-
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).
-
公开(公告)号：US20210179557A1
公开(公告)日：2021-06-17
申请号：US17259751
申请日：2019-07-25
Applicant: Arbutus Biopharma Corporation
Inventor： Andrew G. COLE , Steven KULTGEN
IPC: C07D209/44
Abstract: The present invention includes novel substituted bicyclic compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infection and/or hepatitis D virus (HDV) infection in a patient.
![SUBSTITUTED TETRAHYDROCYCLOPENTA[C]PYRROLES, SUBSTITUTED DIHYDROPYRROLIZINES, ANALOGUES THEREOF, AND METHODS USING SAME](/docs/US/2021-06-17/US20210179557A1/abs.jpg.600x600.jpg)
-
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.
-
94.发明授权
公开(公告)号：US11001564B2
公开(公告)日：2021-05-11
申请号：US16330328
申请日：2017-09-13
Applicant: ARBUTUS BIOPHARMA CORPORATION
Inventor： Andrew G. Cole , Steven Kultgen
IPC: C07D311/58 , C07D335/06 , C07D405/12 , C07D407/12 , C07D409/12 , C07D417/12 , C07D405/04 , C07C201/00 , C07D401/12 , C07D311/68 , C07D215/42 , C07D213/30 , C07D311/22 , C07C275/26 , C07C271/24 , A61P31/20 , C07D311/20 , C07D413/12 , C07D413/14
Abstract: The present invention includes novel substituted bicyclic (such as 4-substituted-chromane-8-carboxamide compounds), and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infections in a patient. In certain embodiments, the compounds and compositions of the invention are capsid inhibitors.
-
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：US20200297870A1
公开(公告)日：2020-09-24
申请号：US16799052
申请日：2020-02-24
Applicant: ARBUTUS BIOPHARMA CORPORATION
Inventor： James HEYES , Lorne R. PALMER , Stephen P. REID , Edward D. YAWORSKI , Ian MACLACHLAN , Mark WOOD , Alan D. MARTIN
IPC: A61K48/00 , C07C229/12 , A61K9/127 , C12N15/88 , A61K9/00 , A61K9/14 , A61K31/7105 , A61K9/50 , A61K47/10 , A61K47/14 , A61K47/24 , A61K47/28
Abstract: The present invention provides compositions comprising mRNA molecules encapsulated within lipid particles. The lipid particles comprise a cationic lipid, a non-cationic lipid, and an mRNA molecule that is encapsulated within the lipid particle. The compositions are useful, for example, to introduce the mRNA molecules into a human subject where they are translated to produce a polypeptide that functions to ameliorate one or more symptoms of a disease. The invention also provides cationic lipids that are useful for preparing the compositions of the invention.
-
公开(公告)号：US20200282060A1
公开(公告)日：2020-09-10
申请号：US16787912
申请日：2020-02-11
Applicant: ARBUTUS BIOPHARMA CORPORATION
Inventor： James Heyes , Alan Martin , Mark Wood
IPC: A61K47/18 , C07C217/08 , C07C229/12 , C07C237/06 , C07C271/20 , C07C327/06 , C07D233/60 , C07D249/04 , C12N15/113 , C07C217/46 , C12N15/11 , C07C229/30 , A61K47/14 , A61K48/00 , C07C327/22 , A61K31/713 , A61K47/22
Abstract: The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic 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. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
-
公开(公告)号：US20190240354A1
公开(公告)日：2019-08-08
申请号：US16312162
申请日：2017-06-30
Applicant: ARBUTUS BIOPHARMA CORPORATION
Inventor： Michael J. ABRAMS , James HEYES , Adam JUDGE , Kieu Mong LAM , Lorne Ralph PALMER , Stephen P. REID , Edward D. YAWORSKI
IPC: A61K48/00 , A61K31/573 , A61K47/69 , C12N15/11 , A61K31/58 , A61K31/7105 , A61K31/713 , A61K9/51 , B82Y5/00 , A61K9/00 , A61K47/54 , A61K47/60 , A61K45/06
CPC classification number: A61K48/0083 , A61K9/0019 , A61K9/5123 , A61K31/573 , A61K31/58 , A61K31/7105 , A61K31/713 , A61K45/06 , A61K47/544 , A61K47/60 , A61K47/6909 , A61K47/6911 , B82Y5/00 , C12N15/111 , C12N2320/32 , A61K2300/00
Abstract: The present invention provides compositions comprising nucleic acid molecules, such as mRNA molecules, encapsulated within lipid particles. The compositions are useful, for example, to introduce the mRNA molecules into a human subject where they are translated to produce a polypeptide that functions to ameliorate one or more symptoms of a disease.
-
99.发明授权
公开(公告)号：US10358447B2
公开(公告)日：2019-07-23
申请号：US16204584
申请日：2018-11-29
Applicant: ARBUTUS BIOPHARMA CORPORATION
Inventor： Ramesh Kakarla , Bruce D. Dorsey
IPC: C07D471/04 , A61K31/4375 , A61P31/20 , A61K45/06
Abstract: The present invention includes novel substituted 2-N-hydroxy-1,3-dioxo-1,2,3,4-tetrahydronaphthyridines, which can be used to treat or prevent hepatitis B virus (HBV) infections in a patient. In certain embodiments, the compounds and compositions of the invention inhibit HBV RNAse H activity.
-
公开(公告)号：US20190153443A1
公开(公告)日：2019-05-23
申请号：US16036550
申请日：2018-07-16
Applicant: Arbutus Biopharma Corporation
Inventor： Kevin Fitzgerald , Maria Frank-Kamenetsky , Akin Akinc , Martin A. Maier
IPC: C12N15/113 , A61K31/366 , A61K9/127 , C12N9/64 , C12N15/11 , A61K31/7088 , A61K31/567
Abstract: This invention relates to methods for increasing the efficiency of siRNA administrations via pre-administration of an agent that lowers LDL receptor levels.
