公开(公告)号：US06908763B1

公开(公告)日：2005-06-21

申请号：US08918537

申请日：1997-08-22

申请人： Koichi Akashi ,  Motonari Kondo ,  Irving L. Weissman

发明人： Koichi Akashi ,  Motonari Kondo ,  Irving L. Weissman

IPC分类号： A61K38/00 ,  C12N5/0781 ,  C12N5/0789 ,  C12N5/02 ,  C12N5/06 ,  C12N5/08 ,  C12N15/87

CPC分类号： C12N5/0635 ,  A61K38/00 ,  C12N5/0647 ,  C12N2501/125 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2510/00

摘要： A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for lymphoid lineages, but lacking the potential to differentiate into myeloid and erythroid lineages. Methods are provided for the isolation and culture of this common lymphoid progenitor cell (CLP). The cell enrichment methods employ reagents that specifically recognize CDw127 (IL-7 receptor α); CD117 (c-kit) protein, in conjunction with other markers expressed on lineage committed cells. The murine cells are also characterized as expressing low levels of sca-1 (Ly-6E and Ly-6A). The CLPs are predominantly cycling, blast cells. These cells give rise to B cells, T cells and natural killer cells, as evidenced by their growth and differentiation in vitro and in vivo.

公开(公告)号：US07297329B2

公开(公告)日：2007-11-20

申请号：US11093951

申请日：2005-03-29

申请人： Koichi Akashi ,  Irving L. Weissman ,  Motonari Kondo

发明人： Koichi Akashi ,  Irving L. Weissman ,  Motonari Kondo

IPC分类号： A01N65/00

CPC分类号： C12N5/0635 ,  A61K38/00 ,  C12N5/0647 ,  C12N2501/125 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2510/00

摘要： A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for lymphoid lineages, but lacking the potential to differentiate into myeloid and erythroid lineages. Methods are provided for the isolation and culture of this common lymphoid progenitor cell (CLP). The cell enrichment methods employ reagents that specifically recognize CDw127 (IL-7 receptor α); CD117 (c-kit) protein, in conjunction with other markers expressed on lineage committed cells. The murine cells are also characterized as expressing low levels of sca-1 (Ly-6E and Ly-6A). The CLPs are predominantly cycling, blast cells. These cells give rise to B cells, T cells and natural killer cells, as evidenced by their growth and differentiation in vitro and in vivo.

摘要翻译： 提供了基本上富集的哺乳动物造血细胞亚群，其特征在于淋巴谱系的祖细胞活性，但缺乏分化为骨髓和红系谱系的潜力。 提供了用于分离和培养这种常见淋巴祖细胞（CLP）的方法。 细胞富集方法使用特异性识别CDw127（IL-7受体α）的试剂; CD117（c-kit）蛋白，与在谱系确定细胞上表达的其他标志物结合。 鼠细胞也被表征为表达低水平的sca-1（Ly-6E和Ly-6A）。 CLP主要是循环，胚细胞。 这些细胞产生B细胞，T细胞和自然杀伤细胞，这通过其体外和体内的生长和分化证明。

公开(公告)号：US20080131408A1

公开(公告)日：2008-06-05

申请号：US11874841

申请日：2007-10-18

申请人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi ,  Markus Gabriel Manz ,  Toshihiro Miyamoto

发明人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi ,  Markus Gabriel Manz ,  Toshihiro Miyamoto

IPC分类号： A01N63/00 ,  C12N5/00

CPC分类号： C12N5/0647 ,  C12N2501/125 ,  C12N2501/14 ,  C12N2501/145 ,  C12N2501/22 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2503/00 ,  C12Q1/6881 ,  C12Q2600/158

摘要： A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for myeloid lineages, but lacking the potential to differentiate into lymphoid lineages. This population is further divided into specific myeloid progenitor subsets, including a common myeloid progenitor cells (CMP), megakaryocyte/erythroid progenitor cells (MEP) and granulocyte/monocyte lineage progenitor (GMP). Methods are provided for the isolation and culture of these subpopulations. The CMP population gives rise to all myeloid lineages, and can give rise to the two additional and isolatable progenitor populations that are exclusively committed to either the erythroid/megakaryocytic or myelomonocytic lineages. Tηε χελλ ενιχημεντ μετηoδσ εμπλoψεαγεντσ τηατ σπεχαλλψεψoγνιζε Tηψ-1; ανδIΛ-7 Pα, in conjunction with other markers expressed on lineage committed cells. These cells give rise to a variety of myeloid cells, including megakaryocytes, granulocytes, dendritic cells and erythroid cells, as evidenced by their growth and differentiation in vitro and in vivo.

摘要翻译： 提供了基本上富集的哺乳动物造血细胞亚群，其特征在于骨髓谱系的祖细胞活性，但缺乏分化成淋巴谱系的潜力。 该群体进一步分为特定的骨髓祖细胞亚群，包括常见的髓系祖细胞（CMP），巨核细胞/红细胞祖细胞（MEP）和粒细胞/单核细胞谱系祖细胞（GMP）。 提供了用于分离和培养这些亚群体的方法。 CMP群体产生所有骨髓谱系，并且可以产生专门致力于红细胞/巨核细胞或骨髓单核细胞谱系的两个另外的和可分离的祖细胞群体。 “=”2.46mm“wi =”1.78mm“file =”US20080131408A1-20080605-P00001.TIF“img-content =”character“img-format =”tif“=”CUSTOM-CHARACTER-00001“ “/> iotachietamuepsilonnutau muepsilontauetaodeltasigma epsilonmupilambdaopsi epsilonalphagammaepsilonnutphaigma tauetaalphatau sigmapiepsilonchialphalambdalambdapsi epsilonpsiogammanuiotazetaepsilon Tetapsi-1; alphanudeltaILambda-7 Palpha，与在谱系确定的细胞上表达的其他标志物结合。 这些细胞产生各种骨髓细胞，包括巨核细胞，粒细胞，树突状细胞和红细胞，其体外和体内的生长和分化证明。

公开(公告)号：US06465247B1

公开(公告)日：2002-10-15

申请号：US09607529

申请日：2000-06-29

申请人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi

发明人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi

IPC分类号： C12N506

CPC分类号： C12Q1/6881 ,  C12N5/0647 ,  C12N2501/125 ,  C12N2501/14 ,  C12N2501/145 ,  C12N2501/22 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2503/00 ,  C12Q2600/158

摘要： A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for myeloid lineages, but lacking the potential to differentiate into lymphoid lineages. This population is further divided into specific myeloid progenitor subsets, including a common myeloid progenitor cells (CMP), megakaryocyte/erythroid progenitor cells (MEP) and granulocyte/monocyte lineage progenitor (GMP). Methods are provided for the isolation and culture of these subpopulations. The CMP population gives rise to all myeloid lineages, and can give rise to the two additional and isolatable progenitor populations that are exclusively committed to either the erythroid/megakaryocytic or myelomonocytic lineages. The cell enrichment methods employ reagents that specifically recognize CDw127 (IL-7 receptor &agr;); CD117 (c-kit) protein, in conjunction with other markers expressed on lineage committed cells. These cells give rise to a variety of myeloid cells, including megakaryocytes, granulocytes, dendritic cells and erythroid cells, as evidenced by their growth and differentiation in vitro and in vivo.

摘要翻译： 提供了基本上富集的哺乳动物造血细胞亚群，其特征在于骨髓谱系的祖细胞活性，但缺乏分化成淋巴谱系的潜力。 该群体进一步分为特定的骨髓祖细胞亚群，包括常见的髓系祖细胞（CMP），巨核细胞/红细胞祖细胞（MEP）和粒细胞/单核细胞谱系祖细胞（GMP）。 提供了用于分离和培养这些亚群体的方法。 CMP群体产生所有骨髓谱系，并且可以产生专门致力于红细胞/巨核细胞或骨髓单核细胞谱系的两个另外的和可分离的祖细胞群体。 细胞富集方法使用特异性识别CDw127（IL-7受体α）的试剂; CD117（c-kit）蛋白，与在谱系确定细胞上表达的其他标志物结合。 这些细胞产生各种骨髓细胞，包括巨核细胞，粒细胞，树突状细胞和红细胞，其体外和体内的生长和分化证明。

公开(公告)号：US07618654B2

公开(公告)日：2009-11-17

申请号：US11874841

申请日：2007-10-18

申请人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi ,  Markus Gabriel Manz ,  Toshihiro Miyamoto

发明人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi ,  Markus Gabriel Manz ,  Toshihiro Miyamoto

IPC分类号： A61K35/28 ,  G01N33/53

CPC分类号： C12N5/0647 ,  C12N2501/125 ,  C12N2501/14 ,  C12N2501/145 ,  C12N2501/22 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2503/00 ,  C12Q1/6881 ,  C12Q2600/158

摘要： A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for myeloid lineages, but lacking the potential to differentiate into lymphoid lineages. This population is further divided into specific myeloid progenitor subsets, including a common myeloid progenitor cells (CMP), megakaryocyte/erythroid progenitor cells (MEP) and granulocyte/monocyte lineage progenitor (GMP). Methods are provided for the isolation and culture of these subpopulations. The CMP population gives rise to all myeloid lineages, and can give rise to the two additional and isolatable progenitor populations that are exclusively committed to either the erythroid/megakaryocytic or myelomonocytic lineages. Tηε χελλ ενιχημεντ μετηoδσ εμπλoψεαγεντσ τηατ σπεχαλλψεψoγνιζε Tηψ-1; ανδIΛ-7 Pα, in conjunction with other markers expressed on lineage committed cells. These cells give rise to a variety of myeloid cells, including megakaryocytes, granulocytes, dendritic cells and erythroid cells, as evidenced by their growth and differentiation in vitro and in vivo.

摘要翻译： 提供了基本上富集的哺乳动物造血细胞亚群，其特征在于骨髓谱系的祖细胞活性，但缺乏分化成淋巴谱系的潜力。 该群体进一步分为特定的骨髓祖细胞亚群，包括常见的髓系祖细胞（CMP），巨核细胞/红细胞祖细胞（MEP）和粒细胞/单核细胞谱系祖细胞（GMP）。 提供了用于分离和培养这些亚群体的方法。 CMP群体产生所有骨髓谱系，并且可以产生专门致力于红细胞/巨核细胞或骨髓单核细胞谱系的两个另外的和可分离的祖细胞群体。 “=”2.46mm“wi =”1.78mm“file =”US07618654-20091117-P00001.TIF“alt =”自定义字符“img-content =”character“ img-format =“tif”/> iotachietamuepsilonnutau muepsilontauetaodeltasigma epsilonmupilambdaopsi epsilonalphagammaepsilonnutausigma tauetaalphatau sigmapiepsilonchialphalambdalambdapsi epsilonpsiogammanuiotazetaepsilon Tetapsi-1; alphanudeltaILambda-7 Palpha，与在谱系确定的细胞上表达的其他标志物结合。 这些细胞产生各种骨髓细胞，包括巨核细胞，粒细胞，树突状细胞和红细胞，其体外和体内的生长和分化证明。

公开(公告)号：US06761883B2

公开(公告)日：2004-07-13

申请号：US09956279

申请日：2001-09-17

申请人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi ,  Markus Gabriel Manz ,  Toshihiro Miyamoto

发明人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi ,  Markus Gabriel Manz ,  Toshihiro Miyamoto

IPC分类号： A01N6300

CPC分类号： C12N5/0647 ,  C12N2501/125 ,  C12N2501/14 ,  C12N2501/145 ,  C12N2501/22 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2503/00 ,  C12Q1/6881 ,  C12Q2600/158

摘要： A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for myeloid lineages, but lacking the potential to differentiate into lymphoid lineages. This population is further divided into specific myeloid progenitor subsets, including a common myeloid progenitor cells (CMP), megakaryocyte/erythroid progenitor cells (MEP) and granulocyte/monocyte lineage progenitor (GMP). Methods are provided for the isolation and culture of these subpopulations. The CMP population gives rise to all myeloid lineages, and can give rise to the two additional and isolatable progenitor populations that are exclusively committed to either the erythroid/megakaryocytic or myelomonocytic lineages. The cell enrichment methods employ reagents that specifically recognize Thy-1; and IL-7R&agr;, in conjunction with other markers expressed on lineage committed cells. These cells give rise to a variety of myeloid cells, including megakaryocytes, granulocytes, dendritic cells and erythroid cells, as evidenced by their growth and differentiation in vitro and in vivo.

公开(公告)号：US07300760B2

公开(公告)日：2007-11-27

申请号：US10737576

申请日：2003-12-15

申请人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi ,  Markus Gabriel Manz ,  Toshihiro Miyamoto

发明人： Irving L. Weissman ,  David Jeffrey Traver ,  Koichi Akashi ,  Markus Gabriel Manz ,  Toshihiro Miyamoto

IPC分类号： G01N33/53 ,  C12N5/00 ,  C12N5/02

CPC分类号： C12N5/0647 ,  C12N2501/125 ,  C12N2501/14 ,  C12N2501/145 ,  C12N2501/22 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2503/00 ,  C12Q1/6881 ,  C12Q2600/158

摘要： A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for myeloid lineages, but lacking the potential to differentiate into lymphoid lineages. This population is further divided into specific myeloid progenitor subsets, including a common myeloid progenitor cells (CMP), megakaryocyte/erythroid progenitor cells (MEP) and granulocyte/monocyte lineage progenitor (GMP). Methods are provided for the isolation and culture of these subpopulations. The CMP population gives rise to all myeloid lineages, and can give rise to the two additional and isolatable progenitor populations that are exclusively committed to either the erythroid/megakaryocytic or myelomonocytic lineages. The cell enrichment methods employ reagents that specifically recognize Thy-1; and IL-7Rα, in conjunction with other markers expressed on lineage committed cells. These cells give rise to a variety of myeloid cells, including megakaryocytes, granulocytes, dendritic cells and erythroid cells, as evidenced by their growth and differentiation in vitro and in vivo.

摘要翻译： 提供了基本上富集的哺乳动物造血细胞亚群，其特征在于骨髓谱系的祖细胞活性，但缺乏分化成淋巴谱系的潜力。 该群体进一步分为特定的骨髓祖细胞亚群，包括常见的髓系祖细胞（CMP），巨核细胞/红细胞祖细胞（MEP）和粒细胞/单核细胞谱系祖细胞（GMP）。 提供了用于分离和培养这些亚群体的方法。 CMP群体产生所有骨髓谱系，并且可以产生专门致力于红细胞/巨核细胞或骨髓单核细胞谱系的两个另外的和可分离的祖细胞群体。 细胞富集方法采用特异性识别Thy-1的试剂; 和IL-7Rα，与在谱系承诺细胞上表达的其他标志物结合。 这些细胞产生各种骨髓细胞，包括巨核细胞，粒细胞，树突状细胞和红细胞，其体外和体内的生长和分化证明。

公开(公告)号：US20050191284A1

公开(公告)日：2005-09-01

申请号：US11093951

申请日：2005-03-29

申请人： Koichi Akashi ,  Irving Weissman ,  Motonari Kondo

发明人： Koichi Akashi ,  Irving Weissman ,  Motonari Kondo

IPC分类号： A61K38/00 ,  C12N5/0781 ,  C12N5/0789 ,  A61K48/00 ,  C12N5/08

CPC分类号： C12N5/0635 ,  A61K38/00 ,  C12N5/0647 ,  C12N2501/125 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2510/00

摘要： A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for lymphoid lineages, but lacking the potential to differentiate into myeloid and erythroid lineages. Methods are provided for the isolation and culture of this common lymphoid progenitor cell (CLP). The cell enrichment methods employ reagents that specifically recognize CDw127 (IL-7 receptor α); CD117 (c-kit) protein, in conjunction with other markers expressed on lineage committed cells. The murine cells are also characterized as expressing low levels of sca-1 (Ly-6E and Ly-6A). The CLPs are predominantly cycling, blast cells. These cells give rise to B cells, T cells and natural killer cells, as evidenced by their growth and differentiation in vitro and in vivo.

摘要翻译： 提供了基本上富集的哺乳动物造血细胞亚群，其特征在于淋巴谱系的祖细胞活性，但缺乏分化为骨髓和红系谱系的潜力。 提供了用于分离和培养这种常见淋巴祖细胞（CLP）的方法。 细胞富集方法使用特异性识别CDw127（IL-7受体α）的试剂; CD117（c-kit）蛋白，与在谱系确定细胞上表达的其他标志物结合。 鼠细胞也被表征为表达低水平的sca-1（Ly-6E和Ly-6A）。 CLP主要是循环，胚细胞。 这些细胞产生B细胞，T细胞和自然杀伤细胞，这通过其体外和体内的生长和分化证明。

公开(公告)号：US5821108A

公开(公告)日：1998-10-13

申请号：US418534

申请日：1995-04-07

申请人： Koichi Akashi ,  Irving Weissman

发明人： Koichi Akashi ,  Irving Weissman

IPC分类号： A61K35/12 ,  A61K35/14 ,  A61K35/17 ,  C07K16/28 ,  C12N5/078 ,  C12N15/85 ,  G01N33/53 ,  A61K39/395

CPC分类号： C07K16/28 ,  A61K35/17 ,  C12N5/065 ,  A61K2035/124 ,  C12N2500/32

摘要： A subpopulation in the CD4.sup.+ 8.sup.+ (DP) thymic blast population is identified that is the precursor for thymic T cells. All such progenitors are c-kit.sup.+. The c-kit.sup.+ subset expresses lower levels of CD4 and CD8 than the large and small DP c-kit- cells. These DP.sup.int c-kit.sup.+ cells differentiate to thymic T cells rapidly on heterogenous thymic stromal cell cultures. Similar maturation takes place in vivo over 4 days. A method for isolating the cells which are c-kit.sup.+ and which express intermediate or low levels of CD4+/CD8+ is also disclosed.

摘要翻译： 鉴定出CD4 + 8 +（DP）胸腺细胞群中的亚群是胸腺T细胞的前体。 所有这些祖细胞都是c-kit +。 c-kit +子集表达比大和小的DP c-kit-细胞更低水平的CD4和CD8。 这些DPint c-kit +细胞在异源胸腺基质细胞培养物上快速分化为胸腺T细胞。 类似的成熟在体内发生4天以上。 还公开了分离c-kit +并表达中等或低水平的CD4 + / CD8 +的细胞的方法。

公开(公告)号：US08647623B2

公开(公告)日：2014-02-11

申请号：US13263434

申请日：2010-04-09

申请人： Shinichiro Takayanagi ,  Yoshimasa Inagaki ,  Koichi Akashi ,  Yoshikane Kikushige

发明人： Shinichiro Takayanagi ,  Yoshimasa Inagaki ,  Koichi Akashi ,  Yoshikane Kikushige

IPC分类号： A61K39/395

CPC分类号： G01N33/57426 ,  A61K2039/505 ,  C07K16/2803 ,  C07K16/3061 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  G01N33/57407 ,  G01N2333/70503

摘要： Disclosed is a therapeutic method comprising administering a TIM-3 antibody to a subject who is suspected to be suffering from blood tumor and in whom TIM-3 has been expressed in a Lin(−)CD34(+)CD38(−) cell fraction of bone marrow or peripheral blood or a subject who has been received any treatment for blood tumor. Also disclosed is a composition for preventing or treating blood tumor, which comprises a TIM-3 antibody as an active ingredient. Conceived diseases include those diseases which can be treated through the binding or targeting of the TIM-3 antibody to blood tumor cells (AML cells, CML cells, MDS cells, ALL cells, CLL cells, multiple myeloma cells, etc.), helper T cell (e.g., Th1 cells, Th17 cells), and antigen-presenting cells (e.g., dendritic cells, monocytes, macrophages, and cells resembling to the aforementioned cells (hepatic stellate cells, osteoclasts, microglial cells, intraepidermal macrophages, dust cells (alveolar macrophages), etc)), all of which are capable of expressing TIM-3. The diseases for which the therapeutic use is to be examined include blood diseases in which the expression of TIM-3 is observed in bone marrow or peripheral blood, particularly blood tumor.

摘要翻译： 公开了一种治疗方法，其包括对怀疑患有血液肿瘤的受试者施用TIM-3抗体，并且在其中已经表达TIM-3的Lin（ - ）CD34（+）CD38（ - ）细胞级分中 骨髓或外周血或受到血肿治疗的受试者。 还公开了用于预防或治疗血液肿瘤的组合物，其包含TIM-3抗体作为活性成分。 想象中的疾病包括可以通过TIM-3抗体对血液肿瘤细胞（AML细胞，CML细胞，MDS细胞，ALL细胞，CLL细胞，多发性骨髓瘤细胞等）的结合或靶向治疗的那些疾病，辅助T 细胞（例如，Th1细胞，Th17细胞）和抗原呈递细胞（例如，树突状细胞，单核细胞，巨噬细胞和类似于上述细胞的细胞（肝星状细胞，破骨细胞，小神经胶质细胞，表皮内巨噬细胞，尘埃细胞（肺泡 巨噬细胞）等）），所有这些都能表达TIM-3。 要检查治疗用途的疾病包括在骨髓或外周血，特别是血肿瘤中观察到TIM-3的表达的血液疾病。