Manufacture, formulation and dosing of apraglutide
Inventors
BOLOGNANI, Federico • Feldman, Gleb
Assignees
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Publication Number
US-11766470-B2
Publication Date
2023-09-26
Expiration Date
Abstract
The present disclosure relates to methods of making, formulating and administering GLP-2 analogs.
Core Innovation
The document relates to treating short bowel syndrome associated intestinal failure (SBS-IF) or short bowel syndrome associated intestinal insufficiency (SBS-II) by administering apraglutide, or a pharmaceutically acceptable salt thereof, to a subject. Apraglutide is administered once weekly, and the dose is selected based on body weight, including about 2.5 mg/week when the subject has a body weight of less than 50 kg and about 5 mg/week when the subject has a body weight greater than or equal to 50 kg.
The document further addresses apraglutide sodium salt quality attributes, including an overall purity of at least 97% and quantitative limits for named apraglutide peptide impurities, including Des-Gly4, Des-Ser7, Aspartimide3, Asp33-OH, β-Asp3, D-His, D-Aspartimide3, and [Trp25, 2-(2,4,6-trimethoxyphenyl)] apraglutide impurity. The disclosed approach emphasizes improved solid phase peptide synthesis (SPPS) and downstream purification, together with substantially pure apraglutide and, in particular, a sodium salt of apraglutide.
The document also defines the downstream product format for apraglutide sodium salt as a lyophilized powder and includes pharmaceutical compositions with pharmaceutically acceptable excipients, including glycine, L-histidine, and mannitol, and a two-chamber powder syringe format. In addition, formulation and presentation details include counterion conversion to sodium and lyophilization/packaging, with reported stability at 2–8°C for up to 3 months.
Claims Coverage
The consolidated content includes one independent claim centered on once-weekly treatment of SBS-IF or SBS-II using apraglutide with body-weight-based dosing. Dependent refinements also appear in the input and include salt purity, subcutaneous injection, colon-in-continuity, and reduction of parenteral support.
Weight-based once-weekly administration of apraglutide for SBS-IF/SBS-II
A method of treating short bowel syndrome associated intestinal failure (SBS-IF) or short bowel syndrome associated intestinal insufficiency (SBS-II) by administering apraglutide, or a pharmaceutically acceptable salt thereof, once weekly, with a weekly dose of about 2.5 mg/week when the subject has a body weight of less than 50 kg and about 5 mg/week when the subject has a body weight greater than or equal to 50 kg.
Apraglutide sodium salt purity
The sodium salt of apraglutide has a purity of at least 97% as determined by high-performance liquid chromatography (HPLC).
Subcutaneous injection administration
The method includes administering apraglutide via subcutaneous injection.
Reduction of parenteral support after dosing
For a subject receiving parenteral support, the amount of the parenteral support administered is reduced after administering apraglutide, or a salt thereof.
Colon-in-continuity subject subset
The method is performed for a subject having colon-in-continuity (CIC).
The claim coverage centers on once-weekly apraglutide treatment for SBS-IF or SBS-II with dosing determined by body weight. The inputs also support dependent features relating to sodium salt purity by HPLC, subcutaneous injection, colon-in-continuity, and reduction of parenteral support.
Stated Advantages
Increased citrulline (PD marker).
Improved fluid absorption outcomes in SBS-IF patients, including increased urine volume output.
Improved fluid absorption outcomes in SBS-IF patients, including increased urine sodium excretion.
Documented Applications
Treatment of short bowel syndrome associated intestinal failure (SBS-IF) or short bowel syndrome associated intestinal insufficiency (SBS-II) by administering apraglutide once weekly with body-weight-based dosing.
Treatment of SBS-IF patients, including reported physiological effects such as increased citrulline and improved urine output and urine sodium excretion.
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