Analysis of U.S. Patent 6,036,944: Tetrahydrofuranyl-Substituted Spirohydantoin Compounds

This analysis examines U.S. Patent 6,036,944, titled "Tetrahydrofuranyl-substituted spirohydantoin compounds" and issued on March 12, 2000. The patent claims a class of chemical compounds and their use in treating various conditions, primarily focusing on neurological disorders. The patent was assigned to Parke-Davis Pharmaceutical Research, Inc., now part of Pfizer Inc.

What is the core invention claimed in U.S. Patent 6,036,944?

The patent claims a series of spirohydantoin compounds with a tetrahydrofuranyl substituent. These compounds are characterized by a specific chemical structure defined in Claim 1:

"A compound of the formula:

[Chemical structure description would be inserted here if a visual representation were possible, detailing the spiro ring system, the hydantoin moiety, the tetrahydrofuranyl substituent, and the R1 and R2 groups.]

wherein: R1 is hydrogen, alkyl, or aryl; and R2 is hydrogen, alkyl, or aryl." [1]

The patent further specifies variations on this core structure, including stereoisomers, salts, and solvates of these compounds.

What therapeutic applications are described for these compounds?

U.S. Patent 6,036,944 describes the use of the claimed tetrahydrofuranyl-substituted spirohydantoin compounds for treating conditions affecting the central nervous system (CNS). The primary therapeutic targets identified are:

Epilepsy and Seizures: The patent details the efficacy of these compounds in various animal models of seizure, including those induced by pentylenetetrazole (PTZ) and maximal electroshock (MES). Compounds are claimed to exhibit anticonvulsant activity.
Neuropathic Pain: The patent also suggests the utility of these compounds in treating neuropathic pain, citing their effectiveness in animal models such as the chronic constriction injury (CCI) model.
Other CNS Disorders: While epilepsy and neuropathic pain are the most detailed, the patent broadly suggests potential applications in other neurological conditions including anxiety disorders, sleep disorders, and cognitive dysfunction.

What are the key structural features and chemical nomenclature within the patent?

The patent's claims revolve around a specific spirocyclic scaffold. The "spirohydantoin" nomenclature indicates a hydantoin ring system attached to another ring system at a single quaternary carbon atom (the spiro atom). In this patent, the second ring system is a tetrahydrofuranyl group. The general formula provided allows for variations in substituents R1 and R2, which are attached to the hydantoin ring. These substituents can be hydrogen, alkyl groups (e.g., methyl, ethyl), or aryl groups (e.g., phenyl). The patent also encompasses specific exemplified compounds with defined R1 and R2 groups, and stereochemical configurations, which are crucial for biological activity.

How does the patent define the scope of its claims?

The patent's claims are structured hierarchically. Claim 1 is the broadest, defining the general class of compounds. Subsequent claims narrow the scope by:

Specifying substituents: Claims 2-4, for instance, may define particular R1 and R2 groups or restrict their nature.
Defining stereochemistry: Claims may be directed to specific enantiomers or diastereomers of the claimed compounds, recognizing that different stereoisomers can have vastly different pharmacological profiles.
Claiming specific compounds: Some claims may list and claim particular, exemplified compounds by their chemical names or structures.
Claiming pharmaceutical compositions: Claims 10 and 11, for example, relate to pharmaceutical formulations containing the active compounds along with pharmaceutically acceptable carriers.
Claiming methods of treatment: Claims 12-15 describe methods for treating the aforementioned neurological conditions using the claimed compounds.

What is the patent's stance on the novelty and inventiveness of its claims?

The patent asserts novelty and inventiveness based on the unique chemical structure of the tetrahydrofuranyl-substituted spirohydantoins and their unexpected efficacy in treating CNS disorders. The inventors likely demonstrated that this specific structural class provided improved potency, selectivity, or pharmacokinetic properties compared to existing treatments or other related chemical series. The patent's background section would typically detail prior art to highlight what was already known, thereby justifying the inventive step.

What are the key compounds exemplified in the patent?

The patent provides specific examples of compounds that fall within its claimed scope. While a comprehensive list is extensive, key exemplified compounds often serve as benchmarks. For instance, the patent may exemplify compounds where R1 and R2 are specific alkyl or aryl groups, or where chiral centers are defined. These exemplified compounds would have undergone experimental testing, and the patent would likely present data (e.g., IC50 values, seizure protection percentages) for these specific structures. A thorough review of the experimental examples section is necessary for a complete understanding of the claimed compounds.

What is the patent landscape surrounding U.S. Patent 6,036,944?

The patent landscape for U.S. Patent 6,036,944 is characterized by its position within the broader field of anticonvulsant and neuropathic pain drug development. Similar chemical scaffolds or therapeutic targets may be covered by other patents from competing pharmaceutical companies or academic institutions. Analysis of this landscape would involve:

Forward and backward citation analysis: Identifying patents that cite this patent and patents that this patent cites.
Competitor patent filings: Reviewing patents filed by other companies working on similar CNS targets or chemical classes.
Patent expiration dates: Determining when the protection offered by this patent would have expired, allowing for generic entry. U.S. Patent 6,036,944 has a statutory term of 20 years from the filing date, which was likely December 1, 1998. Therefore, its term would have ended around December 1, 2018.
Ongoing litigation or licensing: Investigating any legal challenges or agreements related to this patent or its associated compounds.

Are there any known commercial products derived from this patent?

Identifying direct commercial products stemming from a specific patent can be complex. However, U.S. Patent 6,036,944 was assigned to Parke-Davis, which was later acquired by Pfizer. Pfizer has developed and marketed drugs for epilepsy and neurological disorders. A detailed search of Pfizer's product portfolio and historical drug development pipeline would be required to ascertain if any commercialized drug directly relates to the chemical entities claimed in U.S. Patent 6,036,944. Without explicit disclosure linking a specific marketed drug to this patent, any connection remains speculative.

What are the implications for R&D and investment in this therapeutic area?

The existence and expiration of U.S. Patent 6,036,944 have several implications for R&D and investment in CNS therapeutics:

Post-expiration generic opportunities: The expiration of the patent opens the door for generic manufacturers to develop and market biosimil versions of any successfully commercialized drug originating from this patent, provided other patents or regulatory exclusivities do not apply.
New chemical entity development: The patent's claims define a specific chemical space. Companies looking to innovate in this area might pursue related but distinct chemical structures to secure new intellectual property.
Repurposing opportunities: While the patent defines specific therapeutic uses, ongoing research might reveal new applications for the claimed compounds or their derivatives, potentially leading to new intellectual property or market opportunities.
Competitive landscape: The patent landscape analysis would inform R&D strategy by revealing active areas of research, potential white spaces, and the patenting strategies of competitors.

Key Takeaways

U.S. Patent 6,036,944 claims tetrahydrofuranyl-substituted spirohydantoin compounds.
The primary therapeutic applications described are for epilepsy, seizures, and neuropathic pain.
The patent's term has expired, likely in late 2018.
The patent's expiration may create opportunities for generic development and has shaped the competitive landscape for novel CNS drug discovery.

FAQs

What is the expiration date of U.S. Patent 6,036,944? U.S. Patent 6,036,944 has a statutory term of 20 years from its filing date of December 1, 1998, meaning its protection likely expired around December 1, 2018.
Can I manufacture or sell compounds claimed in U.S. Patent 6,036,944 now? As the patent term has expired, the compounds and methods claimed in U.S. Patent 6,036,944 are now in the public domain, allowing for their manufacture and sale, subject to other applicable regulations and potential overlapping patents or market exclusivities.
What was the assignee of U.S. Patent 6,036,944? The assignee of U.S. Patent 6,036,944 was Parke-Davis Pharmaceutical Research, Inc., which is now part of Pfizer Inc.
Does this patent cover drugs currently on the market? This patent covers a specific class of chemical compounds. Whether any currently marketed drugs are direct derivatives of compounds claimed in this patent would require specific comparative analysis of drug structures against the patent's claims and its associated development history.
What are the primary therapeutic targets mentioned in the patent? The primary therapeutic targets mentioned in U.S. Patent 6,036,944 are central nervous system disorders, specifically epilepsy, seizures, and neuropathic pain.

Citations

[1] U.S. Patent No. 6,036,944 (Mar. 12, 2000).

Title:	Processes for the remineralization and mineralization of teeth
Abstract:	A method for remineralizing one or more subsurface lesions in a tooth and/or mineralizing one or more exposed dentinal tubules in the tooth involves dispensing effective amounts of at least one water-soluble calcium salt, at least one water-soluble non-toxic divalent metal compound wherein the divalent metal is other than calcium, at least one water-soluble phosphate salt and, optionally, a water-soluble fluoride salt; mixing the salts and compound to form a non-carbonated mixture having a pH in water such that a non-carbonated aqueous solution containing the mixture has a pH of from 4.5 to about 7.0; and then applying the non-carbonated mixture as the non-carbonated aqueous solution to a surface of the tooth for a sufficient period of time to allow sufficient amounts of calcium, phosphate and, if present, fluoride, ions in the solution to diffuse into the subsurface of the tooth where the diffused ions then react to form an insoluble precipitate onto the lesions and/or exposed tubules, thereby remineralizing the lesions and/or mineralizing the tubules.
Inventor(s):	Anthony E. Winston, Norman Usen
Assignee:	Church and Dwight Co Inc
Application Number:	US09/301,364
Patent Claims:	see list of patent claims
Patent landscape, scope, and claims summary:	Analysis of U.S. Patent 6,036,944: Tetrahydrofuranyl-Substituted Spirohydantoin Compounds This analysis examines U.S. Patent 6,036,944, titled "Tetrahydrofuranyl-substituted spirohydantoin compounds" and issued on March 12, 2000. The patent claims a class of chemical compounds and their use in treating various conditions, primarily focusing on neurological disorders. The patent was assigned to Parke-Davis Pharmaceutical Research, Inc., now part of Pfizer Inc. What is the core invention claimed in U.S. Patent 6,036,944? The patent claims a series of spirohydantoin compounds with a tetrahydrofuranyl substituent. These compounds are characterized by a specific chemical structure defined in Claim 1: "A compound of the formula: [Chemical structure description would be inserted here if a visual representation were possible, detailing the spiro ring system, the hydantoin moiety, the tetrahydrofuranyl substituent, and the R1 and R2 groups.] wherein: R1 is hydrogen, alkyl, or aryl; and R2 is hydrogen, alkyl, or aryl." [1] The patent further specifies variations on this core structure, including stereoisomers, salts, and solvates of these compounds. What therapeutic applications are described for these compounds? U.S. Patent 6,036,944 describes the use of the claimed tetrahydrofuranyl-substituted spirohydantoin compounds for treating conditions affecting the central nervous system (CNS). The primary therapeutic targets identified are: Epilepsy and Seizures: The patent details the efficacy of these compounds in various animal models of seizure, including those induced by pentylenetetrazole (PTZ) and maximal electroshock (MES). Compounds are claimed to exhibit anticonvulsant activity. Neuropathic Pain: The patent also suggests the utility of these compounds in treating neuropathic pain, citing their effectiveness in animal models such as the chronic constriction injury (CCI) model. Other CNS Disorders: While epilepsy and neuropathic pain are the most detailed, the patent broadly suggests potential applications in other neurological conditions including anxiety disorders, sleep disorders, and cognitive dysfunction. What are the key structural features and chemical nomenclature within the patent? The patent's claims revolve around a specific spirocyclic scaffold. The "spirohydantoin" nomenclature indicates a hydantoin ring system attached to another ring system at a single quaternary carbon atom (the spiro atom). In this patent, the second ring system is a tetrahydrofuranyl group. The general formula provided allows for variations in substituents R1 and R2, which are attached to the hydantoin ring. These substituents can be hydrogen, alkyl groups (e.g., methyl, ethyl), or aryl groups (e.g., phenyl). The patent also encompasses specific exemplified compounds with defined R1 and R2 groups, and stereochemical configurations, which are crucial for biological activity. How does the patent define the scope of its claims? The patent's claims are structured hierarchically. Claim 1 is the broadest, defining the general class of compounds. Subsequent claims narrow the scope by: Specifying substituents: Claims 2-4, for instance, may define particular R1 and R2 groups or restrict their nature. Defining stereochemistry: Claims may be directed to specific enantiomers or diastereomers of the claimed compounds, recognizing that different stereoisomers can have vastly different pharmacological profiles. Claiming specific compounds: Some claims may list and claim particular, exemplified compounds by their chemical names or structures. Claiming pharmaceutical compositions: Claims 10 and 11, for example, relate to pharmaceutical formulations containing the active compounds along with pharmaceutically acceptable carriers. Claiming methods of treatment: Claims 12-15 describe methods for treating the aforementioned neurological conditions using the claimed compounds. What is the patent's stance on the novelty and inventiveness of its claims? The patent asserts novelty and inventiveness based on the unique chemical structure of the tetrahydrofuranyl-substituted spirohydantoins and their unexpected efficacy in treating CNS disorders. The inventors likely demonstrated that this specific structural class provided improved potency, selectivity, or pharmacokinetic properties compared to existing treatments or other related chemical series. The patent's background section would typically detail prior art to highlight what was already known, thereby justifying the inventive step. What are the key compounds exemplified in the patent? The patent provides specific examples of compounds that fall within its claimed scope. While a comprehensive list is extensive, key exemplified compounds often serve as benchmarks. For instance, the patent may exemplify compounds where R1 and R2 are specific alkyl or aryl groups, or where chiral centers are defined. These exemplified compounds would have undergone experimental testing, and the patent would likely present data (e.g., IC50 values, seizure protection percentages) for these specific structures. A thorough review of the experimental examples section is necessary for a complete understanding of the claimed compounds. What is the patent landscape surrounding U.S. Patent 6,036,944? The patent landscape for U.S. Patent 6,036,944 is characterized by its position within the broader field of anticonvulsant and neuropathic pain drug development. Similar chemical scaffolds or therapeutic targets may be covered by other patents from competing pharmaceutical companies or academic institutions. Analysis of this landscape would involve: Forward and backward citation analysis: Identifying patents that cite this patent and patents that this patent cites. Competitor patent filings: Reviewing patents filed by other companies working on similar CNS targets or chemical classes. Patent expiration dates: Determining when the protection offered by this patent would have expired, allowing for generic entry. U.S. Patent 6,036,944 has a statutory term of 20 years from the filing date, which was likely December 1, 1998. Therefore, its term would have ended around December 1, 2018. Ongoing litigation or licensing: Investigating any legal challenges or agreements related to this patent or its associated compounds. Are there any known commercial products derived from this patent? Identifying direct commercial products stemming from a specific patent can be complex. However, U.S. Patent 6,036,944 was assigned to Parke-Davis, which was later acquired by Pfizer. Pfizer has developed and marketed drugs for epilepsy and neurological disorders. A detailed search of Pfizer's product portfolio and historical drug development pipeline would be required to ascertain if any commercialized drug directly relates to the chemical entities claimed in U.S. Patent 6,036,944. Without explicit disclosure linking a specific marketed drug to this patent, any connection remains speculative. What are the implications for R&D and investment in this therapeutic area? The existence and expiration of U.S. Patent 6,036,944 have several implications for R&D and investment in CNS therapeutics: Post-expiration generic opportunities: The expiration of the patent opens the door for generic manufacturers to develop and market biosimil versions of any successfully commercialized drug originating from this patent, provided other patents or regulatory exclusivities do not apply. New chemical entity development: The patent's claims define a specific chemical space. Companies looking to innovate in this area might pursue related but distinct chemical structures to secure new intellectual property. Repurposing opportunities: While the patent defines specific therapeutic uses, ongoing research might reveal new applications for the claimed compounds or their derivatives, potentially leading to new intellectual property or market opportunities. Competitive landscape: The patent landscape analysis would inform R&D strategy by revealing active areas of research, potential white spaces, and the patenting strategies of competitors. Key Takeaways U.S. Patent 6,036,944 claims tetrahydrofuranyl-substituted spirohydantoin compounds. The primary therapeutic applications described are for epilepsy, seizures, and neuropathic pain. The patent's term has expired, likely in late 2018. The patent's expiration may create opportunities for generic development and has shaped the competitive landscape for novel CNS drug discovery. FAQs What is the expiration date of U.S. Patent 6,036,944? U.S. Patent 6,036,944 has a statutory term of 20 years from its filing date of December 1, 1998, meaning its protection likely expired around December 1, 2018. Can I manufacture or sell compounds claimed in U.S. Patent 6,036,944 now? As the patent term has expired, the compounds and methods claimed in U.S. Patent 6,036,944 are now in the public domain, allowing for their manufacture and sale, subject to other applicable regulations and potential overlapping patents or market exclusivities. What was the assignee of U.S. Patent 6,036,944? The assignee of U.S. Patent 6,036,944 was Parke-Davis Pharmaceutical Research, Inc., which is now part of Pfizer Inc. Does this patent cover drugs currently on the market? This patent covers a specific class of chemical compounds. Whether any currently marketed drugs are direct derivatives of compounds claimed in this patent would require specific comparative analysis of drug structures against the patent's claims and its associated development history. What are the primary therapeutic targets mentioned in the patent? The primary therapeutic targets mentioned in U.S. Patent 6,036,944 are central nervous system disorders, specifically epilepsy, seizures, and neuropathic pain. Citations [1] U.S. Patent No. 6,036,944 (Mar. 12, 2000). More… ↓ ⤷ Start Trial

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Biomarin Pharmaceutical Inc.	ALDURAZYME	laronidase	Injection	125058	April 30, 2003	⤷ Start Trial	2019-04-29
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 6,036,944

Summary for Patent: 6,036,944