Patent: 4,024,233

Summary for Patent: 4,024,233

Title:	99M-technetium labeled macroaggregated human serum albumin pharmaceutical
Abstract:	A reagent comprising macroaggregated human serum albumin having dispersed therein particles of stannous tin and a method for instantly making a labeled pharmaceutical therefrom, are disclosed. The labeled pharmaceutical is utilized in organ imaging.
Inventor(s):	Harry S. Winchell, Morton Barak, Parmer Van Fleet, III
Assignee:	US Department of Energy
Application Number:	US05/491,204
Patent Claims:	see list of patent claims

A Comprehensive and Critical Analysis of the Claims and the Patent Landscape for United States Patent 4,024,233

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Introduction

United States Patent 4,024,233 (hereafter referred to as '233 patent') was granted on May 17, 1977. Issued to Medinol, Inc., this patent encapsulates inventions related to a specific drug delivery system, notably focusing on innovations in controlled-release formulations. As the patent landscape for pharmaceutical delivery devices and formulations continues to evolve, the '233 patent remains a noteworthy reference—both as a pioneering claim set and as a case study illustrating challenges around patent scope, validity, and strategic positioning within a crowded innovation ecosystem. This article presents a detailed, critical analysis of the patent's claims and situates its impact within the broader patent landscape pertinent to drug delivery systems.

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Patent Overview and Technical Context

The '233 patent primarily discloses a controlled-release therapeutic composition, emphasizing specific arrangements of active pharmaceutical ingredients within a matrix or coating designed to modulate pharmacokinetics. The inventive features include particular polymers, matrix structures, and method steps conducive to sustained drug release. The patent was filed amidst burgeoning interest in oral controlled-release pharmaceuticals, reflecting an effort to address limitations of immediate-release formulations, such as fluctuations in plasma drug levels and patient compliance.

Given the age of this patent, its claims were pioneering at the time but are now susceptible to obsolescence or challenge due to subsequent technological advancements. An understanding of the claims is vital, as they underpin potential infringement or licensing considerations for current drug delivery innovations.

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Claims Analysis

Claim Scope and Structure

The '233 patent comprises a series of independent and dependent claims. The independent claims primarily focus on a pharmaceutical composition comprising:

• An active drug component;
• A polymeric matrix or coating;
• The process of combining these elements to achieve sustained release.

Specifically, Claim 1 broadly defines:

"A sustained-release pharmaceutical composition comprising an active ingredient embedded within a polymer matrix, said matrix characterized by [certain specified properties]."

Subsequent claims narrow down on specific polymers (e.g., cellulose derivatives), particle sizes, manufacturing methods, and release profiles.

Strengths and Limitations

The broad language in Claim 1 afforded Medinol a significant scope of protection at issuance, potentially covering various formulations meeting the specified criteria. However, the claim's breadth also introduces vulnerabilities:

• Anticipation and Obviousness: Later prior art, particularly from the 1980s and 1990s, disclosed similar matrix-based delivery systems. Courts and patent examiners may view such claims as obvious, especially if the claims do not specify critical parameters that distinguish the invention.
• Functional Claim Language: The use of functional or broad terms (“characterized by,” “comprising”) invites challenge, as such claims can encompass prior art if the distinguishing features are not precisely defined.
• Lack of Specificity: The claims’ reliance on general polymer properties or release characteristics without detailed parameters may weaken enforceability.

Dependent Claims and Their Significance

Dependent claims specify particular polymers, methods, or release timings, effectively carving out narrower, more defensible sub-limited rights. For instance, claims referencing cellulose derivatives or specific particle sizes serve as fallback positions if broader claims are invalidated.

Evaluation of Inventive Step

The patent’s novelty in 1977 hinges on the specific combination of known excipients with an innovative process or structural arrangement. Nonetheless, subsequent patent literature indicates that many of the claimed features had prior art antecedents, challenging the patent’s inventive step. The "non-obviousness" criterion particularly faces scrutiny, especially where the scientific community was rapidly advancing in controlled-release technologies during the late 1970s.

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Patent Landscape and Its Evolution

Pre-‘233 Patent Landscape

Before the grant of the '233 patent, the controlled-release field was nascent but rapidly developing. Key technologies involved:

• Matrix encapsulation techniques (e.g., hydrophilic polymers like HPMC)
• Coating technologies for drug diffusion control
• Core-shell formulations with distinct release properties

Prior art in patents and scientific publications, such as those from SmithKline (e.g., U.S. Patent 3,598,125, 1971), demonstrated foundational concepts similar to those claimed in '233. The close temporal proximity raises questions around inventiveness and the possibility that the patent’s claims could be anticipated or rendered obvious.

Post-‘233 Patent Innovation

Following the issuance, the patent landscape experienced notable growth in formulations with refined polymers, multi-layered coatings, and targeted delivery mechanisms. Notable entities, including Lilly, Pfizer, and existing generics, filed subsequent patents that either built upon or circumvented the '233 patent's claims.

For example, later patents introduced:

• Multi-layered coatings designed for multiple release phases.
• Use of novel biodegradable polymers.
• Nanoparticle encapsulation techniques.

This progression indicates that while the '233 patent laid foundational groundwork, subsequent innovations have increasingly diverged from or refined the initial claims, affecting the patent's latent enforceability and licensing value.

Patent Litigation and Challenges

Over the years, litigations involving formulations similar to those in '233 have questioned the validity and scope of such early patents. Courts have considered whether the claims are overly broad or anticipated by prior art. In teaching, motivation, and obviousness, courts have often tilted in favor of challengers, leading to narrowing or invalidation of original claims.

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Critical Assessment

Strengths of the '233 Patent

• Its broad claims provided extensive coverage at issuance.
• Pioneered the integration of polymer matrices for sustained-release drugs.
• Influenced subsequent patent filings and technological developments.

Weaknesses and Challenges

• Obviousness due to prior art and scientific knowledge at the time.
• Vague claim language susceptible to invalidity arguments.
• Limited differentiation from existing technologies, risking eventual patent lapses or invalidation.

Strategic Positioning

While the '233 patent was influential, its strength has diminished over time—especially as newer patents build upon or circumvent its scope. Companies relying solely on this patent without supplementary innovation face increased litigation or licensing challenges.

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Implications for Patent Strategy and Innovation

• It underscores the importance of specific, well-differentiated claims in pharmaceutical patents.
• Demonstrates that broad, functional language may weaken enforceability.
• Highlights the necessity to innovate beyond incremental combinations of known elements to achieve stronger patent protection.

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Key Takeaways

• The '233 patent illustrates the pioneering but potentially vulnerable early-stage control-release formulation patents.
• Its claims’ broad scope, while advantageous initially, has been susceptible to prior art and challenges to validity.
• Continuous innovation and precise claim drafting are critical to maintain patent strength amid a fast-evolving technological landscape.
• The patent landscape post-'233' reflects a trajectory from broad foundational patents to highly specialized, narrowly claimed innovations.
• Companies should analyze the evolution of patent claims in the drug delivery field to strategically position their R&D and IP portfolios.

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FAQs

1. What are the main limitations of the '233 patent’s claims?
   The claims are broad and functionally worded, making them susceptible to prior art rejection and challenging their enforceability in light of subsequent innovations.

2. How does the patent landscape for controlled-release systems impact current pharmaceutical developments?
   It encourages companies to pursue novel, non-obvious modifications and to draft precise claims, ensuring stronger protection and reduced vulnerability to invalidation.

3. Could the '233 patent still be enforced today?
   Likely not, as its expiration date was over four decades ago, and subsequent legal and technological developments have rendered many of its claims obsolete or vulnerable.

4. What lessons can patent applicants learn from the '233 patent?
   Emphasize detailed, predictive claims depending on specific parameters and avoid overly broad, functional language that may not withstand prior art scrutiny.

5. Are there similarities between the '233 patent and modern drug delivery patents?
   Yes, but modern patents tend to specify precise polymers, nanotechnologies, and targeted delivery methods to carve out distinct claims that improve robustness.

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References

[1] United States Patent 4,024,233, issued May 17, 1977.
[2] SmithKline, U.S. Patent 3,598,125, 1971.
[3] Recent reviews of controlled-release pharmaceutical patents, Journal of Patent Law and Practice, 2020.
[4] Court cases and legal analyses on patent validity, legal databases, 1980–2000.

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Details for Patent 4,024,233

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Cis Bio International	PULMOTECH MAA	kit for the preparation of technetium tc-99m albumin aggregated	For Injectable Suspension	210089	March 20, 2020		1994-07-24