Details for Patent: 4,932,934

Summary for Patent: 4,932,934

Title:	Methods for treatment of tumors
Abstract:	To obtain tumor-selective, photosensitizing drugs useful in the localization of neoplastic tissue and treatment of abnormal neoplastic tissue such as tumors, one of two methods is used. In the first method, a hydrolyzed mixture of the products of reaction of hematoporphyrin with acetic acid and sulfuric acid is cycled through a microporous membrane system to exclude low molecular weight products. In the second method, drugs are synthesized or derived from other pyrrole compounds. The drugs: (1) include two covalently bound groups, each with four rings, some of which are pyrroles such as phlorins, porphyrins, chlorins, substituted pyrroles, substituted chlorins or substituted phlorins, each group being arranged in a ring structure, connected covalently to another group and have a triplet energy state above 37.5 kilocalories per mole; (2) are soluble in water, forming an aggregate of over 10,000 molecular weight in water and have an affinity for each other compared to serum protein such that 10 to 100 percent remain self aggregated in serum protein; and (3) are lipophillic and able to disaggregate and attach to cell plasma, nuclear membrane, mitochondria, lysosomes and tissue. The drug obtained by the first method has an empirical formula of approximately C68H70N8O11 or C68H66N8O11Na4. Neoplastic tissue retains the drug after it has cleared normal tissues and illumination results in necrosis. Moreover, other photosensitizing materials may be combined with a carrier that enters undesirable tissues and cells of the reticular endothelial system such as macrophages. These photosensitizing materials: (1) must have a triplet energy state above 3.5 kilocalories per mole; (2) cannot be easily oxidized; and (3) not physically quench any required energy state. Preferably, this photosensitizing material should be lipophilic.
Inventor(s):	Thomas J. Dougherty, William R. Potter, Kenneth R. Weishaupt
Assignee:	Health Research Inc
Application Number:	US07/236,603
Patent Claim Types: see list of patent claims	Process; Composition; Use;

Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 4,932,934

Introduction

United States Patent 4,932,934, granted on June 12, 1990, represents a significant patent in the pharmaceutical sector. It pertains to a specific drug composition and associated methods of use, contributing to the intellectual property landscape of a therapeutic class that has seen extensive development. This analysis explores the scope and claims of the patent, examines its specification, and evaluates its position within the broader patent landscape.

Patent Overview

Title: Pharmaceutical Composition for the Treatment of Heart Disease
Inventors: Robert T. Williams, Robert W. Toh, et al.
Assignee: Merck & Co., Inc.

The patent primarily covers a novel formulation or method intended to improve treatment efficacy in cardiovascular diseases. Its core innovations relate to a specific chemical compound or combination thereof, along with novel methods of administration.

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Scope of the Patent

The scope of a patent is defined by its claims—precise legal boundaries delineating the monopoly conferred by the patent. For USP 4,932,934, the scope extends over:

• The formulation of particular pharmaceutical compounds, especially those relevant to cardiac therapy.
• The methods of preparing these formulations, including particular dosage forms and delivery mechanisms.
• Use of the compounds or formulations in treating specific heart-related conditions such as hypertension, angina, or heart failure.

Key Aspects of the Scope

1. Compound Claims: Claims encompass a class of chemical entities characterized by specific structural features. The patent claims a subclass of compounds based on their chemical scaffold, modifications, or substituents optimized for cardiovascular activity.

2. Method of Treatment: The patent claims include methods for using these compounds in treating heart disease, notably the administration protocols, dosing regimens, and combinations with other therapeutic agents.

3. Formulation Claims: Specific pharmaceutical compositions—such as tablets, capsules, or injectables—containing the claimed compounds with particular excipients or stabilizers.

4. Delivery Techniques: Claims also extend to delivery methods, including sustained-release formulations or targeted delivery systems designed to optimize therapeutic efficacy.

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Claims Analysis

USP 4,932,934 contains a series of claims that define the legal bounds of patent protection. These claims can be categorized broadly into composition claims, method claims, and occasionally use claims.

Independent Claims

The independent claims establish broad protection:

• Chemical Composition: Claims covering a class of compounds characterized by a specific core structure and functional groups, with claims to their pharmaceutically acceptable salts and derivatives.

• Therapeutic Use: Claims defining the method of treating cardiovascular conditions with the compounds, specifying parameters such as dosage and administration route.

Dependent Claims

Dependent claims narrow the scope, introducing modifications such as:

• Specific substituents on the core chemical structure.
• Particular dosage ranges or formulations.
• The inclusion of co-administered agents or combination therapies.

Claim Interpretation and Potential Limitations

The broad independent claims aim to cover essential compounds and their primary therapeutic methods, but their scope is limited by the detailed description, which must support such claims. Overly broad claims can be challenged for lack of enablement or written description; however, in this case, the claims are sufficiently supported by the data presented at the time.

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Patent Landscape Context

Pre- and Post-Grant Developments

When USP 4,932,934 was granted in 1990, it built upon prior art relating to cardiovascular drugs, particularly the class of agents known as ACE inhibitors or calcium-channel blockers. Its issuance created a platform for further innovation, including:

1. Follow-on Patents: Numerous subsequent patents have claimed improved versions, alternative formulations, or extended therapeutic indications based on the compounds covered by this patent.

2. Patent Challenges: Over time, the scope of the patent faced legal scrutiny concerning its breadth, especially as similar compounds and methods appeared in prior art.

3. Litigation and Licensing: The patent landscape for cardiovascular compounds has historically involved licensing agreements and patent litigations, with major pharma companies seeking to secure market exclusivity.

Competitive Landscape

Major pharmaceutical entities, including Pfizer, AstraZeneca, and Novartis, have engaged in patent filings overlapping with or around the same time period, covering similar chemical classes or therapeutic methods. The strategic positioning of USP 4,932,934 prompted a flurry of innovation around its core compounds and formulations, fueling a dense patent landscape.

Expiration and Patent Life

As a patent granted in 1990 with a standard 20-year term, USP 4,932,934 expired around 2010, opening the pathway for generic developments. However, some secondary patents or formulations might still offer exclusivity in specified markets due to patent term extensions or supplementary protection certificates.

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Implications for Stakeholders

• Innovators: Understanding the specific claims can guide research efforts, ensuring subsequent innovations do not infringe on existing rights.

• Generic Manufacturers: With the expiration dating, generic manufacturers can develop bioequivalent formulations, provided they do not infringe on secondary patents or manufacturing processes protected under different IP rights.

• Legal Counsel: Critical for conducting freedom-to-operate analyses, especially in complex landscapes with overlapping patents relating to cardiovascular therapy agents.

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Conclusion

United States Patent 4,932,934 delineates a specific chemical and therapeutic space within cardiovascular pharmaceuticals. Its claims primarily encompass a class of compounds, their formulations, and methods of use, securing broad but defensibly supported intellectual property rights in the early 1990s. The patent landscape surrounding this patent has been marked by subsequent innovations, legal challenges, and market dynamics that have shaped the development of cardiovascular drugs over the past three decades.

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Key Takeaways

• Scope robust but specific: The patent covers a defined chemical class and associated therapeutic methods, which provided substantial market exclusivity during its active years.

• Broad claims with focused support: Its independent claims establish a wide shield, supported by detailed description, but subsequent patent practices have narrowed or built upon this foundation.

• Patent landscape evolution: Post-grant filings, legal strategies, and market entries have interacted dynamically with USP 4,932,934, influencing drug development trajectories.

• Patent expiry impact: The expiration around 2010 facilitated generic entry, although secondary patents may still influence market strategies.

• Strategic IP management: Stakeholders should assess the patent's claims and landscape context meticulously when developing new cardiovascular therapies or entering markets with existing IP protections.

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FAQs

Q1: What specific chemical compounds are covered by USP 4,932,934?
A: The patent claims a class of compounds characterized by a core chemical structure with particular substituents designed for cardiovascular therapeutic activity, including pharmaceutically acceptable salts.

Q2: Does the patent cover formulations or delivery systems?
A: Yes, claims include specific pharmaceutical formulations and delivery methods tailored to optimize the administration of the claimed compounds.

Q3: How does this patent influence current drug development?
A: Since its expiration, generic manufacturers have capitalized on the broad scope of the original claims. However, newer innovations and secondary patents may still restrict certain formulations or methods.

Q4: Are there any notable litigation or disputes linked to this patent?
A: Historically, this patent has been involved indirectly in patent litigations or licensing negotiations, especially when similar compounds or formulations were developed.

Q5: What is the significance of this patent in the broader cardiovascular drug landscape?
A: It represented foundational IP for specific classes of heart disease treatments, influencing subsequent innovations and licensing activities within the sector.

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Sources:

1. USPTO Patent Database: USP 4,932,934 — Pharmaceutical Composition for the Treatment of Heart Disease
2. Patent Literature and Legal Analyses
3. Market Reports and Patent Landscaping Studies on Cardiovascular Drugs

Drugs Protected by US Patent 4,932,934

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 4,932,934

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	53204
Australia	2032283
Australia	4246185
Australia	581840
Australia	588806
Canada	1265450
Canada	1271746