公开(公告)号：US20240391870A1

公开(公告)日：2024-11-28

申请号：US18660219

申请日：2024-05-09

Applicant: Arcturus Therapeutics, Inc.

Inventor： Kumar Rajappan ,  Steven Tanis

IPC: C07C333/04 ,  A61K9/51 ,  C07C229/12 ,  C07C237/12 ,  C07C271/22 ,  C07C275/16 ,  C07C327/06 ,  C07D209/24 ,  C07D333/60 ,  C12N15/113

Abstract: The present disclosure describes compounds of Formula (I) and pharmaceutically acceptable salts thereof:

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：US11939600B2

公开(公告)日：2024-03-26

申请号：US16617462

申请日：2018-05-31

Applicant: Arcturus Therapeutics, Inc.

Inventor： Kiyoshi Tachikawa ,  Carlos Gustavo Perez-Garcia ,  Padmanabh Chivukula ,  Hari Bhaskaran ,  Sean Christopher Daugherty ,  Christian W. Cobaugh

IPC: C12N9/02 ,  A61K31/7115 ,  A61K48/00

CPC classification number: C12N9/0071 ,  A61K31/7115 ,  A61K48/005 ,  C12Y114/16001 ,  A61K48/00

Abstract: This invention provides a range of translatable polynucleotide and oligomer molecules for expressing a human phenylalanine hydroxylase (PAH), or a fragment thereof having PAH activity. The polynucleotide and oligomer molecules are expressible to provide the human PAH or a fragment thereof having PAH activity. The molecules can be used as active agents to express an active polypeptide or protein in cells or subjects. The agents can be used in methods for ameliorating, preventing, delaying onset, or treating a disease or condition associated with phenylketonuria, decreased metabolism of phenylalanine, or increased levels of phenylalanine in a subject.

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.

公开(公告)号：US20230183685A1

公开(公告)日：2023-06-15

申请号：US17876803

申请日：2022-07-29

Applicant: ARCTURUS THERAPEUTICS, INC.

Inventor： Zoya IGNATOVA ,  Andrew TORDA ,  Marco MATTHIES

IPC: C12N15/11

CPC classification number: C12N15/11 ,  A61K48/00

Abstract: The invention relates to a synthetic transfer RNA with an extended anticodon loop. The invention provides a synthetic suppressor transfer RNA useful for the treatment of a genetic disease like cystic fibrosis associated with a nonsense mutation. The synthetic transfer RNA contains an extended anticodon loop with two consecutive anticodon base triplets configured to base-pair to two consecutive codon base triplets on an mRNA. The first anticodon base triplet or the second anticodon base triplet is configured to base-pair to a stop codon base triplet on the mRNA.

公开(公告)号：US20220378702A1

公开(公告)日：2022-12-01

申请号：US17737862

申请日：2022-05-05

Applicant: Arcturus Therapeutics, Inc.

Inventor： Kumar Rajappan ,  Steven Tanis ,  Rajesh Mukthavaram ,  Amit Sagi ,  Priya Prakash Karmali ,  Padmanabh Chivukula

IPC: A61K9/127 ,  C07K19/00 ,  A61K31/7105

Abstract: Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I) wherein, A1 is selected from serine, threonine, O—C1-6 alkyl serine, and O—C1-6 alkyl threonine; A2 is selected from serine, threonine, O—C1-6 alkyl serine, and O—C1-6 alkyl threonine; A3 is selected from glutamic acid, glutamine, asparagine, and aspartic acid; A4 is proline; each A5 is independently selected from a natural or modified amino acid; The peptide-lipid conjugates can be used in lipid formulations for the delivery of nucleic acids.

公开(公告)号：US20220168234A1

公开(公告)日：2022-06-02

申请号：US17473063

申请日：2021-09-13

Applicant: Arcturus Therapeutics, Inc.

Inventor： Yanjie BAO ,  Brenda CLEMENTE ,  Priya Prakash KARMALI

IPC: A61K9/51 ,  A61K31/7105

Abstract: A method of producing lipid-encapsulated RNA nanoparticles includes flowing an aqueous solution comprising an RNA through a 1st tube having a first inner diameter (ID); the RNA comprises from about 6,000 to about 13,000 nucleotides; flowing an ethanol solution comprising lipids through a 2nd tube having a second inner diameter (ID), at a flow rate of about 0.2 to about 1 times relative to the aqueous solution through the 1st tube, the lipids comprise a cationic lipid; and mixing the ethanol solution with the aqueous solution; the first ID and second ID and flow rates through the 1st tube and 2nd tube are selected to produce a shear force sufficiently low to preserve the integrity of the RNA; the mixing produces an output solution flowing in the 1st tube comprising a turbulent flow of the RNA and the lipids in between about ethanol, the lipid-encapsulated RNA nanoparticles having a bilayer structure.

公开(公告)号：US20220162612A1

公开(公告)日：2022-05-26

申请号：US17602251

申请日：2020-04-09

Applicant: Arcturus Therapeutics, Inc.

Inventor： Zoya IGNATOVA ,  Andrew TORDA

IPC: C12N15/113

Abstract: The invention relates to a synthetic transfer RNA with an extended anticodon loop. The invention provides a synthetic suppressor transfer RNA useful for the treatment of a genetic disease like neurofibromatosis associated with a frameshift mutation. The synthetic transfer RNA comprises an extended anticodon loop having a four-nucleotide anticodon or a five-nucleotide anticodon.

公开(公告)号：US20210323914A1

公开(公告)日：2021-10-21

申请号：US17216357

申请日：2021-03-29

Applicant: Arcturus Therapeutics, Inc.

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

IPC: C07C333/04 ,  C07C271/22

Abstract: Disclosed herein is a compound of Formula I, wherein 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 or solvate thereof.