KR20220083699A - 약물 독성 평가 방법 - Google Patents

약물 독성 평가 방법 Download PDF

Info

Publication number
KR20220083699A
KR20220083699A KR1020227012303A KR20227012303A KR20220083699A KR 20220083699 A KR20220083699 A KR 20220083699A KR 1020227012303 A KR1020227012303 A KR 1020227012303A KR 20227012303 A KR20227012303 A KR 20227012303A KR 20220083699 A KR20220083699 A KR 20220083699A
Authority
KR
South Korea
Prior art keywords
drug
cells
toxicity
organoid
drugs
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
KR1020227012303A
Other languages
English (en)
Korean (ko)
Inventor
다카노리 다케베
노리카즈 사이키
Original Assignee
고리츠다이가쿠호진 요코하마시리츠다이가쿠
다케다 야쿠힌 고교 가부시키가이샤
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 고리츠다이가쿠호진 요코하마시리츠다이가쿠, 다케다 야쿠힌 고교 가부시키가이샤 filed Critical 고리츠다이가쿠호진 요코하마시리츠다이가쿠
Publication of KR20220083699A publication Critical patent/KR20220083699A/ko
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0697—Artificial constructs associating cells of different lineages, e.g. tissue equivalents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • 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
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/025—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5014—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing toxicity
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/5055—Cells of the immune system involving macrophages
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5082—Supracellular entities, e.g. tissue, organisms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/115—Basic fibroblast growth factor (bFGF, FGF-2)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/12—Hepatocyte growth factor [HGF]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/165—Vascular endothelial growth factor [VEGF]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/237—Oncostatin M [OSM]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells
    • C12N2502/1157—Monocytes, macrophages
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/14—Coculture with; Conditioned medium produced by hepatocytes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/28—Vascular endothelial cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2503/00—Use of cells in diagnostics
    • C12N2503/04—Screening or testing on artificial tissues
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2513/00—3D culture
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/10—Screening for compounds of potential therapeutic value involving cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Toxicology (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Food Science & Technology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
KR1020227012303A 2019-10-17 2020-10-16 약물 독성 평가 방법 Ceased KR20220083699A (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JPJP-P-2019-189838 2019-10-17
JP2019189838 2019-10-17
PCT/JP2020/039023 WO2021075528A1 (ja) 2019-10-17 2020-10-16 薬物毒性評価方法

Publications (1)

Publication Number Publication Date
KR20220083699A true KR20220083699A (ko) 2022-06-20

Family

ID=75537427

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020227012303A Ceased KR20220083699A (ko) 2019-10-17 2020-10-16 약물 독성 평가 방법

Country Status (6)

Country Link
US (1) US20240125767A1 (https=)
EP (1) EP4047082A4 (https=)
JP (1) JP7738296B2 (https=)
KR (1) KR20220083699A (https=)
CN (1) CN114585746A (https=)
WO (1) WO2021075528A1 (https=)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20240110155A1 (en) * 2020-12-17 2024-04-04 Genome Biologics Ug A dual cardiac-blood model system for disease modelling and drug screening
KR102511631B1 (ko) * 2022-06-15 2023-03-20 오가노이드사이언스 주식회사 Pbmc 유래 세포독성 t 세포의 신규 용도
JPWO2024157891A1 (https=) * 2023-01-24 2024-08-02
WO2025009590A1 (ja) * 2023-07-06 2025-01-09 インテグリカルチャー株式会社 組織由来の細胞の培養方法および組織由来の細胞を含む培養装置
CN117757885A (zh) * 2023-12-26 2024-03-26 首都医科大学 一种基于高内涵的肠道菌群代谢物筛选方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016202032A (ja) 2015-04-17 2016-12-08 国立大学法人東北大学 アレルギー型薬物性肝障害の評価方法

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5841760A (ja) 1981-09-01 1983-03-11 旭化成株式会社 繊維状ヒレブランダイト及びその製造方法
US8846576B2 (en) * 2011-05-27 2014-09-30 Xenotech Llc In vitro test system to evaluate xenobiotics as immune-modulators of drug transport and metabolism in human hepatocytes
CN106062181A (zh) 2014-02-27 2016-10-26 公立大学法人横滨市立大学 自发组织用细胞集合体的制作方法
WO2017110724A1 (ja) * 2015-12-24 2017-06-29 公立大学法人横浜市立大学 血液細胞を用いた組織・臓器の作製方法
US20170285002A1 (en) 2016-03-16 2017-10-05 Public University Corporation Yokohama City University Method for reconstituting tumor with microenvironment
JP2019129707A (ja) * 2016-05-19 2019-08-08 株式会社サイフューズ ヒト由来細胞を含むヘテロスフェロイド
US11760977B2 (en) * 2016-05-25 2023-09-19 Salk Institute For Biological Studies Compositions and methods for organoid generation and disease modeling
BR112018075920A2 (pt) * 2016-06-15 2019-03-26 Mimetas B.V. dispositivo e métodos de cultura celular
EP3496774A1 (en) * 2016-08-15 2019-06-19 Organovo, Inc. Three dimensional bioprinted tumor models for drug testing
GB201622149D0 (en) 2016-12-23 2017-02-08 Insphero Ag Screenable liver disease models and methods
KR20200018505A (ko) * 2017-05-29 2020-02-19 스템셀 테크놀러지스 캐나다 인크. 오가노이드를 수득하기 위한 조성물 및 방법
GB201721615D0 (en) * 2017-12-21 2018-02-07 Koninklijke Nederlandse Akademie Van Wetenschappen Immune cell organoid co-cultures
JP7191041B2 (ja) * 2017-12-27 2022-12-16 明弘 梅澤 機能的肝前駆細胞もしくは肝細胞または機能的小腸上皮前駆細胞もしくは小腸上皮細胞を調製する方法
WO2020170239A1 (en) * 2019-02-21 2020-08-27 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Methods of generating organoids for high throughput screening of drugs

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016202032A (ja) 2015-04-17 2016-12-08 国立大学法人東北大学 アレルギー型薬物性肝障害の評価方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
A. Granitzny et al. Toxicology Reports 4 (2017) 89-103

Also Published As

Publication number Publication date
WO2021075528A1 (ja) 2021-04-22
EP4047082A4 (en) 2023-08-16
CN114585746A (zh) 2022-06-03
EP4047082A1 (en) 2022-08-24
JP7738296B2 (ja) 2025-09-12
JPWO2021075528A1 (https=) 2021-04-22
US20240125767A1 (en) 2024-04-18

Similar Documents

Publication Publication Date Title
JP7738296B2 (ja) 薬物毒性評価方法
Masuda et al. Methodological development of a clonogenic assay to determine endothelial progenitor cell potential
Ray et al. Secreted CXCL12 (SDF-1) forms dimers under physiological conditions
Auffray et al. CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation
Cipriani et al. Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis
Alvarez et al. Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity
EP1391505B1 (en) Stem cells and method of separating the same
Farha et al. Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities
Lucendo-Villarin et al. Development of a cost-effective automated platform to produce human liver spheroids for basic and applied research
Caetano-Pinto et al. Fluorescence-based transport assays revisited in a human renal proximal tubule cell line
Palenski et al. Lack of Cyp1b1 promotes the proliferative and migratory phenotype of perivascular supporting cells
Mion et al. Mast cells control the expansion and differentiation of IL-10–competent B cells
Beilmann et al. Application of new approach methodologies for nonclinical safety assessment of drug candidates
Clanchy et al. Detection and properties of the human proliferative monocyte subpopulation
Gehmert et al. Angiogenesis: the role of PDGF-BB on adiopse-tissue derived stem cells (ASCs)
Li et al. Integration of Kupffer cells into human iPSC-derived liver organoids for modeling liver dysfunction in sepsis
Neo et al. Expansion of human bone marrow-derived mesenchymal stromal cells with enhanced immunomodulatory properties
Rupert et al. In vitro, in vivo, and in silico methods for assessment of muscle size and muscle growth regulation
Papait et al. Perinatal derivatives: How to best validate their immunomodulatory functions
Bajetto et al. Metformin potentiates immunosuppressant activity and adipogenic differentiation of human umbilical cord-mesenchymal stem cells
Eckert et al. Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver
US20100233705A1 (en) Method or system using biomarkers for the monitoring of a treatment
Park et al. Three-dimensional organoids as a model to study nonalcoholic fatty liver disease
Theret et al. Elevated numbers of infiltrating eosinophils accelerate the progression of Duchenne muscular dystrophy pathology in mdx mice
Barthelmes et al. Diabetes impairs mobilization of mouse bone marrow-derived Lin−/VEGF-R2+ progenitor cells

Legal Events

Date Code Title Description
PA0105 International application

St.27 status event code: A-0-1-A10-A15-nap-PA0105

PG1501 Laying open of application

St.27 status event code: A-1-1-Q10-Q12-nap-PG1501

PA0201 Request for examination

St.27 status event code: A-1-2-D10-D11-exm-PA0201

P22-X000 Classification modified

St.27 status event code: A-2-2-P10-P22-nap-X000

E902 Notification of reason for refusal
PE0902 Notice of grounds for rejection

St.27 status event code: A-1-2-D10-D21-exm-PE0902

B15 Application refused following examination

Free format text: ST27 STATUS EVENT CODE: N-2-6-B10-B15-EXM-PE0601 (AS PROVIDED BY THE NATIONAL OFFICE)

PE0601 Decision on rejection of patent

St.27 status event code: N-2-6-B10-B15-exm-PE0601

R18 Changes to party contact information recorded

Free format text: ST27 STATUS EVENT CODE: A-3-3-R10-R18-OTH-X000 (AS PROVIDED BY THE NATIONAL OFFICE)

R18-X000 Changes to party contact information recorded

St.27 status event code: A-3-3-R10-R18-oth-X000