公开(公告)号：US11458138B2

公开(公告)日：2022-10-04

申请号：US15963816

申请日：2018-04-26

Applicant: Novartis AG

Inventor： Dirk Behnke ,  Frada Berenshteyn ,  Xueshi Hao ,  Timothy Hoffman ,  Qihui Jin ,  Arnaud Lacoste ,  Cameron Lee ,  Jun Liu ,  Yahu Liu ,  Juergen Klaus Maibaum ,  Tingting Mo ,  Jianfeng Pan ,  Xin Qu ,  Jan Tchorz ,  Yun Feng Xie ,  Shanshan Yan ,  Yefen Zou

IPC: A61K31/4375 ,  A61K31/519 ,  C07D487/04 ,  C12N5/079 ,  C07D519/00 ,  A61P17/02 ,  A61K9/00 ,  A61K31/47 ,  A61K31/506 ,  A61K35/30 ,  C12N15/52 ,  C12N15/864

Abstract: The present invention is related to 6-6 Fused Bicyclic Heteroaryl Compounds of the Formula A2 or A1 and their Use as LATS Inhibitors, or a salt, stereoisomer or pharmaceutical composition thereof; wherein the variables are as defined herein. The present invention further relates to a method of LATS inhibition in a cell population using a compound of Formula A1, or a salt, stereoisomer or pharmaceutical composition thereof. The present invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, their use in the treatment and management of diseases or disorders.

公开(公告)号：US20150125857A1

公开(公告)日：2015-05-07

申请号：US14380776

申请日：2013-02-22

Applicant: NOVARTIS AG

Inventor： Feng Cong ,  Huaixiang Hao ,  Mindy Hsin-I Hsieh ,  Xiaomo Jiang ,  Jun Liu ,  Nicholas Ng

IPC: C12Q1/68 ,  G01N33/574 ,  A61K31/497

CPC classification number: C12Q1/6886 ,  A61K31/497 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/57438 ,  G01N33/57492 ,  G01N2800/52

Abstract: Disclosed are biomarkers, methods and assay for the identification of cancer patients who are predicted to benefit from the therapeutic administration of Wnt antagonist. The biomarkers include detection of RNF43 and ZNRF3 gene deletion, reduced RNF43 and ZNRF3 mRNA expression, reduced RNF43 and ZNRF3 protein expression, RNF43 and ZNRF3 inactivation mutation, phosphorylated LRP6, phophorylated Dishevelleds, and the expression of Frizzleds. These biomarkers can be associated with the better outcome for cancer patients treated with Wnt pathway inhibitors.

Abstract translation: 公开了预测从Wnt拮抗剂的治疗施用中受益的癌症患者的鉴定的生物标志物，方法和测定。 生物标志物包括RNF43和ZNRF3基因缺失的检测，RNF43和ZNRF3 mRNA表达的降低，RNF43和ZNRF3蛋白表达的降低，RNF43和ZNRF3失活突变，磷酸化的LRP6，磷酸化的Dishevelleds和Frizzleds的表达。 这些生物标志物可以与用Wnt途径抑制剂治疗的癌症患者的更好的结果相关联。

公开(公告)号：US10034940B2

公开(公告)日：2018-07-31

申请号：US14599301

申请日：2015-01-16

Applicant: GENENTECH, INC. ,  Novartis AG

Inventor： Jun Liu ,  Steven J. Shire

IPC: A61K39/395 ,  A61K9/00 ,  A61K47/18 ,  A61K47/26 ,  C07K16/42 ,  A61K45/06 ,  A61K47/22 ,  A61K9/08 ,  A61M5/20 ,  A61K39/00

CPC classification number: A61K39/39591 ,  A61K9/0019 ,  A61K9/08 ,  A61K39/39566 ,  A61K45/06 ,  A61K47/183 ,  A61K47/22 ,  A61K47/26 ,  A61K2039/505 ,  A61M5/20 ,  C07K16/4291 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/94 ,  Y10S435/80

Abstract: The present application relates to highly concentrated antibody and protein formulations with reduced viscosity that are stable, relatively isotonic and are of low turbidity. The formulations are particularly suitable for subcutaneous administration. The application further describes articles of manufacture containing such formulations and method for using them to treat disorders treatable by the formulated antibody or protein.

公开(公告)号：US10166293B2

公开(公告)日：2019-01-01

申请号：US14201346

申请日：2014-03-07

Applicant: Genentech, Inc. ,  Novartis AG

Inventor： Jun Liu ,  Steven J. Shire

IPC: A61K47/02 ,  A61K39/395 ,  C07K16/42 ,  A61K9/19 ,  A61K39/00

Abstract: The present application concerns concentrated protein formulations with reduced viscosity, which are particularly suitable for subcutaneous administration. The application further concerns a method for reducing the viscosity of concentrated protein formulations.