公开(公告)号：US20180221510A1

公开(公告)日：2018-08-09

申请号：US15788575

申请日：2017-10-19

Applicant: Arbutus Biopharma Corporation

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

IPC: A61K48/00 ,  A61K47/18 ,  A61K47/14 ,  C07C229/12 ,  A61K31/7088 ,  C07D491/113 ,  C07C323/25 ,  C07C251/38 ,  A61K31/713

CPC classification number: A61K48/0033 ,  A61K31/7088 ,  A61K31/713 ,  A61K47/14 ,  A61K47/18 ,  C07C229/12 ,  C07C251/38 ,  C07C323/25 ,  C07C2601/02 ,  C07D491/113

Abstract: A lipid particle can include a cationic lipid. The cationic lipid can include one or more hydrophobic tails, which can include one or more sites of unsaturation. The sites of unsaturation can include cycloalkyl groups, e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl groups. The lipid particle is suitable for delivering an active agent.

公开(公告)号：US20180221494A1

公开(公告)日：2018-08-09

申请号：US15837785

申请日：2017-12-11

Applicant: Arbutus Biopharma Corporation

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

IPC: A61K47/54 ,  A61K47/55 ,  A61K48/00 ,  C12N15/11 ,  C12N15/113 ,  C12N15/87

CPC classification number: A61K47/554 ,  A61K47/545 ,  A61K47/549 ,  A61K47/551 ,  A61K48/0008 ,  C12N15/111 ,  C12N15/1137 ,  C12N15/87 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/3513 ,  C12N2320/32 ,  C12Y304/21021

Abstract: The invention relates to compositions and methods for site-specific delivery of nucleic acids by combining them with targeting ligands and endosomolytic components.

公开(公告)号：US20180104342A1

公开(公告)日：2018-04-19

申请号：US15594244

申请日：2017-05-12

Applicant: Arbutus Biopharma Corporation

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

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

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：US20180064807A1

公开(公告)日：2018-03-08

申请号：US15474911

申请日：2017-03-30

Applicant: Arbutus Biopharma Corporation

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

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

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:

公开(公告)号：US20240042039A1

公开(公告)日：2024-02-08

申请号：US18194540

申请日：2023-03-31

Applicant: ARBUTUS BIOPHARMA CORPORATION

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

IPC: A61K47/44 ,  A61K31/7088 ,  A61K31/713 ,  A61K39/00 ,  A61K39/39 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  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 ,  C12N15/11 ,  C12N15/113 ,  A61K9/127

CPC classification number: A61K47/44 ,  C12N2320/32 ,  A61K31/713 ,  A61K39/00 ,  A61K39/39 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  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 ,  A61K9/1272 ,  Y02A50/30 ,  A61K2039/55555 ,  A61K2039/55561 ,  C12N2310/14 ,  C12N2310/3515 ,  A61K31/7088

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; and E is C(O)O or OC(O).

公开(公告)号：US20220023427A1

公开(公告)日：2022-01-27

申请号：US17357122

申请日：2021-06-24

Applicant: ARBUTUS BIOPHARMA CORPORATION

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

IPC: A61K47/44 ,  A61K39/39 ,  C07C229/08 ,  A61K31/713 ,  C07D319/06 ,  C07D317/28 ,  C07D203/10 ,  C07C229/30 ,  C12N15/113 ,  A61K39/00 ,  C12N15/11 ,  A61K9/127 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  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 formula (I) provides lipids having the following structure XXXIII 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; and E is C(O)O or OC(O).

公开(公告)号：US09814777B2

公开(公告)日：2017-11-14

申请号：US14060353

申请日：2013-10-22

Applicant: Arbutus Biopharma Corporation

Inventor： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jayaprakash K. Nair ,  Muthusamy Jayaraman

IPC: A61K31/7088 ,  A61K31/713 ,  A61K47/16 ,  A61K47/22 ,  A61K47/28 ,  A61K31/7004 ,  A61K31/7052 ,  A61K31/70 ,  A61K47/48 ,  C07H21/02 ,  A61K48/00

CPC classification number: A61K47/28 ,  A61K31/70 ,  A61K31/7004 ,  A61K31/7052 ,  A61K31/7088 ,  A61K31/713 ,  A61K47/16 ,  A61K47/22 ,  A61K47/543 ,  A61K47/549 ,  A61K47/60 ,  A61K48/00 ,  C07H21/02 ,  Y02A50/385 ,  Y02A50/411 ,  Y02A50/467 ,  Y02P20/55

Abstract: The present invention provides targeting lipids of structure L100-linker-L101  (CI), where L100 is a lipid, lipophile, alkyl, alkenyl or alkynyl, L101 is a ligand or —CH2CH2(OCH2CH2)pO(CH2)qCH2-ligand, p is 1-1000, and q is 1-20. In addition, the invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo.

公开(公告)号：US20170143631A1

公开(公告)日：2017-05-25

申请号：US15187633

申请日：2016-06-20

Applicant: Arbutus Biopharma Corporation

Inventor： Jianxin Chen ,  Steven Ansell ,  Akin Akinc ,  Joseph Robert Dorkin ,  Xiaojun Qin ,  William Cantley ,  Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jayaprakash K. Nair ,  Muthusamy Jayaraman

IPC: A61K9/127 ,  A61K31/713 ,  A61K31/712 ,  C12N15/113

CPC classification number: A61K9/1272 ,  A61K9/1278 ,  A61K31/22 ,  A61K31/7088 ,  A61K31/712 ,  A61K31/713 ,  A61K38/1709 ,  A61K38/4846 ,  A61K47/14 ,  A61K47/549 ,  A61K47/551 ,  A61K47/6911 ,  A61K48/0033 ,  A61P9/00 ,  A61P25/28 ,  C07C29/58 ,  C07C227/18 ,  C07C227/40 ,  C07C229/12 ,  C07D475/04 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/3515 ,  C12N2320/32 ,  Y02A50/463 ,  A61K2300/00 ,  C12N2310/3521 ,  C12N2310/3533

Abstract: The invention features a cationic lipid of formula I, an improved lipid formulation comprising a cationic lipid of formula I and corresponding methods of use. Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.

公开(公告)号：US20230381319A1

公开(公告)日：2023-11-30

申请号：US18110791

申请日：2023-02-16

Applicant: ARBUTUS BIOPHARMA CORPORATION

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

IPC: A61K47/44 ,  A61K39/39 ,  C07C229/08 ,  A61K31/713 ,  C07D319/06 ,  C07D317/28 ,  C07D203/10 ,  C07C229/30 ,  C12N15/113 ,  A61K39/00 ,  C12N15/11 ,  A61K9/127 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  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

CPC classification number: A61K47/44 ,  A61K39/39 ,  C07C229/08 ,  A61K31/713 ,  C07D319/06 ,  C07D317/28 ,  C07D203/10 ,  C07C229/30 ,  C12N15/113 ,  A61K39/00 ,  C12N15/111 ,  A61K9/1272 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  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 ,  A61K2039/55555 ,  A61K2039/55561 ,  C12N2310/14 ,  C12N2310/3515 ,  C12N2320/32 ,  Y02A50/30

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 (I) 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：US11077197B2

公开(公告)日：2021-08-03

申请号：US15617520

申请日：2017-06-08

Applicant: Arbutus Biopharma Corporation

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

IPC: A61K47/44 ,  A61K39/39 ,  C07C229/08 ,  A61K31/713 ,  C07D319/06 ,  C07D317/28 ,  C07D203/10 ,  C07C229/30 ,  C12N15/113 ,  A61K39/00 ,  C12N15/11 ,  A61K9/127 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  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 XXXIII, 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; and E is C(O)O or OC(O).