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.
Type:
Application
Filed:
May 11, 2020
Publication date:
September 9, 2021
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Thazha P. Prakash, Punit P. Seth, Eric E. Swayze, Susan M. Freier, Huynh-Hoa Bui
Abstract: Provided herein are methods, compounds, and compositions for safely reducing thrombopoietin in a cell or an individual. Such methods, compounds, and compositions maintain platelet count within a safe hemostatic range. Such methods, compounds, and compositions are useful to safely treat, prevent, or ameliorate a disease that can benefit from platelet count reduction in an individual. Such methods, compounds, and compositions are useful for treating or preventing diseases in which thrombopoietin contributes to the presence or activation of platelets contributes to and promotes disease initiation or progression, and/or adversely affects disease outcome.
Type:
Application
Filed:
July 16, 2019
Publication date:
September 9, 2021
Applicants:
Aronora, Inc., Oregon Health & Science University, Ionis Pharmaceuticals, Inc.
Inventors:
Andras Gruber, Erik Tucker, Brett P. Monia, Alexey Revenko
Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of UBE3A-ATS, the endogenous antisense transcript of ubiquitin protein ligase E3A (UBE3A) in a cell or subject, and in certain instances increasing the expression of paternal UBE3A and the amount of UBE3A protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurogenetic disorder. Such symptoms and hallmarks include developmental delays, ataxia, speech impairment, sleep problems, seizures, and EEG abnormalities. Such neurogenetic disorders include Angelman Syndrome.
Type:
Application
Filed:
April 21, 2021
Publication date:
September 9, 2021
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Susan M. Freier, Huynh-Hoa Bui, Paymaan Jafar-nejad, Frank Rigo
Abstract: Disclosed herein are antisense compounds and methods for decreasing Ataxin 2 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Ataxin 2 associated diseases, disorders, and conditions. Such Ataxin 2 associated diseases include spinocerebellar ataxia type 2 (SCA2), amyotropic sclerosis (ALS), and parkinsonism.
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.
Type:
Application
Filed:
September 15, 2020
Publication date:
September 2, 2021
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Stanley T. Crooke, Xue-hai Liang, Wen Shen
Abstract: 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.
Type:
Application
Filed:
February 10, 2021
Publication date:
August 26, 2021
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Punit P. Seth, Michael Oestergaard, Michael T. Migawa, Xue-hai Liang, Wen Shen, Stanley T. Crooke, Eric E. Swayze
Abstract: Provided are compounds, methods, and pharmaceutical compositions for increasing the amount or activity of STMN2 RNA in a cell or animal, and in certain embodiments increasing the amount of STMN2 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disease. Such symptoms include ataxia, neuropathy, synaptic dysfunction, deficits in cognition, and decreased longevity. Such neurodegenerative diseases include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and dementia with Lewy bodies (DLB).
Type:
Application
Filed:
June 14, 2019
Publication date:
August 19, 2021
Applicants:
Ionis Pharmaceuticals, Inc., Ludwig Institute For Cancer Research
Inventors:
Huynh-Hoa Bui, Don W. Cleveland, Ze'ev Melamed
Abstract: The present invention provides gapped oligomeric compounds comprising from 1 to about 3 internucleoside linkages having one of formulas I to XVI. In certain embodiments, inclusion of from 1 to about 3 internucleoside linkages of one of formulas I to XVI, improves selectivity for a target RNA relative to an off target RNA. In certain embodiments, the improved selectivity also provides an improved toxicity profile. 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 of activity or expression of the target nucleic acid in a cell.
Type:
Application
Filed:
June 17, 2019
Publication date:
August 19, 2021
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Michael T. Migawa, Eric E. Swayze, Punit P. Seth
Abstract: The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
Type:
Grant
Filed:
August 30, 2018
Date of Patent:
August 10, 2021
Assignee:
Ionis Pharmaceuticals, inc.
Inventors:
Thazha P. Prakash, Punit P. Seth, Eric E. Swayze
Abstract: The present invention 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.
Type:
Application
Filed:
September 3, 2020
Publication date:
August 5, 2021
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Punit P. Seth, Michael Oestergaard, Eric E. Swayze
Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN2 RNA in a cell or animal, and in certain instances reducing the amount of Ataxin-2 protein in a cell or animal. 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 ataxia, neuropathy, and aggregate formation. Such neurodegenerative diseases include spinocerebellar ataxia type 2 (SCA2), amyotrophic lateral sclerosis (ALS), and parkinsonism.
Abstract: The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.
Type:
Grant
Filed:
February 26, 2019
Date of Patent:
August 3, 2021
Assignee:
Ionis Pharmaceuticals, Inc.
Inventors:
Charles Allerson, Balkrishen Bhat, Anne B. Eldrup, Muthiah Manoharan, Richard H. Griffey, Brenda F. Baker, Eric E. Swayze
Abstract: Disclosed herein are compositions and methods for reducing expression of C9ORF72 mRNA and protein in an animal. Such methods are useful to treat, prevent, ameliorate, or slow progression of neurodegenerative diseases in an individual in need thereof.
Abstract: Disclosed herein are compounds, compositions and methods for modulating the expression of huntingtin in a cell, tissue or animal. Further provided are methods of slowing or preventing Huntington's Disease (HD) progression using an antisense compound targeted to huntingtin. Additionally provided are methods of delaying or preventing the onset of Huntington's Disease (HD) in an individual susceptible to Huntington's Disease (HD). Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders.
Abstract: The present disclosure provides compounds comprising oligonucleotides complementary to a portion of the IKBKAP gene. Certain such compounds are useful for hybridizing to a portion of the IKBKAP gene, including but not limited to a portion of the IKBKAP gene in a cell. In certain embodiments, such hybridization results in modulation of splicing of the IKBKAP gene. In certain embodiments, the IKBKAP gene includes a mutation that results in defective splicing and a truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in a decrease in the amount of defective splicing and truncated IKAP protein. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the IKBKAP gene results in an increase in the amount of normal splicing and functional, full-length IKAP protein. In certain embodiments, oligonucleotides are used to treat Familial Dysautonomia.
Type:
Grant
Filed:
May 24, 2019
Date of Patent:
July 20, 2021
Assignees:
Ionis Pharmaceuticals, Inc., Cold Spring Harbor Laboratory
Inventors:
C. Frank Bennett, Frank Rigo, Adrian R. Krainer, Rahul Sinha
Abstract: 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.
Abstract: Provided herein are methods, compounds, and compositions for reducing expression of a MaTAR in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate breast cancer in an individual in need.
Type:
Grant
Filed:
December 5, 2016
Date of Patent:
July 13, 2021
Assignees:
Ionis Pharmaceuticals, Inc., Cold Spring Harbor Laboratory
Inventors:
David L. Spector, Sarah Daniela Diermeier, Frank Rigo, C. Frank Bennett, Susan M. Freier, Gayatri Arun, Kung-Chi Chang
Abstract: The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with excess growth hormone using antisense compounds or oligonucleotides targeted to growth hormone receptor (GHR).
Type:
Application
Filed:
August 4, 2020
Publication date:
July 8, 2021
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Thazha P. Prakash, Punit P. Seth, Eric E. Swayze, Sanjay Bhanot, Susan M. Freier, Huynh-Hoa Bui
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.
Type:
Application
Filed:
October 31, 2018
Publication date:
June 17, 2021
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Jeffrey R. Crosby, Shuling Guo, Huynh-Hoa Bui, Andrew T. Watt, Susan M. Freier
Abstract: Provided herein are methods, compounds, and compositions for reducing expression of Inc05 in a cell or individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a cancer in an individual.
Type:
Grant
Filed:
December 1, 2017
Date of Patent:
June 15, 2021
Assignees:
Cold Spring Harbor Laboratory, Ionis Pharmaceuticals, Inc.
Inventors:
Allen Tingjin Yu, David L. Spector, Frank Rigo, Susan M. Freier, Jan Bergmann, Carmen Berasain