Basf Aktiengesellschaft

Warner-lambert Company

Other

Basf Aktiengellschaft

Abbvie Inc.

Basf Aktiengesellsschaft

Robert V Talanian

Tariq Ghayur

John C Hodges

John A Mankovich

Hamish John Allen

Kenneth Dale Brady

Catherine R Ferenz

Catherine R Kostlan

Subhashis Banerjee

Anna M Ericsson

Bradley W Caprathe

Kristine E Frank

Thomas D Gordon

Richard W Dixon

David J Calderwood

Maria A Argiriadi

Neil Wishart

Joseph Scott Warmus

Biqin C Li

David Wayne Borhani

Kelly Mullen

Lu Wang

Sheryl Jeanne Hays

Andrew Burchat

Kevin Patrick Cusack

Nigel P Walker

Xiaoyun Wu

Claude E Barberis

John Lodge Gilmore

Paul Galatsis

Lily K Abbott

Xiaolei Zhang

Biqin Li

Kelly D Mullen

David W Borhani

Lu X Wang

The present invention discloses methods used to estimate the in vivo half-life of a binding protein of interest. The disclosed methods involve (a) determining for a binding protein of interest and for each of at least two different reference binding proteins an in vitro half-life using an in vitro protease reaction assay, wherein said reference binding proteins have known different in vivo half-lives, (b) determining the correlation between the known in vivo half-lives and the in vitro proteolytic half-lives of each of the reference binding proteins, and (c) estimating from said correlation between the known in vivo half-lives and the in vitro proteolytic half-lives of the reference binding proteins the in vivo half-life of the binding protein of interest that correlates with the in vitro proteolytic half-life of the binding protein of interest.

In vitro estimation of in vivo half-life binding proteins

Novel compounds of Formula (I) or pharmaceutically acceptable salts, prodrugs and biologically active metabolites thereof of Formula (I) wherein the substituents are as defined herein, which are useful as therapeutic agents.

Indazole compounds

Modified forms of human interleukin-1&bgr; converting enzyme (ICE) that display proteolytic activity and, furthermore, have increased stability compared to unmodified human ICE are disclosed. Nucleic acid molecules encoding a modified p10 subunit of ICE, and recombinant vectors and host cells incorporating such nucleic acid molecules, are also disclosed. A modified ICE protein of the invention can be used to cleave proteolytically ICE substrates and to identify modulators of ICE activity in screening assays. Moreover, due to its enhanced stability, the modified ICE of the invention is particularly suitable for use in the preparation of ICE crystals for X-ray crystallography.

Modified interleukin-1&bgr; converting enzyme with increased stability

Substrates and inhibitors for the cysteine protease Ich-1 are disclosed. These compounds are designed based on an optimal minimal substrate for Ich-1 and include reversible inhibitors, irreversible inhibitors, selectively reversible inhibitors, chromogenic substrates, fluorogenic substrates and radiolabeled substrates/inhibitors. Pharmaceutical compositions comprising the compounds of the invention are also provided. Methods for inhibiting the proteolytic activity of Ich-1, methods for detecting the presence of Ich-1 and methods for isolating Ich-1 using the compounds of the invention are also disclosed.

Substrates and inhibitors for cysteine protease ICH-1

The present invention relates to N-substituted derivatives of glutamic acid of pharmaceutical interest, to pharmaceutical compositions which include compounds of the invention and pharmaceutically acceptable carriers, to methods of their preparation, and to their use in purification of interleukin-1.beta. converting enzyme (ICE).

N-substituted glutamic acid derivatives with interleukin-1.beta.

The present invention relates to compounds that are inhibitors of interleukin-1.beta. converting enzyme that have the Formula II ##STR1## This invention also relates to a method of treatment of stroke, inflammatory diseases, septic shock, reperfusion injury, Alzheimer's disease, shigellosis, and to a pharmaceutically acceptable composition that contains a compound that is an inhibitor of interleukin-1.beta. converting enzyme.

Hydroxamate inhibitors of interleukin-1.beta. converting enzyme

Modified forms of human interleukin-1.beta. converting enzyme (ICE) that display proteolytic activity and, furthermore, have increased stability compared to unmodified human ICE are disclosed. Nucleic acid molecules encoding a modified p10 subunit of ICE, and recombinant vectors and host cells incorporating such nucleic acid molecules, are also disclosed. A modified ICE protein of the invention can be used to cleave proteolytically ICE substrates and to identify modulators of ICE activity in screening assays. Moreover, due to its enhanced stability, the modified ICE of the invention is particularly suitable for use in the preparation of ICE crystals for X-ray crystallography.

Modified interleukin-1.beta. converting enzyme with increased stability

N-substituted glutamic acid derivatives with interleukin-1 .beta.

Growing community of inventors

Harvard, MA, United States of America

Robert V Talanian