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    HETEROAROMATIC COMPOUNDS USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES
    82.
    发明公开
    HETEROAROMATIC COMPOUNDS USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES 有权
    HETEROAROMATISCHE VERBINDUNGEN ZUR BEHANDLUNG PROLIFERATIVER ERKRANKUNGEN

    公开(公告)号：EP3057955A1

    公开(公告)日：2016-08-24

    申请号：EP14799918.9

    申请日：2014-10-17

    申请人： Syros Pharmaceuticals, Inc. ,  Dana-Farber Cancer Institute, Inc.

    发明人： CIBLAT, Stephane ,  DEROY, Patrick ,  GRAY, Nathanael ,  LEBLANC, Melissa ,  MARINEAU, Jason, J. ,  MOORE, Joel ,  SPROTT, Kevin ,  ZHANG, Tinghu ,  SIDDIQUI, M., Arshad ,  KABRO, Anzhelika ,  LEGER, Serge ,  MILLER, Tom ,  ROY, Stephanie ,  SCHMIDT, Darby ,  WINTER, Dana, K. ,  BRADLEY, Michael

    IPC分类号： C07D401/14 ,  A61K31/506 ,  A61P35/02

    CPC分类号： C07D401/14 ,  A61K31/506 ,  A61K45/06

    摘要： The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

    摘要翻译： 本发明提供新的式（I）化合物及其药学上可接受的盐，溶剂合物，水合物，互变异构体，立体异构体，同位素标记的衍生物及其组合物。 还提供了涉及用于治疗或预防受试者的增殖性疾病（例如，癌症（例如白血病，黑素瘤，多发性骨髓瘤），良性肿瘤，血管生成，炎性疾病，自身炎性疾病和自身免疫性疾病）的化合物或组合物的方法和试剂盒 。 使用本发明的化合物或组合物治疗具有增殖性疾病的受试者可以抑制激酶例如细胞周期蛋白依赖性激酶（CDK）（例如，细胞周期蛋白依赖性激酶7（CDK7））的异常活性，因此 ，诱导受试者的细胞凋亡和/或抑制转录。

    METHODS OF BH3 PROFILING
    83.
    发明公开
    METHODS OF BH3 PROFILING 审中-公开
    方法BH3谱

    公开(公告)号：EP3047276A1

    公开(公告)日：2016-07-27

    申请号：EP14845952.2

    申请日：2014-09-18

    申请人： Dana-Farber Cancer Institute, Inc.

    发明人： RYAN, Jeremy ,  LETAI, Anthony

    IPC分类号： G01N33/574

    CPC分类号： G01N33/5079 ,  G01N33/5011 ,  G01N33/5035 ,  G01N33/5748 ,  G01N33/582 ,  G01N2333/82 ,  G01N2800/52

    摘要： In various aspects the invention provides methods of predicting sensitivity of a cancer cell to a therapeutic agent by contacting a test cell population BH3 domain peptide; measuring the amount of BH3 domain peptide induced mitochondrial outer membrane permeabilization in the test cell population; and comparing the amount of BH3 domain peptide induced mitochondrial outer membrane permeabilization in the test cell population to a control cell population that has not been contacted with the therapeutic agent. An increase in mitochondrial membrane permeabilization in the test cell population compared to the control cell population indicates the cell is sensitive to the therapeutic agent.

    COMPOSITIONS OF TUMOR SPECIFIC NEOANTIGENS
    85.
    发明公开
    COMPOSITIONS OF TUMOR SPECIFIC NEOANTIGENS 审中-公开
    ZUSAMMENSETZUNGEN TUMORSPEZIFISCHER NEOANTIGENE

    公开(公告)号：EP3023788A1

    公开(公告)日：2016-05-25

    申请号：EP15198284.0

    申请日：2011-05-16

    申请人： The General Hospital Corporation ,  Dana-Farber Cancer Institute, Inc.

    发明人： HACOHEN, Nir ,  WU, Catherine

    IPC分类号： G01N33/53 ,  G01N33/68 ,  A61K39/395 ,  A61P35/00 ,  C12Q1/68 ,  C07K14/47 ,  G01N33/50 ,  C07K7/06

    摘要： Two or more peptides or polypeptides and an adjuvant for use in a method of inducing a tumor specific immune response, wherein the peptides or polypeptides have been identified by a method comprising:
    identifying a plurality of neoantigenic peptides for preparing a subject-specific immunogenic composition, each neoantigenic peptide comprising a tumor-specific neoepitope comprising a tumor-specific mutation, the method comprising:
    a. identifying a plurality of subject-specific tumor mutations in expressed genes of a subject having cancer by whole genome or whole exome nucleic acid sequencing of tumor and normal tissue samples from the subject, wherein the mutations are present in the genome of cancer cells of the subject but not in normal tissue from the subject;
    b. wherein when a mutation identified in step (a) is a point mutation:
    i. identifying a mutant peptide having the mutation identified in step (a), wherein said mutant peptide comprises a tumor-specific neoepitope which binds to a class I HLA protein with a greater affinity than a wild -type peptide; and has an IC50 less than 500 nm;

    c. wherein when a mutation identified in step (a) is a splice-site, frameshift, read-through or gene-fusion mutation:
    i. identifying a mutant polypeptide encoded by the mutation identified in step (a), wherein said mutant polypeptide comprises a tumor-specific neoepitope which binds to a class I HLA protein.

    摘要翻译： 两种或更多种肽或多肽和用于诱导肿瘤特异性免疫应答的方法的佐剂，其中所述肽或多肽已经通过包括以下的方法鉴定：鉴定用于制备受试者特异性免疫原性组合物的多种新抗原肽， 每个新生抗原肽包含肿瘤特异性新表位，其包含肿瘤特异性突变，所述方法包括：a。 通过对受试者的肿瘤和正常组织样品的全基因组或整个外显子核酸测序鉴定患有癌症的受试者的表达基因中的多个受试者特异性肿瘤突变，其中所述突变存在于受试者的癌细胞的基因组中 但不在受试者的正常组织中; 湾 其中当步骤（a）中鉴定的突变是点突变时： 鉴定具有步骤（a）中鉴定的突变的突变肽，其中所述突变肽包含以比野生型肽更大的亲和力结合I类HLA蛋白的肿瘤特异性新表皮; 并且具有小于500nm的IC 50; C。 其中当步骤（a）中鉴定的突变是剪接位点，移码，读通或基因融合突变时： 鉴定由步骤（a）中鉴定的突变编码的突变多肽，其中所述突变多肽包含结合I类HLA蛋白的肿瘤特异性新表皮。