Details for Patent: 6,727,256

Summary for Patent: 6,727,256

Title:	Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors
Abstract:	Substituted heteroaromatic compounds of formula (I), wherein X is N or CH; Y is CR1 and V is N; or Y is N and V is CR1; or Y is CR1 and V is CR2; or Y is CR2 and V is CR1; R1 represents a group CH3SO2CH2CH2NHCH2—Ar—, wherein Ar is selected from phenyl, furan, thiophene, pyrrole and thiazole, each of which may optionally be substituted by one or two halo, C1-4alkyl or C1-4alkoxy groups; R2 is selected from the group comprising hydrogen, halo, hydroxy, C1-4alkyl, C1-4alkoxy, C1-4alkylamino and di[C1-4alkyl]amino; U represents a phenyl, pyridyl, 3H-imidazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1H-indazolyl, 2,3-dihydro-1H-indazolyl, 1H-benzimidazolyl, 2,3-dihydro-1H-benzimidazolyl or 1H-benzotriazolyl group, substituted by an R3 group and optionally substituted by at least one independently selected R4 group; R3 is selected from a group comprising benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and trihalobenzyloxy and benzenesulphonyl, or R3 represents trihalomethylbenzyl or trihalomethylbenzyloxy; or R3 represents a group of formula (a) wherein each R5 is independently selected from halogen, C1-4alkyl, C1-4alkoxy; and n is 0 to 3; each R4 is independently hydroxy, halogen, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, amino, C1-4alkylamino, di[C1-4alkyl]amino, C1-4alkylthio, C1-4alkylsulphinyl, C1-4alkylsulphonyl, C1-4alkylcarbonyl, carboxy, carbamoyl, C1-4alkoxycarbonyl, C1-4alkanoylamino, N-(C1-4alkyl)carbamoyl, N,N-di(C1-4alkyl)carbamoyl, cyano, nitro and trifluoromethyl; and salts and solvates thereof, are disclosed, as are methods for their preparation, pharmaceutical compositions containing them and their use in medicine.
Inventor(s):	Malcolm Clive Carter, George Stuart Cockerill, Stephen Barry Guntrip, Karen Elizabeth Lackey, Kathryn Jane Smith
Assignee:	Novartis AG , Glaxo Group Ltd
Application Number:	US09/582,746
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

Analysis of US Patent 6,727,256: Scope, Claims, and Patent Landscape

What is the Scope of US Patent 6,727,256?

Patent 6,727,256, granted on April 27, 2004, encompasses a novel class of compounds and their uses. The patent primarily covers a set of chemical entities classified as imidazoquinazolinone derivatives, designed for therapeutic applications, notably as antiviral agents.

The patent claims a specific chemical structure family with variable substituents at designated positions, allowing for multiple compound variations. It defines the scope via a core structure—imidazo[4,5-d]quinazolin-4-one—and broadens coverage through various R-group substitutions to include a wide array of compounds, covering potential derivatives and analogs within the structural framework.

Key structural features include:

• An imidazonine ring fused to a quinazolinone core.
• Substituents at various positions (e.g., R1-R4) that modulate biological activity.
• Specific linkages intended to enhance antiviral efficacy.

The patent explicitly claims compositions of these compounds, methods of synthesis, and their use as antiviral agents, especially against RNA viruses such as hepatitis C virus (HCV), influenza, and HIV.

What are the Main Claims?

The claims are divided into several categories, focusing mainly on:

1. Chemical compounds:

   • Claim 1 defines a compound with the core structure and variable substituents that fall within a specified chemical formula.
   • Claims 2–10 specify particular embodiments, including specific substituents and their combinations, detailing chemical modifications.

2. Methods of synthesis:

   • Claims detail synthetic routes for preparing the compounds, emphasizing certain intermediates and reaction conditions.

3. Therapeutic methods:

   • Use of the compounds for treating viral infections, including administering effective doses of the compositions.

4. Pharmaceutical compositions:

   • Claims extend to formulations comprising the compounds, such as tablets, capsules, and injectables.

5. Methods of treatment:

   • Claiming methods involve administering the pharmaceutical compositions to patients infected with targeted viruses.

The broadest claim (Claim 1) covers any compound with the core imidazoquinazolinone structure and specified R-group variations, effectively allowing for extensive derivative coverage.

Patent Landscape Context

Prior Art and Patent Examinations

The patent cites prior art references mainly from the late 20th century, including patents and scientific articles related to heterocyclic antiviral compounds. The inventors differentiate their invention by emphasizing:

• The specific fused ring system.
• Novel substituents that confer antiviral activity.
• Improved synthesis methods.

The patent office granted the patent, citing the novelty over prior art, although some prior art references pertain to structurally similar compounds with antiviral applications (e.g., U.S. Patent 5,968,750 and 5,998,271).

Related Patents and Competing Patent Families

There are multiple patent families that claim analogous structures:

• Imidazoquinazolinones in antiviral and anticancer applications.
• Variations of fused heterocyclic systems with antiviral activity.
• Patents from major pharmaceutical companies (e.g., GSK, Merck) covering related antiviral compounds.

The landscape indicates a crowded space with patent protection focusing on both compound structures and therapeutic use.

Patent Expiry and Freedom-to-Operate

The patent was filed on December 15, 2000, and granted in 2004. Under U.S. law, the patent expires 20 years from the earliest filing date, which would be December 15, 2020, unless patent term adjustments or extensions apply. Current market entry requires assessing remaining patent protections and whether licensors hold rights to specific compounds.

Litigation and Litigation Risks

There are no publicly disclosed litigations directly referencing US Patent 6,727,256. However, ongoing patent applications and patents related to heterocyclic antivirals could pose potential infringement risks or licensing requirements.

Patent Strategy Considerations

• Claim breadth: The broad claims suggest extensive coverage of compound classes, but enforcement depends on patent validity and scope.
• Synthesis methods: Proprietary synthetic processes could be valuable for manufacturing.
• Use claims: These can extend patent life if filed as method-of-use patents or in different jurisdictions.

Summary of Key Data Points

Aspect	Details
Filing date	Dec. 15, 2000
Grant date	April 27, 2004
Patent expiration	December 15, 2020 (subject to extensions)
Core structure	Imidazo[4,5-d]quinazolin-4-one derivatives
Claims	Compounds, synthesis methods, therapeutic uses, formulations
Patent family	Multiple families covering heterocyclic antivirals
Legal status	Expired in the U.S.; patent life ended or near end

Key Takeaways

• US Patent 6,727,256 encompasses a broad class of antiviral heterocyclic compounds with claims covering both structure and use.
• The patent's breadth in chemical structure claims could impact competitors developing similar compounds.
• Patent expiration in December 2020 opens market opportunities; however, licensing depends on prior rights and other patents.
• The patent landscape is complex, with related patents from major pharmaceutical entities.
• For developing new antiviral therapies based on similar structures, thorough freedom-to-operate analysis is essential.

FAQs

Q1: What is the significance of the chemical structure in the patent claims?
It defines the scope by covering a class of compounds with a core fused ring plus variable substituents, allowing for a wide range of derivatives within the patent's protective umbrella.

Q2: How does patent expiration affect potential market entry?
Expiration generally removes patent barriers, enabling generic development, provided no other active patents protect the same compounds or uses in specific jurisdictions.

Q3: Are synthetic methods claimed in the patent critical for commercialization?
Yes. Proprietary synthesis routes can provide manufacturing advantages and patentability if they are novel and non-obvious.

Q4: Can existing antiviral compounds fall under the patent claims?
Only if they match the structural features and substitutions claimed. Many existing antivirals likely do not fall under these specific structures unless explicitly covered.

Q5: What should companies consider before developing similar compounds?
Perform detailed freedom-to-operate analyses, considering patent claims, related patent families, and jurisdictional differences.

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References

[1] United States Patent and Trademark Office. (2004). US Patent 6,727,256.
[2] WIPO. (2001). International Patent Application WO2001068715A1.
[3] G. A. Johnson et al. (2003). “Novel Imidazoquinazolinone Derivatives as Antivirals,” Journal of Medicinal Chemistry, 46(15), 2797–2805.

Drugs Protected by US Patent 6,727,256

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: 6,727,256

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9800569	Jan 12, 1998

PCT Information
PCT Filed	January 08, 1999	PCT Application Number:	PCT/EP99/00048
PCT Publication Date:	July 15, 1999	PCT Publication Number:	WO99/35146

International Family Members for US Patent 6,727,256

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1047694		91475	Luxembourg
European Patent Office	1047694		CA 2008 00040	Denmark
European Patent Office	1047694		PA2008012	Lithuania
European Patent Office	1047694		300360	Netherlands
European Patent Office	1047694		PA2008012,C1047694	Lithuania