公开(公告)号：US10961535B2

公开(公告)日：2021-03-30

申请号：US16117994

申请日：2018-08-30

Applicant: Arcturus Therapeutics, Inc.

Inventor： Pattraranee Limphong ,  Kiyoshi Tachikawa ,  Christine Esau ,  Padmanabh Chivukula

IPC: C12N15/113

Abstract: This invention encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting Hepatitis B virus in a subject. The compounds have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers comprising UNA monomers and nucleic acid monomers, and the compounds are targeted to a sequence of an HBV genome.

公开(公告)号：US20200181584A1

公开(公告)日：2020-06-11

申请号：US16705102

申请日：2019-12-05

Applicant: Arcturus Therapeutics, Inc.

Inventor： Carlos G. PEREZ-GARCIA ,  Kiyoshi TACHIKAWA ,  Daiki MATSUDA ,  Padmanabh CHIVUKULA

IPC: C12N9/10 ,  A61P9/00

Abstract: The present disclosure provides a modified human OTC protein having improved properties for the treatment of OTC deficiency in a patient. Preferably, the protein of the disclosure is produced from a codon optimized mRNA suitable for administration to a patient suffering from OTC deficiency wherein upon administration of the mRNA to the patient, the protein of the disclosure is expressed in the patient in therapeutically effective amounts to treat OTC deficiency. The present disclosure also provides codon optimized mRNA sequences encoding wild type human OTC comprising a 5′ UTR derived from a gene expressed by Arabidopsis thaliana for use in treating OTC deficiency in a patient.

公开(公告)号：US10604758B2

公开(公告)日：2020-03-31

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

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：US10556861B2

公开(公告)日：2020-02-11

申请号：US15400691

申请日：2017-01-06

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula

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

Abstract: What is described is a compound of formula III or IV wherein R1 is a branched alkyl with 12 to 20 carbons; R2 is a linear alkyl with 5 to 10 carbons or a branched alkyl with 12 to 20 carbons; L1 and L2 are each a bond or a linear alkylene having 1 to 3 carbon atoms, when L3 is a bond; L1 and L2 are each a linear alkylene or alkenylene 5 to 18 carbon atoms, when L3 is an alkylene of 5 to 18 carbons; X is S or O; R3 is of a lower alkyl; and R4 and R5 are the same or different, each a lower alkyl; or a pharmaceutically acceptable salt thereof.

公开(公告)号：US10526284B2

公开(公告)日：2020-01-07

申请号：US15849573

申请日：2017-12-20

Applicant: Arcturus Therapeutics, Inc.

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

IPC: C07C333/04 ,  C07C271/22

Abstract: What is described is a compound of formula I consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons; L1 and L2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

公开(公告)号：US10457945B2

公开(公告)日：2019-10-29

申请号：US15952680

申请日：2018-04-13

Applicant: Arcturus Therapeutics, Inc.

Inventor： Jesper Wengel

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

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：US20180371463A1

公开(公告)日：2018-12-27

申请号：US16117994

申请日：2018-08-30

Applicant: Arcturus Therapeutics, Inc.

Inventor： Pattraranee Limphong ,  Kiyoshi Tachikawa ,  Christine Esau ,  Padmanabh Chivukula

IPC: C12N15/113

Abstract: This invention encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting Hepatitis B virus in a subject. The compounds have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers comprising UNA monomers and nucleic acid monomers, and the compounds are targeted to a sequence of an HBV genome.

公开(公告)号：US20180148725A1

公开(公告)日：2018-05-31

申请号：US15876127

申请日：2018-01-20

Applicant: Arcturus Therapeutics, Inc.

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

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

Abstract: This invention encompasses compounds and compositions useful in methods for medical therapy, in general, for inhibiting expression of a TTR gene in a subject. The compounds have a first strand and a second strand, the monomers comprising UNA monomers and nucleic acid monomers, and the compounds are targeted to a sequence of a TTR gene.

公开(公告)号：US20180105816A1

公开(公告)日：2018-04-19

申请号：US15563579

申请日：2016-04-01

Applicant: Arcturus Therapeutics, Inc.

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

IPC: C12N15/113 ,  A61P31/14 ,  A61P25/00 ,  A61P9/00

CPC classification number: C12N15/1131 ,  A61K31/7105 ,  A61K31/7115 ,  A61K31/7125 ,  A61K31/713 ,  A61P9/00 ,  A61P25/00 ,  A61P31/14 ,  C07H21/00 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/323 ,  C12N2310/346 ,  C12N2320/51 ,  C12N2320/52 ,  A61K2300/00

Abstract: This invention provides UNA oligomers for regulating the expression of a target gene. The UNA oligomers contain UNA monomer linkers, and may contain one or more nucleotides modified with a 2′-O-methyl group, one or more nucleotides modified with a 2′-deoxy-2′-fluoro group, and one or more phosphorothioate or chiral phosphorothioate intermonomer linkages. UNA oligomers can be used as active agents for preventing or treating disease.

公开(公告)号：US20180105551A1

公开(公告)日：2018-04-19

申请号：US15788742

申请日：2017-10-19

Applicant: Arcturus Therapeutics, Inc.

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

IPC: C07H19/16 ,  C07H19/207 ,  C07H19/20

CPC classification number: C07H19/16 ,  A61K45/06 ,  C07H19/20 ,  C07H19/207 ,  C07H21/02

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.