公开(公告)号：US12215128B2

公开(公告)日：2025-02-04

申请号：US17261313

申请日：2019-07-19

Applicant: COLD SPRING HARBOR LABORATORY ,  DEPYMED, INC.

Inventor： Nicholas Tonks ,  Navasona Krishnan ,  Andreas Grill

IPC: C07D213/38 ,  C07D401/12 ,  C07J43/00

Abstract: Compounds of formula: are described herein. The compounds selectively complex copper and are therefore useful both abiotically for measuring and detecting small amounts of copper and, in biological systems, for treating diseases associated with inappropriate copper levels, such as Wilson's disease and gastric cancer.

公开(公告)号：US20250011765A1

公开(公告)日：2025-01-09

申请号：US18649873

申请日：2024-04-29

Applicant: Duke University ,  Cold Spring Harbor Laboratory

Inventor： Z. Josh Huang ,  Yongjun Qian

IPC: C12N15/11 ,  A61P25/08 ,  A61P25/28

Abstract: A readrRNA (RNA sensing by Endogenous ADAR) molecule is a modular RNA molecule that facilitates sensing and detection of a cell type or cell status of a cell, including a cell of a mammalian nervous system, such as a neuronal or non-neuronal cell of the mammalian central and/or peripheral nervous system, and/or facilitates delivery of an effector protein to the selected cell. A composition that includes such a modular RNA molecule and another nucleic acid (linked or unlinked to the modular RNA molecule) is a CellREADR (Cell access through RNA sensing by Endogenous ADAR). CellREADR senses the presence of a selected cell RNA in a cell of a mammalian nervous system via readrRNA and leverages RNA editing mediated by ADAR (adenosine deaminase acting on RNA) for coupling the detection of a cell-defining RNA with translation of one or more effector proteins in a cell of a mammalian nervous system.

公开(公告)号：US20230270067A1

公开(公告)日：2023-08-31

申请号：US18001370

申请日：2021-06-09

Applicant: University of Georgia Research Foundation, Inc. ,  Cold Spring Harbor Laboratory

Inventor： R. Kelly Dawe ,  David Jackson

IPC: A01H1/08 ,  C12N15/11 ,  C12N9/22 ,  C12N15/82 ,  C12Q1/6895 ,  C07K14/415

CPC classification number: A01H1/08 ,  C07K14/415 ,  C12N9/22 ,  C12N15/11 ,  C12N15/8213 ,  C12Q1/6895 ,  C12N2310/20 ,  C12N2800/80 ,  C12Q2600/13

Abstract: Monocot plants heterozygous for centromeric histone 3 (CenH3) and optionally expressing gene editing constructs, for use in inducing haploids of a monocot target plant and optionally pass-through gene editing are provided. The monocot haploid inducer plants are typically composed of diploid plant cells having only one allele encoding a functional CENH3 protein. The diploid plant cells can also include, for example, one CenH3 allele encoding non-functional CENH3 protein. In some embodiments, the allele encoding non-functional CENH3 protein is a frameshift mutation, protein null allele, an RNA null allele, or a combination thereof. The monocot haploid inducer plant can also include gene editing machinery, such as a site-directed nuclease and optionally a guide RNA stably expressed by cells of the monocot plant. Methods of inducing formation of a target haploid monocot plant while optionally simultaneously modifying the target monocot plant’s genome are also provided.

公开(公告)号：US11660306B2

公开(公告)日：2023-05-30

申请号：US16377875

申请日：2019-04-08

Applicant: Cold Spring Harbor Laboratory

Inventor： Nicholas Tonks ,  Navasona Krishnan

IPC: A61K31/662 ,  C07F9/38 ,  C12Q1/6883

CPC classification number: A61K31/662 ,  C07F9/3808 ,  C12Q1/6883 ,  C12Q2600/156

Abstract: The present invention relates to agents and methods for treating autism spectrum disorders, such as Rett Syndrome.

公开(公告)号：US11406647B2

公开(公告)日：2022-08-09

申请号：US16761631

申请日：2018-11-06

Applicant: COLD SPRING HARBOR LABORATORY ,  DEPYMED, INC.

Inventor： Nicholas Tonks ,  Navasona Krishnan ,  Andreas Grill ,  Howard Sard

IPC: A61K31/58 ,  A61K31/4184

Abstract: Provided is a method of forming a copper-containing complex, including contacting a sample containing copper with a compound of Formula I: wherein R is —OH or —O—CH3. Also provided is a method of inhibiting enzymatic activity of a kinase in a sample, including contacting the sample with a compound of Formula I. Further provided is a method of administering to a subject a pharmaceutical composition including a compound of Formula I optionally complexed with copper. Also provided is a pharmaceutical composition including copper complexed with a compound of Formula I.

公开(公告)号：US11352624B2

公开(公告)日：2022-06-07

申请号：US16839034

申请日：2020-04-02

Applicant: Cold Spring Harbor Laboratory

Inventor： Adrian Krainer ,  Isabel Aznarez ,  Tomoki Nomakuchi

IPC: C12N15/11 ,  A61K31/713 ,  C12Q1/6883 ,  A61K31/4245 ,  A61K31/726

Abstract: The present disclosure relates to compositions and methods for inhibiting nonsense-mediated mRNA decay in a gene-specific manner, for example in the treatment of diseases or disorders caused by nonsense mutations.

公开(公告)号：US20220143066A1

公开(公告)日：2022-05-12

申请号：US17348125

申请日：2021-06-15

Applicant: Cold Spring Harbor Laboratory ,  Ionis Pharmaceuticals, Inc.

Inventor： David L. Spector ,  Sarah Daniela Diermeier ,  Frank Rigo ,  C. Frank Bennett ,  Susan M. Freier ,  Gayatri Arun ,  Kung-Chi Chang

IPC: A61K31/713 ,  A61P35/00 ,  A61K31/175 ,  A61K31/712 ,  A61K31/7125 ,  C07H21/04 ,  C12N15/113

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.

公开(公告)号：US11236330B2

公开(公告)日：2022-02-01

申请号：US16149941

申请日：2018-10-02

Applicant: Ionis Pharmaceuticals, Inc. ,  Cold Spring Harbor Laboratory

Inventor： Frank Rigo ,  C. Frank Bennett ,  Adrian R. Krainer ,  Zhenxun Wang

IPC: C07H21/04 ,  C12N15/113

Abstract: The present invention provides compounds comprising oligonucleotides complementary to a pyruvate kinase M transcript. Certain such compounds are useful for hybridizing to a pyruvate kinase M transcript, including but not limited to a pyruvate kinase M transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the pyruvate kinase M transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with cancer.

公开(公告)号：US11096956B2

公开(公告)日：2021-08-24

申请号：US16007435

申请日：2018-06-13

Applicant: Stoke Therapeutics, Inc. ,  Cold Spring Harbor Laboratory

Inventor： Isabel Aznarez ,  Huw M. Nash ,  Adrian Krainer

IPC: A61K31/7125 ,  A61K47/68 ,  C12N15/113 ,  A61P43/00 ,  A61K38/00 ,  A61K38/17 ,  C12N15/62 ,  C12N15/11

Abstract: Provided herein are methods and compositions for increasing the expression of a protein, and for treating a subject in need thereof, e.g., a subject with deficient protein expression or a subject having a disease described herein.

公开(公告)号：US11066668B2

公开(公告)日：2021-07-20

申请号：US16422128

申请日：2019-05-24

Applicant: Ionis Pharmaceuticals, Inc. ,  Cold Spring Harbor Laboratory

Inventor： C. Frank Bennett ,  Frank Rigo ,  Adrian R. Krainer ,  Rahul Sinha

IPC: C12N15/113 ,  C12N15/11

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.