公开(公告)号：WO2017087947A2

公开(公告)日：2017-05-26

申请号：PCT/US2016/063085

申请日：2016-11-21

Applicant: PHARMACYCLICS LLC ,  WANG, Zhengyuang

Inventor： WANG, Zhengyuang ,  CHANG, Betty ,  CHEUNG, Leo ,  ECKERT, Karl ,  SCHWEIGHOFER, Karl ,  WU, Shiquan

IPC: A61K39/395 ,  C12Q1/68

CPC classification number: C12Q1/6886 ,  A61K31/519 ,  C12Q2600/106 ,  C12Q2600/158

Abstract: Disclosed herein are methods of treating follicular lymphoma in an individual in need thereof wherein the individual has an overexpression of one or more genes selected from CALB2, P2RY11 (PPAN-P2RY11), DNAJC8, TTC19, VCAMl, CSAG3, GP1BA, RPA1, RSC1A1, STS-1 (UBASH3B), ADPRM (C170RF48) and FILIPl, or a normal expression or underexpression of one or more genes selected from CERCAM, POM121C (LOC100131972), PPP1R3D, PLOD2, SDHA (SDHAP3), OSBPL2, HCFC1R1, and DHRS7, which method comprises administering or continuing to administer to the individual a therapeutically effective amount of ibrutinib or a pharmaceutically acceptable salt or solvate thereof.

公开(公告)号：WO2017040617A1

公开(公告)日：2017-03-09

申请号：PCT/US2016/049638

申请日：2016-08-31

Applicant: PHARMACYCLICS LLC

Inventor： BILOTTI, Elizabeth ,  GRAEF, Thorsten

IPC: A61K31/519 ,  A61K31/454 ,  A61K31/573 ,  A61K35/00

CPC classification number: A61K31/573 ,  A61K9/0053 ,  A61K9/20 ,  A61K9/48 ,  A61K31/454 ,  A61K31/519 ,  A61K2300/00

Abstract: Disclosed herein are pharmaceutical combinations, dosing regimen, and methods of administering a combination of a BTK inhibitor (e.g., ibrutinib), an immunomodulatory agent, and a steroid for the treatment of a hematologic malignancy.

Abstract translation: 本文公开了药物组合，给药方案和施用BTK抑制剂（例如伊布他丁），免疫调节剂和类固醇的组合以治疗血液恶性肿瘤的方法。

公开(公告)号：WO2016196776A3

公开(公告)日：2017-01-05

申请号：PCT/US2016035489

申请日：2016-06-02

Applicant: PHARMACYCLICS LLC

Inventor： ATALLAH GORDANA BABIC ,  CHEN WEI ,  JIA ZHAOZHONG J ,  POZZAN ALFONSO ,  RAVEGLIA LUCAL FRANCESCO ,  ZANALETTI RICCARDO

IPC: C07D403/12 ,  A61K31/497 ,  A61K31/53

CPC classification number: C07D417/14 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D471/08

Abstract: Disclosed herein are reversible and irreversible inhibitors of Bruton's tyrosine kinase (Btk). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are describeded, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract translation: 本文公开了可逆和不可逆的Bruton酪氨酸激酶（Btk）抑制剂。 还公开了包含化合物的药物组合物。 描述了使用Btk抑制剂单独或与其它治疗剂组合用于治疗自身免疫疾病或病症，异种免疫疾病或病症，癌症，包括淋巴瘤和炎性疾病或病症的方法。

公开(公告)号：WO2015143400A8

公开(公告)日：2017-01-05

申请号：PCT/US2015021871

申请日：2015-03-20

Applicant: PHARMACYCLICS LLC

Inventor： BYRD JOHN C ,  WOYACH JENNIFER A

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  A61K31/519 ,  C12Q2600/106 ,  C12Q2600/156 ,  G01N33/57426 ,  G01N2333/916 ,  G01N2800/52

Abstract: Described herein is a mutation that confers resistance to the treatment with a BTK inhibitor. Described herein is a modified PLCy2 polypeptide that is modified at amino acid position 742, 845, or 1140 and the modified PLCy2 polypeptide exhibits decreased inhibition (e.g., resistance) to a covalent and/or irreversible BTK inhibitor. Described herein are diagnostic methods for detecting the modified polypeptide and nucleic acid encoding the modified polypeptide and applications of the methods thereof. Described herein are compositions, combinations, and kits containing the modified polypeptide and methods of using the modified polypeptide. Also described herein are methods of using the modified polypeptide as screening agents for the identification and design of inhibitors of PLCy2.

Abstract translation: 本文描述了赋予对用BTK抑制剂治疗的抗性的突变。 本文描述的是在氨基酸位置742,845或1140修饰的修饰的PLCy2多肽，并且修饰的PLCy2多肽对共价和/或不可逆的BTK抑制剂表现出降低的抑制（例如抗性）。 本文描述了用于检测修饰的多肽和编码经修饰的多肽的核酸的诊断方法及其方法的应用。 本文描述的是含有修饰多肽的组合物，组合和试剂盒，以及使用修饰多肽的方法。 本文还描述了使用修饰的多肽作为用于鉴定和设计PLCy2的抑制剂的筛选剂的方法。

公开(公告)号：WO2016081460A1

公开(公告)日：2016-05-26

申请号：PCT/US2015/061091

申请日：2015-11-17

Applicant: PHARMACYCLICS LLC

Inventor： CHANG, Betty, Y. ,  BEAUPRE, Darrin ,  KUO, Hsu-ping

IPC: A61K31/519 ,  A61K31/517 ,  A61P35/00

CPC classification number: A61K31/517 ,  A61K31/519 ,  A61K45/06

Abstract: Provided are compositions for and methods of treating a B-cell malignancy in a subject in need thereof, by administering to the subject a therapeutically effective amount of a combination comprising an inhibitor of a BTK inhibitor and a TLR inhibitor.

Abstract translation: 提供了通过向受试者施用治疗有效量的包含BTK抑制剂抑制剂和TLR抑制剂的组合物的组合物和治疗有需要的受试者的B细胞恶性肿瘤的方法。

公开(公告)号：WO2016022853A1

公开(公告)日：2016-02-11

申请号：PCT/US2015/044095

申请日：2015-08-06

Applicant: PHARMACYCLICS LLC ,  BALASUBRAMANIAN, Sriram

Inventor： BALASUBRAMANIAN, Sriram ,  KUO, Hsu-Ping ,  HSIEH, Hsin-Kang ,  CHANG, Betty ,  XUE, Ling ,  CHEUNG, Leo

IPC: A61P35/02

CPC classification number: A61K31/519 ,  A61K31/4164 ,  A61K31/4196 ,  A61K31/426 ,  A61K31/454 ,  A61K31/69 ,  A61K38/005 ,  A61K38/191 ,  A61K38/2013 ,  A61K38/21 ,  A61K45/06 ,  A61K2300/00 ,  A61K38/31

Abstract: Disclosed herein are methods, compositions, and kits for treating a B-cell malignancy comprising administering a combination of a BTK inhibitor (e.g. ibrutinib) and a PIM inhibitor. Also disclosed herein are methods, compositions, and kits for treating a BTK-resistant B-cell malignancy comprising administering a combination of a BTK inhibitor (e.g. ibrutinib) and a PIM inhibitor.

Abstract translation: 本文公开了用于治疗B细胞恶性肿瘤的方法，组合物和试剂盒，其包括施用BTK抑制剂（例如伊布他丁）和PIM抑制剂的组合。 本文还公开了用于治疗BTK抗性B细胞恶性肿瘤的方法，组合物和试剂盒，其包括施用BTK抑制剂（例如伊布他丁）和PIM抑制剂的组合。

公开(公告)号：WO2016019341A1

公开(公告)日：2016-02-04

申请号：PCT/US2015/043300

申请日：2015-07-31

Applicant: PHARMACYCLICS LLC

Inventor： SCHWEIGHOFER, Karl ,  ECKERT, Karl ,  KUO, Hsu-Ping ,  CHANG, Betty ,  BEAUPRE, Darrin ,  CHEUNG, Leo

IPC: A61K31/519

CPC classification number: C12Q1/6886 ,  A61K31/519 ,  A61K31/635 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/57407 ,  G01N2333/4706 ,  G01N2333/70503 ,  G01N2333/82 ,  G01N2440/00 ,  G01N2800/52 ,  A61K2300/00

Abstract: Disclosed herein, are methods, systems, compositions, arrays, and kits for using biomarkers or biomarker genes (e.g. EP300, MLL2, BCL-2, RB1, LRP1B, PIM1, TSC2, TNFRSF11A, SMAD4, PAX5, CARD11, ACTG2, LOR, GAPT, CCND2, SELL, GEN1, HDAC9 , CD79B, MYD88, and ROS1) or biomarker gene expression levels for stratifying a patient having a hematological malignancy such as DLBCL for treatment, and administering a TEC inhibitor to selected patients. Also disclosed herein are methods, systems, compositions, arrays, and kits for using biomarkers, biomarker genes, or biomarker gene expresison levels for monitoring a patient during treatment of a hematological malignancy such as DLBCL or FL or for optimizing a treatment regimen with a TEC inhibitor.

Abstract translation: 本文公开了使用生物标志物或生物标记基因的方法，系统，组合物，阵列和试剂盒（例如EP300，MLL2，BCL-2，RB1，LRP1B，PIM1，TSC2，TNFRSF11A，SMAD4，PAX5，CARD11，ACTG2，LOR， GAPT，CCND2，SELL，GEN1，HDAC9，CD79B，MYD88和ROS1）或用于分层患有血液恶性肿瘤的患者例如DLBCL的用于治疗的生物标记基因表达水平，以及向所选患者施用TEC抑制剂。 本文还公开了用于在治疗血液恶性肿瘤例如DLBCL或FL期间用于监测患者的生物标志物，生物标志物基因或生物标记基因表达水平的方法，系统，组合物，阵列和试剂盒，或用于优化具有TEC的治疗方案 抑制剂。

公开(公告)号：WO2016019233A1

公开(公告)日：2016-02-04

申请号：PCT/US2015/043097

申请日：2015-07-31

Applicant: PHARMACYCLICS LLC

Inventor： CHEN, Wei ,  WANG, Longcheng ,  JIA, Zhaozhong, J.

IPC: A61K31/519 ,  C07D487/00 ,  A61P35/00

CPC classification number: C07D487/04 ,  A61K31/4162

Abstract: Disclosed herein are amido compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract translation: 本文公开了与Bruton酪氨酸激酶（Btk）形成共价键的酰氨基化合物。 还描述了Btk的不可逆抑制剂。 还公开了包含化合物的药物组合物。 公开了使用Btk抑制剂的方法，单独或与其它治疗剂组合用于治疗自身免疫性疾病或病症，异种免疫疾病或病症，癌症，包括淋巴瘤和炎性疾病或病症。

公开(公告)号：WO2017023815A1

公开(公告)日：2017-02-09

申请号：PCT/US2016/044916

申请日：2016-07-29

Applicant: PHARMACYCLICS LLC

Inventor： CHANG, Betty ,  CHEN, Jun ,  HSU, Ssucheng, Jeff ,  HUANG, Yujun ,  JAMES, Danelle ,  KINOSHITA, Taisei

IPC: A61K31/4162 ,  A61K31/519 ,  A61K31/436 ,  A61P35/00

CPC classification number: A61K31/519 ,  A61K31/337 ,  A61K31/436 ,  A61K31/506 ,  A61K39/3955 ,  A61K45/06 ,  C07K16/2863 ,  C07K2317/24 ,  C07K2317/76 ,  A61K2300/00

Abstract: Disclosed are compositions, methods, and kits for treating a solid tumor comprising co-administering to an individual in need thereof a BTK inhibitor and an mTOR inhibitor; a taxane, or an EGFR inhibitor.

Abstract translation: 公开了用于治疗实体瘤的组合物，方法和试剂盒，其包括向有需要的个体共同施用BTK抑制剂和mTOR抑制剂; 紫杉烷或EGFR抑制剂。

公开(公告)号：WO2016161054A1

公开(公告)日：2016-10-06

申请号：PCT/US2016/025124

申请日：2016-03-31

Applicant: PHARMACYCLICS LLC

Inventor： SCHOENMAKERS, Henricus Franciscus Petrus, Maria

IPC: C12Q1/68 ,  C12N15/09

CPC classification number: C12N15/09 ,  C12N15/1031 ,  C12Q1/68 ,  C12Q1/6853 ,  C12Q2525/161 ,  C12Q2525/197 ,  C12Q2531/113 ,  C12Q2537/143 ,  C12Q2537/159

Abstract: The present invention provides methods and compositions for parallel single cell-based multiplexed primer dimer-mediated amplification of multiple target sequences in complex cell mixtures. The invention provides primer dimer-mediated concatenation of multiple targets in multi-target fusion amplicon products for evaluation of two or more target sequences as present individual cells across a population or mixture of cells.

Abstract translation: 本发明提供了用于复杂细胞混合物中多个靶序列的并行单细胞复合引物二聚体介导扩增的方法和组合物。 本发明提供了多靶标融合扩增子产物中多个靶点的引物二聚体介导的连接，用于评估两个或更多个目标序列作为跨细胞群体或混合物存在的个体细胞。