公开(公告)号：EP3344759A1

公开(公告)日：2018-07-11

申请号：EP16758177.6

申请日：2016-08-31

申请人： Miltenyi Biotec GmbH

发明人： GRANZIN, Markus ,  HUPPERT, Volker

IPC分类号： C12N5/0783

摘要： The present invention provides a method for in-vitro culturing and expanding natural killer (NK) cells in a cell culture medium comprising a population of NK cells, the method comprising a) adding an effective concentration of interleukin-21 (IL-21) at the beginning of the culturing process to said medium, b) adding repeatedly an effective concentration of interleukin-2 (IL-2) and/or interleukin-15 (IL-15) to said medium, and c) adding repeatedly feeder cells or membrane particles thereof to said medium, wherein said feeder cells are B cell derived which are EBV immortalized; and wherein said expansion of NK cells in said cell culture medium is maintained for at least 3 weeks.

公开(公告)号：EP3315511A1

公开(公告)日：2018-05-02

申请号：EP16196487.9

申请日：2016-10-29

申请人： Miltenyi Biotec GmbH

发明人： KAISER, Andrew ,  MITTELSTAET, Joerg ,  HUPPERT, Volker ,  MILTENYI, Stefan ,  SCHLEGEL, Patrick ,  SEITZ, Christian ,  LANG, Peter ,  HANDGRETINGER, Rupert

IPC分类号： C07K14/725 ,  A61K31/4188 ,  C07K16/28

CPC分类号： C07K14/7051 ,  A61K31/4188 ,  C07K14/70503 ,  C07K14/70517 ,  C07K14/70578 ,  C07K16/18 ,  C07K16/2896 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C07K2319/33

摘要： The present invention provides an extracellular anti-linker/label epitope chimeric antigen receptor (anti-LLE CAR) comprising I) a linker/label epitope (LLE) binding domain, II) a transmembrane domain, and III) a signal transduction domain, wherein said extracellular LLE binding domain binds a target cell binding molecule (TCBM) comprising i) an antigen binding moiety (ABM), wherein said ABM binds specifically to an antigen expressed on a target cell, ii) a label moiety (LaM), wherein said LaM is a naturally occurring molecule in a subject or a derivative thereof, iii) a linker moiety (LiM) conjugating said ABM and said LaM, thereby forming a linker/label epitope (LLE), wherein said extracellular LLE binding domain binds said LLE with a higher preference than said naturally occurring molecule.

摘要翻译： 本发明提供了包含I）接头/标记表位（LLE）结合结构域，II）跨膜结构域和III）信号转导结构域的细胞外抗接头/标记表位嵌合抗原受体（抗LLE CAR），其中 所述细胞外LLE结合结构域结合包含i）抗原结合部分（ABM），其中所述ABM特异性结合靶细胞上表达的抗原的靶细胞结合分子（TCBM），ii）标记部分（LaM），其中所述 LaM是受试者或其衍生物中天然存在的分子，iii）缀合所述ABM和所述LaM的接头部分（LiM），由此形成接头/标记表位（LLE），其中所述胞外LLE结合结构域将所述LLE与 比所述天然存在的分子更优选。

公开(公告)号：EP3138905A1

公开(公告)日：2017-03-08

申请号：EP15183968.5

申请日：2015-09-04

申请人： Miltenyi Biotec GmbH

发明人： GRANZIN, Markus ,  HUPPERT, Volker

IPC分类号： C12N5/0783

CPC分类号： C12N5/0646 ,  C12N2501/2302 ,  C12N2501/2315 ,  C12N2501/2321

摘要： The present invention provides a method for in-vitro culturing and expanding natural killer (NK) cells in a cell culture medium comprising a population of NK cells, the method comprising a) adding an effective concentration of interleukin-21 (IL-21) at the beginning of the culturing process to said medium, b) adding repeatedly an effective concentration of interleukin-2 (IL-2) and/or interleukin-15 (IL-15) to said medium, and c) adding repeatedly feeder cells or membrane particles thereof to said medium, wherein said feeder cells are B cell derived which are EBV immortalized; and wherein said expansion of NK cells in said cell culture medium is maintained for at least 3 weeks.

摘要翻译： 本发明提供了在包含NK细胞群的细胞培养基中体外培养和扩增天然杀伤（NK）细胞的方法，所述方法包括：a）将有效浓度的白细胞介素-21（IL-21）加入到 培养过程开始于所述培养基，b）向所述培养基反复加入白细胞介素-2（IL-2）和/或白细胞介素-15（IL-15）的有效浓度，c）重复加入饲养细胞或膜 其中所述饲养细胞是B细胞衍生的，其是EBV永生化的; 并且其中所述细胞培养基中NK细胞的所述扩增保持至少3周。

公开(公告)号：EP2686417B1

公开(公告)日：2016-06-08

申请号：EP12712611.8

申请日：2012-03-19

申请人： Miltenyi Biotec GmbH

发明人： HANDGRETINGER, Rupert ,  HUPPERT, Volker

IPC分类号： C12N5/00 ,  C12N5/078

CPC分类号： C12N5/0634 ,  C12N5/0087

公开(公告)号：EP3342855A1

公开(公告)日：2018-07-04

申请号：EP17208723.1

申请日：2017-12-20

申请人： Miltenyi Biotec GmbH

发明人： HUPPERT, Volker ,  MILTENYI, Stefan ,  DZIONEK, Julia ,  LEUNG, Wing

IPC分类号： C12N5/00

摘要： The invention is directed to a method for the preparation of a cell population from a sample originating from bone marrow or blood, comprising the steps a) dividing the sample into a first fraction containing 50 to 99 % of the cells of the sample and a second fraction containing 50 to 1 % of the cells of the sample, b) labeling the cells of the first fraction with a first marker against TCR alpha/beta, c) labeling the cells of the second fraction with a second marker against CD45RA, d) removing the labeled cells from the first and second fraction and combining the remaining cells to a cell population.
Furthermore, the invention is directed to a cell composition and the use of the cell composition

公开(公告)号：EP2686417A1

公开(公告)日：2014-01-22

申请号：EP12712611.8

申请日：2012-03-19

申请人： Miltenyi Biotec GmbH

发明人： HANDGRETINGER, Rupert ,  HUPPERT, Volker

IPC分类号： C12N5/00

CPC分类号： C12N5/0634 ,  C12N5/0087

摘要： The invention relates to a composition, comprising a cell population that can be obtained from bone marrow or from blood, wherein the cell population is depleted of cells that express TCR alpha/beta and cells that express CD19. Such a pharmaceutical composition makes the reconstitution of the immune defense of a person as part of a bone marrow transplant possible. By means of the invention, the time until the immune reconstitution is considerably shortened and the immune responses after treatment are considerably reduced, in particular the occurrence of GVHD. The survival rate of the patients is considerably increased.

公开(公告)号：EP3037171B1

公开(公告)日：2018-10-10

申请号：EP15199104.9

申请日：2015-12-10

申请人： Miltenyi Biotec GmbH

发明人： KAULING, M. Burgund ,  HUPPERT, Volker ,  DOSE, Christian ,  STEINBRÜCK, Philipp

IPC分类号： G01N1/40 ,  C12N13/00 ,  B03C1/28 ,  G01N33/543 ,  B03C1/01 ,  C12N5/00

CPC分类号： C12N13/00 ,  B03C1/01 ,  B03C1/288 ,  B03C2201/26 ,  C12N5/0087 ,  G01N1/40 ,  G01N33/54333 ,  G01N2001/4038

摘要： The invention is directed to a method for enriching target cells from a sample of cells characterized by: a) contacting the sample with a cell aggregation agent and first magnetic particles having an iron content of 0.1 pg to 5000 pg, coupled to a first antigen recognizing moiety; and second magnetic particles having an iron content of 0.05 fg to 100 fg and coupled to a second antigen recognizing moiety to obtain mixture a) b) applying a first magnetic field gradient to the mixture a) thereby removing the cells bound to the first antigen recognizing moiety coupled to the first magnetic particles, to obtain a mixture b) and obtaining an agglomerate comprising the cells of mixture a) bound to the cell aggregation agent c) applying a second magnetic field gradient to the mixture b) thereby immobilizing the cells bound to the second antigen recognizing moiety coupled to the second magnetic particles d) recovering the immobilized cells from the second magnetic field gradient as target cells.

公开(公告)号：EP3037171A1

公开(公告)日：2016-06-29

申请号：EP15199104.9

申请日：2015-12-10

申请人： Miltenyi Biotec GmbH

发明人： KAULING, M. Burgund ,  HUPPERT, Volker ,  DOSE, Christian ,  STEINBRÜCK, Philipp

IPC分类号： B03C1/00 ,  C12N5/00 ,  G01N33/543 ,  B03C1/01 ,  B03C1/28

CPC分类号： C12N13/00 ,  B03C1/01 ,  B03C1/288 ,  B03C2201/26 ,  C12N5/0087 ,  G01N1/40 ,  G01N33/54333 ,  G01N2001/4038

摘要： The invention is directed to a method for enriching target cells from a sample of cells characterized by:
a) contacting the sample with a cell aggregation agent and first magnetic particles having an iron content of 0.1 pg to 5000 pg, coupled to a first antigen recognizing moiety; and second magnetic particles having an iron content of 0.05 fg to 100 fg and coupled to a second antigen recognizing moiety to obtain mixture a)
b) applying a first magnetic field gradient to the mixture a) thereby removing the cells bound to the first antigen recognizing moiety coupled to the first magnetic particles, to obtain a mixture b) and obtaining an agglomerate comprising the cells of mixture a) bound to the cell aggregation agent
c) applying a second magnetic field gradient to the mixture b) thereby immobilizing the cells bound to the second antigen recognizing moiety coupled to the second magnetic particles
d) recovering the immobilized cells from the second magnetic field gradient as target cells.

摘要翻译： 本发明涉及用于从细胞样品中富集靶细胞的方法，其特征在于：a）使样品与细胞聚集剂和铁含量为0.1pg至5000pg的第一磁性颗粒接触，第一磁性颗粒与第一抗原识别 部分; 和铁含量为0.05fg至100fg并与第二抗原识别部分偶联以获得混合物的第二磁性颗粒a）b）向混合物施加第一磁场梯度a）从而除去结合到第一抗原识别的细胞 部分偶联至第一磁性颗粒，以获得混合物b）并获得包含与细胞聚集剂结合的混合物a）的细胞的附聚物c）向混合物施加第二磁场梯度b）从而将结合到 耦合到第二磁性颗粒的第二抗原识别部分d）从作为靶细胞的第二磁场梯度回收固定化细胞。