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1. 发明授权

US11639717B2 Perestaltic pump and device for isolating cells from biological tissue 有权
公开(公告)号：US11639717B2
公开(公告)日：2023-05-02
申请号：US16833694
申请日：2020-03-30
申请人： Miltenyi Biotec B.V. & Co. KG
发明人： Frederik Fritzsch , Ralf-Peter Peters
IPC分类号： F04B43/14 , A01N1/02 , A61M60/279
摘要： The invention is directed to a peristaltic pump (10), comprising: a flexible membrane (1) forming a at least one bladder (2) against a support, wherein each bladder is provided with one input orifice (4) which admits a fluid to the bladder (2) and one outlet orifice (5) which releases the fluid from the bladder (2); and at least one roller bearing (6) is configured to rotate about an axis (7) and to apply a compressive force against the at least one bladder (2). The peristaltic pump may be in fluid communication with a tapered jet (11).

2. 发明申请

US20230101711A1 LABELED PROBES WITH DIFFERENTIALLY CLEAVABLE LINKERS AND THEIR USE IN DE-CODING DNA AND RNA MOLECULES 有权
公开(公告)号：US20230101711A1
公开(公告)日：2023-03-30
申请号：US17952980
申请日：2022-09-26
申请人： Miltenyi Biotec B.V. & Co. KG
发明人： Mong Sano , Michel Perbost , Robert Pinard , Xiao-Pei Guan , Sameh Soliman , Emily Neil
IPC分类号： C12Q1/6874 , C12N15/10
摘要： The invention is directed to a method for detecting RNA, DNA or protein target sequences by a) Hybridizing a library of probes having the general formula (I) P—(CL-D)x (I) With P: probes having at least 10 nucleotides or amino acids CL: cleavable linker D: fluorescent dye X: integer between 1 and 5 to RNA, DNA or protein target sequences wherein the library comprises probes P having different sequences of nucleotides or amino acids and cleavable linkers CL of different groups which are cleavable with different means b) Removing unhybridized probes and detecting the hybridized probes via the fluorophores D by a first image c) Cleaving sequentially by different means each group of chemical linkers CL from the hybridized probes; removing the thus cleaved fluorophores D and detecting the remaining hybridized probes via their fluorophores D by a second image d) Detecting the removed fluorophores D by comparing the first and second image. e) Obtaining a part of the sequence information of the target sequences via the sequence information of the probes P associated with the removed fluorophores D f) Repeating step c) until all groups of chemical linkers CL are cleaved.

3. 发明申请

US20230100000A1 Immune cell expressing adapter chimeric antigen receptor for sensing soluble antigens 有权
公开(公告)号：US20230100000A1
公开(公告)日：2023-03-30
申请号：US17797419
申请日：2021-02-03
申请人： Miltenyi Biotec B.V. & Co. KG
发明人： Niels Werchau , Bettina Kotter , Joerg Mittelstaet , Andrew Kaiser
IPC分类号： A61K35/17 , C12N5/0783
摘要： The present invention provides a composition comprising a) an immune cell comprising a polynucleotide encoding an adapter CAR specific for an adapter, b) the adapter specific for a soluble antigen, and c) the soluble antigen. In an embodiment of the invention, the immune cell expressing said adapter CAR comprises in addition a nucleic acid comprising an inducible promoter operably linked to a nucleic acid encoding an effector such as a synthetic.

4. 发明申请

US20220403462A1 METHOD OF SPATIAL SEQUENCING OF GENES FROM TISSUE USING PADLOCKS WITH GAPS ON SUBSTRATE 有权
公开(公告)号：US20220403462A1
公开(公告)日：2022-12-22
申请号：US17745977
申请日：2022-05-17
申请人： Miltenyi Biotec B.V. & Co. KG
发明人： Hansueli MEYER , Robert PINARD
IPC分类号： C12Q1/6869 , C12Q1/6806 , C12Q1/6853
摘要： The invention is directed to a method to obtain the spatial location and sequence information of a target sequence in a sample comprising at least one m-RNA strand comprising the steps a. providing a surface with a plurality of spacer units capable of binding at least one m-RNA strand and with at least one fiducial marker b. providing a sample comprising at least one m-RNA strand to the surface wherein at least one m-RNA strand of the sample binds to at least one spacer unit creating at least one single stranded oligomer c. taking a first image of the surface to obtain the spatial information of the sample relative to the fiducial marker d. removing sample form surface e. hybridizing at least one oligonucleotide comprising 50-1000 nucleic acids with its 5′ and 3′ ends to complementary parts of the single stranded oligomer thereby forming a padlock-shaped structure that is ligated to create a single strand circular template f. multiplying the single strand circular template by a polymerase capable of rolling circle amplification into a plurality of DNA concatemers thereby forming rolonies g. obtaining the sequence information of the rolonies h. linking the spatial information of the sample with the sequence information of the rolonies.

5. 发明授权

US11499977B2 Equipment and procedure for culturing, separating, and genetically modifying donor cells for reinfusion into a patient 有权
公开(公告)号：US11499977B2
公开(公告)日：2022-11-15
申请号：US17725388
申请日：2022-04-20
申请人： MILTENYI BIOTEC B.V. & CO. KG
发明人： Stefan Miltenyi , Winfried Schimmelpfennig , Holger Lantow , Niklas Elmar Neuschaefer , Martin Biehl , Eiad Kabaha , Juergen Schulz
IPC分类号： C12M3/00 , B01L3/00 , G01N33/58 , A61M1/36 , B03C1/28 , B04B5/04 , B04B13/00 , B03C1/032 , B03C1/00 , B03C1/027 , B03C1/033 , B03C1/034 , A61M1/02 , G01N35/00 , C12N5/00 , C12M1/26 , C12M1/00 , B01D21/26 , B04B5/00 , B04B5/10 , B04B1/12 , B04B7/08 , B01D15/38 , C12N5/0789 , C12N5/077 , C12N5/0783 , C12M1/36
摘要： The invention relates to a system, comprising: a) a sample processing unit, comprising an input port and an output port coupled to a rotating container having at least one sample chamber, the sample processing unit configured provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample; and b) a sample separation unit coupled to the output port of the sample processing unit, the cell separation unit comprising separation column holder (42), a pump (64) and a plurality of valves (1-11) configured to at least partially control fluid flow through a fluid circuitry and a separation column (40) positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.

6. 发明申请

US20220220504A1 Method for Generation of Genetically Modified T Cells 有权
公开(公告)号：US20220220504A1
公开(公告)日：2022-07-14
申请号：US17612410
申请日：2020-05-27
申请人： Miltenyi Biotec B.V. & Co. KG
发明人： Thomas Schaser , Andrew Kaiser , Mario Assenmacher
IPC分类号： C12N15/86 , C12N5/0783 , C12N15/62 , C07K14/725 , C07K14/705
摘要： The present invention provides a method for the generation of genetically modified T cells comprising the steps a) a sample provided comprising T cells, b) preparation of said sample by centrifugation, c) enrichment of the T cells, d) activation of the T cells using modulatory agents, e) genetic modification of the T cells by transduction with lentiviral vector particles, f) removal of said modulatory agents, thereby generating a sample of genetically modified T cells, wherein said method is performed in equal or less than 144 hours, less than 120 hours, less than 96 hours, less than 72 hours, less than 48 hours, or less than 24 hours. In one embodiment of the invention said enrichment of T cells is performed by magnetic cell separation using magnetic particles that are directly or indirectly coupled to antibodies or antigen binding fragments thereof specific for CD4 and/or CD8 wherein said magnetic particles can be removed from the cells after separation.

7. 发明申请

US20220133791A1 A Combination of compositions for elimination and enhanced engraftment of hematopoietic stem cells in the bone marrow of a subject 有权
公开(公告)号：US20220133791A1
公开(公告)日：2022-05-05
申请号：US17424749
申请日：2020-01-22
申请人： Miltenyi Biotec B.V. & Co. KG
发明人： Eleni Papanikolaou , Stefan Miltenyi , Andreas Bosio , Mario Assenmacher , Andrew Kaiser
IPC分类号： A61K35/17 , A61K35/28
摘要： The present invention provides a combination of compositions comprising i) a composition comprising I) a population of T cells, NK cells or cytotoxic immune effector cells comprising a chimeric antigen receptor specific for a stem cell antigen and/or, II) α) a population of T cells, NK cells or cytotoxic immune effector cells comprising a chimeric antigen receptor specific for a tag of a tagged polypeptide, wherein said tagged polypeptide binds specifically to a stem cell antigen, and β) said tagged polypeptide, and ii) a composition comprising a) a population of CD34+ hematopoietic stem cells, and b) one or more accessory or contributory cell populations selected from the group consisting of myeloid cell lineages expressing CD14, CD11b, CD11c, CD123, CD33; CD36; CD47, CD66b, CD235a, CD146 and CD326. A method applying these compositions to a subject in need thereof are also provided.

8. 发明申请

US20210372999A1 METHOD FOR DETECTION OF CELLS BY REPETITIVE STAINING AND DESTAINING 有权
公开(公告)号：US20210372999A1
公开(公告)日：2021-12-02
申请号：US17316685
申请日：2021-05-10
申请人： Miltenyi Biotec B.V. & Co. KG
发明人： Jonathan Fauerbach , Christian Dose , Dirk Meineke , Daniel Berndt
IPC分类号： G01N33/533 , G01N33/537 , G01N33/53 , G01N33/542
摘要： The invention is directed to a method for detecting a target moiety in a sample of biological specimens by providing a conjugate with the general formula (I) characterized in contacting the sample of biological specimens with at least one conjugate (I), thereby labeling the target moiety recognized by an antigen recognizing moiety with the conjugate (I); exciting the labelled target moieties with light having a wavelength within the absorbance spectrum of the fluorescent moiety FL; detecting the labelled target moieties by detecting the fluorescence radiation emitted by the fluorescent moiety FL and degrading the fluorescent moiety FL of the labelled target moieties by irradiating the conjugate with light having a wavelength within the absorbance spectrum of fluorescent moiety FL for a time sufficient to deliver enough energy to reduce the fluorescence radiation emitted by the fluorescent moiety FL at least by 75% of the initial fluorescence radiation.

9. 发明申请

US20210338814A1 COMBINATION OF IMMUNE EFFECTOR CELLS SPECIFIC FOR A TARGET ANTIGEN AND HEMATOPOIETIC CELLS THAT EXPRESS THE TARGET ANTIGEN IN AN ALTERED FORM 有权
公开(公告)号：US20210338814A1
公开(公告)日：2021-11-04
申请号：US17318914
申请日：2021-05-12
申请人： Miltenyi Biotec B.V. & Co. Kg
发明人： Michael Lutteropp , Anne Richter , Andrew Kaiser , Mario Assenmacher , Stefan Miltenyi
IPC分类号： A61K39/395 , A61K38/17 , A61K39/00 , A61K35/12
摘要： The invention provides a system that comprises pharmaceutical agents for use in immunotherapy for reducing the side-effects of an antigen-recognizing receptor against antigen-expressing non-target cells in an individual. The system includes an antigen-recognizing receptor that specifically recognizes an antigen on target cells and at least on one hematopoietic cell type in the individual. The antigen-recognizing receptor is exemplified by chimeric antigen receptors (CAR) be expressed on the surface of an immune effector cells. The system also includes hematopoietic cells resistant to recognition of the same antigen by the antigen-recognizing receptor.

10. 发明申请

US20210181489A1 MICROSCOPE DEVICE WITH VIRTUAL OBJECTIVE 有权
公开(公告)号：US20210181489A1
公开(公告)日：2021-06-17
申请号：US17267886
申请日：2019-08-12
申请人： Miltenyi Biotec B.V. & CO. KG
发明人： Rainer UHL
IPC分类号： G02B21/00 , G02B21/36
摘要： There is provided a microscope device comprising: a microscope objective (18), a sample stage (12) for holding a sample (16) and moving the sample in a plane perpendicular to the optical axis of the microscope objective, a light source (20) and an illumination pattern generator unit (22) for illuminating the sample with a line-type illumination pattern, an area-detector detector (40, 44) for detecting light from the sample collected by the microscope objective, a scanning unit (24) for moving the illumination pattern in a scanning direction across the field of view, wherein the scanning direction is perpendicular to the longitudinal axis of the illumination pattern, and a control unit (42) configured to selectively operate the microscope arrangement in a normal magnification mode or in a lower magnification mode, wherein in the lower magnification mode the sample is moved in a direction antiparallel to the scanning direction while the illumination pattern is moved across the field of view by the scanning unit so as to obtain an at least unidirectionally compressed image, whereby the compression-factor is given by the ratio of the stage- and scan-speed.

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