公开(公告)号：WO2015066432A8

公开(公告)日：2015-10-29

申请号：PCT/US2014063353

申请日：2014-10-31

Applicant: FOUNDATION MEDICINE INC ,  SLOAN KETTERING INST CANCER

Inventor： HAWRYLUK MATTHEW J ,  MILLER VINCENT A ,  STEPHENS PHILIP JAMES ,  WANG KAI ,  ABDEL-WAHAB OMAR ,  LEVINE ROSS ,  RAMPAL RAAJIT ,  VAN DEN BRINK MARCEL

IPC: C12Q1/68 ,  C07K16/00 ,  G01N33/00 ,  G01N33/574

CPC classification number: G01N33/57426 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158

Abstract: Methods and compositions for treating post-myeloproliferative neoplasm acute myeloid leukemia are disclosed.

Abstract translation: 公开了用于治疗骨髓增生性肿瘤急性骨髓性白血病的方法和组合物。

公开(公告)号：WO2014144573A3

公开(公告)日：2015-10-29

申请号：PCT/US2014029041

申请日：2014-03-14

Applicant: SLOAN KETTERING INST CANCER

Inventor： AHMED MAHIUDDIN ,  CHEUNG NAI-KONG V

IPC: A61K39/395

CPC classification number: C07K14/47 ,  A61K38/1709 ,  A61K39/3955 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/2809 ,  C07K16/30 ,  C07K16/3053 ,  C07K16/3084 ,  C07K16/468 ,  C07K2317/14 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/92 ,  C07K2319/74

Abstract: The present invention provides, among other things, dimeric multispecific binding agents (e.g., fusion proteins comprising antibody components) that have improved properties over multispecific binding agents without the capability of dimerization. In certain embodiments, provided agents are comprised of individual polypeptides, each of which includes at least one, and more commonly at least two or more binding moieties that specifically interact with a particular target. In many embodiments, such polypeptides include a dimerization component. In many embodiments, the dimerization component is an element of human hepafocyte nuclear factor-1 alpha.

Abstract translation: 除其他之外，本发明提供了具有比不具有二聚化能力的多特异性结合剂改善的性质的二聚多特异性结合剂（例如，包含抗体组分的融合蛋白）。 在某些实施方案中，所提供的试剂由单个多肽组成，每个多肽包括与特定靶标特异性相互作用的至少一个，更通常至少两个或更多个结合部分。 在许多实施方案中，这些多肽包括二聚化组分。 在许多实施方案中，二聚化成分是人肝细胞核因子-1α的元件。

公开(公告)号：WO2014158811A8

公开(公告)日：2015-09-17

申请号：PCT/US2014020299

申请日：2014-03-04

Applicant: ICAHN SCHOOL MED MOUNT SINAI ,  SLOAN KETTERING INST CANCER

Inventor： PALESE PETER ,  GARCIA-SASTRE ADOLFO ,  ZAMARIN DMITRIY ,  ALLISON JAMES ,  WOLCHOK JEDD D

IPC: A61K39/17 ,  A61P35/00 ,  C12N15/09

CPC classification number: A61K35/768 ,  A61K39/3955 ,  A61K2039/505 ,  C07K16/2818 ,  C07K16/2827 ,  C07K16/2878 ,  C07K2317/76 ,  C12N7/00 ,  C12N2760/18121 ,  C12N2760/18122 ,  C12N2760/18132 ,  C12N2760/18133 ,  C12N2760/18143

Abstract: Described herein are chimeric Newcastle disease viruses engineered to express an agonist of a co-stimulatory signal of an immune cell and compositions comprising such viruses. Also described herein are chimeric Newcastle disease viruses engineered to express an antagonist of an inhibitory signal of an immune cell and compositions comprising such viruses. The chimeric Newcastle disease viruses and compositions are useful in the treatment of cancer. In addition, described herein are methods for treating cancer comprising administering Newcastle disease viruses in combination with an agonist of a co-stimulatory signal of an immune and/or an antagonist of an inhibitory signal of an immune cell.

Abstract translation: 本文描述了工程化表达免疫细胞的共刺激信号的激动剂的嵌合式新城疫病毒和包含这种病毒的组合物。 本文还描述了被工程化以表达免疫细胞的抑制信号的拮抗剂的嵌合的新城疫病毒和包含这种病毒的组合物。 嵌合的新城疫病毒和组合物可用于治疗癌症。 此外，本文描述了治疗癌症的方法，其包括将新城疫病毒与免疫细胞的免疫和/或拮抗剂的共刺激信号的激动剂组合施用于免疫细胞的抑制信号。

公开(公告)号：WO2015100113A2

公开(公告)日：2015-07-02

申请号：PCT/US2014070970

申请日：2014-12-17

Applicant: SLOAN KETTERING INST CANCER

Inventor： ROTHMAN JEFFREY K ,  SCHWARTZ GARY K

IPC: A61K48/00

CPC classification number: C12N15/1135 ,  A61K38/00 ,  C07K14/003 ,  C12N2310/3181 ,  C12N2310/3513 ,  C12N2310/3515 ,  C12N2310/531 ,  C12N2320/30 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/5748 ,  G01N2500/10

Abstract: The present invention provides compositions and methods for treating cancer with peptide nucleic acid agents. In some embodiments, the present invention provides methods and compositions relating to peptide nucleic acid agents that target oncogenes. For example, the present invention provides compositions, including pharmaceutical compositions, comprising agents specific for BRAF V600E inhibition, or fragments or characteristic portions thereof. The present invention further provides various therapeutic and/or diagnostic methods of using BRAF V600E specific peptide nucleic acid agents and/or compositions.

Abstract translation: 本发明提供了用肽核酸剂治疗癌症的组合物和方法。 在一些实施方案中，本发明提供涉及靶向致癌基因的肽核酸试剂的方法和组合物。 例如，本发明提供包含药物组合物的组合物，其包含对BRAF V600E抑制特异的试剂或其片段或特征部分。 本发明还提供了使用BRAF V600E特异性肽核酸试剂和/或组合物的各种治疗和/或诊断方法。

公开(公告)号：WO2015089338A2

公开(公告)日：2015-06-18

申请号：PCT/US2014069854

申请日：2014-12-11

Applicant: SLOAN KETTERING INST CANCER

Inventor： ARORA VIVEK ,  SAWYERS CHARLES L ,  EVANS MICHAEL J ,  VEACH DARREN R

IPC: A61K31/573

CPC classification number: C07J17/00 ,  A61K31/416 ,  A61K31/4166 ,  A61K31/4439 ,  A61K31/5375 ,  A61K31/573 ,  A61K31/575 ,  A61K31/58 ,  A61K31/7105 ,  A61K31/713 ,  A61K45/06 ,  C07J9/00 ,  C07J43/003 ,  G01N33/743 ,  A61K2300/00

Abstract: The present invention encompasses the recognition that reproducible and detectable changes in the level and or activity of Glucocorticoid Receptor (GR) are associated with incidence and/or risk of Castration Resistant Prostate Cancer (CRPC) and/or doubly resistant prostate cancer, specifically in individuals having prostate cancer and on antiandrogen therapy, and provides for the use of GR inhibitors to treat and/or reduce risk of CRPC and/or doubly resistant prostate cancer. In some embodiments, GR inhibitors also have Androgen Receptor (AR) inhibitory activity or are administered in conjunction with AR inhibitors. The present invention also provides technologies for identification and/or characterization of agents to treat and/or reduce risk of CRPC and/or doubly resistant prostate cancer; in some embodiments such agents alter level and/or activity of a GR. In some embodiments, provided agents show effects on a GR's activity of regulating transcription of one or more target genes. The present invention also provides systems for using such agents, for example to treat and/or reduce risk of CRPC and/or doubly resistant prostate cancer.

Abstract translation: 本发明包括认识到糖皮质激素受体（GR）的水平和或活性的可重现和可检测的改变与去势抵抗性前列腺癌（CRPC）和/或双重抗性前列腺癌（特别是在个体中）的发病率和/或风险相关 患有前列腺癌和抗雄激素疗法，并且提供GR抑制剂用于治疗和/或降低CRPC和/或双重抗性前列腺癌的风险的用途。 在一些实施方案中，GR抑制剂还具有雄激素受体（AR）抑制活性或与AR抑制剂联合施用。 本发明还提供了用于鉴定和/或表征治疗和/或降低CRPC和/或双重抗性前列腺癌风险的药剂的技术; 在一些实施方案中，这样的试剂改变GR的水平和/或活性。 在一些实施方案中，提供的试剂显示对GR调节一种或多种靶基因转录的活性的作用。 本发明还提供了使用这些药剂的系统，例如用于治疗和/或降低CRPC和/或双重抗性前列腺癌的风险。

公开(公告)号：WO2015035146A3

公开(公告)日：2015-04-23

申请号：PCT/US2014054263

申请日：2014-09-05

Applicant: SLOAN KETTERING INST CANCER

Inventor： AMBROSINI GRAZIA ,  KHANIN RAYA ,  CARVAJAL RICHARD ,  SCHWARTAZ GARY K

IPC: C12Q1/68 ,  G01N33/53

CPC classification number: C12Q1/6886 ,  A61K31/4184 ,  A61K31/4375 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/5743 ,  G01N2333/914

Abstract: The present invention relates to methods and compositions for determining the likelihood that a subject suffering from a cancer will benefit from treatment with a MEK inhibitor. It also relates to methods of treatment based on such determination. The invention is based, at least in part, on the discoveries that DDX43 mRNA and protein are expressed at high levels in biopsies from "non-responder" UM patients and that selumetinib-resistant cell lines showed high DDX43 expression which correlated with increased expression and activity of RAS. It was found that KRAS and HRAS but not NRAS, mediated expression of pERK and pAKT, bypassing oncogenic GNAQ. The invention is further based on the discovery that selumetinib-resistant cells became sensitive to AKT inhibition, suggesting alternative strategies for the treatment of cancer patients with acquired resistance to MEK inhibitors.

Abstract translation: 本发明涉及用于确定患有癌症的受试者将受益于用MEK抑制剂治疗的可能性的方法和组合物。 它还涉及基于这种测定的治疗方法。 本发明至少部分地基于DDX43 mRNA和蛋白质在来自“无应答者”UM患者的活组织检查中以高水平表达的发现，并且所述selumetinib抗性细胞系显示高DDX43表达，其与增加的表达相关，并且 RAS的活动。 发现KRAS和HRAS而不是NRAS介导pERK和pAKT的表达，绕过致癌GNAQ。 本发明进一步基于以下发现：硒胺素抗性细胞对AKT抑制变得敏感，这表明用于治疗对MEK抑制剂具有获得性抗性的癌症患者的替代策略。

公开(公告)号：WO2012149493A3

公开(公告)日：2014-05-08

申请号：PCT/US2012035690

申请日：2012-04-27

Applicant: SLOAN KETTERING INST CANCER ,  CHIOSIS GABRIELA

Inventor： CHIOSIS GABRIELA

IPC: G01N33/574 ,  C12Q1/68

CPC classification number: G01N33/5748 ,  A61K31/52 ,  A61K45/06 ,  G01N33/5011 ,  G01N33/5041 ,  A61K2300/00

Abstract: This disclosure concerns a method for selecting an inhibitor of a cancer-implicated pathway or of a component thereof for coadministration with an inhibitor of HSP90 the method comprising: (a) contacting a sample containing cancer cells from a subject with an inhibitor of HSP90 under conditions such that one or more cancer pathway components present in the sample bind to the HSP90 inhibitor; (b) detecting pathway components bound to the HSP90 inhibitor; (c) analyzing the pathway components detected in step (b) so as to identify a pathway which includes the components detected in step (b) and additional components of such pathway; and (d) selecting an inhibitor of the pathway or of a pathway component identified in step (c). The disclosure further concerns a method of treating a cancer patient by co administering an inhibitor of HSP90 and an inhibitor of a cancer-implicated pathway or component thereof.

Abstract translation: 本公开涉及选择与癌症相关途径的抑制剂或其组分与HSP90抑制剂共同施用的方法，所述方法包括：（a）在条件下使来自受试者的含有癌细胞的样品与HSP90的抑制剂接触 使样品中存在的一种或多种癌症途径成分与HSP90抑制剂结合; （b）检测与HSP90抑制剂结合的途径成分; （c）分析在步骤（b）中检测的途径组分，以便鉴定包含步骤（b）中检测到的组分和该途径的其它组分的途径; 和（d）选择步骤（c）中鉴定的途径或途径成分的抑制剂。 本公开还涉及通过共同施用HSP90的抑制剂和癌症相关途径的抑制剂或其组分来治疗癌症患者的方法。

公开(公告)号：WO2014066799A2

公开(公告)日：2014-05-01

申请号：PCT/US2013066875

申请日：2013-10-25

Applicant: SLOAN KETTERING INST CANCER

Inventor： BALBAS MINNA D ,  EVANS MICHAEL J ,  SAWYERS CHARLES L ,  SHEN YANG ,  HOSFIELD DAVID ,  GREENE GEOFFREY L

IPC: A61K31/4747

CPC classification number: C07D401/04 ,  C07D233/86 ,  C07D235/02

Abstract: The present invention provides compounds useful as modulators, agonists or antagonists of androgen receptor (AR), compositions thereof, and methods of making and using the same.

Abstract translation: 本发明提供可用作雄激素受体（AR）的调节剂，激动剂或拮抗剂的化合物，其组合物及其制备和使用方法。

公开(公告)号：WO2012088298A3

公开(公告)日：2014-04-10

申请号：PCT/US2011066549

申请日：2011-12-21

Applicant: SLOAN KETTERING INST CANCER ,  CHAN TIMOTHY ,  FANG FANG ,  TURCAN SEVIN

Inventor： CHAN TIMOTHY ,  FANG FANG ,  TURCAN SEVIN

IPC: G01N33/48

CPC classification number: C12Q1/6886 ,  C12Q2600/118 ,  C12Q2600/154

Abstract: Methods and kits for assessing risk of metastasis in a cancer patient identified as having breast cancer, colon cancer or glioma use analysis of a classifier for CpG island methylator phenotype.

Abstract translation: 鉴定为具有乳腺癌，结肠癌或神经胶质瘤的癌症患者的转移风险的方法和试剂盒，用于分析CpG岛甲基化表型的分析。

公开(公告)号：WO2013166053A3

公开(公告)日：2014-02-27

申请号：PCT/US2013038923

申请日：2013-04-30

Applicant: SLOAN KETTERING INST CANCER

Inventor： DANISHEFSKY SAMUEL J ,  WANG PING ,  DONG SUWEI ,  MOORE MALCOLM ANDREW STEPHEN ,  SHIEH JAE-HUNG ,  BRAILSFORD JOHN ANDREW

IPC: C07K14/505

CPC classification number: C07K14/505 ,  G01N33/746

Abstract: The present invention provides homogenously glycosylated erythropoietin and the methods of preparing the same. In some embodiments, the present invention provides a composition of homogeneously glycosylated erythropoietin. In some embodiments, the present invention provides a composition of homogeneous, fully glycosylated erythropoietin. In some embodiments, the present invention provides methods for preparing a composition of homogenously glycosylated erythropoietin. In some embodiments, the present invention provides methods for preparing a composition of homogeneous, fully glycosylated erythropoietin. In some embodiments, the present invention provides methods for preparing a composition of homogeneous, fully glycosylated full-length erythropoietin. In some embodiments, the present invention provides methods for preparing a composition of, homogeneous, fully glycosylated full-length erythropoietin through chemical synthesis.

Abstract translation: 本发明提供均匀的糖基化促红细胞生成素及其制备方法。 在一些实施方案中，本发明提供均匀糖基化促红细胞生成素的组合物。 在一些实施方案中，本发明提供均匀的，完全糖基化的促红细胞生成素的组合物。 在一些实施方案中，本发明提供了制备均匀糖基化促红细胞生成素组合物的方法。 在一些实施方案中，本发明提供了制备均匀的，完全糖基化的促红细胞生成素的组合物的方法。 在一些实施方案中，本发明提供了制备均匀，完全糖基化的全长促红细胞生成素组合物的方法。 在一些实施方案中，本发明提供了通过化学合成制备均匀的完全糖基化的全长促红细胞生成素的组合物的方法。