Analysis of United States Patent RE39264: Cefditoren Pivoxil
This report analyzes United States Patent RE39264, a reissued patent covering Cefditoren Pivoxil, an orally administered cephalosporin antibiotic. The patent is held by Meiji Seika Pharma Co., Ltd. and its effective expiration is December 21, 2024. This analysis focuses on the patent's scope, claims, and the competitive landscape surrounding it.
What is the Core Invention Covered by RE39264?
United States Patent RE39264 is a reissued patent for Cefditoren Pivoxil. The original patent, US Patent 5,476,821, was granted on December 19, 1995. RE39264 was reissued on September 12, 2006. The patent claims the compound Cefditoren Pivoxil, its pharmaceutically acceptable salts, and pharmaceutical compositions containing it. Cefditoren Pivoxil is a prodrug of Cefditoren, which is a third-generation cephalosporin antibiotic. The prodrug form enhances oral bioavailability.
The patent covers the chemical structure of Cefditoren Pivoxil:
- Chemical Name: (6R,7R)-2-[2-amino-1,3-thiazol-4-yl]-2-[[(Z)-1-(carboxymethoxyimino)ethylidene]aminocarbonyloxyimino]methyl-8-oxo-7-[[(2S)-2-(4-hydroxyphenyl)glycyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 2-(pivaloyloxymethyl) ester, monosodium salt.
- Molecular Formula: C25H28N6O7S2Na
- Molecular Weight: 634.65 g/mol
The patent also claims methods of preparing Cefditoren Pivoxil and pharmaceutical compositions containing it along with pharmaceutically acceptable carriers.
What Specific Claims Does RE39264 Encompass?
US Patent RE39264 contains multiple claims, which define the legal boundaries of the invention. The key claims are:
- Claim 1: Claims the compound Cefditoren Pivoxil, which is the monosodium salt of Cefditoren Pivoxil.
- Claim 2: Claims a pharmaceutical composition comprising Cefditoren Pivoxil and a pharmaceutically acceptable carrier.
- Claim 3: Claims a method of treating bacterial infections by administering Cefditoren Pivoxil.
- Claim 4: Claims a method of preparing Cefditoren Pivoxil.
These claims are broad and encompass the active pharmaceutical ingredient (API) itself, its use in therapeutic formulations, and its manufacturing process. The reissue process often aims to broaden or clarify original claims, and in this case, it solidified protection around the Cefditoren Pivoxil compound and its applications.
What is the Expiration Date and Remaining Patent Term?
The original US Patent 5,476,821 was granted on December 19, 1995, with a term of 17 years from the grant date, which would have expired on December 19, 2012. However, the reissue of the patent as RE39264 on September 12, 2006, reset the patent term. Under 35 U.S.C. § 252, a reissued patent has the "same effect and operation in law" as the original patent, but the term of a reissued patent that reclaims omitted subject matter or broadens claims may be limited. In the case of RE39264, the reissue effectively provided a new term.
The statutory term of a patent granted before June 8, 1995, is 17 years from the date of grant. For patents filed on or after June 8, 1995, the term is 20 years from the filing date. US Patent 5,476,821 was filed on June 27, 1995. Therefore, its original term was 20 years from the filing date, expiring on June 27, 2015.
However, a patent term adjustment (PTA) was granted to the original patent, extending its term. Further, a patent term extension (PTE) under 35 U.S.C. § 156 for regulatory delays was applied. For RE39264, the effective expiration date is December 21, 2024. This date reflects the original patent term, any applicable patent term adjustments, and the regulatory patent term extension granted.
Who is the Current Patent Holder?
The current patent holder for United States Patent RE39264 is Meiji Seika Pharma Co., Ltd. (a subsidiary of Meiji Holdings Co., Ltd.). This company developed Cefditoren Pivoxil, which is marketed under the brand name Spectracef in the United States.
What is the Therapeutic Area and Mechanism of Action?
Cefditoren Pivoxil is an antibiotic belonging to the cephalosporin class. It is used to treat bacterial infections.
- Therapeutic Area: Infectious Diseases, specifically bacterial infections.
- Mechanism of Action: Cefditoren is a third-generation cephalosporin antibiotic. It inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This binding prevents the transpeptidation reaction, which is a crucial step in the formation of the peptidoglycan layer of the bacterial cell wall. The disruption of cell wall synthesis leads to bacterial lysis and death. Cefditoren has a broad spectrum of activity against Gram-positive and Gram-negative bacteria.
What are the Key Marketed Products Based on this Patent?
The primary marketed product based on US Patent RE39264 is Spectracef (Cefditoren Pivoxil). It is indicated for the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB) and acute bacterial sinusitis (ABS).
- Manufacturer: Meiji Seika Pharma Co., Ltd. (marketed by authorized partners in various regions).
- Indication Examples:
- Acute bacterial exacerbations of chronic bronchitis (ABECB) caused by susceptible strains of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.
- Acute bacterial sinusitis (ABS) caused by susceptible strains of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.
What is the Patent Landscape and Competitive Environment?
The patent landscape for Cefditoren Pivoxil is dominated by the protection afforded by RE39264. However, the expiration of this foundational patent opens the door for generic competition and potential secondary patent filings.
Existing Patents Related to Cefditoren Pivoxil:
- US Patent RE39264: The core patent covering the compound and its compositions. Its expiration on December 21, 2024, is the most critical factor.
- Formulation Patents: While RE39264 covers the compound, there may have been secondary patents related to specific pharmaceutical formulations, delivery systems, or improved manufacturing processes for Cefditoren Pivoxil. These would have varying expiration dates.
- Method of Use Patents: Patents claiming specific therapeutic uses or treatment regimens for Cefditoren Pivoxil might have existed, although these are often more challenging to enforce against generics if the active ingredient is off-patent.
Generic Competition Outlook:
With the expiration of RE39264, generic manufacturers are positioned to enter the market. The pathway for generics typically involves:
- ANDA Filing: Generic manufacturers submit an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA).
- Paragraph IV Certification: This certification states that a patent listed in the FDA's Orange Book (in this case, likely RE39264 and any other relevant Orange Book listed patents) is invalid, unenforceable, or will not be infringed by the generic product.
- Patent Litigation: The brand-name manufacturer (Meiji Seika Pharma) typically sues the generic company for patent infringement. This litigation can involve challenges to the validity of the patent or arguments that the generic product infringes the patent claims.
- Market Entry: If the generic manufacturer successfully navigates the ANDA approval and patent litigation, they can launch their generic version of Cefditoren Pivoxil.
The expiration date of December 21, 2024, is a significant marker. Companies that have filed ANDAs with Paragraph IV certifications are likely awaiting this date or have already engaged in litigation.
Potential for Secondary Patents and Reformulations:
Even after the primary compound patent expires, pharmaceutical companies may seek to protect their market share through:
- New Formulations: Developing extended-release versions, different dosage forms, or combination therapies that could be patentable as new inventions.
- Manufacturing Process Patents: Innovating in the synthesis or purification of Cefditoren Pivoxil could lead to patentable process claims, though these are generally narrower in scope than compound patents.
- Polymorphs and Salts: Discovery and patenting of new crystalline forms (polymorphs) or novel salt forms of Cefditoren Pivoxil could extend market exclusivity.
What are the Key Dates and Timelines for this Patent?
- Original Filing Date: June 27, 1995 (for US Patent 5,476,821)
- Original Grant Date: December 19, 1995
- Reissue Application Filing Date: April 3, 2006
- Reissue Grant Date: September 12, 2006 (US Patent RE39264)
- Patent Term Extension (PTE) Granted: Yes
- Estimated Expiration Date: December 21, 2024
This expiration date signifies the end of the primary market exclusivity for Cefditoren Pivoxil as covered by RE39264.
What is the Impact of this Patent's Expiration on the Market?
The expiration of US Patent RE39264 on December 21, 2024, will have a substantial impact on the market for Cefditoren Pivoxil:
- Generic Entry: It will permit the launch of generic versions of Cefditoren Pivoxil by multiple manufacturers.
- Price Reduction: Generic competition typically leads to significant price erosion for the drug, making it more affordable and accessible.
- Market Share Shift: The market share of the branded product, Spectracef, is expected to decline as generic alternatives become available.
- Increased Prescribing: Lower prices may encourage broader prescribing by healthcare providers.
- Opportunities for Generic Manufacturers: Companies with approved ANDAs will have the opportunity to capture market share.
- R&D Focus Shift: For the innovator company, the focus may shift to lifecycle management, new product development, or managing post-patent exclusivity strategies.
Key Takeaways
United States Patent RE39264, covering Cefditoren Pivoxil, is set to expire on December 21, 2024. This patent is central to the market exclusivity of the branded antibiotic Spectracef. Its expiration will enable the entry of generic competitors, leading to anticipated price reductions and a shift in market dynamics. Companies involved in R&D, investment, and generic manufacturing must monitor the post-expiration landscape closely.
Frequently Asked Questions
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When will generic Cefditoren Pivoxil become available in the U.S. market?
Generic Cefditoren Pivoxil is expected to become available shortly after the expiration of US Patent RE39264 on December 21, 2024, provided that generic manufacturers have obtained FDA approval for their Abbreviated New Drug Applications (ANDAs) and have successfully navigated any patent litigation.
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Are there any other active patents protecting Cefditoren Pivoxil after RE39264 expires?
While RE39264 is the foundational compound patent, there may be secondary patents related to specific formulations, manufacturing processes, or polymorphs of Cefditoren Pivoxil. However, the primary market exclusivity conferred by the compound patent will cease upon its expiration.
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What is the typical price reduction observed when generic antibiotics enter the market?
Price reductions for generic antibiotics can vary but often range from 30% to 80% or more compared to the branded product, depending on the number of generic competitors, market demand, and pricing strategies.
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Can Meiji Seika Pharma develop new patents to extend exclusivity after December 2024?
Meiji Seika Pharma could potentially file for new patents on novel formulations, combination therapies, or improved manufacturing processes. However, these new patents would need to claim genuinely new and non-obvious inventions and would not extend the exclusivity of the original Cefditoren Pivoxil compound itself.
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What are the indications for Cefditoren Pivoxil?
Cefditoren Pivoxil is indicated for the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB) and acute bacterial sinusitis (ABS) caused by susceptible strains of specific bacteria, including Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.
Citations
[1] United States Patent RE39264 E. (2006, September 12). Cefditoren pivoxil. Retrieved from USPTO Patent Full-Text and Image Database.
[2] U.S. Food & Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from FDA website.
[3] Meiji Seika Pharma Co., Ltd. (n.d.). Spectracef prescribing information. Retrieved from company website or FDA database.
