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：CA2942528A1

公开(公告)日：2015-09-24

申请号：CA2942528

申请日：2015-03-20

Applicant: PHARMACYCLICS LLC

Inventor： BYRD JOHN C ,  WOYACH JENNIFER A

IPC: C12Q1/68

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.

公开(公告)号：EP3119910A4

公开(公告)日：2018-02-21

申请号：EP15764524

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 PLCγ2 polypeptide that is modified at amino acid position 742, 845, or 1140 and the modified PLCγ2 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 PLCγ2.