Stabilized peptide composition
Inventors
Murakami, Takashi • TAKATA, Kazuyuki • NIWA, Yoshie • HATANO, Shuichi • KAWASAKI, Hidenori • FUJITA, Satoko
Assignees
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Publication Number
US-12491229-B2
Publication Date
2025-12-09
Expiration Date
Abstract
Provided herein is a peptide composition that is highly stable and can be stored long term, said composition containing one or more types of peptides having an amino acid sequence represented by any of SEQ ID Nos. 1-5, or a peptide in which one or two of the amino acids of the abovementioned peptides are independent and may be substituted, deleted or added, and saccharides and an inorganic salt.
Core Innovation
The disclosure relates to a stabilized peptide composition comprising peptides with the amino acid sequences of SEQ ID NOs: 1 to 5, and optionally peptide analogues, impurities, and combinations thereof. The composition is formulated with a saccharide and an inorganic salt to improve long-term stability and water solubility, including for lyophilized (freeze-dried) formulations.
A key aspect of the disclosure is a lyophilization manufacturing approach that uses high-pH mixing and stepwise pH adjustment prior to lyophilization. The solution includes specified peptides, sucrose, and sodium chloride, and the pH is adjusted in stages before lyophilizing, with solution pH and sugar/salt selection and amounts influencing solubility and stability outcomes.
Another key aspect is controlling oxygen in the final vial environment to limit formation of peptide analogues, notably for SEQ ID NO: 3 analogues. The disclosure positions the saccharide/inorganic salt formulation, controlled pH conditioning during manufacturing, and oxygen-limited vial storage as measures to improve the stability profile of the lyophilized product.
Claims Coverage
The provided independent claims cover two independent manufacturing methods for producing a lyophilized formulation from specified peptide sequences using sucrose and sodium chloride with stepwise high-pH to near-neutral pH conditioning, followed by lyophilization. The coverage identifies the independent inventive method features and a dependent storage refinement that quantitatively limits oxygen concentration in a vial.
Stepwise high-pH formulation with defined peptides, sucrose, and sodium chloride, then lyophilization
Mixing peptides consisting of the amino acid sequences of SEQ ID NOs: 1, 4, 2, 3, and 5, sucrose, and sodium chloride in a solution of pH 12.0 to pH 13.0; adjusting pH in stages with an acid substance; and lyophilizing the solution or mixture solution.
Vial storage with controlled oxygen concentration to limit analogue formation
Placing the lyophilized formulation in a vial and controlling the oxygen concentration in the vial to between 0.01% and 3.0%.
Across the independent claims, the inventive coverage is directed to manufacturing a lyophilized formulation from peptides defined by SEQ ID NOs with sucrose and sodium chloride under strongly basic starting pH, followed by stepwise pH adjustment to near-neutral conditions prior to lyophilization. The dependent claims add vial storage oxygen-concentration control to manage analogue/impurity formation.
Stated Advantages
Improves long-term stability of the stabilized peptide composition.
Improves water solubility of the stabilized peptide composition.
Limits formation of peptide analogues/impurities during storage, including notably analogue formation for SEQ ID NO: 3.
Documented Applications
Manufacturing a lyophilized (freeze-dried) stabilized peptide formulation for storage in a vial with controlled oxygen concentration.
Stability/solubility evaluation of the formulated peptides under described pH-dependent conditions and lyophilized-form product observations.
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