公开(公告)号：US12220485B2

公开(公告)日：2025-02-11

申请号：US18457090

申请日：2023-08-28

Applicant: Arcturus Therapeutics, Inc.

Inventor： Priya Karmali ,  Padmanabh Chivukula ,  Joseph E. Payne ,  Yanjie Bao ,  Michael Figa ,  Scott A. Roberts ,  Andreas Wagner

IPC: A61K47/69 ,  A61K9/14 ,  A61K47/60 ,  B82Y5/00

Abstract: A method of producing a lipid-encapsulated RNA nanoparticle, comprising the steps a) flowing an aqueous solution comprising an RNA through a 1st tube having an inner diameter (ID) of between about 0.1″ and 0.132″; b) flowing an ethanol solution comprising lipids through a 2nd tube having an ID of between about 0.005″ and 0.02″ at one third the flow rate of the aqueous solution through the 1st tube, wherein the lipids comprise a cationic lipid; and c) mixing the ethanol solution with the aqueous solution by flowing the ethanol solution and the aqueous solution into a mixing module consisting of the 2nd tube perpendicularly joined to the 1st tube; wherein the mixing produces an output solution flowing in the 1st tube comprising a turbulent flow of the RNA and the lipids in between about 10% to 75% ethanol v/v, and wherein the lipid-encapsulated RNA nanoparticles have a bilayer structure.

公开(公告)号：US20240316090A1

公开(公告)日：2024-09-26

申请号：US18259535

申请日：2021-12-10

Applicant: ARCTURUS THERAPEUTICS, INC. ,  JANSSEN PHARMACEUTICALS, INC.

Inventor： Ramón Díaz TRELLES ,  Man Lu LAM ,  Kiyoshi TACHIKAWA ,  Priya Prakash KARMALI ,  Padmanabh CHIVUKULA

IPC: A61K31/7105 ,  A61K45/06 ,  A61P31/20 ,  C12N9/22 ,  C12N15/90

CPC classification number: A61K31/7105 ,  A61K45/06 ,  A61P31/20 ,  C12N9/22 ,  C12N15/907

Abstract: Nucleic acid molecules encoding transcription activator like effector nucleases (TALENs) for targeting a hepatitis B virus (HBV) genome are described. Also described are compositions, host cells, lipids, and pharmaceutical compositions containing the TALENs. Methods for treating hepatitis infection, particularly in individuals having chronic HBV infection, using the pharmaceutical compositions of the invention are also described.

公开(公告)号：US20230227826A1

公开(公告)日：2023-07-20

申请号：US18001574

申请日：2021-06-17

Applicant: Arcturus Therapeutics, Inc. ,  National University Corporation Tokai National Higher Education and Research System

Inventor： Kiyoshi TACHIKAWA ,  Angel I-Jou LEU ,  Padmanabh CHIVUKULA ,  Priya Prakash KARMALI ,  Tomoki HIRUNAGI ,  Kentaro SAHASHI ,  Masahisa KATSUNO

IPC: C12N15/113 ,  A61P3/00

CPC classification number: C12N15/113 ,  A61P3/00 ,  C12N2310/11 ,  C12N2320/35 ,  C12N2310/32 ,  C12N2310/31

Abstract: A method for inhibiting expression of an mRNA having an expanded trinucleotide repeat region is provided comprising administering an oligomer comprising a sense strand and an antisense strand wherein: a) the antisense strand comprises a sequence of Formula (I): rGrCrUrGrCrUrGrCX1X2rCrUrGrCrUrGrCrUrG (I), wherein X1 and X2 are each independently selected from 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; b) 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 oligomer can be formulated in a lipid delivery vehicle, and can inhibit expression of Atrophin-1, Huntingtin, Ataxin-1, Ataxin-2, Ataxin-3, Ataxin-7, Alpha1A-voltage-dependent calcium channel subunit, TATA-box binding protein (TBP), Androgen Receptor, PP2A-PR55beta, FMR-1 Protein (FMRP), FMR-2 protein, Frataxin, Dystrophy Protein Kinase (DMPK), or Ataxin-8.

公开(公告)号：US11685921B2

公开(公告)日：2023-06-27

申请号：US16724122

申请日：2019-12-20

Applicant: Arcturus Therapeutics, Inc.

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

IPC: C12N15/11 ,  C12N15/113 ,  A61K9/127 ,  A61K47/69

CPC classification number: C12N15/1131 ,  A61K9/1271 ,  A61K47/6911 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/323 ,  C12N2310/344 ,  C12N2310/3515 ,  C12N2320/32

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：US20220370624A1

公开(公告)日：2022-11-24

申请号：US17737884

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: A61K47/54 ,  A61K47/26 ,  C07K7/04 ,  C07K14/00 ,  C07K19/00 ,  A61P35/00 ,  A61K9/00

Abstract: A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.

公开(公告)号：US11015204B2

公开(公告)日：2021-05-25

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: C12N15/52 ,  C12N15/82 ,  C07K14/805 ,  C07K14/775 ,  C07K14/75 ,  C07K14/47 ,  C07K14/415 ,  C07K14/505 ,  A61K38/01 ,  A61K38/17 ,  A61K38/42 ,  A61K38/36 ,  A61K38/18

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：US20210060168A1

公开(公告)日：2021-03-04

申请号：US17011880

申请日：2020-09-03

Applicant: Arcturus Therapeutics, Inc.

Inventor： Kumar RAJAPPAN ,  Padmanabh CHIVUKULA ,  Kiyoshi TACHIKAWA ,  Steven TANIS ,  Priya KARMALI

IPC: A61K47/54 ,  C07H15/04 ,  C12N15/113

Abstract: ASGP-R binding molecular conjugates are provided. The conjugates are useful to deliver therapeutically effective amounts of biologically active molecules to target cells and tissues of a subject. Compositions are also provided comprising the molecular conjugates.

公开(公告)号：US20200140380A9

公开(公告)日：2020-05-07

申请号：US15925670

申请日：2018-03-19

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula

IPC: C07C323/52 ,  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：US09982259B2

公开(公告)日：2018-05-29

申请号：US14667678

申请日：2015-03-25

Applicant: Arcturus Therapeutics, Inc.

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

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

CPC classification number: C12N15/113 ,  A61K9/127 ,  A61K31/685 ,  A61K31/713 ,  C12N2310/14 ,  C12N2310/32 ,  C12N2310/323 ,  C12N2310/344

Abstract: This invention provides UNA oligomers for selectively inhibiting V30M TTR expression, which can be used in treating amyloidosis. 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 nucleic acid monomers. Embodiments include pharmaceutical compositions and methods for treating or preventing TTR-related amyloidosis by administering a UNA oligomer to a subject.

公开(公告)号：US09962449B2

公开(公告)日：2018-05-08

申请号：US15224474

申请日：2016-07-29

Applicant: Arcturus Therapeutics, Inc.

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

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

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.