Oligonucleotides, compositions and methods thereof

US12403156B2 · kind B2 · utility

Assignee

• WAVE LIFE SCIENCES LTD. · SG

Inventors

• Jason Jingxin Zhang · Walpole, US
• Naoki Iwamoto · Watertown, US
• Christopher J. Francis · Arlington, US
• Chandra Vargeese · Schwenksville, US
• David Butler · Medford, US
• Sethumadhavan Divakaramenon · Lexington, US
• Genliang Lu · Winchester, US
• Subramanian Marappan · Acton, US

Key dates

• Filing date: Feb 16, 2021
• Grant date: Sep 2, 2025
• Expiry date: Apr 11, 2044

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2310/3515
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described. In some embodiments, no immune modulation is desired, and the present disclosure provides methods of identifying chirally controlled oligonucleotide compositions which have decreased immune modulation.