公开(公告)号：US10968248B2

公开(公告)日：2021-04-06

申请号：US16600336

申请日：2019-10-11

Applicant: c/o Arcturus Therapeutics, Inc.

Inventor： Padmanabh Chivukula ,  Steven P. Tanis ,  Joseph E. Payne

IPC: C07H21/00 ,  C07H19/16 ,  C07H19/20 ,  C07H19/207 ,  C07H21/02 ,  A61K31/7125

Abstract: What is described is a trinucleotide cap analog comprising m7G(5′)p3-N1pN2 for increased efficiency of in vitro transcription of m7G(5′)p3-RNA, wherein m7G is N7-methylguanosine or analog, (5′)p3 is a 5′,5′-triphosphate bridge, and N1 or N2 or both ribonucleotide analogs linked to each other by a phosphate, p, and wherein the trinucleotide cap analog increases the efficiency of in vitro transcription.

公开(公告)号：US20210002217A1

公开(公告)日：2021-01-07

申请号：US17026473

申请日：2020-09-21

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula

IPC: C07C323/52 ,  C07C271/22 ,  C07C235/12 ,  C07C237/12 ,  C12N15/11 ,  C07C323/60 ,  C07J41/00 ,  C07C333/04 ,  C11C3/04 ,  A61K47/18 ,  A61K47/20 ,  C07C323/25 ,  C12N15/113

Abstract: What is described is a method of synthesis of the compound of formula 1A, or a salt thereof, wherein R3 is a linear or branched alkene of 1, 2, 3, 4, 5 or 6 carbons; R4 and R5 are the same or different, each a hydrogen, or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons; and L3 is a bond or an alkane of 1, 2, 3, 4, 5 or 6 carbons.

公开(公告)号：US20200046830A1

公开(公告)日：2020-02-13

申请号：US16482500

申请日：2018-03-30

Applicant: The Government of the United States, as Represented by the Secretary of the Army ,  Arcturus Therapeutics, Inc.

Inventor： Jay W. HOOPER ,  Eric M. MUCKER ,  Padmanabh CHIVUKULA

IPC: A61K39/39 ,  A61K39/12 ,  A61K39/275 ,  C12N7/00

Abstract: A nucleic acid vaccine composition comprising one or more of a plasmid-based nucleic acid vaccine and immunotherapy, as well as a lipid formulation, is provided. In addition, the present invention provides a method of enhancing the potency of plasmid-based DNA vaccines and immunotherapies, by formulating a vaccine and/or immunotherapy in a lipid formulation, which is stable when refrigerated or stored frozen, is then delivered to a vaccinee by either needle/syringe, jet injection, or microneedles. The lipid formulation of the present invention comprises one or more lipid excipients selected from 1,2-Distearoyl-sn-glycero-3-phosphocholine, Cholest-5-en-3β-ol, 1,2-Dimyristoyl-rac-glycero-3-methylpolyoxyethlene, and or more symmetric ionizable cationic lipids. The present invention increases vaccine potency dramatically. It was unexpectedly discovered that the level of immunogen, or immune response molecules, produced in vivo is increased (versus administering merely the vaccine or immunotherapy) and, in the case of a vaccine immunogen, the immune response is enhanced.

公开(公告)号：US20180237780A1

公开(公告)日：2018-08-23

申请号：US15952680

申请日：2018-04-13

Applicant: Arcturus Therapeutics, Inc.

Inventor： Jesper WENGEL

IPC: C12N15/113 ,  C12N15/11 ,  C07H21/00

CPC classification number: C12N15/113 ,  C07H21/00 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/31 ,  C12N2310/321 ,  C12N2310/323 ,  C12N2310/3231 ,  C12N2320/51

Abstract: This invention provides UNA oligomers for therapeutics having prolonged stability. The UNA oligomers can be composed of one or more 2′-3′-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used for therapeutics that target oligonucleotides, nucleic acids, or RNAs to reduce their activity.

公开(公告)号：US20180135051A1

公开(公告)日：2018-05-17

申请号：US15859571

申请日：2017-12-31

Applicant: Arcturus Therapeutics, Inc.

Inventor： Kiyoshi Tachikawa ,  Joseph E. Payne ,  Padmanabh Chivukula

IPC: C12N15/113 ,  A61K9/127 ,  A61K31/685 ,  A61K31/713 ,  C12N15/11

CPC classification number: C12N15/113 ,  A61K9/127 ,  A61K31/685 ,  A61K31/713 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/32 ,  C12N2310/323 ,  C12N2320/32 ,  C12N2320/34

Abstract: This invention provides pharmaceutical compositions containing a UNA oligomer targeted to TTR and a pharmaceutically acceptable carrier. The compositions can be used in methods for treating or preventing TTR-related amyloidosis in a primate. The compositions, upon administering a single dose to the primate, can reduce TTR protein in the primate for a period of days to weeks.

公开(公告)号：US20180072664A1

公开(公告)日：2018-03-15

申请号：US15818424

申请日：2017-11-20

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula

IPC: C07C323/52 ,  C12N15/113

CPC classification number: C07C323/52 ,  A61K47/18 ,  A61K47/20 ,  C07C235/12 ,  C07C237/12 ,  C07C271/22 ,  C07C323/25 ,  C07C323/60 ,  C07C333/04 ,  C07J41/0055 ,  C11C3/04 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2320/32

Abstract: What is described is a compound having the formula wherein R1 is branched alkyl of the structure (CH3(CH2)m)2CH—, wherein m is 2 or 3; R2 is a linear alkyl of 1, 2, 3, 4, 5, 6, 7, 8, or 9 carbons, a branched alkyl of 3, 4, 5, 6, 7, 8, or 9 carbons, or an alkenyl or alkynyl of 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbons; R3 is —(CH2)p—, wherein p is 2, 3, 4, 5 or 6; R4 and R5 are the same or different, each a hydrogen, or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons; L1 and L2 are the same or different, of the structure —(CH2)n—, wherein n is 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18; L3 is a bond; X1 is —CO—O— whereby —L1—CO—O—R2 is formed; X2 is S or O; and X3 is —CO—O— whereby —L1—CO—O—R1 is formed; and wherein m+n+p is 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27; or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20170267631A1

公开(公告)日：2017-09-21

申请号：US15614499

申请日：2017-06-05

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula

IPC: C07C323/25 ,  C07C333/04 ,  C07C271/22 ,  A61K47/18 ,  A61K47/20

CPC classification number: C07C323/52 ,  A61K47/18 ,  A61K47/20 ,  C07C235/12 ,  C07C237/12 ,  C07C271/22 ,  C07C323/25 ,  C07C323/60 ,  C07C333/04 ,  C07J41/0055 ,  C11C3/04 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2320/32

Abstract: What is described is a compound of formula I wherein R1 is a linear alkyl, alkenyl, or alkynyl of 2 to 12 carbons, or a branched alkyl with 12 to 20 carbons, R2 is a branched alkyl with 12 to 20 carbons, L1 and L2 are independently a linear alkylene with 1-18 carbons or alkenylene with 2-18 carbons, X is S or O, L3 is a bond or an alkylene with 1 to 6 carbons, R3 is an alkylene with 1 to 6 carbons, and R4 and R5 are the same or different, each a linear or branched alkyl with 1 to 6 carbons.

公开(公告)号：US20170190661A1

公开(公告)日：2017-07-06

申请号：US15393840

申请日：2016-12-29

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula ,  Steven P. Tanis

IPC: C07C333/04

CPC classification number: C07C333/04 ,  C07C271/22

Abstract: What is described is a compound of formula I wherein X is an ethene, or an unsubstituted or substituted arene or heteroarene; Y is a bond, an ethene, or an unsubstituted or substituted arene or heteroarene; Z is S or O; L is a linear or branched alkylene of 1 to 6 carbons; R1 and R2 are independently a linear or branched alkyl or alkenyl of 1 to 18 carbons; R3 and R4 are independently a linear or branched alkyl of 1 to 6 carbons; n is 0 to 6; and m, p, q, and r are independently 1-18; or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20170080107A1

公开(公告)日：2017-03-23

申请号：US15272107

申请日：2016-09-21

Applicant: Arcturus Therapeutics, Inc.

Inventor： Padmanabh Chivukula ,  Rachel Wilkie-Grantham ,  Kiyoshi Tachikawa

IPC: A61K48/00

CPC classification number: A61K48/005 ,  C12N15/113 ,  C12N15/907 ,  C12N2310/20 ,  C12N2310/323 ,  C12N2320/34

Abstract: This invention encompasses compounds, structures, compositions and methods for therapeutic guide molecules that direct CRISPR gene editing. A guide molecule for directing gene editing can be allele selective, or disease allele selective, and can exhibit reduced off target activity. A guide molecule can be composed of monomers, including UNA monomers, nucleic acid monomers, and modified nucleotides, wherein the compound is targeted to a genomic DNA. The guide molecules of this invention can be used as active ingredients for editing or disrupting a gene in vitro, ex vivo, or in vivo.

公开(公告)号：US20170028074A1

公开(公告)日：2017-02-02

申请号：US15224474

申请日：2016-07-29

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula ,  Steven P. Tanis

IPC: A61K47/48 ,  A61K9/00 ,  C12N15/113 ,  A61K31/713

CPC classification number: A61K47/554 ,  A61K9/0019 ,  A61K31/713 ,  A61K47/549 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/3515 ,  C12N2320/32

Abstract: Described herein is a compound having the structure of formula I, II, or III, wherein R comprises a double stranded RNA molecule, and L1, L2, and L3 independently for each occurrence comprise a ligand selected from the group consisting of a carbohydrate, a cholesteryl, or a peptide; a pharmaceutically accepted salt or pharmaceutical composition thereof; and a method of making the compound.

Abstract translation: 其中R包含双链RNA分子，并且每次出现的L1，L2和L3独立地包含选自碳水化合物，胆固醇基或肽的配体; 其药学上可接受的盐或其药物组合物; 和制备该化合物的方法。