Discontinuous Oligonucleotide Ligands

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent discloses a novel class of oligonucleotide conjugates consisting of four RNA (or analog) strands linked in a specific manner—two are covalently joined by a bivalent linker, and each of these is hybridized with a complementary, unlinked RNA strand. This structure enables highly effective activation of the cytosolic immune receptor RIG-I, a key sensor of viral RNA in cells, and can be synthetically produced using efficient methods. The invention covers these conjugates, their pharmaceutical compositions, manufacturing methods, and their use in treating cancers, viral infections, or disorders involving immune dysregulation by stimulating innate immune responses.

Use CasesContent extracted from patent full text and abstract with AI.

• Development of new immunotherapeutic drugs to treat cancers (neoplasias) by enhancing the body's innate immune response against tumors.
• Treatment of viral infections (such as those caused by influenza, hepatitis, herpesviruses, etc.) by activating RIG-I to induce antiviral responses.
• Modulation or correction of uncontrolled immune responses (autoimmunity, inflammation) through targeted activation of innate immunity.
• In vitro research tools for studying RIG-I biology, immune signaling, or drug screening requiring robust and specific activation of cytosolic RNA sensors.
• Formulation of vaccine adjuvants that can boost immune response through RIG-I activation.
• Combination therapies with existing anticancer, antiviral, or immunomodulatory agents to enhance treatment efficacy.

BenefitsContent extracted from patent full text and abstract with AI.

• Highly potent and robust activation of RIG-I, leading to strong induction of interferon and other protective immune components.
• Enhanced biological and storage stability through chemical modifications and linker incorporation, overcoming previous issues with RNA ligand degradation.
• Synthetic flexibility and efficiency—various linker types and nucleotide modifications are permitted, enabling tailored properties and scalable manufacturing processes.
• Versatility of application: effective against a wide range of targets (tumors, viruses, immune disorders), in both humans and animals.
• Potential use as both therapeutic agents and research reagents due to precise, predictable innate immune activation.
• Ability to fine-tune immune responses through structure (e.g., triphosphate addition or sequence modification), making these molecules adaptable to specific medical or scientific needs.

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

The present invention relates to an oligonucleotide conjugate K of the structure RNA1-B-RNA2 RNA3 RNA4 or a pharmaceutically active salt thereof, wherein each RNA1, RNA2, RNA3 and RNA4 is a strand of a ribonucleic acid or of an analogue or of a derivative thereof, wherein B is a divalent linker that covalently bonds the 5' terminus of RNA1 to the 5' terminus of RNA2 or the 3' terminus of RNA1 to the 3' terminus of RNA2, and wherein RNA3 and RNA4 are not covalently bonded to each other. The invention further relates to the medical and non-medical use of such an oligonucleotide conjugate K and to corresponding manufacturing methods.