DE19902550A1 - A novel aspartate protease, coding sequence, inhibitors and antibodies, useful for treatment and diagnosis of Alzheimer's disease - Google Patents

A novel aspartate protease, coding sequence, inhibitors and antibodies, useful for treatment and diagnosis of Alzheimer's disease

Info

Publication number
DE19902550A1
DE19902550A1 DE19902550A DE19902550A DE19902550A1 DE 19902550 A1 DE19902550 A1 DE 19902550A1 DE 19902550 A DE19902550 A DE 19902550A DE 19902550 A DE19902550 A DE 19902550A DE 19902550 A1 DE19902550 A1 DE 19902550A1
Authority
DE
Germany
Prior art keywords
aspartate
aspartate protease
psnlike
inhibitors
protease
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
DE19902550A
Other languages
German (de)
Inventor
Kay Hofmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
MEMOREC BIOTEC GMBH, 50829 KOELN, DE
Original Assignee
MEMOREC MEDICAL MOLECULAR RESE
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 MEMOREC MEDICAL MOLECULAR RESE filed Critical MEMOREC MEDICAL MOLECULAR RESE
Priority to DE19902550A priority Critical patent/DE19902550A1/en
Priority to EP00903587A priority patent/EP1144603A3/en
Priority to AU25421/00A priority patent/AU2542100A/en
Priority to PCT/EP2000/000390 priority patent/WO2000043505A2/en
Priority to CA002360585A priority patent/CA2360585A1/en
Publication of DE19902550A1 publication Critical patent/DE19902550A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

A novel aspartate protease (AP) has two aspartate residues in a catalytically active structure, where the first aspartate residue is present in motif (I) and a second aspartate residue is present in motif (II), where (I) and (II) are present in a transmembrane region. A novel aspartate protease has two aspartate residues in a catalytically active structure, where the first aspartate residue is present in motif (I) and a second aspartate residue is present in motif (II): where (I) and (II) are present in a transmembrane region. X1, X2, X3, X5 = Ala, Val, Leu, Met, Ile chosen independently from one another; X4 = an aromatic amino acid . Independent claims are also included for the following: (1) a nucleic acid sequence encoding (AP); (2) compounds that inhibit expression or activity of (AP); (3) an antibody targeted against (AP); and (4) a method to identify inhibitors of the aspartate protease activity.

Description

Gegenstand der vorliegenden Erfindung sind eine Aspartatprotease, Nucleinsäuren kodierend für die Aspartatprotease sowie die damit in Verbindung stehenden Inhibitoren, Antikörper, Arznei- und Diagnostikmittel.The present invention relates to an aspartate protease, nucleic acids coding for the aspartate protease and the related Inhibitors, antibodies, medicines and diagnostic agents.

Die vorliegende Erfindung stellt eine Aspartatprotease mit zwei Asparatresten in einer katalytisch aktiven Struktur, wobei ein erster Asparatrest in einem Motiv X1GX2GD liegt und ein zweiter Aspartatrest in einem Motiv X3X4DX5 liegt, wobei X1, X2, X3 und X5 unabhängig voneinander ausgewählt werden aus Ala, ValLeu, Met und Ile und X4 eine aromatische Aminosäure ist, und die Motive X1GX2GD und X3X4DX5 in einer Transmembranregion liegen, zur Verfügung. Für die Motive wurde der Einbuchstabencode der Aminosäuren verwendet, d. h. D = Asp, G = Gly usw.The present invention provides an aspartate protease with two aspartate residues in a catalytically active structure, a first aspartate residue being in a motif X 1 GX 2 GD and a second aspartate residue being in a motif X 3 X 4 DX 5 , where X 1 , X 2 , X 3 and X 5 are independently selected from Ala, ValLeu, Met and Ile and X 4 is an aromatic amino acid, and the motifs X 1 GX 2 GD and X 3 X 4 DX 5 are located in a transmembrane region. The single letter code of the amino acids was used for the motifs, ie D = Asp, G = Gly etc.

Solche Aspartatproteasen sind mit hoher Wahrscheinlichkeit an der Spaltung des Amyloid Precursor Proteins (APP) beteiligt. In einer Ausführungsform der Erfindung stellt die erfindungsgemäße Aspartatprotease die bisher nicht identifizierte γ-Secretase dar, die an der Prozessierung des APP zu den als Aß bezeichneten Amyloidpeptiden beteiligt ist.Such aspartate proteases are very likely to cleave the Amyloid precursor proteins (APP) involved. In one embodiment of the invention represents the aspartate protease according to the invention the previously unidentified γ-secretase represents the processing of the APP to the amyloid peptides referred to as Aß is involved.

Ein Überblick über die Rolle der y-Secretasen bei der Entstehung der Alzheimerschen Erkrankung geben S. L. Ross et al. in J. of Biol. Chem. 273 (1998), 15309-15312. An overview of the role of y-secretases in the development of Alzheimer's Disease give S. L. Ross et al. in J. of Biol. Chem. 273 (1998), 15309-15312.  

Bevorzugte Aspartatproteasen der vorliegenden Erfindung weisen zusätzlich eine Sequenz PALX6YX7VP auf, wobei X6 und X7 die gleiche Bedeutung haben wie X1. Es wird jedoch bevorzugt, daß X6 und X7 Leucin oder Isoleucin sind.Preferred aspartate proteases of the present invention additionally have a sequence PALX 6 YX 7 VP, where X 6 and X 7 have the same meaning as X1. However, it is preferred that X 6 and X 7 are leucine or isoleucine.

Insbesondere handelt es sich bei den Aspartatproteasen um Aspartatproteasen von Säugetieren, insbesondere von Menschen.In particular, the aspartate proteases are aspartate proteases from Mammals, especially humans.

Die erfindungsgemäßen Aspartatproteasen weisen die katalytisch aktiven Aspartat­ reste in einer Region auf, die innerhalb eines Transmembranbereichs liegt. Transmembranbereiche lassen sich bei Kenntnis der Sequenz eines Proteins aufgrund verschiedener Modelle vorhersagen. Sie sind dadurch gekennzeichnet, daß in einem Bereich überwiegend hydrophobe Aminosäuren liegen, die von Bereichen flankiert werden, in denen eher hydrophile Aminosäuren liegen.The aspartate proteases according to the invention have the catalytically active aspartate remains in a region that lies within a transmembrane region. Transmembrane regions can be based on knowledge of the sequence of a protein predict different models. They are characterized in that in one The range is predominantly hydrophobic amino acids flanked by areas which contain more hydrophilic amino acids.

Besonders bevorzugte Aspartatproteasen der vorliegenden Erfindung werden als psnlike 1 bis 4 bezeichnet. Die humanen und murinen Aminosäuresequenzen sind in der Fig. 1 gezeigt.Particularly preferred aspartate proteases of the present invention are referred to as psnlike 1 to 4. The human and murine amino acid sequences are shown in FIG. 1.

Weiterhin sind Varianten der erfindungsgemäßen Aspartatproteasen Gegenstand der Erfindung. Varianten sind Proteine, die durch einen oder mehrere Mutationen, Insertionen und Deletionen, insbesondere durch konservative Austausche, von den erfindungsgemäßen Aspartatproteasen abgeleitet sind. Auch Nucleinsäuren, die für die erfindungsgemäßen Aspartatproteasen kodieren, sind Gegenstand der Erfindung. Bevorzugte erfindungsgemäße Nucleinsäuren sind solche, die in der Fig. 2 gezeigt sind. Auch komplementäre Nucleinsäuren sind Bestandteil der Erfindung.The invention furthermore relates to variants of the aspartate proteases according to the invention. Variants are proteins which are derived from the aspartate proteases according to the invention by one or more mutations, insertions and deletions, in particular by conservative exchanges. The invention also relates to nucleic acids which code for the aspartate proteases according to the invention. Preferred nucleic acids according to the invention are those shown in FIG. 2. Complementary nucleic acids are also part of the invention.

Die erfindungsgemäßen Aspartatproteasen sind an der Spaltung des APP zum Aβ beteiligt und sind damit indirekt an der Entstehung beispielsweise der Alzheimerschen Erkrankung beteiligt. Daher sind auch Inhibitoren, die die Expression oder die Aktivität der Aspartatproteasen hemmen, Gegenstand der Erfindung. Solche Inhibitoren können in einfachen Verfahren identifiziert werden. Entsprechende Inhibitoren können beispielsweise durch Messung der Expression oder der Aktivität der Aspartatproteasen in Gegenwart von potentiellen Inhibitoren identifiziert werden. Insbesondere zur Messung der Expression eignen sich gegen die Aspartatprotesasen gerichtete Antikörper, die somit ebenfalls Bestandteil der Erfindung sind.The aspartate proteases according to the invention are at the cleavage of the APP to Aβ and are indirectly involved in the development of Alzheimer's, for example  Disease involved. Therefore are also inhibitors that the expression or the Inhibit the activity of aspartate proteases, object of the invention. Such Inhibitors can be identified in simple procedures. Appropriate Inhibitors can be, for example, by measuring expression or activity of the aspartate proteases can be identified in the presence of potential inhibitors. The aspartate protesases are particularly suitable for measuring expression directed antibodies, which are therefore also part of the invention.

Die erfindungsgemäßen Aspartatproteasen, Nucleinsäuren, Inhibitoren und Antikörper können in Arznei- und Diagnostikmitteln enthalten sein. Sie eignen sich insbesondere zur Behandlung oder Diagnose von Erkrankungen, die mit der Spaltung des Amyloid IPrecursor Proteins ursächlich verbunden sind, insbesondere der Alzheimerschen Erkrankung.The aspartate proteases, nucleic acids, inhibitors and antibodies according to the invention can be contained in medicinal and diagnostic agents. They are particularly suitable for the treatment or diagnosis of diseases associated with the cleavage of the amyloid IPrecursor proteins are causally linked, especially to Alzheimer's Illness.

Claims (15)

1. Aspartatprotease mit zwei Asparatresten in einer katalytisch aktiven Struktur, wobei ein erster Asparatrest in einem Motiv X1GX2GD liegt und ein zweiter Aspartatrest in einem Motiv X3X4DX5 liegt, wobei X1, X2, X3 und X5 unabhängig voneinander ausgewählt werden aus Ala, Val, Leu, Met und Ile und X4 eine aromatische Aminosäure ist, und die Motive X1GX2GD und X3X4DX5 in einer Transmembranregion liegen.1. Aspartate protease with two residues of asparagus in a catalytically active structure, with a first aspartate residue in a motif X 1 GX 2 GD and a second aspartate residue in a motif X 3 X 4 DX 5 , where X 1 , X 2 , X 3 and X 5 is independently selected from Ala, Val, Leu, Met and Ile and X 4 is an aromatic amino acid, and the motifs X 1 GX 2 GD and X 3 X 4 DX 5 lie in a transmembrane region. 2. Aspartatprotease nach Anspruch 1, dadurch gekennzeichnet, daß die Aspartatprotease die Sequenz PALX6YX7VP aufweist, wobei X6 und X7 die gleiche Bedeutung haben wie X1.2. Aspartate protease according to claim 1, characterized in that the aspartate protease has the sequence PALX 6 YX 7 VP, where X 6 and X 7 have the same meaning as X 1 . 3. Aspartatprotease nach Anspruch 2, dadurch gekennzeichnet, daß X6 und X7 ausgewählt sind aus Leucin und Isoleucin.3. Aspartate protease according to claim 2, characterized in that X 6 and X 7 are selected from leucine and isoleucine. 4. Aspartatprotease nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, daß die Transmembranregion eine Region ist, bei der die Aminosäuren überwiegend hydrophob sind.4. aspartate protease according to any one of claims 1 to 3, characterized in that the transmembrane region is a region in which the amino acids are predominantly hydrophobic. 5. Aspartatprotease nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, daß die Aspartatprotease eine der Sequenzen psnlike 1, psnlike 2, psnlike 3 oder psnlike 4 aufweist.5. aspartate protease according to any one of claims 1 to 4, characterized in that the aspartate protease is one of the sequences psnlike 1, psnlike 2, psnlike 3 or psnlike 4. 6. Nucleinsäuren kodierend für eine Aspartatprotease nach mindestens einem der Ansprüche 1 bis 5. 6. Nucleic acids coding for an aspartate protease according to at least one of claims 1 to 5.   7. Nucleinsäuren nach Anspruch 6, dadurch gekennzeichnet, daß sie die Sequenzen psnlike 1, psnlike 2, psnlike 3 oder psnlike 4 aufweisen.7. Nucleic acids according to claim 6, characterized in that they are the Sequences psnlike 1, psnlike 2, psnlike 3 or psnlike 4 have. 8. Inhibitoren, dadurch gekennzeichnet, daß sie die Expression der Aspartatprotease nach einem der Ansprüche 1 bis 5 hemmen.8. Inhibitors, characterized in that they express the expression of Inhibit aspartate protease according to one of claims 1 to 5. 9. Inhibitoren, dadurch gekennzeichnet, daß sie die Aktivität der Aspartatprotease nach einem der Ansprüche 1 bis 5 hemmen.9. Inhibitors, characterized in that they have the activity of Inhibit aspartate protease according to one of claims 1 to 5. 10. Antikörper, gerichtet gegen Aspartatproteasen nach einem der Ansprüche 1 bis 5.10. Antibody directed against aspartate proteases according to one of claims 1 until 5. 11. Verfahren zur Identifizierung von Inhibitoren, dadurch gekennzeichnet, daß die Aktivität der Aspartatproteasen nach einem der Ansprüche 1 bis 5 in Gegenwart von potentiellen Inhibitoren gemessen wird.11. A method for identifying inhibitors, characterized in that the activity of the aspartate proteases according to any one of claims 1 to 5 in Presence of potential inhibitors is measured. 12. Arzneimittel enthaltend eine Aspartatprotease nach einem der Ansprüche 1 bis 5, eine Nucleinsäure nach einem der Ansprüche 6 bis. 7, einen Inhibitor nach Anspruch 8 oder 9 oder einen Antikörper gemäß Anspruch 10.12. Medicament containing an aspartate protease according to one of claims 1 to 5, a nucleic acid according to any one of claims 6 to. 7, an inhibitor according to claim 8 or 9 or an antibody according to claim 10. 13. Verwendung eines Arzneimittels nach Anspruch 12 zur Behandlung von Erkrankungen, die mit der Spaltung des Amyloid Precursor Proteins ursächlich verbunden sind, insbesondere der Alzheimerschen Erkrankung.13. Use of a medicament according to claim 12 for the treatment of Diseases associated with the cleavage of the amyloid precursor protein are causally linked, especially Alzheimer's disease. 14. Diagnostikmittel enthaltend eine Aspartatprotease nach einem der Ansprüche 1 bis 5, eine Nucleinsäure nach einem der Ansprüche 6 bis 7, einen Inhibitor nach Anspruch 8 oder 9 oder einen Antikörper gemäß Anspruch 10. 14. Diagnostic agent containing an aspartate protease according to one of the claims 1 to 5, a nucleic acid according to any one of claims 6 to 7, an inhibitor according to claim 8 or 9 or an antibody according to claim 10.   15. Verwendung des Diagnostikmittels nach Anspruch 14 zur Diagnose von Erkrankungen, die mit der Spaltung des Amyloid Precursor Proteins ursächlich verbunden sind, insbesondere der Alzheimerschen Erkrankung.15. Use of the diagnostic agent according to claim 14 for the diagnosis of Diseases associated with the cleavage of the amyloid precursor protein are causally linked, especially Alzheimer's disease.
DE19902550A 1999-01-22 1999-01-22 A novel aspartate protease, coding sequence, inhibitors and antibodies, useful for treatment and diagnosis of Alzheimer's disease Withdrawn DE19902550A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
DE19902550A DE19902550A1 (en) 1999-01-22 1999-01-22 A novel aspartate protease, coding sequence, inhibitors and antibodies, useful for treatment and diagnosis of Alzheimer's disease
EP00903587A EP1144603A3 (en) 1999-01-22 2000-01-19 Protease
AU25421/00A AU2542100A (en) 1999-01-22 2000-01-19 Protease
PCT/EP2000/000390 WO2000043505A2 (en) 1999-01-22 2000-01-19 Protease with two aspartate radicals in the catalytically active structure
CA002360585A CA2360585A1 (en) 1999-01-22 2000-01-19 Protease

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19902550A DE19902550A1 (en) 1999-01-22 1999-01-22 A novel aspartate protease, coding sequence, inhibitors and antibodies, useful for treatment and diagnosis of Alzheimer's disease

Publications (1)

Publication Number Publication Date
DE19902550A1 true DE19902550A1 (en) 2000-07-27

Family

ID=7895129

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19902550A Withdrawn DE19902550A1 (en) 1999-01-22 1999-01-22 A novel aspartate protease, coding sequence, inhibitors and antibodies, useful for treatment and diagnosis of Alzheimer's disease

Country Status (1)

Country Link
DE (1) DE19902550A1 (en)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6887677B1 (en) 1999-07-12 2005-05-03 Trustees Of Dartmouth College Compounds and methods for identifying compounds which inhibit a new class of aspartyl proteases
EP1444522B1 (en) * 2001-11-07 2007-01-03 Medical Research Council Screening for antiviral agents affecting signal peptidase
US8497072B2 (en) 2005-11-30 2013-07-30 Abbott Laboratories Amyloid-beta globulomer antibodies
US8609087B2 (en) 1999-07-12 2013-12-17 Trustees Of Dartmouth College Compounds and methods for identifying compounds which inhibit a new class of aspartyl proteases
US8691224B2 (en) 2005-11-30 2014-04-08 Abbvie Inc. Anti-Aβ globulomer 5F7 antibodies
US8877190B2 (en) 2006-11-30 2014-11-04 Abbvie Inc. Aβ conformer selective anti-Aβ globulomer monoclonal antibodies
US8895004B2 (en) 2007-02-27 2014-11-25 AbbVie Deutschland GmbH & Co. KG Method for the treatment of amyloidoses
US8987419B2 (en) 2010-04-15 2015-03-24 AbbVie Deutschland GmbH & Co. KG Amyloid-beta binding proteins
US9062101B2 (en) 2010-08-14 2015-06-23 AbbVie Deutschland GmbH & Co. KG Amyloid-beta binding proteins
US9176150B2 (en) 2003-01-31 2015-11-03 AbbVie Deutschland GmbH & Co. KG Amyloid beta(1-42) oligomers, derivatives thereof and antibodies thereto, methods of preparation thereof and use thereof

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8609087B2 (en) 1999-07-12 2013-12-17 Trustees Of Dartmouth College Compounds and methods for identifying compounds which inhibit a new class of aspartyl proteases
US6887677B1 (en) 1999-07-12 2005-05-03 Trustees Of Dartmouth College Compounds and methods for identifying compounds which inhibit a new class of aspartyl proteases
EP1444522B1 (en) * 2001-11-07 2007-01-03 Medical Research Council Screening for antiviral agents affecting signal peptidase
US10464976B2 (en) 2003-01-31 2019-11-05 AbbVie Deutschland GmbH & Co. KG Amyloid β(1-42) oligomers, derivatives thereof and antibodies thereto, methods of preparation thereof and use thereof
US9176150B2 (en) 2003-01-31 2015-11-03 AbbVie Deutschland GmbH & Co. KG Amyloid beta(1-42) oligomers, derivatives thereof and antibodies thereto, methods of preparation thereof and use thereof
US9540432B2 (en) 2005-11-30 2017-01-10 AbbVie Deutschland GmbH & Co. KG Anti-Aβ globulomer 7C6 antibodies
US8497072B2 (en) 2005-11-30 2013-07-30 Abbott Laboratories Amyloid-beta globulomer antibodies
US8691224B2 (en) 2005-11-30 2014-04-08 Abbvie Inc. Anti-Aβ globulomer 5F7 antibodies
US10538581B2 (en) 2005-11-30 2020-01-21 Abbvie Inc. Anti-Aβ globulomer 4D10 antibodies
US10323084B2 (en) 2005-11-30 2019-06-18 Abbvie Inc. Monoclonal antibodies against amyloid beta protein and uses thereof
US10208109B2 (en) 2005-11-30 2019-02-19 Abbvie Inc. Monoclonal antibodies against amyloid beta protein and uses thereof
US9359430B2 (en) 2006-11-30 2016-06-07 Abbvie Inc. Abeta conformer selective anti-Abeta globulomer monoclonal antibodies
US9394360B2 (en) 2006-11-30 2016-07-19 Abbvie Inc. Aβ conformer selective anti-Aβ globulomer monoclonal antibodies
US9951125B2 (en) 2006-11-30 2018-04-24 Abbvie Inc. Aβ conformer selective anti-Aβ globulomer monoclonal antibodies
US8877190B2 (en) 2006-11-30 2014-11-04 Abbvie Inc. Aβ conformer selective anti-Aβ globulomer monoclonal antibodies
US8895004B2 (en) 2007-02-27 2014-11-25 AbbVie Deutschland GmbH & Co. KG Method for the treatment of amyloidoses
US9822171B2 (en) 2010-04-15 2017-11-21 AbbVie Deutschland GmbH & Co. KG Amyloid-beta binding proteins
US8987419B2 (en) 2010-04-15 2015-03-24 AbbVie Deutschland GmbH & Co. KG Amyloid-beta binding proteins
US10047121B2 (en) 2010-08-14 2018-08-14 AbbVie Deutschland GmbH & Co. KG Amyloid-beta binding proteins
US9062101B2 (en) 2010-08-14 2015-06-23 AbbVie Deutschland GmbH & Co. KG Amyloid-beta binding proteins

Similar Documents

Publication Publication Date Title
EP0276723B1 (en) Precursor protein of APC polypeptide, DNA coding therefor and diagnostic use of the DNA and protein
EP0885904B1 (en) Peptides as agonists and/or inhibitors of amyloid formation and/or cytotoxicity and their use against Alzheimer's disease, type II diabetes mellitus and spongiform encephalopathy
DE19902550A1 (en) A novel aspartate protease, coding sequence, inhibitors and antibodies, useful for treatment and diagnosis of Alzheimer's disease
DE69737754T2 (en) SUBSTANCES FOR PRESYMPTOMATIC RECOGNITION AND TARGETED THERAPY OF ALZHEIMER DISEASE IN HUMANS.
EP0149468A2 (en) Biologically active substance with hormonal characteristics, process for its preparation and use of histons for medicinal ends
Maule et al. KSAYMRFamide: a novel FMRamide-related heptapeptide from the free-living nematode, Panagrellus redivivus, which is myoactive in the parasitic nematode, Ascaris suum
ATE254172T1 (en) PREVENTIVE OR THERAPEUTIC AGENTS FOR ALZHEIMER'S DISEASE, A SEVEN TEST METHOD, AND HUMAN TAU PROTEIN KINASE
DE19641180A1 (en) A method of displaying APP secretase modulation and its use as an agent for the treatment of Alzheimer's disease
EP1630171B1 (en) Streptavidin binding peptides
EP1161524B1 (en) CELLS COEXPRESSING AN AMYLOID PRECURSOR PROTEIN AND AN $g(a)-SECRETASE AND THEIR USES IN TEST METHODS AND DIAGNOSTICS
DE10131899A1 (en) In Vitro Screening Assay for Gamma Secretase
EP0535059A1 (en) Dna sequence for a serine protease and associated items.
EP2566882A1 (en) Agents for treating alzheimer's disease
DE3833936C1 (en)
Wahlberg et al. Contact sensitivity to quinidine sulfate from occupational exposure
DE69631516T2 (en) Family of mammalian potassium channels, their cloning and use for drug screening
EP2914616B1 (en) Peptides that bind to amino-terminal truncated amyloid-beta-peptide and use of said peptides
Prianti Jr et al. Effect of Bothrops leucurus venom in chick biventer cervicis preparations
EP1156811B1 (en) Copper agonist that binds on the copper binding site of amyloid precursor protein (app) and/or exerts an inhibiting effect on the release of amyloid-beta-peptide
Dowson A sensitive method for the demonstration of senile plaques in the dementing brain
DE3708198A1 (en) METHOD FOR ISOLATING BASAL MEMBRANE PROTEINS FROM HUMAN AND ANIMAL TISSUES
EP3271374A1 (en) Peptides which bind to a specific a-beta-species for the therapy and/or diagnosis of alzheimer's disease
EP1144603A2 (en) Protease
WO1999042574B1 (en) Sequences of an ih ionic channel and the use thereof
DE60224002T2 (en) Cathepsin Y inhibitors for the development of pain medication

Legal Events

Date Code Title Description
8127 New person/name/address of the applicant

Owner name: MEMOREC STOFFEL GMBH - MEDIZINISCH-MOLEKULARE ENTW

8127 New person/name/address of the applicant

Owner name: MEMOREC BIOTEC GMBH, 50829 KOELN, DE

8139 Disposal/non-payment of the annual fee