公开(公告)号：US12042541B2

公开(公告)日：2024-07-23

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 ,  A61K9/127 ,  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

CPC classification number: A61K47/44 ,  A61K9/1272 ,  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 ,  C12N15/111 ,  C12N15/113 ,  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




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：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：US11712476B2

公开(公告)日：2023-08-01

申请号：US17357122

申请日：2021-06-24

Applicant: ARBUTUS BIOPHARMA CORPORATION

Inventor： Muthiah Mancharan ,  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

CPC classification number: A61K47/44 ,  A61K9/1272 ,  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 ,  C12N15/111 ,  C12N15/113 ,  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 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：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：US20240424105A1

公开(公告)日：2024-12-26

申请号：US18736363

申请日：2024-06-06

Applicant: ARBUTUS BIOPHARMA CORPORATION

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

IPC: A61K47/44 ,  A61K9/127 ,  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

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：US20180092971A1

公开(公告)日：2018-04-05

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: A61K39/39 ,  A61K9/127 ,  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

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).

公开(公告)号：US09764036B2

公开(公告)日：2017-09-19

申请号：US14953677

申请日：2015-11-30

Applicant: ARBUTUS BIOPHARMA CORPORATION

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

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

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 structures:

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.

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.