公开(公告)号：US10117941B2

公开(公告)日：2018-11-06

申请号：US15603069

申请日：2017-05-23

Applicant: Arbutus Biopharma Corporation

Inventor： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Muthusamy Jayaraman ,  David Butler ,  Jayaprakash K. Nair ,  Martin Maier ,  Laxman Eltepu

IPC: A61K39/39 ,  C07D203/10 ,  A61K47/18 ,  A61K47/28 ,  A61K31/713 ,  A61K39/00 ,  A61K47/44 ,  C07C229/08 ,  C07C229/30 ,  C07D317/28 ,  C07D319/06 ,  C12N15/113 ,  A61K9/127 ,  C12N15/11 ,  A61K47/10 ,  A61K47/20 ,  C07C237/16 ,  C07C251/38 ,  C07C251/78 ,  C07C271/12 ,  C07C271/20 ,  C07C323/25 ,  A61K31/7088 ,  C07D317/44 ,  C07D317/46 ,  C07D317/72 ,  C07D405/12 ,  C07D491/056 ,  C07D491/113

Abstract: 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 R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-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═N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, ω-aminoalkyl, ω-(substituted)aminoalky, ω-phosphoalkyl or ω-thiophosphoalkyl.

公开(公告)号：US09707292B2

公开(公告)日：2017-07-18

申请号：US14884489

申请日：2015-10-15

Applicant: ARBUTUS BIOPHARMA CORPORATION

Inventor： Muthiah Manoharan ,  Muthusamy Jayaraman ,  Kallanthottathil G. Rajeev ,  Laxman Eltepu ,  Steven Ansell ,  Jianxin Chen

IPC: A61K39/39 ,  A61K9/127 ,  C07C229/08 ,  A61K31/713 ,  C07D203/10 ,  C12N15/113 ,  C07C229/30 ,  C07D317/28 ,  C07D319/06 ,  A61K39/00 ,  C12N15/11 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  C07C237/16 ,  C07C251/38 ,  C07C251/78 ,  C07C271/12 ,  C07C271/20 ,  C07C323/25

CPC classification number: A61K47/44 ,  A61K9/1272 ,  A61K31/7088 ,  A61K31/713 ,  A61K39/00 ,  A61K39/39 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  A61K2039/55555 ,  A61K2039/55561 ,  C07C229/08 ,  C07C229/30 ,  C07C237/16 ,  C07C251/38 ,  C07C251/78 ,  C07C271/12 ,  C07C271/20 ,  C07C323/25 ,  C07D203/10 ,  C07D317/28 ,  C07D317/44 ,  C07D317/46 ,  C07D317/72 ,  C07D319/06 ,  C07D405/12 ,  C07D491/056 ,  C07D491/113 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/3515 ,  C12N2320/32 ,  Y02A50/464

Abstract: 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: R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-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).

公开(公告)号：US09694077B2

公开(公告)日：2017-07-04

申请号：US14508805

申请日：2014-10-07

Applicant: ARBUTUS BIOPHARMA CORPORATION

Inventor： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Muthusamy Jayaraman ,  David Butler ,  Michael E. Jung

IPC: A61K47/22 ,  C12N15/113 ,  C07D295/13 ,  A61K9/127

CPC classification number: A61K47/22 ,  A61K9/1272 ,  C07D295/13 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  Y02A50/463

Abstract: Disclosed herein are lipid compositions comprising a cationic lipid of formula (I), a neutral lipid, a sterol and a PEG or PEG-modified lipid, wherein formula (I) is Also disclosed are methods of producing the cationic lipid of formula (I).

公开(公告)号：US09663449B2

公开(公告)日：2017-05-30

申请号：US14149496

申请日：2014-01-07

Applicant: ARBUTUS BIOPHARMA CORPORATION

Inventor： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Akin Akinc ,  Jayaprakash K. Nair ,  Muthusamy Jayaraman ,  Martin Maier

IPC: A61K9/48 ,  C07C229/00 ,  A61K9/127 ,  A61K47/34 ,  C07C233/36 ,  C07C209/78 ,  C07C219/06 ,  A61K31/325 ,  C07C271/10 ,  C07C323/25

Abstract: Compositions and methods useful in administering nucleic acid based therapies, for example association complexes such as liposomes and lipoplexes are described.