公开(公告)号：US20220065864A1

公开(公告)日：2022-03-03

申请号：US17291458

申请日：2019-11-08

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： Steven CORSELLO ,  Ryan SPANGLER ,  Rohith NAGARI ,  Todd GOLUB

IPC分类号： G01N33/574 ,  C12Q1/6886 ,  A61K31/415 ,  A61K45/06 ,  A61P35/00

摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers that exhibit elevated expression and/or amplification of the ABCB1 (MDR1) transporter, optionally for reasons related to development of chemotherapeutic resistance having occurred during treatment with an initial chemotherapeutic drug. In particular, the instant disclosure provides for identification of a cancer as possessing elevated ABCB1 expression and/or exhibiting resistance to a non-tepoxalin chemotherapeutic drug, and selecting and/or administering tepoxalin, a tepoxalin derivative and/or metabolite thereof as a therapeutic agent for such a cancer and/or subject having or at risk of developing such a cancer. Methods and compositions for therapies that combine such tepoxalin or tepoxalin-related compounds with other cancer therapies and/or chemotherapeutic agents are also provided.

公开(公告)号：US20210169827A1

公开(公告)日：2021-06-10

申请号：US17161431

申请日：2021-01-28

申请人： THE BROAD INSTITUTE, INC. ,  THE BRIGHAM & WOMEN'S HOSPITAL, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  Instituto Carlos Slim de la Salud, A.C.

发明人： Anna Greka ,  Moran Dvela-Levitt ,  Maria Alimova ,  Eric Lander ,  Todd R. Golub ,  Florence Wagner ,  Brian Chamberlain ,  Valeria Padovano ,  Joseph Growney

IPC分类号： A61K31/13 ,  A61P13/12 ,  A61P27/02 ,  C12Q1/6883

摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.

公开(公告)号：US20190350938A1

公开(公告)日：2019-11-21

申请号：US16312775

申请日：2017-06-27

申请人： THE BROAD INSTITUTE, INC. ,  PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： EITAN HOCH ,  SUZANNE BETH ROSENBERG JACOBS ,  VICTOR RUSU ,  LIPING ZHAO ,  JOSE M. MERCADER BIGAS

IPC分类号： A61K31/5377 ,  A61K31/4436 ,  A61K38/17

摘要： The invention features compositions and methods that are useful for increasing the level or activity of SLC16A11 in a subject, there by treating or preventing type 2 diabetes in the subject.

公开(公告)号：US11555031B2

公开(公告)日：2023-01-17

申请号：US16494744

申请日：2018-03-19

申请人： The Broad Institute, Inc. ,  The General Hospital Corporation ,  Instituto Carlos Slim de la Salud, A.C.

发明人： Sean M. Burns ,  Bridget K. Wagner ,  Amedeo Vetere

IPC分类号： C07D413/12 ,  A61P3/08 ,  C07C235/84 ,  C07D213/30 ,  C07D231/12 ,  C07D237/08 ,  C07D261/08 ,  C07D495/04

摘要： Disclosed herein are methods for inducing insulin secretion in a glucose-dependent manner and compounds for use in these methods. The compounds may have the structure of formula I(a): wherein the substituents are as described in the description; or a pharmaceutically acceptable form thereof.

公开(公告)号：US20220242815A1

公开(公告)日：2022-08-04

申请号：US17560997

申请日：2021-12-23

申请人： The Broad Institute, Inc. ,  Instituto Carlos Slim de la Salud, A.C. ,  The Brigham and Women's Hospital, Inc.

发明人： Brian T. Chamberlain ,  David Kornfilt ,  Florence F. Wagner ,  Maria Alimova ,  Anna Greka ,  Joseph Growney

IPC分类号： C07C211/38 ,  A61P13/12 ,  C07D311/96 ,  C07C217/52 ,  C07C209/22 ,  C07D295/185 ,  C07C215/44 ,  C07C229/50

摘要： The present disclosure relates to compositions and methods related to bicyclo[2.2.1] heptanamine-containing compounds and salts.

公开(公告)号：US10370697B2

公开(公告)日：2019-08-06

申请号：US15600475

申请日：2017-05-19

申请人： THE BROAD INSTITUTE, INC. ,  The General Hospital Corporation ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： Sean Burns ,  David Altshuler ,  Amedeo Vetere

IPC分类号： C12N9/02 ,  C12Q1/66 ,  C07K14/62 ,  G01N33/50 ,  G01N33/58 ,  C07K14/575 ,  C07K14/605 ,  C12Q1/6897

摘要： The present invention provides nucleic acid constructs that encode fusion peptides comprising a bioluminescent protein and a precursor of a secreted peptide or protein expressed at the cell surface and high throughput screening assays using same.

公开(公告)号：US09657329B2

公开(公告)日：2017-05-23

申请号：US14356864

申请日：2012-11-07

申请人： THE BROAD INSTITUTE, INC. ,  The General Hospital Corporation ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： Sean Burns ,  David Altshuler ,  Amedeo Vetere

IPC分类号： C40B30/06 ,  C12Q1/66 ,  C12Q1/68 ,  G01N33/50 ,  C07K14/575 ,  C07K14/605 ,  C07K14/62 ,  C12N9/02 ,  G01N33/58

CPC分类号： C12Q1/66 ,  C07K14/575 ,  C07K14/605 ,  C07K14/62 ,  C07K2319/00 ,  C07K2319/50 ,  C07K2319/60 ,  C12N9/0069 ,  C12Q1/6897 ,  G01N33/5008 ,  G01N33/5035 ,  G01N33/5073 ,  G01N33/581

摘要： The present invention provides nucleic acid constructs that encode fusion peptides comprising a bioluminescent protein and a precursor of a secreted peptide or protein expressed at the cell surface and high throughput screening assays using same.

公开(公告)号：US11492670B2

公开(公告)日：2022-11-08

申请号：US15298895

申请日：2016-10-20

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： William C. Hahn ,  Andrew Aguirre ,  April Cook ,  Glenn Cowley ,  Robin Meyers ,  David E. Root ,  Aviad Tsherniak ,  Barbara Weir ,  Francisca Vazquez

IPC分类号： C12Q1/68 ,  C07K1/00 ,  C12Q1/6886 ,  A61K38/46 ,  A61K45/06 ,  C12N9/22 ,  C12N9/96 ,  C12N15/113 ,  A61K48/00 ,  B82Y5/00

摘要： The present invention relates to compositions and methods for targeting cancer-specific DNA sequences, such as copy number amplifications and other types of cancer-specific sequence variations, such as cancer-specific polymorphisms, insertions, or deletions. The present invention provides hereto sequence-specific DNA targeting agents targeting a sequence within the amplified DNA region or a sequence otherwise specific for a cancer cell compared to a non-cancer cell. The invention further relates to methods for treating cancer, comprising administering such sequence-specific DNA targeting agents. The invention further relates to methods for preparing sequence-specific DNA targeting agent, as well as screening methods using the DNA targeting agents.

公开(公告)号：US20220023233A1

公开(公告)日：2022-01-27

申请号：US17494830

申请日：2021-10-06

申请人： THE BROAD INSTITUTE, INC. ,  THE BRIGHAM & WOMEN'S HOSPITAL, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  Instituto Carlos Slim de la Salud, A.C.

发明人： Anna Greka ,  Moran Dvela-Levitt ,  Maria Alimova ,  Eric Lander ,  Todd R. Golub ,  Florence Wagner ,  Brian Chamberlain ,  Valeria Padovano ,  Joseph Growney

IPC分类号： A61K31/13 ,  A61P27/02 ,  A61P13/12 ,  C12Q1/6883

摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.

公开(公告)号：US20220017524A1

公开(公告)日：2022-01-20

申请号：US17293255

申请日：2019-11-14

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： Steven CORSELLO ,  Ryan SPANGLER ,  Rohith NAGARI ,  Todd GOLUB ,  Amael MADEC

IPC分类号： C07D487/04 ,  C07D471/14 ,  A61K45/06

摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit elevated expression of FOXA1 and/or FOXA1 gene targets, such as certain breast, liver and/or prostate cancers, including luminal and/or ER-positive forms of breast cancer. Three previously identified adenosine receptor antagonists, CGS-15943, MRS-1220 and SCH-58261, as well as furan ring moiety-possessing derivatives of CGS-15943 are specifically provided for killing cancer cells in a manner that appears to involve activation of the aryl hydrocarbon receptor (AHR) by such compounds. The instant disclosure therefore provides for selecting and/or administering CGS-15943, MRS-1220, SCH-58261 and/or a furan-possessing derivative of CGS-15943, MRS-1220 and/or SCH-58261 as a therapeutic agent to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided