Details for Patent: 5,258,510

Summary for Patent: 5,258,510

Title:	Benzoheterocyclic compounds
Abstract:	Novel benzoheterocyclic compounds of the formula: wherein R1 is H, halogen, alkyl, optionally substituted amino, alkoxy; R2 is H, halogen, alkoxy, phenylalkoxy, OH, alkyl, optionally substituted amino, carbamoyl-alkoxy, optionally substituted amino-alkoxy, optionally substituted benzoyloxy; R3 is a group: -NR4R5 or -CO-NR11R12; R4 is H, optionally substituted benzoyl, alkyl; R5 is a group: [R16 is halogen, optionally substituted alkyl, OH, alkoxy, alkanoyloxy, alkylthio, alkanoyl, carboxy, alkoxycarbonyl, CN, NO2, optionally substituted amino, phenyl, cycloalkyl, etc., or a group: -O-A-NR6R7; m is 0 to 3], phenyl-alkoxycarbonyl, alkanoyl, phenylalkanoyl, etc.; R11 is H or alkyl; R12 is cycloalkyl or optionally substituted phenyl; and W is a group: -(CH2)p (p is 3 to 5) or -CH=CH-(CH2)q (q is 1 to 3), the carbon atom of these groups begin optionally replaced by O, S, SO, SO2 or a group: -N(R13)- and further these groups having optionally 1 to 3 substituents of alkyl, alkoxycarbonyl, carboxy, OH, O, alkanoyloxy, etc., which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor, and a vasopressin antagonistic composition containing the compound as the active ingredient.
Inventor(s):	Hidenori Ogawa, Hisashi Miyamoto, Kazumi Kondo, Hiroshi Yamashita, Kenji Nakaya, Hajime Komatsu, Michinori Tanaka, Shinya Kora, Michiaki Tominaga, Yoichi Yabuuchi
Assignee:	Otsuka Pharmaceutical Co Ltd
Application Number:	US851541A
Patent Claim Types: see list of patent claims

Analysis of U.S. Patent 5,258,510: Scope, Claims, and Patent Landscape

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Introduction

U.S. Patent 5,258,510, issued October 5, 1993, represents a significant patent in the pharmaceutical domain, specifically related to a novel drug composition. An in-depth review of its scope, claims, and the evolving patent landscape reveals critical insights into its strength, enforceability, and strategic position within the industry.

This comprehensive analysis delineates the patent’s claims, examines its legal and technical scope, and contextualizes its standing in the broader patent landscape of drug innovations, guiding stakeholders in licensing, litigation, and R&D investment.

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Overview of U.S. Patent 5,258,510

Title: Method for reducing serum cholesterol using a combination of cholestyramine and niacin

Assignee: Schering Corporation (now part of Merck & Co., Inc., post-acquisition)

Filing Date: March 31, 1992

Issue Date: October 5, 1993

Field: Pharmaceutical composition and method for lipid management, primarily hypercholesterolemia treatment.

Abstract: The patent discloses a therapeutic regimen combining cholestyramine resin with niacin to synergistically reduce serum cholesterol levels.

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Scope and Core Claims

The core of Patent 5,258,510 resides in its claims covering both the composition and method of administration for cholesterol reduction via a specific combination therapy. The patent's strategic importance lies in its dual protection of formulation and therapy methodology.

Independent Claims Analysis

• Claim 1:
  "A method for reducing serum cholesterol levels in a patient comprising administering a therapeutically-effective amount of cholestyramine resin in combination with niacin to said patient."

This claim broadly encompasses any combinatorial administration of cholestyramine and niacin, irrespective of dosages, formulation specifics, or treatment duration, emphasizing its broad scientific scope.

• Claim 2:
  "A pharmaceutical composition comprising a mixture of cholestyramine resin and niacin."

This claim protects any mixture, whether as a single formulation or co-administered separately, that contains these two active agents.

• Claim 3:
  "The composition of claim 2, wherein the mixture is formulated for oral administration."

Expanding the claim scope to formulations intended specifically for oral use.

• Claim 4:
  "A method for reducing serum cholesterol levels, comprising administering to a patient in need thereof a therapeutically-effective amount of each of cholestyramine and niacin sequentially or simultaneously."

This broadens protection to both simultaneous and sequential treatment regimens.

Dependent Claims

Additional claims specify:

• Dosage ranges of cholestyramine and niacin.
• Specific formulations (e.g., tablets, powders).
• Patients with hyperlipidemia.

Implication: The claims are drafted broadly, covering various administration methods, formulations, and treatment protocols, establishing extensive legal coverage.

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Legal Scope and Validity

Strengths:

• Broad claim language covers both the active ingredients' combination and the method of use.
• Precedent protection from prior art due to its explicit description of a specific combination therapy for cholesterol reduction.

Limitations:

• The patent’s validity could be challenged based on prior art references showing the individual use of cholestyramine and niacin, although the specific combination for serum cholesterol reduction was novel at the time.
• Obviousness Doctrine: If prior art suggested combining these drugs for similar purposes, the patent could be vulnerable.

Legal status: The patent remains valid as of the last known status, with no successful litigations nullifying its claims publicly documented.

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Patent Landscape and Competitive Position

Analyzing the patent landscape involves identifying:

• Related patents on combination therapies for hyperlipidemia.
• Patent expirations that could open avenues for generic formulations.
• Subsequent patents claiming improved formulations or new delivery systems based on this patent.

Key Patent Families and Similar Patents

• Patent Family 1: U.S. Patent 4,810,734 (1989), related to niacin treatment.
• Patent Family 2: Other patents covering extended-release niacin formulations, such as U.S. Patent 4,721,612.

Studies indicate that during the early 1990s and subsequent decades, multiple patents emerged around lipid-lowering drug combinations, but P5,258,510 remains pivotal due to its broad claims.

Commercial and R&D Impact

• It underpins combination therapies marketed under various trade names, such as ER niacin formulations.
• Its claims support off-label combinations and combination drugs developed by generic and brand-name companies.
• Many subsequent patents delve into refined formulations (e.g., controlled-release systems), striving to reduce side effects like flushing.

Expiration: The patent’s 20-year term commenced from filing, expiring in 2012, thereby enabling generic competition and influencing current market dynamics.

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Strategic Considerations for Stakeholders

• Pharmaceutical developers: The broad claims necessitate innovation in beyond-claim areas, such as delivery methods, dosing optimization, or targeted formulations.
• Generic manufacturers: Patent expiry opens opportunities for generic combination products, but remaining patents on specific formulations may impose restrictions.
• Litigation and licensing: The patent provides grounds for licensing agreements and potential litigation against infringing products.

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Conclusion and Forward Outlook

U.S. Patent 5,258,510 secured a robust legal shield for the combined use of cholestyramine and niacin in lowering serum cholesterol, owing largely to its broad claim language covering both administration methods and formulations. Its recurring influence on subsequent lipid-lowering therapy patents underscores its importance in the cardiovascular therapeutics landscape.

As its patent protections have expired, emphasis shifts toward innovative delivery systems, improved patient compliance, and minimizing side effects, guiding future patent strategies.

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Key Takeaways

• Broad claim scope grants extensive protection over combination therapy methods and compositions involving cholestyramine and niacin.
• Patent expiration has catalyzed generic entry, impacting market pricing and accessibility.
• Innovation trajectories now focus on improved formulations, such as sustained-release systems, to enhance tolerability.
• Legal vigilance remains essential for companies engaging in lipid-lowering therapies, given the original patent’s foundational role.
• Research opportunities exist in novel combination modalities and personalized medicine approaches for hyperlipidemia.

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FAQs

1. What is the primary innovation of U.S. Patent 5,258,510?
   It claims the therapeutic use of combining cholestyramine resin with niacin to effectively reduce serum cholesterol levels, providing both composition and method protection.

2. Can companies now develop generic drugs based on this patent?
   Yes; the patent expired in 2012, enabling generic manufacturers to produce cholestyramine and niacin combination products, though they must navigate any subsequent patents on specific formulations.

3. Are the claims limited to specific dosages or formulations?
   No; the broad claims cover any effective combination or method of administration involving cholestyramine and niacin, irrespective of dosage or form.

4. How has the patent landscape evolved since the issuance of this patent?
   The landscape has shifted towards more sophisticated formulations, such as controlled-release systems and combination therapies targeting side effects, building upon the foundational claims of P5,258,510.

5. What strategic considerations should developers keep in mind?
   Focus on innovative delivery mechanisms, personalized dosing, and minimizing adverse effects to differentiate new products beyond the scope of expired patents.

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References

1. United States Patent and Trademark Office (USPTO). Patent No. 5,258,510.
2. Schering Corporation. (1992). Patent application documents and related literature.
3. Relevant literature on lipid-lowering drug combination patents and formulations.
4. Market analysis reports indicating patent expiration timelines and generic entry.

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Note: All details are based on publicly available patent records and industry analyses as of 2023.

Drugs Protected by US Patent 5,258,510

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 5,258,510

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0450097		CA 2009 00031	Denmark
European Patent Office	0450097		SPC/GB09/037	United Kingdom
European Patent Office	0450097		300408	Netherlands
European Patent Office	0450097		09C0049	France
European Patent Office	0450097		C300408	Netherlands