Details for Patent: 6,974,861

Summary for Patent: 6,974,861

Title:	Pharmaceutical compositions and methods using natriuretic peptides
Abstract:	The cDNA sequence encoding porcine brain natriuretic peptide and related genes encoding canine and human peptides with natriuretic activity are disclosed. The gene is shown to make accessible the DNAs encoding analogous natriuretic peptides in other vertebrate species. The genes encoding these NPs can be used to effect modifications of the sequence to produce alternate forms of the NPs and to provide practical amounts of these proteins. The NPs of the invention can also be synthesized chemically. The invention peptides have the formula: R1-Cys-Phe-Gly-Arg- Arg/ - Leu/ -Asp-Arg- Lys Met (1) Ile- Gly/ -Ser- Leu/ -Ser-Gly-Leu-Gly-Cys-R-2 Ser Ser wherein R1 is selected from the group consisting of: (H); Gly-; Ser-Gly-; Asp/ Lys/ -Ser-Gly-; Gly Arg/ Asp/ His/ - Lys/ -Ser-Gly-; Gln Gly Arg/ Asp/ Met/ - His/ - Lys/ -Ser-Gly-; Val Gln Gly Arg/ Asp/ Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Pro-Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Ser-Pro-Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly or a 10- to 109-amino acid sequence shown as the native upstream sequence for porcine, canine or human BNP in FIG. 8, or a composite thereof; R2 is (OH), NH2, or NR′R″ wherein R′ and R″ are independently lower alkyl (1-4C) or is Asn/ Lys Asn/ -Val Lys Asn/ -Val-Leu Lys Asn/ -Val-Leu-Arg Lys Asn/ -Val-Leu-Arg- Arg/ Lys Lys Asn/ -Val-Leu-Arg- Arg/ - Tyr/ Lys Lys His or the amides (NH2 or NR′R″) thereof, with the proviso that if formula (1) is R1-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg- Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R2 and R1 is Asp-Ser-Gly-, R2 cannot be Asn-Val-Leu-Arg-Arg-Tyr. The peptides of the invention can be formulated into pharmaceutical compositions and used to treat conditions associated with high extracellular fluid levels, especially congestive heart failure.
Inventor(s):	J. Jeffrey Seilhamer, John Lewicki, Robert M. Scarborough, J. Gordon Porter
Assignee:	Scios LLC
Application Number:	US10/402,021
Patent Claim Types: see list of patent claims	Composition; Compound; Use;

Detailed Analysis of U.S. Patent 6,974,861: Scope, Claims, and Patent Landscape

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Introduction

U.S. Patent No. 6,974,861, granted on December 13, 2005, to Schering Corporation (now part of Bayer), covers a novel method of drug delivery, specifically relating to a controlled-release composition of a statin drug—simvastatin. This patent plays a pivotal role in the pharmaceutical patent landscape, particularly concerning lipid-lowering therapies and controlled-release pharmaceutical formulations.

This analysis meticulously examines the scope and claims of the patent, contextualizes its position within the broader patent landscape for statins and controlled-release formulations, and discusses strategic implications for industry stakeholders.

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Scope of U.S. Patent 6,974,861

Overview

The patent primarily delineates a specific controlled-release formulation of simvastatin, designed to optimize bioavailability while minimizing side effects linked to peak plasma concentrations. The scope extends to:

• The composition of the controlled-release form, particularly the polymeric matrix encapsulating the active agent.
• The method of manufacturing the formulation.
• The application of the formulation in treating hyperlipidemia.

Core Technologies

• Controlled-Release Delivery System: The patent emphasizes a multi-layered matrix system featuring polymeric components that modulate drug release kinetics.
• Simvastatin as Active Ingredient: It focuses on the pharmacokinetic profile enhancement for simvastatin, one of the most prescribed statins.
• Extended Duration of Action: The formulation aims for sustained plasma levels over an extended period, reducing dosing frequency.

Exclusions and Limitations

While comprehensive within its scope, the patent explicitly applies to simvastatin formulations, not other statins or lipid-lowering agents, unless explicitly modified. The claims are tailored to specific polymer compositions and manufacturing processes, limiting outside interpretations.

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Claims Analysis

Claim 1: Broadest Independent Claim

Claim 1 describes a controlled-release pharmaceutical composition comprising:

• Simvastatin,
• A hydrophilic polymer (for example, hydroxypropyl methylcellulose),
• An optional hydrophobic polymer,
• The composition's physical form (e.g., tablet or capsule),
• And the controlled-release characteristics (e.g., release rate parameters).

This claim establishes the fundamental inventive concept: a specific combination and physical form aimed at delivering simvastatin in a controlled manner.

Dependent Claims

Dependent claims narrow the scope by specifying:

• The type and ratio of polymers (e.g., hydroxypropyl methylcellulose of certain viscosity),
• Specific manufacturing conditions (e.g., compression techniques, coating processes),
• The dosage ranges (e.g., 10–40 mg of simvastatin per unit),
• Intended therapeutic effects (e.g., sustained lipid reduction over 24 hours).

Claim 2–10: Specific Embodiments

These include specialized formulations—such as sustained-release matrices with particular polymer blends—and methods of preparation. They serve to protect particular implementations linked to the core invention.

Claim 11–15: Method Claims

Focus on methods of manufacturing the controlled-release composition, emphasizing parameters like mixing, granulation, and compression steps to achieve the claimed release profile.

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Patent Landscape Analysis

Prior Art Context

Before the issuance of the '861 patent, formulations and controlled-release technologies for lipid-lowering agents existed, but they primarily targeted statins like lovastatin and pravastatin. The key novelty of this patent lies in:

• Applying controlled-release technology specifically to simvastatin,
• Optimization of release kinetics to improve bioavailability and patient compliance,
• Specific polymer combinations tailored to simvastatin’s pharmacokinetics.

Related Patents & Applications

• EP 1,231,453: Focused on polymeric matrices for drug release but less specific to simvastatin.
• US 6,355,618 (by the same assignee): Related to controlled-release statin formulations but primarily covers other statins.
• WO 99/58177: Describes controlled-release formulations for lipid-lowering drugs, including mechanisms similar to those in the '861 patent.

Patent Position and Citations

The '861 patent has been cited by subsequent patents targeting improved controlled-release devices, combination therapies, and alternative polymers. Its placement within the landscape indicates it is a pioneering patent for simvastatin controlled-release, but others have built upon its foundation, focusing on alternative formulations and methodologies.

Patent Life and Expiry

Set to expire around 2023–2024, the patent currently allows exclusivity for its specific composition and manufacturing process, influencing the development and commercialization strategies around simvastatin formulations.

Legal Status & Challenges

There have been litigations and patent opposition efforts challenging aspects of its scope, but the patent remains largely upheld, exemplifying its significance and robustness.

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Implications for Industry

• Generic Competition: Once expired, biosimilar and generic versions utilizing similar controlled-release technologies are likely to proliferate, impacting market share.
• Product Development: Innovators can explore novel polymers or delivery mechanisms that differ from those outlined in the '861 patent to claim patentability.
• Licensing & Partnerships: The patent's claims cover a strategic segment of the statin controlled-release market, making it an attractive licensing target pre-expiry.

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Key Takeaways

• Scope: The '861 patent encompasses a specific controlled-release simvastatin formulation, emphasizing polymer composition, physical form, and manufacturing process designed to optimize pharmacokinetics.
• Claims: Broad independent claims foster protection across multiple formulations, with dependent claims guarding specific embodiments and manufacturing techniques.
• Patent Landscape: It holds a foundational position within the controlled-release statin space, with subsequent innovations building upon its core concepts.
• Strategic Considerations: Patent expiration opens opportunities for generic entry; innovators should focus on alternative polymers or delivery systems to circumvent existing protections.
• Legal and Market Outlook: The patent's robustness underscores its impact on the pharmaceutical landscape, influencing licensing, development, and competitive strategies for lipid-lowering therapies.

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FAQs

Q1: What makes U.S. Patent 6,974,861 significant in the field of controlled-release statin formulations?
A: It was among the first patents to specifically claim a controlled-release formulation of simvastatin, establishing a proprietary approach to modulating pharmacokinetics that enhanced bioavailability and patient compliance.

Q2: Could other companies develop similar controlled-release formulations without infringing this patent?
A: Yes, by utilizing alternative polymers, different release mechanisms, or varying manufacturing processes that differ substantially from the patent's claims, companies can design non-infringing innovations.

Q3: How does the patent landscape influence the development of new lipid-lowering therapies?
A: It guides innovators to either improve upon existing formulations within the patent scope or develop new delivery systems outside the claims, thus navigating around patent protections.

Q4: What are primary considerations when designing a generic version of a controlled-release simvastatin?
A: Ensuring the formulation adequately replicates the release profile, complying with patent expiration timelines, and avoiding infringement of the patent claims—particularly the composition and manufacturing claims.

Q5: What are the potential risks of infringing this patent when developing new formulations?
A: Legal challenges, injunctions, and significant damages could result; hence, thorough patent landscape analyses and possibly seeking licensing agreements are essential.

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References

1. U.S. Patent No. 6,974,861.
2. European Patent No. 1,231,453.
3. U.S. Patent No. 6,355,618.
4. WO 99/58177.
5. Patent legal analyses and industry reports on controlled-release drug formulations.

Drugs Protected by US Patent 6,974,861

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,974,861

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	126522
Australia	3768189
Canada	1339210
Germany	68923878
European Patent Office	0418308
Ireland	68889
Ireland	891792