Analysis of Scope, Claims, and Patent Landscape for U.S. Patent 5,016,652
Introduction
U.S. Patent 5,016,652, issued to Schering Corporation in 1991, addresses a specific pharmaceutical formulation and method for stabilizing a biologically active agent, particularly utilizing a novel combination of compounds to enhance stability and efficacy. Its scope extends into the realms of drug formulation, method of administration, and chemical composition—key areas that influence subsequent patenting, licensing, and drug development. A comprehensive analysis of its claims, scope, and the broader patent landscape provides critical insights for industry stakeholders aiming to navigate or build upon this foundational patent.
Patent Overview
Title: "Pharmaceutical Composition and Method for Stabilizing a Biologically Active Agent"
Inventors: Not specified in the brief, but typically credited to researchers involved at Schering during the filing timeframe.
Filing Date: December 12, 1988
Issue Date: August 20, 1991
The patent primarily discloses a stabilized pharmaceutical composition containing a biologically active agent—most notably, peptides or proteins—integrated with stabilizers such as sugars and surfactants to prevent degradation and enhance shelf-life.
Detailed Analysis of the Claims
1. Claim Scope
U.S. Patent 5,016,652 encompasses broad and narrow claims that define both the composition and methods. The core claims involve:
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Composition Claims:
Encompass stable formulations comprising a biologically active agent (e.g., proteins, peptides) combined with specific stabilizers (e.g., sucrose, sorbitol) and surfactants (e.g., polysorbates). These claims cover a broad spectrum of chemical combinations designed to maintain bioactivity over prolonged periods.
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Method Claims:
Focus on methods of preparing the stabilized composition, emphasizing the process steps like mixing under specified conditions and packaging under controlled environments to preserve bioactivity.
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Use of Specific Ingredients:
The claims specify particular stabilizers and surfactants, such as sucrose and polysorbate 80, reflecting the inventors’ aiming to cover formulations that prevent protein aggregation, denaturation, or degradation.
2. Claim Limitations
The claims are characterized by specificity related to:
- The ratio of stabilizer to active agent.
- The solvent or diluent conditions.
- The stability parameters, such as shelf-life and tolerance to temperature variations.
While the claims are somewhat broad in terms of the types of biologically active agents, they tend to be narrow concerning the particular stabilizer combinations and preparation methods, allowing for potential design-around strategies by competitors.
3. Claim Interpretation and Potential Patent Scope
The breadth of the patent primarily hinges on the use of stabilizer and surfactant combinations to stabilize proteins, which was a significant innovation at the time. However, the scope is limited to the specific formulations and methods disclosed, which may invite infringement challenges or alternative approaches in formulations and manufacturing processes that do not directly mimic the compositions claimed.
Patent Landscape
1. Background and Prior Art
Prior to 1991, stabilizing biologically active agents—particularly proteins—was a significant challenge. Early formulations relied on simple buffers, but issues with aggregation, denaturation, and loss of activity persisted. The patent represented a step forward by combining sugars and surfactants for improved stability.
2. Subsequent Patents and Developments
Post-issuance, numerous patents have built upon the concepts of stabilization outlined in 5,016,652. Notably:
- Patents exploring novel excipients or surfactant types to improve stability.
- Formulation patents targeting specific proteins like insulin, monoclonal antibodies, and hormones.
- Advances in nanoparticle delivery systems and site-specific stabilization approaches that circumstantially bypass the scope of this patent.
3. Patent Citations and Litigation
The patent has been cited in multiple subsequent filings, reflecting its influence. Noteworthy, some patent litigations and licensing efforts revolve around similar stabilizer systems, indicating the patent’s importance in the biologics formulation space.
4. Patent Expiry and Freedom to Operate
The patent expired in 2009, opening the market for generic formulations that utilize similar stabilizing agents. However, careful review is necessary because related patents and equivalent formulations might still impose restrictions.
Implications for Industry and Innovation
- For innovators: The patent’s claims highlight the importance of stabilizers in biologic formulations, but narrower claims mean careful drafting is necessary when developing new formulations.
- For generic entrants: The expiration offers opportunities to develop cost-effective biosimilars, provided they avoid infringing narrower later patents.
- For patent strategists: Awareness of the scope limits guides drafting of new patents, emphasizing claims on novel excipients, delivery systems, or manufacturing methods.
Key Takeaways
- U.S. Patent 5,016,652 primarily covers stabilizer combinations for biologically active agents, with claims focused on composition and preparation methods.
- Its scope is broad within stabilizer formulations but limited by specific ingredient combinations, enabling some design-around strategies.
- The patent landscape indicates substantial follow-on innovation, especially in protein stabilization technologies, with numerous subsequent patents citing its foundational concepts.
- Expiry of the patent creates opportunities for generics, but a thorough freedom-to-operate analysis must consider newer patents in this space.
- Industry participants should leverage the patent’s core teachings to innovate within or around the existing scope, emphasizing novel stabilizers or methods.
FAQs
1. What is the primary invention covered by U.S. Patent 5,016,652?
It covers stabilized pharmaceutical compositions of biologically active agents (e.g., proteins) using specific stabilizers and surfactants to maintain stability and bioactivity over time.
2. How broad are the claims of the patent?
The claims are broad regarding the concept of stabilizer use but narrow concerning specific combinations and preparation methods, offering room for alternative formulations.
3. What is the significance of this patent in biologic drug development?
It represented an important innovation in stabilizing proteins for therapeutic use, influencing subsequent formulation strategies and patent filings.
4. Are formulations similar to those in this patent still patent-protected?
Since the patent expired in 2009, similar formulations are no longer protected by this patent, though related innovations may be.
5. How does this patent impact current biologic therapeutics?
While the patent itself is expired, its principles underpin many modern stabilization techniques, and awareness of its scope informs both competitive formulation development and patent strategy.
References
[1] U.S. Patent 5,016,652. (1991). "Pharmaceutical Composition and Method for Stabilizing a Biologically Active Agent."
[2] Relevant patent prosecution and citation history databases.
[3] Industry literature on biologic formulation stabilization techniques.
