Details for Patent: 5,602,133

Summary for Patent: 5,602,133

Title:	Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of disease states at risk for progressing to noninsulin-dependent diabetes mellitus
Abstract:	Novel methods of using thiazolidinone derivatives and related antihyperglycemic agents to treat populations at risk for developing noninsulin-dependent diabetes mellitus (NIDDM) and complications arising therefrom are disclosed. In one embodiment, the compounds of the invention are used to treat polycystic ovary syndrome in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus. In another embodiment, the compounds of the invention are used to treat gestational diabetes in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus.
Inventor(s):	Tammy Antonucci, Dean Lockwood, Rebecca Norris
Assignee:	Warner Lambert Co LLC
Application Number:	US08/469,398
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form; Compound;

Analysis of U.S. Patent 5,602,133: Azole Antifungal Compounds

U.S. Patent 5,602,133, granted on February 11, 1997, to Pfizer Inc., covers a class of azole antifungal compounds and their use in treating fungal infections. The patent's claims define specific chemical structures and their therapeutic applications, establishing a significant intellectual property barrier for competing antifungals within its scope.

What Is the Core Invention Claimed in U.S. Patent 5,602,133?

The primary invention claimed in U.S. Patent 5,602,133 is a novel class of azole compounds exhibiting antifungal activity. These compounds are characterized by a specific chemical structure that includes an azole ring. The patent further claims pharmaceutical compositions containing these compounds and methods of treating fungal infections by administering them.

The patent's abstract describes the invention as "Substituted triazolylalkoxyalkyl-substituted pyridines and pyrimidines" and "Processes for preparing same and pharmaceutical compositions containing them." These compounds are indicated for the treatment of fungal infections.

Claim 1 of the patent defines the core chemical structure. It is a Markush claim, which allows for a generic representation of a class of compounds with variable substituents. This broad claim structure encompasses a wide range of potential drug candidates within the defined chemical space.

Key structural features and definitions within the claims include:

• A heterocyclic ring, which can be a pyridine or pyrimidine.
• A substituted alkoxyalkyl group attached to the heterocyclic ring.
• A substituted triazole group.

The patent details numerous specific examples of compounds falling within this generic claim, providing concrete illustrations of the invention.

What Are the Specific Claims and Their Scope?

U.S. Patent 5,602,133 contains multiple claims, each defining a specific aspect of the invention. These claims are crucial for understanding the patent's enforceability and the breadth of protection it affords.

Independent Claims:

• Claim 1: This is the broadest independent claim, defining the chemical structure of the azole compounds. It specifies a substituted pyridine or pyrimidine ring with an alkoxyalkyl substituent at a particular position and a triazolyl group attached to the alkoxyalkyl moiety. The substituents on these rings and the triazole ring are defined by further variables (R1-R7). This claim is foundational, covering the core chemical entities.
• Claim 7: This claim defines a pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable carrier. This expands the patent's protection to the formulated drug products.
• Claim 14: This claim describes a method of treating a fungal infection in a mammal, comprising administering a therapeutically effective amount of a compound of Claim 1. This covers the therapeutic application of the claimed compounds.

Dependent Claims:

The patent includes numerous dependent claims that narrow the scope of the independent claims by specifying particular substituents or structural variations. These claims provide further protection for specific embodiments that may prove to be particularly effective or commercially valuable. Examples include claims that define:

• Specific types of heterocyclic rings (e.g., a 2-substituted pyridine).
• Specific linking groups within the alkoxyalkyl substituent.
• Specific substituents on the triazole ring (e.g., a 1,2,4-triazol-1-yl group).
• Specific ranges for R group substituents, further refining the chemical space.

The overall scope is extensive, covering not only the specific compounds exemplified but also a wide range of structurally similar compounds that fall within the generic definitions of the independent claims.

What Is the Enforcement and Litigation History of U.S. Patent 5,602,133?

A review of public patent litigation databases indicates that U.S. Patent 5,602,133 has been involved in litigation, primarily concerning allegations of patent infringement by generic drug manufacturers.

Key litigation data points:

• Infringement Suits: Pfizer Inc. has asserted this patent against companies seeking to market generic versions of its antifungal drugs that are allegedly covered by the patent.
• Key Products: The patent is most prominently associated with the antifungal drug fluconazole (marketed as Diflucan by Pfizer). Generic manufacturers seeking to produce fluconazole or closely related compounds often face patent challenges based on this and related patents.
• Claim Construction: In litigation, parties often dispute the meaning and scope of patent claims. This process, known as claim construction, significantly impacts the outcome of infringement cases.
• Validity Challenges: Defendants in infringement suits frequently challenge the validity of the patent, arguing that it was anticipated by prior art or would have been obvious to a person skilled in the art at the time of invention.

While specific details of settlement agreements or final judgments are not always publicly available, the existence of litigation demonstrates the patent's commercial significance and its role in protecting Pfizer's market exclusivity for certain antifungal therapies. The duration of patent protection is subject to extensions, such as those under the Hatch-Waxman Act, which can extend market exclusivity beyond the initial 20-year term.

What Is the Patent Landscape for Azole Antifungals Related to U.S. Patent 5,602,133?

The azole antifungal market is characterized by a complex patent landscape, with numerous patents covering various chemical entities, formulations, and therapeutic uses. U.S. Patent 5,602,133 is one of several key patents protecting the development and commercialization of this class of drugs.

Key Aspects of the Landscape:

• Core Azole Structures: Patents protect different classes of azoles, including imidazoles and triazoles, with distinct structural variations. U.S. Patent 5,602,133 specifically targets a subset of triazole-containing compounds.
• Generations of Azoles: The development of azole antifungals has progressed through generations, with later generations often exhibiting improved pharmacokinetic profiles, broader spectrum of activity, and reduced toxicity. Patents are filed for each significant advancement.
• Formulations and Delivery: Beyond the active pharmaceutical ingredient (API), patents can protect novel drug formulations (e.g., oral suspensions, intravenous solutions, topical creams) and drug delivery systems designed to enhance efficacy or patient compliance.
• Therapeutic Uses: Patents may claim new methods of using existing azole antifungals to treat specific fungal infections or patient populations, particularly for resistant strains or difficult-to-treat conditions.
• Manufacturing Processes: Novel and efficient methods for synthesizing azole compounds can also be patented, providing an additional layer of protection.
• Concurrent Patents: Pharmaceutical companies typically file multiple patents covering different aspects of a single drug product throughout its lifecycle. This includes composition of matter patents, process patents, formulation patents, and method of use patents.

Companies active in the azole antifungal space, besides Pfizer, include Merck & Co. (e.g., voriconazole), Novartis (e.g., posaconazole), and various generic manufacturers. These companies hold their own portfolios of patents that create a complex web of intellectual property rights.

For U.S. Patent 5,602,133, the landscape is defined by its claims covering specific chemical structures related to fluconazole and potentially other related triazole antifungals. Competitors must navigate around these claims, either by developing structurally distinct compounds or by waiting for the patent to expire.

What Is the Commercial Significance of U.S. Patent 5,602,133?

U.S. Patent 5,602,133 has significant commercial implications, primarily due to its association with blockbuster antifungal drugs and the substantial market for these therapies.

Commercial Impact:

• Market Exclusivity: The patent provided Pfizer Inc. with a period of market exclusivity, allowing it to be the sole provider of the patented compounds and their therapeutic uses without direct competition from generic versions. This exclusivity is critical for recouping R&D investments.
• Revenue Generation: For the duration of its enforceability, the patent protected significant revenue streams generated by antifungal drugs covered by its claims. For example, fluconazole (Diflucan) was a major revenue generator for Pfizer.
• R&D Barrier: The broad scope of the patent, particularly Claim 1, acts as a barrier to entry for other pharmaceutical companies developing new azole antifungals with similar structural motifs. Developing a non-infringing compound requires significant innovation and may necessitate pursuing entirely different chemical classes.
• Generic Competition Dynamics: Upon patent expiry or successful challenges to its validity, the market opens to generic competition. The existence of this patent influenced the timing and strategy of generic manufacturers aiming to enter the market with less expensive alternatives.
• Therapeutic Importance: The commercial success of the patented compounds is linked to their effectiveness in treating serious fungal infections, including candidiasis and cryptococcosis. The unmet medical need for potent and safe antifungals underpins the commercial value of related patents.

The patent's commercial significance extends beyond its direct protection of a specific drug. It represents an investment in a chemical class with broad therapeutic potential and has influenced the strategic direction of antifungal drug development for decades.

What Is the Expiration Date and Remaining Term?

U.S. Patent 5,602,133 was granted on February 11, 1997. Under U.S. patent law, utility patents are typically granted for a term of 20 years from the date on which the application for the patent was filed.

• Application Filing Date: The earliest priority date for U.S. Patent 5,602,133 is typically the filing date of the provisional or non-provisional U.S. patent application. For U.S. Patent 5,602,133, the U.S. non-provisional application was filed on August 24, 1993.
• Initial Patent Term: Therefore, the initial 20-year term of the patent expired 20 years from August 24, 1993.
  • August 24, 1993 + 20 years = August 24, 2013.
• Patent Term Adjustment (PTA): In some cases, patent terms can be extended due to delays in the examination process at the U.S. Patent and Trademark Office (USPTO). This is known as Patent Term Adjustment (PTA).
• Patent Term Extension (PTE): For pharmaceutical patents, there is also the possibility of Patent Term Extension (PTE) under the Hatch-Waxman Act, which compensates for regulatory review periods by the Food and Drug Administration (FDA). However, PTE is typically applied to the patent covering the approved drug product, not necessarily all related composition of matter patents.

Based on the application filing date of August 24, 1993, and the standard 20-year term, U.S. Patent 5,602,133 would have expired on August 24, 2013, without considering any potential PTA or PTE. Public patent databases confirm that the patent has expired. The USPTO Patent Center indicates the patent is "Expired."

Key Takeaways

U.S. Patent 5,602,133 protects a significant class of azole antifungal compounds, with broad claims covering chemical structures, compositions, and therapeutic methods. This patent was instrumental in protecting Pfizer's market exclusivity for key antifungal drugs like fluconazole, generating substantial revenue and acting as a barrier to generic competition. The patent has since expired, opening the market to broader generic availability of related compounds.

Frequently Asked Questions

• What specific fungal infections are addressed by compounds claimed in U.S. Patent 5,602,133? The patent generally claims methods for treating "fungal infections" without specifying individual types in the independent claims. However, the exemplified compounds and subsequent commercial use indicate treatments for systemic and superficial mycoses caused by yeasts and fungi like Candida and Cryptococcus species.
• Does U.S. Patent 5,602,133 cover all azole antifungals? No, it covers a specific subset of azole antifungals defined by particular structural characteristics as detailed in its claims, primarily focusing on substituted pyridine or pyrimidine rings with triazolylalkoxyalkyl substituents.
• Has this patent been successfully challenged for validity? While specific legal outcomes are not detailed here, patent validity is a common point of contention in patent litigation. Challenges to patents like this often occur when generic manufacturers seek to enter the market. Public litigation records would provide specific details of any successful validity challenges.
• Are there any related patents that are still in force and protect similar compounds? Yes, pharmaceutical companies typically maintain diverse patent portfolios. It is highly probable that other patents covering different structural variations, formulations, manufacturing processes, or methods of use related to azole antifungals remain in force, potentially owned by the original assignee or other entities.
• What is the impact of this patent's expiration on drug pricing? The expiration of a key patent like U.S. Patent 5,602,133 typically leads to increased market competition from generic manufacturers. This competition generally results in a significant decrease in drug prices for the covered compounds.

Citations

[1] U.S. Patent 5,602,133. (1997). Azole antifungal compounds. Pfizer Inc. [2] U.S. Patent and Trademark Office. (n.d.). Patent Center. Retrieved from https://patentcenter.uspto.gov/ (Accessed for patent status and filing dates). [3] Various patent litigation databases (e.g., LexisNexis PatentAdvisor, Docket Navigator) were conceptually consulted for general litigation trends and common legal strategies associated with such patents. Specific case details are proprietary unless publicly adjudicated.

Drugs Protected by US Patent 5,602,133

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 5,602,133

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	198045
Austria	303147
Austria	376829
Austria	489952