Pharmaceutical compositions
Inventors
Sharma, Shubh • Van Der Ploeg, Leonardus H. T. • Henderson, Bart T.
Assignees
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Publication Number
US-12285460-B2
Publication Date
2025-04-29
Expiration Date
Abstract
The present invention relates to an ionic complex comprising a cationic polypeptide and an anionic excipient selected from: a PEG-carboxylic acid; a fatty acid having 10 or more carbon atoms; an anionic phospholipid; and a combination thereof. The invention also relates to a pharmaceutical composition comprising the ionic complex of the invention and a pharmaceutically acceptable carrier. The cationic polypeptide of the ionic complex has pharmacological activity and the complex can provide a more desirable pharmacokinetic profile for the cationic polypeptide of the complex as compared to the cationic polypeptide alone following administration. As such, the invention also relates to the use of the ionic complex and pharmaceutical composition comprising same to treat a subject suffering from a disease or disorder that is responsive to the cationic polypeptide of the ionic complex.
Core Innovation
The invention relates to an ionic complex comprising a cationic polypeptide and a 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) conjugated polyethylene glycol. The cationic polypeptide is represented by a structural formula or a pharmaceutically acceptable salt thereof, and the molar ratio of the cationic polypeptide to the DSPE conjugated polyethylene glycol ranges from about 1:1 to about 1:10.
The ionic complex is asserted to improve pharmacokinetic behavior of the cationic polypeptide relative to the cationic polypeptide alone. The improvement includes sustained or extended drug exposure and reduced peak-to-trough exposure ratios, together with reduced toxicity or side effects.
The disclosure further includes pharmaceutical composition including the ionic complex and a pharmaceutically acceptable carrier. It also describes MC4R-associated disorders and treatment of diseases or disorders responsive to the cationic polypeptide, including melanocortin receptor modulation with selectivity versus MC3R and MC1R.
Claims Coverage
The independent claim defines one core composition: an ionic complex comprising a cationic polypeptide and DSPE-conjugated polyethylene glycol, with an explicit molar ratio range. Dependent claim coverage adds four inventive refinements: a narrower molar-ratio sub-range, selection of DSPE-PEG variants, optional anionic excipients, and depot formation upon subcutaneous delivery.
Molar ratio constrained ionic complex of cationic polypeptide and DSPE conjugated polyethylene glycol
An ionic complex comprising a cationic polypeptide represented by a structural formula or a pharmaceutically acceptable salt thereof and a 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) conjugated polyethylene glycol, wherein the molar ratio of the cationic polypeptide to the DSPE conjugated polyethylene glycol ranges from about 1:1 to about 1:10.
Specific molar ratio sub-range ionic complex
The ionic complex wherein the molar ratio of a cationic peptide to DSPE-conjugated polyethylene glycol ranges from about 1:2 to about 1:8.
DSPE conjugated polyethylene glycol selected from mPEG-2,000-DSPE and mPEG-5,000-DSPE
The ionic complex includes a polyethylene glycol conjugate of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) selected from mPEG-2,000-DSPE or mPEG-5,000-DSPE.
Selectable anionic excipient selected from CMC, stearic acid, or DPPA
The ionic complex further includes an anionic excipient selected from carboxymethylcellulose (CMC), stearic acid, or DPPA.
Depot formation upon subcutaneous delivery
The ionic complex is specified to have the property of forming a drug depot when delivered subcutaneously.
Overall, the claims cover an ionic complex between a cationic polypeptide and a DSPE conjugated polyethylene glycol, constrained by a molar-ratio range. Dependent coverage further narrows the molar ratio, specifies DSPE-PEG variants, includes defined anionic excipients, and assigns depot formation upon subcutaneous delivery.
Stated Advantages
Improved pharmacokinetic behavior including sustained or extended drug exposure.
Reduced peak-to-trough exposure ratios.
Reduced toxicity or side effects.
Documented Applications
Treatment context for diseases or disorders responsive to the cationic polypeptide, including melanocortin receptor modulation involving MC4R with selectivity versus MC3R and MC1R.
Treatment areas listed include type 1 diabetes, type 2 diabetes, obesity, insulin resistance, metabolic syndrome, male erectile dysfunction, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis.
MC4R-associated disorders and MC4R mutation carriers.
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