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1. 发明申请

WO2003010292A2 METHODS AND APPARATUS FOR ENRICHMENT AND CULTURE OF MONOCYTIC DENDRITIC CELL PRECURSORS 审中-公开
标题翻译：用于富集和培养单核细胞树突状细胞前体的方法和设备
公开(公告)号：WO2003010292A2
公开(公告)日：2003-02-06
申请号：PCT/US2002/023865
申请日：2002-07-25
申请人： NORTHWEST BIOTHERAPEUTICS, INC. , BOSCH, Marnix, L. , TJOA, Benjamin, A. , HARRIS, Paul, C.
发明人： BOSCH, Marnix, L. , TJOA, Benjamin, A. , HARRIS, Paul, C.
IPC分类号： C12N
CPC分类号： C12N5/0087 , C12N5/0639 , C12N2501/22 , C12N2501/23 , G01N33/5005 , G01N33/56972
摘要： The present invention provides methods and materials for isolating, culturing and differentiating monocytic dendritic cell precursors to form immature and/or mature dendritic cells. In a related aspect, methods, materials, and a system are provided for isolating, culturing and differentiating monocytic dendritic cell precursors under aseptic conditions to obtain immature and/or mature dendritic cells.
摘要翻译：本发明提供用于分离，培养和分化单核细胞树突细胞前体以形成未成熟和/或成熟树突细胞的方法和材料。在相关方面，提供了用于在无菌条件下分离，培养和分化单核细胞树突细胞前体以获得未成熟和/或成熟树突细胞的方法，材料和系统。

2. 发明申请

WO2004076651A2 GENERATION OF DENDRITIC CELLS FROM MONOCYTIC DENDRITIC PRECURSOR CELLS WITH GM-CSF IN THE ABSENCE OF ADDITIONAL CYTOKINES 审中-公开
标题翻译：在含有GM-CSF的单核细胞前体细胞中产生增殖细胞因子
公开(公告)号：WO2004076651A2
公开(公告)日：2004-09-10
申请号：PCT/US2004/006119
申请日：2004-02-27
申请人： NORTHWEST BIOTHERAPEUTICS, INC. , TJOA, Benjamin A. , BOSCH, Marnix, L.
发明人： TJOA, Benjamin A. , BOSCH, Marnix, L.
IPC分类号： C12N
CPC分类号： C12N5/0639 , C12N2500/10 , C12N2500/30 , C12N2500/72 , C12N2500/90 , C12N2501/22 , C12N2501/23 , C12N2501/24 , C12N2502/70 , C12N2533/12
摘要： The present invention it was determined that dendritic cells could be derived from various sources including peripheral blood monocytes in the presence of only GM-CSF without other cytokines if the monocytes were not activated. By preventing activation, such as by preventing binding of the cells to the surface of the culture vessel, the monocytes do not require the presence of additional cytokines, such as IL-4 or IL-13, to prevent differentiation into a non-dendritic cell lineage. The immature DCs generated and maintained in this manner were CD14 - and expressed high levels of CD1a. Upon maturation by contact with an agent such as, for example, BCG and IFNγ, the cells were determined to express surface molecules typical of mature dendritic cells purified by prior methods and cultured in the presence of GM-CSF and IL-4. The mature dendritic cells produced from monoxytes without activation and cultured in GM-CSF alone are suitable for use in dendritic cell-based immunotherapy methods, such as for use in the treatment of disease, including cancer.
摘要翻译：本发明确定如果单核细胞未被激活，则在存在只有GM-CSF的情况下，树突状细胞可以来源于各种来源，包括外周血单核细胞。通过防止活化，例如通过防止细胞与培养容器表面的结合，单核细胞不需要另外的细胞因子如IL-4或IL-13的存在，以防止分化成非树突状细胞血统。以这种方式产生和维持的未成熟DCs是CD14 - 并且表达高水平的CD1a。通过与例如BCG和IFNγ的试剂接触成熟，测定细胞表达通过现有方法纯化并在GM-CSF和IL-4存在下培养的成熟树突状细胞的典型表达分子。由单核细胞产生的成熟树突状细胞无活化并单独在GM-CSF中培养，适用于树突细胞基免疫治疗方法，例如用于治疗包括癌症在内的疾病。

3. 发明申请

WO2004000444A1 TANGENTIAL FLOW FILTRATION DEVICES AND METHODS FOR LEUKOCYTE ENRICHMENT 审中-公开
标题翻译：水龙头渗流装置及其制备方法
公开(公告)号：WO2004000444A1
公开(公告)日：2003-12-31
申请号：PCT/US2003/019428
申请日：2003-06-19
申请人： NORTHWEST BIOTHERAPEUTICS, INC. , BOSCH, Marnix, L. , HARRIS, Paul, C. , MONAHAN, Steven, J. , TURNER, Allen , BOYNTON, Alton, L. , LODGE, Patricia, A.
发明人： BOSCH, Marnix, L. , HARRIS, Paul, C. , MONAHAN, Steven, J. , TURNER, Allen , BOYNTON, Alton, L. , LODGE, Patricia, A.
IPC分类号： B01D61/14
CPC分类号： A61M1/3496 , A61M1/3633 , A61M1/38 , A61M2202/0439 , B01D61/147 , B01D61/16 , B01D61/18 , B01D61/22 , B01D2315/10 , Y10T436/255
摘要： The present invention provides tangential flow filtration devices and methods for enriching a heterogeneous mixture of blood constituents for leukocytes by removal of non-leukocyte blood constituents. In one particular embodiment the device can provide a composition enriched in monocytes. One embodiment includes a remover unit (1) having a crossflow chamber (3) separated by a microporous filter (5) from a filtrate chamber (4), the remover unit (1) also having a tangential flow inlet (6), a fluid outlet (7) for a fluid enriched in leukocytes and a filtrate outlet (8).
摘要翻译：本发明提供切向流过滤装置和通过去除非白细胞血液成分来富集白细胞的血液成分的非均相混合物的方法。在一个具体实施方案中，该装置可以提供富含单核细胞的组合物。一个实施例包括具有从滤液室（4）与微孔过滤器（5）分离的交叉流室（3）的去除单元（1），所述去除单元（1）还具有切向流入口（6），流体出口（7），用于富含白细胞的液体和滤液出口（8）。

4. 发明申请

WO2003022215A3 COMPOSITIONS AND METHODS FOR PRIMING MONOCYTIC DENDRITIC CELLS AND T CELLS FOR TH-1 RESPONSE 审中-公开
公开(公告)号：WO2003022215A3
公开(公告)日：2003-03-20
申请号：PCT/US2002/028620
申请日：2002-09-06
申请人： NORTHWEST BIOTHERAPEUTICS, INC. , BOSCH, Marnix, L.
发明人： BOSCH, Marnix, L.
IPC分类号： A01N63/00
摘要： The present invention provides compositions and methods for inducing maturation of immature dendritic cells (DC) and for priming those cells for inducing a type 1 immune response. The present invention also provides dendritic cell populations useful for activating and for preparing T cells polarized towards production of type 1 cytokines and/or a type 1 response. Similarly, activated, polarized T cell populations, and methods of making the same are provided.

5. 发明申请

WO2004053072A2 ADMINISTRATION OF DENDRITIC CELLS PARTIALLY MATURED IN VITRO FOR THE TREATMENT OF TUMORS 审中-公开
标题翻译：肿瘤治疗肿瘤部位成形细胞的管理
公开(公告)号：WO2004053072A2
公开(公告)日：2004-06-24
申请号：PCT/US2003/038672
申请日：2003-12-05
申请人： NORTHWEST BIOTHERAPEUTICS, INC. , BOSCH, Marnix, L.
发明人： BOSCH, Marnix, L.
IPC分类号： C12N
CPC分类号： C12N5/0639 , A61K39/0011 , A61K2039/5154 , C12N2500/72 , C12N2501/05 , C12N2501/24
摘要： The present invention provides populations of cells comprising partially matured dendritic cells that can be used for administration individuals having a tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 1 to about 10 hours, or more, efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in the lymph node the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNFα and IL-12) and contact T cells inducing a substantial anti-tumor immune response.
摘要翻译：本发明提供包含部分成熟的树突状细胞的细胞群，其可用于给予具有肿瘤的个体。部分成熟的树突状细胞，与树突状细胞成熟剂接触约1至约10小时或更长时间，有效地占据和处理肿瘤部位的肿瘤抗原，完全成熟，并随后迁移至淋巴结被治疗的个体。一旦在淋巴结中，现在完全成熟的抗原呈递树突状细胞分泌适当的细胞因子（例如TNFα和IL-12）并接触诱导大量抗肿瘤免疫应答的T细胞。

6. 发明申请

WO2003022215A2 COMPOSITIONS AND METHODS FOR PRIMING MONOCYTIC DENDRITIC CELLS AND T CELLS FOR TH-1 RESPONSE 审中-公开
标题翻译：用于促进TH-1反应的单核细胞和T细胞的组合物和方法
公开(公告)号：WO2003022215A2
公开(公告)日：2003-03-20
申请号：PCT/US2002/028620
申请日：2002-09-06
申请人： NORTHWEST BIOTHERAPEUTICS, INC. , BOSCH, Marnix, L.
发明人： BOSCH, Marnix, L.
IPC分类号： A61K
CPC分类号： C12N5/0639 , A61K2039/5154 , A61K2039/5158 , A61K2039/55522 , A61K2039/55594 , A61K2039/57 , C07K14/5428 , C07K14/5434 , C12N2500/72 , C12N2501/24
摘要： The present invention provides compositions and methods for inducing maturation of immature dendritic cells (DC) and for priming those cells for inducing a type 1 immune response. The present invention also provides dendritic cell populations useful for activating and for preparing T cells polarized towards production of type 1 cytokines and/or a type 1 response. Similarly, activated, polarized T cell populations, and methods of making the same are provided.
摘要翻译：本发明提供用于诱导未成熟树突状细胞（DC）成熟并引发这些细胞诱导1型免疫应答的组合物和方法。本发明还提供了可用于激活和制备向1型细胞因子产生和/或1型反应产生极化的T细胞的树突状细胞群。类似地，提供了活化的，极化的T细胞群体及其制备方法。

7. 发明申请

WO2005052137A1 TANGENTIAL FLOW FILTRATION DEVICES AND METHODS FOR STEM CELL ENRICHMENT 审中-公开
公开(公告)号：WO2005052137A1
公开(公告)日：2005-06-09
申请号：PCT/US2004/038805
申请日：2004-11-19
申请人： NORTHWEST BIOTHERAPEUTICS, INC. , BOSCH, Marnix, L. , LODGE, Patricia, A. , MCEARCHERN, Julie, Anna , BOYNTON, Alton, L. , HUGENHOLTZ, Paul, G.
发明人： BOSCH, Marnix, L. , LODGE, Patricia, A. , MCEARCHERN, Julie, Anna , BOYNTON, Alton, L. , HUGENHOLTZ, Paul, G.
IPC分类号： C12N5/00
CPC分类号： C12N5/0663 , A61K2035/124 , C12N5/0647 , C12N2500/35 , Y10T436/25375 , Y10T436/255
摘要： The present invention provides methods for enriching a heterogenous mixture of bone marrow or blood constituents for stem cells by removal of non-stem cell constituents comprising separation of the non-stem cell constituents using a tangential flow filtration device.
摘要翻译：本发明提供了通过去除非干细胞成分来富集干细胞的骨髓或血液成分的异源混合物的方法，包括使用切向流过滤装置分离非干细胞成分。

8. 发明申请

WO2017048875A1 METHODS RELATING TO ACTIVATED DENDRITIC CELL COMPOSITIONS AND IMMUNOTHERAPEUTIC TREATMENTS FOR SUBJECTS WITH ADVANCED CANCERS 审中-公开
标题翻译：与激活的细胞组合物相关的方法和用于先进癌症的受试者的免疫治疗
公开(公告)号：WO2017048875A1
公开(公告)日：2017-03-23
申请号：PCT/US2016/051781
申请日：2016-09-14
申请人： NORTHWEST BIOTHERAPEUTICS, INC
发明人： BOSCH, Marnix, L.
IPC分类号： C12N5/0784 , C12N5/02 , C07K14/535 , C07K14/54 , C07K14/57 , C07K14/525 , A61K35/15
CPC分类号： A61K35/15 , C07K14/525 , C07K14/5412 , C07K14/5421 , C07K14/5434 , C12N5/0639 , C12N2500/72 , C12N2501/22
摘要： The present disclosure provides partially mature and activated dendritic cells that produce levels of cytokines/chemokines, for example, one or any combination of, and/or all of IL-6, IL-8, IL-12 and/or TNFα, that are correlated with improved clinical outcomes, significantly increased survival times and significantly increased times to tumor or cancer recurrence. The determined threshold amounts of these cytokines can be used for (i) a immunotherapeutic potency test for activated dendritic cells, (ii) selecting responder patients, (iii) rejecting non-responder patients, and (iv) to screen for dendritic cell activation or maturation agents that can also induce the production of the threshold amount of the cytokines/chemokines.
摘要翻译：本公开提供部分成熟和活化的树突细胞，其产生细胞因子/趋化因子水平，例如IL-6，IL-8，IL-12和/或TNFα的一种或任何组合，和/或全部，其是与临床结果改善相关，显着增加存活时间，并显着增加肿瘤或癌症复发时间。这些细胞因子的确定阈值可用于（i）活化的树突状细胞的免疫治疗效力测试，（ii）选择应答者患者，（iii）拒绝无反应者患者，和（iv）筛选树突细胞活化或成熟剂也可以诱导产生阈值量的细胞因子/趋化因子。

9. 发明申请

WO2017004230A1 OPTIMALLY ACTIVATED DENDRITIC CELLS THAT INDUCE AN IMPROVED OR INCREASED ANTI-TUMOR IMMUNE RESPONSE 审中-公开
标题翻译：诱发改善或增加的抗肿瘤免疫应答的最佳激活的细胞
公开(公告)号：WO2017004230A1
公开(公告)日：2017-01-05
申请号：PCT/US2016/040134
申请日：2016-06-29
申请人： NORTHWEST BIOTHERAPEUTICS, INC.
发明人： BOSCH, Marnix, L.
IPC分类号： C12N5/0784 , C12N5/24 , A61P35/00 , A61K39/00 , A61K35/14
CPC分类号： C12N5/064 , A61K35/15 , A61K39/0011 , A61K2039/5154 , A61P35/00 , C12N2501/22 , C12N2506/11
摘要： The present disclosure provides populations of cells comprising partially mature and optimally activated dendritic cells that can be used for administration to individuals having a cancer and/or tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 10 to about 19 hours, upon administration efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in a lymph node the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNFa, IL-6, IL-8, and/or IL-12) and contact T cells inducing a substantial and optimal clinical and/or anti -tumor immune response.
摘要翻译：本公开提供包含部分成熟和最佳活化的树突状细胞的细胞群，其可以用于向具有癌症和/或肿瘤的个体施用。部分成熟的树突状细胞，与树突状细胞成熟剂接触约10至约19小时，在施用时有效地占据并处理肿瘤部位的肿瘤抗原，完全成熟，并随后迁移到淋巴结被处理的个人。一旦在淋巴结中，现在完全成熟的抗原呈递树突状细胞分泌适当的细胞因子（例如TNFα，IL-6，IL-8和/或IL-12）并接触T细胞，诱导实质性和最佳临床和/或抗肿瘤免疫反应。

10. 发明授权

EP1604016B1 GENERATION OF DENDRITIC CELLS FROM MONOCYTIC DENDRITIC PRECURSOR CELLS WITH GM-CSF IN THE ABSENCE OF ADDITIONAL CYTOKINES 失效转让
标题翻译：从与前置GM-CSF单核细胞树突状细胞生产的树突状细胞，无需额外细胞因子的存在
公开(公告)号：EP1604016B1
公开(公告)日：2009-01-14
申请号：EP04715780.5
申请日：2004-02-27
申请人： NorthWest Biotherapeutics, Inc.
发明人： TJOA, Benjamin A. , BOSCH, Marnix, L.
IPC分类号： C12N5/00 , C12N5/02
CPC分类号： C12N5/0639 , C12N2500/10 , C12N2500/30 , C12N2500/72 , C12N2500/90 , C12N2501/22 , C12N2501/23 , C12N2501/24 , C12N2502/70 , C12N2533/12
摘要： The present invention it was determined that dendritic cells could be derived from various sources including peripheral blood monocytes in the presence of only GM-CSF without other cytokines if the monocytes were not activated. By preventing activation, such as by preventing binding of the cells to the surface of the culture vessel, the monocytes do not require the presence of additional cytokines, such as IL-4 or IL-13, to prevent differentiation into a non-dendritic cell lineage. The immature DCs generated and maintained in this manner were CD14- and expressed high levels of CD1a. Upon maturation by contact with an agent such as, for example, BCG and IFNϜ, the cells were determined to express surface molecules typical of mature dendritic cells purified by prior methods and cultured in the presence of GM-CSF and IL-4. The mature dendritic cells produced from monoxytes without activation and cultured in GM-CSF alone are suitable for use in dendritic cell-based immunotherapy methods, such as for use in the treatment of disease, including cancer.

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