Patent US2959964A successfully refreshed from Google Patents.
Patent US5861397A successfully refreshed from Google Patents.
US5861397A
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Piperazine based cytofectins
Assignee: Fresh Tracks Therapeutics Inc
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Filing: 1996-10-03
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Granted: 1999-01-19
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Expires: 2016-10-03
Abstract
Abstract The present invention relates to piperazine based amphilic cationic lipids useful for gene therapy, transfection, and introducing immunogenic compounds for the purpose of vaccination. The disclosed compounds have lipophilic moieties linked to the ring nitrogens. In addition, at least one of the ring nitrogens is quatranized and linked to a hydrocarbon having at least one heteroatom.
Inventors
- 👤 Carl J. Wheeler
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 15:39
CPC Classifications
C; C07; C07D; C07D295/00; C07D295/04; C07D295/08; C07D295/084; C07D295/088; C07D295/12; C07D295/125; C07D295/13; C07D295/16; C07D295/20; C07D295/215; Y; Y10; Y10S; Y10S424/00; Y10S424/812
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
430 words
A piperazine based cytofectin of the following structure: ##STR8## wherein R 1 , and R 4 are independently H, linear C 1 -C 23 groups, or branched C 1 -C 23 groups, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alky, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; R 2 is a linear C 1 -C 23 group, or a branched C 1 -C 23 group, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; R 3 is absent, H, an amino acid, peptide, polypeptide, protein, nucleic acid, nucleotide, nucleoside, polynucleotide, polynucleoside, monosaccharide, disaccharide, polysacchararide, bioactive agent, pharmaceutical agent, a linear C 1 -C 23 group, or a branched C 1 -C 23 group, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms, or a group having the following structure: ##STR9## wherein R 7 through R 12 are independently absent, H, an amino acid, nucleotide, polynucleotide, monosaccharide, disaccharide, polysaccharide, bioactive agent, pharmaceutical agent, linear C 1 -C 23 groups, or branched C 1 -C 23 groups, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; G is absent, O, N, NH, S, SH, Se, C, CH, or CR 1 ; T is O, N, S, Se, or C; A is O, N, S, Se, or C; Y 1 and Y 2 are independently O, N, NH, S, or Se; X 1 is absent, O, N, NH, S, or Se; m and p are independently 1-6; W is a pharmaceutically acceptable anion; and wherein when X 1 is absent then at least one of R 2 and R 3 contains a heteroatom.
Claim 2
Dependent Claim
430 words
A piperazine based cytofectin of the following structure: ##STR8## wherein R 1 , and R 4 are independently H, linear C 1 -C 23 groups, or branched C 1 -C 23 groups, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alky, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; R 2 is a linear C 1 -C 23 group, or a branched C 1 -C 23 group, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; R 3 is absent, H, an amino acid, peptide, polypeptide, protein, nucleic acid, nucleotide, nucleoside, polynucleotide, polynucleoside, monosaccharide, disaccharide, polysacchararide, bioactive agent, pharmaceutical agent, a linear C 1 -C 23 group, or a branched C 1 -C 23 group, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms, or a group having the following structure: ##STR9## wherein R 7 through R 12 are independently absent, H, an amino acid, nucleotide, polynucleotide, monosaccharide, disaccharide, polysaccharide, bioactive agent, pharmaceutical agent, linear C 1 -C 23 groups, or branched C 1 -C 23 groups, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; G is absent, O, N, NH, S, SH, Se, C, CH, or CR 1 ; T is O, N, S, Se, or C; A is O, N, S, Se, or C; Y 1 and Y 2 are independently O, N, NH, S, or Se; X 1 is absent, O, N, NH, S, or Se; m and p are independently 1-6; W is a pharmaceutically acceptable anion; and wherein when X 1 is absent then at least one of R 2 and R 3 contains a heteroatom.
Claim 3
Dependent Claim
13 words
The piperazine based cytofectins of claim 1 wherein m and p are 2.
Claim 4
Dependent Claim
15 words
The piperazine based cytofectins of claim 2 wherein Y 1 and Y 2 are O.
Claim 5
Dependent Claim
36 words
The piperazine based cytofectins of claim 3 wherein R 1 and R 4 are selected from the group consisting of C 10 H 21 , C 12 H 25 , and C 14 H 29 .
Claim 6
Dependent Claim
48 words
The piperazine based cytofectins of claim 4 wherein R 2 is selected from the group consisting of absent, CH 2 , (CH 2 ) 2 , (CH 2 ) 3 , (CH 2 ) 4 ,(CH 2 ) 5 , (CH 2 ) 6 and CO--CH--NH 2 .
Claim 7
Dependent Claim
21 words
The piperazine based cytofectins of claim 5 wherein X 1 is selected from the group consisting of absent, NH and O.
Claim 8
Dependent Claim
32 words
The piperazine based cytofectins of claim 6 wherein X 1 is NH and R 3 is selected from the group consisting of H, CO--NH--CH 3 , and CO--CH 2 --NH 2 .
Claim 9
Dependent Claim
17 words
The piperazine based cytofectins of claim 6 wherein X 1 is O and R 3 is H.
Claim 10
Dependent Claim
23 words
The piperazine based cytofectins of claim 6 wherein X 1 is absent and R 3 is CH 2 --CH 2 --NH 2 .
Claim 11
Dependent Claim
23 words
The piperazine based cytofectins of claim 6 wherein R 2 is (CH 2 )2, X 1 is O and R 3 is H.
Claim 12
Dependent Claim
25 words
The piperazine based cytofectins of claim 6 wherein R 2 is (CH 2 ) 3 , X 1 is NH and R 3 is H.
Claim 13
Dependent Claim
25 words
The piperazine based cytofectins of claim 6 wherein R 2 is (CH 2 ) 4 , X 1 is NH and R 3 is H.
Claim 14
Dependent Claim
25 words
The piperazine based cytofectins of claim 6 wherein R 2 is (CH 2 ) 5 , X 1 is NH and R 3 is H.
Claim 15
Dependent Claim
25 words
The piperazine based cytofectins of claim 6 wherein R 2 is (CH 2 ) 6 , X 1 is NH and R 3 is H.
Claim 16
Dependent Claim
27 words
The piperazine based cytofectins of claim 6 wherein R 2 is (CH 2 ) 3 , X 1 is NH and R 3 is CO--CH2--NH 2 .
Claim 17
Dependent Claim
27 words
The piperazine based cytofectins of claim 6 wherein R 2 is (CH 2 ) 3 , X 1 is NH and R 3 is CO--NH--CH 3 .
Claim 18
Dependent Claim
28 words
The piperazine based cytofectins of claim 6 wherein R 2 is CO--CH(NH 2 ), X 1 is absent and R 3 ═--CH 2 --CH 2 --NH 2 .
Claim 19
Dependent Claim
393 words
A piperazine based cytofectin of the following structure: ##STR10## wherein R 1 , R 2 , R 4 , and R 5 are independently H, linear C 1 -C 23 groups, or branched C 1 -C 23 groups said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; R 3 and R 6 are each independently absent, H, an amino acid, peptide, polypeptide, protein, nucleic acid, nucleotide, nucleoside, polynucleotide, polynucleoside, monosaccharide, disaccharide, polysacchararide, bioactive agent, pharmaceutical agent, a linear C 1 -C 23 group, or a branched C 1 -C 23 group, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms, or a group having the following structure: ##STR11## wherein R 7 through R 12 are independently absent, H, an amino acid, nucleotide, polynucleotide, monosaccharide, disaccharide, polysaccharide, bioactive agent, pharmaceutical agent, linear C 1 -C 23 groups, or branched C 1 -C 23 groups, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; G is absent, O, N, NH, S, SH, Se, C, CH, or CR 1 ; T is O,N, S, Se, or C; A is O, N, S, Se, or C; Y 1 and Y 2 are independently O, N, NH, S, or Se; X 1 and X 2 are independently absent, O, N, NH, S, or Se; m and p are independently 1-6; W is a pharmaceutically acceptable anion; and wherein both R 2 and R 5 are not H and wherein when X 1 or X 2 is absent then at least one of R 2 , R 3 , R 5 , and R 6 contains a heteroatom.
Claim 20
Dependent Claim
393 words
A piperazine based cytofectin of the following structure: ##STR10## wherein R 1 , R 2 , R 4 , and R 5 are independently H, linear C 1 -C 23 groups, or branched C 1 -C 23 groups said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; R 3 and R 6 are each independently absent, H, an amino acid, peptide, polypeptide, protein, nucleic acid, nucleotide, nucleoside, polynucleotide, polynucleoside, monosaccharide, disaccharide, polysacchararide, bioactive agent, pharmaceutical agent, a linear C 1 -C 23 group, or a branched C 1 -C 23 group, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms, or a group having the following structure: ##STR11## wherein R 7 through R 12 are independently absent, H, an amino acid, nucleotide, polynucleotide, monosaccharide, disaccharide, polysaccharide, bioactive agent, pharmaceutical agent, linear C 1 -C 23 groups, or branched C 1 -C 23 groups, said linear or branched C 1 -C 23 groups being alkyl, acyl, alkene or heteroalkyl groups, said alkyl, acyl, alkene or heteroalkyl groups being unsubstituted or substituted, having 0 to 6 sites of unsaturation, containing 0 to 5 heteroatoms, or containing cyclic or aryl groups, said cyclic or aryl groups containing 0-5 heteroatoms; G is absent, O, N, NH, S, SH, Se, C, CH, or CR 1 ; T is O,N, S, Se, or C; A is O, N, S, Se, or C; Y 1 and Y 2 are independently O, N, NH, S, or Se; X 1 and X 2 are independently absent, O, N, NH, S, or Se; m and p are independently 1-6; W is a pharmaceutically acceptable anion; and wherein both R 2 and R 5 are not H and wherein when X 1 or X 2 is absent then at least one of R 2 , R 3 , R 5 , and R 6 contains a heteroatom.
Claim 21
Dependent Claim
24 words
The piperazine based cytofectins of claim 18, wherein both R 2 --X 1 --R 3 and R 5 --X 2 --R 6 are heteroatomic.
Claim 22
Dependent Claim
28 words
The piperazine based cytofectins of claim 18, wherein either R 2 --X 1 --R 3 or R 5 --X 2 --R 6 , but not both, is heteroatomic.
Claim 23
Dependent Claim
13 words
The piperazine based cytofectins of claim 18 wherein m and p are 2.
Claim 24
Dependent Claim
15 words
The piperazine based cytofectins of claim 21 wherein Y 1 and Y 2 are O.
Claim 25
Dependent Claim
48 words
The piperazine based cytofectins of claim 22, wherein R 5 and R 2 are selected from the group consisting of absent, CH 2 , (CH 2 ) 2 , (CH 2 ) 3 , (CH 2 ) 4 ,(CH 2 ) 5 and (CH 2 ) 6 .
Claim 26
Dependent Claim
36 words
The piperazine based cytofectins of claim 23 wherein R 1 and R 4 are selected from the group consisting of C 10 H 21 , C 12 H 25 , and C 14 H 29 .
Claim 27
Dependent Claim
24 words
The piperazine based cytofectins of claim 24, wherein X 1 and X 2 are selected from the group consisting of absent, NH and O.
Claim 28
Dependent Claim
51 words
The piperazine based cytofectins of claim 25, wherein R 1 and R 4 are C 12 H 25 , R 2 is CH 3 ; X 1 and R 3 are absent, R 5 is CH 2 CH 2 CH 2 , X 2 is NH and R 6 is H.
Claim 29
Dependent Claim
68 words
A method of delivering a molecule into a cell comprising the steps of (a) contacting the molecule with an effective amount of any of the cytofectins of any one of claim 1 or claim 18 to form a complex with the lipid; and (b) contacting a cell with the lipid complex formed in step (a); whereby a biologically effective amount of the molecule is inserted into the cell.
Claim 30
Dependent Claim
12 words
The method of claim 27 wherein the molecule is an anionic molecule.
Claim 31
Dependent Claim
25 words
The method of claim 27 wherein the complex further includes one or more lipids in addition to said cytofectins of claim 1 or claim 18.
Claim 32
Dependent Claim
31 words
The method of claim 29 wherein the lipids in addition to said cytofectin of claim 1 or claim 18 are selected from the group consisting of neutral lipids, phospholipids, and cholesterol.
Claim 33
Dependent Claim
14 words
The method of claim 27, wherein said cell is contacted under in vitro conditions.
Claim 34
Dependent Claim
14 words
The method of claim 27, wherein said cell is contacted under in vivo conditions.
Claim 35
Dependent Claim
37 words
The method of claim 32, wherein said cells are in an assay selected from the group consisting of the murine lung transfection, murine intraperitoneal tumor, murine intramuscular, porcine intraarterial, rabbit intraarterial, Renca tumor, and subcutaneous tumor assays.
Claim 36
Dependent Claim
11 words
The method of claim 28 wherein the anionic molecule is mRNA.
Claim 37
Dependent Claim
11 words
The method of claim 28 wherein the anionic molecule is DNA.
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