公开(公告)号：US20240287513A1

公开(公告)日：2024-08-29

申请号：US18363244

申请日：2023-08-01

申请人： Ionis Pharmaceuticals, Inc.

发明人： Frank Rigo ,  Paymaan Jafar-Nejad

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/3341 ,  C12N2310/345 ,  C12N2310/346

摘要： Provided are compounds, methods, and pharmaceutical compositions for modulating splicing of a pre-mRNA in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a disease or disorder.

公开(公告)号：US11833221B2

公开(公告)日：2023-12-05

申请号：US17823854

申请日：2022-08-31

申请人： Ionis Pharmaceuticals, Inc.

发明人： Frank Rigo ,  Chrissa A. Dwyer

IPC分类号： A61K47/68 ,  A61K47/54 ,  C12N15/113

CPC分类号： A61K47/6849 ,  A61K47/549 ,  A61K47/6807 ,  C12N15/1137 ,  C12N2310/315 ,  C12N2310/3231

摘要： Provided are oligomeric compounds, methods, and pharmaceutical compositions for DMPK the amount or activity of DMPK RNA in a cell or animal, and in certain instances reducing the amount of DMPK protein in a cell or animal. Such oligomeric compounds, methods, and pharmaceutical compositions are useful to treat type 1 myotonic dystrophy.

公开(公告)号：US20230201374A1

公开(公告)日：2023-06-29

申请号：US17812401

申请日：2022-07-13

申请人： Ionis Pharmaceuticals, Inc.

发明人： Frank Rigo

IPC分类号： A61K48/00 ,  A61K47/54 ,  A61K9/00 ,  A61K31/7115 ,  A61K31/712 ,  A61K31/7125 ,  A61K35/30 ,  C07K14/705

CPC分类号： A61K48/0066 ,  A61K47/549 ,  A61K9/0019 ,  A61K31/7115 ,  A61K31/712 ,  A61K31/7125 ,  A61K35/30 ,  A61K48/0016 ,  A61K48/0075 ,  C07K14/705

摘要： Provided herein are methods, compounds, and compositions useful for targeted delivery of compounds to non-native cells ectopically expressing cell surface receptors. Such methods, compounds, and compositions are useful, for example, in gene therapy mediated ectopic expression of cell surface receptors and targeted delivery of compounds, such as conjugated oligonucleotides, to the non-native cells ectopically expressing cell surface receptors. Such methods, compounds, and compositions can be useful, for example, to treat, prevent, delay or ameliorate disease in an individual by targeted reduction of a gene of interest in the non-native cell ectopically expressing cell surface receptors.

公开(公告)号：US11339393B2

公开(公告)日：2022-05-24

申请号：US16248612

申请日：2019-01-15

申请人： Ionis Pharmaceuticals, Inc.

发明人： Susan M. Freier ,  Frank Rigo

IPC分类号： C12N15/113 ,  G01N33/68

摘要： Disclosed herein are compositions and methods for reducing expression of C9ORF72 mRNA and protein in an animal with C9ORF72 specific inhibitors. Also disclosed herein are compositions and methods of selectively inhibiting a C9ORF72 pathogenic associated mRNA variant by administering an antisense compound targeting the region beginning at the start site of exon 1A to the start site of exon 1B of a C9ORF72 pre-mRNA. Such methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Such C9ORF72 specific inhibitors include antisense compounds.

公开(公告)号：US11299737B1

公开(公告)日：2022-04-12

申请号：US17356961

申请日：2021-06-24

申请人： Ionis Pharmaceuticals, Inc.

发明人： Frank Rigo

IPC分类号： C12N15/113

摘要： Provided are compounds, methods, and pharmaceutical compositions for modulating SMN2 RNA and/or protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disorder. Such symptoms include reduced muscle strength; inability or reduced ability to sit upright, to stand, and/or walk; reduced neuromuscular activity; reduced electrical activity in one or more muscles; reduced respiration; inability or reduced ability to eat, drink, and/or breathe without assistance; loss of weight or reduced weight gain; and/or decreased survival.

公开(公告)号：US20220064638A1

公开(公告)日：2022-03-03

申请号：US17187018

申请日：2021-02-26

申请人： Ionis Pharmaceuticals, Inc.

发明人： Frank Rigo ,  Thazha P. Prakash ,  Kar Yun Karen Ling ,  W. Brad Wan ,  William John Drury, III

IPC分类号： C12N15/113

摘要： Provided are compounds, methods, and pharmaceutical compositions for modulating SMN2 RNA and/or protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disorder. Such symptoms include reduced muscle strength; inability or reduced ability to sit upright, to stand, and/or walk; reduced neuromuscular activity; reduced electrical activity in one or more muscles; reduced respiration; inability or reduced ability to eat, drink, and/or breathe without assistance; loss of weight or reduced weight gain; and/or decreased survival.

公开(公告)号：US11193128B2

公开(公告)日：2021-12-07

申请号：US16554115

申请日：2019-08-28

申请人： Ionis Pharmaceuticals, Inc.

发明人： Frank Rigo

IPC分类号： C12N15/113 ,  A61P21/00 ,  A61P25/28

摘要： Disclosed herein are compositions and methods for reducing expression of C9ORF72 antisense transcript in an animal with C9ORF72 antisense transcript specific inhibitors. Such methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Such C9ORF72 antisense transcript specific inhibitors include antisense compounds.

公开(公告)号：US20210214725A1

公开(公告)日：2021-07-15

申请号：US17005213

申请日：2020-08-27

申请人： Ionis Pharmaceuticals, Inc.

发明人： Frank Rigo

IPC分类号： C12N15/113 ,  A61K45/06 ,  A61K31/7125 ,  A61K31/712 ,  A61K9/00 ,  A61K31/713

摘要： Disclosed herein are compositions and methods for reducing expression of C9ORF72 antisense transcript in an animal with C9ORF72 antisense transcript specific inhibitors. Such methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Such C9ORF72 antisense transcript specific inhibitors include antisense compounds.

公开(公告)号：US20210038629A1

公开(公告)日：2021-02-11

申请号：US16938826

申请日：2020-07-24

申请人： Ionis Pharmaceuticals, Inc.

发明人： Berit Elissa Powers ,  Huynh-Hoa Bui ,  Susan M. Freier ,  Frank Rigo

IPC分类号： A61K31/711 ,  A61K31/7105 ,  A61K47/46

摘要： Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of GFAP RNA in a cell or subject, and in certain instances reducing the amount of GFAP in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a leukodystrophy. Such symptoms and hallmarks include motor delays, cognitive delays, paroxysmal deterioration, seizures, vomiting, swallowing difficulties, ataxic gait, palatal myoclonus, autonomic dysfunction, and presence of intra-astrocytic inclusions called Rosenthal fibers. Such leukodystrophies include Alexander Disease.

公开(公告)号：US10851371B2

公开(公告)日：2020-12-01

申请号：US15565488

申请日：2016-04-11

申请人： Ionis Pharmaceuticals, Inc. ,  The Johns Hopkins University

发明人： Frank Rigo ,  C. Frank Bennett ,  Constantin Van Outryve D'Ydewalle ,  Charlotte J. Sumner

IPC分类号： C12N15/113 ,  C07H21/02 ,  C12Q1/68

摘要： Certain embodiments are directed to methods and compounds for inhibiting SMN-NAT, the natural antisense transcript of SMN. Such methods and compounds are useful for increasing expression of SMN in cells and animals.