公开(公告)号：WO2021091747A1

公开(公告)日：2021-05-14

申请号：PCT/US2020/057814

申请日：2020-10-29

申请人： MERCK SHARP & DOHME CORP. ,  AYERS, Mark, D. ,  CRISTESCU, Razvan ,  LOBODA, Andrey ,  LUNCEFORD, Jared, K. ,  MA, Hua ,  MCCLANAHAN, Terrill, K. ,  NEBOZHYN, Michael ,  ZHANG, Chunsheng

发明人： AYERS, Mark, D. ,  CRISTESCU, Razvan ,  LOBODA, Andrey ,  LUNCEFORD, Jared, K. ,  MA, Hua ,  MCCLANAHAN, Terrill, K. ,  NEBOZHYN, Michael ,  ZHANG, Chunsheng

IPC分类号： C07K16/28 ,  C12Q1/68 ,  G06F19/20

摘要： The invention relates to (i) an angiogenesis gene signature and (ii) a monocytic myeloid-derived suppressor cell (mMDSC) gene signature that are each predictive of patient response to treatment with a PD-1 antagonist, wherein the angiogenesis signature comprises five or more genes. More specifically, a lower angiogenesis score is associated with favorable response to a PD-1 antagonist in a patient with cancer. Similarly, a lower mMDSC score is associated with favorable response to a PD-1 antagonist in a patient with cancer. Also provided are methods of treating a cancer patient with a PD-1 antagonist that were identified as either (i) positive for the angiogenesis gene signature biomarker of the invention or (ii) positive for the mMDSC gene signature biomarker of the invention.

公开(公告)号：WO2016094377A1

公开(公告)日：2016-06-16

申请号：PCT/US2015/064445

申请日：2015-12-08

申请人： MERCK SHARP & DOHME CORP. ,  AYERS, Mark, D. ,  LOBODA, Andrey ,  LUNCEFORD, Jared, K. ,  MCCLANAHAN, Terrill, K. ,  MURPHY, Eric, E. ,  NEBOZHYN, Michael

发明人： AYERS, Mark, D. ,  LOBODA, Andrey ,  LUNCEFORD, Jared, K. ,  MCCLANAHAN, Terrill, K. ,  MURPHY, Eric, E. ,  NEBOZHYN, Michael

IPC分类号： C40B30/04 ,  A61K39/00 ,  A61K39/395

CPC分类号： C07K16/2818 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/76 ,  C12Q1/68 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158

摘要： A gene expression platform, which is a combination of a set of genes that are correlated with response to a PD-1 antagonist in multiple tumor types and a normalization gene set, is disclosed. A method and system of using the gene expression platform to derive gene signature biomarkers of anti-tumor response to a PD-1 antagonist and to test patient samples for predictive gene signature biomarkers are also disclosed.

摘要翻译： 公开了一种基因表达平台，其是与多种肿瘤类型中的PD-1拮抗剂的反应和归一化基因组相关的一组基因的组合。 还公开了使用该基因表达平台来衍生对PD-1拮抗剂的抗肿瘤反应的基因特征生物标志物和测试患者样品用于预测基因特征生物标志物的方法和系统。

公开(公告)号：WO2020167619A1

公开(公告)日：2020-08-20

申请号：PCT/US2020/017408

申请日：2020-02-10

申请人： MERCK SHARP & DOHME CORP. ,  LOBODA, Andrey ,  LUNCEFORD, Jared K. ,  ZHANG, Chunsheng ,  NEBOZHYN, Michael ,  CRISTESCU, Razvan ,  AYERS, Mark D. ,  MCCLANAHAN, Terrill K. ,  MA, Hua

发明人： LOBODA, Andrey ,  LUNCEFORD, Jared K. ,  ZHANG, Chunsheng ,  NEBOZHYN, Michael ,  CRISTESCU, Razvan ,  AYERS, Mark D. ,  MCCLANAHAN, Terrill K. ,  MA, Hua

IPC分类号： C12Q1/6886 ,  C07K16/30 ,  C07K16/28 ,  A61K39/395 ,  A61P35/00

摘要： The invention relates to a stromal/EMT/TGFβ signature that is predictive of patient response to treatment with a PD-1 antagonist, wherein the stromal/EMT/TGFβ signature comprises five or more genes selected from Table 1 disclosed herein. More specifically, a lower stromal/EMT/TGF-β score is associated with favorable response to a PD-1 antagonist in a patient with cancer. Also provided are methods of treating a cancer patient with a PD-1 antagonist that were identified as positive for the stromal/EMT/TGFβ biomarker of the invention. The disclosure also provides methods and kits for testing tumor samples for the biomarkers.