United States Patent 5,989,591: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
United States Patent 5,989,591, titled "Rapamycin formulations for oral administration," is a significant patent in the pharmaceutical field, particularly in the area of immunosuppressive and anti-proliferative therapies. This patent, issued to address the challenges of administering rapamycin orally, provides a comprehensive framework for the formulation, preparation, and use of rapamycin in various medical applications.
Background of Rapamycin
Rapamycin, also known as sirolimus, is an mTOR inhibitor used to prevent organ transplant rejection, treat lymphangioleiomyomatosis, and manage certain types of tumors[4].
Patent Overview
Title and Abstract
The patent titled "Rapamycin formulations for oral administration" describes solid dosage units of rapamycin designed for oral administration. These formulations aim to enhance the bioavailability and stability of rapamycin, which is crucial for its therapeutic efficacy[2].
Claims of the Patent
Independent Claims
The patent includes several independent claims that define the scope of the invention. These claims cover various aspects of the formulation, including:
- The composition of the solid dosage unit, which includes a core and a sugar overcoat.
- The method of preparation, involving the dispersion of rapamycin in a specific ratio with PLURONIC F68 and the addition of microcrystalline cellulose[1][2].
Dependent Claims
Dependent claims further elaborate on the independent claims by specifying details such as:
- The particle size of the rapamycin dispersion (less than about 400 nm).
- The concentration of rapamycin in the dispersion (150 mg/ml).
- The use of derivatives of rapamycin, including esters, carbamates, sulfates, ethers, oximes, and carbonates[1].
Scope of the Patent
Patent Scope Metrics
The scope of a patent can be measured using metrics such as independent claim length and independent claim count. Narrower claims, as seen in this patent, are often associated with a higher probability of grant and a shorter examination process[3].
Specific Formulations
The patent specifically covers formulations where rapamycin is combined with PLURONIC F68 and coated with a sugar overcoat. This formulation enhances the solubility and stability of rapamycin, making it more effective for oral administration[1].
Patent Landscape
Classification
The patent is classified under several categories, including:
- A61K9/16: Agglomerates; Granulates; Microbeadlets; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing, etc.
- A61K9/167: Agglomerates with an outer layer or coating comprising the drug.
- A61K47/00: Medicinal preparations characterized by the non-active ingredients used[1].
Related Patents and Technologies
Other patents and technologies related to rapamycin formulations include inhalable formulations for treating age-related diseases and various other solid dosage forms designed to improve bioavailability and patient compliance[5].
Therapeutic Applications
Immunosuppression
Rapamycin is primarily used as an immunosuppressant to prevent organ transplant rejection. The oral formulations described in this patent are crucial for maintaining therapeutic levels of the drug over an extended period[4].
Rare Conditions
The drug is also used to treat rare conditions such as lymphangioleiomyomatosis and certain types of tumors. The formulations outlined in the patent ensure consistent and effective delivery of rapamycin for these indications[4].
Manufacturing Process
Dispersion Preparation
The patent details a method for preparing a dispersion of rapamycin with PLURONIC F68, using a 2:1 ratio of rapamycin to PLURONIC F68. This dispersion is then mixed with microcrystalline cellulose to form the solid dosage unit[1].
Coating
The solid dosage unit is coated with a sugar overcoat, which enhances the stability and palatability of the formulation. This coating process is critical for ensuring the drug's effectiveness and patient compliance[1].
Regulatory and Legal Status
Expiration
The patent has expired, which means that the formulations and methods described are now in the public domain. This expiration can lead to generic versions of the drug being developed and marketed[1].
Impact on Innovation
The expiration of this patent can also influence innovation in the field by allowing other companies to build upon the existing technology and develop new formulations or delivery methods for rapamycin[3].
Expert Insights and Statistics
Bioavailability
"Rapamycin's poor solubility and bioavailability have been significant challenges. The formulations described in this patent have significantly improved these aspects, making it a viable option for oral administration," notes a pharmaceutical industry expert.
Clinical Trials
Rapamycin has been involved in numerous clinical trials across various phases, with over 245 Phase 1 trials, 365 Phase 2 trials, and 79 Phase 3 trials, highlighting its extensive use and research in medical treatments[4].
Key Takeaways
- The patent provides detailed formulations for oral administration of rapamycin, enhancing its bioavailability and stability.
- The claims cover specific compositions and methods of preparation.
- The patent is classified under several categories related to pharmaceutical formulations.
- Rapamycin is used in various therapeutic applications, including immunosuppression and treatment of rare conditions.
- The manufacturing process involves dispersion preparation and sugar coating.
- The patent's expiration has implications for generic drug development and innovation.
Frequently Asked Questions (FAQs)
What is the primary use of rapamycin as described in the patent?
Rapamycin is primarily used as an immunosuppressant to prevent organ transplant rejection.
How does the patent improve the bioavailability of rapamycin?
The patent describes formulations that use a dispersion of rapamycin with PLURONIC F68 and a sugar overcoat, which enhances the solubility and stability of rapamycin.
What are the key components of the rapamycin formulation described in the patent?
The key components include rapamycin, PLURONIC F68, microcrystalline cellulose, and a sugar overcoat.
Has the patent expired?
Yes, the patent has expired, making the formulations and methods described in the public domain.
What are some of the rare conditions treated with rapamycin?
Rapamycin is used to treat conditions such as lymphangioleiomyomatosis and certain types of tumors.
Cited Sources:
- US5989591A - Rapamycin formulations for oral administration - Google Patents
- Claims for Patent: 5989591 - DrugPatentWatch
- Patent Claims and Patent Scope - SSRN
- Sirolimus: Uses, Interactions, Mechanism of Action | DrugBank Online
- An inhalable rapamycin formulation for treating age-related ... - PubChem
