Schering Corporation

Merck Sharp + Dohme Corp.

Pharmacopeia Drug Discovery, Inc.

Pharmacopeia Inc.

Merck Gmbh

Corey Strickland

Andrew William Stamford

Ulrich Iserloh

Jared N Cumming

Tao Guo

Yusheng Wu

Suresh D Babu

Kurt William Saionz

Johannes H Voigt

William J Greenlee

Zhaoning Zhu

Brian Alexander McKittrick

Ying Huang

Thuy X H Le

Elizabeth M Smith

Lingyan Wang

John P Caldwell

Zhong-Yue Sun

Yuanzan C Ye

Rachael Catherine Hunter

Michelle Lee Morris

Gang Qian

Dawit Tadesse

Guoqing Li

Robert D Mazzola, Jr

Brian M Beyer

Huizhong Gu

Paul Reichert

Jianping Pan

Douglas Walsh Hobbs

Peter Orth

Yaolin Wang

Rumin Zhang

Johannes H Voight

Samuel Chackalamannil

Vincent Stewart Madison

Yan Xia

William T Windsor

Jose S Duca

Shahriar Shane Taremi

Yuefei Shao

Richard N Ingram

Gaifa Lai

Thomas E Hesson

Jeffrey A Misiaszek

Jingqi Duo

Chuanxing Qu

Ronald J Doll

Gerald Wayne Shipps, Jr

Patricia C Weber

Xiaoxiang Liu

Bruce A Malcolm

Wenyan Wang

Robert Mazzola

Yao Ma

Eileen Wilson

Jeffrey F Lowrie

Thuy X E Le

Viyyoor Moopil Girijavallabhan

Arthur G Taveras

Timothy J Guzi

Alan K Mallams

Alan B Cooper

Joseph Michael Kelly

Dinanath F Rane

Hung V Le

Jianping Chao

Anthony F Mannarino

Gaolian Xie

Jeffrey H Lowrie

Xiaoiang Liu

Stephane L Bogen

Matthew Ernst Voss

Michael H Gelb

Zhuyan Guo

Li Xiao

Craig R Gibeau

Latha G Nair

Nicholas J Murgolo

Weidong Pan

Yuan Tian

Mihirbaran Mandal

Winifred W Prosise

Ramesh Kashi

Brian Robert Lahue

Giovanna Scapin

Mark A McCoy

Xiaoyu Yang

Thuy Xe Le

Lorraine Hernandez

Payal Sheth

Alex Therien

Rachel C Hunter

Elise M Siegel

Zhen Wu

Brian Mckittrick

Robert D Mazzola

Thuy X Le

Crystals of pembrolizumab and structurally similar anti-PD-1 monoclonal antibodies are provided, as well as methods of producing such crystals, and uses of compositions comprising such antibody crystals, e.g. in treatment of cancers. The present invention satisfies these needs and more by providing pembrolizumab crystals and a method producing pembrolizumab crystals. One embodiment of the method of the invention produces crystals suitable for X-ray diffraction, and the inventors herein used such crystals to solve the three-dimensional structure of pembrolizumab to 2.3 A resolution.

Crystals of anti-human PD-1 monoclonal antibodies

The present invention provides polypeptide domains oftoxin B (B1, B2, B3, B4) and complexes between the polypeptides and antibodies that bind specifically for the polypeptide. Methods of using the polypeptides to generate antibodies are also provided.

C.difficile toxin B CROP domain peptides, antibodies and complexes thereof

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein  and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a &#x3b2;-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

Cyclic amide BACE-1 inhibitors having a benzamide substituent

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein each variable in Formula 1 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic magonist or mantagonist.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic magonist or mantagonist.

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein each variable in Formula I are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic magonist or mantagonist.

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein Ris  R is &#x2014;C(O)&#x2014;N(R)(R) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a &#x3b2;-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

Cyclic amine BACE-1 inhibitors having a benzamide substituent

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof,wherein Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic magonist or mantagonist.

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W, U, X, R, R, R, and Rare as defined herein, and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of using such compounds to inhibit aspartyl protease and to treat a variety of disease or disorders, including cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist

The present application relates to methods for growing crystals of both the uncomplexed and complexed forms of &#x3b2;-secretase (BACE) polypeptide. The present application also relates to crystalline forms of uncomplexed BACE and the three-dimensional structure of BACE, as determined from the crystals. In addition, the present application relates to the use of crystalline forms of BACE to identify ligands, preferably inhibitors (antagonists), which bind to, and preferably inhibit the enzymatic activity of, BACE. Furthermore, the present application relates to nucleic acid sequences encoding BACE polypeptide, and methods for making BACE in greater quantity than prior methods, resulting in more effective crystallization.

Refolded recombinant &#x3b2;-secretase crystals and methods for preparing and using the same

The present invention discloses modified Hdm2 proteins that are soluble. In addition, the present invention discloses nucleic acids that encode the modified Hdm2 proteins of the present invention. The invention also provides crystals of modified Hdm2 proteins that are suitable for X-ray crystallization analysis. The present invention also discloses methods of using the modified Hdm2 proteins and crystals thereof to identify, select and/or design compounds that may be used as anticancer agents. The present invention further discloses compounds that bind to modified Hdm2 proteins in protein-ligand complexes.

Polynucleotides encoding soluble, stable forms of human double minute 2 polypeptides

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R, R, R, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of &#x3b2;-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

Macrocyclic beta-secretase inhibitors

Growing community of inventors

Martinsville, NJ, United States of America

Corey Strickland