US5264618A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Cationic lipids for intracellular delivery of biologically active molecules
Assignee: Fresh Tracks Therapeutics Inc
•
Filing: 1991-04-16
•
Granted: 1993-11-23
•
Expires: 2011-04-16
Abstract
Abstract Disclosed are cationic lipids capable of facilitating transport of biologically active agents into cells, including the transfection of cells by therapeutic polynucleotides, the delivery of antiviral drugs, and the introduction of immunogenic peptides. The cationic lipids, comprising an ammonium group, have the general structure <IMAGE> (I) Also disclosed are adducts of these compounds comprising additional cationic sites that enhance the transfective or transport activity. Structure-activity correlations provide for the selection of preferred compounds to be synthesized for this purpose. Compositions disclosed for use of these cationic lipid include formulations for in vitro transfection and pharmaceutical formulations for parenteral and topical administration of therapeutic agents.
Inventors
- 👤 Philip L. Felgner
- 👤 Raj Kumar
- 👤 Channa Basava
- 👤 Richard C. Border
- 👤 Jiin-Yu Hwang-Felgner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 17:08
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/87; C12N15/88; A; A61; A61K; A61K47/00; A61K47/06; A61K47/16; A61K47/18; A61K47/186; A61K47/50; A61K47/51; A61K47/54; A61K47/543; A61K47/544; A61K47/62; A61K47/64; A61K47/645; A61K9/00; A61K9/0012; A61K9/0014; A61K9/0019; A61K9/10; A61K9/127; A61K9/1271; A61K9/1272; A61P; A61P31/00; A61P31/12
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
254 words
A composition having the structure ##STR15## wherein Y 1 and Y 2 are the same or different and are, --O--C(O)--, or --O--; R 1 is H, or C 1 to C 24 alkyl or alkenyl; R 2 is C 1 to C 24 alkyl or alkenyl; R 3 and R 4 are the same or different and are C 1 to C 24 alkyl, or H; R 5 is C 1 to C 24 alkyl straight chain or branched chain; R 6 is --C(O)--(CH 2 ) m --NH--, a diaminocarboxylate ester group which is alkyl, aryl, or aralkyl, or --C(O)--(CH 2 ) m --NH-- linked to said diaminocarboxylate ester group, or is absent; R 7 is H, spermine, spermidine, a histone, or a protein with DNA-binding specificity, or the same groups wherein the amine functionalities of the R 7 moiety are quaternized with R 3 , R 4 , or R 5 groups; or R 7 is an L- or D-alpha amino acid having a positively charged group on the side chain, said amino acids comprising arginine, histidine, lysine or ornithine or analogues thereof, or wherein the amine of the R 7 moiety is quaternized with R 3 , R 4 or R 5 groups; or R 7 is a polypeptide selected from the group consisting of L-or D-alpha amino acids, wherein at least one of the amino acids residues comprises arginine, histidine, lysine, ornithine, or analogues thereof; n is 1 to 8; m is 1 to 18; and X is a non-toxic anion.
Claim 2
Dependent Claim
254 words
A composition having the structure ##STR15## wherein Y 1 and Y 2 are the same or different and are, --O--C(O)--, or --O--; R 1 is H, or C 1 to C 24 alkyl or alkenyl; R 2 is C 1 to C 24 alkyl or alkenyl; R 3 and R 4 are the same or different and are C 1 to C 24 alkyl, or H; R 5 is C 1 to C 24 alkyl straight chain or branched chain; R 6 is --C(O)--(CH 2 ) m --NH--, a diaminocarboxylate ester group which is alkyl, aryl, or aralkyl, or --C(O)--(CH 2 ) m --NH-- linked to said diaminocarboxylate ester group, or is absent; R 7 is H, spermine, spermidine, a histone, or a protein with DNA-binding specificity, or the same groups wherein the amine functionalities of the R 7 moiety are quaternized with R 3 , R 4 , or R 5 groups; or R 7 is an L- or D-alpha amino acid having a positively charged group on the side chain, said amino acids comprising arginine, histidine, lysine or ornithine or analogues thereof, or wherein the amine of the R 7 moiety is quaternized with R 3 , R 4 or R 5 groups; or R 7 is a polypeptide selected from the group consisting of L-or D-alpha amino acids, wherein at least one of the amino acids residues comprises arginine, histidine, lysine, ornithine, or analogues thereof; n is 1 to 8; m is 1 to 18; and X is a non-toxic anion.
Claim 3
Dependent Claim
79 words
A composition according to claim 1 wherein R 3 and R 4 are individually C 1 to C 23 alkyl groups, R 5 is --(CH 2 ) m --, R 6 is absent, R 7 is H, and R 1 and R 2 individually have from 0 to 6 sites of unsaturation, and have the structure CH.sub.3 --(CH.sub.2).sub.a --(CH═CH--CH.sub.2).sub.b --(CH.sub.2).sub.c -- wherein the sum of a and c is from 1 to 23; and b is 0 to 6.
Claim 4
Dependent Claim
17 words
A composition according to claim 2, wherein Y 1 and Y 2 are alike and are --O--C(O)--.
Claim 5
Dependent Claim
12 words
A composition according to claim 3, which is DL-1,2-dioleoyl-3-dimethylaminopropyl-β-hydroxyethylammonium and its salts.
Claim 6
Dependent Claim
17 words
A composition according to claim 2 wherein Y 1 and Y 2 are alike and are --O--.
Claim 7
Dependent Claim
12 words
A composition according to claim 5, which is 1,2-O-dioleyl-3-dimethylaminopropyl-β-hydroxyethylammonium and its salts.
Claim 8
Dependent Claim
20 words
A composition according to claim 2 wherein Y 1 and Y 2 are different and are either --O-- or --O--C(O)--.
Claim 9
Dependent Claim
12 words
A composition according to claim 7 which is 1-O-oleyl-2-oleyl-3-dimethylaminopropyl-β-hydroxyethylammonium and its salts.
Claim 10
Dependent Claim
1 words
3,5-(N,N-dilysyl)-diaminobenzoyl-3-(DL-1,2-dioleoyl-dimethylaminopropyl-β-hydroxyethylamine).
Claim 11
Dependent Claim
1 words
3,5-(N,N-dilysyl)-diaminobenzoyl-3-(DL-1,2-dioleoyl-dimethylaminopropyl-β-hydroxyethylamine).
Claim 12
Dependent Claim
1 words
3,5-(N,N-dilysyl)-diaminobenzoylglycyl-3-(DL-1,2-dioleoyl-dimethylaminopropyl-β-hydroxyethylamine).
Claim 13
Dependent Claim
1 words
3,5-(N,N-dilysyl)-diaminobenzoylglycyl-3-(DL-1,2-dioleoyl-dimethylaminopropyl-β-hydroxyethylamine).
Claim 14
Dependent Claim
1 words
L-spermine-5-carboxyl-3-(DL-1,2-dioleoyldimethylaminopropyl-β-hydroxyethylamine).
Claim 15
Dependent Claim
1 words
L-spermine-5-carboxyl-3-(DL-1,2-dioleoyldimethylaminopropyl-β-hydroxyethylamine).
Claim 16
Dependent Claim
108 words
A composition having the structure ##STR16## or an optical isomer thereof, wherein Y 1 and Y 2 are different and are either, --O--C(O)-- or --O--; R 1 is C 1 to C 24 alkyl or alkenyl, or H; R 2 is C 1 to C 24 alkyl or alkenyl; R 3 , R 4 and R 5 are the same or different and are H, C 1 to C 14 alkyl, C 7 to C 11 aryl or alkaryl, or at least two of R 3 , R 4 and R 5 are taken together to form quinuclidino, piperidino, pyrrolidino, or morpholino; and X is a non-toxic anion.
Claim 17
Dependent Claim
108 words
A composition having the structure ##STR16## or an optical isomer thereof, wherein Y 1 and Y 2 are different and are either, --O--C(O)-- or --O--; R 1 is C 1 to C 24 alkyl or alkenyl, or H; R 2 is C 1 to C 24 alkyl or alkenyl; R 3 , R 4 and R 5 are the same or different and are H, C 1 to C 14 alkyl, C 7 to C 11 aryl or alkaryl, or at least two of R 3 , R 4 and R 5 are taken together to form quinuclidino, piperidino, pyrrolidino, or morpholino; and X is a non-toxic anion.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1996-11-22 | 1997-05-24 | 1997-11-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-11-22 | 2001-05-24 | 2001-11-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-11-22 | 2005-05-24 | 2005-11-23 | $7700.00 | Window Closed / Lapsed |