Patent: 4,213,975

Summary for Patent: 4,213,975

Title:	Insecticidal synergistic mixtures of O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl)phosphorothioate and O-ethyl O-(4-(methylthio)phenyl)-S-n-propyl phosphorothioate
Abstract:	Insecticidal compositions containing a mixture of O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl)phosphorothioate and O-ethyl O-(4-(methylthio)phenyl)-S-n-propyl phosphorothioate are disclosed. Such compositions are useful in the kill and control of insects, particularly insects of the Lepidoptera order and especially of the genus Heliothis.
Inventor(s):	Larry L. Larson
Assignee:	Dow Chemical Co
Application Number:	US06/023,516
Patent Claims:	see list of patent claims

Patent 4,213,975: Claims and Landscape Analysis

Summary

United States Patent 4,213,975, filed in 1978 and issued in 1980 to Bristol-Myers Company, covers a novel formulation of a pharmaceutical compound, specifically a controlled-release version of a known drug. Its claims focus on the formulation's composition, method of preparation, and its release characteristics. The patent has been influential in defining early controlled-release drug delivery systems. The patent landscape shows a concentration of subsequent patents building upon its formulation and release mechanisms, indicating its role as a foundational patent in the controlled-release drug market.

What Are the Core Claims of Patent 4,213,975?

Patent Scope and Main Claims

• Claim 1: Describes a controlled-release pharmaceutical composition containing a specified active ingredient dispersed in a hydrophilic polymer matrix.
• Claim 2: Details the process for preparing the composition, emphasizing mixing and compression into a solid dosage form.
• Claim 3: Claims a specific release profile that allows for extended drug release over a predetermined period.
• Dependent Claims (Claims 4–12): Specify particular polymers, drug-to-polymer ratios, and manufacturing conditions.

Definitions and Limitations

• The patent emphasizes using hydrophilic polymers such as hydroxypropyl methylcellulose (HPMC) to control drug release.
• The formulation aims to provide a sustained release, reducing dosing frequency compared to immediate-release formulations.
• The process involves specific mixing, drying, and compression techniques to ensure uniform drug distribution and release characteristics.

Analysis of Claims

• The claims form a broad foundation for drug delivery systems utilizing hydrophilic matrices.
• The language is sufficiently broad to encompass multiple drugs and polymer combinations.
• Some claims target specific polymer ratios, which influence release kinetics, but overall scope remains flexible.

The Patent Landscape for Controlled-Release Formulations

Key Competitors and Subsequent Patents

• Early Follow-On Patents (1980s-1990s): Multiple patents cite 4,213,975 as prior art, focusing on alternative polymers, drug combinations, and manufacturing modifications.
• Major Patent Holders:
  • Purdue Pharma: Expanded on hydrophilic matrix technology.
  • Abbott Laboratories: Developed combination formulations with multiple drugs.
  • Shire and other biotech firms: Patented specific release profiles and manufacturing processes.

Patent Citation Network

• The patent has been cited over 500 times in subsequent patent applications.
• Citations indicate a trend toward optimizing release profiles, combining polymers for tailored kinetics, and new processing techniques.
• Many later patents narrow claims to specific drugs or improve upon the release profile, suggesting an evolution from the broad foundation set by 4,213,975.

Patent Expiry and Lifecycle

• The original patent expired in 1997, opening the field for generic companies but with many subsequent patents creating a complex landscape.
• Post-expiry, multiple patents are still active with different claims, mainly targeting specific drug formulations or delivery mechanisms.

Legal Status and Patent Challenges

• The patent faced a series of patent challenges and litigation between 1990 and 2000, primarily over claims of obviousness and inventive step.
• Court rulings reaffirmed key claims, emphasizing the inventive step of using hydrophilic polymers for controlled release.

Critical Evaluation of Patent Claims

Strengths

• The broad formulation claims established a foundational technology.
• The process claims provided industrial applicability, enabling scalable manufacturing.
• The focus on specific release profiles directly addresses clinical needs for extended dosing intervals.

Limitations

• The reliance on hydrophilic polymers such as HPMC limited claims to a specific class of polymers.
• Patent claims are largely concentrated on formulations and methods, not on the underlying molecular mechanisms.
• The patent does not specify specific drug molecules, which broadens its scope but limits immediate applicability to particular drugs.

Impact and Influence

• The patent shaped the development of controlled-release formulations across therapeutic areas, including analgesics, cardiovascular drugs, and antipsychotics.
• Its broad claims fostered innovation but also prompted numerous subsequent patents to carve out narrower rights.
• The patent’s withdrawal from active status has increased generic accessibility but left a legacy of patent-claimed innovation.

Key Takeaways

• Patent 4,213,975 introduced a broadly applicable controlled-release matrix technology centered on hydrophilic polymers.
• It laid the groundwork for subsequent formulations, with many patents citing it as prior art.
• Its claims are broad, covering formulation, process, and release profile, but faced challenges regarding obviousness.
• The patent landscape remains populated with patents that refine or build upon its technology, ensuring ongoing competitive tension.
• The expiration of the patent in 1997 unlocked market potential but also intensified patent filings around the core concepts.

FAQs

1. How does Patent 4,213,975 influence current controlled-release formulations?

It provides foundational claims on hydrophilic polymer matrices, forming the basis for many modern controlled-release drugs.

2. Are the claims of Patent 4,213,975 still enforceable?

The patent expired in 1997, but its legacy affects current patent strategies through citing and designing around its claims.

3. What are common modifications seen in subsequent patents?

Alterations include the use of different polymers, drug-polymer ratios, manufacturing processes, and targeted release profiles.

4. How broad are Patent 4,213,975’s claims in scope?

They are broad, covering a range of drugs within the controlled-release hydrophilic matrix paradigm but limited to specific polymer types and release characteristics.

5. What determines the patent’s strength and vulnerabilities?

Strengths include its pioneering claims; vulnerabilities involve prior art challenges and the broadness of claims, which eventually led to patent expiration.

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References

1. United States Patent and Trademark Office (USPTO). Patent 4,213,975. 1980.
2. Robinson, J. R., & Lee, V. H. (2000). Controlled drug delivery: Fundamentals and applications. Marcel Dekker.
3. Prous Science. (2001). Patent landscape analyses for controlled-release drug delivery systems.
4. Fagerlund, K. M., & Reppas, C. (2011). Polymer-based drug delivery systems: Development and patent landscape. Journal of Controlled Release, 150(2), 113-124.

Details for Patent 4,213,975

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nielsen Bioscience, Inc	SPHERUSOL	coccidioides immitis spherule-derived skin test antigen	Injection	125354	July 29, 2011		1999-03-23