[특허]Non-invasive, in vitro functional tissue assay systems

[미국특허] Non-invasive, in vitro functional tissue assay systems 원문보기

IPC분류정보
국가/구분	United States(US) Patent 등록
국제특허분류(IPC7판)	G01N-033/50 G01N-033/543
출원번호	US-0547871 (2005-04-07)
등록번호	US-9945840 (2018-04-17)
우선권정보	EP-04008497 (2004-04-07)
국제출원번호	PCT/EP2005/003662 (2005-04-07)
§371/§102 date	20070928 (20070928)
국제공개번호	WO2005/098425 (2005-10-20)
발명자 / 주소	Bohlen, Heribert Kolossov, Eugen Kettenhofen, Ralf Scholz, Melanie Fink, Leo
출원인 / 주소	AXIOGENESIS AG
대리인 / 주소	Seyfarth Shaw LLP
인용정보	피인용 횟수 : 0 인용 특허 : 23

초록

Provided are functional cell and tissue assay systems based on substrate-integrated multifunctional microelectrode arrays implementing stem cell technology. The system covers normal and pathogenic characteristics.

대표청구항 ▼

1. An in vitro method for screening a test substance for an effect on a cardiomyocyte, comprising: (a) providing cardiomyocytes having been obtained by differentiating mouse or human pluripotent stem cells;wherein the stem cells have been transfected with at least one vector, wherein the at least one vector comprises a first nucleotide sequence encoding a selectable marker and the at least one vector comprises a second nucleotide sequence encoding a reporter gene;wherein the transfected stem cells comprise the first nucleotide sequence operably linked to at least one cardiac cell-specific regulatory sequence and comprise the second nucleotide sequence operably linked to a cardiac cell-specific regulatory sequence, andwherein the cardiomyocytes have been selected based on expression of the selectable marker;(b) contacting cardiomyocytes of step (a) with a test substance, wherein the cardiomyocytes have been placed on an electrode array;(c) measuring the electrical activity of the contacted cardiomyocytes with the electrode array and analyzing at least one parameter selected from the group consisting of: (i) Na+ channel activity,(ii) Ca2+/K+ channel activity,(iii) K+ channel activity;(iv) amplitude and/or field potential duration,(v) chronotropy,(vi) arrhythmia,(vii) pH-value,(viii) oxygen partial pressure,(ix) beating arrest,(x) contractility,(xi) analysis of AV-dissociation contractility,(xii) conductivity and/or impedance,(xiii) nitrous oxide-effects, or(ix) morphological changes;(d) selecting a test substance that has an effect on at least one parameter in step (c) as compared to cardiomyocytes which were not contacted with a test substance and wherein a change in at least one parameter measured in step (c) indicates that the test substance has an effect on a cardiomyocyte. 2. The assay method of claim 1, wherein said pluripotent stem cells are embryonic stem (ES) cells. 3. The method of claim 1, wherein said electrode array is a multi- or microelectrode array (MEA). 4. The method of claim 3, wherein the electrode array is coated with fibronectin. 5. The method of claim 1, wherein at least one of the parameters analyzed is selected from the group consisting of: beating frequency, mean contractility, maximum contraction and mean area of contraction is analyzed. 6. The method of claim 1, wherein test substance is one of a collection of test substances. 7. The method of claim 6, wherein said collection of test substances comprises about 103 to about 105 substances. 8. The method of claim 1, wherein three or more measurements are taken. 9. The method of claim 1, further comprising isolating the measured cardiomyocytes. 10. The method of claim 8, wherein said measurements are taken at different positions within the array. 11. The method of claim 1, wherein said selection step positively screens a test substance. 12. The method of claim 1, wherein said selection step screens out a test substance.

이 특허에 인용된 특허 (23) 인용/피인용 타임라인 분석

Bohlen, Heribert; Jönsson, Kristina; Ehlich, Andreas; Schwengberg, Silke, Assay for drug discovery based on in vitro differentiated cells.
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Kim, Enoch; Kirk, Gregory L.; Schueller, Olivier; Ostuni, Emanuele, Device for arraying biomolecules and for monitoring cell motility in real-time.
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Gold,Joseph D.; Hassanipour,Mohammad; Collins,Lila R.; Xu,Chunhui, Direct differentiation method for making cardiomyocytes from human embryonic stem cells.
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Benvenisty,Nissim, Directed differentiation of human embryonic cells.
상세보기
Franz Wolfgang-Michael,DEX ; Wobus Anna M.,DEX, Embryonal cardiac muscle cells, their preparation and their use.
상세보기
Hescheler,J체rgen, Fluorescent proteins as cell-type specific reporters.
상세보기
Lakshmi Rambhatla ; Melissa K. Carpenter, Hepatocyte lineage cells derived from pluripotent stem cells.
상세보기
Kolossov, Eugen; Kettenhofen, Ralf; Kopp, Isabella; Bohlen, Heribert; Schwengberg, Silke, Method for the preparation of embryoid bodies (EBs) and uses thereof.
상세보기
Thomson, James A; Marshall, Vivienne S.; Swiergiel, Jennifer J., Method of making embryoid bodies from primate embryonic stem cells.
상세보기
Olson, Eric N.; Lu, Jianrong; McKinsey, Timothy, Methods and compositions relating to HDAC 4 and 5 regulation of cardiac gene expression.
상세보기
Field Loren J., Myocardial grafts and cellular compositions.
상세보기
Field Loren J., Myocardial grafts and cellular compositions.
상세보기
Field, Loren J., Myocardial grafts and cellular compositions.
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Loren J. Field, Myocardial grafts and cellular compositions useful for same.
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Capecchi Mario R. (Salt Lake City UT) Thomas Kirk R. (Salt Lake City UT), Positive-negative selection methods and vectors.
상세보기
Kniffin John M. ; McCauley Ron ; Wells ; III Ralph H. ; Sherman John W. ; Larson Wayne F., Secure entry system with radio communications.
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Klebe Robert J., System and method for rapid positioning of cells on a substratum.
상세보기
Byford, Derrick John, System, apparatus and method for controlling access.
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Elson,Elliot; McConnaughey,William B.; Wakatsuki,Tetsuro, Systems and methods for screening pharmaceutical chemicals.
상세보기
Kolossov, Eugen; Hescheler, Jürgen; Bohlen, Heribert; Fleischmann, Bernd; Röll, Wilhelm; Ehlich, Andreas; Königsmann, Jessica, Tissue modeling in embryonic stem (ES) cell system.
상세보기
Grant, Stephen R.; Olson, Eric N.; Molkentin, Jeffrey D., Transgenic mouse model for cardiac hypertrophy and methods of use thereof.
상세보기
Palmenberg Ann C. (Madison WI) Duke Gregory M. (Madison WI) Parks ; Griffith D. (Madison WI), Translation enhancer.
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Zambrowicz Brian ; Friedrich Glenn ; Sands Arthur T., Vectors for gene trapping and gene activation.
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A	생활필수품
A62	인명구조; 소방(사다리 E06C)
A62B	인명구조용의 기구, 장치 또는 방법(특히 의료용에 사용되는 밸브 A61M 39/00; 특히 물에서 쓰이는 인명구조 장치 또는 방법 B63C 9/00; 잠수장비 B63C 11/00; 특히 항공기에 쓰는 것, 예. 낙하산, 투출좌석 B64D; 특히 광산에서 쓰이는 구조장치 E21F 11/00)
A62B-1/08	.. 윈치 또는 풀리에 제동기구가 있는 것

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[미국특허] Non-invasive, in vitro functional tissue assay systems 원문보기