Stabilizing alkylglycoside compositions and methods thereof
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Publication Number
US-10046025-B2
Publication Date
2018-08-14
Expiration Date
Abstract
The present invention relates to alkylglycoside-containing compositions and methods for increasing the stability, reducing the aggregation and immunogenicity, increasing the biological activity, and reducing or preventing fibrillar formation of a cyclic polypeptide.
Core Innovation
The invention relates to alkylglycoside/saccharide-alkyl ester surfactant formulations for stabilizing self-associating cyclic or other therapeutic peptides/proteins. It addresses peptide/protein instability that can lead to aggregation and fibril formation, and it further targets immunogenicity while aiming to maintain or improve biological activity.
A key aspect is the use of alkylglycosides or saccharide-alkyl esters, including alkylglycosides such as dodecyl β-D-maltoside and related materials such as sucrose mono-dodecanoate and related sucrose mono-alkyl esters. The disclosure defines considerations such as critical micelle concentration (CMC) and emphasizes low-CMC nonionic surfactants, and it also emphasizes β-anomer purity by reducing α-anomer contamination to improve stabilization.
The disclosure further describes examples showing reduced immunogenicity and improved stability of cyclic polypeptides, including insulin and cyclic PTH (Ostabolin C/PTH 1-31). It also describes inhibition of DAPTA/Peptide T fibril formation and preservation of anti-HIV activity in the presence of agents such as trifluoroethanol (TFE) and/or alkylglycosides.
Claims Coverage
Not explicitly described in patent.
Not explicitly described in patent.
Stated Advantages
Increases stability of cyclic polypeptides and other therapeutic peptides/proteins.
Reduces aggregation and fibril formation.
Decreases immunogenicity.
Improves or maintains biological activity.
Inhibits DAPTA/Peptide T fibril formation.
Preserves anti-HIV activity.
Potentially reduces cold-chain handling requirements.
Documented Applications
Stabilizing self-associating cyclic or other therapeutic peptides/proteins in pharmaceutical compositions, including cyclic PTH (Ostabolin C/PTH 1-31) and insulin.
Decreasing immunogenicity of cyclic polypeptides, including via anti-human insulin antibodies measured by ELISA.
Inhibiting fibril formation for DAPTA/Peptide T while retaining anti-HIV activity assessed in a GHOST CD4 CCR5 assay.
Reducing protein aggregation for multiple proteins including insulin, hGH, cyclic PTH (Ostabolin C/PTH 1-31), PTH 1-34, interferons (Rebif/Betaseron), pramlintide, and calcitonin.
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