EP1917531A2 - Marqueurs polypeptidiques pour le diagnostic du cancer de la vessie - Google Patents

Marqueurs polypeptidiques pour le diagnostic du cancer de la vessie

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Publication number
EP1917531A2
EP1917531A2 EP06793031A EP06793031A EP1917531A2 EP 1917531 A2 EP1917531 A2 EP 1917531A2 EP 06793031 A EP06793031 A EP 06793031A EP 06793031 A EP06793031 A EP 06793031A EP 1917531 A2 EP1917531 A2 EP 1917531A2
Authority
EP
European Patent Office
Prior art keywords
markers
bladder cancer
sample
polypeptide
amplitude
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.)
Ceased
Application number
EP06793031A
Other languages
German (de)
English (en)
Inventor
Harald Mischak
Stefan Wittke
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.)
Mosaiques Diagnostics and Therapeutics AG
Original Assignee
Mosaiques Diagnostics and Therapeutics AG
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 Mosaiques Diagnostics and Therapeutics AG filed Critical Mosaiques Diagnostics and Therapeutics AG
Priority to EP20100183092 priority Critical patent/EP2333550A3/fr
Priority to EP06793031A priority patent/EP1917531A2/fr
Publication of EP1917531A2 publication Critical patent/EP1917531A2/fr
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44704—Details; Accessories
    • G01N27/44717—Arrangements for investigating the separated zones, e.g. localising zones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B10/007—Devices for taking samples of body liquids for taking urine samples
    • 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
    • G01N33/575—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • 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
    • G01N33/575—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57557—Immunoassay; Biospecific binding assay; Materials therefor for cancer of other specific parts of the body, e.g. brain
    • 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
    • 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
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6848—Methods of protein analysis involving mass spectrometry

Definitions

  • the present invention relates to the use of the presence or absence or amplitude of one or more peptide markers in a sample of an individual for (differential) diagnosis of bladder cancer, and a method of diagnosing bladder cancer, wherein the presence or absence or amplitude of the peptide marker (s) (s) is indicative of the presence as well as the tumor stage of bladder cancer.
  • Bladder cancer is a malignant tumor on the urinary bladder.
  • Bladder cancer is one of the most common malignant diseases. In the urological field, it is the second most common cancer after prostate cancer. In the German-speaking world about 22 out of every 100,000 people are affected each year. In men, bladder cancer occurs about two to three times more often than in women. Every year, an estimated 13,000 men and 5,000 women fall ill in the Federal Republic of Germany. Bladder cancer is a disease of old age. The risk of disease increases with age from the age of 40.
  • bladder cancer There is no real screening for bladder cancer. For urinary or urinary problems, it is highly recommended that you see a doctor quickly. This may cause bladder cancer to be detected earlier. If there is a suspicion of a tumor in the bladder, eg if blood has been detected in the urine or if there are persistent symptoms of bladder irritation, a cystoscopy is performed. If the examiner sees a tumor in the urinary bladder wall, he can estimate which wall layers the tumor penetrates and also take samples, which are then examined microscopically. Depending on tumor growth, a distinction is made between superficial and infiltrating (ins Tissue invaded) carcinomas.
  • the latter have already grown into the muscles of the urinary bladder and can spread to the neighboring organs (in the case of a male, for example, a prostate, in the case of a woman, for example, a womb).
  • the histological-pathological classification of the mucosal tumors is carried out according to the TNM system.
  • pTa non invasive papillary carcinoma of the mucosa (urothelium)
  • pTcis carcinoma in situ
  • pTl infiltration under the mucosa (subepithelial connective tissue), subclassification pTla-c
  • a radiographic examination of the entire urinary tract can be carried out.
  • the urine is examined microscopically for malignant cells.
  • stage staging further diagnostic procedures are used such as ultrasound, CT (computerized tomography) or MRI (magnetic resonance tomography).
  • CT computerized tomography
  • MRI magnetic resonance tomography
  • the object of the present invention was to overcome the mentioned disadvantages of the prior art, in particular to define polypeptide markers which can be unambiguously assigned to individual peptides and are suitable for the diagnosis of bladder cancer and / or for the determination of the tumor stage.
  • certain peptide markers can be used in a sample of an individual both for the diagnosis of bladder cancer and for the assessment of the tumor stage of a bladder carcinoma.
  • an object of the present invention is the use of the presence or absence or amplitude of at least one polypeptide marker in a sample of an individual for the diagnosis of bladder cancer, wherein the polypeptide marker is selected from the polypeptide labels Nos. 1 to 836, which are replaced by those described in U.S. Pat Table 1 molecular masses and their migration times are characterized.
  • Table 1 Polypeptide markers for diagnosis of bladder cancer and their molecular masses and migration times (CE time):
  • the present invention it is possible to diagnose bladder cancer very early.
  • the disease can be treated at an early stage by known methods.
  • the invention further enables a cost-effective, rapid and reliable estimation of the tumor stage as well as a diagnosis in the case of interventions which are in part not or only minimally invasive.
  • the migration time is determined by capillary electrophoresis (CE), e.g. determined in example under point 2).
  • CE capillary electrophoresis
  • a 90 cm long glass capillary with an inner diameter (ID) of 50 ⁇ m and an outer diameter (OD) of 360 ⁇ m is operated at an applied voltage of 30 kV.
  • Eluant for example, 30% methanol, 0.5% formic acid in water is used.
  • CE migration time can vary. Nevertheless, the order in which the polypeptide labels elute is typically the same for each CE system used under the conditions indicated. To even out any differences in migration time, the system can be normalized using standards for which migration times are known. These standards may e.g. be the polypeptides given in the examples (see example point 3).
  • the characterization of the polypeptides shown in Tables 1 to 8 was carried out by capillary electrophoresis mass spectrometry (CE-MS), a method which was described e.g. In detail by Neuhoff et al., Rapid Comm. in mass spectrometry 2004 (20) 149-156.
  • the variation of molecular masses between individual measurements or between different mass spectrometers is relatively small with exact calibration, typically in the range of ⁇ 0.1%, preferably in the range of ⁇ 0.05%, more preferably ⁇ 0.03%.
  • the polypeptide markers according to the invention are proteins or peptides or degradation products of proteins or peptides.
  • polypeptide markers may be chemically modified, eg by post-translational modifications such as glycolization, phosphorylation, alkylation or disulfide bridging, or altered by other reactions, eg in the context of degradation.
  • polypeptide markers can also be chemically modified, eg oxidized, during the purification of the samples.
  • polypeptide markers molecular mass and migration time
  • the polypeptides according to the invention are used on the one hand to diagnose bladder cancer and, on the other hand, to make it possible to distinguish between different tumor stages. Diagnosis is the process of gaining knowledge by assigning symptoms or phenomena to a disease or injury. In the present case, the presence or absence or amplitude of certain polypeptide markers is indicative of the presence of bladder cancer as well as the tumor stage of bladder carcinoma.
  • the polypeptide markers according to the invention are determined in a sample of an individual, wherein, in the case of frequency markers, their presence or absence or, in the case of amplitude markers, the difference in signal intensity indicates the presence of bladder cancer. The presence or absence or amplitude of a polypeptide marker can be measured by any method known in the art.
  • a polypeptide marker is present when its reading is at least as high as the threshold. If its reading is below that, the polypeptide marker is absent.
  • the threshold value can either be determined by the sensitivity of the measurement method (detection limit) or defined based on experience.
  • the threshold is preferably exceeded when the sample reading for a given molecular mass is at least twice that of a blank (e.g., only buffer or solvent).
  • the polypeptide marker (s) is / are used to measure its presence or absence, the presence or absence being indicative of bladder cancer (frequency marker).
  • polypeptide markers that are typically present in patients with bladder cancer (diseased) such as Polypeptide marker Nos. 1 to 44, but are not or only rarely present in subjects without bladder cancer (control).
  • polypeptide markers that are present in individuals without bladder cancer, but more rarely or not at all in individuals with bladder cancer e.g. Nos. 45 to 149 (Table 2)
  • a frequency marker is a variant of the amplitude marker, in which the amplitude is low in some samples. It is possible to convert such frequency markers into amplitude markers in which, in the calculation of the amplitude, the corresponding samples in which the marker is not found, with a very small amplitude - in the range of the detection limit - is included in the calculation.
  • the amplitude markers indicated in Tables 3 and 4 can also be used for the diagnosis of bladder cancer (number 150-836). Amplitude markers are used in a manner that does not determine the presence or absence, but decides the magnitude of the signal (amplitude) in the presence of the signal in both groups. In Tables 3 and 4, the mean normalized amplitudes of the respective signals (characterized by mass and migration time) are reported across all the samples measured. Two standardization methods are possible in order to achieve comparability between differently concentrated samples or different measurement methods:
  • markers 150-185 is particularly preferred. All groups used consist of at least 40 individual patients or control samples to obtain a reliable mean amplitude. The decision to make a diagnosis (bladder cancer or not) will depend on how high the amplitude of the respective polypeptide markers in the patient sample is compared to the mean amplitudes in the control group or bladder cancer group. If the amplitude corresponds more closely to the mean amplitudes of the bladder cancer group, bladder cancer is assumed to correspond more closely to the mean amplitudes of the control group and can not be assumed to be of bladder cancer. The distance between the measured value and the mean amplitude can be considered as a probability of belonging to a group.
  • the polypeptide markers are also suitable for determining a tumor stage.
  • the frequencies according to Table 5 and the amplitudes according to Table 6 are suitable.
  • Table 7 Frequency markers to distinguish infiltrating BC and patients without BC
  • Table 8 Amity markers to distinguish infiltrating BC and patients without BC
  • the markers according to the invention can also be used for the differential diagnosis of the individual stages pTa to pT4.
  • the individual from whom the sample is derived, in which the presence or absence or amplitude of one or more polypeptide markers is determined may be any individual who is susceptible to bladder cancer, e.g. an animal or a human.
  • the subject is a mammal, most preferably a human.
  • a polypeptide marker not only a polypeptide marker, but a combination of markers is used to diagnose bladder cancer. It is concluded by their presence or absence and / or the magnitude of the amplitude on the presence of bladder cancer. By comparing a plurality of polypeptide markers, the falsification of the overall result can be reduced or avoided by individual individual deviations from the typical probability of presence in the patient or control individual.
  • the sample measuring the presence or absence or amplitude of the polypeptide marker (s) of the invention may be any sample recovered from the subject's body.
  • the sample is a sample having a polypeptide composition suitable for making statements about the condition of the individual (bladder cancer or not).
  • it may be blood, urine, synovial fluid, tissue fluid, body secretions, sweat, cerebrospinal fluid, lymph, intestinal, gastric, pancreatic, bile, tears, tissue, sperm, vaginal fluid, or a stool sample.
  • it is a liquid sample.
  • the sample is a urine sample or a blood sample, where a blood sample may be a serum (blood) or plasma (blood) sample.
  • Urine samples may be known as known in the art.
  • a mid-jet urine sample is used.
  • the urine sample can be removed, for example, by means of a catheter or else by means of a urination apparatus as described in WO 01/74275.
  • Blood samples may be taken by methods known in the art, for example from a vein, artery or capillary.
  • a blood sample is obtained by giving an individual venous blood by means of a syringe, e.g. is removed from the arm.
  • the term blood sample also includes samples obtained from blood by further purification and separation techniques known in the art, e.g. Blood plasma or blood serum.
  • the presence or absence or amplitude of a polypeptide marker in the sample can be determined by any method known in the art suitable for measuring polypeptide markers. Those skilled in such methods are known. In principle, the presence or absence or amplitude of a polypeptide marker can be determined by direct methods such as e.g. Mass spectrometry, or indirect methods, e.g. by ligands.
  • the sample of the subject eg, the urine or blood sample
  • the treatment may include, for example, purification, separation, dilution or concentration.
  • the methods may be, for example, centrifugation, filtration, ultrafiltration, dialysis, precipitation or chromatographic methods such as affinity separation or separation by ion exchange chromatography, or electrophoretic separation. Special Examples include gel electrophoresis, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), capillary electrophoresis,
  • IMAC Metal Affinity Chromatography
  • Lectin Affinity Chromatography Liquid Chromatography
  • HPLC High Performance Liquid Chromatography
  • Normal and Reverse Phase HPLC Normal and Reverse Phase HPLC
  • Cation Exchange Chromatography Cation Exchange Chromatography
  • Selective Binding to Surfaces All of these methods are well known to those skilled in the art and one skilled in the art will be able to select the method depending on the sample used and the method for determining the presence or absence or amplitude of the polypeptide marker (s).
  • the sample is separated before its measurement by capillary electrophoresis, purified by ultracentrifugation and / or separated by ultrafiltration into fractions containing Polypeptidmarker certain molecular size.
  • a mass spectrometric method is used to determine the presence or absence or amplitude of a polypeptide marker, which method may precede purification or separation of the sample.
  • the mass spectrometric analysis has the advantage over current methods that the concentration of many (> 500) polypeptides of a sample can be determined by a single analysis. Any type of mass spectrometer can be used. With mass spectrometry, it is possible to routinely measure 10 fmoles of a polypeptide marker, that is, 0.1 ng of a 10 kDa protein with a measurement accuracy of approximately ⁇ 0.01% from a complex mixture. In mass spectrometers, an ion-forming unit is coupled to a suitable analyzer.
  • electrospray ionization (ESI) interfaces are commonly used to measure ions from liquid samples
  • matrix assisted laser desorption / ionization (MALDI) technique is used to extract ions from to measure a sample crystallized from a matrix.
  • ESI electrospray ionization
  • MALDI matrix assisted laser desorption / ionization
  • quadrupoles, ion traps, FT-ICR or time-of-flight (TOF) analyzers can be used to analyze the resulting ions.
  • electrospray ionization the molecules present in solution i.a. is sprayed under the influence of high voltage (e.g., 1-8 kV) to form charged droplets, which become smaller due to evaporation of the solvent.
  • high voltage e.g. 1-8 kV
  • Coulomb explosions lead to the formation of free ions, which can then be analyzed and detected.
  • TOF analyzers have a very high scanning speed and achieve a high resolution.
  • Preferred methods for determining the presence or absence or amplitude of polypeptide labels include gas phase ion spectrometry, such as laser desorption / ionization mass spectrometry, MALDI-TOF-MS, SELDI-TOF-MS (surface enhanced laser desorption ionization), LC-MS (liquid chromatography mass spectrometry), 2D-PAGE-MS and
  • gas phase ion spectrometry such as laser desorption / ionization mass spectrometry, MALDI-TOF-MS, SELDI-TOF-MS (surface enhanced laser desorption ionization), LC-MS (liquid chromatography mass spectrometry), 2D-PAGE-MS and
  • CE-MS Capillary electrophoresis mass spectrometry
  • CE-MS in which capillary electrophoresis is coupled with mass spectrometry.
  • the CE-MS technique allows to determine the presence of several hundreds of polypeptide markers of a sample simultaneously in a short time, a small volume and high sensitivity. After a sample has been measured, a pattern of the measured polypeptide markers is prepared. This can be compared with reference patterns of ill or healthy individuals. In most cases it is sufficient to use a limited number of polypeptide markers for the diagnosis of bladder cancer and the differential diagnosis between different stages of bladder cancer, for example at least 6, 8, 10, 20, 50 or 100 markers.
  • CE-MS method which includes CE coupled online to an ESI-TOF-MS.
  • solvents for CE-MS, the use of volatile solvents is preferred, and it is best to work under essentially salt-free conditions.
  • suitable solvents include acetonitrile, methanol and the like.
  • the solvents may be diluted with water and treated with a weak acid (e.g., 0.1% to 1% formic acid) to protonate the analyte, preferably the polypeptides.
  • Capillary electrophoresis makes it possible to separate molecules according to their charge and size. Neutral particles migrate at the rate of electroosmotic flow upon application of a current, cations are accelerated to the cathode and anions are retarded.
  • the advantage of capillaries in electrophoresis is the favorable ratio of surface area to volume, which enables a good removal of the Joule heat arising during the current flow. This in turn allows the application of high voltages (usually up to 30 kV) and thus a high separation efficiency and short analysis times.
  • quartz glass capillaries with internal diameters of typically 50 to 75 ⁇ m are normally used. The used lengths are 30-100 cm.
  • the capillaries are usually made of plastic-coated quartz glass.
  • the capillaries can be both untreated, ie show their hydrophilic groups on the inside, and be coated on the inside.
  • a hydrophobic coating (coating: a method which, for example, masks the negative polarized surface of the quartz) can be used to improve the resolution.
  • a pressure which is typically in the range of 0-1 psi may also be applied. The pressure can also be created during the separation or changed during the process.
  • the markers of the sample are separated by capillary electrophoresis, then directly ionized and transferred online to a mass spectrometer coupled thereto for detection.
  • polypeptide markers can be used to diagnose bladder cancer in the method of the invention.
  • At least three polypeptide markers may be used, for example, markers 1, 2 and 3; 1, 2 and 4; etc.
  • Urine was used to detect the polypeptide markers for bladder cancer. Urine was withdrawn from healthy donors (peer group) and bladder cancer patients.
  • the proteins also found in urine of patients in higher concentration such as albumin and
  • Immunoglobulins are separated by ultrafiltration. In addition were
  • CE-MS measurements were carried out using a Beckman Coulter capillary electrophoresis system (P / ACE MDQ system, Beckman Coulter Ine, Fullerton, USA) and Bruker ESI-TOF mass spectrometer (micro-TOF MS, Bruker Daltonik, Bremen, D).
  • the CE capillaries were purchased from Beckman Coulter, having an ID / OD of 50/360 ⁇ m and a length of 90 cm.
  • the mobile phase for the CE separation consisted of 20% acetonitrile and 0.25% M formic acid in Water. 30% isopropanol with 0.5% formic acid was used for the "sheath flow" on the MS, here with a flow rate of 2 ⁇ l / min.
  • the coupling of CE and MS was performed by a CE-ESI-MS sprayer kit (Agilent Technologies , Waldbronn, DE).
  • the duration of the injection was 99 seconds. With these parameters about 150 to 900 nl of the sample was injected into the capillary, this corresponds to about 10% to 50% of the capillary volume.
  • a "stacking" technique was used, injecting an IM NH 3 solution for 7 sec (at 1 psi) before injecting the sample, and then injecting a 2M formic acid solution for 5 sec after sample injection the separation voltage (30 kV), the analytes are automatically concentrated between these solutions.
  • CE separation was performed with a pressure method: 40 minutes at 0 psi, then 0.1 psi for 2 minutes, 0.2 psi for 2 minutes, 0.3 psi for 2 minutes, 0.4 psi for 2 minutes , finally 32 min at 0.5 psi.
  • the total duration of a separation run was thus 80 minutes.
  • the "Nebulizer gas" was set to the lowest possible value.
  • the applied voltage for generating the electrospray was 3700 - 4100 V.
  • the other settings on the mass spectrometer were made according to the manufacturer's instructions The spectra were recorded over a mass range from m / z 400 to m / z 3000 and accumulated every 3 seconds. 3. Standards for the CE measurement
  • the proteins / polypeptides are each used in a concentration of 10 pmol / ⁇ l in water.
  • REV "REV”, "ELM”, “KINCON” and “GIVLY” represent synthetic peptides.

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Abstract

L'invention concerne un procédé pour diagnostiquer un cancer de la vessie et/ou déterminer un stade tumoral d'un cancer de la vessie. Ce procédé consiste à déterminer la présence ou l'absence ou l'amplitude d'au moins six marqueurs polypeptidiques dans un échantillon, ces marqueurs polypeptidiques étant choisis parmi les marqueurs 1 à 836 et lesdits marqueurs polypeptidiques étant caractérisés par des valeurs pour les masses moléculaires et le temps de migration (temps CE).
EP06793031A 2005-08-26 2006-08-28 Marqueurs polypeptidiques pour le diagnostic du cancer de la vessie Ceased EP1917531A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP20100183092 EP2333550A3 (fr) 2005-08-26 2006-08-28 Marqueurs polypeptidiques pour la diagnose du cancer de la vessie
EP06793031A EP1917531A2 (fr) 2005-08-26 2006-08-28 Marqueurs polypeptidiques pour le diagnostic du cancer de la vessie

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP20050107840 EP1757939A1 (fr) 2005-08-26 2005-08-26 Marqueurs polypeptidiques pour la diagnose du cancer de la vessie
EP06793031A EP1917531A2 (fr) 2005-08-26 2006-08-28 Marqueurs polypeptidiques pour le diagnostic du cancer de la vessie
PCT/EP2006/065742 WO2007023191A2 (fr) 2005-08-26 2006-08-28 Marqueurs polypeptidiques pour le diagnostic du cancer de la vessie

Publications (1)

Publication Number Publication Date
EP1917531A2 true EP1917531A2 (fr) 2008-05-07

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EP20050107840 Withdrawn EP1757939A1 (fr) 2005-08-26 2005-08-26 Marqueurs polypeptidiques pour la diagnose du cancer de la vessie
EP06793031A Ceased EP1917531A2 (fr) 2005-08-26 2006-08-28 Marqueurs polypeptidiques pour le diagnostic du cancer de la vessie
EP20100183092 Withdrawn EP2333550A3 (fr) 2005-08-26 2006-08-28 Marqueurs polypeptidiques pour la diagnose du cancer de la vessie

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EP20050107840 Withdrawn EP1757939A1 (fr) 2005-08-26 2005-08-26 Marqueurs polypeptidiques pour la diagnose du cancer de la vessie

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EP20100183092 Withdrawn EP2333550A3 (fr) 2005-08-26 2006-08-28 Marqueurs polypeptidiques pour la diagnose du cancer de la vessie

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US (2) US20100047840A1 (fr)
EP (3) EP1757939A1 (fr)
JP (1) JP2009506310A (fr)
KR (1) KR20080066664A (fr)
CN (1) CN101248354A (fr)
AU (1) AU2006283851B2 (fr)
BR (1) BRPI0615393A2 (fr)
CA (1) CA2621159A1 (fr)
MX (1) MX2008002602A (fr)
RU (1) RU2008111496A (fr)
WO (1) WO2007023191A2 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060286602A1 (en) * 2004-05-10 2006-12-21 Harald Mischak Method and markers for the diagnosis of renal diseases
JP5351773B2 (ja) * 2007-03-07 2013-11-27 モザイクヴェス ディアグノシュティクス アンド テラポイティクス アクチェン ゲゼルシャフト 尿試料中の検体の濃度を正規化するための方法
EP1972940A1 (fr) * 2007-03-14 2008-09-24 mosaiques diagnostics and therapeutics AG Procédé et marqueur destinés à diagnostiquer des maladies des reins
WO2009047280A2 (fr) * 2007-10-09 2009-04-16 Mosaiques Diagnostics And Therapeutics Ag Marqueur polypeptidique pour le diagnostic du cancer de la prostate
EP2051078A1 (fr) * 2007-10-19 2009-04-22 mosaiques diagnostics and therapeutics AG Procédé et marqueur destinés à diagnostiquer le diabète sucré
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CN101248354A (zh) 2008-08-20
MX2008002602A (es) 2008-03-14
WO2007023191A2 (fr) 2007-03-01
RU2008111496A (ru) 2009-10-10
EP2333550A3 (fr) 2011-09-28
US20150122650A1 (en) 2015-05-07
CA2621159A1 (fr) 2007-03-01
KR20080066664A (ko) 2008-07-16
AU2006283851B2 (en) 2013-02-07
WO2007023191A3 (fr) 2007-08-16
AU2006283851A1 (en) 2007-03-01
EP2333550A2 (fr) 2011-06-15
EP1757939A1 (fr) 2007-02-28
JP2009506310A (ja) 2009-02-12
US20100047840A1 (en) 2010-02-25

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