Eli Lilly and Company

Scios Inc.

Sheila P Little

Edward Marion Johnstone

Nils U Bang

Barbara Cordell

Qiang Xu

Ziyang Zhong

S Richard Jaskunas

Mei-Huei T Lai

Robert J Beckmann

Robert F Santerre

Yu-Wang Liu

George L Long

Diana Hom Quon

Paul Andrew Hyslop

Frauke Schimmöller

Steven Wyatt Queener

Tinggui Yin

Eric P Dixon

Brigitte E Schoner

Franklin H Norris

Barbara J Weigel

The invention concerns a novel &#x3b2;-secretase, a method of partially purifying this novel &#x3b2;-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel &#x3b2;-secretase has an estimated molecular weight of about 32-39 kDa or 22-26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5-7.0.

&#x3b2;-secretase and modulation of &#x3b2;-secretase activity

The invention concerns a novel &#x3b2;-secretase, a method of partially purifying this novel &#x3b2;-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel &#x3b2;-secretase has an estimated molecular weight of about 32&#x2013;39 kDa or 22&#x2013;26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5&#x2013;7.0.

Amyloid precursor protein protease

This invention provides an APP-cleaving protein and related nucleic acid compounds. The invention also provides methods, materials and assays. The compounds of this invention will further the characterization of neurological diseases such as Alzheimer's disease and Down's syndrome.

The present invention comprises novel DNA compounds which encode human protein C activity. A variety of eukaryotic and prokaryotic recombinant DNA expression vectors have been constructed that comprise the novel protein C activity-encoding DNA and drive expression of protein C activity when transformed into an appropriate host cell. The novel expression vectors can be used to produce protein C derivatives, such as non-carboxylated, non-glycosylated, or non-hydroxylated protein C, and to produce protein C precursors, such as nascent or zymogen protein C, and to produce subfragments of protein C, such as active or inactive light and heavy chain. The recombinant-produced protein C activity is useful in the treatment and prevention of a variety of vascular disorders.

Vectors and compounds for expression of human protein C

The invention discloses modified forms of the enzyme tissue plasminogen activator (t-PA) in which recombinant DNA techniques are utilized to modify the structure of the t-PA cDNA to express a modified t-PA which retains the ability to activate plasminogen yet binds less efficiently to plasmin inhibitor. The invention provides novel DNA compounds and recombinant DNA expression vectors that encode modified human t-PA wherein all or a portion of the kringle protein domains of native human t-PA are removed. Both eukaryotic and prokaryotic expression vectors containing the modified t-PA DNA have been constructed and used to transform Chinese hamster ovary cells and Escherichia coli cells.

DNA encoding novel tissue plasminogen activator derivatives having

The present invention comprises novel DNA compounds which encode human protein C activity. A variety of eukaryotic and prokaryotic recombinant DNA expression vectors have been constructed that comprise the novel protein C activity-encoding DNA and drive expression of protein C activity when transformed into an appropriate host cell. The novel expression vectors can be used to produce protein C derivatives, such as non-carboxylated, non-glycosylated, or non-hydroxylated protein C, and to produce protein C precursors, such as nascent or zymogen protein C, and to produce sub-fragments of protein C, such as active or inactive light and heavy chain. The recombinant-produced protein C activity is useful in the treatment and prevention of a variety of vascular disorders.

Methods of using recombinant human protein C

Growing community of inventors

Indianapolis, IN, United States of America

Sheila P Little