公开(公告)号：US12188020B2

公开(公告)日：2025-01-07

申请号：US17323826

申请日：2021-05-18

Applicant: Ionis Pharmaceuticals, Inc.

Inventor： Frank Rigo

IPC: C07H21/04 ,  A61K31/7088 ,  A61P25/28 ,  C12N5/0793 ,  C12N15/113

Abstract: Provided herein are methods for decreasing Ataxin-2 mRNA expression. Such methods are useful to ameliorate symptoms of Ataxin-2 associated diseases. Such Ataxin-2 associated diseases include amyotrophic lateral sclerosis (ALS). Such symptoms include loss of motor function, reduced CMAP amplitude, denervation, and loss of motor neurons.

公开(公告)号：US12180479B2

公开(公告)日：2024-12-31

申请号：US18047973

申请日：2022-10-19

Applicant: Ionis Pharmaceuticals, Inc.

Inventor： Susan M. Freier

IPC: C07H21/04 ,  A61K31/712 ,  A61K35/30 ,  A61K47/02 ,  A61P25/00 ,  C12N15/113

Abstract: 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.

公开(公告)号：US12168766B2

公开(公告)日：2024-12-17

申请号：US18053447

申请日：2022-11-08

Applicant: Ionis Pharmaceuticals, Inc.

Inventor： Susan M. Freier

IPC: C07H21/04 ,  A61P13/02 ,  C12N15/113

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting APOL1 expression, which may be useful for treating, preventing, or ameliorating a disease associated with APOL1.

公开(公告)号：US20240382605A1

公开(公告)日：2024-11-21

申请号：US18696199

申请日：2022-09-29

Applicant: Ionis Pharmaceuticals, Inc. ,  BicycleTx Limited

Inventor： Punit P. Seth ,  Michael Oestergaard ,  Michele Carrer ,  Michael Tanowitz ,  Michael Rigby ,  Michael Skynner ,  Steven Stanway ,  Liudvikas Urbonas ,  Katerine Van Rietschoten

IPC: A61K47/64 ,  A61K9/00 ,  A61P21/00 ,  C12N15/113

Abstract: Provided herein are oligomeric compounds comprising a bicycle ligand and a modified oligonucleotide. This compound may comprise a bicycle ligand as the cell-targeting moiety, and may also comprise a conjugate linker to connect the bicycle ligand and modified oligonucleotide. This compound may be used in conjunction with a pharmaceutically acceptable salt.

公开(公告)号：US20240327838A1

公开(公告)日：2024-10-03

申请号：US18492683

申请日：2023-10-23

Applicant: IONIS PHARMACEUTICALS, INC.

Inventor： Jeffrey R. Crosby ,  Shuling Guo ,  Huynh-Hoa Bui ,  Andrew T. Watt ,  Susan M. Freier

IPC: C12N15/113 ,  A61K9/00 ,  A61K31/404 ,  A61K31/47 ,  A61K31/7105 ,  A61K31/713 ,  A61M11/00 ,  A61P11/00

CPC classification number: C12N15/113 ,  A61K9/0019 ,  A61K9/0075 ,  A61K9/0078 ,  A61K31/404 ,  A61K31/47 ,  A61K31/7105 ,  A61K31/713 ,  A61P11/00 ,  A61M11/005 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/345 ,  C12N2310/346 ,  C12N2320/31 ,  C12N2320/32 ,  C12N2320/35

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting ENaC expression, which may be useful for treating, preventing, or ameliorating a disease associated with ENaC.

公开(公告)号：US20240318183A1

公开(公告)日：2024-09-26

申请号：US18489316

申请日：2023-10-18

Applicant: Ionis Pharmaceuticals, Inc.

Inventor： Susan M. Freier ,  Huynh-Hoa Bui

IPC: C12N15/113 ,  A61K31/7088 ,  A61K38/36 ,  C07H21/04

CPC classification number: C12N15/1137 ,  A61K31/7088 ,  A61K38/36 ,  C07H21/04 ,  C12N15/113 ,  C12Y304/21034 ,  C12N2310/11 ,  C12N2310/111 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/323 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/351 ,  C12N2310/3525 ,  C12N2320/31 ,  C12N2320/35

Abstract: Disclosed herein are antisense compounds and methods for decreasing PKK mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate PKK-associated diseases, disorders, and conditions.

公开(公告)号：US20240309452A1

公开(公告)日：2024-09-19

申请号：US18487664

申请日：2023-10-16

Applicant: Ionis Pharmaceuticals, Inc. ,  The University of British Columbia

Inventor： C. Frank Bennett ,  Michael Hayden ,  Susan M. Freier ,  Sarah Greenlee ,  Jeffrey Carroll ,  Simon Warby ,  Eric E. Swayze

IPC: C12Q1/6883 ,  C12N15/113 ,  C12Q1/6811 ,  C12Q1/6897

CPC classification number: C12Q1/6883 ,  C12N15/113 ,  C12Q1/6811 ,  C12Q1/6897 ,  C12N2310/11 ,  C12N2320/34 ,  C12Q2539/107 ,  C12Q2600/136 ,  C12Q2600/156 ,  C12Q2600/158

Abstract: Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD).

公开(公告)号：US20240301411A1

公开(公告)日：2024-09-12

申请号：US18443619

申请日：2024-02-16

Applicant: Ionis Pharmaceuticals, Inc.

Inventor： Hien Thuy Zhao ,  Punit P. Seth

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N2310/11 ,  C12N2310/315

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of APP RNA in a cell or a subject, and in certain instances reducing the amount of APP protein in a cell or a subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease or disorder associated with APP. Such symptoms and hallmarks include cognitive impairment, including a decline in memory and language skills, behavioral and psychological symptoms such as apathy and lack of motivation, gait disturbances, seizures, progressive dementia, and abnormal amyloid deposits.

公开(公告)号：US20240294923A1

公开(公告)日：2024-09-05

申请号：US18448392

申请日：2023-08-11

Applicant: Ionis Pharmaceuticals, Inc.

Inventor： Michael Oestergaard ,  Punit P. Seth ,  Eric E. Swayze

IPC: C12N15/113 ,  C07H21/02

CPC classification number: C12N15/1138 ,  C07H21/02 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/33 ,  C12N2310/3341 ,  C12N2310/335 ,  C12N2310/341 ,  C12N2310/351 ,  C12N2320/34 ,  C12N2320/53

Abstract: The present disclosure provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. In certain embodiments, certain oligomeric compounds selectively reduce the expression of a target nucleic acid transcript relative to a non-target nucleic acid transcript.

公开(公告)号：US12030910B2

公开(公告)日：2024-07-09

申请号：US17021510

申请日：2020-09-15

Applicant: Ionis Pharmaceuticals, Inc.

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

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

CPC classification number: 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

Abstract: 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.