The present invention provides a pseudotyped retroviral vector particle for activating and transducing T cells in-vitro or in-vivo, wherein said retroviral vector particle comprises an envelope protein with antigen-binding activity, wherein said envelope protein is recombinant protein and is fused at its ectodomain to a polypeptide that specifically binds to a target antigen expressed on the surface of a target cell, and wherein said envelope protein is protein G of the Nipah virus (NiV-G), and wherein said polypeptide that specifically binds to a target antigen expressed on the surface of a target cell comprises an antigen binding domain specific for the antigen CD3, wherein said antigen binding domain specific for the antigen CD3 comprises a humanized and optimized scFv sequence as disclosed herein, wherein said retroviral vector particle comprises at least one nucleic acid sequence encoding a transgene, and wherein said retroviral vector particle is a lentiviral or gammaretroviral vector particle.
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The invention is directed to a flow cell (100) for examination of a tissue sample wherein the flow cell (100) is provided with at least 2 fixing points (56) capable of fixing the flow cell in a consistent position in a support structure.
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)
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)
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)
Wherein the fluorescent moiety FL of the labelled target moieties is degraded 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.
G01N 33/542 - ImmunoassayBiospecific binding assayMaterials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
4.
IMMUNE CELL EXPRESSING CHIMERIC ANTIGEN RECEPTOR AND TRANSGENIC T CELL RECEPTOR
The present invention provides T cells that express both a CAR and a tTCR (CARTCR T cells) and compositions comprising said CARTCR T cells together with T cells that express only said CAR ("CAR T cells") and/or with T cells that express only said tTCR ("tTCR T cells") for treatment of a disease. Methods for generation of these compositions are also provided.
The present invention provides an in-vitro method for the generation of a population of genetically modified natural killer (NK) cells comprising the steps in the following order: a) obtaining a sample comprising NK cells and other cells, b) enrichment of NK cells from said sample, c) introducing a genetic modifier 1 into said NK cells by electroporation, d) introducing a genetic modifier 2 into said NK cells by transduction, e) expanding said genetically modified NK cells, thereby generating a population of genetically modified NK cells.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
17 - Rubber and plastic; packing and insulating materials
Goods & Services
Scientific, optical and measuring apparatus and instruments, especially for and in connection with the separation, analysis, processing and cultivation of biological material; apparatus for recording, transmission or reproduction of images, data processing equipment, computer software, especially for or in connection with the separation, analysis, processing and cultivation of biological material, scientific, electrical and electronic apparatus and instruments for conducting enzymatic reactions; laboratory equipment, in particular cytometer for measuring physical and/or chemical properties of cells and other particles in suspensions. Apparatus for magnetic cell separation for medical purposes; tubing sets for medical purposes; columns for analysis for medical purposes; sacks, bags, sheets, tubes and connectors for medical, scientific or biotechnological purposes, especially for cell separation; dialysis machines for medical use; apheresis machines for medical use. Sacks, bags, sheets, tubes and joints of rubber, gutta-percha, rubber, plastics, included in this class, for medical, scientific or biotechnological purposes, especially for cell separation; films for the manufacture of the aforesaid goods; hoses, hose assemblies and fittings, especially for medical, scientific or biotechnological purposes, all especially for cell separation.
7.
Chemically Inducible Heterodimerizing System and A Method For Generation Thereof
The present invention provides a method of creating a chemically-induced heterodimerizing system having three different components that form a ternary complex by amendment of a chemically induced homodimerizing system, wherein said chemically induced homodimerizing system comprises two components for the homodimerization, wherein the antigen binding domain comprising SEQ ID NO:1 (AB0) is the first component and a small molecule such as caffeine is the second component of the homodimerization, and wherein said AB0 and said small molecule form a complex of AB0/AB0/small molecule. Heterodimerizing systems obtained by said method are also disclosed herein.
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07K 16/44 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere
8.
METHOD AND APPARATUS FOR HIGH RESOLUTION MICROSCOPY
The invention concerns a microscopy method and a microscopy apparatus (100), with an illumination modulator (17) which is configured so as to produce a plurality of points of illumination (8, 11) during a scan of a light strip (3) of the illuminating light (27a) with an illumination modulator (17a), the points being in the form of an asymmetrical 2D Bravais lattice (G4, G5, G6) with a first, longer primitive vector (a) and a second, shorter primitive vector (b) and wherein the projection of the first primitive vector (a) onto the axial direction (3a) of the light strip (3) is longer than the projection of the second primitive vector (b) onto the axial direction (3a) of the light strip (3). In combination with a ROI of a detector synchronised to the illumination line, a more rapid confocal acquisition method is obtained with a better signal-to-noise ratio.
The invention relates to a method for controlling the quality of T cells during and/or after cultivating said T cells and/or for controlling and optimizing the cultivation of T cells. The method has the steps of: a) isolating at least one nucleic acid molecule of at least one T cell during and/or after the cultivation; b) determining the methylation degree of at least one CpG dinucleotide of the nucleic acid molecule, wherein the CpG dinucleotide is selected from the group consisting of the CpG dinucleotides cg08364283, cg03898320, cg20606093, cg21108925, cg07279377, cg14117392, cg04455867, cg13298528, cg06175418, cg04867484, cg18387515, cg12067423, cg09801824, cg13789303, and at least one CpG dinucleotide which is located within the region of 500 nucleotides upstream and/or downstream of each of the aforementioned CpG dinucleotides; and c) comparing the methylation degree determined in step b) with at least one reference value which corresponds to the methylation degree of the CpG dinucleotide of uncultivated primary T cells. The result of the comparison directly indicates whether the cultivated T cells are suitable for therapeutic purposes or if the cultivation conditions should be modified.
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
10.
PSEUDOTYPED RETROVIRAL VECTOR PARTICLE WITH ANTI-CD3 DISPLAY
The present invention provides a pseudotyped retroviral vector particle for activating and transducing T cells, wherein said retroviral vector particle comprises a modulating protein comprising a functional ectodomain comprising an antigen binding domain specific for the antigen CD3, wherein said antigen binding domain specific for the antigen CD3 comprises a humanized and optimized scFV sequence,wherein said retroviral vector particle comprises at least one nucleic acid sequence encoding a transgene, and wherein said retroviral vector particle is a lentiviral or gammaretroviral vector particle. A pharmaceutical composition thereof is also disclosed.
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present invention provides a pseudotyped retroviral vector particle, wherein said retroviral vector particle comprises a) an envelope protein with antigen-binding activity, wherein said envelope protein is a recombinant protein that does not interact with at least one of its native receptors and is fused at its ectodomain to a polypeptide that specifically binds to a target antigen expressed on the surface of a target cell, and wherein said envelope protein is protein H of a virus of the Paramyxoviridae family, b) an envelope protein with fusion activity of a virus of the Paramyxoviridae family, and wherein said Paramyxoviridae virus is a virus of the morbillivirus genus, and wherein said virus of the morbillivirus genus is a canine distemper virus (CDV), and wherein said retroviral vector particle comprises at least one nucleic acid sequence encoding a transgene, and wherein said retroviral vector particle is a lentiviral or gammaretroviral vector particle.
This disclosure provides a system for preventing or reducing side effects in a patent undergoing immunotherapy to remove diseased cells that express a target antigen: for example, by CAR T cell therapy. Side effects can ensue from concurrent depletion of hematopoietic cells bearing the same target antigen. A population of engineered hematopoietic cells is prepared by obtaining healthy hematopoietic cells from the patient or a third party donor, and using them to produce engineered hematopoietic cells. The engineered cells either do not express the target antigen, express it at a lower density, or express it in a modified form. The engineered hematopoietic cells are formulated for administration to the patient, whereupon they reconstitute hematopoietic cell function, thereby preventing or reducing the side effects.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
13.
Reducing side effects of immunotherapy using genetically modified hematopoietic cells
This disclosure provides a system for preventing or reducing side effects in a patent undergoing immunotherapy to remove diseased cells that express a target antigen: for example, by CAR T cell therapy. Side effects can ensue from concurrent depletion of hematopoietic cells bearing the same target antigen. A population of engineered hematopoietic cells is prepared by obtaining healthy hematopoietic cells from the patient or a third party donor, and using them to produce engineered hematopoietic cells. The engineered cells either do not express the target antigen, express it at a lower density, or express it in a modified form. The engineered hematopoietic cells are formulated for administration to the patient, whereupon they reconstitute hematopoietic cell function, thereby preventing or reducing the side effects.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
14.
UNIT-DNA COMPOSITION FOR SPATIAL BARCODING AND SEQUENCING
The invention is directed to a method to provide a polynucleotide molecule comprising a first and a second strand with a barcode nucleotide sequence characterized in that the first strand is provided at its 5′ end with an overhang of at least one universal base and the corresponding recessed 3′ end of the second strand of the polynucleotide with at least one nucleotide provided with a blocking group, wherein the blocking groups are removed from the incorporated nucleotides by irradiation with light.
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.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
16.
METHOD AND KIT FOR CHARACTERIZING DOPAMINERGIC PROGENITOR CELLS OBTAINED BY DIFFERENTIATING PLURIPOTENT STEM CELLS
The present invention provides an in-vitro method for analyzing a cell composition comprising human floorplate mesDA progenitor cells, the method comprising a) contacting the cells of said cell composition or the cells of a sample thereof with antigen binding molecules specific for the antigens FOXA2, OTX2, PAX6, and NKX6.1, thereby labeling the cells of said cell composition or of said sample, b) determining the percentage of said cells that are labelled with said antigen binding molecules for each of said antigens, and wherein the cells of said cell composition qualify as human floorplate mesDA progenitor cells if the protein expression profile of said cells is: 80-100% of said cells are positive for FOXA2, 80-100% of said cells are positive for OTX2, less than 10% of said cells are positive for PAX6, and less than 10% of said cells are positive for NKX6.1. A kit comprising said antigen binding molecules for use in said method is also provided.
01 - Chemical and biological materials for industrial, scientific and agricultural use
02 - Paints, varnishes, lacquers
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical, biological and biochemical products for
industrial, scientific purposes, namely products for use in
separation processes for biological materials; reagents for
cell separation; reagents for DNA, RNA, and/or
polynucleotide detection; reagents for amplification,
sequencing and detection of genetic material; reagents for
Polymerase Chain Reaction (PCR); in situ polynucleotide
detection reagents; in situ hybridization (ISH) reagents;
fluorescence in situ hybridization (FISH) reagents;
polynucleotide hybridization reagents; spatial multi-omics
reagents; spatial transcriptomics reagents; polynucleotide
detection probes; labeling reagents; media for cell culture
for research laboratories; substances and ingredients for
the preparation of media; reagents for the processing,
separation, isolation, enrichment, depletion, detection,
screening, analysis and counting of chemical and biological
material; reagents with magnetic beads; tissue staining
reagents; antibody reagents (other than for medical or
veterinary purposes); buffer solutions and reagents for use
with laboratory instruments, especially imaging instruments,
reagents for processing of biological material, especially
tissue, bone marrow, cells, blood and its components (other
than for medical or veterinary purposes); culture media,
cell culture media, freezing media, contrast agents,
contrast agents for in-vivo imaging, all for scientific
purposes; reagents for use in biotechnology, and in the
biotechnology industry; enzymes (other than for medical or
veterinary use); polynucleotides, polynucleotide, DNA, and
RNA primers and probes, fluorescence primers and probes,
fluorophores, chemical additives for dyeing, all for
scientific purposes; all the above for industrial or
scientific purposes. Primers and dyes used in pharmaceutical or scientific
industries. Nucleotides, polynucleotides, polynucleotides, namely as
primers or probes for dna and rna, fluorescence primers and
probes (complexes of molecules) all for medical purposes. Apparatus for imaging, namely spatial biology imaging;
instruments for polynucleotide sequencing; instruments for
amplification and detection of genetic material; instruments
for tissue visualization, in situ hybridization (ISH)
instruments, fluorescence in situ hybridization (FISH)
instruments; Polymerase Chain Reaction (PCR) instruments;
apparatus for spatial multi-omics and spatial
transcriptomics; apparatus for histology, all for scientific
purposes; histopathology slides and chambers; all the
aforesaid being for laboratory use. Apparatus for imaging; instruments for spatial biology;
instruments for polynucleotide sequencing; instruments for
amplification and detection of genetic material; instruments
for tissue visualization, in situ hybridization (ISH)
instruments, fluorescence in situ hybridization (FISH)
instruments; Polymerase Chain Reaction (PCR) instruments;
apparatus for spatial multi-omics and spatial
transcriptomics; apparatus for histology, all for medical
and diagnostic purposes; histopathology slides and chambers;
columns for analysis for medical purposes; all the
aforementioned for medical purposes; apparatus and
instruments for medical purposes. Scientific and technological services, research and design
services; services for design of polynucleotide probes and
genetic panels; all of the aforementioned services for and
in connection with detection, localization and analysis of
proteins and genetic material for biological and medical
research, medical diagnostics and therapy.
The invention is directed to a much faster way of combining multiple colour channels in fluorescence microscopy for complex fast diagnostic and research purposes. The advantage is that the procedure and the microscope setting can be simplified and miniaturised to an extend that the construction of such automatic systems become much easier and by omitting the erasing step the speed of analysis is faster and moved to the processing of the images by image processing systems, nowadays working at almost real time.
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, a pump and a plurality of valves configured to at least partially control fluid flow through a fluid circuitry and a separation column positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.
A61M 1/36 - Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
B01D 21/26 - Separation of sediment aided by centrifugal force
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B04B 1/12 - Centrifuges with rotary bowls provided with solid jackets for separating predominantly liquid mixtures with or without solid particles with discharging outlets in the plane of the maximum diameter of the bowl with continuous discharge
A cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135-45° to the rotational axis of the centrifugation chamber, wherein the centrifugation chamber comprises at least one input/output port and the cells to be modified are immobilized at the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g. In an embodiment, the device is used as a point-of-care and/or portable device. Further, the present disclosure describes software that, when executed by a processor, causes the device to perform the disclosed functions.
Method for determination of the kinetic binding parameters for a molecule binder conjugated to a fluorophore. Repeated staining of the antigen and detection of the emission radiation generates a titration series. Fitting of the emission radiation over the titration series allows for determination of kinetic binding parameters. The emission radiation is detected with a camera and single pixel fitting using a global analysis permits discrimination of the specific binding signal from non-specific background in each pixel.
G01N 33/557 - ImmunoassayBiospecific binding assayMaterials therefor using kinetic measurement, i.e. time rate of progress of an antigen-antibody interaction
22.
ARTIFICIAL TARGET FOR ANTIGEN-SPECIFIC ACTIVATION AND EXPANSION OF CAR T CELLS
The invention is directed to a method for activating CAR cells having at least one chimeric antigen binding receptor in a sample by incubating the sample with at least one substrate provided on its surface with at least one anti-CAR idiotype antibody and/or at least one antigen selected from the group consisting of CD19, CD20, CD22, BCMA, CD33, MSLN, CD123, HER2, GD2, EGFR, PSMA, MUC1, CD318, TSPAN8, CD66c, CEA, CLA, CD276, FolR1, CLEC12A, CLL-1 and CD371, and with at least one costimulatory molecule selected from the group consisting of CD28, CD2, CD6, CD26, CD53 and LFA-1 characterized in that the sample is incubated with the at least substrate in suspension thereby activating the CAR T cells to express markers selected from the group consisting of mRNA, effector molecules or cell surface activation markers.
The invention is directed to a method for determining the spatial localisation and a sequence of interest of at least a part of at least one RNA strand comprising the steps a. providing a plurality of oligonucleotides comprising a unit complementary to the sequence of interest and at least one unit comprising 5 to 30 nucleotides as detection sequences. b. hybridizing the oligonucleotides to the at least one RNA strand via the sequence of interest and removing unhybridized oligonucleotides characterized in c. providing a plurality of detection probes comprising a first fluorescence dye and a first detection oligonucleotide which is at least in part complementary to at least one detection sequence in the oligonucleotides and hybridizing the detection probes to the at least one detection sequences of the oligonucleotide d. removing unhybridized detection probes e. detecting the detection probes thereby determining the sequence of interest and the spatial localisation of the RNA strands on the surface.
The present invention provides an in-vitro method for transferring one or more nucleic acids sequences comprising one or more transgenes into γδ T cells with a pseudotyped retroviral vector particle or a virus-like particle thereof, wherein said pseudotyped retroviral vector particle or virus-like particle thereof comprises a modified baboon endogenous retrovirus (BaEV) envelope glycoprotein, the method comprising the steps a) activation of γδ T cells, b) contacting said pseudotyped retroviral vector particle or virus-like particle thereof with said activated γδ T cells using a low concentration of said pseudotyped retroviral vector particle, c) expanding said genetically modified γδ T cells in the absence of an aminobisphosphonate and in the presence of IL-2 and IL-15, wherein said expansion is in the absence of feeder cells and in the absence of human serum, and wherein at least 75% of the transduced and expanded γδ T cells are CD45RA-γδ T cells.
The present invention provides a chimeric antigen receptor (CAR) comprising: an antigen binding domain specific for folate receptor 1 (FolR1), a spacer, a transmembrane domain and an intracellular signaling domain. Moreover it was found that an antigen binding domain that comprises from the N- to the C-terminus the heavy chain variable region of an antibody (VH) comprising the amino acid sequence Seq ID No:2 a light chain variable region of an antibody (VL) comprising the amino acid sequence Seq ID No:4 shows superior killing properties compared to other variants.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
The invention is directed to a method to obtain the spatial location and sequence information of a target sequence of at least one m-RNA strand on a tissue sample comprising the steps
a. providing a linear probe, containing a) a binding region capable of binding to the at least one m-RNA strand and b) an anchor sequence comprising a UMI region located between a first and a second locator regions and c) a primer region;
b. hybridizing the linear probe with its binding region to the m-RNA strand;
c. complementing the linear probe using the m-RNA strand as template thereby obtaining a reversed transcribed c-DNA strand
d. hybridizing a locator molecule with its 3′ and 5′ ends to the first and second locator regions thereby creating a gap corresponding to the length of the UMI of the linear probe
e. Filling the gap in the locator molecule with nucleotides complementary to the UMI using a non-strand displacement enzyme thereby creating a circular template comprising a copy of the UMI region from the linear probe.
f. multiplying the circular template molecule by RCA on the tissue sample, starting from a primer region thereby creating a rolony
g. Sequencing at least the UMI portion of the rolonies thereby obtaining the spatial location of the m-RNA on the tissue
h. removing the reversed transcribed c-DNA strand from the tissue and dehybridizing the m-RNA strand thereby obtaining a single stranded c-DNA oligomer
i. providing the single stranded cDNA oligomer with a first and a second adaptor primer at the 3′ and 5′ ends obtaining a primed single stranded oligomer; amplification of the primed single stranded oligomer by PCR
j. Sequencing the amplified primed single stranded oligomer and linking the spatial information of the rolonies with the sequence information of the amplified primed single stranded oligomer via the UMI sequence
The present invention provides a chimeric antigen receptor (CAR) comprising: an antigen binding domain specific for folate receptor 1 (Fo1R1), a spacer, a transmembrane domain and an intracellular signaling domain. Moreover it was found that an antigen binding domain that comprises from the N- to the C-terminus the heavy chain variable region of an antibody (VH) comprising the amino acid sequence Seq ID No:2 a light chain variable region of an antibody (VL) comprising the amino acid sequence Seq ID No:4 shows superior killing properties compared to other variants.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The invention is directed to a method for detecting a target moiety in a sample of biological specimens by the steps
a) providing at least one conjugate with the general formula (I) Xn— P—Ym, with X is a detection moiety, P an acidic or basic degradable spacer and Y an antigen or oligonucleotide recognizing moiety and n, m are integers between 1 and 100 and wherein X and Y are covalently bound to P,
b) binding the conjugate to the target moiety target via the antigen or oligonucleotide recognizing moiety Y, thereby labelling the target moiety,
c) detecting the target moiety labelled with the conjugate by detecting the detecting moiety X,
d) providing at least one precursor which is capable of releasing an acid or base when provided with radiation wherein the acid or base is capable of cleaving P,
e) activating the precursor by providing radiation, thereby releasing the acid or base capable of cleaving P, and
f) degrading spacer P with the released acid or base, thereby cleaving the detection moiety X from the conjugated detection moiety.
The invention is directed to a method for obtaining a nucleic acid library of a sample comprising polynucleotides comprising the steps a. multiplying the polynucleotides by a polymerase b. fragmenting the multiplied polynucleotides by creating nicks c. coupling an oligonucleotide sequence to the nicks to create the target library wherein step a) is performed by providing A, T, G, C and U nucleotides wherein the molar ratio of T and U is between 200:1 and 5:1 and step b) is performed by excision of the U nucleotides. characterized in that after step b), the nicks are provided with a polymerase exhibiting 5′ #3′ exonuclease activity, thereby filling in the 3′ recessing ends and removing the 5′ overhangs of the nicks.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical, biological and biochemical preparations for
industrial, scientific and diagnostic purposes, including
medical diagnostics and in-vitro diagnostics; reagents for
cell separation, labelling reagents; reagents, media,
substances and components for preparing media, all being for
industrial and scientific purposes, included in this class;
reagents for the processing, separation, isolation,
enrichment, depletion, detection, screening, cultivation,
analysis and counting of material, in particular of
chemicals and biological material; reagents featuring
magnetic beads; antibody reagents (other than for medical or
veterinary purposes); buffer solutions and reagents for use
with laboratory apparatus, in particular separation
apparatus, analysis apparatus, reactors and imaging
apparatus; reagents for processing biological material, in
particular tissues, bone marrow, cells, blood and components
thereof (other than for medical or veterinary purposes);
diagnostic reagents and preparations for scientific
purposes; culture media, cell culture media, freezing media,
all being for scientific purposes, reagents for use in
biotechnology, biological processing operations and the
biotechnological industry; pharmaceutical, medical and
veterinary preparations for use in science and in-vitro
diagnostics (ivd). Pharmaceutical products and medicinal products;
pharmaceutical and other preprations for medical purposes;
reagents, media, substances and components for the
preparation of media, all being for medical or veterinary
purposes; reagents for treating, separating, isolating,
enriching, depleting, detecting, screening, cultivating,
analysing and counting materials, in particular biological
materials; reagents featuring magnetic beads, antibody
reagents, all being for medical or veterinary purposes;
buffer solutions and reagents for use with medical
apparatus, in particular separation apparatus, analysing
apparatus, reactors and imaging apparatus; reagents for
processing biological material, in particular tissues, bone
marrow, cells, blood and components thereof, all being for
medical or veterinary purposes; diagnostic preparations and
reagents for medical and veterinary use; culture media, cell
culture media, freezing media, all being for medical and
veterinary purposes; pharmaceutical preparations, in
particular pharmaceutical preparations for cellular therapy;
chemical, biological and biochemical preparations used for
therapeutic purposes, including medical diagnostics and
in-vitro diagnostics (ivd); reagents, media, substances and
components for the preparation of media for use in medical
laboratories; diagnostic reagents and preparations for use
in medical laboratories. Scientific and technological services and research and
design relating thereto; industrial analysis and research
services; design and development of computer hardware and
software for analysis; all of the aforesaid services for and
in connection with the analysis of biological and
biochemical material, in particular of cell material for
biological and medical research and therapy.
The invention provides a method which allows the separation of different workflow steps for barcoding of target nucleic acids and therefore providing optimal reaction conditions for each workflow step, especially for template switching reactions. Moreover this method provides the opportunity to perform the reactions such as barcoding reactions of two different nucleic acid molecules from one cell such as RNA and genomic DNA molecules in a single step. The method comprises the steps: (a) Providing a plurality of cells comprising target RNA molecules and at least one solid support comprising capture oligonucleotides for said target RNA molecules and barcode oligonucleotides; (b) Partitioning said plurality of cells and said solid supports such that each cell is included into a separate partition and each partition comprises a solid support; (c) Lysing said cell, thereby obtaining a mixture of target and non¬ target RNA molecules; (d) Hybridizing said target RNA molecules to the capture oligonucleotides for said target RNA molecules, thereby obtaining target RNA molecules attached to said solid support (e) Disrupting the partitions and separating the non-target RNA molecules from the target RNA molecules attached to said solid support (f) Generating double stranded nucleic acids from the target RNA molecules by nucleic acid synthesis, wherein the capture oligonucleotides serve as primer and the target RNA molecules serve as templates (g) Attaching the barcode oligonucleotides to the double stranded nucleic acids from target RNA molecules, thereby generating barcoded nucleic acids from target RNA molecules; Characterized in that in step a) said plurality of cells additionally comprise target genomic DNA molecules and said at least one solid support additionally comprise capture oligonucleotides for target genomic DNA molecules and in that the capture oligonucleotides for target RNA and target genomic DNA molecules are different.
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemicals used in industry, science and photography, as well
as in agriculture, horticulture and forestry; unprocessed
artificial resins, unprocessed plastics; manures; fire
extinguishing compositions; tempering and soldering
preparations; chemical substances for preserving foodstuffs;
tanning substances; adhesives used in industry. Scientific, optical and measuring apparatus and instruments;
apparatus for recording, transmission or reproduction of
images; data processing equipment; computer software; all
the aforesaid solely for analysis of biological material. Scientific and technological services and research and
design relating thereto; industrial analysis and research
services; design and development of computer hardware and
software for analysis of biological material.
01 - Chemical and biological materials for industrial, scientific and agricultural use
02 - Paints, varnishes, lacquers
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical, biological and biochemical products for industrial, scientific purposes, namely, peptides, fluorescent dyes and conjugates thereof for use in separation processes for biological materials; reagents for cell separation; reagents for DNA, RNA, and polynucleotide detection; reagents for amplification, sequencing and detection of genetic material; reagents for Polymerase Chain Reaction (PCR); in situ polynucleotide detection reagents; in situ hybridization (ISH) reagents; fluorescence in situ hybridization (FISH) reagents; polynucleotide hybridization reagents; spatial multi-omics reagents; spatial transcriptomics reagents; polynucleotide detection probes; labeling reagents; media for cell culture for research laboratories; substances and ingredients for the preparation of media; reagents for the processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of chemical and biological material; reagents with magnetic beads; tissue staining reagents; antibody reagents used for the detection of antigens in cells and tissue, other than for medical or veterinary purposes; buffer solutions and reagents for use with laboratory instruments, namely, imaging instruments, reagents for processing of biological material, namely, tissue, bone marrow, cells, blood other than for medical or veterinary purposes; culture media, cell culture media, freezing media, contrast agents, contrast agents for in-vivo imaging, all for scientific purposes; reagents for use in biotechnology, and in the biotechnology industry; enzymes, other than for medical or veterinary use; polynucleotides, polynucleotide, DNA, and RNA primers and probes, fluorescence primers and probes, fluorophores, chemical additives for dyeing, all for scientific purposes; all the above for industrial or scientific purposes Primers and surgical dyes for use in pharmaceutical or scientific industries Nucleotides, polynucleotides, polynucleotides, namely, primers or probes for dna and rna, fluorescence primers and probes, complexes of molecules; all for medical purposes Apparatus for imaging for use in the study of spatial biology imaging; Scientific laboratory research instruments for polynucleotide sequencing; scientific laboratory research instruments for amplification and detection of genetic material; scientific laboratory research instruments for tissue visualization, in situ hybridization (ISH) instruments, fluorescence in situ hybridization (FISH) instruments; Scientific apparatus, namely, for spatial multi-omics and spatial transcriptomics for use in the science industry; apparatus for histology, namely, fluorescent imaging apparatuses and microscopes all for scientific purposes; histopathology slides and chambers; all the aforesaid being for laboratory use Medical imaging apparatus; instruments for spatial biology; instruments for polynucleotide sequencing; instruments for amplification and detection of genetic material; instruments for tissue visualization, in situ hybridization (ISH) instruments, fluorescence in situ hybridization (FISH) instruments; Polymerase Chain Reaction (PCR) instruments; apparatus for spatial multi-omics and spatial transcriptomics; apparatus for histology, all for medical and diagnostic purposes; histopathology slides and chambers; columns for analysis for medical purposes; all the aforementioned for medical purposes; apparatus and instruments for medical purposes Scientific and technological services, namely, research and design services; services for design of polynucleotide probes and genetic panels; all of the aforementioned services for and in connection with detection, localization and analysis of proteins and genetic material for biological and medical research, medical diagnostics and therapy
34.
MICROFABRICATED DROPLET DISPENSOR WITH IMMISCIBLE FLUID AND GENETIC SEQUENCER
A microfabricated droplet dispensing structure is described, which may include a MEMS microfluidic fluidic valve, configured to open and close a microfluidic channel. The opening and closing of the valve may separate a target biological particle containing genomic material, and a bead from a sample stream, and direct these two particle into a single droplet formed at the edge of the substrate. The droplet may then be encased in a sheath flow of an immiscible fluid, and provided to a downstream workflow. A third microfluidic channel upstream of the valve may add a biologically reactive material to the sample stream.
The present invention provides a composition comprising A) immune cells such as T cells comprising a) an inducible gene expression system comprising I) a first nucleic acid comprising a drug-inducible promoter operably linked to a second nucleic acid, and II) said second nucleic acid encoding a polypeptide or a non-coding RNA (ncRNA) which decreases cell surface expression level of major histocompatibility complex (MHC) class I relative to cell surface expression level of MHC class I of an immune cell that does not express said polypeptide or ncRNA; and b) a third nucleic acid encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR); and B) a drug that induces said drug-inducible promoter. Preferentially, said polypeptide may be a viral protein which decreases cell surface expression level of major histocompatibility complex (MHC) class I relative to cell surface expression level of MHC class I of an immune cell that does not express the viral protein.
The invention is directed to a method to simultaneously obtain both the spatial location and sequence information of a target sequence with a higher resolution than the known technologies. The method comprises steps to spatially localize the mRNA expressed on a tissue by the use of a hybrid circular/linear DNA probe with an UMI and—after several amplification steps, the obtaining sequence information by NGS.
The invention is directed to a method to simultaneously obtain both the spatial location and sequence information of a target sequence with a higher resolution than the known technologies. The method comprises steps to spatially localize the mRNA expressed on a tissue by the use of a hybrid circular/linear DNA probe with an UMI and ¨ after several amplification steps, the obtaining sequence information by NGS.
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
The present invention is directed to a chimeric antigen receptor (CAR), comprising an antigen binding domain specific for MSLN in combination with one or more antigen binding domains specific for an antigen selected from the group consisting of CLA, CD66c, TSPAN8 and CD318; cell populations expressing such CARs and the use of the cell populations for cancer therapy.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
(1) Chemicals used in industry, science and photography, as well as in agriculture, horticulture and forestry; unprocessed artificial resins, unprocessed plastics; manures; fire extinguishing compositions; tempering and soldering preparations; chemical substances for preserving foodstuffs; tanning substances; adhesives used in industry.
(2) Scientific, optical and measuring apparatus and instruments; apparatus for recording, transmission or reproduction of images; data processing equipment; computer software; all the aforesaid solely for analysis of biological material. (1) Scientific and technological services and research and design relating thereto; industrial analysis and research services; design and development of computer hardware and software for analysis of biological material.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Chemical, biological and biochemical preparations for scientific and diagnostic purposes; reagents for cell separation and labelling reagents for scientific purposes; preparations consisting of chemical, biological and biochemical reagents, media, substances and components for preparing antibody dye media, for scientific purposes; reagents for the processing, separation, isolation, enrichment, depletion, detection, screening, cultivation, analysis and counting of chemicals and biological material for scientific and research purposes; reagents featuring magnetic beads, other than for medical or veterinary purposes; antibody reagents, other than for medical or veterinary purposes; buffer solutions and reagents for use with laboratory apparatus, laboratory separation apparatus, laboratory analysis apparatus, laboratory reactors and imaging apparatus; reagents for processing biological material, in particular tissues, bone marrow, cells, blood and components thereof, other than for medical or veterinary purposes; diagnostic reagents and preparations for scientific purposes; culture media, cell culture media, freezing media, all being for scientific purposes, reagents for use in biotechnology, biological processing operations and the biotechnological industry reagents, media, substances and components for the preparation of media, all being for medical or veterinary purposes; reagents for treating, separating, isolating, enriching, depleting, detecting, screening, cultivating, analysing and counting biological materials; reagents featuring magnetic beads, antibody reagents, all being for medical or veterinary purposes; buffer solutions and reagents for use with medical apparatus, in particular separation apparatus, analysing apparatus, reactors and imaging apparatus; reagents for processing biological material, in particular tissues, bone marrow, cells, blood and components thereof, all being for medical or veterinary purposes; diagnostic preparations and reagents for medical and veterinary use; culture media, cell culture media, freezing media, all being for medical and veterinary purposes; pharmaceutical preparations for cellular therapy; chemical, biological and biochemical preparations used for therapeutic purposes, including medical diagnostics and in-vitro diagnostics (ivd); reagents, media, substances and components for the preparation of media for use in medical laboratories; diagnostic reagents and preparations for use in medical laboratories
41.
Method Combining In Situ Target Amplification and Spatial Unique Molecular Identifier (SUMI) Identification Using RT-PCR
Microscopy imaging that allows for multiple mRNAs, proteins and metabolites to be spatially resolved at a subcellular level provides valuable molecular information which is a crucial factor for understanding tissue heterogeneity as for example within the tumor micro environment. The current invention describes a method (High Density-SUMI-Seq) which combines the use of Spatial Unique Molecular Identifier in situ localization and identification (by in situ sequencing or sequential fluorescence hybridization) of rolonies derived from rolling circle amplification of circular oligonucleotides and in vitro sequencing of target amplified RNA or DNA in combination with SUMI identification at a subcellular level with no optical diffraction limitation in the amount of amplified target information that can be analyzed per cell. Apart from amplified RNA or DNA, the High Density-SUMI-Seq method can also be applied using linear oligonucleotides to spatially resolve proteins and metabolites to provide multiomics results.
The invention is directed to a method for obtaining a nucleic acid library of a sample comprising polynucleotides comprising the steps: a. Providing a plurality of modified primer to the polynucleotides, wherein said modified primer is a starting point for a polymerase for nucleic acid amplification b. Amplification of the polynucleotides using a polymerase c. Fragmentation of amplified polynucleotides, thereby obtaining a mixture of fragmented and un-fragmented polynucleotides comprising said modified primer d. Ligation of a plurality of adapter oligonucleotides to the mixture obtained in step c), thereby obtaining a mixture of polynucleotides comprising said adapter oligonucleotides, wherein said adapter oligonucleotides comprise a binding site for an amplification primer e. Providing an amplification primer to the mixture obtained in step d), wherein said amplification primer is a starting point for a polymerase for nucleic acid amplification f. initiate a nucleic acid amplification by providing a polymerase Characterized in that the modified primer provided in step a) comprises a functional group wherein said functional group is a blocking group at the 5' end of said modified primer, thereby preventing the ligation of the adapter oligonucleotides or wherein said functional group is at least one nucleotide analogue, and wherein the nucleotide analogue is excised after step d) by an endonuclease, thereby removing the primer binding site provided by the adapter oligonucleotides, thereby preventing binding of the amplification primer provided in step f) and a nucleic acid amplification of fragmented polynucleotides comprising the modified primer
The present invention provides an endogenous signaling molecule activating chimeric antigen receptor (ESMA-CAR) comprising a) an antigen binding domain specific for an antigen, b) a first transmembrane domain, and c) an intracellular signaling domain comprising a co- stimulatory domain but no stimulatory domain, wherein said first transmembrane domain, when expressed on the cell surface of an immune cell, is able to recruit a stimulatory domain of an endogenous signaling molecule of said immune cell, wherein said endogenous signaling molecule is a protein comprising a second transmembrane domain and an intracellular signaling domain comprising a stimulatory domain, and wherein the interaction of the first transmembrane domain and the second transmembrane domain activates said immune cell upon binding of said antigen to said antigen binding domain of said ESMA-CAR. The present invention also discloses an immune cell expressing said ESMA-CAR and an in-vitro method for the generation of said ESMA-CAR.
The present invention provides a composition comprising A) a nucleic acid sequence comprising encoding I) a) a fusion protein comprising from N-terminus to C -terminus i) IL-15Rα and, ii) the intracellular signaling domain of CD2, and b) IL-15, or II) a fusion protein comprising from N-terminus to C-terminus i) IL-15, ii) a linker, iii) IL-15Ra, and iv) the intracellular signaling domain of CD2, or B) a first nucleic acid sequence and a second nucleic acid sequence, said first nucleic acid sequence comprising encoding a fusion protein comprising from N-terminus to C-terminus i) IL-15Ra and ii) the intracellular signaling domain of CD2, said second nucleic acid sequence comprising encoding IL-15. Said composition may additionally comprise a transgene such as a CAR. Also disclosed are immune cells expressing the nucleic acids of said composition.
Biotinylation reagent has a structure according to formula (I)
Biotinylation reagent has a structure according to formula (I)
With
R1=alkyl, hydroxyalkyl or carboxyalkyl residue comprising 1 to 50 carbon atoms
R2=alkyl, glycol, amine or peptide reside with 1 to 50 carbon atoms
R3=Aryl, heteroaryl, with 3 to 50 carbon atoms
R4, R5=Aryl, hetero-aryl, Alkyl with 3 to 50 carbon atoms
Biotinylation reagent has a structure according to formula (I)
With
R1=alkyl, hydroxyalkyl or carboxyalkyl residue comprising 1 to 50 carbon atoms
R2=alkyl, glycol, amine or peptide reside with 1 to 50 carbon atoms
R3=Aryl, heteroaryl, with 3 to 50 carbon atoms
R4, R5=Aryl, hetero-aryl, Alkyl with 3 to 50 carbon atoms
Use of the agent in cell separation processes.
Instruments and apparatus for medical purposes, apparatus
for magnetic cell separation for medical purposes, sets of
flexible tubes for medical purposes, columns for analysis
for medical purposes.
The invention is directed to a conjugate complex for detecting a target moiety in a sample of biological specimens having the general formula (I) An - Bm...Cq-Xo (I) with A: antigen recognizing moiety; B: first binding moiety C second binding moiety X: detection moiety; n, m, q, o integers between 1 and 100, wherein B and C are non-covalently bound to each other characterised in that B comprises a thiamine unit and C is a moiety recognizing thiamine. Futher, the invention is directed to a method detecting a target moiety in a sample of biological specimens with a conjugate complex having the general formula (I).
The invention is directed to a method for obtaining the sequence information of a target sequence from a tissue comprising at least one RNA or c-DNA strand comprising two-fold RCA.
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
Goods & Services
(1) Chemical, biological and biochemical products for industrial, scientific and diagnostic purposes, other than for medical or veterinary use; chemical, biological and biochemical products for use in separation processes for biological materials; reagents for cell separation or cell fragmentation, labeling reagents, reagents, media, substances and ingredients for the preparation of media, all for commercial and scientific purposes and for the use in medical research laboratories, as far as included in this class; reagents for the fragmentation, processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of materials, especially of chemical and biological material; reagents with magnetic beads; antibody reagents (other than for medical or veterinary purposes); buffer solutions and reagents for use with laboratory instruments, especially fragmentation or separation instruments, analysis instruments, reactors and imaging instruments; reagents for processing of biological material, especially tissue, bone marrow, cells, blood and its components (other than for medical or veterinary purposes); diagnostic reagents and preparations for scientific purposes and for use in medical research laboratories; culture media, cell culture media, freezing media, contrast agents, contrast agents for in-vivo imaging, all for scientific purposes; reagents for use in biotechnology, in biological treatment processes and in the biotechnology industry.
(2) Scientific, optical and measuring apparatus and instruments, especially for and in connection with the fragmentation, separation, analysis, processing and cultivation of biological material; apparatus for recording, transmission or reproduction of images, data processing equipment, computer software, especially for or in connection with the separation, analysis, processing and cultivation of biological material, scientific, electrical and electronic apparatus and instruments for conducting enzymatic reactions; laboratory equipment, in particular cytometer for measuring physical and / or chemical properties of cells and other particles in suspensions; tissue fragmetation machines for research use; tissue fragmetation vessels for research use; sacks, bags, sheets, tubes and connectors for scientific or biotechnological purposes, in particular for cryopreservation; columns for analysis for medical purposes; apparatus and instruments for scientific purposes.
(3) Apparatus for magnetic cell separation for medical purposes; tubing sets for medical purposes; columns for analysis for medical purposes; sacks, bags, sheets, tubes and connectors for medical purposes, in particular for cryopreservation; apparatus and instruments for medical purposes and for biotechnological treatment of medical conditions; accessories and spare parts for the aforesaid goods; tissue fragmentation machines for medical use; tissue fragmentation vessels for medical use; medical apparatus and instruments.
50.
CONJUGATES HAVING AN ENZYMMATICALLY RELEASABLE DETECTION MOIETY AND A BARCODE MOIETY
The invention is directed to a conjugate having the general formula (I): Xn—P—YmBo (I), with X is an detection moiety, P is a spacer unit, Y an antigen recognizing moiety, B an oligonucleotide comprising 2 to 300 nucleotide residues and n, m, o are independent integers between 1 and 100 wherein P and B are covalently bound to Y and X is covalently bound to P and wherein X is erasable. Further, the invention is directed to a library of such conjugates and a method of detecting target cells utilizing the conjugates or the library of conjugates.
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
51.
METHOD COMBINING IN SITU TARGET CAPTURE AND SPATIAL UNIQUE MOLECULAR IDENTIFIER (SUMI) IDENTIFICATION WITH IN VITRO SEQUENCING FOR HIGH DENSITY SPATIAL MULTIOMICS
Microscopy imaging that allow for multiple mRNAs, proteins and metabolites to be spatially resolved at a subcellular level provides valuable molecular information which is a crucial factor for understanding tissue heterogeneity as for example within the tumor micro environment. The current invention describes a method (High Density—SUMI-Seq) which combines the use of Spatial Unique Molecular Identifier in situ localization and identification (by in situ sequencing or sequential fluorescence hybridization) of rolonies derived from rolling circle amplification of circular oligonucleotides and in vitro sequencing of target captured RNA or DNA in combination with SUMI identification at a subcellular level with no optical diffraction limitation in the amount of captured target information that can be analyzed per cell. Apart from captured RNA or DNA, the High Density—SUMI-Seq method can also be applied using linear oligonucleotides to spatially resolve proteins and metabolites to provide multiomics results.
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
Goods & Services
(1) Pharmaceutical and veterinary preparations; sanitary preparations for medical use; dietetic substances adapted for medical use, food for babies; plasters, materials for dressings; material for stopping teeth, dental wax; disinfectants; preparations for destroying vermin; fungicides, herbicides.
(2) Scientific, nautical, surveying, photographic, cinematographic, optical, weighing, measuring, signalling, checking (supervision), life-saving and teaching apparatus and instruments; apparatus and instruments for conducting, switching, transforming, accumulating, regulating or controlling electricity; apparatus for recording, transmission or reproduction of sound or images; magnetic data carriers, recording discs; automatic vending machines and mechanisms for coin-operated apparatus; cash registers, calculating machines, data processing equipment and computers; fire-extinguishing apparatus.
(3) Surgical, medical, dental and veterinary apparatus and instruments, artificial limbs, eyes and teeth; orthopedic articles; suture materials.
53.
System for inducible expression of an adapter in immune cells
The present invention provides a system for inducible expression of an adapter in immune cells comprising a) an inducible gene expression system comprising I) a first nucleic acid comprising an inducible promoter operably linked to a second nucleic acid, II) said second nucleic acid encoding an adapter comprising i) a first (poly)peptide, wherein said first (poly)peptide comprises an antigen binding domain that binds specifically to an antigen, ii) a second (poly)peptide, wherein said second (poly)peptide binds to an antigen binding domain of a chimeric antigen receptor (CAR), b) a third nucleic acid encoding said CAR specific for said second polypeptide of said adapter, wherein said CAR comprises i) said antigen binding domain specific for said second (poly)peptide of said adapter, ii) a transmembrane domain, iii) an intracellular signaling domain. The gene expression system may be antigen-activated or drug-induced. The system may be a one-cell or a two-cell approach.
The present invention provides a system for drug-inducible expression of a polynucleotide comprising a) a first nucleic acid sequence comprising a first promoter inducible by said drug, wherein the first promoter is operably linked to said polynucleotide, wherein said first promotor comprises a binding site for a DNA binding domain, wherein said binding site comprises at least one responsive element that is recognized by said DNA binding domain (DBD), and b) a second nucleic acid sequence comprising a second promoter, wherein the second promoter is operably linked to a nucleic acid sequence encoding a synthetic transcription factor, wherein said synthetic transcription factor comprises i) an activation domain (AD), wherein said AD comprises the p65 activation domain of the human transcription factor NFκB or a functional variant thereof, ii) said DNA binding domain (DBD), wherein said DBD comprises or consists of 3 zinc finger domains, iii) a ligand-binding domain (LBD), wherein said LBD is a modified human estrogen receptor which is able to bind said drug, and wherein said ligand-binding domain (LBD) is positioned at the C-terminus of said synthetic transcription factor, and c) said drug, wherein said drug is tamoxifen or a metabolite of tamoxifen.
The invention is directed to a device for the detection of target molecules, comprising - a transparent substrate provided with binding sites on one surface of the substrate, wherein the binding sites are capable of binding at least one target molecule - at least one light source - means for coupling light provided by the light source into the substrate, wherein at least a part of the light generates an evanescent field of light propagating along the surface provided with the binding sites, wherein the evanescent field of light is diffracted by target molecules bound to the binding sites, thereby creating a plurality of detection signals which are detected by at least one detector characterized in that the detection signals are space-filtered by at least one optical element located in the Fourier plane of the plane of the binding sites.
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
56.
IN SITU-COMBINED FUNCTIONALIZATION AND READOUT IN OPTICAL BIOMOLECULE INTERACTION ANALYSIS
The invention is directed to a device for the detection of target molecules, comprising - a transparent substrate provided with binding sites on one surface of the substrate, wherein the binding sites are capable of binding at least one target molecule - at least one light source providing at least a first and a second beam of light - a first means for coupling at least the first beam of light into the substrate, wherein at least a part of the light generates an evanescent field of light propagating along the surface provided with the binding sites, wherein the evanescent field of light is diffracted by target molecules bound to the binding sites, thereby creating at least one detection signal which is detected by at least one detector characterized in that a second means for coupling the second beam of light into the substrate, wherein the first and a second beam of light create an interference pattern on the surface of the substrate and wherein the binding sites are generated at the interference pattern.
G01N 21/45 - RefractivityPhase-affecting properties, e.g. optical path length using interferometric methodsRefractivityPhase-affecting properties, e.g. optical path length using Schlieren methods
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
The invention is directed to a device for the detection of target molecules, comprising - a transparent substrate provided with binding sites on one surface of the substrate, wherein the binding sites are capable of binding at least one target molecule - at least one light source - means for coupling light provided by the light source into the substrate, wherein at least a part of the light generates an evanescent field of light propagating along the surface provided with the binding sites, wherein the evanescent field of light is diffracted by target molecules bound to the binding sites, thereby creating a plurality of detection signals which are detected by at least one detector characterized in that the binding sites are bound to a plurality of subareas on one surface of the substrate and the and the detection signals of the binding sites in the subareas are detected subsequently.
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
G01N 21/45 - RefractivityPhase-affecting properties, e.g. optical path length using interferometric methodsRefractivityPhase-affecting properties, e.g. optical path length using Schlieren methods
The present invention is to provide a method for hybridization of a photo-responsive oligonucleotide to a nucleic acid by providing the nucleic acid with a complementary oligonucleotide, wherein the oligonucleotide functions as a starting point for a polymerase for nucleic acid synthesis characterized in that the photo-responsive oligonucleotide comprises at least two photo-responsive elements which change from a first to a second conformation upon irradiation with light thereby disabling or enabling the oligonucleotide hybridization. In addition to that, the current invention provides a method for spatially controlled oligonucleotide hybridization to specific sites by spatial illumination of areas of no interest, thus changing the oligonucleotide conformation to a non-binding state. The reversable hybridization of the oligonucleotide can be used for controlling several reactions such as rolling circle amplification and a sequencing reaction.
The invention is directed to a device for the detection of target molecules, comprising - a transparent substrate provided with binding sites on one surface of the substrate, wherein the binding sites are capable of binding at least one target molecule - a light source - means for coupling light provided by the light source into the substrate, wherein at least a part of the light generates an evanescent field of light propagating along the surface provided with the binding sites, wherein the evanescent field of light is diffracted by target molecules bound to the binding sites, thereby creating at least one detection signal which is detected by at least one detector characterized in that the light source provides low coherent or non-coherent light and the dispersion of the detection signal generated by the diffraction of low coherent or non-coherent light is reduced by at least 50% by one or more dispersive elements.
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
The invention is directed to a conjugate having the general formula (I) With AR, MU and L1 as repeating units of a polymer MU is a polymer modifying unit or band gap modifying unit that is evenly or randomly distributed along the polymer main chain, L1 is an aryl or a heteroaryl group evenly or randomly distributed along the polymer, L2 is an aryl or a heteroaryl group located on the ends of the polymer, FL is a fluorescent moiety, G1 and G2 stand for hydrogen, halogen or an antigen recognizing moiety, with the provision than at least one of G1 or G2 is an antigen recognizing moiety, characterized in that AR is connected in the polymer chain via the 2,2′ or 3,3′ or 5,5′ or 6,6′ or 7,7′ or 8,8′ position according to general formula (II)
The invention is directed to a conjugate having the general formula (I) With AR, MU and L1 as repeating units of a polymer MU is a polymer modifying unit or band gap modifying unit that is evenly or randomly distributed along the polymer main chain, L1 is an aryl or a heteroaryl group evenly or randomly distributed along the polymer, L2 is an aryl or a heteroaryl group located on the ends of the polymer, FL is a fluorescent moiety, G1 and G2 stand for hydrogen, halogen or an antigen recognizing moiety, with the provision than at least one of G1 or G2 is an antigen recognizing moiety, characterized in that AR is connected in the polymer chain via the 2,2′ or 3,3′ or 5,5′ or 6,6′ or 7,7′ or 8,8′ position according to general formula (II)
O222222SSR protecting group can be cleaved off by chemical treatment pre-requisites for enzymatic nucleic acids synthesis. By adding nucleotide in pre-determined fashion and cleave reaction after each step, longer DNA strands can be synthesized in solution or on solid surface starting from a short seeding DNA strands.
C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C07H 1/00 - Processes for the preparation of sugar derivatives
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/20 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
62.
DIRECT SYNTHESIS OF OLIGONUCLEOTIDES ON MICROTOMED TISSUE SLICES
The invention is directed to a method to synthesize oligonucleotides on the surface of a biological sample comprising the steps a. Binding a plurality of primer molecules to spatial locations on the surface of the biological sample with a stochastic surface distribution thereby creating a oligonucleotides bound to the biological sample b. providing the biological sample with A, T, C or G nucleotides having a protecting unit at their 3' positions c. incorporating one of the A, T, C or G nucleotides having a protecting unit at their 3' positions at the 3'end of at least one oligonucleotides bound to the biological sample by addition of a terminal transferase thereby extending the oligonucleotides d. adding at least one photo-activated cleave agent capable of removing the protection unit from the incorporated protected nucleotide e. removing the protecting unit from the incorporated protected nucleotide by activating the photo-activated cleave agent with light provided to at least one spatial location of the biological sample f. Repeating steps b) to e) to incorporate further nucleotides to at least one oligonucleotide.
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.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
The invention is directed to an connector comprising a first part and a second part, each provided with a contact surface and at least one non-contact surface facing away from the contact surface, at least one opening in the contact surface having an fluid connection to at least one opening of the non-contact surface, a releasable covering of the opening in the contact surface, and complementary means for mechanically coupling the parts at the contact surfaces to form the connector. The complementary means for mechanically coupling the parts are configured to mechanically interlock with each other.
The invention is directed to a conjugate having the general formula (I)
The invention is directed to a conjugate having the general formula (I)
Wherein AR, MU and MU* are repeating units of a polymer and MU and MU* are polymer modifying units or band gap modifying units which are evenly or randomly distributed along the polymer main chain,
G1 and G2 stand for hydrogen, halogen or an antigen recognizing moiety, with the provision that at least one of G1 or G2 is an antigen recognizing moiety,
a is 10 to 100 mol %,
b is 0 to 90 mol %
c is 0.1 to 90 mol %
d is 1 to 10 000; with the provisio that a+b+c=100 mol %
characterized in that AR is connected in the polymer chain via the 2,2′ or 3,3′ or 4,4′ or 5,5′ or 6,6′ or 7,7′ or 8,8′ positions according to general formula (II)
The invention is directed to a conjugate having the general formula (I)
Wherein AR, MU and MU* are repeating units of a polymer and MU and MU* are polymer modifying units or band gap modifying units which are evenly or randomly distributed along the polymer main chain,
G1 and G2 stand for hydrogen, halogen or an antigen recognizing moiety, with the provision that at least one of G1 or G2 is an antigen recognizing moiety,
a is 10 to 100 mol %,
b is 0 to 90 mol %
c is 0.1 to 90 mol %
d is 1 to 10 000; with the provisio that a+b+c=100 mol %
characterized in that AR is connected in the polymer chain via the 2,2′ or 3,3′ or 4,4′ or 5,5′ or 6,6′ or 7,7′ or 8,8′ positions according to general formula (II)
Wherein the remaining positions 2,2′; 3,3′; 4,4′; 5,5′; 6,6′; 7,7′ and 8,8′ are substituted with same or different residues selected from the group consisting of H, SO2CF3, SO2Ra, CF3, CCl3, CN, SO3H, NO2, NRaRbRc+, CHO, CORa, CO2Ra, COCl, CONRaRb, F, Cl, Br, I, Ra, ORa, SRa, OCORa, NRaRb, NHCORa, CCRa, aryl-, heteroaryl-, C6H4ORa or C6H4NRaRb, with Ra-c independently hydrogen, alkyl-, alkenyl-, alkinyl-, heteroalkyl-, aryl-, heteroaryl-, cycloalkyl-, alkylcycloalkyl-, heteroalkylcycloalkyl-, heterocycloalkyl-, aralkyl- or a heteroaralkyl residue or (CH2)x(OCH2CH2)yO(CH2)zCH3, wherein x is an integer from 0 to 20; y is an integer from 0 to 50 and z is an integer from 0 to 20.
The invention is directed to a conjugate having the general formula (I)
The invention is directed to a conjugate having the general formula (I)
Wherein AR and MU are repeating units of a polymer
MU is a polymer modifying unit or band gap modifying unit that is evenly or randomly distributed along the polymer main chain,
G1 and G2 stand for hydrogen, halogen or an antigen recognizing moiety, with the provision that at least one of G1 or G2 is an antigen recognizing moiety,
a is 10 to 100 mol %,
b is 0 to 90 mol %
c is 1 to 10 000; with the provisio that a+b=100 mol %
characterized in that AR is connected in the polymer chain via the 2,2′ or 3,3′ or 5,5′ or 6,6′ or 7,7′ or 8,8′ positions according to general formula (II)
The invention is directed to a conjugate having the general formula (I)
Wherein AR and MU are repeating units of a polymer
MU is a polymer modifying unit or band gap modifying unit that is evenly or randomly distributed along the polymer main chain,
G1 and G2 stand for hydrogen, halogen or an antigen recognizing moiety, with the provision that at least one of G1 or G2 is an antigen recognizing moiety,
a is 10 to 100 mol %,
b is 0 to 90 mol %
c is 1 to 10 000; with the provisio that a+b=100 mol %
characterized in that AR is connected in the polymer chain via the 2,2′ or 3,3′ or 5,5′ or 6,6′ or 7,7′ or 8,8′ positions according to general formula (II)
Wherein the remaining positions 2,2′; 3,3′; 4,4′; 5,5′; 6,6′; 7,7′ and 8,8′ are substituted with same or different residues selected from the group consisting of H, SO2CF3, SO2Ra, CF3, CCl3, CN, SO3H, NO2, NRaRbRc+, CHO, CORa, CO2Ra, COCl, CONRaRb, F, Cl, Br, I, Ra, ORa, SRa, OCORa, NRaRb, NHCORa, CCRa, aryl-, heteroaryl-, C6H4ORa or C6H4NRaRb, with Ra-c independently hydrogen, alkyl-, alkenyl-, alkinyl-, heteroalkyl-, aryl-, heteroaryl-, cycloalkyl-, alkylcycloalkyl-, heteroalkylcycloalkyl-, heterocycloalkyl-, aralkyl- or a heteroaralkyl residue or (CH2)x(OCH2CH2)yO(CH2)zCH3, wherein x is an integer from 0 to 20; y is an integer from 0 to 50 and z is an integer from 0 to 20
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
16 - Paper, cardboard and goods made from these materials
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Blood component separation apparatus for medical purposes; apparatus for recording, transmission or reproduction of images, data processing equipment; downloadable and recorded computer software for use in operating a cell incubator, cell separating and cell imaging devices; chromatography columns for laboratory use apparatus for magnetic cell separation for medical purposes; blood tubing sets for medical purposes; kits comprised of capillary tubes for samples for medical use; bags for medical cell products, tubes and connectors for medical purposes, in particular for cryopreservation of human tissue; Apheresis machines for medical use Plastic materials for packaging, namely, bags, foils, for the cryopreservation of biological and biochemical material, especially cellular material for biological and medical research and therapy Scientific and technological services and research and design of medical devices; industrial research in the field of medical devices; design and development of computer hardware and software for the analysis of biological and biochemical material, especially of cellular material for biological and medical research and therapy Medical analysis services for diagnostic and treatment purposes provided by medical laboratories
68.
Compositions and Methods for Treating Cancer Expressing CD90 and CD326
The present invention provides a combination comprising a) an antigen binding domain specific for CD90, and b) an antigen binding domain specific for CD326, for use in treatment of human cancer comprising cancerous cells that co-express CD90 and CD326. In one embodiment of the invention the combination comprises a) an immune cell comprising a CAR comprising an antigen binding domain specific for a tag of a first and a second polypeptide, b) said tagged first polypeptide that has an antigen binding domain specific for CD90, and c) said tagged second polypeptide that has an antigen binding domain specific for CD326, wherein the tag of the first polypeptide and the tag of the second polypeptide are identical. In a further embodiment the concentrations used for said first and that second polypeptide are below the activation threshold of said CAR, respectively, but the sum of both concentrations is above the activation threshold of said CAR.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
DNA sequencing by sequential addition/incorporation of non 3’capped and fluorescently labeled nucleotides. Each incorporation of individual nucleotides (A, or T or G or C) are separated by a wash. After all incorporation using all four bases, the substrate is imaged then the dyes are cleaved, and the following cycle of incorporations, washes, imaging and cleave is resumed.
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.
A61M 1/36 - Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
B01D 21/26 - Separation of sediment aided by centrifugal force
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B04B 1/12 - Centrifuges with rotary bowls provided with solid jackets for separating predominantly liquid mixtures with or without solid particles with discharging outlets in the plane of the maximum diameter of the bowl with continuous discharge
The invention is directed to a conjugate characterized by high brightness to enable detection of rarely expressed epitopes and release of the label from the epitope to enable downstream applications such as sequential imaging or cell sorting and with the general formula (I) Yn−P1(P2−Xm)o, with X: detection moiety; P1: first enzymatically degradable spacer; P2: second enzymatically degradable spacer; Y: antigen recognizing moiety and n, m, o integers between 1 and 100 with the provision that first spacer P1 and second spacer P2 are not degradable by the same enzyme.
C08F 293/00 - Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule
The present invention provides an in-vitro method for the generation of a population of genetically modified natural killer (NK) cells comprising the steps in the following order: a) obtaining a sample comprising NK cells and other cells, b) enrichment of NK cells from said sample, c) introducing a genetic modifier 1 into said NK cells by electroporation, d) introducing a genetic modifier 2 into said NK cells by transduction, e) expanding said genetically modified NK cells, thereby generating a population of genetically modified NK cells.
The present invention provides a method for generating a composition of immune cells expressing a plurality of transgenes under the control of an endogenous promoter of said immune cells, wherein each single immune cell of said composition that underwent the process of allelic exclusion with regard to said endogenous locus expresses only one transgene wherein the transgene encodes a therapeutic protein or therapeutic nucleic acid, thereby generating a plurality of immune cells within said composition of immune cells expressing a plurality of transgenes.
The present invention provides a method for expressing and displaying desired proteins of interest (POI) on the surface of a lower eukaryote in a form that is accessible for detection and isolation of desired cell clones by introducing two kinds of nucleic acids into the lower eukaryotic host cell: I) a first nucleic acid sequence comprising i) a gene encoding a polypeptide comprising a cell surface anchoring protein fused to a first binding moiety domain, and ii) an antimicrobial resistant marker encoding a protein that provides resistance to a chemical, wherein said nucleic acid sequence is a plasmid comprising an autonomously replicating sequence (ARS) elements, and II) a second nucleic acid sequence comprising i) a gene or genes encoding said desired POI, wherein said desired POI comprises a second binding moiety that is capable of specifically interacting with said first binding moiety and ii) a second antimicrobial resistant marker encoding a protein that provides resistance to a chemical or anti-microbial drug.
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)
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.
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.
The invention is directed to a method to obtain the spatial location and sequence information of an m-RNA target sequence on a tissue sample comprising providing a solid surface, attaching anchor molecules, binding scaffolding molecules, incorporating adenine, guanine, cytosine and thymine, incorporating thymine to the anchor molecules, removing the scaffolding, providing a tissue sample, reverser transcrining to create c-DNA, removing the c-DNA and obtaining the sequence information of the c-DNA.
The invention is directed to a process for providing a cell comprising a chimeric antigen receptor (CAR) specific for one or more target antigens exposed on tumor microenvironment cells characterized by providing a cell sample comprising tumor microenvironment cells and non-tumor microenvironment cells and repeating the steps of—contacting the cell tissue with a conjugate comprising a fluorescent moiety and an antigen recognizing moiety—removing unbound conjugate from the cell tissue and detecting cells bound to the conjugate by the fluorescence radiation emitted by the fluorescent moieties of the first conjugates—erasing the fluorescence emitted by the fluorescent moieties of the conjugates until identifying at least two conjugates provided with antigen recognizing moieties recognizing different antigens, allowing in combination to discriminate between tumor microenvironment cells and non-tumor microenvironment cells and providing cells with the identified at least two antigen recognizing moieties as chimeric antigen receptor (CAR). Preferable, the tumor microenvironment cells are tumor microenvironment cells from tumor stromal cells or PaCa cells.
01 - Chemical and biological materials for industrial, scientific and agricultural use
02 - Paints, varnishes, lacquers
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical, biological and biochemical products for industrial, scientific purposes, namely products for use in separation processes for biological materials; reagents for cell separation; reagents for DNA, RNA, and/or polynucleotide detection; reagents for amplification, sequencing and detection of genetic material; reagents for Polymerase Chain Reaction (PCR); in situ polynucleotide detection reagents; in situ hybridization (ISH) reagents; fluorescence in situ hybridization (FISH) reagents; polynucleotide hybridization reagents; spatial multi-omics reagents; spatial transcriptomics reagents; polynucleotide detection probes; labeling reagents; media; substances and ingredients for the preparation of media; reagents for the processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of chemical and biological material; reagents with magnetic beads; tissue staining reagents; antibody reagents (other than for medical or veterinary purposes); buffer solutions and reagents for use with laboratory instruments, especially imaging instruments, reagents for processing of biological material, especially tissue, bone marrow, cells, blood and its components (other than for medical or veterinary purposes); culture media, cell culture media, freezing media, contrast agents, contrast agents for in-vivo imaging, all for scientific purposes; reagents for use in biotechnology, and in the biotechnology industry; Enzymes (other than for medical or veterinary use); Polynucleotides, Polynucleotide, DNA, and RNA primers and probes, Fluorescence primers and probes, Fluorophores, dyes, all especially for scientific purposes; All the above for industrial or scientific purposes. Nucleotides, Polynucleotides, Polynucleotides, namely as primers or probes for DNA and RNA, Fluorescence primers and probes, namely as primers or probes for DNA and RNA, Fluorophores, dyes, all especially for pharmaceutical or scientific purposes. Nucleotides, Polynucleotides, Polynucleotides, namely as primers or probes for DNA and RNA, Fluorescence primers and probes, namely as primers or probes for DNA and RNA, Fluorophores, dyes, all especially for medical purposes. Apparatus for imaging, namely spatial biology imaging; instruments for polynucleotide sequencing; instruments for amplification and detection of genetic material; instruments for tissue visualization, in situ hybridization (ISH) instruments, fluorescence in situ hybridization (FISH) instruments; Polymerase Chain Reaction (PCR) instruments; apparatus for spatial multi-omics and spatial transcriptomics; apparatus for histology, all for scientific purposes; histopathology slides and chambers; all the aforesaid being for laboratory use. Apparatus for imaging; instruments for spatial biology; instruments for polynucleotide sequencing; instruments for amplification and detection of genetic material; instruments for tissue visualization, in situ hybridization (ISH) instruments, fluorescence in situ hybridization (FISH) instruments; Polymerase Chain Reaction (PCR) instruments; apparatus for spatial multi-omics and spatial transcriptomics; apparatus for histology, all for medical and diagnostic purposes; histopathology slides and chambers; columns for analysis for medical purposes; all the aforementioned for medical purposes; apparatus and instruments for medical purposes. Scientific and technological services, research and design services; services for design of polynucleotide probes and genetic panels; all of the aforementioned services for and in connection with detection, localization and analysis of proteins and genetic material for biological and medical research, medical diagnostics and therapy.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Chemical, biological and biochemical products for
industrial, scientific and diagnostic purposes; chemical,
biological and biochemical products for use in separation
processes for biological materials; reagents for cell
separation, labeling reagents, reagents, media, substances
and ingredients for the preparation of media, all for
commercial and scientific purposes, included in this class;
chemical reagents with magnetic beads; chemical antibody
reagents (other than for medical or veterinary purposes);
buffer solutions for scientific purposes and chemical
reagents for use with laboratory instruments, especially
separation instruments, analysis instruments, reactors and
imaging instruments; reagents for processing of biological
material, especially tissue, bone marrow, cells, blood and
its components (other than for medical or veterinary
purposes); diagnostic reagents and preparations for
scientific purposes; culture media, cell culture media,
freezing media, contrast agents, contrast agents for in-vivo
imaging, all for scientific purposes; chemical reagents for
use in biotechnology, in biological treatment processes and
in the biotechnology industry. Pharmaceutical, medical and veterinary products as well as
products for the pharmaceutical, medical and veterinary
science, pharmaceutical and other preparations for medical
or veterinary purposes; reagents, media, materials and
ingredients for the preparation of media, all for medical or
veterinary purposes; reagents for the processing,
separation, isolation, enrichment, depletion, detection,
screening, analysis and counting of material, especially of
biological materials, reagents with magnetic beads, antibody
reagents, all for medical or veterinary purposes; buffer
solutions and reagents for use with medical instruments,
especially separation instruments, analysis instruments,
reactor and imaging instruments; reagents for the processing
of biological material, especially tissue, bone marrow,
cells, blood and its components, all for medical or
veterinary purposes; culture media, cell culture media,
diagnostic reagents and preparations for medical and
veterinary purposes; freezing media, contrast agents,
contrast agents for in-vivo imaging, all for medical and
veterinary purposes; pharmaceutical products, especially
pharmaceutical products for the cellular therapy; chemical,
biological and biochemical products for therapeutic and
diagnostic purposes, including medical diagnostic purposes;
reagents for cell separation, labeling reagents, reagents,
media, substances and ingredients for the preparation of
media, all for the use in medical laboratories, included in
this class; diagnostic reagents and preparations for use in
medical laboratories. Services of medical, pharmaceutical or biotechnological
laboratories, medical and pharmaceutical services, namely
services of a medical and pharmaceutical laboratory, in
particular in connection with the manufacture of cell
therapeutic agents, cell compounds, cell preparation,
cellular medicines, the selection, stimulation, activation
of cells, as well as the manufacture of kits or reagents. Medical services, in particular the field of extracorporeal
plasma therapy; medical treatment services.
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
Goods & Services
Chemical, biological and biochemical products for
industrial, scientific and diagnostic purposes, other than
for medical or veterinary use; chemical, biological and
biochemical products for use in separation processes for
biological materials; reagents for cell separation or cell
fragmentation, labeling reagents, reagents, media,
substances and ingredients for the preparation of media, all
for commercial and scientific purposes and for the use in
medical research laboratories, as far as included in this
class; reagents for the fragmentation, processing,
separation, isolation, enrichment, depletion, detection,
screening, analysis and counting of materials, especially of
chemical and biological material; reagents with magnetic
beads; antibody reagents (other than for medical or
veterinary purposes); buffer solutions and reagents for use
with laboratory instruments, especially fragmentation or
separation instruments, analysis instruments, reactors and
imaging instruments; reagents for processing of biological
material, especially tissue, bone marrow, cells, blood and
its components (other than for medical or veterinary
purposes); diagnostic reagents and preparations for
scientific purposes and for use in medical research
laboratories; culture media, cell culture media, freezing
media, contrast agents, contrast agents for in-vivo imaging,
all for scientific purposes; reagents for use in
biotechnology, in biological treatment processes and in the
biotechnology industry. Scientific, optical and measuring apparatus and instruments,
especially for and in connection with the fragmentation,
separation, analysis, processing and cultivation of
biological material; apparatus for recording, transmission
or reproduction of images, data processing equipment,
computer software, especially for or in connection with the
separation, analysis, processing and cultivation of
biological material, scientific, electrical and electronic
apparatus and instruments for conducting enzymatic
reactions; laboratory equipment, in particular cytometer for
measuring physical and / or chemical properties of cells and
other particles in suspensions; tissue fragmetation machines
for research use; tissue fragmetation vessels for research
use; sacks, bags, sheets, tubes and connectors for
scientific or biotechnological purposes, in particular for
cryopreservation; columns for analysis for medical purposes;
apparatus and instruments for scientific purposes. Apparatus for magnetic cell separation for medical purposes;
tubing sets for medical purposes; columns for analysis for
medical purposes; sacks, bags, sheets, tubes and connectors
for medical purposes, in particular for cryopreservation;
apparatus and instruments for medical purposes and for
biotechnological treatment of medical conditions;
accessories and spare parts for the aforesaid goods; tissue
fragmentation machines for medical use; tissue fragmentation
vessels for medical use; medical apparatus and instruments.
82.
Synthesis of reversible nucleotide terminators by in-situ thio-alkyl group transfer for use in DNA sequencing by synthesis
The invention is directed to a method for production of a deoxynucleotide triphosphate according to general formula (7)
wherein B is a nucleobase and R is an alkyl group having 1 to 4 carbon atoms and n is an integer from 1 to 10 by reaction of reaction precursor of compound 6
3 are independently H, O-Alkyl with alkyl residues having 1 to 4 carbon atoms or halogen and n is an integer from 1 to 10 with dialkyl(alkylthio)sulfonium salt (8B)
2− in aqueous solution having a pH between 3 and 7.
The invention is directed to a Conjugate for labelling a target moiety on a cell, characterized by general formula (II): Xo-P-Ym, with Y: MHC-complex targeting TCR molecules, P: enzymatically degradable spacer, X: detection moiety, o: integer between 5 and 25, m: integer between 2 and 1000, wherein X and P; P and Y are covalently bound to each other and Y is bound to P via the C-terminus.
The invention is directed to a method to provide a polynucleotide molecule comprising a first and a second strand with a barcode nucleotide sequence characterized in that the first strand is provided at its 5´ end with an overhang of at least one universal base and the corresponding recessed 3´ end of the second strand of the polynucleotide with at least one nucleotide provided with a blocking group, wherein the blocking groups are removed from the incorporated nucleotides by irradiation with light.
The invention is directed to a method to obtain the spatial location and sequence information of at least a part of a RNA or cDNA strand (006) in a sample comprising the steps
a. hybridizing a first detection probe oligonucleotide (204) comprising 50-1000 nucleotides with its 3′ and/or 5′ end to the complementary part of the at least one RNA or cDNA strand, wherein the detection probe oligonucleotide is partially hybridized to a bridge oligonucleotide (205) comprising 5-100 nucleotides wherein a gap region (206) capable of binding oligonucleotides is created
b. filling the gap region (206) in part with 1 to 16 barcode oligonucleotides comprising 4-20 nucleotides, wherein the barcode oligonucleotides determine the spatial information of the RNA or cDNA strand in the sample
c. partially hybridizing a second detection probe oligonucleotide (204′) comprising 50-1000 nucleotides with its 3′ and/or 5′ end to the complementary part of the same or cDNA strand and with the respective other end to the bridge oligonucleotide (205) to create a circular template
d. multiplying the circular template by a polymerase capable of rolling circle amplification into rolonies comprising a plurality of concatemers
e. determining the sequence of nucleotides of the rolonies
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.
01 - Chemical and biological materials for industrial, scientific and agricultural use
02 - Paints, varnishes, lacquers
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
16 - Paper, cardboard and goods made from these materials
17 - Rubber and plastic; packing and insulating materials
39 - Transport, packaging, storage and travel services
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Chemical, biological and biochemical products for industrial, scientific, therapeutic and diagnostic purposes, including medical diagnostic purposes; products for use in separation processes for biological materials; reagents for cell separation, labeling reagents, reagents, media, substances and ingredients for the preparation of media, all for commercial and scientific purposes and for the use in medical laboratories, as far as included in this class; reagents for the processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of materials, especially of chemical and biological material; reagents with magnetic beads; antibody reagents (other than for medical or veterinary purposes); buffer solutions and reagents for use with laboratory instruments, especially separation instruments, analysis instruments, reactors and imaging instruments; reagents for processing of biological material, especially tissue, bone marrow, cells, blood and its components (other than for medical or veterinary purposes); diagnostic reagents and preparations for scientific purposes and for use in medical laboratories; culture media, cell culture media, freezing media, contrast agents, contrast agents for in-vivo imaging, all for scientific purposes; reagents for use in biotechnology, in biological treatment processes and in the biotechnology industry. Dyestuffs; colorants; all especially for pharmaceutical, medical, or scientific purposes. Pharmaceutical, medical and veterinary products as well as products for the pharmaceutical, medical and veterinary science, pharmaceutical and other preparations for medical or veterinary purposes; reagents, media, materials and ingredients for the preparation of media, all for medical or veterinary purposes; reagents for the processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of material, especially of biological materials, reagents with magnetic beads, antibody reagents, all for medical or veterinary purposes; buffer solutions and reagents for use with medical instruments, especially separation instruments, analysis instruments, reactor and imaging instruments; reagents for the processing of biological material, especially tissue, bone marrow, cells, blood and its components, all for medical or veterinary purposes; culture media, cell culture media, diagnostic reagents and preparations for medical and veterinary purposes; freezing media, contrast agents, contrast agents for in-vivo imaging, all for medical and veterinary purposes; pharmaceutical products, especially pharmaceutical products for the cellular therapy. Scientific, optical and measuring apparatus and instruments, especially for and in connection with the separation, analysis, processing and cultivation of biological material; apparatus for recording, transmission or reproduction of images, data processing equipment, computer software, especially for or in connection with the separation, analysis, processing and cultivation of biological material, scientific, electrical and electronic apparatus and instruments for conducting enzymatic reactions; laboratory equipment, in particular cytometer for measuring physical and / or chemical properties of cells and other particles in suspensions. apparatus for magnetic cell separation for medical purposes; tubing sets for medical purposes; columns for analysis for medical purposes; sacks, bags, sheets, tubes and connectors for medical, scientific or biotechnological purposes, in particular for cryopreservation; apparatus and instruments for medical, biotechnological and scientific purposes; accessories and spare parts for the aforesaid goods; Dialysis machines for medical use; Apheresis machines for medical use; Veterinary apparatus and instruments; Surgical apparatus and instruments; Dental apparatus and instruments; Medical apparatus and instruments. Plastic materials for packaging, especially bags, bags, foils, included in this class, for the cryopreservation of biological and biochemical material, especially cellular material for biological and medical research and therapy. Sacks, bags, sheets, tubes and joints of rubber, gutta-percha, rubber, plastics, included in this class, for medical, scientific or biotechnological purposes, especially for cryopreservation; films for the manufacture of the aforesaid goods; hoses, hose assemblies and fittings, especially for medical, scientific or biotechnological purposes. Biological and biochemical storage, especially cryopreserved material for medical, scientific and biotechnological purposes; Storage services in connection with medical, pharmaceutical or biotechnology laboratories. Scientific and technological services and research and design services relating herto; industrial analysis and research services; design and development of computer hardware and software for the analysis, all of the aforementioned services for and in connection with the analysis of biological and biochemical material, especially of cellular material for biological and medical research and therapy. Services of medical, pharmaceutical or biotechnological laboratories, medical and pharmaceutical services,namely services of a medical and pharmaceutical laboratory, in particular in connection with the manufacture of cell therapeutic agents, cell compounds, cell preparation, cellular medicines, the selection, stimulation, activation of cells, as well as the manufacture of kits or reagents, medical services, in particular the field of extracorporeal plasma therapy; medical treatment services.
88.
COLOR AND BARDCODED BEADS FOR SINGLE CELL INDEXING
The present invention is directed to a method for identifying nucleic acids of a target cell from a cell population comprising—isolating at least one target cell from the cell population and at least one color-coded composition comprising a solid particle conjugated to an oligonucleotide into one compartment—lysing the isolated target cells—coupling the nucleic acid molecules of the lysed isolated target cells with the oligonucleotide of the color-coded composition forming a first conjugate—determining the sequence of the first conjugate, thereby identifying the target cell. characterized in that at least one target cell and the at least one color-coded composition are selected to be isolated into one compartment according to at least one pre-selected physical property of the target cell combined with at least one pre-selected physical property of the color-coded composition.
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.
B04B 5/10 - Centrifuges combined with other apparatus, e.g. electrostatic separatorsSets or systems of several centrifuges
B04B 1/12 - Centrifuges with rotary bowls provided with solid jackets for separating predominantly liquid mixtures with or without solid particles with discharging outlets in the plane of the maximum diameter of the bowl with continuous discharge
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
The present invention provides an in-vitro method of reducing the efficiency of transducing malignant cells of the blood system of a subject that are not derived from T cells with lentiviral vector particles without reducing the efficiency of transducing T cells in a sample comprising T cells and said malignant cells. A combination of compositions comprising a first composition and a second composition is also disclosed, wherein said first composition comprises i) transduced T cells of a subject, wherein said transduced T cells express a CAR comprising an antigen binding domain, wherein the antigen binding domain of said CAR binds specifically to a tag of a tagged polypeptide, and ii) non-transduced malignant cells of the blood system of said subject, and wherein said second composition comprises said tagged polypeptide, wherein said tagged polypeptide binds specifically to an antigen expressed on the surface of said malignant cells. Alternatively, the transduced T cells of said first composition may comprise a nucleic acid encoding a CAR and an inducible gene expression system, and said second composition may comprise an induction agent inducing said gene system.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
91.
METHOD TO USE DNA NANOBALLS GENERATED BY RCA USING OLIGONUCLEOTIDE BASED DNA ORIGAMI TO CREATE HIGH DENSITY FLOWCELL FOR SEQUENCING
The invention is directed to a method for single cell gene sequencing of a sample comprising at least one RNA or c-DNA strand comprising the steps a. binding an oligonucleotide having 50 - 1000 nucleic acids to two adjacent portions of the RNA or c-DNA strand thereby obtaining circular molecules b. multiplying the circular molecules into concatemers by RCA reaction forming a rolony characterized in that the rolony is provided with scaffolding oligonucleotides having 5 - 100 nucleic acids which bind to two or more adjacent portions of different concatemer of the same rolony creating a shaped rolony; immobilizing the shaped rolony on a surface and determining the sequences of nucleotides of the concatemers of the immobilized shaped rolony.
The invention is directed to a method for activating CAR cells having at least one chimeric antigen binding receptor in a sample by incubating the sample with at least one substrate provided on its surface with at least one anti-CAR idiotype antibody and/or at least one antigen selected from the group consisting of CD19, CD20, CD22, BCMA, CD33, MSLN, CD123, HER2, GD2, EGFR, PSMA, MUC1, CD318, TSPAN8, CD66c, CEA, CLA, CD276, FolR1, CLEC12A, CLL-1 and CD371, and with at least one costimulatory molecule selected from the group consisting of CD28, CD2, CD6, CD26, CD53 and LFA-1 characterized in that the sample is incubated with the at least substrate in suspension thereby activating the CAR T cells to express markers selected from the group consisting of mRNA, effector molecules or cell surface activation markers.
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
Goods & Services
Chemical, biological and biochemical products for industrial, scientific and diagnostic purposes, other than for medical or veterinary use, namely, biological tissue cultures, diagnostic preparations for scientific use, enzymes and lysing reagent for tissue fragmentation; chemical preparations for use in separation processes for biological materials; reagents for scientific research and use, namely, reagents for cell separation or cell fragmentation, labeling reagents, and reagents for the preparation of media, all for commercial and scientific purposes and for the use in medical research laboratories; chemical reagents, not for medical or veterinary purposes, for the fragmentation, processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of chemical and biological materials; chemical reagents with magnetic beads; chemical antibody reagents, other than for medical or veterinary purposes; buffer solutions and chemical reagents for use with laboratory instruments, especially fragmentation or separation instruments, chemical analysis instruments, reactors and imaging instruments; reagents other than for medical or veterinary purposes, for processing of biological material, especially tissue, bone marrow, cells, blood and its components; diagnostic reagents and preparations for scientific purposes and for use in medical research laboratories; cell culture media for in-vivo imaging, all for scientific purposes; chemical reagents for use in biotechnology, in biological treatment processes and in the biotechnology industry Scientific, optical and measuring apparatus and instruments, namely, laboratory apparatus and instruments for the fragmentation, separation, analysis, processing and cultivation of biological material; apparatus for recording, transmission or reproduction of images; data processing equipment; downloadable computer software, for use in operating and controlling equipment in connection with the separation, analysis, processing and cultivation of biological material; scientific, laboratory apparatus being electrical and electronic apparatus and instruments for conducting enzymatic reactions; laboratory equipment, in particular cytometer for measuring physical and chemical properties of cells and other particles in suspensions; laboratory equipment being tissue fragmentation machines for research use, namely, for use in pathology; laboratory equipment being tissue fragmentation vessels for research use; laboratory equipment, being sacks, bags, sheets, tubes and connectors for scientific or biotechnological purposes, in particular for tissue fragmentation for use in cryopreservation; laboratory apparatus and instruments for scientific purposes, namely, tissue fragmentation equipment Medical apparatus for magnetic cell separation for medical purposes; blood tubing sets, sold empty, for medical purposes; medical apparatus being columns for analysis for medical purposes; sacks, bags, sheets, tubes and connectors for medical purposes, in particular for tissue and blood collection for cryopreservation; tissue fragmentation machines for medical use, namely, machines for use in pathology; tissue fragmentation vessels being test tubes for medical use; medical apparatus and instruments, namely, tissue fragmentation equipment
The invention is directed to a Method for detecting differentiated hematopoietic cells comprising the steps: a) isolation of undifferentiated hematopoietic stem cells in groups of 1-1000 cells on a support b) proliferating the isolated cells to form cell colonies of differentiated hematopoietic cells by providing cell media comprising a growth factor c) contacting the cell colonies with one or more marker conjugates comprising at least one detection moiety and at least one antigen recognizing moiety against CD14, CD235a and CD15 d) detecting the relative amount of differentiated hematopoietic stem cells in a cell colony labelled with the marker conjugates.
The invention is directed to a conjugate for labelling a target moiety on a cell, characterized with the general formula (I) (Xo-L)n-P-Ym, with Y: antigen recognizing moiety recognizing the target moiety, P: enzymatically degradable spacer, X: fluorescent moiety, L: linker unit comprising one or more polyethyleneglycol residues n, m: integer between 1 and 100, o integer between 1 and 100 wherein L covalent bounds the fluorescent moiety X and the enzymatically degradable spacer P and Y is covalently bound to the enzymatically degradable spacer P and wherein the enzymatically degradable spacer P is selected from the group consisting of polysaccharides, polyesters, nucleic acids, and derivatives thereof. Method of detecting a target moiety in a sample of biological specimen with the conjugate.
Microscopy imaging that allow for multiple mRNAs, proteins and metabolites to be spatially resolved at a subcellular level provides valuable molecular information which is a crucial factor for understanding tissue heterogeneity as for example within the tumor micro environment. The current invention describes a method (SUMI-Seq) which combines the use of Spatial Unique Molecular Identifier in situ sequencing and in vitro sequencing of rolonies derived from rolling circle amplification from padlock oligonucleotides targeting portion of RNA or cDNA transcript at a subcellular level with less limitation in the amount of transcripts and the length of the sequence that can be analyzed. Apart from padlocks oligonucleotides, the SUMI-Seq method can also be applied using circular oligonucleotides to spatially resolve proteins and metabolites to provide multiomics results.
The invention is directed to a method for obtaining a nucleic acid library of a sample comprising polynucleotides comprising the steps a. multiplying the polynucleotides by a polymerase b. fragmenting the multiplied polynucleotides by creating nicks c. coupling an oligonucleotide sequence to the nicks to create the target library wherein step a) is performed by providing A, T, G, C and U nucleotides wherein the molar ratio of T and U is between 200:1 and 5:1 and step b) is performed by excision of the U nucleotides. characterized in that after step b), the nicks are provided with a polymerase exhibiting 5' 3' exonuclease activity, thereby filling in the 3' recessing ends and removing the 5' overhangs of the nicks.
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.
B04B 5/10 - Centrifuges combined with other apparatus, e.g. electrostatic separatorsSets or systems of several centrifuges
B04B 1/12 - Centrifuges with rotary bowls provided with solid jackets for separating predominantly liquid mixtures with or without solid particles with discharging outlets in the plane of the maximum diameter of the bowl with continuous discharge
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
(1) Chemical, biological and biochemical products for industrial, scientific and diagnostic purposes; chemical, biological and biochemical products for use in separation processes for biological materials; reagents for cell separation, labeling reagents, reagents, media, substances and ingredients for the preparation of media, all for commercial and scientific purposes, included in this class; chemical reagents with magnetic beads; chemical antibody reagents (other than for medical or veterinary purposes); buffer solutions for scientific purposes and chemical reagents for use with laboratory instruments, especially separation instruments, analysis instruments, reactors and imaging instruments; reagents for processing of biological material, especially tissue, bone marrow, cells, blood and its components (other than for medical or veterinary purposes); diagnostic reagents and preparations for scientific purposes; culture media, cell culture media, freezing media, contrast agents, contrast agents for in-vivo imaging, all for scientific purposes; chemical reagents for use in biotechnology, in biological treatment processes and in the biotechnology industry.
(2) Pharmaceutical, medical and veterinary products as well as products for the pharmaceutical, medical and veterinary science, pharmaceutical and other preparations for medical or veterinary purposes; reagents, media, materials and ingredients for the preparation of media, all for medical or veterinary purposes; reagents for the processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of material, especially of biological materials, reagents with magnetic beads, antibody reagents, all for medical or veterinary purposes; buffer solutions and reagents for use with medical instruments, especially separation instruments, analysis instruments, reactor and imaging instruments; reagents for the processing of biological material, especially tissue, bone marrow, cells, blood and its components, all for medical or veterinary purposes; culture media, cell culture media, diagnostic reagents and preparations for medical and veterinary purposes; freezing media, contrast agents, contrast agents for in-vivo imaging, all for medical and veterinary purposes; pharmaceutical products, especially pharmaceutical products for the cellular therapy; chemical, biological and biochemical products for therapeutic and diagnostic purposes, including medical diagnostic purposes; reagents for cell separation, labeling reagents, reagents, media, substances and ingredients for the preparation of media, all for the use in medical laboratories, included in this class; diagnostic reagents and preparations for use in medical laboratories. (1) Services of medical, pharmaceutical or biotechnological laboratories, medical and pharmaceutical services, namely services of a medical and pharmaceutical laboratory, in particular in connection with the manufacture of cell therapeutic agents, cell compounds, cell preparation, cellular medicines, the selection, stimulation, activation of cells, as well as the manufacture of kits or reagents.
(2) Medical services, in particular the field of extracorporeal plasma therapy; medical treatment services.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Chemical, biological and biochemical products for industrial, scientific, and diagnostic purposes, namely, biological tissue cultures, diagnostic preparations for scientific use; Chemical preparations for use in separation processes for biological materials; reagents for scientific and research use, namely, reagents for cell separation, labeling reagents, and reagents for the preparation of media, all for commercial and scientific purposes and for the use in medical laboratories; chemical reagents, other than for medical or veterinary purposes with magnetic beads; chemical antibody reagents, other than for medical or veterinary purposes; buffer solutions for scientific purposes in analytical chemistry and chemical reagents, for non-medical purposes, for use with laboratory instruments, especially separation instruments, chemical analysis instruments, reactors and imaging instruments; reagents, other than for medical or veterinary purposes, for processing of biological material, especially tissue, bone marrow, cells, blood; diagnostic reagents and preparations for scientific purposes and for use in medical laboratories; cell culture media, for in-vivo imaging, all for scientific purposes; chemical reagents for non-medical purposes, namely, for use in biotechnology, in biological treatment processes and in the biotechnology industry Pharmaceutical preparations for use in treating cancer or autoimmune diseases; veterinary preparations for use in treating cancer or autoimmune diseases in household animals and horses; medicinal preparations for cancer or autoimmune diseases; Reagents and media for medical and veterinary diagnostic purposes; diagnostic reagents for medical use and veterinary diagnostic reagents, namely, reagents containing magnetic beads, antibody reagents and reagents for the processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of material, especially of biological materials; Reagents for medical use and clinical medical reagents, namely, reagents for use with medical instruments, especially separation instruments, analysis instruments, reactor and imaging instruments; reagents for the processing of biological material, especially tissue, bone marrow, cells, blood and its components, all for medical or veterinary purposes; Media for bacteriological cultures; diagnostic reagents and preparations for medical and veterinary purposes; contrast agents for in-vivo imaging, all for medical and veterinary purposes; pharmaceutical preparations for cellular therapy Medical, pharmaceutical and biotechnological laboratory services; medical laboratory services and laboratory research services relating to pharmaceuticals, in particular in connection with the manufacture of cell therapeutic agents, cell compounds, cellular medicines, and featuring the selection, stimulation, and activation of cells, as well as the manufacture of medical and scientific kits and reagents Medical services, in particular the field of extracorporeal plasma therapy; medical treatment services, namely, medical treatment of cancer or autoimmune diseases
