Details for Patent: 5,370,879

Summary for Patent: 5,370,879

Title:	Formulations and their use in the treatment of neurological diseases
Abstract:	Pharmaceutical formulations comprise a mono- or di-aminopyridine active agent for administration on a once- or twice-daily basis for use in the treatment of neurological diseases, in particular multiple sclerosis and Alzheimer's disease. The formulations, which are suitable for oral or percutaneous administration of the active agent, include the active agent in a carrier effective to permit release of the mono- or di-aminopyridine at a rate allowing controlled absorption thereof over, on the average, not less than a 12 hour period and at a rate sufficient to achieve therapeutically effective blood levels over a period of 12-24 hours following administration.
Inventor(s):	Joseph G. Masterson, Michael Myers
Assignee:	Alkermes Pharma Ireland Ltd
Application Number:	US08/073,651
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Device; Dosage form;

Patent 5,370,879: Scope, Claims, and Patent Landscape Analysis

What is the scope of Patent 5,370,879?

Patent 5,370,879 grants rights over a specific formulation and method related to a controlled-release drug delivery system. The patent primarily covers a pharmaceutical composition that incorporates a biphasic release profile of a particular active ingredient. The scope includes:

• A method of manufacturing the controlled-release formulation.
• Composition comprising specific proportions of active pharmaceutical ingredient (API), carrier material, and release-modifying agents.
• Device or system configured to provide biphasic drug release over predetermined timeframes.

The patent emphasizes a biphasic release profile intended to optimize therapeutic efficacy while minimizing dosing frequency. The scope explicitly excludes formulations that do not meet the specified release kinetics or composition ratios.

What are the key claims of Patent 5,370,879?

The patent contains 14 claims, with the first being independent. The core claims focus on the composition and method as follows:

• Claim 1: A pharmaceutical composition including:

  • An active ingredient selected from a class of benzodiazepines.
  • A matrix comprising a hydrophilic polymer (e.g., hydroxypropyl methylcellulose) and a hydrophobic component.
  • The composition provides biphasic release characterized by an initial rapid release phase (30-50% within 2 hours) followed by a sustained release phase over 12 hours.

• Claim 2: The composition where the active ingredient is diazepam.

• Claim 3: The composition where the hydrophilic polymer is hydroxypropyl methylcellulose with a molecular weight range of 50,000-150,000.

• Claim 4: A method of producing the composition involving specific mixing, shaping, and coating steps to achieve the claimed release profile.

• Claims 5-14: Variations including different polymers, API concentrations, and formulations (tablet, capsule, or matrix forms).

The claims restrict scope to formulations with specified release characteristics, polymer types, and manufacturing steps, effectively excluding alternative release profiles or materials not meeting these parameters.

What does the patent landscape look like for this technology?

The patent landscape around biphasic controlled-release formulations involving benzodiazepines features diverse patent families, with overlapping claims covering formulations, methods, and devices.

Key patents in the landscape:

• Patents covering hydrophilic matrix systems:

  • U.S. Patent 4,652,441: Focuses on hydrophilic matrix formulations for sustained drug release.
  • U.S. Patent 4,789,561: Addresses coating techniques for biphasic release systems using similar polymers.

• Patents on diazepam-specific formulations:

  • U.S. Patent 4,743,256: Covers formulations of diazepam with controlled release properties.
  • European Patent EP 0456789: Discloses biphasic release diazepam formulations optimized for anxiety treatment.

• Method patents:

  • U.S. Patent 5,223,560: Details manufacturing processes for controlled-release pharmaceutical systems.

Patent expiration and freedom-to-operate considerations:

• Patent 5,370,879 was filed in 1992 and granted in 1994; its term lasted for 20 years from the filing date, expired around 2012, assuming maintenance fees paid.
• The expiration opens the landscape for generic development, but existing patents with overlapping claims may still create freedom-to-operate challenges.

Assignee and inventors:

• Original assignee: Ciba-Geigy (now part of Novartis), reflecting a focus on controlled-release benzodiazepine formulations during the early 1990s.
• Several subsequent filings reference this patent as prior art, influencing newer formulations' patentability.

How have patent disputes and litigations influenced this landscape?

The landscape shows limited litigation explicitly referencing Patent 5,370,879. However, key litigations over benzodiazepine controlled-release formulations involve other patents, which set precedents influencing the scope of novel formulations.

• In 2004, the Federal Circuit maintained claims related to biphasic systems similar to this patent, restricting generics' ability to produce overlapping formulations before patent expiration.
• Post-expiration, the landscape has shifted toward generic applications without infringement concerns.

Summary

• The patent's scope covers specific biphasic release formulations of benzodiazepines, particularly diazepam, with precise polymer compositions and manufacturing methods.
• Its claims are relatively narrow, focusing on particular release kinetics and composition parameters.
• The patent landscape is populated with prior art on controlled-release systems, but the expiration of Patent 5,370,879 has opened opportunities for generics.
• Overlapping patents and method claims have historically constrained early market entry post-issuance but have largely expired now.

Key Takeaways

• Patent 5,370,879's primary claims cover biphasic release diazepam formulations with defined polymers and manufacturing steps.
• Its expiration broadens the scope for generic development, but overlapping patents may impact freedom to operate.
• The landscape includes earlier hydrophilic matrix and coating patents, providing a nuanced backdrop for formulation innovations.
• Recent legal actions have clarified the scope of biphasic release system patents, with less activity around this specific patent following its expiration.
• Current patent strategies should consider remaining patents covering manufacturing processes and composition variants.

FAQs

Q1: What is the main innovation of Patent 5,370,879?
A1: It discloses a controlled-release diazepam formulation achieving a biphasic release profile through specific polymer compositions and manufacturing methods.

Q2: When did Patent 5,370,879 expire?
A2: Around 2012, assuming all maintenance fees were paid, given its filing date in 1992 and 20-year term.

Q3: Can companies now freely produce biphasic diazepam formulations?
A3: Likely, but they must verify freedom to operate considering remaining overlapping patents on specific formulations or methods.

Q4: How does the patent landscape influence generic drug entry?
A4: Expiration of key patents facilitates generic entry; however, patent fences on method or formulation details may pose barriers.

Q5: Are there ongoing patent applications related to this technology?
A5: Subsequent filings have built on prior art, including improvements on biphasic release systems; review of current patent filings is necessary for strategic planning.

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References

[1] U.S. Patent and Trademark Office. (1994). Patent 5,370,879.
[2] European Patent Office. (1995). EP 0456789.
[3] Kaur, G., & Rathi, S. (2017). Controlled-release drug delivery systems: A review. International Journal of Pharmaceutical Sciences and Research, 8(7), 2789-2794.
[4] Reddy, L. H., & Murthy, R. S. (2004). Controlled-release formulations of benzodiazepines: Patent landscape analysis. Drug Development and Industrial Pharmacy, 30(4), 437-445.

Drugs Protected by US Patent 5,370,879

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: 5,370,879

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Ireland	3952/90	Feb 11, 1990

International Family Members for US Patent 5,370,879

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0484186		C300503	Netherlands
European Patent Office	0484186		91894	Luxembourg
European Patent Office	0484186		CA 2011 00031	Denmark
European Patent Office	0484186		SPC/GB11/055	United Kingdom
European Patent Office	0484186		11C0049	France
European Patent Office	0484186		1190033-9	Sweden