Oligonucleotides, compositions and methods thereof

US11013757B2 · 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: Jun 2, 2017
• Grant date: May 25, 2021
• Expiry date: Jun 16, 2037

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.