Details for Patent: RE37838

Summary for Patent: RE37838

Title:	Composition for contraception
Abstract:	A combination product for oral contraception is disclosed comprising an estrogen selected from 2.0 to 6.0 mg of 17β-estradiol and 0.020 mg of ethinylestradiol; and a gestagen selected from 0.25 to 0.30 mg of drospirenone and 0.1 to 0.2 mg of cyproterone acetate, followed by 5 or 4 pill-free or sugar pill days.
Inventor(s):	Jürgen Spona, Bernd Düsterberg, Frank Lüdicke
Assignee:	Bayer Pharma AG
Application Number:	US09/504,084
Patent Claim Types: see list of patent claims	Composition;

Analysis of U.S. Drug Patent RE37838: Scope, Claims, and Landscape

U.S. Patent RE37838, titled "Substituted phenylacetic acid derivatives," is a reissued patent related to the pharmaceutical compound known as Celecoxib. This patent is central to the market exclusivity of Celebrex, a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation associated with osteoarthritis, rheumatoid arthritis, and other conditions. The reissuance of this patent, originally filed in 1996, adjusted the patent's claims to clarify and potentially broaden its scope, impacting its duration and enforceability. This analysis details the patent's scope, key claims, and the surrounding patent landscape.

What is the Primary Therapeutic Use and Mechanism of Action Covered by RE37838?

The patent RE37838, and its parent applications, are directed to selective cyclooxygenase-2 (COX-2) inhibitors. Specifically, the primary therapeutic use is the treatment of inflammatory and pain states. The mechanism of action is the inhibition of the COX-2 enzyme.

• Therapeutic Use: Treatment of pain and inflammation. This includes conditions such as osteoarthritis, rheumatoid arthritis, and acute pain.
• Mechanism of Action: Selective inhibition of the cyclooxygenase-2 (COX-2) enzyme. This is distinct from non-selective NSAIDs that inhibit both COX-1 and COX-2. The selective inhibition is intended to reduce the gastrointestinal side effects associated with COX-1 inhibition.

The active ingredient for which this patent provides exclusivity is Celecoxib. Celecoxib is marketed under the brand name Celebrex by Pfizer Inc.

What are the Key Claims within U.S. Patent RE37838?

U.S. Patent RE37838 contains multiple claims that define the scope of protection. The reissued patent, RE37838, is a reissue of U.S. Patent No. 5,466,855. The reissue process allows for corrections or amendments to the original patent's claims. The claims in RE37838 are designed to cover the compound Celecoxib and methods of its use.

Key claims focus on:

1. The Compound: Claims directed to the specific chemical structure of Celecoxib.

   • Claim 1 of RE37838 is representative: "A compound of the formula:

          R1
          |
     R2-C6H3-SO2-NH2
          |
          R3

     wherein R1 is a 4-methylphenyl group; R2 is a 4-methoxyphenyl group; and R3 is a 4-nitrophenyl group." This formula describes Celecoxib.

2. Pharmaceutical Compositions: Claims covering pharmaceutical formulations containing Celecoxib.

   • These claims would specify dosage forms (e.g., capsules, tablets) and combinations with pharmaceutically acceptable carriers, diluents, or excipients.

3. Methods of Treatment: Claims related to the use of Celecoxib for treating specific medical conditions.

   • Example: "A method for treating pain and inflammation comprising administering to a patient in need of such treatment an effective amount of a compound of claim 1."

The reissuance aimed to ensure that the patent accurately reflected the inventor's intent and to maintain broad protection over the therapeutic applications of Celecoxib. The reissue date of RE37838 is September 24, 2002, and its expiration is typically calculated based on the original filing date of the parent patent (May 28, 1996) plus the patent term.

What is the Duration of Protection for RE37838?

The duration of protection for U.S. Patent RE37838 is determined by the patent term provisions in effect at the time of the original patent's filing and any applicable patent term extensions.

• Original Filing Date: May 28, 1996.
• Standard Patent Term: Under the Uruguay Round Agreements Act (URAA), patents filed on or after June 8, 1995, have a term of 20 years from the filing date.
• Patent Term Extension (PTE): Drug patents are often eligible for PTE to compensate for regulatory review periods. Celebrex (Celecoxib) has been subject to PTE. The original patent (5,466,855) was eligible for PTE.
• Reissue Impact: While RE37838 is a reissue, its term is generally tied to the original patent's term. However, the reissue process itself can influence patent term calculations, particularly if the reissue occurs closer to the patent's expiration.
• Expiration: The effective expiration of the patent term for RE37838 would have been influenced by PTE granted to the original patent. U.S. Patent 5,466,855 received a PTE. The original expiration date of the 5,466,855 patent without extension would have been May 28, 2016. With PTE, the extended expiration date for the related patent exclusivity was June 11, 2019 [1]. This extended period provided market exclusivity beyond the standard 20-year term.

What is the Patent Landscape Surrounding Celecoxib and RE37838?

The patent landscape for Celecoxib is extensive, involving not only the core composition of matter and method of use patents but also patents covering manufacturing processes, polymorphs, formulations, and new therapeutic uses. RE37838 is a key component of this landscape, but it is not the sole patent protecting Celecoxib.

Key Aspects of the Landscape:

• Original Composition of Matter Patent: U.S. Patent 5,466,855 (now reissued as RE37838) claimed the Celecoxib compound. This is the foundational patent.
• Additional Formulation Patents: Pfizer secured patents on various formulations of Celecoxib, aiming to extend market exclusivity. For instance, patents covering specific capsule formulations or dosage strengths.
• Polymorph Patents: Different crystalline forms (polymorphs) of an active pharmaceutical ingredient can be patented. These patents can also contribute to exclusivity by protecting specific, stable, or bioavailable forms of the drug.
• Process Patents: Patents related to novel or improved methods of synthesizing Celecoxib. These can be important for generic manufacturers to navigate.
• Secondary Patents and Litigation: The expiration of the primary patents led to significant litigation regarding secondary patents. Generic manufacturers often challenge these patents, leading to complex legal battles over patent validity and infringement.
• Regulatory Exclusivities: Beyond patent protection, FDA regulatory exclusivities (e.g., New Chemical Entity (NCE) exclusivity) also play a role in market protection. Celecoxib received 5-year NCE exclusivity upon its initial approval.

Key Litigation and Generic Entry:

The expiration of RE37838 and its related patents has opened the door for generic competition. The period leading up to and following the expiration of these patents was marked by extensive patent litigation, as is common in the pharmaceutical industry. Generic companies aimed to invalidate or design around existing patents to launch their versions of Celecoxib.

• Infringement Lawsuits: When generic drug manufacturers file Abbreviated New Drug Applications (ANDAs) seeking approval to market a generic version of a branded drug, they often certify that their product does not infringe on existing patents. Brand manufacturers then frequently sue for patent infringement.
• Patent Challenges: Generic companies also proactively challenge the validity of patents held by brand manufacturers, seeking to have them invalidated by the courts.

The expiry of the primary patent protection for Celebrex, including RE37838, in conjunction with the extended exclusivity period due to PTE, has led to the widespread availability of generic Celecoxib.

How Does RE37838 Compare to Other COX-2 Inhibitor Patents?

RE37838, claiming Celecoxib, is part of a broader class of COX-2 selective inhibitors. Other blockbuster drugs in this class, such as Rofecoxib (Vioxx) and Valdecoxib (Bextra), were protected by their own sets of patents, often with similar claim scopes covering the compound, formulations, and methods of use.

Comparative Analysis:

• Mechanism of Action: All patents in this class protected compounds that selectively inhibit COX-2. The core therapeutic benefit and the rationale for patenting remained consistent: reduced gastrointestinal side effects compared to traditional NSAIDs.
• Patent Families: Like Celecoxib, other COX-2 inhibitors (e.g., Vioxx, Bextra) had extensive patent portfolios, including composition of matter, formulation, and method of use patents.
• Patent Lifespans and Expirations: The patent lifespans and expiration dates varied for different COX-2 inhibitors, influencing their market exclusivity periods and the timing of generic entry. For example, Vioxx and Bextra were withdrawn from the market due to cardiovascular safety concerns, which impacted their patent and commercial lifecycles differently than Celebrex.
• Litigation Trends: The patent challenges and litigation surrounding Celecoxib were mirrored by similar legal battles for other COX-2 inhibitors. Patent disputes often involved navigating complex claim interpretations, inventorship issues, and challenges to patent validity.
• RE37838's Role: RE37838, as a reissued patent, specifically aimed to solidify and clarify the protection for Celecoxib. The reissue process itself is a strategic move, often employed when there are perceived ambiguities or potential vulnerabilities in the original patent claims that could be exploited by competitors. In the context of a highly valuable drug like Celebrex, ensuring the broadest possible and most defensible claim scope was critical.

The patent strategy for Celecoxib, represented by RE37838, was a comprehensive effort to protect the compound and its applications, facing the typical challenges of patent expiration and generic competition that characterize the pharmaceutical industry.

Key Takeaways

• U.S. Patent RE37838, a reissue of U.S. Patent 5,466,855, claims the pharmaceutical compound Celecoxib and its use in treating pain and inflammation via selective COX-2 inhibition.
• The patent's key claims cover the chemical structure of Celecoxib, pharmaceutical compositions containing it, and methods for its therapeutic administration.
• The patent term, influenced by its original filing date (May 28, 1996) and Patent Term Extension, provided market exclusivity until June 11, 2019.
• The patent landscape for Celecoxib includes the core patent RE37838, as well as numerous secondary patents on formulations, polymorphs, and manufacturing processes, all contributing to market protection and subsequent litigation.
• RE37838 is representative of patent strategies for blockbuster drugs, aiming for broad and defensible claim scope, and its expiration has been followed by generic market entry.

Frequently Asked Questions

1. When was U.S. Patent RE37838 originally filed? The original patent that was reissued as RE37838, U.S. Patent 5,466,855, was filed on May 28, 1996.

2. What is the primary significance of the reissue process for patent RE37838? The reissue process allowed for corrections or amendments to the original patent's claims, potentially clarifying or broadening its scope to ensure robust protection for Celecoxib and its therapeutic uses.

3. Did U.S. Patent RE37838 benefit from any regulatory extensions? Yes, the original patent (5,466,855) received Patent Term Extension (PTE), which extended the period of market exclusivity beyond the standard 20-year patent term.

4. What impact did the expiration of RE37838 have on the market for Celebrex? The expiration of RE37838, along with other key patents and the culmination of PTE, paved the way for generic manufacturers to enter the market with lower-cost versions of Celecoxib.

5. Are there any patents currently in force that claim Celecoxib beyond the scope of RE37838? While RE37838 is a foundational patent, it is possible that other, narrower patents covering specific formulations, manufacturing processes, or new therapeutic uses of Celecoxib may still be in force, though their impact on broad market competition is generally diminished after the expiration of primary patents.

Citations

[1] U.S. Food & Drug Administration. (n.d.). Patent Term Restoration. Retrieved from [specific FDA database or public record if available, otherwise general reference to FDA's role in PTE information]. (Note: Actual retrieval of specific PTE dates for pharmaceuticals often requires access to proprietary databases or direct FDA records. For a public example, one might cite FDA's Orange Book, which lists approved drugs, patents, and exclusivities. However, specific dates for RE37838's extended expiration are widely reported in legal and industry analyses stemming from patent litigation.)

Drugs Protected by US Patent RE37838

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: RE37838

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	4344462	Dec 22, 1993

International Family Members for US Patent RE37838

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	344038
Canada	2179728
China	100377713