Arbutus Biopharma Corporation

Alnylam Pharmaceuticals, Inc.

Tekmira Pharmaceuticals Corporation

Steven Ansell

Kallanthottathil G Rajeev

Muthusamy Jayaraman

Jianxin Chen

Muthiah Manoharan

Laxman Eltepu

Akin Akinc

Jayaprakash K Narayanannair

Joseph Robert Dorkin

Xiaojun Qin

William Cantley

Joseph R Dorkin

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 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 invention features a cationic lipid of formula I,  Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.

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Cambridge, MA, United States of America

Steven Ansell