JP5904569B2 - 癌治療を受けている患者の同定、判定および処置のための方法 - Google Patents

癌治療を受けている患者の同定、判定および処置のための方法 Download PDF

Info

Publication number
JP5904569B2
JP5904569B2 JP2008515977A JP2008515977A JP5904569B2 JP 5904569 B2 JP5904569 B2 JP 5904569B2 JP 2008515977 A JP2008515977 A JP 2008515977A JP 2008515977 A JP2008515977 A JP 2008515977A JP 5904569 B2 JP5904569 B2 JP 5904569B2
Authority
JP
Japan
Prior art keywords
marker
predictive
patient
expression
markers
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.)
Active
Application number
JP2008515977A
Other languages
English (en)
Japanese (ja)
Other versions
JP2008544223A5 (https=
JP2008544223A (ja
Inventor
バーバラ エム． ブライアント，
バーバラ エム． ブライアント，
アンドリュー アイ． ダモコシュ，
アンドリュー アイ． ダモコシュ，
ジョージ マリガン，
ジョージ マリガン，
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.)
Millennium Pharmaceuticals Inc
Original Assignee
Millennium Pharmaceuticals Inc
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 Millennium Pharmaceuticals Inc filed Critical Millennium Pharmaceuticals Inc
Publication of JP2008544223A publication Critical patent/JP2008544223A/ja
Publication of JP2008544223A5 publication Critical patent/JP2008544223A5/ja
Application granted granted Critical
Publication of JP5904569B2 publication Critical patent/JP5904569B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/69—Boron compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • G01N33/57505—Immunoassay; Biospecific binding assay; Materials therefor for cancer of the blood, e.g. leukaemia
    • 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
    • G01N33/57515—Immunoassay; Biospecific binding assay; Materials therefor for cancer of the breast
    • 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
    • G01N33/5752—Immunoassay; Biospecific binding assay; Materials therefor for cancer of the lungs
    • 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
    • G01N33/57525—Immunoassay; Biospecific binding assay; Materials therefor for cancer of the liver or pancreas
    • 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
    • G01N33/57535—Immunoassay; Biospecific binding assay; Materials therefor for cancer of the large intestine, e.g. colon, rectum or anus
    • 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
    • G01N33/57545—Immunoassay; Biospecific binding assay; Materials therefor for cancer of the ovaries
    • 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
    • G01N33/57555—Immunoassay; Biospecific binding assay; Materials therefor for cancer of the 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
    • G01N33/53—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
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06Q—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR ADMINISTRATIVE, COMMERCIAL, FINANCIAL, MANAGERIAL OR SUPERVISORY PURPOSES; SYSTEMS OR METHODS SPECIALLY ADAPTED FOR ADMINISTRATIVE, COMMERCIAL, FINANCIAL, MANAGERIAL OR SUPERVISORY PURPOSES, NOT OTHERWISE PROVIDED FOR
    • G06Q20/00—Payment architectures, schemes or protocols
    • G06Q20/38—Payment protocols; Details thereof
    • G06Q20/40—Authorisation, e.g. identification of payer or payee, verification of customer or shop credentials; Review and approval of payers, e.g. check credit lines or negative lists
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
    • G16B25/10—Gene or protein expression profiling; Expression-ratio estimation or normalisation
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
    • G16B40/10—Signal processing, e.g. from mass spectrometry [MS] or from PCR
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H10/00—ICT specially adapted for the handling or processing of patient-related medical or healthcare data
    • G16H10/40—ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/40—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
    • 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
    • C12Q2600/136—Screening for pharmacological compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/44—Multiple drug resistance
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
    • Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Urology & Nephrology (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medical Informatics (AREA)
  • Genetics & Genomics (AREA)
  • Public Health (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Theoretical Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Evolutionary Biology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Veterinary Medicine (AREA)
  • Primary Health Care (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Business, Economics & Management (AREA)
JP2008515977A 2005-06-08 2006-06-08 癌治療を受けている患者の同定、判定および処置のための方法 Active JP5904569B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US68863405P 2005-06-08 2005-06-08
US60/688,634 2005-06-08
PCT/US2006/022515 WO2006133420A2 (en) 2005-06-08 2006-06-08 Treatment of patients with cancer therapy

Related Child Applications (2)

Application Number Title Priority Date Filing Date
JP2011193341A Division JP5796857B2 (ja) 2005-06-08 2011-09-05 癌治療を受けている患者の同定、判定および処置のための方法
JP2016023487A Division JP2016101174A (ja) 2005-06-08 2016-02-10 癌治療を受けている患者の同定、判定および処置のための方法

Publications (3)

Publication Number Publication Date
JP2008544223A JP2008544223A (ja) 2008-12-04
JP2008544223A5 JP2008544223A5 (https=) 2009-07-23
JP5904569B2 true JP5904569B2 (ja) 2016-04-13

Family

ID=37499155

Family Applications (3)

Application Number Title Priority Date Filing Date
JP2008515977A Active JP5904569B2 (ja) 2005-06-08 2006-06-08 癌治療を受けている患者の同定、判定および処置のための方法
JP2011193341A Expired - Fee Related JP5796857B2 (ja) 2005-06-08 2011-09-05 癌治療を受けている患者の同定、判定および処置のための方法
JP2016023487A Withdrawn JP2016101174A (ja) 2005-06-08 2016-02-10 癌治療を受けている患者の同定、判定および処置のための方法

Family Applications After (2)

Application Number Title Priority Date Filing Date
JP2011193341A Expired - Fee Related JP5796857B2 (ja) 2005-06-08 2011-09-05 癌治療を受けている患者の同定、判定および処置のための方法
JP2016023487A Withdrawn JP2016101174A (ja) 2005-06-08 2016-02-10 癌治療を受けている患者の同定、判定および処置のための方法

Country Status (8)

Country Link
US (3) US8278038B2 (https=)
EP (2) EP1899486A4 (https=)
JP (3) JP5904569B2 (https=)
AU (1) AU2006254834B2 (https=)
CA (1) CA2611728A1 (https=)
ES (1) ES2624863T3 (https=)
MX (1) MX2007015416A (https=)
WO (1) WO2006133420A2 (https=)

Families Citing this family (115)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2542328T3 (es) * 2002-12-06 2015-08-04 Millennium Pharmaceuticals, Inc. Métodos para la identificación, evaluación y tratamiento de pacientes con terapia de inhibición del proteasoma
CA2553551C (en) 2004-01-21 2020-12-15 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for determining a graft tolerant phenotype in a subject
CA2563074C (en) 2004-04-09 2014-05-20 Genomic Health, Inc. Gene expression markers for predicting response to chemotherapy
USRE46843E1 (en) 2005-03-14 2018-05-15 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for evaluating graft survival in a solid organ transplant recipient
EP2604703B1 (en) 2005-03-14 2017-02-01 The Board of Trustees of the Leland Stanford Junior University Methods for evaluating graft survival in a solid organ transplant recipient
CA2611728A1 (en) 2005-06-08 2006-12-14 Millennium Pharmaceuticals, Inc. Methods for the identification, assessment, and treatment of patients with cancer therapy
WO2007001943A2 (en) * 2005-06-20 2007-01-04 The Regents Of The University Of California Prefoldin 4 in the treatment and diagnosis of cancer
EP1991701A4 (en) * 2006-02-14 2010-03-17 Dana Farber Cancer Inst Inc COMPOSITIONS, KITS AND METHODS OF IDENTIFICATION, ASSESSMENT, PREVENTION AND THERAPY OF CANCER
EP2046973A4 (en) * 2006-08-10 2010-04-07 Millennium Pharm Inc IDENTIFICATION, ASSESSMENT AND TREATMENT OF CANCER THERAPY PATIENTS
EP2171090B1 (en) * 2007-06-08 2013-04-03 Genentech, Inc. Gene expression markers of tumor resistance to her2 inhibitor treatment
US9551033B2 (en) 2007-06-08 2017-01-24 Genentech, Inc. Gene expression markers of tumor resistance to HER2 inhibitor treatment
US20080317768A1 (en) * 2007-06-21 2008-12-25 Boeing Company Bioconjugated nanoparticles
WO2009042676A1 (en) * 2007-09-24 2009-04-02 University Of South Florida Method for early detection of cancers
US20090094047A1 (en) * 2007-10-04 2009-04-09 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems and methods for predicting a risk utilizing epigenetic data
US20090094261A1 (en) * 2007-10-04 2009-04-09 Jung Edward K Y Systems and methods for correlating epigenetic information with disability data
US20100027780A1 (en) * 2007-10-04 2010-02-04 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems and methods for anonymizing personally identifiable information associated with epigenetic information
US20090094282A1 (en) * 2007-10-04 2009-04-09 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems and methods for correlating past epigenetic information with past disability data
US20090099877A1 (en) * 2007-10-11 2009-04-16 Hyde Roderick A Systems and methods for underwriting risks utilizing epigenetic information
US20090094065A1 (en) * 2007-10-04 2009-04-09 Hyde Roderick A Systems and methods for underwriting risks utilizing epigenetic information
US20090100095A1 (en) * 2007-10-04 2009-04-16 Jung Edward K Y Systems and methods for reinsurance utilizing epigenetic information
US20090094067A1 (en) * 2007-10-04 2009-04-09 Searete LLC, a limited liability corporation of Systems and methods for company internal optimization utilizing epigenetic data
US20090094281A1 (en) * 2007-10-04 2009-04-09 Jung Edward K Y Systems and methods for transferring combined epigenetic information and other information
MX2010005080A (es) 2007-11-07 2010-07-28 Genentech Inc Metodos y composiciones para determinar la sensibilidad de linfoma de celula b al tratamiento con anticuerpos anti-cd40.
DK2568053T3 (da) * 2008-05-12 2014-07-21 Genomic Health Inc Tests til forudsigelse af cancerpatienters respons på forskellige kemoterapeutiske behandlingsmuligheder
WO2010021696A1 (en) * 2008-08-18 2010-02-25 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for determining a graft tolerant phenotype in a subject
US7657446B1 (en) 2008-08-22 2010-02-02 Numoda Technologies, Inc. Automated identification of tasks that must be completed before a clinical trial database can be locked
RU2011111532A (ru) * 2008-08-28 2012-10-10 Онкотерапи Сайенс, Инк. (Jp) Твс1d7 в качестве опухолевого маркера и терапевтической мишени в случае злокачественной опухоли
US20100169115A1 (en) * 2008-12-31 2010-07-01 Tamis Robert H System for matching individuals with health care providers and methods thereof
EP2387618B1 (en) 2009-01-15 2014-05-21 The Board of Trustees of The Leland Stanford Junior University Biomarker panel for diagnosis and prediction of graft rejection
TW201030337A (en) * 2009-02-04 2010-08-16 Tzu Chi Buddhist General Hospital Method and kit for detecting cancers
AU2010223919B2 (en) 2009-03-13 2016-03-31 Les Laboratoires Servier Methods and compositions for cell-proliferation-related disorders
KR101787768B1 (ko) * 2009-04-18 2017-10-18 제넨테크, 인크. 항-ｃｄ４０ 항체를 사용한 치료에 대한 ｂ-세포 림프종의 반응성 평가를 위한 방법
RU2561132C2 (ru) 2009-06-29 2015-08-20 Аджиос Фармасьютикалз, Инк. Производные хинолинсульфонамидов и их применение для модулирования пкм2 активности
CA2767616A1 (en) 2009-07-09 2011-01-13 The Scripps Research Institute Gene expression profiles associated with chronic allograft nephropathy
US20120252028A1 (en) * 2009-08-14 2012-10-04 Michael Shtulman Target genes for cancer therapy
EP3561077B1 (en) 2009-10-21 2022-12-21 Les Laboratoires Servier Methods for cell-proliferation-related disorders
WO2011050211A2 (en) 2009-10-21 2011-04-28 Agios Pharmaceuticals, Inc. Methods and compositions for cell-proliferation-related disorders
US9493833B1 (en) * 2009-11-06 2016-11-15 The Regents Of The University Of California Methods for preventing induced synthesis of proteasomes in human cells
US20120231472A1 (en) * 2009-11-07 2012-09-13 Astute Medical, Inc. Methods and compositions for diagnosis and prognosis of renal injury and renal failure
US9290813B2 (en) 2009-12-02 2016-03-22 The Board Of Trustees Of The Leland Stanford Junior University Biomarkers for determining an allograft tolerant phenotype
EP3178944B1 (en) 2010-01-11 2019-05-15 Genomic Health, Inc. Method to use gene expression to determine likelihood of clinical outcome of renal cancer
WO2011119980A1 (en) 2010-03-25 2011-09-29 The Board Of Trustees Of The Leland Stanford Junior University Protein and gene biomarkers for rejection of organ transplants
US20110236582A1 (en) 2010-03-29 2011-09-29 Scheuing David R Polyelectrolyte Complexes
US9309435B2 (en) 2010-03-29 2016-04-12 The Clorox Company Precursor polyelectrolyte complexes compositions comprising oxidants
JP2013526863A (ja) * 2010-05-13 2013-06-27 ユニバーシテート チューリッヒ バイオマーカーとして用いるための不連続状態
MX338883B (es) 2010-07-27 2016-05-04 Genomic Health Inc Metodo para usar expresion de gen para determinar el pronostico de cancer de prostata.
US20140322705A1 (en) * 2010-08-20 2014-10-30 Thomas Jefferson University Cancer diagnostic and cancer therapeutic
WO2012139051A2 (en) 2011-04-06 2012-10-11 The Board Of Trustees Of The Leland Stanford Junior University Autoantibody biomarkers for iga nephropathy
SG194697A1 (en) 2011-05-03 2013-12-30 Agios Pharmaceuticals Inc Pyruvate kinase activators for use in therapy
CN102827170A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN102827073A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
MX357429B (es) 2011-08-11 2018-07-09 Janssen Pharmaceutica Nv Predictores para el tratamiento del cáncer.
EP2771489B1 (en) * 2011-10-28 2018-07-04 Millennium Pharmaceuticals, Inc. Biomarkers of response to nae inhibitors
CA2855368A1 (en) * 2011-11-11 2013-05-16 Millennium Pharmaceuticals, Inc. Biomarkers of response to proteasome inhibitors
NZ627096A (en) 2012-01-06 2017-02-24 Agios Pharmaceuticals Inc Triazinyl compounds and their methods of use
US9474779B2 (en) 2012-01-19 2016-10-25 Agios Pharmaceuticals, Inc. Therapeutically active compositions and their methods of use
CA2862320A1 (en) * 2012-01-24 2013-08-01 Millennium Pharmaceuticals, Inc. Method of treatment of nasopharyngeal cancer
JP6215235B2 (ja) * 2012-01-24 2017-10-18 ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 癌の治療方法
GB2523211B (en) 2012-01-27 2020-03-18 Univ Jefferson MCT protein inhibitor-related prognostic and therapeutic methods
US8725426B2 (en) 2012-01-31 2014-05-13 Genomic Health, Inc. Gene expression profile algorithm and test for determining prognosis of prostate cancer
WO2014062511A1 (en) 2012-10-15 2014-04-24 Agios Pharmaceuticals, Inc. Therapeutic compounds and compositions
ES2702183T3 (es) * 2013-03-15 2019-02-27 Mayo Found Medical Education & Res Identificación y monitorización de inmunoglobulinas monoclonales por masa molecular
WO2014172627A1 (en) 2013-04-19 2014-10-23 Thomas Jefferson University Caveolin-1 related methods for treating glioblastoma with temozolomide
JP2016521979A (ja) 2013-05-30 2016-07-28 ジェノミック ヘルス， インコーポレイテッド 腎臓がんを有する患者に対する再発スコアを計算するための遺伝子発現プロファイルアルゴリズム
CN105593215B (zh) 2013-07-11 2019-01-15 安吉奥斯医药品有限公司 用于治疗癌症的作为idh2突变体抑制剂的2,4-或4,6-二氨基嘧啶化合物
US9579324B2 (en) 2013-07-11 2017-02-28 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
WO2015003360A2 (en) 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
WO2015003355A2 (en) 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
US20150031627A1 (en) 2013-07-25 2015-01-29 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
EA038246B1 (ru) * 2013-08-08 2021-07-29 Оникс Терапьютикс, Инк. Уровни экспрессии иммуноглобулинов в качестве биологического маркера для реакции на ингибитор протеасом
KR20240010105A (ko) 2014-03-14 2024-01-23 아지오스 파마슈티컬스 아이엔씨. 치료적으로 활성인 화합물의 약제학적 조성물
WO2015154052A1 (en) 2014-04-04 2015-10-08 Mayo Foundation For Medical Education And Research Isotyping immunoglobulins using accurate molecular mass
CN106414726A (zh) 2014-04-07 2017-02-15 米纳瓦生物技术公司 抗nme抗体
US11104951B2 (en) 2014-05-22 2021-08-31 The Scripps Research Institute Molecular signatures for distinguishing liver transplant rejections or injuries
US10443100B2 (en) 2014-05-22 2019-10-15 The Scripps Research Institute Gene expression profiles associated with sub-clinical kidney transplant rejection
US20160018414A1 (en) * 2014-07-21 2016-01-21 The Florida International University Board Of Trustees SAB as a Biomarker for Degenerative Diseases and Therapeutic Sensitivity in Cancers
EP3175242A4 (en) 2014-07-29 2017-12-27 Mayo Foundation for Medical Education and Research Quantifying monoclonal antibody therapeutics by lc-ms/ms
WO2016161153A2 (en) * 2015-04-01 2016-10-06 The Regents Of The University Of California Prognostic and diagnostic methods for colorectal cancer
FI3307271T3 (fi) 2015-06-11 2023-10-17 Agios Pharmaceuticals Inc Pyruvaattikinaasin aktivaattorien käyttämisen menetelmä
CN108026164A (zh) 2015-09-24 2018-05-11 梅约医学教育与研究基金会 通过质谱鉴定免疫球蛋白游离轻链
PT3362066T (pt) 2015-10-15 2021-11-16 Celgene Corp Terapia de combinação para tratar malignidades
SG11201803088PA (en) 2015-10-15 2018-05-30 Agios Pharmaceuticals Inc Combination therapy for treating malignancies
EP3377646A1 (en) * 2015-11-20 2018-09-26 Université de Strasbourg Method for identifying personalized therapeutic strategies for patients affected with a cancer
MX391039B (es) * 2016-04-07 2025-03-21 Univ Leland Stanford Junior Diagnostico no invasivo por medio de la secuenciacion del adn libre de celulas 5-hidroxi-metilado.
US20170298422A1 (en) 2016-04-18 2017-10-19 The Board Of Trustees Of The Leland Stanford Junior University Simultaneous single-molecule epigenetic imaging of dna methylation and hydroxymethylation
AU2017325022B2 (en) 2016-09-07 2022-10-13 Mayo Foundation For Medical Education And Research Identification and monitoring of cleaved immunoglobulins by molecular mass
CN118271442A (zh) 2016-12-23 2024-07-02 蓝鳍生物医药公司 抗sez6l2抗体和抗体药物缀合物
EP3655553B1 (en) * 2017-07-21 2022-03-23 Liquid Biopsy Research LLC Methods for detection of plasma cell dyscrasia
EP3681907A4 (en) 2017-09-13 2021-07-07 Mayo Foundation for Medical Education and Research IDENTIFICATION AND MONITORING OF IMMUNOGLOBULIN J-CHAINS
WO2019055634A1 (en) 2017-09-13 2019-03-21 Mayo Foundation For Medical Education And Research IDENTIFICATION AND MONITORING OF A MACROPHAGE APOPTOSIS INHIBITOR
US20190233900A1 (en) * 2018-02-01 2019-08-01 Nantomics, Llc Biomarkers in de novo pyrimidine synthesis pathways and chemoresistance
WO2019222553A1 (en) 2018-05-16 2019-11-21 Forma Therapeutics, Inc. Inhibiting mutant idh-1
US11013733B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mlDH-1)
US11013734B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Treating patients harboring an isocitrate dehydrogenase-1 (IDH-1) mutation
US10532047B2 (en) 2018-05-16 2020-01-14 Forma Therapeutics, Inc. Solid forms of ((S)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile
US11311527B2 (en) 2018-05-16 2022-04-26 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mIDH-1)
US10769307B2 (en) 2018-05-30 2020-09-08 Bank Of America Corporation Processing system using natural language processing for performing dataset filtering and sanitization
EP3810284A4 (en) * 2018-06-01 2022-06-15 Lunella Biotech, Inc. BIOMARKERS AND THERAPEUTICS IN RESISTANCE TO ENDOCRINE THERAPY
US10980788B2 (en) 2018-06-08 2021-04-20 Agios Pharmaceuticals, Inc. Therapy for treating malignancies
CN109190713A (zh) * 2018-09-29 2019-01-11 王海燕 基于血清质谱自适应稀疏特征选择的卵巢癌微创快检技术
SG10201811119XA (en) * 2018-12-12 2020-07-29 Sengenics Sdn Bhd Detection of biomarkers for non-small cell lung cancer
CN109633142B (zh) * 2018-12-22 2021-08-27 中国人民解放军第四军医大学 一种急性髓细胞性白血病诊断模型的建立方法及其应用
US20220081727A1 (en) * 2019-01-17 2022-03-17 Geninus Inc. Biomarker for predicting response to anticancer agent and use thereof
EP3920693A4 (en) 2019-02-04 2022-10-05 Minerva Biotechnologies Corporation ANTI-NME ANTIBODIES AND METHODS OF TREATMENT OF CANCER OR CANCER METASTASIS
WO2020206015A1 (en) * 2019-04-02 2020-10-08 Northwestern University Markers of efficacy of topoisomerase poisons
US20220290243A1 (en) * 2019-07-01 2022-09-15 Rutgers, The State University Of New Jersey Identification of patients that will respond to chemotherapy
WO2021030604A1 (en) * 2019-08-14 2021-02-18 University Of Massachusetts Urinary rna signatures in renal cell carcinoma (rcc)
WO2021108043A1 (en) 2019-11-27 2021-06-03 University Of Cincinnati Assessing treatment response with estimated number of tumor cells
RU2750103C1 (ru) * 2020-02-21 2021-06-22 Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр онкологии имени Н.Н. Петрова" Министерства здравоохранения Российской Федерации Способ дифференциальной диагностики диффузных в-клеточных крупноклеточных лимфом
CN116367857A (zh) 2020-06-08 2023-06-30 米纳瓦生物技术公司 抗nme抗体及治疗癌症或癌症转移的方法
KR20230028796A (ko) 2020-06-26 2023-03-02 미네르바 바이오테크놀로지 코포레이션 항-nme 항체 및 암 또는 암 전이의 치료 방법
CN112501278A (zh) * 2020-12-03 2021-03-16 中国医学科学院病原生物学研究所 Smim26作为结核病诊断分子标识的用途
CN113092757B (zh) * 2021-02-23 2024-02-06 承德医学院 一种肺癌肝转移早期诊断试剂盒及制备使用方法
CN115372618B (zh) * 2022-09-19 2025-01-14 首都医科大学附属北京胸科医院 一种检测蛋白标志物水平的试剂在制备用于评估肿瘤治疗效果的诊断产品中的应用
CN116500266B (zh) * 2023-03-07 2025-06-17 南通大学附属医院 MRPS21基因及其RNAi干扰系统的应用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2445431A1 (en) * 2001-04-23 2002-10-31 Metabometrix Limited Methods for the diagnosis and treatment of bone disorders
JP2005512557A (ja) 2001-11-07 2005-05-12 ザ ボード オブ トラスティーズ オブ ザ ユニヴァーシティー オブ アーカンソー 遺伝子発現プロファイリングに基づく多発性骨髄腫の診断、予後、および治療標的候補の同定
ES2542328T3 (es) 2002-12-06 2015-08-04 Millennium Pharmaceuticals, Inc. Métodos para la identificación, evaluación y tratamiento de pacientes con terapia de inhibición del proteasoma
CA2611728A1 (en) 2005-06-08 2006-12-14 Millennium Pharmaceuticals, Inc. Methods for the identification, assessment, and treatment of patients with cancer therapy

Also Published As

Publication number Publication date
JP2016101174A (ja) 2016-06-02
JP2011239792A (ja) 2011-12-01
US8889354B2 (en) 2014-11-18
AU2006254834B2 (en) 2012-09-20
US8278038B2 (en) 2012-10-02
ES2624863T3 (es) 2017-07-17
US20130013334A1 (en) 2013-01-10
EP1899486A2 (en) 2008-03-19
AU2006254834A1 (en) 2006-12-14
WO2006133420A2 (en) 2006-12-14
EP1899486A4 (en) 2009-07-22
WO2006133420A3 (en) 2008-01-17
EP2687608A1 (en) 2014-01-22
US20060281122A1 (en) 2006-12-14
US9963747B2 (en) 2018-05-08
JP2008544223A (ja) 2008-12-04
US20150252430A1 (en) 2015-09-10
EP2687608B1 (en) 2017-02-08
MX2007015416A (es) 2008-02-19
JP5796857B2 (ja) 2015-10-21
CA2611728A1 (en) 2006-12-14

Similar Documents

Publication Publication Date Title
JP5904569B2 (ja) 癌治療を受けている患者の同定、判定および処置のための方法
JP5725711B2 (ja) 癌治療法を有する患者の同定、評価、および治療のための方法
JP5896593B2 (ja) プロテアソーム阻害療法を用いた患者の同定、判定および治療方法
JP6486826B2 (ja) 阻害剤に対する応答を予測するためのバイオマーカーおよび方法、ならびにそれらの使用
US20160312309A1 (en) Assessment of chromosomal alterations to predict clinical outcome of bortezomib treatment
US10953013B2 (en) Biomarkers of response to NAE inhibitors

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20090604

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20090604

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20100531

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20110224

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20110308

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20110607

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20110614

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20110707

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20110714

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20110805

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20110812

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20110905

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20121003

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20121217

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20121225

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20130118

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20131101

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20140127

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20140203

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20140320

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20141003

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20141216

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20141224

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20150127

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20150227

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20150316

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20150810

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20151109

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20151209

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20160108

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20160210

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20160309

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20160310

R150 Certificate of patent or registration of utility model

Ref document number: 5904569

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250