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US 6,034,137 AGranted
Cationic lipids for gene therapy
AssigneeSyntex (U.S.A.) Inc.
InventorsPaula N. Belloni, Donald R. Hirschfeld, John O. Link, John J. Nestor, Jr., Gary A. Peltz
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Abstract
This invention provides novel cationic lipids, particularly guanidino lipids, and methods for their preparation. Also provided are polyanionic-lipid complexes comprising the lipids of the invention, their preparation and use to deliver biologically active substances, particularly nucleic acids to cells.
Claims12
A compound of Formula I
- R.sub.1 R.sub.2 N--C(O)--A--X Formula I
- wherein:
- R.sub.1 and R.sub.2, which may be the same or different, are C.sub.10 -C.sub.26 hydrocarbyl groups;
- A is a alkylene group wherein one or more methylene groups is optionally replaced by a group Y (provided that none of the Y groups are adjacent to each other), where each Y is independently in the direction shown, --O--, --OC(O)--, --C(O)O--, --NR.sub.5 --, --NR.sub.5 C(O)--, --C(O)NR.sub.5 --, NR.sub.5 C(O)NR.sub.5 --, --NR.sub.5 C(O)O--, --OC(O)NR.sub.5 --, --S(O).sub.n -- (where n is 0, 1 or 2) or --NZ--C(.dbd.NZ)NZ--, wherein each Z is independently H or --(CH.sub.2).sub.m NR.sub.5 --C(.dbd.NR.sub.5)NR.sub.5 with m being an integer from 1-10, and each R.sub.5 is independently H or lower alkyl;
- X is:
- a --NH--C(.dbd.NR.sub.3)NHR.sub.4, wherein R.sub.3 and R.sub.4 are independently hydrocarbyl, haloalkyl, hydroxyalkyl, O-protected hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, aryloxyalkyl, aminoalkyl, mono- or di-substituted aminoalkyl, N-protected-aminoalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl, --C(O)NR.sub.6 R.sub.7 (where R.sub.6 and R.sub.7 are independently H or hydrocarbyl) or a nitrogen protecting group;
- provided that:
- when R.sub.1 and R.sub.2 are both identical C.sub.16 alkyl groups, A is not a butylene chain;
- and salts, solvates, resolved and unresolved enantiomers, diastereomers and mixtures thereof.
6 more elements
Dependencies are inferred from the claim text.