Arbutus Biopharma Corporation

Tekmira Pharmaceuticals Corporation

Laxman Eltepu

Kallanthottathil G Rajeev

Muthusamy Jayaraman

Muthiah Manoharan

David Butler

Jianxin Chen

Jayaprakash K Nair

Steven Ansell

Martin A Maier

Steven Michial Ansell

Jayaprakash K Narayanannair

Muthiah Mancharan

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure wherein:

Lipids and compositions for the delivery of therapeutics

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention formula (I) provides lipids having the following structure XXXIII wherein: Rand Rare each independently for each occurrence optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, optionally substituted C-Cacyl, or -linker-ligand; Ris H, optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, &#x3c9;-aminoalkyls, &#x3c9;-(substituted)aminoalkyls, &#x3c9;-phosphoalkyls, &#x3c9;-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure XXXIII, wherein:Rand Rare each independently for each occurrence optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, optionally substituted C-Cacyl, or -linker-ligand; Ris H, optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, &#x3c9;-aminoalkyls, &#x3c9;-(substituted)aminoalkyls, &#x3c9;-phosphoalkyls, &#x3c9;-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structures: 

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure wherein Rand Rare each independently for each occurrence optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, optionally substituted C-Cacyl, or -linker-ligand; Ris H, optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, &#x3c9;-aminoalkyls, &#x3c9;-(substituted)aminoalkyls, &#x3c9;-phosphoalkyls, &#x3c9;-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)N(Q), S(O), N(Q)S(O), SS, O&#x2550;N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, &#x3c9;-aminoalkyl, &#x3c9;-(substituted)aminoalky, &#x3c9;-phosphoalkyl or &#x3c9;-thiophosphoalkyl.

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure wherein:Rand Rare each independently for each occurrence optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, optionally substituted C-Cacyl, or -linker-ligand; Ris H, optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, &#x3c9;-aminoalkyls, &#x3c9;-(substituted)aminoalkyls, &#x3c9;-phosphoalkyls, &#x3c9;-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40 K), optionally substituted mPEG (mw 120-40 K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure wherein Rand Rare each independently for each occurrence optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, optionally substituted C-Cacyl, or -linker-ligand; Ris H, optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, &#x3c9;-aminoalkyls, &#x3c9;-(substituted)aminoalkyls, &#x3c9;-phosphoalkyls, &#x3c9;-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40 K), optionally substituted mPEG (mw 120-40 K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)N(Q), S(O), N(Q)S(O), SS, O&#x2550;N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, &#x3c9;-aminoalkyl, &#x3c9;-(substituted)aminoalky, &#x3c9;-phosphoalkyl or &#x3c9;-thiophosphoalkyl.

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention formula (I) provides lipids having the following structure XXXIII wherein: Rand Rare each independently for each occurrence optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, optionally substituted C-Cacyl, or -linker-ligand; Ris H, optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, alky lhetro cycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, &#x3c9;-aminoalkyls, &#x3c9;-(substituted)aminoalkyls, &#x3c9;-phosphoalkyls, &#x3c9;-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O). 

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure (I) wherein Rand Rare each independently for each occurrence optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, optionally substituted C-Cacyl, or -linker-ligand; Ris H, optionally substituted C-Calkyl, optionally substituted C-Calkenyl, optionally substituted C-Calkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, &#x3c9;-aminoalkyls, &#x3c9;-(substituted)aminoalkyls, &#x3c9;-phosphoalkyls, &#x3c9;-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)2N(Q), S(O)2, N(Q)S(O)2, SS, O&#x2550;N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, &#x3c9;-aminoalkyl, &#x3c9;-(substituted)aminoalky, &#x3c9;-phosphoalkyl or &#x3c9;-thiophosphoalkyl.

Growing community of inventors

Cambridge, MA, United States of America

Laxman Eltepu