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US 2022/0031847 A1Published application
Therapeutic methods
AssigneeGenevant Sciences GmbH
InventorsJames HEYES, Richard J. HOLLAND, Adam JUDGE, Kieu Mong LAM
Life of this patent
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Abstract
The invention provides methods and compositions for delivering a nucleic acid to a cell or the cytosol of the target cell. The method includes contacting the cell with, 1) a membrane-destabilizing polymer; and 2) a nucleic acid conjugate. The nucleic acid conjugate includes a targeting ligand bound to an optional linker and a nucleic acid.
Claims238
A method for delivering a nucleic acid to a cell comprising contacting the cell with, 1) a membrane-destabilizing polymer;
- and 2) a nucleic acid conjugate of Formula (X):
- A-B-C (X)
- wherein:
- A is a targeting ligand, B is an optional linker, and C is a nucleic acid;
- wherein the membrane-destabilizing polymer is a polymer of formula (XX):
- T5-L-[PEGMAm-M2n]v[DMAEMAq-PAAr-BMAs]w (XX)
- wherein:
- PEGMA is polyethyleneglycol methacrylate residue with 2-20 ethylene glycol units;
- M2 is a methacrylate residue selected from the group consisting of
- a (C4-C18)alkyl-methacrylate residue;
- a (C4-C18) branched alkyl-methacrylate residue;
- a cholesteryl methacrylate residue;
- a (C4-C18)alkyl-methacrylate residue substituted with one or more fluorine atoms;
- and
- a (C4-C18) branched alkyl-methacrylate residue substituted with one or more fluorine atoms;
- BMA is butyl methacrylate residue;
- PAA is propyl acrylic acid residue;
- DMAEMA is dimethylaminoethyl methacrylate residue;
- m and n are each a mole fraction greater than 0, wherein m is greater than n and m+n=1;
- q is a mole fraction of 0.2 to 0.75;
- r is a mole fraction of 0.05 to 0.6;
- s is a mole fraction of 0.2 to 0.75;
- q+r+s=1;
- v is 1 to 25 kDa;
- w is 1 to 25 kDa;
- T5 is a targeting moiety;
- and
- L is absent or is a linking moiety.
25 more elements
A method for delivering a nucleic acid to the cytosol of a target cell within an animal, the method comprising:
- administering to the animal, (a) a membrane-destabilizing polymer, and (b) a nucleic acid conjugate of Formula (X):
- A-B-C (X)
- wherein A is a targeting ligand, B is an optional linker, and C is a nucleic acid, wherein the nucleic acid is delivered to the cytosol of the target cell;
- wherein the membrane-destabilizing polymer is a polymer of formula (XX):
- T5-L-[PEGMAm-M2n]v[DMAEMAq-PAAr-BMAs]w (XX)
- wherein:
- PEGMA is polyethyleneglycol methacrylate residue with 2-20 ethylene glycol units;
- M2 is a methacrylate residue selected from the group consisting of
- a (C4-C18)alkyl-methacrylate residue;
- a (C4-C18) branched alkyl-methacrylate residue;
- a cholesteryl methacrylate residue;
- a (C4-C18)alkyl-methacrylate residue substituted with one or more fluorine atoms;
- and
- a (C4-C18) branched alkyl-methacrylate residue substituted with one or more fluorine atoms;
- BMA is butyl methacrylate residue;
- PAA is propyl acrylic acid residue;
- DMAEMA is dimethylaminoethyl methacrylate residue;
- m and n are each a mole fraction greater than 0, wherein m is greater than n and m+n=1;
- q is a mole fraction of 0.2 to 0.75;
- r is a mole fraction of 0.05 to 0.6;
- s is a mole fraction of 0.2 to 0.75;
- q+r+s=1;
- v is 1 to 25 kDa;
- w is 1 to 25 kDa;
- T5 is a targeting moiety;
- and
- L is absent or is a linking moiety.
24 more elements
A method comprising, administering to an animal, 1) a membrane-destabilizing polymer;
- and 2) a nucleic acid conjugate of Formula (X):
- A-B-C (X)
- wherein A is a targeting ligand, B is an optional linker, and C is a nucleic acid;
- wherein the membrane-destabilizing polymer is a polymer of formula (XX):
- T5-L-[PEGMAm-M2n]v-[DMAEMAq-PAAr-BMAs]w (XX)
- wherein:
- PEGMA is polyethyleneglycol methacrylate residue with 2-20 ethylene glycol units;
- M2 is a methacrylate residue selected from the group consisting of
- a (C4-C18)alkyl-methacrylate residue;
- a (C4-C18) branched alkyl-methacrylate residue;
- a cholesteryl methacrylate residue;
- a (C4-C18)alkyl-methacrylate residue substituted with one or more fluorine atoms;
- and
- a (C4-C18) branched alkyl-methacrylate residue substituted with one or more fluorine atoms;
- BMA is butyl methacrylate residue;
- PAA is propyl acrylic acid residue;
- DMAEMA is dimethylaminoethyl methacrylate residue;
- m and n are each a mole fraction greater than 0, wherein m is greater than n and m+n=1;
- q is a mole fraction of 0.2 to 0.75;
- r is a mole fraction of 0.05 to 0.6;
- s is a mole fraction of 0.2 to 0.75;
- q+r+s=1;
- v is 1 to 25 kDa;
- w is 1 to 25 kDa;
- T5 is a targeting moiety;
- and
- L is absent or is a linking moiety.
24 more elements
Dependencies are inferred from the claim text.