Cationic sulfonamide amino lipids and amphiphilic zwitterionic amino lipids
AssigneeBoard of Regents, The University of Texas System
InventorsDaniel J. Siegwart, Jason B. Miller
Life of this patent
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Abstract
The present disclosure provides one or more amino lipids such as an amino lipids containing a sulfonic acid or sulfonic acid derivative of the formulas: wherein the variables are as defined herein. These amino lipids may be used in compositions with one or more helper lipids and a nucleic acid therapeutic agent. These compositions may be used to treat a disease or disorder such as cancer, cystic fibrosis, or other genetic diseases.
Claims26
A pharmaceutical composition comprising a polynucleotide assembled with a lipid composition, the lipid composition comprising a zwitterionic lipid comprising a zwitterionic headgroup, wherein the zwitterionic headgroup comprises an alkylated phosphate anion and a quaternary ammonium cation, wherein the zwitterionic lipid has a structural formula:
- wherein:
- R2 and R3 are independently hydrogen or alkyl(C≤4);
- Ra is hydrogen;
- n and p are independently 1, 2, 3, or 4;
- and
- R1 has the structural formula selected from:
- wherein:
- R4 is hydrogen, alkyl(C≤6), or R;
- A is N-heterocycloalkyl(C≤6);
- x and y are independently 1, 2, 3 or 4;
- R7 is hydrogen, R, alkyl(C1), alkanediyl(C≤6)-N(R)2, alkanediyl(C≤6)-N(R)(alkyl(C≤6));
- R5 and R6 is independently hydrogen, R, alkyl(C≤6), alkanediyl(≤6)-N(R)2, (CH2)2(NR)(CH2)2(N(R)2), or (CH2)2(NR)(CH2)2(NR)(CH2)2(N(R)2);
- and
- R is hydrogen or —ZA′R8;
- wherein:
- Z is alkanediyl(C≤4);
- A′ is —CHRk—, —C(O)O—, or —C(O)NRp—;
- Rp is hydrogen or alkyl(C≤6);
- and
- Rk is hydrogen, hydroxy, or acyloxy(C≤24);
- and
- R8 is alkyl(C6-C24).
A method for delivering a polynucleotide into a cell, the method comprising contacting said cell with a lipid composition assembled with said polynucleotide, which lipid composition comprising a zwitterionic lipid, wherein the zwitterionic lipid has a structural formula:
- wherein:
- R2 and R3 are independently hydrogen or alkyl(C≤4);
- Ra is hydrogen;
- n and p are independently 1, 2, 3, or 4;
- and
- R1 has the structural formula selected from:
- wherein:
- R4 is hydrogen, alkyl(C≤6), or R;
- A is N-heterocycloalkyl(C≤6);
- x and y are independently 1, 2, 3 or 4;
- R7 is hydrogen, R, alkyl(C1), alkanediyl(C≤6)-N(R)2, alkanediyl(C≤6)-N(R)(alkyl(C≤6));
- R5 and R6 is independently hydrogen, R, alkyl(C≤6), alkanediyl(≤6)-N(R)2, (CH2)2(NR)(CH2)2(N(R)2), or (CH2)2(NR)(CH2)2(NR)(CH2)2(N(R)2);
- and
- R is hydrogen or —ZA′R8;
- wherein:
- Z is alkanediyl(C≤4);
- A′ is —CHRk—, —C(O)O—, or —C(O)NRp—;
- Rp is hydrogen or alkyl(C≤6);
- and
- Rk is hydrogen, hydroxy, or acyloxy(C≤24);
- and
- R8 is alkyl(C6-C24).
Dependencies are inferred from the claim text.