公开(公告)号：US20180235961A1

公开(公告)日：2018-08-23

申请号：US15752130

申请日：2016-08-12

申请人： The Broad Institute, Inc. ,  Dana-Farber Cancer Institute, Inc. ,  Bayer Pharma AG

发明人： Luc De Waal ,  Matthew Meyerson ,  Heidi Greulich ,  Monica Schenone ,  Alex Burgin ,  Xiaoyun Wu ,  Ulrike Sack

IPC分类号： A61K31/50 ,  A61K9/00 ,  A61P35/00 ,  G01N33/574

CPC分类号： A61K31/50 ,  A61K9/0019 ,  A61K9/0053 ,  A61K31/519 ,  A61K2300/00 ,  A61P35/00 ,  G01N33/57488 ,  G01N2333/916 ,  G01N2800/52

摘要： The present invention features improved methods of identifying patients having cancer (e.g., melanoma, adenocarcinoma, lung, cervical, liver or breast cancer) using biomarkers (e.g., PDE3A, SLFN12) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., DNMDP, zardaverine, and anagrelide).

公开(公告)号：US20200369633A1

公开(公告)日：2020-11-26

申请号：US16635504

申请日：2018-08-02

申请人： Bayer Aktiengesellschaft ,  Bayer Pharma Aktiengesellschaft ,  The Broad Institute, Inc. ,  Dana-Farber Cancer Institute, Inc.

发明人： Manuel Ellermann ,  Stefan Nikolaus Gradl ,  Charlotte Christine Kopitz ,  Martin Lange ,  Adrian Tersteegen ,  Philip Lienau ,  Christa Hegele-Hartung ,  Detlev Sülzle ,  Timothy A. Lewis ,  Heidi Greulich ,  Xiaoyun Wu ,  Matthew Meyerson ,  Alex Burgin

IPC分类号： C07D273/04 ,  C07D413/10 ,  C07D413/12 ,  C07D417/10 ,  C07D491/107 ,  C07D495/10 ,  C07D471/04

摘要： The present invention provides dihydrooxydiazinone compounds of general formula (I): in which R1, R2, R3, and R4, are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative diseases, as a sole agent or in combination with other active ingredients.

公开(公告)号：US20150197785A1

公开(公告)日：2015-07-16

申请号：US14420750

申请日：2013-08-09

申请人： The Broad Institute, Inc. ,  Dana-Farber Cancer Institute, Inc.

发明人： Scott L. Carter ,  Gad Getz ,  Aaron McKenna ,  Matthew Meyerson

IPC分类号： C12Q1/68

CPC分类号： C12Q1/68 ,  C12Q1/6809 ,  C12Q2535/122 ,  C12Q2537/16 ,  C12Q2537/165

摘要： Methods and apparatus for inferring purity and ploidy from a sample of cells (e.g., a sample comprising cancer and normal cells) are described. Copy number per cell of interest (e.g., cancer cell) is determined by optimizing purity and ploidy for the sample based, at least in part, on relative copy number profile information. One or more likelihood fit scores are determined for each of a plurality of candidate solutions generated by the methods described herein. A solution is selected based, at least in part on the likelihood fit score(s) and the copy number per cancer cell is determined in accordance with the selected solution.

摘要翻译： 描述了从细胞样品（例如包含癌症和正常细胞的样品）中推断纯度和倍性的方法和装置。 至少部分地基于相对拷贝数分布信息，通过优化样品的纯度和倍性来确定每个感兴趣的细胞（例如，癌细胞）的拷贝数。 通过本文描述的方法生成的多个候选解中的每一个确定一个或多个似然拟合分数。 至少部分地基于可能性拟合得分选择解决方案，并且根据所选择的解决方案确定每个癌细胞的拷贝数。

公开(公告)号：US12053476B2

公开(公告)日：2024-08-06

申请号：US17161612

申请日：2021-01-28

申请人： BAYER PHARMA AKTIENGESELLSCHAFT ,  THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC.

发明人： Timothy A. Lewis ,  Alex Burgin ,  Monica Schenone ,  Xiaoyun Wu ,  Heidi Greulich ,  Matthew Meyerson ,  Luc De Waal ,  Antje Margret Wengner ,  Knut Eis ,  Philip Lienau ,  Ulrike Sack ,  Martin Lange

IPC分类号： A61K31/5377 ,  A61K31/50 ,  A61P35/00 ,  C07D413/10

CPC分类号： A61K31/5377 ,  A61K31/50 ,  A61P35/00 ,  C07D413/10

摘要： The present invention features improved compounds, especially




methods of identifying patients having cancer using biomarkers (e.g., PDE3A, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., Compounds 1-6 disclosed herein).

公开(公告)号：US11773070B2

公开(公告)日：2023-10-03

申请号：US17865236

申请日：2022-07-14

申请人： Bayer Aktiengesellschaft ,  Bayer Pharma Aktiengesellschaft ,  The Broad Institute, Inc. ,  Dana-Farber Cancer Institute, Inc.

发明人： Manuel Ellermann ,  Stefan Nikolaus Gradl ,  Charlotte Christine Kopitz ,  Martin Lange ,  Adrian Tersteegen ,  Philip Lienau ,  Christa Hegele-Hartung ,  Detlev Sülzle ,  Timothy A. Lewis ,  Heidi Greulich ,  Xiaoyun Wu ,  Matthew Meyerson ,  Alex Burgin

IPC分类号： C07D273/04 ,  C07D413/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04 ,  C07D491/107 ,  C07D495/10

CPC分类号： C07D273/04 ,  C07D413/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04 ,  C07D491/107 ,  C07D495/10

摘要： The present invention provides dihydrooxydiazinone compounds of general formula (I)




in which R1, R2, R3, and R4, are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative diseases, as a sole agent or in combination with other active ingredients.

公开(公告)号：US11207320B2

公开(公告)日：2021-12-28

申请号：US15752130

申请日：2016-08-12

申请人： The Broad Institute, Inc. ,  Dana-Farber Cancer Institute, Inc. ,  Bayer Pharma Aktiengesellschaft

发明人： Luc De Waal ,  Matthew Meyerson ,  Heidi Greulich ,  Monica Schenone ,  Alex Burgin ,  Xiaoyun Wu ,  Ulrike Sack

IPC分类号： A61K31/50 ,  G01N33/574 ,  A61P35/00 ,  A61K9/00 ,  A61K31/519

摘要： The present invention features improved methods of identifying patients having cancer (e.g., melanoma, adenocarcinoma, lung, cervical, liver or breast cancer) using biomarkers (e.g., PDE3A, SLFN12) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., DNMDP, zardaverine, and anagrelide).

公开(公告)号：US20200247783A1

公开(公告)日：2020-08-06

申请号：US16635513

申请日：2018-08-02

申请人： Bayer Aktiengesellschaft ,  Bayer Pharma Aktiengesellschaft ,  The Broad Institute, Inc. ,  Dana-Farber Cancer Institute, Inc.

发明人： Manuel Ellermann ,  Stefan Nikolaus Gradl ,  Charlotte Christine Kopitz ,  Martin Lange ,  Adrian Tersteegen ,  Philip Lienau ,  Detlev Sülzle ,  Timothy Lewis ,  Heidi Greulich ,  Xiaoyun Wu ,  Matthew Meyerson

IPC分类号： C07D403/10 ,  C07D405/10 ,  C07D401/10 ,  C07D237/04 ,  C07D413/10 ,  A61P35/04

摘要： The present invention provides 6-phenyl-4,5-dihydropyridazin-3(2H)-one derivatives of formula (I): The present invention provides 6-phenyl-4,5-dihydropyridazin-3(2H)-one derivatives of formula (I):

公开(公告)号：US09890127B2

公开(公告)日：2018-02-13

申请号：US14775354

申请日：2014-03-11

申请人： THE BROAD INSTITUTE, INC. ,  DANA FARBER CANCER INSTITUTE, INC.

发明人： Timothy A. Lewis ,  Benito Munoz ,  Lucian De Waal ,  Heidi Greulich ,  Matthew Meyerson ,  Lara Nicole Gechijian

IPC分类号： A61K31/535 ,  C07D237/04 ,  C07D401/10 ,  C07D403/10 ,  C07D413/10

CPC分类号： C07D237/04 ,  C07D401/10 ,  C07D403/10 ,  C07D413/10

摘要： Disclosed are compounds, such as pyridazinones, that can be, inter alia, used for treating cancer.

公开(公告)号：US11142522B2

公开(公告)日：2021-10-12

申请号：US16480498

申请日：2018-02-01

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  BAYER AKTIENGESELLSCHAFT ,  BAYER PHARMA AKTIENGESELLSCHAFT

发明人： Timothy A. Lewis ,  Xiaoyun Wu ,  Heidi Greulich ,  Matthew Meyerson ,  Manuel Ellermann ,  Philip Lienau ,  Knut Eis ,  Antje Margret Wengner ,  Charlotte Christine Kopitz ,  Martin Lange

IPC分类号： C07D413/10 ,  A61P35/02

摘要： The present invention features improved compounds, especially the compound having the structure (1). Compositions and methods of identifying patients having cancer using biomarkers (e.g., PDE3A, PDE3B, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention.

公开(公告)号：US10590473B2

公开(公告)日：2020-03-17

申请号：US15538382

申请日：2015-12-22

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  THE GENERAL HOSPITAL CORPORATION

发明人： Matthew Meyerson ,  Ganesh M. Shankar ,  Joshua M. Francis ,  Daniel P. Cahill ,  Mikael L. Rinne

IPC分类号： C12Q1/68 ,  C12Q1/6853 ,  C12Q1/6827

摘要： Provided are systems, kits, and methods for the quantitative detection of single nucleotide polymorphisms or variants to identify malignant neoplasms. The methods include use of modified oligonucleotide blockers with peptide nucleic acid backbones that hybridize to and block logarithmic amplification of the wild-type alleles of a target, and incorporation of locked nucleic acids into probes that are complementary to a mutant allele of the target sequence to increase specificity. The methods include detection of variants in sequences with high GC content and/or low complexity, such as the TERT promoter, IDH1, BRAF, NRAS, GNAQ, GNA11 and H3F3 A gene variants. The methods include sensitive detection and staging of cancers with low cellularity, and can be used intraoperatively such as for glioma, or to detect cell-free circulating tumor DNA, such as for melanoma.