公开(公告)号：US20200040026A1

公开(公告)日：2020-02-06

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: 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：US20190388562A1

公开(公告)日：2019-12-26

申请号：US16527955

申请日：2019-07-31

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. PAYNE ,  Padmanabh CHIVUKULA ,  Priya KARMALI ,  Steven P. TANIS

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

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 or alkenylene consisting 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：US20250049950A1

公开(公告)日：2025-02-13

申请号：US18732954

申请日：2024-06-04

Applicant: ARCTURUS THERAPEUTICS, INC.

Inventor： Carlos G. PEREZ-GARCIA ,  Kiyoshi TACHIKAWA ,  Daiki MATSUDA ,  Padmanabh CHIVUKULA ,  Priya Prakash KARMALI ,  Yanjie BAO ,  Jerel Boyd Lee VEGA ,  Rajesh MUKTHAVARAM ,  Amit SAGI

IPC: A61K48/00 ,  A61P11/00 ,  C07K14/47

Abstract: Nucleotides encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein are provided herein. Also describe are mRNA constructs that can be used to express CFTR protein in vitro or in vivo. The mRNA constructs can be formulated in a lipid formulation and administered via inhalation to treat cystic fibrosis.

公开(公告)号：US20240002815A1

公开(公告)日：2024-01-04

申请号：US18319977

申请日：2023-05-18

Applicant: ARCTURUS THERAPEUTICS, INC.

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

IPC: C12N9/10 ,  A61P9/00

CPC classification number: C12N9/1018 ,  A61P9/00 ,  C12Y201/03003 ,  A61K48/00

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：US20210290752A1

公开(公告)日：2021-09-23

申请号：US17196890

申请日：2021-03-09

Applicant: Arcturus Therapeutics, Inc.

Inventor： Sean Michael SULLIVAN ,  Daiki MATSUDA ,  Kiyoshi TACHIKAWA ,  Padmanabh CHIVUKULA ,  Priya Prakash KARMALI ,  Jared Henry DAVIS ,  Yanjie BAO

IPC: A61K39/12 ,  C07K14/18 ,  C12N7/00

Abstract: Provided herein are nucleic acid molecules encoding viral replication proteins and antigenic proteins or fragments thereof. Also provided herein are compositions that include nucleic acid molecules encoding viral replication and antigenic proteins, and lipids. Nucleic acid molecules provided herein are useful for inducing immune responses.

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：US20250000957A1

公开(公告)日：2025-01-02

申请号：US18690408

申请日：2022-09-15

Applicant: Arcturus Therapeutics, Inc.

Inventor： Ramon DIAZ TRELLES ,  Kiyoshi TACHIKAWA ,  Padmanabh CHIVUKULA

IPC: A61K38/51 ,  A61K48/00 ,  A61P3/00 ,  C12N9/88 ,  C12N15/88

Abstract: Phenylketonuria (PKU) is caused by a mutation in the phenylalanine hydroxylase (P AH) gene in the liver, Provided herein are compositions and methods for treating phenylketonuria (PKU) and related disorders. Polynucleotides for expressing bacterial and plant-derived phenylalanine ammonia lyase (PAL) are provided herein. Also provided herein are methods of treating PKU and related disorders that include administration of polynucleotides encoding PAL proteins.

公开(公告)号：US20240309366A1

公开(公告)日：2024-09-19

申请号：US18260096

申请日：2021-12-30

Applicant: Arcturus Therapeutics, Inc. ,  CONSORCIO CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED, M.P. ,  INSTITUT D’INVESTIGACIÓ BIOMÉDICA DE GIRONA DR JOSEP TRUETA ,  UNIVERSITAT DE BARCELONA

Inventor： Ramón Díaz TRELLES ,  Kiyoshi TACHIKAWA ,  Priya Prakash KARMALI ,  Rajesh MUKTHAVARAM ,  Padmanabh CHIVUKULA ,  José María MORENO-NAVARRETE ,  Aleix Gavaldá NAVARRO ,  José Manuel FERNÁNDEZ-REAL ,  Marta Giralt OMS ,  Francesc Villarroya GOMBAU

IPC: C12N15/113 ,  A61K9/51 ,  A61K31/713 ,  A61P3/04

CPC classification number: C12N15/113 ,  A61K9/5146 ,  A61K31/713 ,  A61P3/04

Abstract: Provided herein are compositions and methods for treating metabolic disorders, such as hepatic steatosis, adipose tissue dysfunction, and insulin resistance. Small interfering RNAs (siRNAs) targeting LPS-binding protein (LBP) that include unlocked nucleotides (UNA) and their therapeutic applications for the treatment of metabolic disorders are provided herein.

公开(公告)号：US20230390389A1

公开(公告)日：2023-12-07

申请号：US18235432

申请日：2023-08-18

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

CPC classification number: A61K39/39 ,  A61K39/12 ,  A61K39/275 ,  C12N7/00 ,  A61K2039/53

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：US20230323345A1

公开(公告)日：2023-10-12

申请号：US18001571

申请日：2021-06-17

Applicant: Arcturus Therapeutics, Inc.

Inventor： Kiyoshi TACHIKAWA ,  Angel I-Jou LEU ,  Padmanabh CHIVUKULA ,  Priya Prakash KARMALI

IPC: C12N15/113 ,  A61P3/00

CPC classification number: C12N15/113 ,  A61P3/00 ,  C12N2310/11 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3125 ,  C12N2310/3231

Abstract: An oligomer comprising a sense strand and an antisense strand that mediates RNA interference against a target RNA sequence having a trinucleotide repeat expansion is provided, wherein the antisense strand is complementary to the target RNA sequence and comprises a sequence having at least 80% identity to the sequence of Formula (I): rGrCrUrGrCrUrGrCX1X2rCrUrGrCrUrGrCrUrG (I), wherein X1 and X2 are each independently selected from the group consisting of rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X1 and X2 is a UNA monomer; the oligomer comprises a UNA monomer at the first position at the 5′-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomers are useful as therapeutics targeting polyglutamine diseases and other diseases stemming from a trinucleotide repeat expansion.