Double-stranded ribonucleic acids with rugged physico-chemical structure and highly specific biologic activity
AssigneeHEMISPHERx BIOPHARMA
InventorsWilliam A. Carter, David Strayer
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Abstract
The invention relates to our discovery of a novel double-stranded ribonucleic acid (dsRNA) having specific biological activities, which includes acting as a selective agonist for activation of the Toll-like receptor 3. Its “rugged” molecular structure as measured by physico-chemical techniques is resistant to molecular unfolding (i.e., denaturation). This structure appears to be responsible for increased efficacy of dsRNA in therapeutic applications and improved biological activity (e.g., used as an immunoregulatory agent). Medicaments, processes for their manufacture, and methods for their use are provided herein.
Claims19
An isolated double-stranded ribonucleic acid (dsRNA) which is resistant to denaturation under conditions that are able to separate hybridized poly(riboinosinic acid) and poly(ribocytosinic acid) strands.
An isolated double-stranded ribonucleic acid (dsRNA) which is resistant to denaturation under conditions that are able to separate hybridized poly(riboinosinic acid) and poly(ribocytosinic acid) strands, wherein the isolated dsRNA:
- has an HPLC chromatogram substantially the same as the 5 minute peak of FIG. 1B or FIG. 1C;
- is stable to exposure to thermal stress at 40° C.;
- and
- has an increased bioactivity as evidenced by binding to receptor TLR3-ECD as compared to unselected poly(I):poly(C12U).
Dependencies are inferred from the claim text.