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US 2019/0240323 A1Published application
Branched chimeric compounds, and methods of use thereof
AssigneeDynavax Technologies Corporation
InventorsGary S. OTT, Robert J. MILLEY, Robert L. COFFMAN, Radwan KIWAN, Holger KANZLER
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Abstract
The present disclosure relates to branched and linear chimeric compounds containing both nucleic acid and non-nucleic acid moieties, as well as to polynucleotides. The present disclosure also relates to uses thereof for stimulating an immune response, and to methods for preparation of the branched chimeric compounds.
Claims27
A pharmaceutical composition comprising (i) a pharmaceutically acceptable excipient and (ii) a branched chimeric compound of formula (I):
- [D-L1-L2-(PEG)-L3]x-F (I)
- wherein:
- D is a linear chimeric compound;
- L1 is a first linker comprising an alkylthio group;
- L2 is a second linker comprising a succinimide group;
- L3 is a third linker comprising an amide group;
- PEG is of the formula —(OCH2CH2)n—, where n is an integer from 2 to 80;
- x is an integer from 3 to 300;
- and
- F is a branched copolymer of sucrose and epichlorohydrin having a molecular weight of about 100,000 to about 700,000 daltons and is connected to L3 via an ether group;
- and
- wherein the linear chimeric compound of D comprises three nucleic acid moieties and two hexaethylene glycol (HEG) spacers as 5′-TCGGCGC-3′-HEG-5′-AACGTTC-3′-HEG-5′-TCGGCGC-3′ (SEQ ID NO:2), wherein the linear chimeric compound contains less than 50 nucleotides, and wherein one or more linkages between the nucleotides, between the nucleotides and the HEG spacers and between the 3′-terminal nucleotide and L1 are phosphorothioate ester linkages.
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Dependencies are inferred from the claim text.