公开(公告)号：WO2019186283A3

公开(公告)日：2019-10-03

申请号：PCT/IB2019/000498

申请日：2019-03-28

Applicant: NOVOHEART LIMITED

Inventor： LI, Ronald, A. ,  COSTA, Kevin, D.

IPC: G01N33/50

Abstract: A system for screening compounds for therapeutic cardiac effects in the cells, tissues and organoids (1) of patients having diseases such as neurological diseases or disorders with significant cardiac comorbidities. The system comprises a medical device apparatus that can be suitable for a single-tier screen for cardio-active compounds that comprises a human ventricular cardiac anisotropic sheet (hvCAS) and human ventricular cardiac tissue strip (hvCTS), a two-tier system further comprising human ventricular cardiac organoid chamber (hvCOC) (20), or a three-tier system still further comprising a medical device comprising multiple organoids (20), which include tissues or organoids (1) of the same or different type ( e.g. , heart, liver, pancreas, kidney). Another aspect of the disclosure is the methods suitable for use with the systems, comprising screens for identifying compounds having cardiac effects on cells, tissues or organoids (1) of patients having a non-cardiac disease exhibiting a cardiac effect, such as neurological diseases. The methods are further useful in assessing the toxicity of compounds to various cells, tissues or organoids (1) of such patients.

公开(公告)号：WO2022015869A1

公开(公告)日：2022-01-20

申请号：PCT/US2021/041656

申请日：2021-07-14

Applicant: NOVOHEART LIMITED

Inventor： KUROKAWA, Yosuke ,  LEE, Eugene, K. ,  TRAN, David, D. ,  COSTA, Kevin, D. ,  LI, Ronald, A.

IPC: B01L3/00 ,  C12M3/00

Abstract: A multi-sample system for engineered tissue strip assay includes a tissue module enabled with a set of channels each configured to house one or more tissue strips, each tissue strip is in contact with a sensor at one end and a tissue lengthening mechanism at the other end, the sensor is displaced or deformed when the tissue strip exerts force against the sensor during the lengthening or contraction of each tissue strip; and a detection system configured to capture change in the sensor in contact with the tissue strips during lengthening or contraction of at least one of the tissue strips.

公开(公告)号：WO2018029535A1

公开(公告)日：2018-02-15

申请号：PCT/IB2017/001130

申请日：2017-08-11

Applicant: NOVOHEART LIMITED

Inventor： LI, Ronald

IPC: G01N33/50

Abstract: The disclosure provides a substrate for the ordered growth and development of cardiomyocytes such as ventricular cardiomyocytes derived from pluripotent stem cells along with methods of culturing the cells on the substrates for use in assays such as cardiotoxicity assays. Further provided are methods for assessing cardiotoxicity using one or more criteria disclosed herein

Abstract translation: 本公开内容提供了用于心肌细胞的有序生长和发育的底物，所述心肌细胞例如源自多能干细胞的心室心肌细胞以及在底物上培养细胞用于测定如心脏毒性测定的方法。 进一步提供了使用本文公开的一种或多种标准评估心脏毒性的方法

公开(公告)号：WO2022011163A1

公开(公告)日：2022-01-13

申请号：PCT/US2021/040923

申请日：2021-07-08

Applicant: NOVOHEART LIMITED

Inventor： ROBERTS, Erin, G. ,  LEE, Eugene, K. ,  TRAN, David, D. ,  MAK, Suet, Yee ,  COSTA, Kevin, D. ,  FERMINI, Bernard ,  WONG, Andy

IPC: C12M3/00 ,  G01N33/50 ,  B01F15/00

Abstract: The present disclosure relates to tissue supports for use with engineered tissues and organoids, such as cardiac organoid chambers. In an embodiment of the present disclosure, the tissue supports are provided with a fluid-impermeable resilient member that is resiliently deformable during testing by cultured tissues formed on the surface of the tissue support.

公开(公告)号：WO2019244044A1

公开(公告)日：2019-12-26

申请号：PCT/IB2019/055118

申请日：2019-06-18

Applicant: NOVOHEART LIMITED

Inventor： LI, Ronald A. ,  COSTA, Kevin D.

IPC: C12N5/22 ,  A61L27/24 ,  A61L27/52 ,  A61L27/50

Abstract: Provided are methods and materials for assaying known and candidate therapeutics for inotropic cardiac effects in one or more in vitro assay formats comprising preloaded cardiac tissues and/or organoids.

公开(公告)号：WO2022150626A1

公开(公告)日：2022-07-14

申请号：PCT/US2022/011671

申请日：2022-01-07

Applicant: NOVOHEART LIMITED

Inventor： KUROKAWA, Yosuke ,  LEE, Eugene

IPC: A61F2/24 ,  A61M39/22 ,  F16K15/14 ,  F16K17/164 ,  F16K31/12

Abstract: A low pressure valve assembly comprising: an elastomeric material including at least one cut that forms a deformable portion, a first backing material including an inlet, and a second backing material including an outlet, wherein the elastomeric material is between the first backing material and the second backing material, and wherein the deformable portion is configured to deform at a range of pressures including a pressure of less than or equal to about 1 mmH20.

公开(公告)号：WO2019186283A2

公开(公告)日：2019-10-03

申请号：PCT/IB2019/000498

申请日：2019-03-28

Applicant: NOVOHEART LIMITED

Inventor： LI, Ronald, A. ,  COSTA, Kevin, D.

Abstract: The disclosure provides a system for screening compounds for therapeutic cardiac effects in the cells, tissues and organoids of patients having diseases such as neurological diseases or disorders with significant cardiac comorbidities. The system comprises a medical device apparatus that can be suitable for a single-tier screen for cardio-active compounds that comprises a human ventricular cardiac anisotropic sheet (hvCAS) and human ventricular cardiac tissue strip (hvCTS), a two-tier system further comprising human ventricular cardiac organoid chamber (hvCOC), or a three-tier system still further comprising a medical device comprising multiple organoids, which include tissues or organoids of the same or different type ( e.g. , heart, liver, pancreas, kidney). Another aspect of the disclosure is the methods suitable for use with the systems, comprising screens for identifying compounds having cardiac effects on cells, tissues or organoids of patients having a non-cardiac disease exhibiting a cardiac effect, such as neurological diseases. The methods are further useful in assessing the toxicity of compounds to various cells, tissues or organoids of such patients.

公开(公告)号：WO2019106438A1

公开(公告)日：2019-06-06

申请号：PCT/IB2018/001535

申请日：2018-11-29

Applicant: NOVOHEART LIMITED

Inventor： TRAN, David, D. ,  COSTA, Kevin, D. ,  LI, Ronald, A.

IPC: G01N33/50 ,  C12N5/10 ,  C12M1/34

Abstract: A two-stage or two-tier system and method for rapid screening of compounds for inotropic effects is disclosed. The system comprises, in a first tier, an engineered cardiac tissue strip (CTS) comprising cardiomyocytes, such as human ventricular cardiomyocytes, embedded in a biocompatible gel wherein the gel comprises at least two biocompatible structural supports such as polydimethylsiloxane posts for elevating the gel. The system further comprises, in a second tier, an apparatus comprising at least one organoid module comprising at least one organoid cartridge, wherein each organoid cartridge comprises an organoid, and a mirror arrangement. The system further comprises at least one detection device, such as a high-speed camera, for detecting deflection of the CTS gel in the first tier of the system and/or for detecting tissue or organoid behavior in the organoid cartridge or cartridges of the second tier of the system. The method comprises application of a compound to the cardiac tissue strip and detection of any deflection of the gel in response to application of the compound to detect compounds showing a possible inotropic effect and introduction of such a compound to an organoid module, wherein modified contractility of the cardiac tissue or organoid in the organoid module identifies a compound having an inotropic effect.. A method of making a cardiac tissue strip is also provided. The second tier system is also useful in methods of producing and monitoring, characterizing, manipulating or testing one or more organoids ( e.g. , human organoids) ex vivo . The system, methods, apparatus, and compositions are useful in a variety of contexts, including the assessment of potential therapeutics for efficacy and/or toxicity.