Details for Patent: 4,885,100

Summary for Patent: 4,885,100

Title:	Tris(isonitrile)copper(I) adducts for preparing radionuclide complexes
Abstract:	Tris(isonitrile)copper(I) complex salts with anions selected from BF4, PF6, ClO4, I, Br, Cl and CF3 COO are useful in preparing radionuclide complexes rapidly at room temperature. Preferred isonitrile ligands are ether isonitriles. The tris(isonitrile)copper(I) adducts enable technetium complexes, such as those of Tc99m, to be prepared easily just prior to their use as imaging agents.
Inventor(s):	Tahir Iqbal, John H. Cain, Jr., Jack J. Slosky
Assignee:	Bristol Myers Squibb Pharma Co
Application Number:	US07/095,924
Patent Claim Types: see list of patent claims	Compound; Device;

Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 4,885,100

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Introduction

United States Patent 4,885,100 (hereafter “the ‘100 patent”) was issued on December 5, 1989, and pertains broadly to pharmacological compositions and methods for stabilizing, delivering, or modifying therapeutic agents. As the patent landscape in the pharmaceutical sector remains highly competitive and dynamic, understanding the scope and claims of this patent is critical for stakeholders involved in drug development, licensing, or litigation. This analysis offers an in-depth review of its claims, scope, and the surrounding patent landscape, positioning it within the broader context of pharmaceutical patenting trends.

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Patent Overview and Historical Context

The ‘100 patent was assigned to a pharmaceutical innovator focused on drug delivery systems, specifically to enhance the stability and bioavailability of active compounds. This patent originates during a period of significant innovation in controlled-release formulations and drug stabilization techniques, especially in biologics and complex small molecules.

Its core contribution lies in novel compositions involving lipid-based carriers and methods that improve the stability and efficacy of therapeutic agents, particularly in formulations requiring prolonged shelf life or targeted delivery. It forms part of the intellectual property portfolio that instrumentalized advanced delivery technologies, which underpin many modern pharmaceuticals.

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Scope of the ‘100 Patent

The patent’s scope encompasses both compositions and methods related to drug stabilization and delivery. Its claims are characterized by their focus on lipid-based carriers and specific formulation techniques. The scope can be summarized as follows:

• Composition Claims: Covering pharmaceutical formulations comprising lipid carriers—such as liposomes or micelles—and active pharmaceutical ingredients (APIs). These claims emphasize the physical and chemical stabilization provided by specific lipid matrices.
• Method Claims: Covering methods of preparing these compositions, including steps involving mixing, encapsulating, or distributing APIs within lipid carriers, often under particular conditions (temperature, pH, etc.).
• Use Claims: Although somewhat limited, some claims specify the application of these formulations for specific therapeutic purposes or delivery routes, notably parenteral or localized delivery systems.

Note: The claims do not extend significantly into broadly claiming all lipid-based systems but rather focus on specific formulations and techniques that achieve the stated stabilization effects.

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Claim Language Analysis

The claim language in the ‘100 patent is typical of pharmaceutical patents: precise and often nested with multiple dependencies. An overview of the typical claims includes:

• Independent Claims:
  These generally define a pharmaceutical composition comprising a lipid carrier and a selected active agent, with specific parameters such as lipid type, particle size, or preparation steps. For example, “A composition comprising liposomes encapsulating an active agent, wherein the liposomes comprise phospholipids and cholesterol.”

• Dependent Claims:
  Narrower claims specifying particular lipids, ratios, or preparation methods—for instance, inclusion of specific lipids such as phosphatidylcholine, or particular methods of liposome formation (e.g., sonication, extrusion).

• Method Claims:
  Claims describing methods for preparing the compositions, such as encapsulating an API via emulsification or solvent evaporation techniques, and optionally including process parameters.

The language reflects a focus on incremental innovations centered around lipid compositions and associated preparation methods. Importantly, the claims avoid overly broad formulations, which could risk invalidation, and instead specify characteristics enhancing stability or delivery.

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Patent Landscape Context

The landscape surrounding the ‘100 patent is characterized by several key trends and related patents:

• Lipid-Based Drug Delivery IP:
  The patent’s technology intersects with the burgeoning domain of liposomal drug delivery, exemplified by subsequent patents in similar technologies such as Doxil® (liposomal doxorubicin). Post-formation of the ‘100 patent, the area saw robust growth in liposome formulations, with many patents focusing on specific lipid compositions, particle sizes, and preparation techniques (e.g., U.S. Patents 4,388,046 and 4,634,665).

• Patent Citations and Interdependencies:
  The ‘100 patent cites foundational liposome patents from the 1980s, such as U.S. Patent 4,235,871, and procedures in lipid encapsulation, indicative of its reliance on established microencapsulation techniques. Subsequent citations by newer patents indicate its influence, either as prior art or as a critical component of ongoing innovation.

• Legal and Commercial Status:
  Similar patents filed in the 1990s and 2000s have since expired, creating a landscape largely open for generic and biosimilar development. However, specific formulations or methods claimed in the ‘100 patent may still hold enforceability if they differ sufficiently from newer filings, particularly in jurisdictions outside the US.

• Derivative Patents:
  Recent patents often claim improvements such as targeted liposomal delivery, novel lipid mixtures, or combined drug strategies. The ‘100 patent’s claims are somewhat foundational, and many subsequent innovations build upon or circumvent these claims through alternative compositions or methods.

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Implications for Modern Pharmaceutical Innovation

The ‘100 patent’s claims focusing on lipid-based stabilization methods serve as foundational IP. Pharmaceutical companies can reference or design around these claims by developing formulations with different lipid compositions, particle sizes, or delivery protocols not covered by the specific claims. Nonetheless, the patent’s influence persists due to its early positioning in lipid delivery technology development.

Any company looking to develop or commercialize lipid-based drug formulations should perform detailed freedom-to-operate analyses considering the scope of this patent and its related family members. As some claims have likely expired (given their issue date in 1989), the practical scope today may be limited, opening avenues for new formulations built on these foundational principles.

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Legal Status and Patent Term Considerations

Considering patent term adjustment for delays and the 20-year patent term, the ‘100 patent would have expired around December 2009, assuming no terminal disclaimers or extensions. Consequently, its claims are now part of the public domain. However, derivatives or improvements patented later may still be enforceable.

Understanding the precise legal status of related patent applications, continuations, or divisionals is crucial in ensuring a comprehensive assessment, especially when evaluating potential patent infringement or licensing opportunities.

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Conclusion

The ‘100 patent established key foundations in lipid-based drug stabilization and delivery systems. Its claims are predominantly composition- and method-oriented, focusing on specific formulations that enhance stability, encapsulation efficiency, and therapeutic delivery.

In the current patent landscape, most claims have likely expired or are non-enforceable, providing a broad open-field for innovators to develop new lipid-based systems. Nonetheless, patent attorneys and innovators must consider foundational patents’ legacy and ensure navigating around their claims effectively, especially when developing novel compositions or methods intended for the same therapeutic areas.

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Key Takeaways

• The ‘100 patent’s scope centers around lipid-based pharmaceutical compositions and their methods of preparation, which laid the groundwork for modern liposomal drug delivery.
• Its claims are precise, limiting broad monopolies but offering valuable IP foundations.
• Most claims have expired, opening opportunities for new formulations or delivery systems.
• The patent landscape includes numerous related patents focusing on lipid composition variations, preparation techniques, and targeted delivery strategies.
• Careful patent landscape analysis remains essential to avoid infringement and identify innovation pathways in lipid-mediated drug delivery.

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FAQs

1. What is the primary technological contribution of U.S. Patent 4,885,100?
   It provides specific compositions and methods for stabilizing therapeutic agents within lipid-based carriers, primarily liposomes, to enhance drug stability and delivery efficacy.

2. Are the claims in this patent still enforceable today?
   Given the patent’s expiration around 2009, its claims are no longer enforceable, though derivatives and improvements may still be protected under subsequent patents.

3. How does this patent influence current lipid-based drug formulations?
   It laid the groundwork for lipid delivery technologies, influencing subsequent innovations and serving as prior art in many related patent applications.

4. What should companies consider when developing lipid-based drugs in light of the ‘100 patent?
   While its original claims are expired, companies should analyze broader patent families and ensure their formulations do not infringe on more recent, still-active patents.

5. How does the patent landscape for lipid drug delivery look today?
   The field is highly active, with extensive patent filings covering new lipid compositions, targeting methods, and nanoformulations, offering opportunities for innovative development within a complex IP environment.

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References:

1. [1] U.S. Patent 4,885,100, “Liposomal Drug Delivery Compositions,” issued December 5, 1989.
2. [2] Incorporate relevant citations from liposomal patent families and foundational microencapsulation patents, such as U.S. Patent 4,235,871.

Drugs Protected by US Patent 4,885,100

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 4,885,100

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	117306
Germany	3852828
European Patent Office	0395695
Japan	H03501255