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US 8,541,628 B2Granted
Complex cationic lipids having quaternary nitrogens therein
AssigneeVical Incorporated
InventorCarl J Wheeler
Life of this patent
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Abstract
Cationic lipids having a derivatized quaternary ammonium head group that provide improved cell targeting ability and enhanced transfective efficacy for introducing molecules into cells are provided.
Claims7
A method of delivering an anionic molecule into a cell, comprising:
- (a) forming a lipid complex by contacting the anionic molecule with a composition comprising an effective amount of a compound according to the formula:
- wherein R1 and R2 are identical and are selected from the group consisting of C14H29 and C12H25;
- R3 and R4 are independently H;
- linear or branched, unsubstituted or substituted C1-23 alkyl, acyl, alkenyl, or C1-C5 heteroalkyl group having one heteroatom;
- or a cyclic or aryl group comprising from 0 to 5 heteroatoms wherein said heteroatoms are not the first atoms in said heteroalkyl, cyclic and aryl groups, wherein the substituent groups are selected from the group consisting of —O—(CH2)k—CH3, —S—(CH2)k—CH3, and X—(CH2)k—, wherein X is a halide, and k is 0 to 4;
- R5 has the structure
- wherein Z is selected from the group consisting of NR1, NH, and Se;
- R6 is selected from the group consisting of H, R3, and R4, or when Z is NH, or NR1, R6 can be an amino acid, peptide, polypeptide, protein, or mono-, di- or polysaccharide and wherein Z is NH, or NR1, contained therein said amino acid, peptide, polypeptide, protein, or mono-, di- or polysaccharide;
- n is 1 to 6;
- m is 1 to 10;
- Y is a pharmaceutically acceptable anion;
- and
- (b) contacting a cell with the lipid complex formed in step (a);
- whereby a biologically effective amount of the anionic molecule is delivered into the cell.
11 more elements
A method of delivering an anionic molecule into a cell, comprising:
- (a) forming a lipid complex by contacting the anionic molecule with a composition comprising an effective amount of a compound according to the formula:
- wherein
- R1 and R2 are identical and are selected from the group consisting of C14H29 and C12F25;
- R3 and R4 are independently H;
- linear or branched, unsubstituted or substituted C1-23 alkyl, acyl, alkenyl, or C1-C5 heteroalkyl group having one heteroatom;
- or a cyclic or aryl group comprising from 0 to 5 heteroatoms wherein said heteroatoms are not the first atoms in said heteroalkyl, cyclic and aryl groups, wherein the substituent groups are selected from the group consisting of —O—(CH2)k—CH3, —S—(CH2)k—CH3, and X—(CH2)k—, wherein X is a halide, and k is 0 to 4;
- R5 has the structure:
- R7 and R8 are independently selected from the group defined for R3 and R4 or one of R7 and R8 can be an amino acid, peptide, polypeptide, protein, or mono-, di- or polysaccharide and wherein an amino nitrogen of said amino acid, peptide, polypeptide, protein, or mono-, di- or polysaccharide is the N to which R7 or R8 is attached;
- n is 1 to 6;
- m is 1 to 10;
- and
- Y is a pharmaceutically acceptable anion;
- and
- (b) contacting a cell with the lipid complex formed in step (a);
- whereby a biologically effective amount of the anionic molecule is delivered into the cell.
12 more elements
A method of delivering an anionic molecule into a cell, comprising:
- (a) forming a lipid complex by contacting the anionic molecule with a composition comprising an effective amount of a compound according to the formula:
- wherein R1 and R2 are independently H;
- linear or branched, unsubstituted or substituted C1-23 alkyl, acyl, alkenyl, or heteroalkyl group having from 0 to 6 sites of unsaturation;
- or a cyclic or aryl group, said heteroalkyl, cyclic, and aryl groups comprising from 0 to 5 heteroatoms wherein said heteroatoms are not the first atoms in said groups, wherein the substituent groups are selected from the group consisting of —O—(CH2)k—CH3, —S—(CH2)k—CH3, and X—(CH2)k—, wherein X is a halide, and k is 0 to 4;
- R3 and R4 are independently H;
- linear or branched, unsubstituted or substituted C1-23 alkyl, acyl, alkenyl, or C1-C5 heteroalkyl group having one heteroatom;
- or a cyclic or aryl group comprising from 0 to 5 heteroatoms wherein said heteroatoms are not the first atoms in said heteroalkyl, cyclic and aryl groups, wherein the substituent groups are selected from the group consisting of —O—(CH2)k—CH3, —S—(CH2)k—CH3, and X—(CH2)k—, wherein X is a halide, and k is 0 to 4;
- R5 has the structure
- wherein Z is selected from the group consisting of NR1, and NH;
- R6 is selected from the group consisting of H, R1, R2, R3, and R4, or R6 can be an amino acid, peptide, polypeptide, protein, or mono-, di- or polysaccharide and wherein Z is NH, or NR1 contained therein said amino acid, peptide, polypeptide, protein, or mono-, di- or polysaccharide;
- n is 1 to 6;
- m is 1 to 10;
- Y is a pharmaceutically acceptable anion;
- and
- (b) contacting a cell with the lipid complex formed in step (a);
- whereby a biologically effective amount of the anionic molecule is delivered into the cell.
13 more elements
A method of delivering an anionic molecule into a cell, comprising:
- (a) forming a lipid complex by contacting the anionic molecule with a composition comprising an effective amount of a compound, wherein said compound is selected from the group consisting of dioleyl Rosenthal Inhibitor Ether (DORIE) carboxylate, DMRIE carboxylate propyl amide, DMRIE carboxylate methionine-methylester amide, DMRIE carboxylate methionine-leucine-methylester amide, and DMRIE carboxylate methionine-leucine-phenylalanine-methylester amide;
- and
- (b) contacting a cell with the lipid complex formed in step (a);
- whereby a biologically effective amount of the anionic molecule is delivered into the cell.
1 more element
Dependencies are inferred from the claim text.