Regeneron Pharmaceuticals, Inc.

Bristol-myers Squibb Compnay

Regeneran Pharmaceuticals, Inc.

Bristol-myers Squibb Holdings Ireland

Min Gao

Lynn Macdonald

Julie A Lemm

Ying Hu

Susan D Croll

Marc R Morra

Michael L LaCroix-Fralish

Nicole M Alessandri-Haber

Nicholas A Meanwell

Makonen Belema

Lawrence B Snyder

Michael H Serrano-Wu

Alexander O Mujica

Yajun Tang

Jeffrey D Lee

Carmelo Romano

Jin-Hua Sun

Donald R O'Boyle

Donald R O'Boyle, Ii

John F Kadow

Milind Deshpande

Piyasena Hewawasam

Omar D Lopez

Jeffrey Lee Romine

Denis R St Laurent

Van N Nguyen

Fukang Yang

Scott W Martin

Alan Xiangdong Wang

Yuping Qiu

Darren Whitehouse

Yong Tu

Ningning Xu

John E Leet

Xuejie Yang

Samayamunthula Venkata Satya Arun Kumar Gupta

Fiona McPhee

Ramesh Kakarla

Ying-Kai Wang

Pothukanuri Srinivasu

Robert A Fridell

Richard Colonno

Ponugupati Suresh Kumar

Indasi Gopi Kumar

Susan E Chaniewski

Peter Nower

Karen Rigat

Stacey A Voss

Chunfu Wang

Amy K Sheaffer

Donald R Ii O'BOYLE

Ramesh Kakaria

Donald R O'BOYLE Ii

David F Gardiner

Fiona Mcphee

Michael L Lacroix-Fralish

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TRKB locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TRKB locus express a human TRKB protein or a chimeric transthyretin protein, fragments of which are from human TRKB. Methods are provided for using such non-human animals comprising a humanized TRKB locus to assess in vivo efficacy of human-TRKB-targeting reagents such as nuclease agents designed to target human TRKB.

Mouse comprising a humanized TRKB locus

The present invention provides antibodies that bind specifically to TrkB and methods of using the same. According to certain embodiments, the antibodies of the invention are agonist antibodies that are neuroprotective, as shown by their effect on enhancing the survival of retinal ganglion cells in vitro. As such, these agonist antibodies may be used to treat diseases or disorders of the eye, such as, but not limited to glaucoma. In addition, other neuronal diseases or disorders may benefit from treatment with these agonist antibodies, including any disease or disorder characterized in part by neuronal damage. In certain embodiments, the invention includes antibodies that bind TrkB and mediate cell signaling. The antibodies of the invention may be fully human, non-naturally occurring antibodies.

Anti-TrkB monoclonal antibodies and methods of use

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The present invention provides antibodies and antigen-binding fragments thereof that specifically bind to cells expressing acid-sensing ion channel-1 (ASIC1). According to certain embodiments of the invention, the antibodies inhibit acid-induced, ASIC1-mediated ion currents in cells expressing human ASIC1. The antibodies of the invention are useful for the treatment of pain, including pain associated with surgical intervention and various diseases and disorders.

Anti-ASIC1 antibodies and uses thereof

The present invention provides antibodies and antigen-binding fragments thereof that specifically bind to cells expressing acid-sensing ion channel-1 (ASIC1). According to certain embodiments of the invention, the antibodies inhibit acid-induced, ASIC1-mediated ion currents in cells expressing human ASIC1. According to certain embodiments, the antibodies of the invention are selective for ASIC1 and do not bind other acid-sensing ion channels in the absence of ASIC1. The antibodies of the invention are useful for the treatment of pain, including pain associated with surgical intervention and various diseases and disorders.

The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.

Hepatitis C virus inhibitors

The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit Hepatitis C virus (HCV), compositions comprising such compounds, and methods for treating Hepatitis C using such combinations.

Combinations of hepatitis C virus inhibitors

Compounds having the structure of formula I are described. The compounds can inhibit hepatitis C virus (HCV) replication, and in particular can inhibit the function of the HCV NS5A protein.

Inhibitors of HCV replication

The present invention includes an assay useful for identifying inhibitors of Hepatitis C virus (HCV) activity. Particularly, the present invention is directed to a dual HCV assay useful for high throughput screening that quantifies both the amount of HCV RNA replication inhibitory activity associated with a test compound and the amount of cytotoxicity associated with that test compound. The present invention also includes compounds discovered using this assay, compositions containing such compounds and methods of treating Hepatitis C by the administration of such compounds. The present invention also includes reporter assays using enzymes associated with HCV RNA replication, as well as a cell line having ATTC Accession No. PTA-4583.

Hepatitis C virus assays

Compounds having the structure of formula I are described  wherein R, R', R, R, and Rare as defined in the specification. The compounds can inhibit hepatitis C virus (HCV) replication, and in particular the function of the HCV NS5A protein.

Iminothiazolidinones as inhibitors of HCV replication

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Montvale, NJ, United States of America

Min Gao