WO1998013488A3 - Procede pour determiner les modulateurs de la secretase de l'app et utilisation de ces derniers comme agents dans le traitement de la maladie d'alzheimer - Google Patents

Procede pour determiner les modulateurs de la secretase de l'app et utilisation de ces derniers comme agents dans le traitement de la maladie d'alzheimer Download PDF

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Publication number
WO1998013488A3
WO1998013488A3 PCT/EP1997/005149 EP9705149W WO9813488A3 WO 1998013488 A3 WO1998013488 A3 WO 1998013488A3 EP 9705149 W EP9705149 W EP 9705149W WO 9813488 A3 WO9813488 A3 WO 9813488A3
Authority
WO
WIPO (PCT)
Prior art keywords
alzheimer
disease
treatment
modulators
app secretase
Prior art date
Application number
PCT/EP1997/005149
Other languages
English (en)
Other versions
WO1998013488A2 (fr
Inventor
Thomas Dyrks
Jonathan-David Turner
Marion Haertel
Original Assignee
Schering Ag
Thomas Dyrks
Turner Jonathan David
Marion Haertel
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Ag, Thomas Dyrks, Turner Jonathan David, Marion Haertel filed Critical Schering Ag
Priority to AU47757/97A priority Critical patent/AU4775797A/en
Publication of WO1998013488A2 publication Critical patent/WO1998013488A2/fr
Publication of WO1998013488A3 publication Critical patent/WO1998013488A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site

Abstract

L'invention concerne un procédé pour déterminer l'activité de la secrétase de l'APP (protéine précurseur de l'amyloïde) à l'aide de systèmes de modèles cellulaires. Ces systèmes cellulaires sont directement utilisés pour analyser les modulateurs pharmacologiques de la libération de l'amyloïde βA4. L'invention traite aussi des modulateurs qui peuvent être identifiés et isolés par ce procédé comme agents pharmaceutiques pour traiter la maladie d'Alzheimer. L'invention a également pour objet des vecteurs d'expression, des cellules transfectées par les vecteurs d'expression, et l'utilisation de ces derniers pour identifier les modulateurs de la secrétase de l'APP, et un ensemble pour déterminer l'activité de cette enzyme.
PCT/EP1997/005149 1996-09-24 1997-09-22 Procede pour determiner les modulateurs de la secretase de l'app et utilisation de ces derniers comme agents dans le traitement de la maladie d'alzheimer WO1998013488A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU47757/97A AU4775797A (en) 1996-09-24 1997-09-22 Process for the determination of app secretase modulators and the use thereof as agents in the treatment of alzheimer's disease

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19641180A DE19641180A1 (de) 1996-09-24 1996-09-24 Verfahren zur Darstellung von APP-Sekretase Modulation und deren Verwendung als Mittel zur Behandlung der Alzheimer'schen Erkrankung
DE19641180.7 1996-09-24

Publications (2)

Publication Number Publication Date
WO1998013488A2 WO1998013488A2 (fr) 1998-04-02
WO1998013488A3 true WO1998013488A3 (fr) 1998-09-11

Family

ID=7807996

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1997/005149 WO1998013488A2 (fr) 1996-09-24 1997-09-22 Procede pour determiner les modulateurs de la secretase de l'app et utilisation de ces derniers comme agents dans le traitement de la maladie d'alzheimer

Country Status (4)

Country Link
AU (1) AU4775797A (fr)
DE (1) DE19641180A1 (fr)
WO (1) WO1998013488A2 (fr)
ZA (1) ZA978557B (fr)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060141036A1 (en) 1997-12-12 2006-06-29 Andrx Labs Llc HMG-CoA reductase inhibitor extended release formulation
US6844148B1 (en) 1998-09-24 2005-01-18 Pharmacia & Upjohn Company Alzheimer's disease secretase, APP substrates therefor, and uses therefor
NZ527053A (en) 1998-09-24 2005-04-29 Upjohn Co Modified amyloid precursor protein polynucleotides and polypeptides
US6699671B1 (en) 1998-09-24 2004-03-02 Pharmacia & Upjohn Company Alzheimer's disease secretase, APP substrates therefor, and uses therefor
US6245884B1 (en) 1998-10-16 2001-06-12 Vivian Y. H. Hook Secretases related to alzheimer's dementia
US6313268B1 (en) 1998-10-16 2001-11-06 Vivian Y. H. Hook Secretases related to Alzheimer's dementia
US7115410B1 (en) 1999-02-10 2006-10-03 Elan Pharmaceuticals, Inc. β-secretase enzyme compositions and methods
US7456007B1 (en) 1998-12-31 2008-11-25 Elan Pharmaceuticals, Inc. β-secretase enzyme compositions and methods
GB2364059B (en) 1999-02-10 2004-01-14 Elan Pharm Inc Beta-Secretase enzyme compositions and methods
DE19920514A1 (de) * 1999-05-05 2000-11-16 Boehringer Ingelheim Pharma Methoden zur Auffindung von Proteasen, die spezifisch membrangebundene Substrate spalten
CA2374610A1 (fr) 1999-06-28 2001-01-04 Jordan J. N. Tang Memapsine recombinante catalytiquement active et procedes d'utilisation
DE19941039A1 (de) * 1999-08-28 2001-03-01 Boehringer Ingelheim Pharma gamma-Sekretase in vitro Testsystem
US7514408B1 (en) 1999-12-02 2009-04-07 Elan Pharmaceuticals, Inc. β-secretase enzyme compositions and methods
WO2001058476A2 (fr) * 2000-02-11 2001-08-16 The European Molecular Biology Laboratory Procedes et compositions pour le traitement de la maladie d'alzheimer par le renforcement de l'activite de la plasmine ou de l'activite du type de la plasmine
CA2401155A1 (fr) * 2000-04-05 2001-10-11 Alcide Barberis Procede d'identification de polypeptides ayant une activite protease
CA2313828A1 (fr) * 2000-08-01 2002-02-01 Institut De Recherches Cliniques De Montreal/Ircm Modification post-traduction de .beta.-secretase(bace) : les domaines cytosolyques pro- et transmembranaires ont des effets sur l'activite cellulaire et sur la production de la proteine .beta.amyloide
WO2002062824A2 (fr) * 2001-02-05 2002-08-15 Andrx Corporation Methode de traitement de troubles de la maturation du precurseur de la proteine ? amyloide
EP1448218A4 (fr) 2001-10-23 2009-01-14 Oklahoma Med Res Found Inhibiteurs de la beta-secretase et leurs procede d'utilisation
US7045311B2 (en) 2001-10-25 2006-05-16 Monogram Biosciences, Inc. Whole cell assay systems for cell surface proteases
CH698246B1 (de) * 2001-12-20 2009-06-30 Hoffmann La Roche Test zur Identifizierung von Inhibitoren von Beta-Sekretasen.
AU2002253468B2 (en) * 2002-04-18 2008-04-03 Esbatech Ag Method for the identification of modulators of a secretase activity
JP2004000060A (ja) * 2002-05-31 2004-01-08 Otsuka Pharmaceut Co Ltd アミロイドβ産生に影響を与える化合物のスクリーニング方法

Citations (8)

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Publication number Priority date Publication date Assignee Title
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EP0569777A2 (fr) * 1992-05-11 1993-11-18 Bayer Corporation Procédés de détection des enzymes de traitement de précurseur de l'amyloide bêta
EP0586790A1 (fr) * 1992-04-20 1994-03-16 The General Hospital Corporation Protéine analogue au précurseur de la substance amyloide et ses utilisations
WO1994010569A1 (fr) * 1992-10-26 1994-05-11 Schenk Dale B PROCEDES ET COMPOSITIONS VISANT A DETECTER UN PEPTIDE β-AMYLOIDE SOLUBLE
WO1996012486A1 (fr) * 1994-10-25 1996-05-02 Smithkline Beecham P.L.C. Utilisation de [r-(z)]-alpha-(methoxyimino)-alpha-(1-azabicyclo [2.2.2] oct-3-yl) acetonitrile pour reduire la formation beta a4 amyloide dans la maladie d'alzheimer
US5523314A (en) * 1992-09-10 1996-06-04 Eli Lilly And Company Compounds useful as hypoglycemic agents and for treating Alzheimer's disease
WO1996040885A2 (fr) * 1995-06-07 1996-12-19 Athena Neurosciences, Inc. β-SECRETASE, ANTICORPS DIRIGES CONTRE LA β-SECRETASE ET DOSAGES PERMETTANT DE DETECTER L'INHIBITION DE LA β-SECRETASE
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Patent Citations (8)

* Cited by examiner, † Cited by third party
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EP0327960A1 (fr) * 1988-02-11 1989-08-16 F. Hoffmann-La Roche Ag Formes sécrétables de phosphatase alcaline
EP0586790A1 (fr) * 1992-04-20 1994-03-16 The General Hospital Corporation Protéine analogue au précurseur de la substance amyloide et ses utilisations
US5652092A (en) * 1992-05-01 1997-07-29 American Cyanamid Company Amyloid precursor proteins and method of using same to assess agents which down-regulate formation of β-amyloid peptide
EP0569777A2 (fr) * 1992-05-11 1993-11-18 Bayer Corporation Procédés de détection des enzymes de traitement de précurseur de l'amyloide bêta
US5523314A (en) * 1992-09-10 1996-06-04 Eli Lilly And Company Compounds useful as hypoglycemic agents and for treating Alzheimer's disease
WO1994010569A1 (fr) * 1992-10-26 1994-05-11 Schenk Dale B PROCEDES ET COMPOSITIONS VISANT A DETECTER UN PEPTIDE β-AMYLOIDE SOLUBLE
WO1996012486A1 (fr) * 1994-10-25 1996-05-02 Smithkline Beecham P.L.C. Utilisation de [r-(z)]-alpha-(methoxyimino)-alpha-(1-azabicyclo [2.2.2] oct-3-yl) acetonitrile pour reduire la formation beta a4 amyloide dans la maladie d'alzheimer
WO1996040885A2 (fr) * 1995-06-07 1996-12-19 Athena Neurosciences, Inc. β-SECRETASE, ANTICORPS DIRIGES CONTRE LA β-SECRETASE ET DOSAGES PERMETTANT DE DETECTER L'INHIBITION DE LA β-SECRETASE

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CITRON M ET AL: "GENERATION OF AMYLOID BETA PROTEIN FROM ITS PRECURSOR IS SEQUENCE SPECIFIC", NEURON, vol. 14, no. 3, 1 March 1995 (1995-03-01), pages 661 - 670, XP000577165 *
E.I. SNYDER ET AL.: "SOME SYNTHESES AND STRUCTURES IN THE 9,10-DIHYDRO-9,10-ETHANOANTHRACENE SERIES", J. ORG. CHEM., vol. 25, 1960, pages 1328 - 1330, XP002068229 *
EFTHIMIOPOULOS ET AL.: "STUDY OF PHORBOL ESTER EFFECT ON ALZHEIMER AMYLOID PRECURSOR PROCESSING:SEQUENCE REQUIREMENTS AND INVOLVEMENT OF A CHOLERA TOXIN SENSITIVE PROTEIN", JOURNAL OF NEUROSCIENCE RESEARCH, vol. 38, 1994, pages 81 - 90, XP002057045 *
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Also Published As

Publication number Publication date
WO1998013488A2 (fr) 1998-04-02
ZA978557B (en) 1998-03-26
AU4775797A (en) 1998-04-17
DE19641180A1 (de) 1998-03-26

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