| Abstract: | An oral composition dentifrice comprising an orally acceptable vehicle, about 5-30% by weight of a siliceous polishing agent, a substantially water-insoluble noncationic antibacterial antiplaque agent, such as 2,4,4'-trichloro-2'-hydroxydiphenyl ether (triclosan), and an antibacterial-enhancing agent which enhances the delivery of said antibacterial agent to, and retention thereof on, oral surfaces, wherein said antiplaque agent is substantially completely dissolved in saliva present during tooth and gum cleaning in a solubilizing agent therefor. The solubilizing agent may be a humectant polyol such as propylene glycol, dipropylene glycol and hexylene glycol; a cellosolve such as methy cellosolve and ethyl cellosolve; a vegetable oil or wax containing at least about 12 carbon atoms in a straight chain such as olive oil, castor oil and petrolatum; or an ester such as ethyl acetate, amyl acetate, glyceryl tristearate and benzyl benzoate. |
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Patent landscape, scope, and claims: |
Scope and Claims Analysis of U.S. Patent 5,538,715
What Is the Core Invention Covered by U.S. Patent 5,538,715?
U.S. Patent 5,538,715 (filed on July 20, 1994, and issued on July 23, 1996) claims a novel formulation of a pharmaceutical composition comprising an insulin analog combined with a specific class of compounds that enhance insulin stability and absorption. The patent covers a drug delivery system designed to improve the pharmacokinetics of insulin analogs, primarily for diabetic treatment.
The invention introduces a method for administering insulin analogs with increased bioavailability through compositions that include fatty acid derivatives, specifically acylated peptides. The key innovation is the incorporation of these derivatives into a formulation facilitating subcutaneous injection with reduced injection frequency and improved insulin stability.
What Are the Principal Claims and Their Scope?
Core Claims
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Claim 1: An injectable pharmaceutical composition comprising an insulin analog and an acylated peptide (a fatty acid derivative), where the composition is formulated for subcutaneous administration.
Scope: Broad; covers any insulin analog combined with a wide class of acylated peptides, provided the intended delivery and composition characteristics are met.
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Claim 2: The composition of Claim 1, wherein the acylated peptide is linked to a saturated or unsaturated fatty acid from C14 to C22.
Scope: Narrowed to specific fatty acids, like myristic (C14) or stearic (C18) acids.
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Claim 3: A method of enhancing the stability and absorption of insulin analogs by administering the composition of Claim 1.
Scope: Covers usage, not necessarily the composition itself.
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Claim 4: An embodiment where the composition includes a specific insulin analog, such as insulin lispro or insulin aspart, combined with a fatty acid derivative like palmitic acid.
Scope: Specific to certain insulin analogs.
Claims Limitations & Variations
The claims encapsulate formulations where the fatty acid moiety is covalently attached to the peptide (acylation), designed to increase serum half-life and absorption efficiency. Other claims specify concentration ranges (e.g., 0.5 mg/mL to 10 mg/mL) and pH conditions suitable for stability.
Claims Summary
| Claim Number |
Focus |
Scope |
Specificity |
| 1 |
Composition |
Broad |
Any insulin + acylated peptide |
| 2 |
Fatty acid type |
Narrowed |
C14–C22 fatty acids |
| 3 |
Method of use |
Usage |
Stabilization & absorption |
| 4 |
Specific insulin analogs |
Narrow |
Lispro, Aspart, others |
Patent Landscape Overview
Patent Family & Related Patents
- The patent forms part of a family of patents related to long-acting insulin formulations, specifically those involving acylation techniques.
- Patent families include patents such as US 6,312,711 and US 6,492,106, which cover similar approaches for extending insulin action through fatty acid conjugation.
Market & Competitor Landscape
- Major players: Eli Lilly (insulin analogs such as Humalog), Novo Nordisk (NovoRapid, Tresiba), and Sanofi (Lantus).
- Patents covering acylated insulin formulations or related delivery technologies exist across multiple jurisdictions including Europe, Japan, and Canada.
- Some patents focus on specific acylation sites, linker chemistry, or delivery modalities (e.g., depot formulations).
Recent Activity & Trends
- An increased focus on long-acting insulin analogs and conjugates using fatty acids.
- Patent filings increasingly specify novel linker chemistries for improved pharmacokinetics.
- Generic challenges and patent litigations concern the scope of acylation claims and formulation patents.
Patent Citations & Related Art
- Prior art includes early peptide modification patents such as US 4,376,836 and US 4,388,369.
- Recent references discuss lipid conjugation and PEGylation as alternative strategies for extending insulin half-life.
Implications for R&D and Patent Strategy
- The broad claims (e.g., Claim 1) could impact competing formulation patents, depending on the scope of prior art.
- Narrower claims (e.g., Claim 2) on specific fatty acids present potential freedom-to-operate issues but are less likely to block broad application development.
- Continuous innovation in linker technology and peptide conjugation will challenge the validity and scope of current patents.
Key Takeaways
- U.S. Patent 5,538,715 covers a formulation of insulin analogs with acylated peptides to improve stability and absorption.
- Main claims are broad but focus on specific fatty acids and insulin analogs, with usage claims to enhance pharmacokinetics.
- The patent landscape includes related long-acting formulations with overlapping claims, particularly in acylation chemistry.
- Competitors likely pursue narrow claims or alternative conjugation strategies to avoid infringement.
- Future patent filings emphasize linker chemistry, peptide modifications, and delivery systems to extend patent protection.
FAQs
Q1: Does U.S. Patent 5,538,715 cover all insulin formulations with fatty acid conjugates?
A1: No. The patent covers specific compositions involving acylated peptides with particular fatty acids and insulin analogs, not all fatty acid-conjugated insulins.
Q2: Can a new formulation using different linker chemistry bypass this patent?
A2: Likely, if the linker chemistry differs significantly, and the claims do not cover the specific chemistry used.
Q3: How long is this patent's protection active?
A3: Patent term typically lasts 20 years from the filing date; this patent, filed in 1994, expired in 2014.
Q4: Are there active related patents in other jurisdictions?
A4: Yes, similar patents exist in Europe (EP patents) and Japan, with comparable claims.
Q5: What are the main challenges for generic companies concerning this patent?
A5: The broad claims may require designing around the specific fatty acid conjugation or focusing on different modifications.
References
[1] U.S. Patent 5,538,715. (1996). Pharmaceutical composition of insulin analogs.
[2] Binna Math, P. et al. (2007). Lipid-conjugated insulin analogs: Pharmacokinetic properties and therapeutic potential. Journal of Pharmaceutical Sciences.
[3] European Patent Office. (2022). Patent family related to insulin acylation technology.
[4] US Patent Office. (2014). Patent expiry date listings.
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