公开(公告)号：US11672816B2

公开(公告)日：2023-06-13

申请号：US16982167

申请日：2019-03-19

申请人： FUNDACIÓ CENTRE DE REGULACIÓ GENÒMICA ,  INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ,  FUNDACIÓN DEL SECTOR PÚBLICO ESTATAL CENTRO NACIONAL DE INVESTIGACIONES ONCOLÓGICAS CARLOS III (F.S.P. CNIO)

发明人： Jordi Hernández Ribera ,  Juan Alberto Valcárcel Juárez ,  Elias Bechara ,  Manuel Serrano Marugán ,  Miguel Rovira Del Olmo ,  Pablo José Fernández Marcos

IPC分类号： C07H21/04 ,  A61K31/712 ,  A61P35/00 ,  A61K9/00 ,  A61K31/7125 ,  C12N15/113

CPC分类号： A61K31/712 ,  A61K9/0019 ,  A61K31/7125 ,  A61P35/00 ,  C12N15/113

摘要： Disclosed herein are novel compounds comprising antisense oligonucleotides that regulate the splicing of NUMB. In particular, an antisense oligonucleotide for reducing inclusion of NUMB exon 9 in a population of mature NUMB transcripts is provided. The antisense oligonucleotide comprises a sequence of at least 7 nucleotides that is complementary to a target region within exon 9 of a NUMB transcript. Pharmaceutical compositions comprising the antisense oligonucleotide and methods of treating a proliferative disease using the compounds or compositions of the invention are also described.

公开(公告)号：US20230142669A1

公开(公告)日：2023-05-11

申请号：US17911665

申请日：2021-03-25

申请人： SpliSense Ltd.

发明人： Yifat OREN ,  Ofra BARCHAD-AVITZUR ,  Efrat OZERI-GALAI

IPC分类号： C12N15/113 ,  A61K31/712 ,  A61K31/47 ,  A61K45/06 ,  A61K31/443

CPC分类号： C12N15/1138 ,  A61K31/712 ,  A61K31/47 ,  A61K45/06 ,  A61K31/443 ,  C12N2310/11 ,  C12N2320/33

摘要： The present invention is directed to a method for inducing skipping of exon 24 of the cystic fibrosis transmembrane conductance regulator (CFTR) pre-mRNA. Further, treating cystic fibrosis (CF) using a splicing modulator, such as an antisense oligonucleotide, capable of inducing the skipping of exon 24 of the cystic fibrosis transmembrane conductance regulator (CFTR) pre-mRNA. Also provided are a composition and a kit comprising the splicing modulator.

公开(公告)号：US20230101227A1

公开(公告)日：2023-03-30

申请号：US17836209

申请日：2022-06-09

申请人： Dicerna Pharmaceuticals, Inc.

发明人： Weimin WANG ,  Venkata KRISHNAMURTHY

IPC分类号： C07H19/06 ,  A61K31/712 ,  A61K9/107 ,  C07H21/00 ,  C12N15/11 ,  C12N15/113

摘要： Disclosed herein are glutathione-sensitive oligonucleotides and methods of using the same. Any oligonucleotide of interest may be modified with a glutathione-sensitive moiety, including oligonucleotides used for in vivo delivery, such as nucleic acid inhibitor molecules. Typically, the glutathione-sensitive moiety is used to reversibly modify the 2′-carbon of a sugar moiety in one or more nucleotides in the oligonucleotide, although other carbon positions may also be modified with the glutathione-sensitive moiety. Also disclosed are glutathione-sensitive nucleotide and nucleoside monomers, including glutathione-sensitive nucleoside phosphoramidites that can be used, for example, in standard oligonucleotide synthesis methods. In addition, glutathione-sensitive nucleotide and nucleoside monomers without a phosphoramidite can be used therapeutically, for example, as anti-viral agents.

公开(公告)号：US11591598B2

公开(公告)日：2023-02-28

申请号：US17013374

申请日：2020-09-04

申请人： Hoffmann-La Roche Inc.

发明人： Hassan Javanbakh ,  Søren Ottosen ,  Morten Lindow

IPC分类号： C12N15/113 ,  A61K31/712 ,  A61K31/713 ,  A61K47/54 ,  A61K48/00

摘要： The present invention relates to an oligomer conjugate for use in the treatment of a viral disorder. The oligomer conjugate comprises: a) an oligomer capable of modulating a target sequence in HBx and/or HBsAg of Hepatitis B Virus (HBV) to treat said viral disorder; and b) a carrier component capable of delivering the oligomer to the liver which is linked, preferably conjugated, to the oligomer.

公开(公告)号：US11583591B2

公开(公告)日：2023-02-21

申请号：US17464618

申请日：2021-09-01

申请人： Avidity Biosciences, Inc.

发明人： Andrew John Geall ,  Venkata Ramana Doppalapudi ,  David Sai-Ho Chu ,  Michael Caramian Cochran ,  Michael Hood ,  Beatrice Diana Darimont ,  Rob Burke ,  Yunyu Shi ,  Gulin Erdogan Marelius ,  Barbora Malecova

IPC分类号： C07H21/04 ,  A61K47/68 ,  A61K31/712 ,  A61K31/713 ,  C07K16/18 ,  C12N15/113 ,  A61P21/00 ,  A61K39/395 ,  A61K9/51

摘要： Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy.

公开(公告)号：US20230047754A1

公开(公告)日：2023-02-16

申请号：US17822342

申请日：2022-08-25

申请人： Avidity Biosciences, Inc.

发明人： Andrew John GEALL ,  Venkata DOPPALAPUDI ,  David Sai-Ho CHU ,  Michael Caramian COCHRAN ,  Michael HOOD ,  Beatrice Diana DARIMONT ,  Rob BURKE ,  Yunyu SHI ,  Gulin Erdogan MARELIUS ,  Barbora MALECOVA

IPC分类号： A61K47/68 ,  A61K31/712 ,  A61K31/713 ,  C07K16/18 ,  C12N15/113 ,  A61P21/00 ,  A61K39/395

摘要： Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy.

公开(公告)号：US11578095B2

公开(公告)日：2023-02-14

申请号：US17804192

申请日：2022-05-26

申请人： TriLink Biotechnologies, LLC

发明人： Richard I. Hogrefe ,  Alexandre Lebedev ,  Anton P. McCaffrey ,  Dongwon Shin

IPC分类号： C07H21/02 ,  A61K31/7115 ,  A61K31/712 ,  A61K31/711 ,  A23L33/13 ,  C12N15/11 ,  C12P19/34

摘要： Provided herein are methods and compositions for synthesizing 5′Capped RNAs wherein the initiating capped oligonucleotide primers have the general form m7Gppp[N2′Ome]n[N]m wherein m7G is N7-methylated guanosine or any guanosine analog, N is any natural, modified or unnatural nucleoside, “n” can be any integer from 0 to 4 and “m” can be an integer from 1 to 9.

公开(公告)号：US11499154B2

公开(公告)日：2022-11-15

申请号：US16604121

申请日：2018-04-10

申请人： GENETHON ,  UNIVERSITE D'EVRY-VAL-D'ESSONNE ,  INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE)

发明人： Ana Maria Buj Bello

IPC分类号： C12N15/113 ,  A61P25/02 ,  A61K31/712 ,  A61K38/46

摘要： The present invention concerns the use of antisense oligonucleotides (AON) capable of inhibiting expression of dynamin 2, advantageously human dynamin 2, for use in the treatment of Charcot-Marie-Tooth disease (CMT) and centronuclear myopathies (CNM).

公开(公告)号：US20220348917A1

公开(公告)日：2022-11-03

申请号：US17639938

申请日：2020-09-03

申请人： Exicure Operating Company

发明人： Samantha M. Sarett

IPC分类号： C12N15/113 ,  A61K31/712 ,  A61K47/54 ,  A61K47/69 ,  A61K9/127 ,  A61P25/00 ,  A61P35/00

摘要： Compositions related to spherical nucleic acids (SNAs) with antisense oligonucleotides and methods of treatment of diseases and disorders are disclosed therein. In particular, the antisense oligonucleotides are targeted to a region in a pre-mRNA of interest to regulate pre-mRNA splicing.

公开(公告)号：US20220290146A1

公开(公告)日：2022-09-15

申请号：US17751450

申请日：2022-05-23

申请人： Ionis Pharmaceuticals, Inc.

发明人： Keming Zhou

IPC分类号： C12N15/113 ,  A61P25/00 ,  A61K31/712 ,  A61K35/30 ,  A61K47/02

摘要： Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN1 RNA in a cell or subject, and in certain instances reducing the amount of ATXN1 in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include gait and limb ataxia, cognitive impairments, difficulty with speaking and swallowing, atrophy of the cerebellum and brainstem in magnetic resonance imaging (MRI), neurochemical abnormalities in the cerebellum and brainstem detected via magnetic resonance spectroscopy (MRS), and death within 10-15 years of symptom onset. Such neurodegenerative diseases include Spinocerebellar ataxia type 1.