United States Patent 5,849,752: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
United States Patent 5,849,752, assigned to Bayer AG, is a significant patent in the pharmaceutical industry, particularly in the context of moxifloxacin, a fourth-generation synthetic fluoroquinolone antibacterial agent. This patent is crucial for understanding the intellectual property landscape surrounding moxifloxacin and its various forms.
Patent Overview
Patent Title and Description
The patent titled "Crystal modification of CDCH and a process for its preparation" focuses on the monohydrated form of moxifloxacin hydrochloride, also known as CDCH (1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid hydrochloride)[2].
Claims and Scope
Independent Claims
The patent includes several independent claims that define the scope of the invention. Key claims include:
- The monohydrated form of moxifloxacin monohydrochloride, which crystallizes as prisms.
- A process for preparing this monohydrate form by suspending anhydrous crystalline moxifloxacin in ethanol/water mixtures, preferably at room temperature[2].
Dependent Claims
Dependent claims elaborate on the independent claims by specifying details such as:
- The moisture content of the monohydrated form, which is about 3.9% w/w.
- The physical characteristics and stability of the monohydrate form[2].
Patent Landscape
Related Patents and Expiry Dates
The patent landscape for moxifloxacin is complex, with multiple patents protecting different aspects of the molecule and its formulations:
- US Patent No. 5,607,942: This patent, also assigned to Bayer, claims the moxifloxacin molecule specifically and expired on March 4, 2014[1][4].
- US Patent No. 6,548,079: This patent expired on July 25, 2020, and was also part of the protection for moxifloxacin formulations[1][4].
Generic Entry and Litigation
The expiration of these patents has been a significant factor in generic entry:
- Generic manufacturers like Fresenius Kabi have submitted Paragraph IV certifications challenging the validity and enforceability of these patents, particularly US Patent No. 5,849,752 and US Patent No. 6,548,079[1].
- Litigation in the US and Canada has been ongoing, with Bayer successfully defending some of its patents against generic manufacturers like Teva and Novopharm[4].
Preparation and Characteristics
Monohydrated Form
The monohydrated form of moxifloxacin hydrochloride, as claimed in US Patent 5,849,752, is prepared by suspending anhydrous crystalline moxifloxacin in ethanol/water mixtures. This form crystallizes as prisms and has a moisture content of about 3.9% w/w[2].
Other Forms of Moxifloxacin
In addition to the monohydrated form, other forms of moxifloxacin have been developed and patented:
- Anhydrous Form: Disclosed in various patents, including those related to the '072 and '414 patent families[2][4].
- Amorphous Form: Prepared using spray drying or freeze-drying techniques, as described in WO 2004/039804[2].
- Polymorphic Forms: New polymorphic forms, such as Form III, have been described and patented, expanding the range of moxifloxacin formulations[2].
Regulatory and Approval Aspects
FDA Approval and NDA Filings
Moxifloxacin was approved by the FDA in 1999 for use in the United States. Generic manufacturers have since filed NDAs, including Fresenius Kabi, which submitted a Paragraph III certification for US Patent No. 5,607,942 and Paragraph IV certifications for US Patents No. 5,849,752 and No. 6,548,079[1][4].
Extractable/Leachable Studies
The FDA has scrutinized the container closure system for moxifloxacin formulations, highlighting the need for adequate extractable/leachable studies to ensure the quality and purity of the drug product[1].
Impact on Innovation and Generic Competition
Patent Quality and Scope
The scope and quality of patents like US Patent 5,849,752 have been subjects of debate. Narrower claims, as seen in this patent, can facilitate a smoother examination process and higher probability of grant, while broader claims may lead to increased litigation and licensing costs[3].
Generic Competition
The expiration of key patents, including US Patent 5,849,752, has opened the door for generic competition. However, ongoing litigation and the presence of other patents in the moxifloxacin family continue to influence the market dynamics[1][4].
Conclusion
US Patent 5,849,752 is a pivotal patent in the moxifloxacin landscape, protecting the monohydrated form of moxifloxacin hydrochloride and its preparation process. Understanding the claims, scope, and surrounding patent landscape is crucial for pharmaceutical companies navigating the complex world of intellectual property and generic competition.
Key Takeaways
- Monohydrated Form: US Patent 5,849,752 claims the monohydrated form of moxifloxacin hydrochloride and its preparation process.
- Patent Expiry: The patent expired on December 5, 2016, but its impact on generic entry and litigation continues.
- Regulatory Scrutiny: Adequate extractable/leachable studies are essential for FDA approval of moxifloxacin formulations.
- Generic Competition: The expiration of this and other related patents has facilitated generic competition, though ongoing litigation affects market dynamics.
- Patent Quality: The scope and quality of patents influence innovation and licensing costs.
Frequently Asked Questions (FAQs)
What is the monohydrated form of moxifloxacin hydrochloride?
The monohydrated form of moxifloxacin hydrochloride is a crystalline form that contains about 3.9% w/w moisture, prepared by suspending anhydrous crystalline moxifloxacin in ethanol/water mixtures[2].
When did US Patent 5,849,752 expire?
US Patent 5,849,752 expired on December 5, 2016[1][4].
What is the significance of extractable/leachable studies for moxifloxacin formulations?
Extractable/leachable studies are crucial to ensure the quality and purity of the drug product by evaluating the impact of the container closure system on the drug[1].
How has the expiration of US Patent 5,849,752 affected generic competition?
The expiration of this patent has allowed generic manufacturers to enter the market, although ongoing litigation related to other patents in the moxifloxacin family continues to influence market dynamics[1][4].
What other forms of moxifloxacin have been patented?
Besides the monohydrated form, other patented forms include anhydrous, amorphous, and various polymorphic forms of moxifloxacin hydrochloride[2][4].
Cited Sources
- FDA NDA Document: "205572Orig1s000MedR.pdf" - accessdata.fda.gov
- Google Patents: "WO2006134491A2 - New crystalline form of moxifloxacin hydrochloride and process for its preparation" - patents.google.com
- Hoover Institution: "Patent Claims and Patent Scope" - hoover.org
- New Drug Approvals: "MOXIFLOXACIN, Bay-12-8039" - newdrugapprovals.org
