EP2622350A2 - Séquences de marqueurs pour la sclérose multiple et utilisation desdites séquences de marqueurs - Google Patents

Séquences de marqueurs pour la sclérose multiple et utilisation desdites séquences de marqueurs

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Publication number
EP2622350A2
EP2622350A2 EP11779356.2A EP11779356A EP2622350A2 EP 2622350 A2 EP2622350 A2 EP 2622350A2 EP 11779356 A EP11779356 A EP 11779356A EP 2622350 A2 EP2622350 A2 EP 2622350A2
Authority
EP
European Patent Office
Prior art keywords
homo sapiens
protein
multiple sclerosis
marker sequences
seq
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Withdrawn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
EP11779356.2A
Other languages
German (de)
English (en)
Inventor
Angelika Lueking
Axel Kowald
Heike GÖHLER
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
Priority to EP11779356.2A priority Critical patent/EP2622350A2/fr
Publication of EP2622350A2 publication Critical patent/EP2622350A2/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Withdrawn legal-status Critical Current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
    • 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
    • C07K14/4713—Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
    • 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
    • G01N33/6854—Immunoglobulins
    • 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
    • C12Q2600/156—Polymorphic or mutational markers
    • 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
    • G01N2800/285—Demyelinating diseases; Multipel sclerosis

Definitions

  • the present invention relates to novel marker sequences for multiple sclerosis and their diagnostic use, including a method for screening potential drugs for multiple sclerosis disorders by means thereof
  • the invention relates to a
  • diagnostic device containing such marker sequences for multiple sclerosis, in particular a protein biochip and its use.
  • Protein biochips are gaining an increasing industrial
  • Protein biochips require the necessary proteins to be available. In particular,
  • GATEWAY recombinational cloning application to the cloning of large numbers of open reading frames or ORFeems. Methods Enzymol, 328, 575-592).
  • ORFeems open reading frames
  • Methods Enzymol, 328, 575-592 are strongly related to the progress of genome sequencing projects and the annotation of these gene sequences.
  • determination of the expressed sequence is due
  • the cDNA of a particular tissue in a bacterial or a eukaryotic expression vector, such as yeast, is cloned.
  • the vectors used for the expression are generally characterized by the fact that they carry inducible promoters, with which the timing of protein expression can be controlled.
  • expression vectors have sequences for so-called
  • Affinity epitopes or proteins on the one hand for the specific detection of the recombinant fusion proteins by means of a directed against the affinity epitope
  • Antibody on the other hand becomes the specific one
  • the object of the present invention is to provide improved marker sequences and their diagnostic
  • the invention relates to the use of
  • Marker sequences for the diagnosis of multiple sclerosis wherein at least one marker sequence of a cDNA selected from the group SEQ 1-308 or in each case a protein coding therefor or in each case a partial sequence or fragment thereof
  • marker sequences according to the invention to or from a patient to be examined.
  • an improved bioinformatic evaluation is strained and the samples are particularly preferably taken from the cerebrospinal fluid (CSF).
  • CSF cerebrospinal fluid
  • specially selected samples are used that meet the high sensitivity of a protein biochip.
  • multiple sclerosis (MS), also encephalomyelitis disseminata) refers to an autoimmune inflammatory /
  • demyelinating and degenerative disease of central nervous system disease (definition, for example, according to Pschyrembel, de Gruyter, 261st edition (2007), Berlin).
  • Essential to the invention is that the samples are not taken from conventional blood banks, but from MS patients
  • the complex sample selection method allows, for example, a sufficient advantageous delimitation of diseases such as MS symptom-like neuroborelliosis. Furthermore, false-positive results are excluded, on the one hand due to the strict bioinformatory evaluation (see examples) and by comparing the results on a protein biochip according to the invention with eg sera from Neuroborelliosis patients who do not have multiple sclerosis
  • the invention therefore also relates to such indication-specific protein biochips according to the invention for the diagnosis of
  • Sclerosis patients can be normalized and in this way false-positive proteins can be removed. Remaining non-false positive proteins can be reassembled on a protein biochip, called rearraying. This also allows the exclusion of autoantibodies that are positive for E. coli. This is another qualitative
  • 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 is made in an ex vivo / in vitro diagnosis.
  • the invention relates to the use of marker sequences as diagnostics, wherein at least one marker sequence of a cDNA is selected from the group SEQ 1-308 or in each case a protein coding therefor or in each case a partial sequence or fragment thereof.
  • the invention relates to a method for the diagnosis of multiple sclerosis, where a.) At least one marker sequence of a cDNA selected from the group SEQ 1-308 or a protein coding therefor, or a partial sequence or fragment thereof is applied to a solid support and b .) with body fluid or tissue extract one
  • the invention also relates to diagnostics for
  • the detection of such an interaction can, for example, by a probe, in particular by an antibody
  • the invention also relates to the task of providing a diagnostic device or an assay, in particular a protein biochip, which allows a diagnosis or examination for multiple sclerosis. Furthermore, the invention relates to a method for
  • Stratify in particular for risk stratification and / or therapy control of a patient with multiple sclerosis, wherein at least one marker sequence of a cDNA selected from the group SEQ 1 - 308 or in each case a protein coding therefor is determined on a patient to be examined.
  • 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 finding of multiple sclerosis by means of
  • Marker sequences of the invention and the assignment of patients to the disease of multiple sclerosis.
  • diagnosis includes medical diagnostics and
  • diagnosis also includes the
  • the term "stratification" includes in particular the
  • patient means any subject - human or mammal - with the proviso that the subject is being examined for multiple sclerosis.
  • marker sequences in the sense of this invention means that the cDNA or the respective polypeptide or protein obtainable therefrom are significant for multiple sclerosis
  • the cDNA or the respectively obtainable polypeptide or protein can interact with substances from the body fluid or tissue extract of a Patients with multiple sclerosis (eg antigen
  • At least one marker sequence of a cDNA selected from the group SEQ 1-308 or in each case a protein coding for it or in each case a partial sequence or fragment thereof on a patient to be examined is determined" that an interaction between the body fluid or tissue extract of a patient and the marker sequences according to the invention is detected.
  • Such an interaction is, for example, 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
  • Hybridization conditions are: 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 about one hour.
  • An example of less stringent hybridization conditions is hybridization in 4 x SSC at 37 ° C, followed by several washes in 1 x SSC at room temperature. Such substances are part of a component according to the invention
  • 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 multiple sclerosis.
  • the relative expression rates sick / healthy of the invention may be present in a significantly higher or lower expression rate or concentration, which points to multiple sclerosis.
  • the marker sequences for multiple sclerosis.
  • the marker sequences have a recognition signal which is addressed to the substance to be bound (for example antibodies,
  • the recognition signal is preferably an epitope and / or paratope and / or hapten and, for a cDNA, a hybridization or hybridization protein
  • the marker sequences of the invention are the subject of Table A and can by the respective cited
  • the invention also relates to the full-length sequences of the markers according to the invention and as defined in Table A on the known database entry, hereinafter called SEQ -308a (cDNA) or SEQ ID-308b (protein).
  • SEQ. 1-308 again represent partial sequences, at least with high homology.
  • marker sequences SEQ 1-308 are according to the invention.
  • marker sequences also include such modifications of the cDNA sequence and the corresponding
  • Amino acid sequence such as chemical modification, such as
  • marker sequences 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.
  • Partial sequences are also those sequences which have 50 to 100 nucleotides, 70-120 nucleotides of a sequence of SEQ 1-308, or peptides obtainable therefrom.
  • Marker sequences are functionally defined and include those sequences which have the same inventive diagnostic function.
  • Marker sequence can be represented in different amounts in one or more areas on a solid support. This allows a variation of the sensitivity.
  • 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.
  • Biomarkers Further preferred are more than 2,500, more preferably 10,000 or more different or the same
  • Marker sequences and optionally other nucleic acids and / or proteins, in particular biomarkers are optionally other 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 a cDNA selected from the group SEQ 1-308 or in each case a protein coding therefor.
  • the group SEQ 1-308 or in each case a protein coding therefor.
  • “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 are in the form of a grid on a solid support. Furthermore, such arrangements are preferred which include a high density array of protein binders
  • 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 includes such
  • Embodiments of a device such as ELISA, bead-based assay, line assay, Western blot, immunochromatographic
  • 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 imprinted, ie applied reproducible.
  • One or more marker sequences can be present multiple times in the totality of all marker sequences and be present in different amounts relative to one spot.
  • the marker sequences can be standardized on the solid support (eg by serial dilution series of eg
  • 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)).
  • such expression libraries become
  • Obtained marker sequences are obtained. These expression vectors preferably contain inducible promoters. The induction of
  • Expression can e.g. by means of an inductor, such as IPTG.
  • IPTG inductor
  • 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, Cold Spring Harbor, New York Further preferred are such expression libraries
  • tissue specific eg human tissue, in particular human organs
  • expression libraries are also included according to the invention, which can be obtained by exon trapping. Instead of expression library can be spoken synonymously from an expression bank.
  • protein biochips or corresponding expression libraries which have no redundancy (so-called: Uniclone® library) and can be prepared, for example, according to the teachings of WO 99/57311 and WO 99/57312. These 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.
  • 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 in the particular form
  • At least one affinity epipope or "tag” contains.
  • 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 cellulose-binding one
  • solid support includes embodiments such as a filter, a membrane, a magnetic or fluorophore-labeled bead
  • Silicon wafer, glass, metal, plastic, a chip, a mass spectrometric target or a matrix 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).
  • nitrocellulose e.g., Immobilon P Millipore, Protran Whatman, Hybond N + Amersham.
  • this corresponds to a grid having the order 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 multiple sclerosis 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 invention relates to a method for identifying and characterizing a substance for multiple sclerosis, 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
  • the substance to be tested may be any native or non-native biomolecule, a synthetic chemical
  • Antigen / antibody or corresponding "means for detecting the binding success" can, for example, by means of
  • reporter enzymes such as alkaline
  • a readout is e.g. by means of a microarray laser scanner, a CCD camera or visually.
  • the invention relates to a drug / prodrug or prodrug developed for multiple sclerosis and obtainable through the use of the
  • the invention also relates to the use of an arrangement according to the invention or an assay for the screening of drugs for multiple sclerosis.
  • the invention also relates to a target for the treatment and therapy of multiple sclerosis, each selected from the group SEQ 1-308 or in each case a protein coding therefor.
  • the invention also relates to the use of the invention
  • Marker sequences preferably in the form of an arrangement, as
  • Affinity material for performing an apheresis or iwS. a blood wash wherein substances from body fluids of a patient with multiple sclerosis, 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. Multiple sclerosis specific expression clones were identified 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.
  • Differential clones are detected by fluorescence labeling and evaluated bioinformatorisch.
  • bioinformatic analyzes In the context of biomarker identification various bioinformatic analyzes are carried out. For each serum, microarray reactivities against about 2000 measured different antigens. These data are used for a ranking of the spotted antigens regarding their
  • Intensity data performed.
  • an internal standard is used, which is spotted on each chip. Since a p-value is calculated for each antigen, methods for correcting the multiple testing are used. As a very conservative approach, a Bonferroni correction is performed and, in addition, the less restrictive False Discovery Rate (FDR) is calculated according to Benjamini & Hochberg.
  • FDR False Discovery Rate
  • the data are used to classify the sera.
  • different multivariate methods are used. These are methods from the statistical
  • Threshold method which is suitable for both classification and visual representation of the data. To avoid overfitting, a 10-fold cross-validation of the data is performed.
  • RNA exonuclease 1 homologue [Homo sapiens]
  • Plasminogen activator inhibitor 1 RNA-binding gi
  • tubulointerstitial nephritis antigen-like 1 [Homo gi
  • rho guanine nucleotide exchange factor 7 isoform a gi
  • gi 5902122 gi 197381953 spectrin beta chain brain 2 [Homo sapiens] gi 23618848 gi 56676380 protein SYS1 homolog isoform a [Homo sapiens] gi 83641870 gi 262331549 nucleophosmin isoform 3 [Homo sapiens] gi 541 12429 gi 541 12428 dedicator of cytokinesis protein 7 [ Homo sapiens] dnaJ homologous subfamily B member 1 [Homo gi
  • angio-associated migratory cell protein [Homo gi
  • nuclease-sensitive element-binding protein 1 [Homo gi
  • ubiquitin-associated protein 1 isoform 1 [Homo gi
  • nuclease-sensitive element-binding protein 1 [Homo gi
  • Immunoglobulin heavy chain variable region [Homo gi
  • gi 22027541 gi 22027540 programmed cell death protein 7 [Homo sapiens] ubiquitin-60S ribosomal protein L40 precursor gi
  • 34147354 Homo sapiens
  • amyloid beta A4 protein isoform b precursor [Homo gi
  • tumor necrosis factor receptor superfamily member gi
  • CD97 Homo sapiens CD97 molecule (CD97); transcript gi 117978489 gi
  • glial fibrillary acidic protein isoform 1 [Homo gi
  • HLA class II histocompatibility antigen DQ beta 1 gi 1150418002 gi 1150418001 chain precursor [Homo sapiens]
  • 28610150 [Homo sapiens] gi 1 19703755 gi 1 19703754 laminin; beta 2 precursor [Homo sapiens].
  • Homo sapiens protein tyrosine phosphatase Homo sapiens protein tyrosine phosphatase
  • Cytoplasmic FMR1 interacting protein 2 [Homo gi
  • interleukin-23 subunit alpha precursor [Homo gi
  • dysbindin domain-containing protein 2 isoform b gi 11 15299754 gi 11 15299753 [Homo sapiens]
  • metastasis-associated protein MTA1 [Homo gi
  • TNFAIP3-interacting protein 2 isoform 1 [Homo gi
  • interleukin-12 subunit alpha precursor [Homo gi
  • interleukin-12 subunit beta precursor [Homo gi
  • neurofascin isoform 4 precursor [Homo sapiens]
  • gi 17158044 gi 17158043 ribosomal protein S6 [Homo sapiens]
  • DEAD (Asp-Glu-Ala-Asp) box polypeptides 50 gi
  • gi 166063995 gi 166063994 general transcription factor INA [Homo sapiens] gi 72534684 gi 166197669 phospholipase D family, member 3 [Homo sapiens] gi 14591909 gi 71772259 ribosomal protein L5 [Homo sapiens]
  • GIY-YIG domain containing 2 isoform 1 [Homo gi 113129004 gi
  • nucleoside diphosphate kinase B [Homo sapiens] ubiquitin-conjugating enzyme E2M (UBC12 gi
  • SH2 domain-containing adapter protein B [Homo gi
  • heterogeneous nuclear ribonucleoprotein A1 [Homo gi
  • nuclease-sensitive element-binding protein 1 [Homo gi
  • A-kinase anchor protein 1 precursor [Homo gi 14502015 gi 1109637793 sapiens]
  • endoplasmic reticulum protein 29 isoform 1 gi
  • GTP-binding protein PTD004 isoform 2 [Homo gi
  • chromosome 12 open reading frame 51 [Homo gi 1157885806 gi 1157885805 sapiens]
  • interleukin enhancer binding factor 2 [Homo gi
  • DEAD (Asp-Glu-Ala-As) box polypeptides 19 isoform gi
  • RNA binding protein [Homo sapiens] trinucleotides repeat containing 4, isoform CRA_a gi
  • F-box and leucine-rich repeat protein 15 [Homo gi
  • gi 122937289 gi 122937288 kinesin family member 18B [Homo sapiens] gi 155029542 gi 155029541 BEN domain containing 7 isoform 1 [Homo sapiens] guanine nucleotide-binding protein, beta-1 subunit gi
  • B-cell CLL / lymphoma 1 1 B isoform 2 [Homo gi 112597635 gi 112597634 sapiens]
  • cyclin-dependent kinase inhibitor 2C (p18, inhibits gi
  • ADP-ribosylation factor-like protein 16 [Homo gi
  • myosin, heavy polypeptide 9, non-muscle [Homo gi 112667788 gi

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Abstract

L'invention concerne de nouvelles séquences de marqueurs pour la sclérose multiple et leur application diagnostique, ainsi qu'un procédé de criblage de substances actives potentielles pour les maladies sclérotiques multiples au moyen de ces séquences de marqueurs. L'invention concerne par ailleurs un dispositif de diagnostic contenant de telles séquences de marqueurs pour la sclérose multiple, en particulier une biopuce à protéines et son utilisation.
EP11779356.2A 2010-10-01 2011-10-04 Séquences de marqueurs pour la sclérose multiple et utilisation desdites séquences de marqueurs Withdrawn EP2622350A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP11779356.2A EP2622350A2 (fr) 2010-10-01 2011-10-04 Séquences de marqueurs pour la sclérose multiple et utilisation desdites séquences de marqueurs

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP10186327A EP2437060A1 (fr) 2010-10-01 2010-10-01 Séquences de marqueurs pour la sclérose multiple et leur utilisation
PCT/EP2011/067285 WO2012042062A2 (fr) 2010-10-01 2011-10-04 Séquences de marqueurs pour la sclérose multiple et utilisation desdites séquences de marqueurs
EP11779356.2A EP2622350A2 (fr) 2010-10-01 2011-10-04 Séquences de marqueurs pour la sclérose multiple et utilisation desdites séquences de marqueurs

Publications (1)

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EP2622350A2 true EP2622350A2 (fr) 2013-08-07

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EP11779356.2A Withdrawn EP2622350A2 (fr) 2010-10-01 2011-10-04 Séquences de marqueurs pour la sclérose multiple et utilisation desdites séquences de marqueurs

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US10261086B2 (en) * 2013-01-10 2019-04-16 Amrita Vishwa Vidyapeetham Differential cerebrospinal fluid reactivity to PFDN5-alpha for detection of B-cell acute lymphoblastic leukemia
US11655510B2 (en) 2015-04-20 2023-05-23 Cellecta, Inc. Experimentally validated sets of gene specific primers for use in multiplex applications
WO2016172126A2 (fr) * 2015-04-20 2016-10-27 Cellecta, Inc. Ensembles validés expérimentalement d'amorces spécifiques d'un gène pour utilisation dans des applications multiplex
EP3586866A1 (fr) * 2018-06-28 2020-01-01 Universität Zürich Protéines et fragments immunodominants dans la sclérose en plaques
WO2020036926A1 (fr) 2018-08-17 2020-02-20 Cellecta, Inc. Préparation multiplex de fragments d'adn spécifiques à un gène à code à barres

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WO2012042062A2 (fr) 2012-04-05
EP2437060A1 (fr) 2012-04-04

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