公开(公告)号：US20210162053A1

公开(公告)日：2021-06-03

申请号：US17065208

申请日：2020-10-07

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

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, alkylheterocycle, 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)aminoalkyl, ω-phosphoalkyl or ω-thiophosphoalkyl.

公开(公告)号：US10821186B2

公开(公告)日：2020-11-03

申请号：US16123209

申请日：2018-09-06

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

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：US20190099493A1

公开(公告)日：2019-04-04

申请号：US15729236

申请日：2017-10-10

Applicant: Arbutus Biopharma Corporation

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

IPC: A61K47/28 ,  A61K47/60 ,  A61K31/7052 ,  A61K31/7004 ,  A61K47/22 ,  A61K47/16 ,  A61K31/70 ,  A61K47/54 ,  C07H21/02 ,  A61K31/7088 ,  A61K31/713 ,  A61K48/00

Abstract: The present invention provides targeting lipids of structure 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：US20180125985A1

公开(公告)日：2018-05-10

申请号：US15671809

申请日：2017-08-08

Applicant: Arbutus Biopharma Corporation

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

IPC: A61K47/44 ,  A61K31/713 ,  A61K31/7088 ,  C07D491/056 ,  C07D317/44 ,  C07D317/46 ,  C07D405/12 ,  C07D317/28 ,  C07D491/113 ,  C07D317/72

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 structures:

公开(公告)号：US20180043009A1

公开(公告)日：2018-02-15

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 ,  A61K31/713 ,  A61K39/00 ,  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 ,  C07D319/06 ,  C12N15/11 ,  C12N15/113 ,  A61K9/127

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-C30alkyl, optionally substituted C10-C30alkenyl, optionally substituted C10-C30alkynyl, optionally substituted C10-C30acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10alkyl, optionally substituted C2-C10alkenyl, optionally substituted C2-C10alkynyl, 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：US09682139B2

公开(公告)日：2017-06-20

申请号：US14629991

申请日：2015-02-24

Applicant: ARBUTUS BIOPHARMA CORPORATION

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

IPC: A61K39/39 ,  A61K9/127 ,  C07C229/30 ,  A61K31/713 ,  C07D203/10 ,  C07C229/08 ,  C07D317/28 ,  C07D319/06 ,  C12N15/113 ,  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; 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：US12023383B2

公开(公告)日：2024-07-02

申请号：US18110654

申请日：2023-02-16

Applicant: ARBUTUS BIOPHARMA CORPORATION

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

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

CPC classification number: A61K47/22 ,  A61K9/1272 ,  C07D295/13 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  Y02A50/30

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 (F). Also disclosed are methods of producing the cationic lipid of formula (I).

公开(公告)号：US20240066129A1

公开(公告)日：2024-02-29

申请号：US18110654

申请日：2023-02-16

Applicant: ARBUTUS BIOPHARMA CORPORATION

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

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

CPC classification number: A61K47/22 ,  A61K9/1272 ,  C07D295/13 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  Y02A50/30

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 (F). Also disclosed are methods of producing the cationic lipid of formula (I).

公开(公告)号：US10953095B2

公开(公告)日：2021-03-23

申请号：US16593661

申请日：2019-10-04

Applicant: Arbutus Biopharma Corporation

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

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

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：US20190167800A1

公开(公告)日：2019-06-06

申请号：US16123209

申请日：2018-09-06

Applicant: Arbutus Biopharma Corporation

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

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

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.