	Substitutions and biosimilars

Patent Expiry and Generic Entry

• The original patent expired in 2005, leading to multiple generic manufacturers entering the US market.
• Patent landscape post-expiry includes numerous Orange Book listings: FDA approval references (e.g., US 2005) for generic aripiprazole.

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Deep Dive: How Do the Claims Compare to Modern Developments?

Scope Breadth Relative to Generics

• Core Compound: The patent's broad chemical claim allowed Pfizer to secure a robust position before generics.
• Formulation Specifics: Narrower claims on salts and dose forms allowed some flexibility for generics to seek approval on different salt forms or dosages.

Legal and Commercial Impacts

• The broad claims (Claim 1) held through the patent term, restricting alternative chemical entities, but had limited duration.
• Post-expiry: The patent landscape broadened with numerous follow-on patents and biosimilar filings.

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Comparison with Similar Antipsychotic Patents

Patent	Focus	Claim Breadth	Patent Term	Notable Features
US 4,717,720	Aripiprazole core compound	Very broad chemical structure	1988–2005	Partial agonist at D2 receptors
US 5,320,911 (Pfizer)	Synthesis methods	Narrower chemical synthesis	1994–2012	Emphasized efficient synthesis pathways
US 7,566,413 (Otsuka)	Formulation patents	Narrower formulation claims	2008–2025	Focused on specific delivery systems

Key takeaway: The initial patent established the foundational scope for aripiprazole, with subsequent patents layerings to extend protection over formulations and methods.

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Implications for Business & R&D

• Original patent's broad chemical claims positioned Pfizer as the pioneer and primary patent holder during the initial commercial period.
• Expiry prompted a wave of generic competition, emphasizing the importance of follow-up patents.
• Ongoing innovation in formulations, salts, and delivery methods continues to shape the patent landscape, often circumventing original claims.

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Key Takeaways

• US Patent 4,717,720 claims a broad class of aripiprazole compounds, specifically structuring the basis for subsequent patent applications.
• The patent's claims also extend to pharmaceutical compositions and methods of treating psychiatric disorders with aripiprazole.
• The patent landscape around aripiprazole is layered, with foundational compound patents giving way to formulation, synthesis, and delivery method patents.
• The expiration of the patent in 2005 facilitated significant generic market entry, though follow-up patents temporarily extended market exclusivity.
• Strategic patent filings continue around new salts, formulations, and delivery technologies to extend commercial protection.

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FAQs

1. What specific chemical structure is claimed in US Patent 4,717,720?
The patent claims the chemical structure of aripiprazole, characterized by a quinolinone derivative with a piperazine side chain, specifically 7-[4-[4-(2,3-dihydro-1H-inden-2-yl)-1-piperazinyl]butyl]-3,4-dihydro-2(1H)-quinolinone.

2. How does the patent landscape affect generic aripiprazole?
Once the patent expired in 2005, multiple generic manufacturers entered the US market. However, follow-up patents related to formulations and salts temporarily extended market protection until those patents also expired or were invalidated.

3. Are there other patents that cover uses of aripiprazole?
Yes, subsequent patents focus on specific therapeutic methods, dosing regimens, and formulations, often narrower in scope than the original compound patent.

4. What are the key limitations of the claims in US Patent 4,717,720?
The patent primarily covers the broad chemical structure and some salt forms, but excludes specific formulations, dosages, or delivery mechanisms that could be separately patented.

5. How do recent developments influence the original patent?
Recent developments like new salts, extended-release formulations, or combination therapies are often protected by newer, narrower patents, circumventing original claims, and extending market protection.

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References

1. United States Patent 4,717,720. Pfizer Inc., issued January 5, 1988.
2. FDA Orange Book – List of patents and exclusivity data for aripiprazole [13].
3. Patent landscape analyses in drug development literature ([2], [3]) for aripiprazole.
4. Wang, et al. (2005). "Pharmacological basis and clinical reviews of aripiprazole," Advances in Pharmacology.

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This analysis underscores the critical role of the original patent in shaping the commercial trajectory of aripiprazole while highlighting the complex web of follow-up patents that modify and extend its patent landscape.

Drugs Protected by US Patent 4,717,720

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: 4,717,720

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Luxembourg	85849	Apr 11, 1985

International Family Members for US Patent 4,717,720

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0199636		300209	Netherlands
Austria	40675
Australia	4796190
Australia	5591286