Abstract: Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.
Abstract: The invention provides an oligonucleotide comprising an inosine, and/or a nucleotide containing a base able to form a wobble base pair or a functional equivalent thereof, wherein the oligonucleotide, or a functional equivalent thereof, comprises a sequence which is complementary to at least part of a dystrophin pre-m RNA exon or at least part of a non-exon region of a dystrophin pre-m RNA said part being a contiguous stretch comprising at least 8 nucleotides. The invention further provides the use of said oligonucleotide for preventing or treating DMD or BMD.
Type:
Grant
Filed:
May 4, 2021
Date of Patent:
April 25, 2023
Inventors:
Judith Christina Theodora van Deutekom, Josephus Johannes de Kimpe, Gerard Johannes Platenburg
Abstract: The present disclosure relates, in general, to oligonucleotides that stimulate STING (STimulator of INterferon Genes) activity and increase activity of immune cells. The disclosed STING activators (STAVs) are useful in the treatment of cancer and other immune-mediated conditions.
Abstract: The invention relates to neurodegenerative disorders, and in particular to novel oligonucleotides for treating such conditions, for example Alzheimer's disease. The invention provides novel antisense oligonucleotides, and compositions comprising such oligos, and therapies and methods for treating neurodegenerative disorders. The invention includes genome editing techniques for achieving similar results as using the novel antisense oligonucleotides.
Type:
Grant
Filed:
February 25, 2019
Date of Patent:
April 11, 2023
Assignee:
Teesside University
Inventors:
Pavlos Alifragis, Linda Popplewell, John George Dickson, Amninder Sangha
Abstract: Disclosed are methods and compositions for treating a neurodevelopmental disorder in a subject in need thereof. In some aspects, the method includes administering an effective amount of an agent, wherein administering the agent modulates expression of one or more isoforms of synaptic GTPase-activating protein (SynGAP).
Type:
Grant
Filed:
October 30, 2020
Date of Patent:
April 4, 2023
Assignee:
The Johns Hopkins University
Inventors:
Richard Huganir, Ingie Hong, Yoichi Araki
Abstract: Provided herein are methods of treating NLRP3 inflammasome-associated diseases and disorders. Also, disclosed are methods for screening for agents useful in such methods.
Type:
Grant
Filed:
November 12, 2020
Date of Patent:
April 4, 2023
Assignee:
The Regents of the University of California
Abstract: The present invention relates a formulation and capsule suitable for oral administration. The invention further relates to the use of the formulation and capsule for treating inflammatory bowel diseases, for instance ulcerative colitis (UC) or Crohn's disease.
Type:
Grant
Filed:
May 3, 2019
Date of Patent:
March 7, 2023
Assignee:
Index Pharmaceuticals AB
Inventors:
Paul Alhadeff, Christine Dieterich Johansson, Peter Zerhouni, Wei Tian, Graeme William Andrew Hamilton Johnston
Abstract: Developed and provided is: a nucleic acid agent that is efficiently delivered to the central nervous system, to which drug delivery is inhibited by the blood brain barrier mechanism, and that provides an antisense effect to a target transcription product at the delivery site; and a composition containing such a nucleic acid agent. Provided is a double-stranded nucleic acid complex consisting of a first nucleic acid strand and a second nucleic acid strand that are annealed to each other; wherein the first nucleic acid strand hybridizes with part of a target transcription product and has an antisense effect on the target transcription product; and wherein the second nucleic acid strand includes a base sequence complementary to the first nucleic acid strand and is conjugated to a phosphatidylethanolamine or an analog thereof.
Type:
Grant
Filed:
March 13, 2019
Date of Patent:
March 7, 2023
Assignees:
National University Corporation Tokyo Medical and Dental University, Takeda Pharmaceutical Company Limited
Abstract: Among other things, the present disclosure provides technologies for altering splicing, particularly for increasing inclusion of exons in splicing products. In some embodiments, the present disclosure provides SMN2 oligonucleotides, compositions, and methods thereof. In some embodiments, the present disclosure provides chirally controlled SMN2 oligonucleotide compositions. In some embodiments, provided oligonucleotides and compositions can increase level of an exon 7-containing SMN2 splicing product and/or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of splicing-related conditions, disorders and diseases. In some embodiments, the present disclosure provides methods for treating SMN2-related conditions, disorders and diseases such as SMA (spinal muscular atrophy) and ALS (amyotrophic lateral sclerosis).
Abstract: Disclosed herein are engineered oligonucleotides for selective inhibition of polypeptide expression and activity. Also disclosed herein are methods of selectively inhibiting polypeptide expression and activity contacting an engineered oligonucleotide with a polynucleotide encoding the polypeptide.
Type:
Grant
Filed:
March 11, 2022
Date of Patent:
March 7, 2023
Assignee:
MIRECULE, INC.
Inventors:
Robert Place, Anthony Saleh, Tishan Williams
Abstract: Synthetic ?v?6 integrin ligands of Formula I having serum stability and affinity for integrin ?v?6, which is a receptor expressed in a variety of cell types, are described. The described ligands are useful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin ?v?6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include ?v?6 integrin ligands and methods of use are also described.
Type:
Grant
Filed:
October 31, 2018
Date of Patent:
March 7, 2023
Assignee:
Arrowhead Pharmaceuticals, Inc.
Inventors:
Zhen Li, Xiaokai Li, Erik W. Bush, Rui Zhu, Dongxu Shu, Jonathan Benson, Patrick Shao, Matthew Fowler-Watters
Abstract: The application relates to methods for compositions for identifying lncRNA loci associated with target genotypes or phenotypes, including desirable plant genotypes or phenotype. The application also relates to regulatory regions and genes associated with drug resistance, such as resistance to BRAF-inhibitors. Such regulatory regions and genes form the basis for methods for identifying resistance to BRAF-inhibitors, which is useful for improving disease prognosis, treatment, and likely outcomes. The regulatory regions and genes are also suitable targets for therapy in melanoma that is resistant to BRAF-inhibitors.
Type:
Grant
Filed:
May 4, 2018
Date of Patent:
February 28, 2023
Assignees:
The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
Inventors:
Julia Joung, Jesse Engreitz, Eric S. Lander, Feng Zhang
Abstract: Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy.
Type:
Grant
Filed:
September 1, 2021
Date of Patent:
February 21, 2023
Assignee:
AVIDITY BIOSCIENCES LLC
Inventors:
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
Abstract: The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.
Type:
Grant
Filed:
August 7, 2020
Date of Patent:
February 14, 2023
Assignee:
Silence Therapeutics GMBH
Inventors:
Klaus Giese, Jörg Kaufmann, Anke Klippel-Giese
Abstract: Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy.
Type:
Grant
Filed:
November 17, 2021
Date of Patent:
February 14, 2023
Assignee:
AVIDITY BIOSCIENCES, INC.
Inventors:
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
Abstract: Provided herein are methods and compositions for treating cancer, including cancer that is not responsive to immunotherapy. In one aspect, the methods of treatment comprise administering to the subject a therapeutically effective amount of a ?-catenin inhibitor and a therapeutically effective amount of an immunotherapeutic agent. Another aspect is directed to pharmaceutical compositions comprising a ?-catenin inhibitor for use in treating cancer, wherein the composition is administered in combination with an immunotherapeutic agent. Yet another aspect is directed to a method of potentiating the therapeutic effect of immunotherapy against a cancer using a ?-catenin inhibitor, such as a ?-catenin nucleic acid inhibitor molecule.
Abstract: The invention provides a single-stranded oligonucleotide represented by the formula (I), wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified-nucleotide, and has a first nucleotide sequence capable of hybridizing with a second oligonucleotide. Y is composed of 4 to 100 nucleotides, enables hybridization with the above-mentioned first oligonucleotide, and has a second nucleotide sequence containing at least one ribonucleotide. At least one of the nucleotide sequences X, Xz and Y has an antisense sequence capable of hybridizing with a target RNA. At least one of L, Lx and Ly is a linking group that contains a non-nucleotide structure.
Abstract: Disclosed herein are methods for inhibiting or activating the transcription of a gene of interest, or inhibiting or activating the transcription of specific mRNA isoforms of a gene by using antisense oligonucleotides and/or small molecules. Also described herein are methods for activating transcription from a promoter and increasing overall gene expression by creating of a new splice site in a gene of a cell.
Abstract: Compositions and methods for treating cancer in a subject in need thereof are described that includes administering a therapeutically effective amount of an oligonucleotide that inhibits the binding of splicing regulator SRSF1 or SRSF2 to MDM2 exon 4 or 11.
Type:
Grant
Filed:
July 23, 2019
Date of Patent:
January 31, 2023
Inventors:
Dawn Suzan Chandler, Daniel Forrest Comiskey
Abstract: The invention relates to the field of RNA stabilisation, and more particularly to the use of deuterium oxide (D2O) during storage and/or synthesis of RNA molecules. Described herein are deuterium-stabilised ribonucleic acid (RNA) molecules that display an increased resistance to thermal and enzymatic hydrolysis. Also described are aqueous compositions comprising stabilized RNA molecules and methods for making same. The invention is particularly useful for in the manufacture of RNA-based therapeutics, such as mRNA vaccines, to render them less sensitive to temperature fluctuations.