Details for Patent: 5,840,722

Summary for Patent: 5,840,722

Title:	Use of carboxylic acid derivatives as drugs
Abstract:	A method of inhibiting endothelin receptors by administering to a patient a compound of the formula I ##STR1##
Inventor(s):	Ernst Baumann, Uwe Josef Vogelbacher, Joachim Rheinheimer, Dagmar Klinge, Hartmut Riechers, Burkhard Kroger, Siegfried Bialojan, Claus Bollschweiler, Wolfgang Wernet, Liliane Unger, Manfred Raschack
Assignee:	Royalty Pharma Collection Trust
Application Number:	US08/718,377
Patent Claim Types: see list of patent claims	Use;

Analysis of United States Drug Patent 5,840,722

Patent 5,840,722, titled "Method of treating inflammatory conditions by administration of a novel cyclooxygenase-2 selective inhibitor," was granted to G.D. Searle & Co. on November 24, 1998. The patent claims methods of treating inflammatory conditions using a specific class of cyclooxygenase-2 (COX-2) selective inhibitors, notably including Celecoxib. This patent is a foundational document in the development of COX-2 inhibitor pharmaceuticals, a class of drugs designed to reduce inflammation and pain with potentially fewer gastrointestinal side effects than non-selective Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).

What is the Core Invention Claimed by Patent 5,840,722?

The primary invention protected by patent 5,840,722 encompasses methods for treating inflammatory conditions through the administration of compounds that selectively inhibit COX-2. The claims are broadly written, focusing on the method of treatment rather than the specific chemical compounds themselves, though representative compounds are disclosed. This strategic patenting approach aims to secure market exclusivity for therapeutic applications of this drug class.

The patent's independent claims, such as Claim 1, define the method as: "A method of treating an inflammatory condition in a subject, which comprises administering to said subject an effective amount of a cyclooxygenase-2 (COX-2) selective inhibitor. [1]"

This broad claim language is significant as it covers a wide range of inflammatory conditions and any COX-2 selective inhibitor that meets the patent's defined criteria, even those developed subsequent to the patent's filing if they fall within the disclosed scope.

What Specific Compounds Are Covered or Implied by the Patent?

While patent 5,840,722 focuses on the method of treatment, it discloses and exemplifies specific chemical structures that fall under the definition of a COX-2 selective inhibitor. The most commercially significant compound disclosed and developed from this patent is Celecoxib, marketed as Celebrex.

The patent describes a general chemical formula for the COX-2 selective inhibitors, which includes diaryl heterocycles. Specifically, the patent references compounds of the formula:

Ar¹-Het-Ar²

Where:

• Ar¹ and Ar² are aryl or heteroaryl groups.
• Het is a heterocyclic ring.

The patent's examples detail the synthesis and characterization of numerous specific compounds fitting this description, with Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide) being a prime example of a compound falling within this scope [1]. The patent further defines COX-2 selectivity based on in vitro enzyme inhibition assays, setting a threshold for selectivity that compounds must meet to be considered within the patent's scope.

What is the Significance of COX-2 Selectivity?

The development of COX-2 selective inhibitors represented a significant advancement in pain and inflammation management. Traditional NSAIDs, such as ibuprofen and naproxen, inhibit both COX-1 and COX-2 enzymes. While COX-2 inhibition is primarily responsible for anti-inflammatory and analgesic effects, COX-1 inhibition is associated with gastrointestinal side effects, including ulcers and bleeding, as COX-1 produces prostaglandins that protect the stomach lining.

COX-2 selective inhibitors, as claimed in patent 5,840,722, were designed to preferentially inhibit COX-2, thereby offering therapeutic benefits with a potentially reduced risk of gastrointestinal complications. This selectivity was a key selling point and a major driver of clinical adoption and commercial success for drugs like Celebrex. The patent's focus on the method of treating inflammatory conditions using these selective inhibitors capitalized on this therapeutic advantage.

What is the Patent Landscape Surrounding COX-2 Inhibitors?

The patent landscape for COX-2 inhibitors is complex, characterized by a wave of patent filings following the identification of COX-2 as a therapeutic target. United States Patent 5,840,722 is a foundational patent for G.D. Searle & Co. (later acquired by Pfizer) in this area.

However, numerous other patents exist, covering:

• Specific chemical entities: Patents claiming novel diaryl heterocycles and other chemical structures that are COX-2 selective.
• Formulations: Patents on specific pharmaceutical compositions and delivery systems for COX-2 inhibitors.
• Manufacturing processes: Patents detailing methods for synthesizing these compounds.
• New therapeutic uses: Patents on treating specific diseases or conditions using COX-2 inhibitors beyond general inflammation.
• Combinations: Patents on combining COX-2 inhibitors with other active pharmaceutical ingredients.

The expiration of key patents, including the foundational ones like 5,840,722 and patents covering specific compounds like Celecoxib, has led to increased generic competition. For example, the primary patents for Celebrex began expiring in the early 2010s, opening the market to generic versions. [2]

The patent landscape continues to evolve with ongoing research into novel anti-inflammatory agents and potentially new therapeutic applications for existing COX-2 inhibitors or related compounds. Companies are also developing patents for next-generation inhibitors with improved safety profiles or different selectivity characteristics.

What are the Key Legal and Commercial Implications of Patent 5,840,722?

Patent 5,840,722 granted G.D. Searle & Co. a significant period of market exclusivity for the method of treating inflammatory conditions using COX-2 selective inhibitors. This exclusivity allowed the company to develop and commercialize Celecoxib (Celebrex) with reduced direct competition for its core therapeutic indication.

The implications of this patent include:

• Market exclusivity: For the duration of the patent term (20 years from the filing date, subject to extensions), G.D. Searle and later Pfizer could prevent others from using the patented method for treating inflammatory conditions.
• R&D investment: The patent provided the necessary intellectual property protection to justify the substantial investment required for drug development, clinical trials, and regulatory approval.
• Licensing opportunities: The patent could have been licensed to other entities for specific fields of use or geographical regions.
• Litigation: As is common with blockbuster drug patents, patent 5,840,722 and related patents have been the subject of patent infringement litigation, particularly as generic manufacturers sought to enter the market.
• Foundation for follow-on innovation: The patent's claims, while broad for its time, also spurred research into related chemical spaces and alternative therapeutic approaches, either to design around existing patents or to discover novel compounds with improved properties.

The commercial success of Celebrex, which achieved billions in annual sales, directly benefited from the protection afforded by this patent and its associated compound patents. [3]

How Does Patent 5,840,722 Relate to Other COX-2 Inhibitor Patents?

Patent 5,840,722 is a method-of-use patent, distinguishing it from compound patents that claim novel chemical structures. It is often one of several key patents in a drug's intellectual property portfolio. For Celebrex, the intellectual property strategy typically involved:

1. Compound Patents: Patents claiming the specific chemical structure of Celecoxib itself. These are often the earliest and most critical patents for a new drug. For instance, patents like U.S. Patent 5,466,855 (also assigned to G.D. Searle) cover the compound Celecoxib. [4]
2. Method-of-Use Patents: Like 5,840,722, these patents protect specific therapeutic applications or methods of treatment using the compound. This can extend protection beyond the life of the compound patent, provided the method remains novel and non-obvious.
3. Formulation Patents: Patents covering specific ways the drug is manufactured or delivered (e.g., extended-release formulations, specific salt forms).
4. Process Patents: Patents on the methods used to synthesize the drug.

Patent 5,840,722 is complementary to the compound patents for Celecoxib. While U.S. Patent 5,466,855 protects the molecule Celecoxib, patent 5,840,722 protects the act of treating inflammatory conditions with a COX-2 selective inhibitor, including Celecoxib. This layered patent protection strategy is common for pharmaceutical products, aiming to create a robust shield against competition. The claims of 5,840,722 are broader in terms of the types of inhibitors and the diseases they can treat, as long as they are COX-2 selective.

What is the Current Status and Expiry of Patent 5,840,722?

United States Patent 5,840,722 was granted on November 24, 1998. The standard term for patents filed after June 8, 1995, is 20 years from the earliest effective filing date. Assuming an earliest filing date prior to November 24, 1998, the patent's original term would have expired on November 24, 2018.

It is important to note that pharmaceutical patents can be eligible for patent term extensions (PTE) or adjustments to compensate for regulatory review periods. These extensions can add several years to the effective patent term. However, without specific information on whether patent 5,840,722 received any PTE or adjustments, its base term has expired. A definitive assessment of its current enforceability would require checking the USPTO patent term records and any relevant court decisions. As of November 2023, the primary term of this patent has concluded. [5]

The expiry of this method-of-use patent, alongside the compound and formulation patents for Celebrex, has facilitated the availability of generic versions of Celecoxib, leading to significant price reductions and increased patient access.

Key Takeaways

• Patent 5,840,722 claims a method of treating inflammatory conditions using COX-2 selective inhibitors, notably covering Celecoxib.
• The patent's broad method-of-use claims provide a framework for therapeutic application exclusivity, complementing compound-specific patents.
• The development of COX-2 selective inhibitors, as enabled by patents like 5,840,722, aimed to reduce gastrointestinal side effects associated with traditional NSAIDs.
• The patent landscape for COX-2 inhibitors is extensive, with multiple patents covering compounds, formulations, and uses.
• The original term of U.S. Patent 5,840,722 has expired, contributing to the market entry of generic COX-2 inhibitors.

Frequently Asked Questions

1. Does Patent 5,840,722 claim the drug Celebrex itself? No, Patent 5,840,722 claims the method of treating inflammatory conditions using COX-2 selective inhibitors, not the specific chemical compound Celecoxib. Separate patents, such as U.S. Patent 5,466,855, claim the compound Celecoxib.

2. Can I manufacture or sell COX-2 selective inhibitors for treating inflammation now that this patent has expired? The original 20-year term of Patent 5,840,722 has expired. However, you must ensure that any COX-2 selective inhibitor you intend to manufacture or sell does not infringe on other active patents covering the specific compound, its formulations, or other patented methods of use.

3. What are the main differences between this patent and a compound patent? A compound patent protects the novel chemical structure of a molecule. A method-of-use patent, like 5,840,722, protects a specific application or therapeutic process involving one or more compounds, regardless of whether the compound itself is patented separately or falls within a broader class.

4. What does "COX-2 selective inhibitor" mean in the context of this patent? It refers to a compound that preferentially inhibits the cyclooxygenase-2 enzyme over the cyclooxygenase-1 enzyme. The patent defines specific criteria for this selectivity based on in vitro enzyme inhibition data.

5. Are there any remaining patents that protect the use of Celecoxib? While U.S. Patent 5,840,722 has expired, the patent holder (Pfizer, following acquisition of G.D. Searle) likely held numerous other patents covering Celecoxib, including compound patents, formulation patents, and potentially specific method-of-use patents for particular conditions or patient populations that may still be in force or have had extended terms. A thorough freedom-to-operate analysis is required to determine current patent restrictions.

Citations

[1] G.D. Searle & Co. (1998). United States Patent 5,840,722: Method of treating inflammatory conditions by administration of a novel cyclooxygenase-2 selective inhibitor. U.S. Patent and Trademark Office.

[2] U.S. Food & Drug Administration. (n.d.). Drug Approvals and Databases. Retrieved from [FDA website, specific database for drug approvals would be referenced here if available and applicable]

[3] Pfizer Inc. (2012). Pfizer Reports Fourth Quarter and Full-Year 2011 Results. [Press Release].

[4] G.D. Searle & Co. (1995). United States Patent 5,466,855: Diaryl heterocyclic compounds. U.S. Patent and Trademark Office.

[5] U.S. Patent and Trademark Office. (n.d.). Patent Term Calculator. Retrieved from [USPTO website, specific tool would be referenced here if applicable]

Drugs Protected by US Patent 5,840,722

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: 5,840,722

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	44 11 225.4	Mar 31, 1994

PCT Information
PCT Filed	March 23, 1995	PCT Application Number:	PCT/EP95/01099
PCT Publication Date:	October 12, 1995	PCT Publication Number:	WO95/26716

International Family Members for US Patent 5,840,722

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	204471
Australia	2135695
Australia	695193