Lipid Nanoparticle Based Compositions and Methods for the Delivery of Biologically Active Molecules

Abstract

The present invention relates to novel cationic lipids, transfection agents, microparticles, nanoparticles, and short interfering nucleic acid (siNA) molecules. The invention also features compositions, and methods of use for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity in a subject or organism. Specifically, the invention relates to novel cationic lipids, microparticles, nanoparticles and transfection agents that effectively transfect or deliver biologically active molecules, such as antibodies (e.g., monoclonal, chimeric, humanized etc.), cholesterol, hormones, antivirals, peptides, proteins, chemotherapeutics, small molecules, vitamins, co-factors, nucleosides, nucleotides, oligonucleotides, enzymatic nucleic acids, antisense nucleic acids, triplex forming oligonucleotides, 2,5-A chimeras, dsRNA, allozymes, aptamers, decoys and analogs thereof, and small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), short hairpin RNA (shRNA), and RNAi inhibitor molecules, to relevant cells and/or tissues, such as in a subject or organism. Such novel cationic lipids, microparticles, nanoparticles and transfection agents are useful, for example, in providing compositions to prevent, inhibit, or treat diseases, conditions, or traits in a cell, subject or organism. The compositions described herein are generally referred to as formulated molecular compositions (FMC) or lipid nanoparticles (LNP).

1 - 10 . (canceled) 
     
     
         11 . A compound having Formula CLXXXII: 
       
         
           
           
               
               
           
         
         wherein each R1, R2 and R5 is independently hydrogen, methyl, ethyl, propyl, isopropyl, or butyl, R3 is a C9-C24 aliphatic saturated or unsaturated hydrocarbon, each L is independently a linker, and R4 is cholesterol, a cholesterol derivative, a steroid hormone, or a bile acid. 
       
     
     
         12 . A compound according to  claim 11  wherein R3 is linoyl, isostearyl, oleyl, elaidyl, petroselinyl, linolenyl, elaeostearyl, arachidyl, myristoyl, palmitoyl, or lauroyl. 
     
     
         13 . A compound according to  claim 11  wherein R4 is cholesterol. 
     
     
         14 . A compound according to  claim 11  wherein each L is independently a C1 to C10 alkyl, alkyl ether, polyether, or polyethylene glycol linker with or without a disulphide linkage. 
     
     
         15 . A compound according to  claim 11  wherein each L is independently an acetal, amide, carbonyl, carbamide, carbamate, carbonate, ester (i.e., monoester, diester), or succinyl linker. 
     
     
         16 . A compound according to  claim 11  wherein R3 is linoyl and R4 is cholesterol. 
     
     
         17 . A compound having Formula CLXXXIII: 
       
         
           
           
               
               
           
         
         wherein each R1, R2 and R5 is independently hydrogen, methyl, ethyl, propyl, isopropyl, or butyl, R3 is a C9-C24 aliphatic saturated or unsaturated hydrocarbon, each L is independently a linker, and R4 is cholesterol, a cholesterol derivative, a steroid hormone, or a bile acid. 
       
     
     
         18 . A compound according to  claim 17  wherein R3 is linoyl, isostearyl, oleyl, elaidyl, petroselinyl, linolenyl, elaeostearyl, arachidyl, myristoyl, palmitoyl, or lauroyl. 
     
     
         19 . A compound according to  claim 17  wherein R4 is cholesterol. 
     
     
         20 . A compound according to  claim 17  wherein each L is independently a C1 to C10 alkyl, alkyl ether, polyether, or polyethylene glycol linker with or without a disulphide linkage. 
     
     
         21 . A compound according to  claim 17  wherein each L is independently an acetal, amide, carbonyl, carbamide, carbamate, carbonate, ester (i.e., monoester, diester), or succinyl linker. 
     
     
         22 . A compound according to  claim 17  wherein R3 is linoyl and R4 is cholesterol.