公开(公告)号：US20180344738A1

公开(公告)日：2018-12-06

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: A61K31/519 ,  A61K9/00 ,  A61K31/4375 ,  A61K31/506 ,  A61K31/47

CPC classification number: C07D519/00 ,  A61K35/30 ,  A61P17/02 ,  C07D487/04 ,  C12N5/0621

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：US20170306409A1

公开(公告)日：2017-10-26

申请号：US15385088

申请日：2016-12-20

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.

公开(公告)号：US20230190751A1

公开(公告)日：2023-06-22

申请号：US17820613

申请日：2022-08-18

Applicant: Novartis AG

Inventor： Dirk BEHNKE ,  Frada BERENSHTEYN ,  Xueshi HAO ,  Timothy Z. HOFFMAN ,  Qihui JIN ,  Arnaud LACOSTE ,  Cameron LEE ,  Jun LIU ,  Yahu A. LIU ,  Juergen Klaus MAIBAUM ,  Tingting MO ,  Jianfeng PAN ,  Xin QU ,  Jan TCHORZ ,  Yun Feng XIE ,  Shanshan YAN ,  Yefen ZOU

IPC: A61K31/519 ,  C07D487/04 ,  C12N5/079 ,  C07D519/00 ,  A61P17/02 ,  A61K9/00 ,  A61K31/4375 ,  A61K31/47 ,  A61K31/506

CPC classification number: A61K31/519 ,  C07D487/04 ,  C12N5/0621 ,  C07D519/00 ,  A61P17/02 ,  A61K9/0048 ,  A61K31/4375 ,  A61K31/47 ,  A61K31/506 ,  A61K35/30

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：US20160367675A1

公开(公告)日：2016-12-22

申请号：US15253571

申请日：2016-08-31

Applicant: Genentech, Inc. ,  Novartis AG

Inventor： Jun LIU ,  Steven J. SHIRE

IPC: A61K47/02 ,  A61K9/19 ,  A61K39/395

CPC classification number: A61K47/02 ,  A61K9/19 ,  A61K39/39566 ,  A61K39/39591 ,  A61K2039/505 ,  C07K16/4291

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

Abstract translation: 本申请涉及具有降低粘度的浓缩蛋白质制剂，其特别适用于皮下给药。 该应用还涉及降低浓缩蛋白质制剂的粘度的方法。

公开(公告)号：US20190231875A1

公开(公告)日：2019-08-01

申请号：US16198171

申请日：2018-11-21

Applicant: Genentech, Inc. ,  Novartis AG

Inventor： Jun LIU ,  Steven J. SHIRE

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

CPC classification number: A61K47/02 ,  A61K9/19 ,  A61K39/39566 ,  A61K39/39591 ,  A61K2039/505 ,  C07K16/4291

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.

公开(公告)号：US20230348852A1

公开(公告)日：2023-11-02

申请号：US17997223

申请日：2021-04-26

Applicant: NOVARTIS AG ,  INTELLIA THERAPEUTICS, INC.

Inventor： Frada BERENSHTEYN ,  Bo HAN ,  Xueshi HAO ,  Jessica HEYDER ,  Timothy Z. HOFFMAN ,  Qihui JIN ,  Arnaud LACOSTE ,  Jun LIU ,  Yahu LIU ,  Tingting MO ,  Bradley Andrew MURRAY ,  Daniel Joseph O’CONNELL ,  Jianfeng PAN ,  Yun Feng XIE ,  Shanshan YAN ,  Yefen ZOU

IPC: A61P27/02 ,  C12N5/079 ,  C12N9/22

CPC classification number: C12N5/0621 ,  A61P27/02 ,  C12N9/22 ,  C12N2310/20 ,  C12N2501/999

Abstract: The present invention provides ocular cells, genetically modified by a CRISPR system targeting the expression of B2M for ocular cell therapy. The invention further provides methods of generating an expanded population of genetically modified ocular cells, for example limbal stem cells (LSCs) or corneal endothelial cells (CECs), wherein the cells are expanded involving the use of a LATS inhibitor and the expression of B2M in the cells has been reduced or eliminated. The present invention also provides cell populations, preparations, uses and methods of therapy comprising said cells.

公开(公告)号：US20200306244A1

公开(公告)日：2020-10-01

申请号：US16311366

申请日：2017-06-20

Applicant: NOVARTIS AG

Inventor： Jennifer Leslie HARRIS ,  Peter GERGELY ,  Jun LIU ,  Eric SVENSSON

IPC: A61K31/497 ,  C07K16/28 ,  A61K9/00 ,  A61P13/12 ,  A61P17/00

Abstract: The present disclosure relates to a Wingless-type (wnt) inhibitor of formula (I) for use in the treatment of fibrosis and some fibrosis mediated disorders such as stiff skin syndrome and systemic sclerosis. The present disclosure also provides a method for the treatment of fibrosis, a pharmaceutical combination comprising a wnt inhibitor of formula (I) and a second active ingredient for use in the treatment of fibrosis and also the use of a wnt inhibitor of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of fibrosis and fibrosis mediated disorders.

公开(公告)号：US20170049888A1

公开(公告)日：2017-02-23

申请号：US15253689

申请日：2016-08-31

Applicant: Genentech, Inc. ,  Novartis AG

Inventor： Jun LIU ,  Steven J. SHIRE

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

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.

Abstract translation: 本申请涉及具有降低的粘度的高度浓缩的抗体和蛋白质制剂，其是稳定的，相对等渗的并且具有低浊度。 制剂特别适用于皮下给药。 本申请进一步描述了含有这些制剂的制品及使用它们治疗由配制的抗体或蛋白质可治疗的疾病的方法。

公开(公告)号：US20150044198A1

公开(公告)日：2015-02-12

申请号：US14201346

申请日：2014-03-07

Applicant: Novartis AG ,  Genentech, Inc.

Inventor： Jun LIU ,  Steven J. SHIRE

IPC: A61K47/02 ,  A61K39/395

CPC classification number: A61K47/02 ,  A61K9/19 ,  A61K39/39566 ,  A61K39/39591 ,  A61K2039/505 ,  C07K16/4291

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.

Abstract translation: 本申请涉及具有降低粘度的浓缩蛋白质制剂，其特别适用于皮下给药。 该应用还涉及降低浓缩蛋白质制剂的粘度的方法。