United States Patent 5,866,591: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
United States Patent 5,866,591, titled "Stable formulations of remifentanil," is a significant patent in the pharmaceutical industry, particularly in the field of anesthetic drugs. This patent, assigned to GlaxoWellcome (now part of GSK), pertains to the development and stabilization of remifentanil hydrochloride formulations.
Background on Remifentanil
Remifentanil hydrochloride is a potent N-phenyl-N-(4-piperidinyl)amide mu-opioid anesthetic used in clinical settings for anesthesia. It is commercially available under the tradename ULTIVA™[4].
Patent Overview
The patent focuses on the formulation and stabilization of remifentanil hydrochloride to ensure its long-term stability and efficacy.
Key Components of the Patent
- Active Ingredient: The patent centers around remifentanil hydrochloride, a mu-opioid anesthetic.
- Formulation: The patent describes various formulations, including lyophilized dosage forms and liquid solutions, designed to enhance the stability of remifentanil hydrochloride[4].
Claims of the Patent
The patent includes several claims that define the scope of the invention:
Formulation Claims
- The patent claims formulations containing remifentanil hydrochloride in combination with excipients such as glycine, mannitol, and sodium chloride. These formulations are designed to be stable over a prolonged period[4].
- Specific claims include the use of glycine to form stable complexes with remifentanil hydrochloride, which helps in maintaining the drug's stability[4].
Stability Claims
- The patent claims that the formulations can maintain a room temperature shelf life stability of at least two years with less than 10% degradation of the active drug substance[1][4].
- Stability studies showed that these formulations, when reconstituted with an aqueous solvent, retained their potency over an extended period[1].
pH Range Claims
- The patent specifies that the formulations are buffered to a pH range of 1.5 to 5, preferably between 2.5 and 3.5, and most preferably between 2.8 and 3.2. This pH range is crucial for maintaining the stability of the drug[4].
Patent Scope
The scope of the patent is defined by its claims and the detailed descriptions provided.
Intravenous Administration
- The patent is specifically focused on formulations suitable for intravenous administration. The diluted solutions contain from 1 mg of remifentanil per 10 to 1,000 mL of solution[4].
Exclusion of Non-Aqueous Solvents
- Unlike other patents that discuss non-aqueous solvents for other opioids, this patent does not include non-aqueous organic solvents as re-suspension agents for intravenous administration of remifentanil[1].
Prior Art and Related Patents
The patent builds upon and distinguishes itself from prior art.
U.S. Pat. No. 5,019,583
- This prior patent by Feldman et al. discusses various forms of remifentanil formulations, including oral, transdermal, rectal, and parenteral routes. However, it does not address the specific stability issues and formulations detailed in the '591 patent[1].
U.S. Pat. No. 6,660,715
- This patent teaches a formulation for pulmonary delivery of bioactive agents like fentanyl using non-aqueous organic solvents, which is distinct from the intravenous administration focus of the '591 patent[1].
Legal Status and Litigation
The patent has been the subject of legal proceedings.
Infringement Cases
- For example, Fresenius was accused of infringing one or more claims of the '591 patent by making, using, offering for sale, and/or selling generic versions of remifentanil formulations[2].
Impact on Pharmaceutical Industry
The '591 patent has significant implications for the pharmaceutical industry.
Stability and Efficacy
- The stable formulations described in the patent ensure that remifentanil hydrochloride remains effective over a longer period, which is crucial for its use in clinical settings[4].
Compliance and Regulation
- The patent's specifications and claims help in setting standards for the manufacture and storage of remifentanil hydrochloride, ensuring compliance with regulatory requirements.
Patent Scope Metrics
The scope of the patent can be analyzed using metrics such as independent claim length and count.
Claim Length and Count
- Research suggests that narrower claims, as seen in this patent, are associated with a higher probability of grant and a shorter examination process. The '591 patent's claims are specific and well-defined, contributing to its validity and enforceability[3].
Conclusion
United States Patent 5,866,591 is a critical patent in the field of anesthetic drugs, particularly for remifentanil hydrochloride. Its claims and descriptions provide a detailed framework for the formulation and stabilization of this potent opioid anesthetic. The patent's focus on stability, pH range, and specific excipients ensures the long-term efficacy of remifentanil hydrochloride, making it a valuable asset in clinical anesthesia.
Key Takeaways
- Stable Formulations: The patent describes stable formulations of remifentanil hydrochloride using glycine and other excipients.
- pH Range: The formulations are buffered to a specific pH range to maintain stability.
- Intravenous Administration: The patent is focused on intravenous administration.
- Legal Implications: The patent has been involved in infringement cases.
- Industry Impact: The patent sets standards for the manufacture and storage of remifentanil hydrochloride.
Frequently Asked Questions
What is the main focus of United States Patent 5,866,591?
The main focus of the patent is on the stable formulations of remifentanil hydrochloride, ensuring its long-term stability and efficacy for intravenous administration.
What excipients are used in the formulations described in the patent?
The formulations use excipients such as glycine, mannitol, and sodium chloride to enhance the stability of remifentanil hydrochloride.
What is the significance of the pH range in the patent?
The pH range of 1.5 to 5, preferably between 2.5 and 3.5, is crucial for maintaining the stability of the drug.
Has the patent been involved in any legal proceedings?
Yes, the patent has been involved in infringement cases, such as the one against Fresenius.
How does the patent impact the pharmaceutical industry?
The patent sets standards for the manufacture and storage of remifentanil hydrochloride, ensuring compliance with regulatory requirements and maintaining the drug's efficacy.
Cited Sources
- US20140179740A1 - Stable liquid remifentanil formulations - Google Patents
- 1:15-cv-06700 Document - Patent Docs
- Patent Claims and Patent Scope - SSRN
- US5866591A - Stable formulations of remifentanil - Google Patents
