公开(公告)号：US12131803B2

公开(公告)日：2024-10-29

申请号：US16757329

申请日：2018-10-17

申请人： THE BROAD INSTITUTE, INC. ,  PRESIDENT AND FELLOWS OF HARVARD COLLEGE

发明人： Giulio Genovese ,  Po-Ru Loh ,  Steven McCarroll

IPC分类号： G16B20/10 ,  C12Q1/6883 ,  C12Q1/6886 ,  G16B5/00 ,  G16B20/20 ,  G16H10/40

CPC分类号： G16B20/10 ,  G16B5/00 ,  G16B20/20 ,  G16H10/40 ,  C12Q1/6883 ,  C12Q1/6886

摘要： Embodiments disclosed herein provide methods, systems, and computer program products that utilize long-range phase information to detect subtle chromosome imbalances in genotype data. Clonal expansions result from mutation followed by selective proliferation, and the embodiments disclosed herein may be used to somatic structural variant events (SVs) predictive or diagnostic of cancer and other diseases.

公开(公告)号：US12131498B2

公开(公告)日：2024-10-29

申请号：US17730377

申请日：2022-04-27

申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  Yeda Research and Development Co. LTD. of Weizmann Institute of Science ,  National University of Ireland Maynooth

发明人： Mehrtash Babadi ,  Luca D'Alessio ,  Muriel Medard ,  Ken Duffy ,  Yonina Eldar ,  Litian Liu

IPC分类号： G06T7/73 ,  G01N21/64 ,  G06V10/98 ,  G06V20/00 ,  G06V20/69

CPC分类号： G06T7/73 ,  G01N21/6458 ,  G06V10/98 ,  G06V20/698 ,  G06V20/95 ,  G01N2021/6441 ,  G06T2207/10056 ,  G06T2207/10064 ,  G06T2207/30242

摘要： A way to design a codebook for estimating the type of a molecule at a particular location in a fluorescence microscopy image makes use of one or both of (1) knowledge of the non-uniform prior distribution of molecule types (i.e., some types are known a priori to occur more frequently than others) and/or knowledge of co-occurrence of molecule types at close locations (e.g., in a same cell); and (2) knowledge of a model of the (e.g., random) process that yields the intensities that are expected at a location when a molecule with a particular subset of markers (i.e., a molecule of a type that has been assigned a codeword that defines that subset) is present at that location. The codebook design may provide experimental efficiency by reducing the number of images that need to be acquired and/or improve classification or detection accuracy by making the codewords for different molecule types more distinctive.

公开(公告)号：US20240336981A1

公开(公告)日：2024-10-10

申请号：US18750868

申请日：2024-06-21

申请人： The Broad Institute, Inc. ,  The General Hospital Corporation

发明人： Yifat GEFFEN ,  Whijae ROH ,  Gad GETZ

IPC分类号： C12Q1/6886 ,  C12Q1/6851

CPC分类号： C12Q1/6886 ,  C12Q1/6851 ,  C12Q2600/106 ,  C12Q2600/158

摘要： The disclosure provides molecular classifiers for use in the characterization and diagnosis of lung cancer and methods of selecting and treating subjects with appropriate personalized cancer treatments, including but not limited to CDK4/6 inhibitors, c-Met inhibitors, PD-1/PD-L1 inhibitors and combinations thereof.

公开(公告)号：US20240294643A1

公开(公告)日：2024-09-05

申请号：US18430961

申请日：2024-02-02

申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK ,  Massachusetts Institute of Technology ,  The Broad Institute, Inc.

发明人： Benjamin IZAR ,  Johannes C. MELMS ,  Pratiksha THAKORE ,  Katie GEIGER-SCHULLER ,  Aviv REGEV ,  Chris FRANGIEH

IPC分类号： C07K16/28 ,  A61K31/7105 ,  A61K45/06 ,  C12N15/113 ,  C12N15/115

CPC分类号： C07K16/2824 ,  A61K31/7105 ,  A61K45/06 ,  C12N15/1138 ,  C12N15/115 ,  C07K2317/76 ,  C12N2310/14

摘要： Methods of targeting CD58 signaling to enhance antitumor immunity and overcome resistance to checkpoint blockade therapy. Gene signatures associated with immune fitness were identified. Markers and therapeutic targets for such immunotherapy resistance.

公开(公告)号：US20240271138A1

公开(公告)日：2024-08-15

申请号：US18568797

申请日：2022-06-10

申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  The General Hospital Corporation

发明人： Nir Hacohen ,  Matteo Gentile ,  Bingxu Liu

IPC分类号： C12N15/113 ,  A61K39/00 ,  A61P37/02 ,  C07K16/18

CPC分类号： C12N15/113 ,  A61P37/02 ,  C07K16/18 ,  A61K2039/505 ,  C12N2310/11 ,  C12N2310/14

摘要： Provided herein are compositions and methods for enhancing the activity of Stimulator of Interferon Genes (STING) with one or more agents for inhibiting the activity of one or more negative regulators of STING, including DNAJC13 and ESCRT.

公开(公告)号：US20240271119A1

公开(公告)日：2024-08-15

申请号：US18292421

申请日：2022-07-27

申请人： The Broad Institute, Inc. ,  President and Fellows of Harvard College

发明人： David R. Liu ,  Tina Wang ,  Mary S. Morrison

IPC分类号： C12N15/10 ,  C12M1/00 ,  C12M1/34 ,  C12N1/20 ,  C12N7/00 ,  C12N15/70 ,  C12R1/19

CPC分类号： C12N15/1024 ,  C12M23/58 ,  C12M29/18 ,  C12M41/36 ,  C12N1/205 ,  C12N7/00 ,  C12N15/1058 ,  C12N15/70 ,  C12R2001/19

摘要： Aspects of the disclosure relate to compositions, systems, and methods for evolving nucleic acids and proteins utilizing continuous directed evolution in the periplasm of a host cell. In some embodiments, the methods comprise passing a nucleic acid from cell-to-cell in a desired, function dependent manner. The linkage of the desired function and passage of the nucleic acid from cell-to-cell allows for continuous selection and mutation of the nucleic acid.

公开(公告)号：US20240262900A1

公开(公告)日：2024-08-08

申请号：US18567197

申请日：2022-06-06

申请人： JANSSEN BIOTECH, INC. ,  The Broad Institute, Inc. ,  The General Hospital Corporation

发明人： Nathan Majewski ,  Ramnik Xavier ,  Thomas Sundberg ,  Gaochao Tian ,  Kyunghye Ahn Wisner ,  Holger Babbe

IPC分类号： C07K16/18 ,  C07K1/22 ,  G01N33/68

CPC分类号： C07K16/18 ,  C07K1/22 ,  G01N33/6854 ,  G01N2440/14

摘要： The present invention provides antigen binding domains that bind phosphorylated versions of CREB-regulated transcription coactivator 3 (CRTC3), polynucleotides encoding them, vectors, host cells, and methods of making and using them.

公开(公告)号：US20240229148A1

公开(公告)日：2024-07-11

申请号：US18388985

申请日：2023-11-13

申请人： The Broad Institute, Inc. ,  The General Hospital Corporation ,  Baylor College of Medicine ,  The Brigham and Women's Hospital, Inc. ,  Northwestern University ,  The Johns Hopkins University ,  United States Government as represented by the U.S. Department of Veterans Affairs

发明人： Jaegil KIM ,  Gad GETZ ,  Seth Paul LERNER ,  David KWIATKOWSKI ,  Joshua MEEKS ,  Joaquim BELLMUNT ,  David MCCONKEY

IPC分类号： C12Q1/6886

CPC分类号： C12Q1/6886 ,  C12Q2600/158

摘要： The present invention features methods for characterizing mutational profiles in patients with bladder cancer.

公开(公告)号：US12018080B2

公开(公告)日：2024-06-25

申请号：US16763834

申请日：2018-11-13

申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  The General Hospital Corporation ,  Dana-Farber Cancer Institute, Inc.

发明人： Mario Suva ,  Kai Wucherpfennig ,  Aviv Regev ,  Itay Tirosh ,  Nathan D. Mathewson

IPC分类号： C07K16/28 ,  A61K31/7105 ,  A61K35/17 ,  A61K38/46 ,  A61K39/00 ,  A61K39/395 ,  A61K45/06 ,  A61K48/00 ,  A61P35/00 ,  C12N5/0783 ,  C12N9/22 ,  C12N15/113 ,  C12N15/90

CPC分类号： C07K16/2851 ,  A61K31/7105 ,  A61K35/17 ,  A61K38/465 ,  A61K39/0011 ,  A61K39/3955 ,  A61K45/06 ,  A61P35/00 ,  C12N5/0636 ,  C12N15/113 ,  C12N15/907 ,  A61K2039/51 ,  A61K48/0016 ,  C07K2317/24 ,  C07K2317/75 ,  C07K2317/76 ,  C12N9/22 ,  C12N2510/00

摘要： Provided are methods and compositions for treating cancer in a subject in need thereof. One of the top gene products in glioblastoma multiforme (GBM) is KLRB1 (also known as CD161), a C-type lectin protein that binds to CLEC2D. Binding of CLEC2D to the KLRB1 receptor inhibits the cytotoxic function of NK cells as well as cytokine secretion. KLRB1 is only expressed by small subpopulations of human blood T cells, and consequently little is known about the function of this receptor in T cells. However, preliminary data demonstrate that KLRB1 expression is induced in T cells within the GBM microenvironment. In an exemplary embodiment, a method is provided comprising administering an agent capable of blocking the interaction of KLRB1 with its ligand. The agent may comprise an antibody or fragment thereof, which may bind KLRB1 or CLEC2D.

公开(公告)号：US20240191223A1

公开(公告)日：2024-06-13

申请号：US18334074

申请日：2023-06-13

申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  President and Fellows of Harvard College

发明人： Feng Zhang ,  Omar O. Abudayyeh ,  Jonathan Gootenberg ,  Eric S. Lander

IPC分类号： C12N15/10 ,  C12N9/22 ,  C12N15/11 ,  C12N15/113 ,  C12N15/82 ,  C12N15/85

CPC分类号： C12N15/102 ,  C12N9/22 ,  C12N15/111 ,  C12N15/113 ,  C12N15/8213 ,  C12N15/8509 ,  C12N2310/20 ,  C12N2800/22

摘要： The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a novel RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.