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1. 发明申请

US20180055881A1 IMMUNOMODULATORY PROPERTIES OF MULTIPOTENT ADULT PROGENITOR CELLS AND USES THEREOF 审中-公开
公开(公告)号：US20180055881A1
公开(公告)日：2018-03-01
申请号：US15804760
申请日：2017-11-06
申请人： ATHERSYS, INC. , OREGON HEALTH AND SCIENCE UNIVERSITY
发明人： Richard MAZIARZ , Magdalena Kovacsovics , Philip Streeter , Robert Deans , Wouter Van't Hof
IPC分类号： A61K35/12 , A61K35/28 , A61N5/10 , C12N5/074 , A61K35/14 , A61K45/06 , A61K39/00
CPC分类号： A61K35/12 , A61K35/14 , A61K35/28 , A61K39/001 , A61K45/06 , A61K2035/122 , A61K2035/124 , A61N5/10 , C12N5/0607
摘要： Isolated cells are described that are not embryonic stem cells, not embryonic germ cells, and not germ cells. The cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal lineages. The cells do not provoke a harmful immune response. The cells can modulate immune responses. As an example, the cells can suppress an immune response in a host engendered by allogeneic cells, tissues, and organs. Methods are described for using the cells, by themselves or adjunctively, to treat subjects. For instance, the cells can be used adjunctively for immunosuppression in transplant therapy. Methods for obtaining the cells and compositions for using them also are described.

2. 发明申请

US20040253591A1 COMPOSITIONS AND METHODS FOR MAKING MUTATIONS IN CELL LINES AND ANIMALS 审中-公开
公开(公告)号：US20040253591A1
公开(公告)日：2004-12-16
申请号：US10342948
申请日：2003-01-15
申请人： Athersys, Inc.
发明人： John Joseph Harrington , Paul David Jackson , Li Jiang
IPC分类号： C12Q001/68 , C12N015/85
CPC分类号： C12N15/102 , C12N15/01 , C12Q1/6897
摘要： Abstract of DisclosureThe present invention is directed generally to reduction or inactivation of gene function or gene expression in cells in vitro and in multiorganisms. The invention encompasses methods for mutating cells using a combination of mutagens, particularly wherein at least one mutagen is an insertional mutagen, to achieve homozygous gene mutation or mutation of multiple genes required cumulatively to achieve a phenotype to create knock-outs, knock-downs, and other modifications in the same cell. The invention is also directed to cells (and libraries thereof) and organisms created by the methods of the invention, including those in which at least one of the genes created by insertional mutagenesis is tagged by means of the insertion sequences thereby allowing identification of the mutated gene(s). The invention is also directed to libraries of mutated cells and their uses. The invention is also directed to methods of identifying mutations with methods of the invention, in cells (and libraries thereof) and organisms, by means of the insertional tag.

3. 发明申请

US20040082018A1 Methods for using osteocalcin 审中-公开
标题翻译：骨钙素的使用方法
公开(公告)号：US20040082018A1
公开(公告)日：2004-04-29
申请号：US10283656
申请日：2002-10-29
申请人： Athersys, Inc.
发明人： George Mbella Ekema , Robert W. Mays , Kurt R. Brunden
IPC分类号： C12Q001/68 , G01N033/567 , A61K031/00
CPC分类号： G01N33/5091 , G01N33/5008 , G01N33/502 , G01N33/5044 , G01N33/6887 , G01N33/6893 , G01N2500/00 , G01N2500/10
摘要： The present invention relates to methods for using osteocalcin. The invention also relates to methods for using polynucleotides encoding osteocalcin. The invention relates to methods using the osteocalcin polypeptides and polynucleotides as a target for diagnosis and treatment osteocalcin related conditions. The invention further relates to drug-screening methods using the osteocalcin polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the osteocalcin polypeptides and polynucleotides. The invention further relates to agonists and antagonists identified by drug screening methods with the osteocalcin polypeptides and polynucleotides as a target. The invention further related to methods of treating a subject suffering from an osteocalcin mediated condition.
摘要翻译：本发明涉及使用骨钙素的方法。本发明还涉及使用编码骨钙素的多核苷酸的方法。本发明涉及使用骨钙素多肽和多核苷酸作为诊断和治疗骨钙素相关病症的靶标的方法。本发明还涉及使用骨钙素多肽和多核苷酸鉴定用于诊断和治疗的激动剂和拮抗剂的药物筛选方法。本发明还包括基于骨钙素多肽和多核苷酸的激动剂和拮抗剂。本发明还涉及通过药物筛选方法鉴定的激动剂和拮抗剂，其中骨钙素多肽和多核苷酸作为靶标。本发明还涉及治疗患有骨钙素介导病症的受试者的方法。

4. 发明申请

US20040018624A1 Compositions and methods for making mutations in cell lines and animals 审中-公开
标题翻译：用于在细胞系和动物中进行突变的组合物和方法
公开(公告)号：US20040018624A1
公开(公告)日：2004-01-29
申请号：US10277612
申请日：2002-10-22
申请人： Athersys, Inc.
发明人： John Joseph Harrington , Paul David Jackson , Li Jiang
IPC分类号： C12N015/85
CPC分类号： C12N15/102 , C12N15/01 , C12Q1/6897
摘要： The present invention is directed generally to reduction or inactivation of gene function or gene expression in cells in vitro and in multicellular organisms. The invention encompasses methods for mutating cells using a combination of mutagens, particularly wherein at least one mutagen is an insertional mutagen, to achieve homozygous gene mutation or mutation of multiple genes required cumulatively to achieve a phenotype to create knock-outs, knock-downs, and other modifications in the same cell. The invention is also directed to cells (and libraries thereof) and organisms created by the methods of the invention, including those in which at least one of the genes created by insertional mutagenesis is tagged by means of the insertion sequences thereby allowing identification of the mutated gene(s). The invention is also directed to libraries of mutated cells and their uses. The invention is also directed to methods of identifying mutations with methods of the invention, in cells (and libraries thereof) and organisms, by means of the insertional tag.
摘要翻译：本发明一般涉及体外和多细胞生物体中细胞中基因功能或基因表达的还原或失活。本发明包括使用诱变剂的组合突变细胞的方法，特别是其中至少一种诱变剂是插入型诱变剂，以实现纯合基因突变或累积需要多个基因的突变以实现表型以产生敲除，敲低，和在同一个单元格中的其他修改。本发明还涉及通过本发明的方法产生的细胞（及其文库）和生物体，包括其中通过插入突变产生的至少一个基因通过插入序列进行标记，从而允许识别突变的基因。本发明还涉及突变细胞的文库及其用途。本发明还涉及借助于插入标签在本发明的方法，细胞（和其文库）和生物体中鉴定突变的方法。

5. 发明申请

US20040253727A1 COMPOSITIONS AND METHODS FOR MAKING MUTATIONS IN CELL LINES AND ANIMALS 有权
公开(公告)号：US20040253727A1
公开(公告)日：2004-12-16
申请号：US10342761
申请日：2003-01-15
申请人： Athersys, Inc.
发明人： John Joseph Harrington , Paul David Jackson , Li Jiang
IPC分类号： C12Q001/68 , C12N015/85
CPC分类号： C12N15/102 , C12N15/01 , C12Q1/6897
摘要： Abstract of DisclosureThe present invention is directed generally to reduction or inactivation of gene function or gene expression in cells in vitro and in multiorganisms. The invention encompasses methods for mutating cells using a combination of mutagens, particularly wherein at least one mutagen is an insertional mutagen, to achieve homozygous gene mutation or mutation of multiple genes required cumulatively to achieve a phenotype to create knock-outs, knock-downs, and other modifications in the same cell. The invention is also directed to cells (and libraries thereof) and organisms created by the methods of the invention, including those in which at least one of the genes created by insertional mutagenesis is tagged by means of the insertion sequences thereby allowing identification of the mutated gene(s). The invention is also directed to libraries of mutated cells and their uses. The invention is also directed to methods of identifying mutations with methods of the invention, in cells (and libraries thereof) and organisms, by means of the insertional tag.

6. 发明申请

US20040253589A1 COMPOSITIONS AND METHODS FOR MAKING MUTATIONS IN CELL LINES AND ANIMALS 审中-公开
标题翻译：用于在细胞系和动物中进行突变的组合物和方法
公开(公告)号：US20040253589A1
公开(公告)日：2004-12-16
申请号：US10342896
申请日：2003-01-15
申请人： Athersys, Inc.
发明人： John Joseph Harrington , Paul David Jackson , Li Jiang
IPC分类号： C12Q001/68 , C12N015/85
CPC分类号： C12N15/102 , C12N15/01 , C12Q1/6897
摘要： Abstract of DisclosureThe present invention is directed generally to reduction or inactivation of gene function or gene expression in cells in vitro and in multiorganisms. The invention encompasses methods for mutating cells using a combination of mutagens, particularly wherein at least one mutagen is an insertional mutagen, to achieve homozygous gene mutation or mutation of multiple genes required cumulatively to achieve a phenotype to create knock-outs, knock-downs, and other modifications in the same cell. The invention is also directed to cells (and libraries thereof) and organisms created by the methods of the invention, including those in which at least one of the genes created by insertional mutagenesis is tagged by means of the insertion sequences thereby allowing identification of the mutated gene(s). The invention is also directed to libraries of mutated cells and their uses. The invention is also directed to methods of identifying mutations with methods of the invention, in cells (and libraries thereof) and organisms, by means of the insertional tag.
摘要翻译：公开内容摘要本发明一般涉及体外和多重生物体中基因功能或基因表达的减少或失活。本发明包括使用诱变剂的组合突变细胞的方法，特别是其中至少一种诱变剂是插入型诱变剂，以实现纯合基因突变或累积需要多个基因的突变以实现表型以产生敲除，敲低，和在同一个单元格中的其他修改。本发明还涉及通过本发明的方法产生的细胞（及其文库）和生物体，包括其中通过插入突变产生的至少一个基因通过插入序列进行标记，从而允许识别突变的基因。本发明还涉及突变细胞的文库及其用途。本发明还涉及借助于插入标签在本发明的方法，细胞（和其文库）和生物体中鉴定突变的方法。

7. 发明申请

US20030180267A1 Compositions and methods for non-targeted activation of endogenous genes 有权
标题翻译：内源基因非靶向激活的组成和方法
公开(公告)号：US20030180267A1
公开(公告)日：2003-09-25
申请号：US10331329
申请日：2002-12-30
申请人： Athersys, Inc.
发明人： John J. Harrington , Bruce Sherf , Stephen Rundlett
IPC分类号： A61K048/00 , C12N015/85 , C12N005/08
CPC分类号： C07K14/705 , A61K48/00 , C07K2319/00 , C12N9/003 , C12N15/1096 , C12N15/63 , C12N15/67 , C12N15/85 , C12N15/90 , C12N2800/107 , C12N2800/108 , C12N2800/204 , C12N2800/60 , C12N2840/20 , C12N2840/203 , C12N2840/44
摘要： The present invention is directed generally to activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention also is directed generally to methods for expressing an endogenous gene in a cell at levels higher than those normally found in the cell. In one embodiment of the invention, expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. In another embodiment, the expression of the endogenous gene may be further increased by co-integration of one or more amplifiable markers, and selecting for increased copies of the one or more amplifiable markers located on the integrated vector. The invention also provides methods for the identification, activation, isolation, and/or expression of genes undiscoverable by current methods since no target sequence is necessary for integration.
摘要翻译：本发明一般涉及通过原位重组方法激活基因表达或引起基因过度表达。本发明还通常涉及用于在细胞中以比通常在细胞中发现的那些更高的水平表达内源基因的方法。在本发明的一个实施方案中，内源基因的表达在通过激活基因表达的调控序列的非同源或非法重组整合入细胞后被激活或增加。在另一个实施方案中，可以通过一个或多个可扩增标记的共同整合以及选择位于整合载体上的一个或多个可扩增标记物的增加拷贝来进一步增加内源基因的表达。本发明还提供了鉴定，激活，分离和/或表达不能被现有方法发现的基因的方法，因为不需要靶序列进行整合。

8. 发明授权

US11351202B2 MAPC treatment of brain injuries and diseases 有权
公开(公告)号：US11351202B2
公开(公告)日：2022-06-07
申请号：US15849181
申请日：2017-12-20
申请人： ATHERSYS, INC. , AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.
发明人： Robert Mays , Robert J. Deans , David C. Hess , James E. Carroll , Cesar V. Borlongan
IPC分类号： A61K35/28 , A61K35/50 , A61K35/545 , A61K38/13 , A61K45/06 , C12N5/074 , A61K31/4353 , A61K31/436 , A61K31/485 , A61K31/52 , A61K31/661 , A61K35/12 , A61K35/30 , A61K35/407 , A61K35/44 , A61K35/48 , A61K35/51
摘要： The invention relates to the treatment of various injuries, disorders, dysfunctions, diseases, and the like of the brain with MAPCs, particularly in some aspects, to the treatment of the same resulting from hypoxia, including that caused by systemic hypoxia and that caused by insufficient blood supply. In some further particulars the invention relates, for example, to the treatment of hypoxic ischemic brain injury with MAPCs, in children for example, and to the treatment of cortical infarcts and stroke with MAPCs in adults, for example.

9. 发明授权

US11000546B2 Immunomodulatory properties of MAPCs and uses thereof 有权
公开(公告)号：US11000546B2
公开(公告)日：2021-05-11
申请号：US15970385
申请日：2018-05-03
申请人： ATHERSYS, INC. , OREGON HEALTH & SCIENCE UNIVERSITY
发明人： Robert Deans , Richard Maziarz , Magdalena Kovacsovics , Philip Streeter , Wouter Van't Hof
IPC分类号： A61K35/12 , A61K45/06 , A61K35/28 , C12N5/074 , A61K35/14 , A61K39/00 , A61N5/10
摘要： Isolated cells are described that are not embryonic stem cells, not embryonic germ cells, and not germ cells. The cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal lineages. The cells do not provoke a harmful immune response. The cells can modulate immune responses. As an example, the cells can suppress an immune response in a host engendered by allogeneic cells, tissues, and organs. Methods are described for using the cells, by themselves or adjunctively, to treat subjects. For instance, the cells can be used adjunctively for immunosuppression in transplant therapy. Methods for obtaining the cells and compositions for using them also are described.

10. 发明申请

US20180296609A1 MAPC TREATMENTOF BRAIN INJURIES AND DISEASES 审中-公开
公开(公告)号：US20180296609A1
公开(公告)日：2018-10-18
申请号：US15849181
申请日：2017-12-20
申请人： ATHERSYS, INC.
发明人： Robert MAYS , Robert J. Deans , David C. Hess , James E. Carroll , Cesar V. Borlongan
IPC分类号： A61K35/50 , A61K35/545 , A61K31/4353 , A61K35/51 , A61K31/436 , A61K31/485 , A61K31/52 , A61K31/661 , A61K35/12 , A61K35/28 , A61K35/30 , A61K35/407 , A61K35/44 , A61K35/48 , A61K38/13
摘要： The invention relates to the treatment of various injuries, disorders, dysfunctions, diseases, and the like of the brain with MAPCs, particularly in some aspects, to the treatment of the same resulting from hypoxia, including that caused by systemic hypoxia and that caused by insufficient blood supply. In some further particulars the invention relates, for example, to the treatment of hypoxic ischemic brain injury with MAPCs, in children for example, and to the treatment of cortical infarcts and stroke with MAPCs in adults, for example.

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