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21. 发明专利

AU2002320376B2 Sterile aspiration/reinjection systems 未知
公开(公告)号：AU2002320376B2
公开(公告)日：2008-04-17
申请号：AU2002320376
申请日：2002-07-10
申请人： MYOCARDIAL THERAPEUTICS INC
发明人： LI HONG , SASAMINE KAZUO , FOURMONT MICHELLE , MALPHUS E THOMAS , CARPENTER KENNETH W
IPC分类号： A61M5/145 , A61B19/00 , A61M1/00 , A61M25/00
摘要： The invention provides systems containing a sterile container for aspiration, filtering, treating and reinjection into a subject of a bodily fluid in a sterile environment. The systems are particularly designed to facilitate transfection of cells within the sterile container by gene therapy molecules and reinjection of the transfected cells into the donor at controlled depth in precisely controlled volumes such as is useful for revascularization of ischemic cardiac tissue. For injection, a pressure actuator, preferably hand-held, applies force to liquids held within the sterile container in precisely controlled increments, thereby expressing liquids through a hollow needle or injection catheter in precisely controlled microvolumes. The invention systems include a hand-held injection device with audible cues that correspond to an operator-selected injection volume and/or audible cues that correspond to needle penetration depth selected by the operator.

22. 发明专利

CA2454157A1 FLEXIBLE TISSUE INJECTION CATHETERS WITH CONTROLLED DEPTH PENETRATION 未知
公开(公告)号：CA2454157A1
公开(公告)日：2003-02-20
申请号：CA2454157
申请日：2002-07-09
申请人： MYOCARDIAL THERAPEUTICS INC
发明人： SASAMINE KAZUO , LI HONG , FOURMONT MICHELLE , MALPHUS E THOMAS , CARPENTER KENNETH W
IPC分类号： A61M5/14 , A61B19/00 , A61M25/00 , A61M25/08 , A61B18/24
摘要： The invention tissue injection catheters are designed to facilitate injectio n of a therapeutic or diagnostic agent to an interior body cavity, especially the myocardium or epicardium of the heart with precisely controlled depth penetration. The invention injection catheters, which include mechanisms for precisely controlling the length of needle tip exposed for tissue penetratio n, are designed to be used in an assemblage with a sterile container and delive ry actuator for reinjection of autologous cell-containing fluids, such as autologous bone marrow aspirate. In preferred embodiments, the assemblage is designed to be hand-held. When used in such an assemblage, the invention catheters are particularly useful as a gene delivery device to effect angiogenesis of ischemic areas of the heart.

23. 发明申请

WO2005007811A2 INJECTION OF BONE MARROW-DERIVED CELLS AND MEDIUM FOR ANGIOGENESIS 审中-公开
标题翻译：骨髓源性细胞注射和血管生成中等
公开(公告)号：WO2005007811A2
公开(公告)日：2005-01-27
申请号：PCT/US2004/021243
申请日：2004-07-01
申请人： MYOCARDIAL THERAPEUTICS, INC. , EPSTEIN, Stephen , FUCHS, Shmuel , KORNOWSKI, Ran , LEON, Martin, B. , CARPENTER, Kenneth, W.
发明人： EPSTEIN, Stephen , FUCHS, Shmuel , KORNOWSKI, Ran , LEON, Martin, B. , CARPENTER, Kenneth, W.
IPC分类号： C12N
CPC分类号： C07K14/4702 , A61K48/00 , A61K2035/124 , C07K14/523 , C07K14/535 , C12N5/0691 , C12N2502/1358 , C12N2799/022
摘要： Methods are provided for enhancing capacity of impaired bone marrow cells to promote angiogenesis when introduced into an ischemic site in a patient by transfecting early attaching cells derived from bone marrow in culture with an angiogenesis promoting transgene. Methods are also provided for utilizing such early attaching cells derived from autologous bone marrow, or media derived from these cells while the cells are grown in culture (which need not be from autologous cells) to deliver angiogenesis-promoting transgenes or proteins to a patient. The transfected early attaching cells, or media derived from these cells while the cells are grown in culture, are introduced into an ischemic tissue, such as the heart, to enhance formation of collateral blood vessels. The cells or media can also be injected into the blood stream (artery supplying the ischemic tissue, or any other artery or vein).
摘要翻译：提供了用于增强受损的骨髓细胞的能力以促进血管生成，当通过在血管生成促进转基因中转染早期附着来自骨髓的细胞的细胞时，将其导入患者的缺血部位。还提供了用于利用衍生自自体骨髓的这种早期附着细胞的方法或来自这些细胞的培养基，同时细胞在培养物中生长（其不需要来自自体细胞）以向患者递送血管生成促进转基因或蛋白质。将细胞在培养物中生长时，转染的早期附着细胞或来自这些细胞的培养基被引入缺血组织如心脏，以增强侧支血管的形成。细胞或培养基也可以注入血液流（供应缺血组织的动脉，或任何其他动脉或静脉）。

24. 发明申请

WO2003013625A3 FLEXIBLE TISSUE INJECTION CATHETERS WITH CONTROLLED DEPTH PENETRATION 审中-公开
公开(公告)号：WO2003013625A3
公开(公告)日：2003-02-20
申请号：PCT/US2002/021676
申请日：2002-07-09
申请人： MYOCARDIAL THERAPEUTICS, INC.
发明人： CARPENTER, Kenneth, W. , FOURMONT, Michelle , MALPHUS, E., Thomas , SASAMINE, Kazuo , LI, Hong
IPC分类号： A61M5/00
摘要： The invention tissue injection catheters (1) are designed to facilitate injection of a therapeutic or diagnostic agent to an interior body cavity, especially the myocardium or epicardium of the heart with precisely controlled depth penetration. The invention injection catheters, which include mechanisms for precisely controlling the length of needle tip (8) exposed for tissue penetration, are designed to be used in an assemblage with a sterile container (38) and delivery actuator (22) for reinjection of autologous cell-containing fluids, such as autologous bone marrow aspirate. In preferred embodiments, the assemblage is designed to be hand-held. When used in such an assemblage, the invention catheters are particularly useful as a gene delivery device to effect angiogenesis of ischemic areas of the heart.

25. 发明申请

WO2003013625A2 FLEXIBLE TISSUE INJECTION CATHETERS WITH CONTROLLED DEPTH PENETRATION 审中-公开
标题翻译：具有控制深度穿透的柔性组织注射导管
公开(公告)号：WO2003013625A2
公开(公告)日：2003-02-20
申请号：PCT/US2002/021676
申请日：2002-07-09
申请人： MYOCARDIAL THERAPEUTICS, INC.
发明人： CARPENTER, Kenneth, W. , FOURMONT, Michelle , MALPHUS, E., Thomas , SASAMINE, Kazuo , LI, Hong
IPC分类号： A61M
CPC分类号： A61M25/0612 , A61B2090/062 , A61M25/0084 , A61M2025/0008 , A61M2025/0089 , A61M2202/0413 , A61M2205/75 , A61M2202/0021
摘要： The invention tissue injection catheters are designed to facilitate injection of a therapeutic or diagnostic agent to an interior body cavity, especially the myocardium or epicardium of the heart with precisely controlled depth penetration. The invention injection catheters, which include mechanisms for precisely controlling the length of needle tip exposed for tissue penetration, are designed to be used in an assemblage with a sterile container and delivery actuator for reinjection of autologous cell-containing fluids, such as autologous bone marrow aspirate. In preferred embodiments, the assemblage is designed to be hand-held. When used in such an assemblage, the invention catheters are particularly useful as a gene delivery device to effect angiogenesis of ischemic areas of the heart.
摘要翻译：本发明的组织注射导管被设计成便于将治疗剂或诊断剂注射到内部体腔，特别是具有精确控制的深度穿透的心脏的心肌或心外膜。本发明的注射导管包括用于精确控制暴露于组织穿透的针尖的长度的机构，被设计成与无菌容器和用于再注射自体含细胞的流体例如自体骨髓的输送致动器组合使用吸出。在优选实施例中，组合被设计为手持式。当用于这种组合时，本发明的导管特别可用作用于实现心脏缺血区域血管生成的基因递送装置。

26. 发明申请

WO2006029262A3 CONDITIONED MEDIUM OF AUTOLOGOUS OR ALLOGENIC PROGENITOR CELLS FOR ANGIOGENESIS TREATMENT 审中-公开
公开(公告)号：WO2006029262A3
公开(公告)日：2006-03-16
申请号：PCT/US2005/031982
申请日：2005-09-07
申请人： MYOCARDIAL THERAPEUTICS, INC. , KORNOWSKI, Ran , FUCHS, Shmuel , EPSTEIN, Stephen, E. , LEON, Martin, B.
发明人： KORNOWSKI, Ran , FUCHS, Shmuel , EPSTEIN, Stephen, E. , LEON, Martin, B.
IPC分类号： C12N5/00 , C07K1/26
摘要： A therapeutic composition is provided that comprises a cell-free conditioned medium containing mixed secretion products of isolated angiogenic progenitor cells obtained from bone marrow, peripheral blood, or adipose tissue. The composition may additionally contain angiogenesis-promoting proteins obtained by transfecting the progenitors cells in culture with an angiogenesis promoting transgene. The composition is useful to promote angiogenesis when introduced into or adjacent to an ischemic site in a patient, such as in myocardium or peripheral limb. Methods are also provided for utilizing such cell-free conditioned medium to deliver angiogenesis-promoting proteins to a patient. The cell-free conditioned medium can also be injected into the blood stream for delivery to the ischemic tissue. The cells can derive from either an autologous or allogenic source and can be lyophilized or frozen for storage.

27. 发明申请

WO2005104766A3 INJECTION OF BONE MARROW-DERIVED CONDITIONED MEDIUM FOR ANGIOGENESIS 审中-公开
标题翻译：注射骨质疏松调节中性粒细胞
公开(公告)号：WO2005104766A3
公开(公告)日：2006-01-12
申请号：PCT/US2005014513
申请日：2005-04-27
申请人： MYOCARDIAL THERAPEUTICS INC , KORNOWSKI RAN , FUCHS SHMUEL , EPSTEIN STEPHEN , LEON MARTIN B
发明人： KORNOWSKI RAN , FUCHS SHMUEL , EPSTEIN STEPHEN , LEON MARTIN B
IPC分类号： A61K48/00 , C12N15/00 , C12N15/09 , C12N21/00
CPC分类号： C07K14/4702 , A01K2227/108 , A01K2267/0375 , A61K35/28 , C07K2319/71 , C12N5/0669 , C12N2501/115 , C12N2501/165 , C12N2501/70 , C12N2502/1394 , C12N2510/00
摘要： Methods are provided for promoting formation of collateral blood supply at an ischemic site in tissue by culturing early attaching cells derived from growth of bone marrow aspirate in vitro, collecting early attaching cells produced by the bone marrow culture and injecting conditioned medium produced by culture of the early attaching cells into an ischemic site in heart or limb. The preferred early attaching cells for use in the invention methods are marrow-derived stromal cells. Any donor's bone marrow can be used in preparation of the conditioned medium. Optionally, the early attaching cells can be transfected with an angiogenesis promoting transgene encoding hypoxia inducing factor I alpha, a fibroblast growth factor and/or a nitric oxide synthase. Conditioned media containing angiogenic cytokines produced such cells are also provided for injection into tissue, such as heart or peripheral limb muscle, requiring formation of collateral blood supply.
摘要翻译：提供了通过体外培养早期粘附来自骨髓吸出物生长的细胞来促进组织缺血部位形成侧支血液供应的方法，收集由骨髓培养产生的早期附着细胞并注入通过培养产生的条件培养基早期将细胞附着到心脏或肢体的缺血部位。用于本发明方法的优选早期附着细胞是骨髓来源的基质细胞。任何供体的骨髓都可用于制备条件培养基。任选地，可以用编码缺氧诱导因子Iα，成纤维细胞生长因子和/或一氧化氮合酶的血管生成促进转基因转染早期附着细胞。还提供了含有产生这种细胞的血管生成细胞因子的条件培养基用于注射到组织中，例如心脏或外周肢肌，需要形成侧支血液供应。

28. 发明申请

WO2003006089A1 METHODS FOR CONTROLLED DEPTH INJECTIONS INTO INTERIOR BODY CAVITIES 审中-公开
标题翻译：控制深度注射入室内机的方法
公开(公告)号：WO2003006089A1
公开(公告)日：2003-01-23
申请号：PCT/US2002/021725
申请日：2002-07-09
申请人： MYOCARDIAL THERAPEUTICS, INC.
发明人： EPSTEIN, Stephen , FUCHS, Shmuel , KORNOWSKI, Ran
IPC分类号： A61M5/00
CPC分类号： A61M25/0084 , A61B2090/062 , A61M2025/0089 , A61M2202/0413 , A61M2205/75 , A61M2202/0021
摘要： A flexible tissue injection catheter (1) is used to accomplish injections at a precisely controlled depth of precisely controlled volumes of a therapeutic or diagnostic agent into an interior body cavity, such as the epicardium or myocardium of the heart. For myocardial injection, depth penetration is controlled by using a catheter that allows the operator to control depth penetration by means of an adjustable needle stop (14) attached to the catheter handle.
摘要翻译：柔性组织注射导管（1）用于在精确控制的治疗或诊断剂量的精确控制的深度上将注射物完成到内部体腔（例如心脏的心外膜或心肌）中。对于心肌注射，通过使用允许操作者通过附接到导管手柄的可调节止针（14）来控制深度穿透的导管来控制深度穿透。

29. 发明申请

US20060051334A1 Injection of bone marrow-derived conditioned medium for angiogenesis 审中-公开
标题翻译：注射用于血管生成的骨髓来源的条件培养基
公开(公告)号：US20060051334A1
公开(公告)日：2006-03-09
申请号：US11117607
申请日：2005-04-27
申请人： Ran Kornowski , Shmuel Fuchs , Stephen Epstein , Martin Leon
发明人： Ran Kornowski , Shmuel Fuchs , Stephen Epstein , Martin Leon
IPC分类号： A61K48/00
CPC分类号： C12N5/0691 , A61K35/28 , A61K38/1825 , A61K38/1866 , A61K38/44 , A61K48/00 , C12N2502/1358 , C12Y114/13039 , A61K2300/00
摘要： Methods are provided for promoting formation of collateral blood supply at an ischemic site in tissue by culturing early attaching cells derived from growth of bone marrow aspirate in vitro, collecting early attaching cells produced by the bone marrow culture and injecting conditioned medium produced by culture of the early attaching cells into an ischemic site in heart or limb. The preferred early attaching cells for use in the invention methods are marrow-derived stromal cells. Any donor's bone marrow can be used in preparation of the conditioned medium. Optionally, the early attaching cells can be transfected with an angiogenesis promoting transgene encoding hypoxia inducing factor 1 alpha, a fibroblast growth factor and/or a nitric oxide synthase. Conditioned media containing angiogenic cytokines produced such cells are also provided for injection into tissue, such as heart or peripheral limb muscle, requiring formation of collateral blood supply.
摘要翻译：提供了通过体外培养早期粘附来自骨髓吸出物生长的细胞来促进组织缺血部位形成侧支血液供应的方法，收集由骨髓培养产生的早期附着细胞并注入通过培养产生的条件培养基早期将细胞附着到心脏或肢体的缺血部位。用于本发明方法的优选早期附着细胞是骨髓来源的基质细胞。任何供体的骨髓都可用于制备条件培养基。任选地，可以用编码缺氧诱导因子1α，成纤维细胞生长因子和/或一氧化氮合酶的血管生成促进转基因转染早期附着细胞。还提供了含有产生这种细胞的血管生成细胞因子的条件培养基用于注射到组织中，例如心脏或外周肢肌，需要形成侧支血液供应。

30. 发明授权

US07097832B1 Intramyocardial injection of autologous bone marrow 有权
标题翻译：心肌内注射自体骨髓
公开(公告)号：US07097832B1
公开(公告)日：2006-08-29
申请号：US09868411
申请日：2000-03-30
申请人： Ran Kornowski , Shmuel Fuchs , Stephen E. Epstein , Martin B. Leon
发明人： Ran Kornowski , Shmuel Fuchs , Stephen E. Epstein , Martin B. Leon
IPC分类号： A01N63/00 , C12N5/00 , C12N5/06
CPC分类号： A61K38/193 , A61K35/28 , A61K38/1709 , A61K2300/00
摘要： A method of treating cardiac or myocardial conditions comprises the administration of an effective amount of autologous bone marrow. The bone marrow may optionally be stimulated and/or administered in combination with a pharmaceutical drug, protein, gene or other factor or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation or migration or blood vessel formation.
摘要翻译：治疗心脏或心肌病症的方法包括施用有效量的自体骨髓。骨髓可以任选地与可以增强血管生成生长因子的骨髓产生和/或促进内皮细胞增殖或迁移或血管形成的药物，蛋白质，基因或其他因子或治疗组合而被刺激和/或施用。

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