JP2018513353A - 血管疾患診断用バイオマーカー及びその用途 - Google Patents
血管疾患診断用バイオマーカー及びその用途 Download PDFInfo
- Publication number
- JP2018513353A JP2018513353A JP2017542865A JP2017542865A JP2018513353A JP 2018513353 A JP2018513353 A JP 2018513353A JP 2017542865 A JP2017542865 A JP 2017542865A JP 2017542865 A JP2017542865 A JP 2017542865A JP 2018513353 A JP2018513353 A JP 2018513353A
- Authority
- JP
- Japan
- Prior art keywords
- receptor
- interleukin
- vascular disease
- protein
- composition
- 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.)
- Granted
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- 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
-
- 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
- G01N33/502—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 non-proliferative effects
- G01N33/5023—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 non-proliferative effects on expression patterns
-
- 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
- G01N33/5061—Muscle cells
-
- 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
-
- 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
- G01N33/6842—Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
-
- 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
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
-
- 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
- C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
- C12Q2525/10—Modifications characterised by
- C12Q2525/205—Aptamer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
- G01N2333/5434—IL-12
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/715—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons
- G01N2333/7155—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2570/00—Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Computational Biology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- General Engineering & Computer Science (AREA)
Abstract
Description
本発明において、動物実験は梨花女子大学の動物管理及び使用委員会機関(Institutional Animal Care and Use Committee、IACUC)のガイドラインに準拠して、アメリカ国立衛生研究所が出版した「実験動物の管理及び使用のためのガイド( The National Academies Press、8th Edition、2011)」に基づいて実施した。
前記実施例1で製造した頸動脈損傷動物モデルの損傷された頸動脈組織にsiRNAを伝達して分子生物学的な変化を確認するために、カテーテル媒介血管壁内のsiRNA伝達の実験を行った。
組織学的分析のために、前記実施例1で開示されたように、ラットはイソフルランガス(N2O:O2/70%:30%)を用いて麻酔させ、3.7%ホルムアルデヒドを含むヘパリン生理食塩水で経心臓灌流固定(transcardiac perfusion -fixation)をした後、頸動脈を切除した。切除した頸動脈の血管は、パラフィン包埋(paraffin embedded)して、回転式ミクロトーム(Leica RM2255)を用いて切断した。総頸動脈の中の部位から2つの連続した組織切片(4um厚)を得て、ヘマトキシリン&エオシン(H&E)で染色した。内腔(luminal)、内部弾力層(internal elastic laminal)及び外部弾力層(external elastic laminal)の面積は、NIH image v1.62を用いて測定した。内膜と内層面積は、内部弾力層の面積から内腔面積と外部弾力層の面積を除外することにより測定した。各ラットごとに二連の組織切片から測定された値の平均値を分析に使用した。
本発明で使用される血液標本は、正常-健康対照群と血管造影術を介して冠動脈疾患と診断された患者群から採取した。これは梨花女子大学医療院(ソウル、韓国)の臨床試験審査委員会の承認を得て行った。
統計学的有意性(P value)を確認するためには、Student's t-testを用いた二集団間の比較または多数集団に対するTukey′s「正直有意差」(「honestly significant difference」)post hocテスト(Windows版SPSS12.0K、SPSS、シカゴ、IL、USA)を用いた一元配置分散分析(one-way ANOVA)を用いて、結果を分析した。P値が0.05以下の場合(P<0.05)は、統計学的に有意であると見た。血液標本を用いたデータは、 クラスカル・ウォリス順位和検定(Kruskal-Wallis rank sum test)とウィルコクソン順位和検定(Wilcoxon rank sum test)の二つのノンパラメトリック検定(non-parametric test)を介して分析した。
風船形成術によって誘導されたラット頸動脈損傷は、血栓症によって誘導された平滑筋(SMC、smooth muscle cell)肥大症と典型的な新生内膜(neointimal)肥厚症を誘導する内皮剥離の症状を現す。これにより、前記風船形成術によって誘導されたラット頸動脈損傷は、風船型塞栓除去用カテーテルを用いて動脈血管に物理的な損傷を与えた場合と同様の症状を現す。本生体内モデルは、SMC肥大症と関連した組織学的及び生化学的研究に使用することができる。
前記実験例1で同定された44個のタンパク質のうち、インターロイキン12受容体β2の変化に注目して、ヒト大動脈平滑筋細胞(Human Aortic SMCs、HASMCs)での細胞機能の有効性検査を実施した。
急速に成長したり、損傷した細胞は、細胞タンパク質またはmicroRNAをエキソソーム(exosomes)の形で放出するため、本発明者らは、前記検証されたIL-12Rβ2タンパク質が冠動脈疾患を有する患者、特に急性心筋梗塞または不安定狭心症のような不安定な症状を有する患者の血液において高発現を現すことを確認した。
Claims (22)
- 血液中インターロイキン12受容体β2(interleukin 12 receptorβ2)タンパク質のレベルを測定する製剤を含む、血管疾患診断用組成物。
- 前記組成物が、血液中で血管内膜の平滑筋細胞由来インターロイキン12受容体β2タンパク質のレベルを測定するものである、請求項1に記載の血管疾患診断用組成物。
- 前記血管内膜の平滑筋細胞由来インターロイキン12受容体β2タンパク質のレベルを測定するための組成物が、i)インターロイキン12受容体β2タンパク質のレベルを測定する製剤としてのインターロイキン12受容体β2タンパク質に特異的な抗体またはアプタマー;及びii)平滑筋マーカーに特異的に結合する抗体またはアプタマーを含むものである、請求項2に記載の血管疾患診断用組成物。
- 前記平滑筋マーカーが、血小板由来成長因子受容体(platelet-derived growth factor receptor、PDGFR)またはα-平滑筋アクチン(alpha-smooth muscle actin)である、 請求項3に記載の血管疾患診断用組成物。
- 前記血管疾患が、アテローム性動脈硬化症、血管再狭窄(in-stent restenosis)、心筋梗塞または不安定狭心症である、請求項1に記載の血管疾患診断用組成物。
- 前記組成物が、心臓発作の危険性がある疾患群の早期診断用に使用されるものである、請求項5に記載の血管疾患診断用組成物。
- 前記インターロイキン12受容体β2タンパク質のレベルを測定する製剤が、インターロイキン12受容体β2タンパク質に特異的な抗体またはアプタマーを含むものである、請求項1に記載の血管疾患診断用組成物。
- 前記血液中インターロイキン12受容体β2タンパク質のレベルを測定することが、血液中に存在する細胞外小包(extracellular vesicle)でインターロイキン12受容体β2タンパク質のレベルを測定するものである、請求項1に記載の血管疾患診断用組成物。
- 前記細胞外小包が、エキソソーム(exosome)である、請求項8に記載の血管疾患診断用組成物。
- 前記組成物が、エキソソームマーカーであるCD81、CD9またはCD63に特異的な抗体またはアプタマーを含むものである、請求項9に記載の血管疾患診断用組成物。
- 前記インターロイキン12受容体β2タンパク質が、全長(full-length)インターロイキン12受容体β2タンパク質である、請求項1に記載の血管疾患診断用組成物。
- 請求項1〜11に記載のいずれか一項の組成物を含む、血管疾患診断用キット。
- 前記キットが、マイクロアレイ、アプタマーチップキット、エライザ(ELISA、enzyme linked immunosorbent assay)キット、ブロッティング(blotting)キット、免疫沈殿法キット、免疫蛍光検査キット、タンパク質チップキット及びこれらの組み合わせからなる群から選択されるものである、請求項12に記載の血管疾患診断用キット。
- (a)血管疾患の疑いのある個体から分離された血液試料中のインターロイキン12受容体β2タンパク質のレベルを測定する段階;及び
(b)前記(a)段階で測定されたインターロイキン12受容体β2タンパク質のレベルと正常対照群の試料とを比較する段階を含む、血管疾患診断のための情報提供方法。 - 前記(a)段階の血液試料が、血漿試料または細胞外小包分画試料である、請求項14に記載の血管疾患診断のための情報提供方法。
- 前記細胞外小包が、エキソソームである、請求項15に記載の血管疾患診断のための情報提供方法。
- 前記血管疾患の疑いのある個体から分離された血液試料中で測定されたインターロイキン12受容体β2タンパク質のレベルが、正常対照群の試料より高い場合、前記個体が血管疾患を有すると診断される、請求項14に記載の血管疾患診断のための情報提供方法。
- 前記血管疾患が、心筋梗塞または不安定狭心症である、請求項14に記載の血管疾患診断のための情報提供方法。
- インターロイキン12受容体β2活性の阻害剤を含む、血管疾患の予防または治療用組成物。
- 前記インターロイキン12受容体β2活性の阻害剤が、抗インターロイキン12受容体β2タンパク質抗体、及びインターロイキン12受容体β2遺伝子に特異的なアンチセンスオリゴヌクレオチド、siRNA、shRNA及びmicroRNAからなる群から選択されるものである、請求項19に記載の血管疾患の予防または治療用組成物。
- 血管疾患治療剤でインターロイキン12受容体β2を発現する平滑筋細胞に処理する段階;及びインターロイキン12受容体β2の発現レベルを測定する段階を含むものである、血管疾患治療剤のスクリーニング方法。
- 前記インターロイキン12受容体β2の発現レベルが血管疾患治療のための候補物質の処理により低下する場合、前記候補物質が血管疾患治療剤として決定される、請求項21に記載の血管疾患治療剤のスクリーニング方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2015-0020481 | 2015-02-10 | ||
KR1020150020481A KR101873499B1 (ko) | 2015-02-10 | 2015-02-10 | 혈관 질환 진단용 바이오 마커 및 이의 용도 |
PCT/KR2016/001301 WO2016129890A1 (en) | 2015-02-10 | 2016-02-05 | A biomarker for diagnosing vascular diseases and the uses thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018513353A true JP2018513353A (ja) | 2018-05-24 |
JP6535385B2 JP6535385B2 (ja) | 2019-06-26 |
Family
ID=56614512
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017542865A Active JP6535385B2 (ja) | 2015-02-10 | 2016-02-05 | 血管疾患診断用バイオマーカー及びその用途 |
Country Status (8)
Country | Link |
---|---|
US (1) | US10539573B2 (ja) |
EP (1) | EP3256859B1 (ja) |
JP (1) | JP6535385B2 (ja) |
KR (1) | KR101873499B1 (ja) |
CN (1) | CN106461681B (ja) |
AU (1) | AU2016216860B2 (ja) |
ES (1) | ES2939299T3 (ja) |
WO (1) | WO2016129890A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102047502B1 (ko) * | 2016-06-20 | 2019-11-22 | 셀라이온바이오메드 주식회사 | 포타슘 채널 단백질을 이용한 암 진단용 조성물 |
KR102067610B1 (ko) * | 2018-05-16 | 2020-01-17 | 전남대학교산학협력단 | 급성관상동맥증후군 장기예후 검사방법 및 진단키트 |
GB2576742A (en) * | 2018-08-29 | 2020-03-04 | Lorico Aurelio | Antigen-binding fragment and aptamer for binding CD9 and therapeutic uses |
CN110093412A (zh) * | 2019-03-29 | 2019-08-06 | 南方医科大学南方医院 | 用于诊断动脉粥样硬化的分子标志物ugp2及应用 |
CN112852821B (zh) * | 2019-11-12 | 2022-11-01 | 苏州吉玛基因股份有限公司 | 一种cd81的适配体及其应用 |
CN112877418A (zh) * | 2021-01-11 | 2021-06-01 | 丰能医药科技(上海)有限责任公司 | 一种用于检测血管通透性的产品及其制备方法 |
CN114184792B (zh) * | 2021-11-17 | 2024-05-28 | 中国人民解放军总医院第二医学中心 | 冠心病标志物il-29及其应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013134786A2 (en) * | 2012-03-09 | 2013-09-12 | Caris Life Sciences Luxembourg Holdings, S.A.R.L. | Biomarker compositions and methods |
JP2014510707A (ja) * | 2011-01-04 | 2014-05-01 | ウニヴェルズィテート チューリッヒ | アルツハイマー病の予防又は治療のためのil−12及び/又はil−23のモジュレーター |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001520877A (ja) * | 1997-10-28 | 2001-11-06 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | 血管平滑筋細胞のインビトロ分化、それに関する方法および試薬 |
US20080220075A1 (en) | 2002-03-20 | 2008-09-11 | Elan Pharma International Ltd. | Nanoparticulate compositions of angiogenesis inhibitors |
EP1901768B1 (en) | 2004-02-17 | 2011-11-16 | Schering Corporation | Methods of modulating il-23 activity; related reagents |
DE06806238T1 (de) * | 2005-10-13 | 2010-04-08 | Hendrik Schulze-Koops | Mittel und verfahren zur vorhersage von gelenkzerstörung |
EP2995951B1 (en) * | 2006-05-02 | 2019-02-13 | Critical Care Diagnostics, Inc. | Method for selecting treatment based on differential diagnosis between pulmonary and cardiovascular disease |
WO2008137762A2 (en) * | 2007-05-04 | 2008-11-13 | Cedars-Sinai Medical Center | Methods of diagnosis and treatment of crohn's disease |
MX2011001992A (es) * | 2008-08-22 | 2011-03-29 | Anthrogenesis Corp | Metodos y composiciones para el tratamiento de defectos oseos con poblaciones de celulas placentarias. |
AU2010230311B9 (en) * | 2009-04-27 | 2012-09-20 | Novartis Ag | Composition and methods of use for therapeutic antibodies specific for the IL-12 receptore betal subunit |
WO2011063198A2 (en) * | 2009-11-20 | 2011-05-26 | St. Jude Children's Research Hospital | Methods and compositions for modulating the activity of the interleukin-35 receptor complex |
GB201002382D0 (en) * | 2010-02-12 | 2010-03-31 | King S College London | Assay |
US10003652B2 (en) | 2012-03-05 | 2018-06-19 | Omnitracs, Llc | Managing selective access of a user equipment to internet-based services based on transport type |
EP2738557A1 (en) * | 2012-12-03 | 2014-06-04 | Université Libre de Bruxelles | Organized immune response in cancer |
-
2015
- 2015-02-10 KR KR1020150020481A patent/KR101873499B1/ko active IP Right Grant
-
2016
- 2016-02-05 WO PCT/KR2016/001301 patent/WO2016129890A1/en active Application Filing
- 2016-02-05 EP EP16749430.1A patent/EP3256859B1/en active Active
- 2016-02-05 CN CN201680001261.2A patent/CN106461681B/zh active Active
- 2016-02-05 ES ES16749430T patent/ES2939299T3/es active Active
- 2016-02-05 JP JP2017542865A patent/JP6535385B2/ja active Active
- 2016-02-05 AU AU2016216860A patent/AU2016216860B2/en active Active
-
2017
- 2017-08-10 US US15/673,618 patent/US10539573B2/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014510707A (ja) * | 2011-01-04 | 2014-05-01 | ウニヴェルズィテート チューリッヒ | アルツハイマー病の予防又は治療のためのil−12及び/又はil−23のモジュレーター |
WO2013134786A2 (en) * | 2012-03-09 | 2013-09-12 | Caris Life Sciences Luxembourg Holdings, S.A.R.L. | Biomarker compositions and methods |
Non-Patent Citations (2)
Title |
---|
JOANA M. XAVIER ET AL.: "Association Study of IL10 and IL23R.IL12RB2 in Iranian Patients With Behcet's Disease", ARTHRITIS & RHEUMATISM, vol. 64, no. 8, JPN6018034405, 2012, pages 2761 - 2772, XP055473075, ISSN: 0003871569, DOI: 10.1002/art.34437 * |
MARI LEVULA ET AL.: "Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study", PLOS ONE, vol. Vol.7,Issue 4,e33787, JPN6018034404, 2012, pages 1 - 10, ISSN: 0003871568 * |
Also Published As
Publication number | Publication date |
---|---|
JP6535385B2 (ja) | 2019-06-26 |
EP3256859B1 (en) | 2022-12-21 |
KR20160098684A (ko) | 2016-08-19 |
AU2016216860B2 (en) | 2019-09-12 |
CN106461681B (zh) | 2019-05-03 |
US10539573B2 (en) | 2020-01-21 |
CN106461681A (zh) | 2017-02-22 |
US20170363640A1 (en) | 2017-12-21 |
WO2016129890A1 (en) | 2016-08-18 |
AU2016216860A1 (en) | 2017-09-28 |
ES2939299T3 (es) | 2023-04-20 |
EP3256859A1 (en) | 2017-12-20 |
EP3256859A4 (en) | 2018-08-01 |
KR101873499B1 (ko) | 2018-07-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6535385B2 (ja) | 血管疾患診断用バイオマーカー及びその用途 | |
EP2628013B1 (en) | Biomarkers of brain injury | |
Aharon et al. | Extracellular vesicles of Alzheimer’s disease patients as a biomarker for disease progression | |
US20140200184A1 (en) | Chitinase-3-Like Protein 1 as a Biomarker of Recovery from Kidney Injury | |
JP7319765B2 (ja) | 過敏性膀胱疾患の診断のためのバイオマーカー及びこれを利用した薬剤のスクリーニング方法 | |
JP2017505428A (ja) | 診断及び治療の方法 | |
WO2018025923A1 (ja) | 抗htlv-1剤、htlv-1関連脊髄症(ham/tsp)治療薬 | |
KR20140108718A (ko) | 가와사키 질환용 바이오마커 | |
Chiang et al. | Bone Marrow Stromal Antigen 2 Is a Novel Plasma Biomarker and Prognosticator for Colorectal Carcinoma: A Secretome‐Based Verification Study | |
CN110678757B (zh) | 诊断或监测肾功能或诊断肾功能障碍的方法 | |
KR101952649B1 (ko) | Lrp-1을 유효성분으로 포함하는 방사선 저항성 암 진단용 또는 방사선 치료 예후 예측용 바이오마커 조성물 | |
JP7432578B2 (ja) | がんマーカーおよびその用途 | |
EP2999967B1 (en) | Use of tenascin-c as an extracellular marker of tumor-derived microparticles | |
KR101810395B1 (ko) | 모야모야병 진단용 바이오마커 및 그 용도 | |
WO2017022634A1 (ja) | グリオーマの予後、遠隔部再発リスク及び浸潤を判定する方法及びキット並びにグリオーマを処置するための医薬組成物 | |
KR102104997B1 (ko) | PI3KC2γ를 표적으로 하는 염증 질환 진단 및 치료용 조성물 | |
WO2008122794A2 (en) | Breast cancer methods, medicaments and agents | |
US10066020B2 (en) | Methods of detecting cancer | |
WO2010030980A2 (en) | Akt and clusterin as biomarkers of chemotherapeutic responsiveness | |
CA3161320A1 (en) | Compositions and methods for identifying and modulating thrombotic conditions in a cancer patient | |
CN117106894A (zh) | Nkrf在病理性心脏重构诊治中的应用 | |
JP2022544942A (ja) | 小児患者における腎機能を診断若しくはモニタリングする、又は腎機能障害を診断する方法 | |
WO2016186173A1 (ja) | 劇症肝不全の診断方法、及び予防又は治療剤 | |
Charlesworth | Hypoxia regulated pathways in urological malignancies |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180905 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181204 |
|
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: 20190514 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190531 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6535385 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |