公开(公告)号：EP2099442A1

公开(公告)日：2009-09-16

申请号：EP07869059.1

申请日：2007-12-07

申请人： PHARMACYCLICS, INC.

发明人： ADIMOOLAM, Shanthi ,  BUGGY, Joseph, J. ,  MAGDA, Darren ,  MILLER, Richard

IPC分类号： A61K31/16 ,  A61K31/166 ,  A61P35/00

CPC分类号： A61K31/164 ,  A61K31/343 ,  A61K31/40 ,  A61K31/4525 ,  A61K45/06 ,  A61K2300/00

摘要： Provided herein are methods for using at least one histone deacetylase inhibitor to decrease cellular DNA repair activity, methods for monitoring the decrease of cellular DNA repair activity using at least one biomarker, methods of treating cancer by using at least one histone deacetylase inhibitor to decrease cellular DNA repair activity in combination therapy, methods of combination therapy where at least one histone deacetylase inhibitor interferes with a DNA repairing mechanism involving RAD51, methods for predicting a induction time period between a first administration of at least one histone deacetylase inhibitor and a second administration of at least one other therapeutic treatment, and pharmaceutical compositions for combination therapy.

公开(公告)号：EP2139487A2

公开(公告)日：2010-01-06

申请号：EP08744513.6

申请日：2008-03-27

申请人： Pharmacyclics, Inc.

发明人： HONIGBERG, Lee ,  VERNER, Erik ,  BUGGY, Joseph, J. ,  LOURY, David ,  CHEN, Wei

IPC分类号： A61K31/52 ,  A61P29/00 ,  A61P35/00 ,  A61K31/519 ,  C07D253/06 ,  C07D487/04 ,  C07D473/34

CPC分类号： C07D487/04 ,  A61K31/52 ,  C07D471/04 ,  C12Q1/485 ,  G01N33/57426 ,  G01N2440/14 ,  G01N2500/00

摘要： Described herein are irreversible kinase inhibitor compounds, methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate irreversible inhibitor of a protein, including a kinase.

摘要翻译： 本文描述的是不可逆的激酶抑制剂化合物，合成这种不可逆抑制剂的方法，以及使用这种不可逆抑制剂治疗疾病的方法。 本文进一步描述了用于确定蛋白质（包括激酶）的适当不可逆抑制剂的方法，测定和系统。

公开(公告)号：EP2265590A2

公开(公告)日：2010-12-29

申请号：EP09733489.0

申请日：2009-04-15

申请人： PHARMACYCLICS, INC.

发明人： VERNER, Erik ,  BALASUBRAMANIAN, Sriram ,  BUGGY, Joseph, J.

IPC分类号： C07D235/06 ,  C07D235/08 ,  C07D235/10 ,  C07D235/12 ,  C07D235/14

CPC分类号： A61K45/06 ,  A61K31/40 ,  A61K31/404 ,  A61K31/4439 ,  A61K31/5377 ,  C07D207/337 ,  C07D209/08 ,  C07D209/12 ,  C07D209/14 ,  C07D235/06 ,  C07D307/79 ,  C07D307/80 ,  C07D333/54 ,  C07D333/56 ,  C07D401/06 ,  C07D401/12 ,  C07D405/06 ,  C07D409/06 ,  C07D471/04 ,  Y02A50/40

摘要： Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of HDAC8 activity.

公开(公告)号：EP2144622A1

公开(公告)日：2010-01-20

申请号：EP08745659.6

申请日：2008-04-11

申请人： PHARMACYCLICS, INC.

发明人： BALASUBRAMANIAN, Sriram ,  BUGGY, Joseph, J. ,  RAMOS, Jason ,  SIRISAWAD, Mint

IPC分类号： A61K38/18

CPC分类号： G01N33/57438 ,  G01N33/6872 ,  G01N33/84 ,  G01N2800/52

摘要： Described herein are methods for using calcium flux as a biomarker to select and predict patients likely to respond to an apoptotic agent as therapy. Further described herein is a method of using calcium flux as a clinical biomarker to determine whether a tumor is sensitive to an HDAC inhibitor.

摘要翻译： 本文描述了使用钙通量作为生物标志物以选择和预测可能对作为治疗的凋亡剂作出反应的患者的方法。 本文进一步描述了使用钙通量作为临床生物标志物以确定肿瘤是否对HDAC抑制剂敏感的方法。

公开(公告)号：EP2877598A1

公开(公告)日：2015-06-03

申请号：EP13745948.3

申请日：2013-07-23

申请人： Pharmacyclics, Inc.

发明人： CHANG, Betty, Y. ,  BUGGY, Joseph, J. ,  STEGGERDA, Susanne, M.

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  A61K31/505 ,  A61K31/506 ,  A61K31/519 ,  A61K31/52 ,  A61K45/06 ,  C07K14/00 ,  C12N9/12 ,  C12N9/16 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/16 ,  C12Y207/10002 ,  C12Y301/04011 ,  G01N33/5041

摘要： Described herein are mutations that confer resistance to treatment with a BTK inhibitor. Described herein are modified BTK polypeptides that exhibit decreased inhibition (i.e. are resistant) to a covalent and/or irreversible BTK inhibitor. Also described herein modifications of PLCy2 and CARD 11 polypeptides that confer resistance to treatment with a BTK inhibitor. Described herein are diagnostic methods for detecting the modified polypeptides and nucleic acids encoding the modified polypeptides and applications of the methods thereof. Described herein are compositions, combinations, and kits containing the modified polypeptides and methods of using the modified polypeptides. Also described herein are methods of using modified BTK polypeptides as screening agents for the identification and design of second- generation BTK inhibitors.

摘要翻译： 本文描述了赋予对用BTK抑制剂治疗的抗性的突变。 本文描述的是对共价和/或不可逆的BTK抑制剂表现出降低的抑制（即抗性）的修饰的BTK多肽。 本文还描述了赋予对用BTK抑制剂治疗抗性的PLCy2和CARD11多肽的修饰。 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，以及使用经修饰的多肽的方法。 本文还描述了使用修饰的BTK多肽作为用于鉴定和设计第二代BTK抑制剂的筛选剂的方法。

公开(公告)号：EP2099442B1

公开(公告)日：2014-11-19

申请号：EP07869059.1

申请日：2007-12-07

申请人： PHARMACYCLICS, INC.

发明人： ADIMOOLAM, Shanthi ,  BUGGY, Joseph, J. ,  MAGDA, Darren ,  MILLER, Richard

IPC分类号： A61K31/164 ,  A61K31/343 ,  A61K31/40 ,  A61K31/4525 ,  A61K45/06 ,  A61P35/00

CPC分类号： A61K31/164 ,  A61K31/343 ,  A61K31/40 ,  A61K31/4525 ,  A61K45/06 ,  A61K2300/00

公开(公告)号：EP2914263A1

公开(公告)日：2015-09-09

申请号：EP13850097.0

申请日：2013-11-01

申请人： Pharmacyclics, Inc.

发明人： BUGGY, Joseph, J. ,  MODY, Tarak ,  LOVE, Richard, B. ,  BYRD, John, C. ,  CHANG, Betty ,  DUBOVSKY, Jason, A. ,  MUTHUSAMY, Natarajan ,  JOHNSON, Amy, Jo

IPC分类号： A61K31/505 ,  A61K38/20 ,  A61P35/00

CPC分类号： A61K31/519 ,  A61K45/06 ,  A61K2300/00

摘要： Described herein are methods and compositions comprising a covalent TEC family kinase inhibitor for use in adjuvant therapy, including adjuvant cancer therapy, vaccination and treatment of immune disorders and pathogenic infections.

摘要翻译： 本文描述了包含用于辅助治疗的共价TEC家族激酶抑制剂的方法和组合物，包括辅助癌症治疗，疫苗接种和治疗免疫疾病和致病性感染。

公开(公告)号：EP2755648A1

公开(公告)日：2014-07-23

申请号：EP11872389.9

申请日：2011-09-13

申请人： Pharmacyclics, Inc. ,  Les Laboratoires Servier SAS

发明人： LOURY, David, J. ,  BUGGY, Joseph, J. ,  MODY, Tarak, D. ,  VERNER, Erik, J. ,  PURRO, Norbert ,  BALASUBRAMANIAN, Sriram ,  KLOOS, Ioana ,  DEPIL, Stéphane

IPC分类号： A61K31/343 ,  A61K31/166 ,  A61K31/16 ,  A61P35/00

CPC分类号： A61K31/343 ,  A61K9/14 ,  A61K9/28 ,  A61K9/70 ,  A61K31/4184 ,  A61K2300/00

摘要： Dosing regimens, methods of treatment, controlled release formulations, and combination therapies that include bendamustine, or a pharmaceutically acceptable salt thereof and an HDAC inhibitor, or a pharmaceutically acceptable salt thereof, are described.

公开(公告)号：EP2575818A2

公开(公告)日：2013-04-10

申请号：EP11790524.0

申请日：2011-06-03

申请人： Pharmacyclics, Inc.

发明人： BUGGY, Joseph, J. ,  ELIAS, Laurence ,  FYFE, Gwen ,  HEDRICK, Eric ,  LOURY, David, J. ,  MODY, Tarak, D.

IPC分类号： A61K31/519 ,  A61K31/505 ,  A61P35/02 ,  A61P35/00

CPC分类号： A61K31/519 ,  A61K9/0014 ,  A61K9/0031 ,  A61K9/0048 ,  A61K9/0056 ,  A61K9/007 ,  A61K9/06 ,  A61K31/195 ,  A61K31/337 ,  A61K31/4184 ,  A61K31/436 ,  A61K31/437 ,  A61K31/454 ,  A61K31/4745 ,  A61K31/475 ,  A61K31/573 ,  A61K31/606 ,  A61K31/664 ,  A61K31/675 ,  A61K31/69 ,  A61K31/7032 ,  A61K31/704 ,  A61K31/7076 ,  A61K39/395 ,  A61K39/39533 ,  A61K39/3955 ,  A61K45/06 ,  C07D487/04 ,  A61K2300/00

摘要： Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.

公开(公告)号：EP2107911A1

公开(公告)日：2009-10-14

申请号：EP08728620.9

申请日：2008-01-30

申请人： PHARMACYCLICS, INC.

发明人： BUGGY, Joseph, J. ,  BALASUBRAMANIAN, Sriram

IPC分类号： A61K49/00 ,  C12Q1/68 ,  G01N33/574

CPC分类号： C12Q1/6886 ,  C07H21/04 ,  C12N5/0693 ,  C12N15/11 ,  C12N2503/02 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/136 ,  C12Q2600/158 ,  C12Q2600/16 ,  G01N33/57419 ,  G01N33/57492 ,  G01N2800/52

摘要： [00153] Described herein are methods and compositions for determining whether a particular cancer is resistant to or susceptible to a histone deacetylase inhibitor or to histone deacetylase inhibitors. The methods include analysis of the expression levels of at least four biomarker genes associated with response to a histone deacetylase inhibitor. Also described herein are methods and compositions for increasing the likelihood of a therapeutically effective treatment in a patient, comprising an analysis of the expression levels of at least four biomarker genes associated with response to a histone deacetylase inhibitor. Also described herein are isolated populations of nucleic acids derived from a cancer sensitive to or resistant to a histone deacetylase inhibitor. Further described are kits and indications that are used in conjunction with the aforementioned methods and compositions.