Cyclosporine formulations for use in the prevention or treatment of pulmonary chronic graft rejection
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Publication Number
US-11744872-B2
Publication Date
2023-09-05
Expiration Date
Abstract
The invention relates to cyclosporine formulations for use in the prevention or treatment of pulmonary chronic graft rejection. In particular, the invention provides a cyclosporine liquid formulation for use as an aerosol for inhalation in a method of preventing or treating pulmonary chronic graft rejection in single lung transplanted patients. The formulation is preferably administered once or twice daily. The formulation may be aerosolized with a nebulizer that comprises features for monitoring the time, date and duration of inhalation by the patient, in order to monitor patient adherence. The formulation according to the invention may be combined with standard immunosuppressants and corticosteroids.
Core Innovation
The invention relates to a method of preventing or treating pulmonary chronic graft rejection in single lung transplanted patients by administering to a patient in need thereof a liposomal cyclosporine liquid formulation as an aerosol for inhalation. The formulation contains cyclosine at a concentration of 1 mg/mL up to 5 mg/mL and is administered as a unit dose of 1 to 3 mL.
The method is directed to human patients of higher age who are co-administered one or more active ingredients used in standard immunosuppressive therapy after lung transplantation, where the one or more active ingredients constitute a standard of care systemic immunosuppression regimen. The documented clinical setting includes preventing or treating pulmonary chronic graft rejection with emphasis on bronchiolitis obliterans syndrome (BOS) in single-lung transplant patients.
A formulation and device approach is used in which the liposomal cyclosporine liquid formulation is aerosolized for inhalation, including characterization of an aerosol for inhalation and delivery by nebulizers described as electronic vibrating membrane nebulizers, including an eFlow® nebulizer. The method also includes monitoring of inhalation time, date, and duration, generating a signal for insufficient patient adherence when inhalation of the formulation is not performed as intended in at least 65% of intended inhalation cycles.
Claims Coverage
The independent claim covers a preventive or therapeutic method of pulmonary chronic graft rejection in single lung transplanted patients using a liposomal cyclosporine liquid aerosol for inhalation with defined cyclosporine concentration and unit-dose volume, while co-administering standard of care systemic immunosuppression in human patients of higher age. The inventive features in the related dependent claims further refine parameters including the aerosol delivery configuration, treatment delivery time, systemic immunosuppression composition, and adherence monitoring signaling with a quantitative threshold.
Liposomal cyclosporine liquid aerosol for inhalation to prevent or treat pulmonary chronic graft rejection
Administering to a patient in need thereof a liposomal cyclosporine liquid formulation as an aerosol for inhalation to prevent or treat pulmonary chronic graft rejection in single lung transplanted patients.
Defined cyclosporine concentration and unit dose volume for the formulation
Using a formulation containing cyclosporine at a concentration of 1 mg/mL up to 5 mg/mL and having a unit dose volume of 1 to 3 mL.
Co-administration with standard of care systemic immunosuppression after lung transplantation
Co-administering one or more active ingredients used in standard immunosuppressive therapy after lung transplantation, wherein the one or more active ingredients constitute a standard of care systemic immunosuppression regimen.
Patient is a human patient of higher age
Applying the method to a human patient of higher age.
Electronic vibrating membrane nebulizer aerosolization
Further aerosolizing the formulation using an electronic vibrating membrane nebulizer.
Nebulization time limit for a unit dose
Limiting the nebulization time for a unit dose of the formulation to no more than about 10 minutes, or not more than about 5 minutes.
Triple drug therapy systemic immunosuppression composition
Including one or more active ingredients formulated as a triple drug therapy consisting of a calcineurin inhibitor, a cell-cycle inhibitor, and a corticosteroid.
Adherence monitoring with signal generation for insufficient patient adherence
Monitoring a patient's inhalation time, date, and duration and generating a signal for insufficient patient adherence if inhalation of the formulation is not performed as intended in at least 65% of intended inhalation cycles.
Overall, the claim set is centered on administering a liposomal cyclosporine liquid aerosol for inhalation with defined concentration and unit dose to single lung transplanted patients, combined with co-administration of standard of care systemic immunosuppression in human patients of higher age, with dependent inventive features directed to specific nebulizer technology, nebulization time constraints, triple drug therapy composition, and adherence monitoring with signal generation tied to a quantitative threshold.
Stated Advantages
Documented Applications
No documented applications found
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