EP2318546A2 - Séquences de marqueurs pour maladies inflammatoires de la prostate, le cancer de la prostate, et leurs utilisations - Google Patents

Séquences de marqueurs pour maladies inflammatoires de la prostate, le cancer de la prostate, et leurs utilisations

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Publication number
EP2318546A2
EP2318546A2 EP09772574A EP09772574A EP2318546A2 EP 2318546 A2 EP2318546 A2 EP 2318546A2 EP 09772574 A EP09772574 A EP 09772574A EP 09772574 A EP09772574 A EP 09772574A EP 2318546 A2 EP2318546 A2 EP 2318546A2
Authority
EP
European Patent Office
Prior art keywords
prostate
marker sequences
seq
inflammatory diseases
marker
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Withdrawn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
EP09772574A
Other languages
German (de)
English (en)
Inventor
Helmut E. Meyer
Angelika Lueking
Jens Beator
Axel Kowald
Georg Bartsch
Helmut Klocker
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 EP20130190149 priority Critical patent/EP2712932A3/fr
Priority to EP20130190158 priority patent/EP2712933A3/fr
Priority to EP15152989.8A priority patent/EP2902505A3/fr
Priority to EP20130190162 priority patent/EP2712934A3/fr
Publication of EP2318546A2 publication Critical patent/EP2318546A2/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Withdrawn legal-status Critical Current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
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57434—Specifically defined cancers of prostate
    • 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
    • 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
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • 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
    • 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
    • C12Q2600/16—Primer sets for multiplex assays
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/34—Genitourinary disorders
    • G01N2800/342—Prostate diseases, e.g. BPH, prostatitis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
    • 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 prostate inflammatory diseases, prostate carcinoma and their diagnostic use, including a method for the screening of potential drugs for such prostate diseases by means of these marker sequences. Furthermore, the invention relates to a diagnostic device containing such marker sequences for prostate inflammatory diseases, prostate carcinoma, in particular a protein biochip and its use.
  • Protein biochips are gaining an increasing industrial
  • Protein biochips have become established as screening tools.
  • 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, 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
  • 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.
  • Laboratory parameters include acid phosphatase (SP) and prostate specific antigen (PSA) for diagnosis of SP.
  • SP acid phosphatase
  • PSA prostate specific antigen
  • Prostate cancer Especially the PSA currently has a high priority in diagnostics. It is specific for the prostate, but not for a tumor, but may also be elevated in inflammation, benign prostatic hyperplasia, urinary retention, or for no apparent reason. A value above 4 ng / ml is already in need of clarification.
  • the object of the present invention is to provide improved marker sequences and their diagnostic use for the treatment of prostate inflammatory diseases to prostate cancer.
  • the invention relates to the use of marker sequences for the diagnosis of
  • Prostate inflammatory diseases to prostate cancer particularly preferably prostate cancer, wherein at least one marker sequence of a cDNA selected from the group SEQ 1-174 or each one coding protein or each a subsequence or fragment thereof (hereinafter: marker sequences according to the invention) to or to a patient to be examined is determined.
  • the marker sequences according to the invention could by means of differential screening of samples and healthy subjects with patient samples with
  • Prostate inflammatory diseases prostate cancer can be identified.
  • these marker sequences according to the invention by means of protein biochips (see examples).
  • prostate inflammatory diseases to prostate cancer includes a group of diseases from prostate to the chronic forms of all prostate inflammations and their establishment as prostate cancer or prostate cancer (definition, for example, according to Pschyrembel, de Gruyter, 261st edition (2007), Berlin).
  • 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 to a patient to be examined.
  • 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 1-174 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 prostate inflammatory diseases to prostate carcinoma, wherein a.) At least one marker sequence of a cDNA selected from the group SEQ 1-174 or each a protein coding therefor or each of a partial sequence or fragment thereof applied to a solid support and b.) are in 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. ) he follows .
  • the invention also relates to diagnostic agents for the diagnosis of prostate inflammatory diseases to
  • the detection of such an interaction can be carried out for example by a probe, in particular by an antibody.
  • the invention therefore likewise has the object of providing a diagnostic device or an assay, in particular a protein biochip, which is suitable for the
  • the invention relates to a method for stratifying, in particular for risk stratification and / or therapy control of a patient with
  • Prostate inflammatory diseases to prostate carcinoma wherein at least one marker sequence of a cDNA selected from the group SEQ 1-174 or in each case a protein coding therefor is determined on a patient to be examined.
  • Prostate inflammatory diseases to prostate cancer as well as the meaningful 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 respect to therapy or its course of therapy.
  • Diagnosis in the sense of this invention means the positive determination of the prostate inflammatory diseases up to prostate cancer by means of the marker sequences according to the invention and the assignment of the patients to the
  • diagnosis includes medical diagnostics and related investigations, in particular in vitro diagnostics and laboratory diagnostics, also proteomics and nucleic acid blots. Further investigation may be needed to secure and exclude other diseases. Therefore, the term diagnosis also includes the differential diagnosis of prostate inflammatory diseases,
  • Prostate cancer by means of the marker sequences of the invention and the prognosis of prostate inflammatory diseases, prostate cancer.
  • 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 that the subject is examined for prostate inflammatory diseases to prostate cancer.
  • marker sequences in the sense of this invention means that the cDNA or the respectively obtainable polypeptide or protein significantly for
  • Prostate inflammatory diseases prostate cancer are.
  • the cDNA or the respective polypeptide or protein obtainable therefrom may interact with substances from the body fluid or tissue extract of a patient with prostate inflammatory diseases up to the
  • Prostate carcinoma eg, antigen (epitope) / antibody (paratope) interaction
  • at least one marker sequence of a cDNA selected from the group SEQ. 1-174 or in each case a protein coding therefor or in each case a partial sequence or fragment thereof on a patient to be examined is determined" in that an interaction between the body fluid or tissue extract
  • Such an interaction is eg a binding, in particular a binding substance on at least one marker sequence according to the invention or in the case of a cDNA hybridization with a suitable substance under selected conditions, in particular stringent conditions (eg as defined in US Pat J. Sambrook, EF Fritsch, T.
  • the marker sequences according to the invention can be present in a significantly higher or lower expression rate or concentration, which points to the prostate inflammatory diseases, prostate carcinoma.
  • the relative expression rates ill / healthy of the marker sequences according to the invention for prostate inflammatory diseases, prostate carcinoma is determined by means of proteomics or nucleic acid blots.
  • the marker sequences have a recognition signal which is addressed to the substance to be bound (for example antibodies,
  • 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 clearly identified by the respective cited database entry (also by means of the Internet: http://www.ncbi.nlm.nih.gov/) (see Table A: there Accession No.), see also the associated sequence listing.
  • the invention also relates to the full-length sequences of the markers according to the invention and indeed as defined in Table 1 on the known database entry according to Table A, hereinafter called SEQ ID NO: 174a.
  • the specific marker sequences SEQ 1-174 are preferred according to the invention.
  • 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,
  • partial sequences or fragments of the marker sequences according to the invention are also included.
  • those partial sequences which have an identity of 95%, 90%, in particular 80% or 70% with the marker sequences according to the invention are also included.
  • Partial sequences are also those sequences having 50 to 100 nucleotides, 70-120 nucleotides of a sequence of SEQ 1-174, or peptides obtainable therefrom.
  • the respective marker sequence may be represented in different amounts in one or more regions on a solid support.
  • the regions can each have an entirety of marker sequences, ie a sufficient number of different marker sequences, in particular 2 to 5 or 10 or more and, if appropriate, 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.
  • Further preferred are more than 2,500, more preferably 10,000 or more different or the same Marker sequences and, if necessary, 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 1-174 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 such that the marker sequences represented on the array are 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 imprinted, ie applied reproducible.
  • 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.
  • the marker sequences can be standardized on the solid support (eg by means of serial dilution series of eg 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 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, and these can be prepared according to standard works, such as Sambrook et al., Molecular Cloning, Laboratory Handbook, 2nd edition (1989), CSH press, CoId Spring Harbor, New York Further preferred are expression libraries which are tissue-specific In addition, according to the invention, expression libraries which can be obtained by exon trapping are also included in the invention, and instead of an expression library it is possible to speak synonymously of an expression library. Also preferred are 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 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.
  • PVDF, nitrocellulose or nylon are also preferred as filters (eg 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
  • Prostate inflammatory diseases Prostate cancer, characterized in that an arrangement or assay according to the invention with a.) At least one substance to be examined is brought into contact and b.) A binding success is detected.
  • the invention further relates to a method for identifying and characterizing a substance for prostate inflammatory diseases, prostate carcinoma, 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.
  • reporter molecules eg Cy, Alexa, Dyomics, FITC or similar fluorescent dyes, colloidal gold or latex particles
  • reporter enzymes such as al
  • the invention relates to a drug / drug or prodrug for prostate inflammatory diseases, prostate carcinoma developed 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 the screening of drugs for prostate inflammatory diseases, prostate carcinoma.
  • the invention also relates to a target for the treatment and therapy of prostate inflammatory diseases, prostate carcinoma, each selected from the group SEQ 1-174 or in each case a protein coding therefor.
  • the invention also relates to the use of the marker sequences according to the invention, 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 prostate inflammatory diseases, prostate cancer, such as blood or plasma, bind to the marker sequences according to the invention and thus the body fluid can be selectively withdrawn.
  • 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.
  • Threshold method which is suitable for both classification and visual representation of the data.

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Abstract

L'invention concerne de nouvelles séquences de marqueurs pour les maladies inflammatoires de la prostate, le cancer de la prostate, ainsi que leur utilisation diagnostique, notamment un procédé de criblage afin d'identifier au moyen desdites séquences de marqueurs des substances actives potentielles pour de telles pathologies de la prostate. L'invention concerne également un dispositif de diagnostic contenant de telles séquences de marqueurs pour les maladies inflammatoires de la prostate, le cancer de la prostate, en particulier une biopuce à protéines, ainsi que l'utilisation de ce dispositif.
EP09772574A 2008-07-04 2009-07-06 Séquences de marqueurs pour maladies inflammatoires de la prostate, le cancer de la prostate, et leurs utilisations Withdrawn EP2318546A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP20130190149 EP2712932A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190158 EP2712933A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP15152989.8A EP2902505A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190162 EP2712934A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE200810031699 DE102008031699A1 (de) 2008-07-04 2008-07-04 Markersequenzen für Prostataentzündungserkrankungen, Prostatakarzinom und deren Verwendung
PCT/EP2009/058534 WO2010000874A2 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour maladies inflammatoires de la prostate, le cancer de la prostate, et leurs utilisations

Related Child Applications (4)

Application Number Title Priority Date Filing Date
EP20130190158 Division EP2712933A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP15152989.8A Division EP2902505A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190162 Division EP2712934A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190149 Division EP2712932A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation

Publications (1)

Publication Number Publication Date
EP2318546A2 true EP2318546A2 (fr) 2011-05-11

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Family Applications (5)

Application Number Title Priority Date Filing Date
EP15152989.8A Withdrawn EP2902505A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190162 Withdrawn EP2712934A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190149 Withdrawn EP2712932A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190158 Withdrawn EP2712933A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP09772574A Withdrawn EP2318546A2 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour maladies inflammatoires de la prostate, le cancer de la prostate, et leurs utilisations

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EP15152989.8A Withdrawn EP2902505A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190162 Withdrawn EP2712934A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190149 Withdrawn EP2712932A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation
EP20130190158 Withdrawn EP2712933A3 (fr) 2008-07-04 2009-07-06 Séquences de marqueurs pour les maladies avec inflammation de la prostate, carcinome de la prostate et leur utilisation

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EP (5) EP2902505A3 (fr)
DE (1) DE102008031699A1 (fr)
WO (1) WO2010000874A2 (fr)

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WO2012115789A2 (fr) 2011-02-24 2012-08-30 Cornell University Mutations spop récurrentes dans le cancer de la prostate
US10060911B2 (en) 2011-08-19 2018-08-28 Protagen Aktiengesellschaft Method for diagnosis of high-affinity binders and marker sequences
US20140371095A1 (en) * 2011-11-14 2014-12-18 Protagen Ag Novel method for identifying specific marker sequences for prostate cancer
AU2014360503A1 (en) * 2013-12-03 2016-06-30 Celestra Life Science Llc Rationale-based design of a targeted therapy for cancer

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Publication number Publication date
US20110275528A1 (en) 2011-11-10
EP2712932A2 (fr) 2014-04-02
WO2010000874A3 (fr) 2010-07-22
US20150197820A1 (en) 2015-07-16
DE102008031699A1 (de) 2010-01-14
EP2712932A3 (fr) 2014-07-30
WO2010000874A2 (fr) 2010-01-07
EP2712934A3 (fr) 2014-07-30
EP2712933A3 (fr) 2014-07-30
EP2712934A2 (fr) 2014-04-02
EP2712933A2 (fr) 2014-04-02
EP2902505A3 (fr) 2015-09-30
US20130217591A1 (en) 2013-08-22
EP2902505A2 (fr) 2015-08-05

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