EP2222880A2 - Séquences de marqueurs pour des maladies neurodégénératives et leur utilisation - Google Patents

Séquences de marqueurs pour des maladies neurodégénératives et leur utilisation

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Publication number
EP2222880A2
EP2222880A2 EP08864285A EP08864285A EP2222880A2 EP 2222880 A2 EP2222880 A2 EP 2222880A2 EP 08864285 A EP08864285 A EP 08864285A EP 08864285 A EP08864285 A EP 08864285A EP 2222880 A2 EP2222880 A2 EP 2222880A2
Authority
EP
European Patent Office
Prior art keywords
neurodegenerative diseases
marker
marker sequences
case
sequence
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Withdrawn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
EP08864285A
Other languages
German (de)
English (en)
Inventor
Heike GÖHLER
Helmut E. Meyer
Katrin Marcus
Axel Kowald
Florian Tribl
Manfred Gerlach
Peter Riederer
Angelika Lueking
Christian Scheer
Jens Beator
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.)
Protagen GmbH
Original Assignee
Protagen GmbH
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 Protagen GmbH filed Critical Protagen GmbH
Publication of EP2222880A2 publication Critical patent/EP2222880A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/2835—Movement disorders, e.g. Parkinson, Huntington, Tourette
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/56—Staging of a disease; Further complications associated with the disease

Definitions

  • the present invention relates to novel marker sequences for neurodegenerative diseases and their diagnostic use, including a method for screening potential drugs for neurodegenerative diseases by means of these marker sequences. Furthermore, the invention relates to a diagnostic device containing such marker sequences for neurodegenerative diseases, in particular a protein biochip and its use.
  • Protein biochips are gaining increasing industrial importance in analytics and diagnostics as well as in pharmaceutical development. Protein biochips have become established as screening tools.
  • expression vectors have sequences for so-called affinity epitopes or proteins, which on the one hand allow the specific detection of the recombinant fusion proteins by means of an antibody directed against the affinity epitope, on the other hand, the specific purification via affinity chromatography (IMAC) allows.
  • affinity epitopes or proteins which on the one hand allow the specific detection of the recombinant fusion proteins by means of an antibody directed against the affinity epitope, on the other hand, the specific purification via affinity chromatography (IMAC) allows.
  • the gene products of a cDNA expression library of human fetal brain tissue in the bacterial expression system Escherichia coli in high density format were placed on a membrane and successfully screened with different antibodies. It could be shown that the proportion of full-length proteins is at least 66%.
  • the recombinant proteins from expression libraries could be expressed and purified at high throughput (Braun P., Hu, Y., Shen, B., Halleck, A., Koundinya, M., Harlow, E. and LaBaer, J.
  • Antibody arrays An embryonic but growing technology, DDT, 7, 143-149, Kusnezow et al., (2003) Antibody microarrays: An evaluation of production parameters, proteomics, 3, 254-264).
  • indication-specific diagnostic devices such as a protein biochip.
  • the object of the present invention is therefore the provision of marker sequences and their diagnostic use.
  • the invention relates to the use of marker sequences for the diagnosis of neurodegenerative diseases, wherein at least one marker sequence of a cDNA selected from the group SEQ 1-927 or in each case a protein coding therefor or in each case a partial sequence or fragment thereof (hereinafter: marker sequences according to the invention) to or from a patient to be examined is determined.
  • the marker sequences according to the invention could be identified by differential screening of samples from healthy subjects with patient samples with neurodegenerative diseases.
  • neurodegenerative diseases ⁇ comprises a group of usually slowly progressive, hereditary or sporadic diseases of the nervous system.
  • Main feature is the progressive loss of nerve cells leading to various neurological symptoms leading to dementia and movement disorders.
  • the diseases can occur and call at different ages characteristic histological damage patterns. Described are in particular Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease ('s Chorea) and Morbus Pick (definition, for example, Pschyrembel, de Gruyter, 261st Edition (2007), Berlin), according to the invention, however, are preferred Alzheimer's, Parkinson's disease, Huntington's disease.
  • the invention relates to the diagnosis of neurodegenerative diseases, preferably Parkinson's disease, wherein at least one marker sequence of a cDNA selected from the group SEQ 1 - 293 or a protein coding therefor or in each case a partial sequence or fragment thereof to or from one to determined by the examining patient.
  • neurodegenerative diseases preferably Parkinson's disease
  • a marker sequence selected from the group SEQ 1 - 20, 21 - 40, 41 - 60, 61 - 80, 81 - 100, 101 - 120, 121 - 140, 141 - 160, 161 - 180, 181 - 200, 201-220, 221-240, 241-260, 261-280, 281-293 or in each case a protein coding therefor or in each case a partial sequence or fragment thereof.
  • the invention relates to the diagnosis of neurodegenerative diseases, preferably Alzheimer's disease, wherein at least one marker sequence of a cDNA selected from the group SEQ 294 - 664 or a protein coding therefor or in each case a partial sequence or fragment thereof to or from one to determined by the examining patient.
  • a marker sequence selected from the group SEQ 294-320, 321-340, 341-360, 361-380, 381-400, 401-420, 421-440, 441-460, 461-480, 481-500, 501-520, 521-540, 541-560, 561-580, 581-600, 601-620, 621-640, 641-664, or in each case a protein coding therefor or in each case a partial sequence or fragment thereof.
  • the invention relates to the diagnosis of neurodegenerative diseases, preferably Huntington's disease, wherein at least one marker sequence of a cDNA selected from the group SEQ 665-927 or a protein coding therefor or in each case a partial sequence or fragment thereof to or from one to determined by the examining patient.
  • neurodegenerative diseases preferably Huntington's disease
  • marker sequence selected from the group SEQ 665-680, 681-700, 701-720, 721-740, 741-760, 761-780, 781-800, 801-820, 821-840, 841-860, 861-880, 881-900, 901-927 or in each case a protein coding therefor or in each case a partial sequence or fragment thereof.
  • At least 2 to 5 or 10 preferably 30 to 50 marker sequences or 50 to 100 or more marker sequences are determined on or from a patient to be examined, in particular those in each case from the group SEQ 1 - 293, 294 - 664, 665 -927.
  • the marker sequences according to the invention can also be combined, supplemented or extended with known biomarkers for this indication.
  • the determination of the marker sequences takes place outside the human body and the determination takes place in an ex vivo / in vitro diagnosis.
  • the invention relates to the use of marker sequences as diagnostic agents, wherein at least one marker sequence of a cDNA selected from the group SEQ 1-927 in particular those in each case from the group SEQ 1 - 293, 294 - 664, 665-927 or in each case is a protein coding therefor or in each case a partial sequence or fragment thereof.
  • the invention relates to a method for the diagnosis of neurodegenerative diseases, wherein a.) At least one marker sequence of a cDNA selected from the group SEQ 1-927 in particular those each from the group SEQ 1 - 293, 294 - 664, 665-927 or one each b.) is brought into contact with body fluid or tissue extract of a patient and c.) the detection of an interaction of the body fluid or tissue extract with the marker sequences from a.) Is carried out ,
  • the invention also relates to diagnostic agents for the diagnosis of neurodegenerative diseases in each case selected from the group SEQ 1-927, in particular those in each case from the group SEQ 1 - 293, 294 - 664, 665-927 or in each case a protein coding therefor or in each case a partial sequence or fragment from that.
  • the detection of such an interaction can be carried out for example by a probe, in particular by an antibody.
  • the invention also has the object of providing a diagnostic device or an assay, in particular a protein biochip, which allows a diagnosis or examination for the neurodegenerative diseases.
  • the invention relates to a method for stratifying, in particular for risk stratification and / or therapy control of a patient with neurodegenerative diseases, wherein at least one marker sequence of a cDNA selected from the group SEQ 1-927 in particular those in each case from the group SEQ 1 - 293, 294 - 664 , 665-927 or in each case a protein coding therefor is determined on or from a patient to be examined. Also included is the stratification of patients with neurodegenerative diseases into new or established subgroups of neurodegenerative diseases, as well as the judicious selection of patient groups for the clinical development of new therapeutics.
  • therapy control also includes the classification of patients into responders and non-responders with regard to a therapy or its course of therapy.
  • Diagnosis in the sense of this invention means the positive determination of the neurodegenerative diseases by means of the marker sequences according to the invention as well as the assignment of the patients to the neurodegenerative diseases.
  • diagnosis includes medical diagnostics and related investigations, in particular in vitro diagnostics and laboratory diagnostics Proteomics and Nucleic Acid Blobs Further investigations may be needed to secure and exclude other diseases Therefore, the term diagnosis also includes the differential diagnosis of neurodegenerative diseases by means of the marker sequences of the invention as well as the prognosis of neurodegenerative diseases.
  • Stratification also: stratification or therapy control
  • stratification means that the method according to the invention allows decisions for the treatment and therapy of the patient, be it hospitalization of the patient, use, effect and / or dosage of one or more drugs, a therapeutic measure or the monitoring of a disease course as well as the course of therapy or etiology or classification of a disease, for example into a new or existing subtype or the differentiation of diseases and their patients.
  • the term "stratification" includes in particular the
  • patient is understood to mean any subject - human or mammal - with the proviso that the subject is examined for neurodegenerative diseases.
  • marker sequences in the sense of this invention means that the cDNA or the respective polypeptide or protein obtainable therefrom are significant for neurodegenerative diseases
  • the cDNA or the respectively obtainable polypeptide or protein can interact with substances from the body fluid or tissue extract of a
  • "at least one marker sequence of a cDNA selected from the group SEQ 1-927 or in each case a protein coding for it or in each case a partial sequence or Fragment of it to or from a patient to be examined is determined "that an interaction between the body fluid or tissue extract of a patient and the marker sequences of the invention is detected.
  • Such an interaction is eg a bond, in particular a binding substance on at least one marker sequence according to the invention or in the case of a cDNA the hybridization with a suitable substance under selected conditions, in particular stringent conditions (eg as defined in J. Sambrook, EF Fritsch, T. Maniatis (1989), Molecular cloning: A laboratory manual, 2nd Edition, CoId Spring Habor Laboratory Press, CoId Spring Habor, USA or Ausubel, "Current Protocols in Molecular Biology", Green Publishing Associates and Wiley Interscience, NY (1989)).
  • stringent conditions eg as defined in J. Sambrook, EF Fritsch, T. Maniatis (1989), Molecular cloning: A laboratory manual, 2nd Edition, CoId Spring Habor Laboratory Press, CoId Spring Habor, USA or Ausubel, "Current Protocols in Molecular Biology", Green Publishing Associates and Wiley Interscience, NY (1989)).
  • stringent hybridization conditions hybridization in 4 x SSC at 65 ° C (alternatively in 50% formamide and 4X SSC at 42 ° C), followed by several washes in 0.1 x SSC at 65 ° C for a total of approximately one hour.
  • An example of less stringent hybridization conditions is hybridization in 4 x SSC at 37 ° C, followed by several washing steps in 1 x SSC at room temperature.
  • such substances are constituents of a body fluid, in particular blood, whole blood, blood plasma, blood serum, patient serum, urine, cerebrospinal fluid, synovial fluid or a tissue extract of the patient.
  • the marker sequences according to the invention may be present in a significantly higher or lower expression rate or concentration, which points to the neurodegenerative diseases.
  • the relative expression rates ill / healthy of the marker sequences according to the invention for neurodegenerative diseases is determined by means of proteomics or nucleic acid blots.
  • the marker sequences have, in another embodiment of the invention, a recognition signal which is addressed to the substance to be bound (e.g., antibody, nucleic acid).
  • the recognition signal for a protein is preferably an epitope and / or paratope and / or hapten and, for a cDNA, a hybridization or binding region.
  • the marker sequences according to the invention are the subject of Table A and can be identified unambiguously by the respectively cited database entry (also by means of the Internet: http://www.ncbi.nlm.nih.gov/) (see Table A: Accession No. there).
  • the marker sequences also include such modifications of the cDNA sequence and the corresponding amino acid sequence, such as chemical modification, such as citrullination, acetylation, phosphorylation, glycosylation or polyA strand and other modifications known to those skilled in the art.
  • chemical modification such as citrullination, acetylation, phosphorylation, glycosylation or polyA strand and other modifications known to those skilled in the art.
  • partial sequences or fragments of the marker sequences according to the invention are also included. In particular, those partial sequences which have an identity of 95%, 90%, in particular 80% or 70% with the marker sequences according to the invention.
  • the respective marker sequence may be represented in different amounts in one or more regions on a solid support.
  • the regions may each comprise a total of marker sequences, i. a sufficient number of different marker sequences, in particular 2 to 5 or 10 or more and optionally further nucleic acids and / or proteins, in particular biomarkers.
  • at least 96 to 25,000 (numerically) or more are preferred from different or identical marker sequences and further nucleic acids and / or proteins, in particular biomarkers.
  • Also preferred are more than 2,500, more preferably 10,000 or more different or identical marker sequences and, if appropriate, further nucleic acids and / or proteins, in particular biomarkers.
  • Another object of the invention relates to an array of marker sequences containing at least one marker sequence of a cDNA selected from the group SEQ 1-927, in particular those in each case from the group SEQ 1 - 293, 294 - 664, 665-927 or in each case a protein coding therefor.
  • the array contains at least 2 to 5 or 10, preferably 30 to 50 marker sequences or 50 to 100 or more marker sequences.
  • “arrangement” synonymously means “array” and insofar as this "array” is used to identify substances on marker sequences, this is to be understood as meaning an “assay” or a diagnostic device.
  • the arrangement is designed such that those represented on the assembly Marker sequences in the form of a grid on a solid support. Further, such arrangements are preferred which allow a high density array of protein binders and spotting the marker sequences. Such high density spotted assemblies are disclosed, for example, in WO 99/57311 and WO 99/57312, and may be advantageously used in a robotic automated high throughput method.
  • test or diagnostic device also encompasses such embodiments of a device as ELISA, bead-based assay, line assay, Western blot, immunochromatographic methods (eg, so-called lateral flow immunoassays) or similar immunological single or Multiplex detection method
  • a protein biochip in the sense of this invention is the systematic arrangement of proteins on a solid support.
  • the marker sequences of the assembly are fixed to a solid support, but preferably spotted or immobilized even printed, i. applied reproducibly.
  • One or more marker sequences may be present several times in the totality of all marker sequences and be present in different amounts relative to one spot. Further, the marker sequences may be standardized on the solid support (e.g., by serial dilution series of, e.g., human globulins as internal calibrators for data normalization and quantitative evaluation).
  • the invention relates to an assay or protein biochip consisting of an array containing marker sequences according to the invention.
  • the marker sequences are present as clones.
  • Such clones can be obtained, for example, by means of a cDNA expression library according to the invention (Büssow et al., 1998 (supra)).
  • expression libraries containing clones are obtained by means of expression vectors from an expressing cDNA library consisting of the cDNA marker sequences.
  • These expression vectors preferably contain inducible promoters. The induction of expression can be done, for example, by means of an inducer, such as IPTG. Suitable expression vectors are described in Terpe et al. (Terpe T Appl Microbiol Biotechnol 2003 Jan; 60 (5): 523-33).
  • Expression libraries are known to the person skilled in the art, these can be prepared according to standard works, such as Sambrook et al., Molecular Cloning, Laboratory Handbook, 2nd edition (1989), CSH press, Gold Spring Harbor, New York Further preferred are expression libraries which are tissue-specific.
  • expression libraries which can be obtained by exon trapping are also included in the scope of the invention, and instead of the expression library, it is possible to speak of an expression bank synonymously.
  • UnicloneO library protein biochips or corresponding expression libraries which have no redundancy
  • UnicloneO library protein biochips or corresponding expression libraries which have no redundancy
  • WO 99/57311 and WO 99/57312 preferred Uniclone libraries have a high content of non-defective, fully expressed proteins of a cDNA expression library.
  • the clones may not be such as transformed bacteria, recombinant phage or transformed cells of mammals, insects, fungi, yeasts or plants.
  • the clones are fixed on a solid support, spotted or immobilized. Therefore, the invention relates to an arrangement wherein the marker sequences are present as clones.
  • the marker sequences may be in the form of a fusion protein containing, for example, at least one affinity epitope or "tag".
  • the tag may be one such as c-myc, His-tag, Arg-tag, FLAG, alkaline phosphatase, V5 tag, T7 tag or Strep tag, HAT tag, NusA, S-tag, SBP tag , Thioredoxin, DsbA, a fusion protein, preferably a cellulosic binding domain, green fluorescent protein, maltose binding protein, calmodulin binding protein, glutathione S-transferase or lacZ.
  • solid support includes embodiments such as a filter, a membrane, a magnetic or fluorophore-labeled bead, a silicon wafer, glass, metal, plastic, a chip, a mass spectrometric target, or a matrix.
  • a filter is preferred according to the invention.
  • the filter is PVDF, nitrocellulose or nylon (e.g., Immobilon P Millipore, Protran Whatman, Hybond N + Amersham).
  • this corresponds to a grid having the size of a microtiter plate (8-12 wells strips, 96 wells, 384 wells or more), a silicon wafer, a chip, a mass spectrometric target or a matrix.
  • the invention relates to an assay or protein biochip for identifying and characterizing a substance for neurodegenerative diseases, characterized in that an arrangement or assay according to the invention with a.) At least one Binding substance is brought into contact and b.) A binding success is detected.
  • the invention relates to a method for identifying and characterizing a substance for neurodegenerative diseases, characterized in that an arrangement or assay according to the invention is brought into contact with a.) At least one substance to be investigated and b.) A binding success is detected.
  • the substance to be assayed may be any native or non-native biomolecule, synthetic chemical molecule, mixture or substance library.
  • the evaluation of the binding success is carried out, for example, using commercially available image analysis software (GenePix Pro (Axon Laboratories), Aida (Raytest), ScanArray (Packard Bioscience).
  • the visualization of protein-protein interactions according to the invention can be, for example, by fluorescence labeling, biotinization, radio-isotopic labeling or colloidal gold or latex particle labeling
  • Bound antibodies are detected by secondary antibodies labeled with commercially available reporter molecules (eg Cy, Alexa, Dyomics, FITC or similar fluorescent dyes, colloidal gold or latex particles), or with reporter enzymes such as alkaline phosphatase, horseradish peroxidase, etc., and the corresponding colorimetric, fluorescent, or chemiluminescent substrates, for example, by means of a microarray laser scanner, a CCD camera, or visually.
  • the invention relates to a drug / drug or prodrug developed for neurodegenerative diseases and obtainable by the use of the assay or protein biochip according to the invention.
  • the invention also relates to the use of an inventive arrangement or an assay for screening drugs for neurodegenerative diseases.
  • the invention also relates to a target for the treatment and therapy of neurodegenerative diseases, each selected from the group SEQ 1-927, in particular those each from the group SEQ 1 - 293, 294 - 664, 665-927 or one each for it coding protein.
  • the invention likewise relates to the use of the marker sequences according to the invention, preferably in the form of an arrangement, as an affinity material for carrying out apheresis or, respectively, for the same.
  • a blood wash wherein substances from body fluids of a patient with neurodegenerative diseases, such as blood or plasma, bind to the marker sequences of the invention and thus the body fluid can be selectively withdrawn.
  • Ten or more patient samples were individually screened against a cDNA expression library.
  • the neurodegenerative disease-specific expression clones were determined by comparison with ten or more healthy samples.
  • the identity of the marker sequences was determined by DNA sequencing.
  • FIG. 1 shows the differential screening between two protein biochips from in each case one cDNA expression bank of a patient and one healthy subject.
  • the Differential clones are detected by fluorescence labeling and evaluated bioinformatorisch.
  • NM_ _000972 307.
  • NT_ 077661 351.
  • NM_ _005861 308.
  • NM_ 001614 352.
  • NM_ _032025 309. NT_ _034880 353.
  • NT_ _008413 311.
  • NM _018023 355.
  • NM_ _005861 325.
  • NT_ _032977 369.
  • NT_ 004350 438 NM_ 016525 482.
  • NM_ JL82923 452.
  • NM_ _018011 496.
  • NM_ _002949 593.
  • NM_ _184041 705.
  • NM_ _002383 851.
  • NM _024040 895.
  • NM_ _031454 852.
  • NM_ _006035 896.

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Abstract

L'invention concerne de nouvelles séquences de marqueurs pour des maladies neurodégénératives et leur utilisation aux fins de diagnostic ainsi qu'un procédé destiné au criblage des principes actifs potentiels pour des maladies neurodégénératives au moyen desdites séquences de marqueurs. L'invention concerne, de plus, un dispositif de diagnostic contenant lesdites séquences de marqueurs pour des maladies neurodégénératives, en particulier une biopuce à protéines, ainsi que son utilisation.
EP08864285A 2007-12-21 2008-12-22 Séquences de marqueurs pour des maladies neurodégénératives et leur utilisation Withdrawn EP2222880A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102007062847A DE102007062847A1 (de) 2007-12-21 2007-12-21 Markersequenzen für neurodegenerative Erkrankungen und deren Verwendung
PCT/DE2008/002144 WO2009080017A2 (fr) 2007-12-21 2008-12-22 Séquences de marqueurs pour des maladies neurodégénératives et leur utilisation

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EP2222880A2 true EP2222880A2 (fr) 2010-09-01

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US (1) US20110184375A1 (fr)
EP (1) EP2222880A2 (fr)
AU (1) AU2008340851A1 (fr)
CA (1) CA2710401A1 (fr)
DE (1) DE102007062847A1 (fr)
WO (1) WO2009080017A2 (fr)

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WO2009030226A2 (fr) * 2007-09-03 2009-03-12 Protagen Ag Séquences de marqueurs de la polyarthrite rhumatoïde et leur utilisation
EP2483694A1 (fr) * 2009-10-01 2012-08-08 Protagen AG Marqueurs biologiques pour la maladie d'alzheimer
EP2441848A1 (fr) * 2010-10-12 2012-04-18 Protagen AG Séquences de marqueur pour le lupus érythémateux systémique et son utilisation
EP2487251A1 (fr) * 2011-02-13 2012-08-15 Protagen AG Séquences de marqueur pour le diagnostic d'un carcinome de la prostate et leur utilisation
CN108034707B (zh) * 2017-12-06 2019-01-08 北京泱深生物信息技术有限公司 Spag7基因在制备老年痴呆诊断制剂中的应用

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WO2009080017A3 (fr) 2009-10-29
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CA2710401A1 (fr) 2009-07-02
US20110184375A1 (en) 2011-07-28

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