公开(公告)号：US10421964B2

公开(公告)日：2019-09-24

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 ,  A61K9/00

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：US10369232B2

公开(公告)日：2019-08-06

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 ,  C12N15/113 ,  C12N15/90

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：US10227302B2

公开(公告)日：2019-03-12

申请号：US15893362

申请日：2018-02-09

Applicant: Arcturus Therapeutics, Inc.

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

IPC: C07D211/60 ,  C07D207/16 ,  A61K31/713 ,  A61K47/54 ,  A61K9/127

Abstract: What is described is a compound wherein R1 and R2 are the same or different, each a linear or branched alkyl consisting of 1 to 20 carbons, or a linear or branched alkenyl or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a bond, a linear alkylene of 1-18 carbons, or a linear alkenylene consisting of 2 to 18 carbons; L3 is a bond or a linear or branched alkylene consisting of 1 to 6 carbons; L4 is a bond or a methylene; X 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：US20190002906A1

公开(公告)日：2019-01-03

申请号：US15994683

申请日：2018-05-31

Applicant: Arcturus Therapeutics, Inc.

Inventor： Pattraranee Limphong ,  Carlos G. Perez-Garcia ,  Kiyoshi Tachikawa ,  Padmanabh Chivukula ,  Arisa Cale ,  Angel I-Jou Leu ,  Jared Davis

IPC: C12N15/82 ,  C12N15/52 ,  C07K14/805 ,  C07K14/775 ,  C07K14/75 ,  C07K14/47 ,  C07K14/415

Abstract: This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5′ UTRs, where a 5′ UTR may be expressed by a gene of a plant. In some embodiments, a 5′ UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.

公开(公告)号：US20180362985A1

公开(公告)日：2018-12-20

申请号：US16109231

申请日：2018-08-22

Applicant: Arcturus Therapeutics, Inc.

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

IPC: C12N15/113 ,  A61K47/14 ,  A61K31/713

Abstract: This invention provides UNA oligomers for gene silencing with reduced off-target effects. The UNA oligomers can have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers being UNA monomers and various nucleic acid monomers. Embodiments include pharmaceutical compositions and methods for treating or preventing TTR-related amyloidosis with reduced off-target effects by administering a UNA oligomer to a subject.

公开(公告)号：US20180222863A1

公开(公告)日：2018-08-09

申请号：US15893362

申请日：2018-02-09

Applicant: Arcturus Therapeutics, Inc.

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

IPC: C07D211/60 ,  C07D207/16 ,  A61K9/127 ,  A61K47/54 ,  A61K31/713

CPC classification number: C07D211/60 ,  A61K9/1272 ,  A61K31/713 ,  A61K47/545 ,  C07D207/16

Abstract: What is described is a compound wherein R1 and R2 are the same or different, each a linear or branched alkyl consisting of 1 to 20 carbons, or a linear or branched alkenyl or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a bond, a linear alkylene of 1-18 carbons, or a linear alkenylene consisting of 2 to 18 carbons; L3 is a bond or a linear or branched alkylene consisting of 1 to 6 carbons; L4 is a bond or a methylene; X 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：US20180169268A1

公开(公告)日：2018-06-21

申请号：US15387067

申请日：2016-12-21

Applicant: Arcturus Therapeutics, Inc.

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

IPC: A61K48/00 ,  C07C333/04 ,  A61K9/51 ,  A61K47/20

CPC classification number: A61K48/0025 ,  A61K9/5123 ,  A61K47/20 ,  C07C333/04

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; L1 and L2 are the same or different, each a linear alkylene of 1 to 20 carbons or a linear alkenylene 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：US09856475B2

公开(公告)日：2018-01-02

申请号：US14807223

申请日：2015-07-23

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：US09670152B2

公开(公告)日：2017-06-06

申请号：US15347647

申请日：2016-11-09

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula

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

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 R is a linear alkyl of 1 to 12 carbons, or a linear alkenyl or alkynyl of 2 to 12 carbons; L is a linear alkylene or alkenylene of 5 to 18 carbons; X is —CO—O— or —O—CO—; Y is S or O; R1 is a linear or branched alkylene consisting of 1 to 6 carbons; and R2 and R3 are the same or different, consisting of a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; and n is 1-6; or a salt, a solvate, or a pharmaceutical formulation thereof.

公开(公告)号：US20150322435A1

公开(公告)日：2015-11-12

申请号：US14807223

申请日：2015-07-23

Applicant: Arcturus Therapeutics, Inc.

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

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

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.

Abstract translation: 本发明提供含有靶向TTR的UNA寡聚物和药学上可接受的载体的药物组合物。 组合物可用于治疗或预防灵长类动物中TTR相关淀粉样变性的方法。 组合物在向灵长类动物施用单一剂量时可以将灵长类动物中的TTR蛋白质减少数天至数周。