公开(公告)号：US20230068063A1

公开(公告)日：2023-03-02

申请号：US17697577

申请日：2022-03-17

申请人： Ionis Pharmaceuticals, Inc.

发明人： Punit P. Seth ,  Michael Oestergaard ,  Michael T. Migawa ,  Xue-hai Liang ,  Wen Shen ,  Stanley T. Crooke ,  Eric E. Swayze

IPC分类号： C12N15/10 ,  C12N15/113

摘要： The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

公开(公告)号：US11492617B2

公开(公告)日：2022-11-08

申请号：US16636485

申请日：2018-08-07

申请人： Ionis Pharmaceuticals, Inc.

发明人： C. Frank Bennett ,  Xue-hai Liang ,  Wen Shen

IPC分类号： C07H21/04 ,  C12N15/113

摘要： In certain embodiments, the present disclosure provides methods comprising contacting a cell with a compound comprising a modified oligonucleotide complementary to a nucleic acid transcript. In certain such embodiments, the modified oligonucleotide does not interact or interacts poorly with a mRNP complex or granule. In certain such embodiments the modifications and/or motifs of the modified oligonucleotide do not promote interaction with a mRNP complex or granule. In certain embodiments, the present disclosure provides methods comprising contacting a cell with a compound comprising a modified oligonucleotide thereby reducing the size or amount of protein aggregation in the cell. In certain such embodiments, the protein aggregate is a mRNP granule. In certain such embodiments, the modifications and/or motifs of the modified oligonucleotide promote interaction with a protein aggregate, such as a mRNP granule, that results in disruption of the protein aggregate.

公开(公告)号：US09845467B2

公开(公告)日：2017-12-19

申请号：US15061843

申请日：2016-03-04

申请人： Ionis Pharmaceuticals, Inc. ,  Cold Spring Harbor Laobratory

发明人： Xue-hai Liang ,  Stanley T. Crooke ,  C. Frank Bennett ,  David L. Spector

IPC分类号： A61K48/00 ,  C12N15/113

CPC分类号： C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/351 ,  C12N2310/3521 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12N2320/30

摘要： The present invention provides compounds and methods for modulating target nucleic acids found in organelles or sub-organelles of cells. The invention includes, but is not limited to compounds and methods that modulate target nucleic acids in a sub-nuclear organelle, such as the nucleolus and/or a cajal body. In certain embodiments, the cell is in an animal.

公开(公告)号：US09695475B2

公开(公告)日：2017-07-04

申请号：US14651344

申请日：2013-12-11

申请人： Ionis Pharmaceuticals, Inc.

发明人： Xue-hai Liang ,  Stanley T. Crooke

IPC分类号： C07H21/02 ,  C07H21/04 ,  C12Q1/68 ,  A61K31/7088 ,  A61K31/7115 ,  A61K31/712 ,  A61K31/7125 ,  A61K31/713 ,  C12N15/11 ,  C12N15/113

CPC分类号： C12Q1/6876 ,  A61K31/7088 ,  A61K31/7115 ,  A61K31/712 ,  A61K31/7125 ,  A61K31/713 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2320/11 ,  C12Q2600/136 ,  C12Q2600/178

摘要： The present invention provides compounds and methods for competitive modulation of microRNAs. Such compounds and methods have profound effects on cells. MicroRNAs (microRNAs), are small (approximately 18-24 nucleotides in length), non-coding RNA molecules encoded in the genomes of plants and animals. In certain instances, microRNAs regulate the expression of genes by binding to the 3′-untranslated regions (3′-UTR) of specific mRNAs. More than 1000 different microRNAs have been identified in plants and animals.

公开(公告)号：US12030910B2

公开(公告)日：2024-07-09

申请号：US17021510

申请日：2020-09-15

申请人： Ionis Pharmaceuticals, Inc.

发明人： Stanley T. Crooke ,  Xue-hai Liang ,  Wen Shen

IPC分类号： C07H21/04 ,  A61K31/7088 ,  C07H21/00 ,  C12N15/113 ,  C12N15/67 ,  C12P19/34

CPC分类号： C07H21/04 ,  A61K31/7088 ,  C07H21/00 ,  C12N15/113 ,  C12N15/1137 ,  C12N15/1138 ,  C12N15/67 ,  C12P19/34 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/3341 ,  C12N2310/346 ,  C12Y301/26004 ,  C12N2310/321 ,  C12N2310/3521 ,  C12N2310/321 ,  C12N2310/3525

摘要： In certain embodiments, the present disclosure provides compounds and methods of increasing the amount or activity of a target protein in a cell. In certain embodiments, the compounds comprise a translation suppression element inhibitor. In certain embodiments, the translation suppression element inhibitor is a uORF inhibitor. In certain embodiments, the uORF inhibitor is an antisense compound.

公开(公告)号：US20210380976A1

公开(公告)日：2021-12-09

申请号：US17282314

申请日：2019-10-04

申请人： Ionis Pharmaceuticals, Inc.

发明人： Punit P. Seth ,  Michael Oestergaard ,  Michael T. Migawa ,  Xue-hai Liang ,  Wen Shen ,  Stanley T. Crooke ,  Eric E. Swayze

IPC分类号： C12N15/113

摘要： The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having one or more chirally enriched phosphorothioate intemucleoside linkages. In certain embodiments, the modified oligonucleotide decreases expression of target mRNA.

公开(公告)号：US20210269472A1

公开(公告)日：2021-09-02

申请号：US17021510

申请日：2020-09-15

申请人： Ionis Pharmaceuticals, Inc.

发明人： Stanley T. Crooke ,  Xue-hai Liang ,  Wen Shen

IPC分类号： C07H21/04 ,  A61K31/7088 ,  C12N15/113 ,  C12N15/67 ,  C07H21/00 ,  C12P19/34

摘要： In certain embodiments, the present disclosure provides compounds and methods of increasing the amount or activity of a target protein in a cell. In certain embodiments, the compounds comprise a translation suppression element inhibitor. In certain embodiments, the translation suppression element inhibitor is a uORF inhibitor. In certain embodiments, the uORF inhibitor is an antisense compound.

公开(公告)号：US20210171945A1

公开(公告)日：2021-06-10

申请号：US16762734

申请日：2018-11-16

申请人： Ionis Pharmaceuticals, Inc.

发明人： Xue-hai Liang ,  Stanley T. Crooke

IPC分类号： C12N15/113 ,  A61K45/06 ,  A61K31/7125

摘要： Disclosed herein are methods for increasing antisense activity by modulating translation. In certain embodiments, a compound comprising an antisense oligonucleotide is co-administered with an inhibitor of translation.

公开(公告)号：US11629348B2

公开(公告)日：2023-04-18

申请号：US17671924

申请日：2022-02-15

申请人： Ionis Pharmaceuticals, Inc.

发明人： Brooke A. Anderson ,  Xue-hai Liang ,  William John Drury, III ,  Michael Oestergaard ,  Michael T. Migawa ,  Punit P. Seth

IPC分类号： C12N15/113

摘要： The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group.

公开(公告)号：US11149264B2

公开(公告)日：2021-10-19

申请号：US17172333

申请日：2021-02-10

申请人： Ionis Pharmaceuticals, Inc.

发明人： Punit P. Seth ,  Michael Oestergaard ,  Michael T. Migawa ,  Xue-hai Liang ,  Wen Shen ,  Stanley T. Crooke ,  Eric E. Swayze

IPC分类号： C12N15/10 ,  C12N15/113

摘要： The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.