Stabilizing alkylglycoside compositions and methods thereof

Inventors

Maggio, Edward T.

Assignees

Aegis Therapeutics LLC

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 peptide, polypeptide, or variant thereof, for example octreotide or variant thereof.

Core Innovation

The disclosed invention relates to alkylglycoside surfactant-containing pharmaceutical formulations that include peptides or proteins, including octreotide and variants, that remain stable and exhibit reduced aggregation and decreased immunogenicity. The background problem addressed is that aggregation and self-association of peptide/protein therapeutics can negatively impact potency, immunogenicity, and shelf life.

The disclosure emphasizes that using alkylglycosides such as dodecyl-β-D-maltoside provides stabilization of the formulated peptide/protein and mitigates fibril formation. It further defines concepts relating to alkylglycoside self-association and the critical micelle concentration (CMC) of the surfactant in the context of formulation stability and reduced aggregation.

In particular, the disclosure links improved stabilization to the α/β anomer purity of dodecyl-β-D-maltoside, stating that β-anomer purity and low α-anomer contamination improve stabilization. Mechanistic and analytical discussions include light scattering (Rayleigh) assays and biological activity assays to support the observed reductions in aggregation, reductions in anti-drug antibody responses, and mitigation or disruption of DAPTA fibrils/aggregation under formulation conditions.

Claims Coverage

The relevant portion includes four independent claims. Across these claims, the inventive coverage is centered on using an alkylglycoside consisting essentially of dodecyl-β-D-maltoside in compositions with octreotide or variants, together with free of naturally occurring octreotide variants and stability for at least one month at about 25 to 37 °C.

All independent claims require octreotide or a variant formulated or combined with an alkylglycoside limited to essentially dodecyl-β-D-maltoside, with the composition free of naturally occurring octreotide variants and stable for at least one month at about 25 to 37 °C; the independent method claims further focus on increasing stability, reducing aggregation, and decreasing immunogenicity.

Stated Advantages

Documented Applications