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.
The invention is directed to a light sheet microscope comprising one or more excitation laser light beams (4); a volume defined by the coordinate system (x'(8), y'(12), z'(35)) containing the object plane (1); a means (38) to form an excitation beam with a wavefront and a power/amplitude density distribution from the excitation laser light beams (4) propagating into one or more continuous or modulated or discontinuous excitation beam waists (TWI) along the x'(8) direction in the object plane (1); one or more means (6) to translate the excitation beam waists (TWI) in the object plane (1); at least one camera detector having at least one active area; a detection optics (7) to image the emission excited in the object plane (1) including the emission excited by excitation beam waists (TWI) onto the camera detector and a means to dynamically confine at least one active area on the camera detectors, characterized in that the excitation beam waists (TWI) are coherently illuminated from one side with respect to the x'(8),z'(35) plane of the volume and synchronizing the image of the emission excited by excitation beam waists (TWI) with at least active area of at least one camera detector.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
The present invention provides a pseudotyped retroviral vector particle comprising a) one envelope protein with antigen-binding activity (protein H of a CDV or protein G of a Nipah virus) fused at its ectodomain to a polypeptide that specifically binds to CD4 and/or CD8, and b) one envelope protein with fusion activity (protein F of the virus as the protein H/G), and c) a nucleic acid molecule encoding a transgene, wherein said transgene is a chimeric antigen receptor (CAR) comprising an antigen-specific targeting region, at least one transmembrane domain, and at least one intracellular signaling domain, wherein said antigen-specific targeting region comprises a first antigen binding domain, specific for a first antigen expressed on the surface of a disease-associated target cell and a second antigen binding domain specific for a second antigen expressed on the surface of said disease-associated target cell, and wherein said retroviral vector particle is a lentiviral or gammaretroviral vector particle. Preferentially said antigen binding domains of the CAR are of human origin, more preferentially the CAR has specificity for CD20 and CD19.
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.
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 about a heterodimeric synthetic transcription factor system. Importantly the domains of the synthetic transcription factor are arranged in a specific order, the system comprising a) a first exogenous nucleic acid molecule encoding a first fusion protein comprising a DNA binding domain N-terminally fused to a first binding moiety, wherein the DNA binding domain is specific for a regulatory element in the promoter operably linked to a nucleic acid encoding an effector molecule, b) a second exogenous nucleic acid molecule encoding a second fusion protein comprising a transcription regulating domain C-terminally fused to a second binding moiety, and c) an inducer molecule, wherein the first and second binding moieties are different from each other, and Wherein the first and second binding moiety are capable to dimerize in presence of the inducer molecule.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/44 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere
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
A61K 40/11 - T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cellsLymphokine-activated killer [LAK] 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
7.
METHOD FOR TARGETED GENE INSERTION INTO IMMUNE 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 combination of compositions comprising a first composition comprising a tagged polypeptide comprising an antigen binding domain specific for CD276 and a tag and a second composition comprising an immune effector cell expressing a chimeric antigen receptor (CAR) comprising an antigen binding domain specific for said tag of said tagged polypeptide. A second aspect of the invention provides a combination of compositions as disclosed herein for use in the treatment of a disease, preferentially cancer. Another aspect of the invention is a combination of compositions for use in a method of treating a disease, said method comprising administering to a subject in need thereof: a first composition comprising a tagged polypeptide comprising an antigen binding domain specific CD276 and a tag; and a second composition comprising an immune effector cell expressing a chimeric antigen receptor comprising an antigen binding domain specific for said tag of said tagged polypeptide.
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
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A system is described that leverages the advantages of TDI scanning by combining it with an innovative illumination methodology. The instrument may include a continuous stage scanning system moving the biological sample in one direction, a sample imaging system with an optical axis perpendicular to the stage scanning direction, and an optical system with an optical axis perpendicular to the stage scanning direction for applying a dynamic light pattern to induce a photochemical or a photophysical modification of the sample, wherein the photochemical or photophysical modification is used as one parameter in a subsequent analysis or processing decision on the same instrument or on a different instrument.
The invention is directed to a device for the detection of target molecules, comprising
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
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,
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
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.
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.
The present invention provides a combination of compositions comprising: A composition (A) comprising a population of immune effector cells comprising: A first exogenous nucleic acid sequence encoding a chimeric antigen receptor (CAR) comprising an antigen binding domain specific for a tag of a tagged polypeptide and a second exogenous nucleic acid sequence encoding an effector molecule operably linked to an antigen activated inducible promoter; and A composition (B) comprising a plurality of tagged polypeptides comprising an antigen binding domain specific for a target antigen expressed on the surface of a target cell and said tag, wherein said antigen-activated inducible promoter drives the expression of said effector molecule upon binding of said antigen binding domain of said CAR to said tagged polypeptide that is bound to said target antigen expressed on said target cell.
The invention is directed to a method for detecting at least one target peptide by binding to a MHC protein by providing a plurality of different MHC proteins with placeholder peptides labelled with at least one fluorescent marker thereby obtaining a plurality of labelled MHC proteins.
Method for single molecule localization microscopy (SMLM) based on conventional fluorescent binder probes, including primary or secondary antibodies, that are applied in a gradual stepwise fashion to a fixed biological sample. In each step of the process, a low dose of the probe is applied in solution to the fixed biological sample to sparsely label target epitopes followed by sample washing to remove the free probe. The remaining bound fluorescent probes that are sparsely distributed over the sample are then imaged until they are photobleached. The high light collection efficiency from each probe in this approach (limited only by photobleaching) enables few Ångstrom lateral resolution and few nm axial resolution. Photobleaching of the probes at the end of each step generates a clean slate for application of the next step in the process, as well as the possibility for applying one or more probes in a consecutive fashion to the same sample for serial SMLM.
The invention is directed to a catheter (1) for injecting a cell suspension into an organism comprising an outer canula (2) and an inner canula (3) characterized in that - the inner canula (3) is designed to be inserted into the outer canula (2) and the inner canula (3) is axially and/or rotationally movable in the outer canula (2) - the catheter is provided with a tapered shaped tip (4), - the outer canula (2) and/or the inner canula (3) is provided with at least one radial opening from which a cell suspension is injected into the organism.
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.
17.
SITE-SPECIFIC CONJUGATION OF SINGLE DOMAIN ANTIBODY FRAGMENTS (VHH) USING EQUILIBRIUM TRANSFER ALKYLATION REAGENT (ETAC)
The invention is directed to a method for providing a polypetide with a detectable label, wherein the polypetide comprises at least 5 amino acids of which a first amino acid is C (Cysteine) and at least one second amino acid is selected from the group consisting of S (Serine), T (Threonine), Y (Tyrosine), K (Lysine), H (Histidine) and R (Arginine) characterized by the steps a) initiating Michael addition between a first and a second amino acid; and b) Adding a nucleophilic agent to remove the Michael addition products between two second amino acid by retro-Michael addition.
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, 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
G01N 33/532 - Production of labelled immunochemicals
18.
BACKGROUND-FREE IMMUNOFLUORESCENCE USING TRANSIENT MOLECULE BINDERS
The invention is directed to method for detecting target epitopes on a fixed biological sample by immunofluorescence comprising the steps - immersion of the fixed biological sample in a first solution containing control probes labeled with a first fluorescent dye that do not specifically bind to the target epitopes; - acquiring a first image set containing at least one image that includes at least one region within the fixed biological sample and at least one image that includes at least one region outside of the fixed biological sample; - immersion of the fixed biological sample in a second solution containing binding probes labeled with a second fluorescent dye capable of specifically binding to the target epitopes; - acquiring a second image set containing at least one image of the at least one region within the fixed biological sample and at least one image of the at least one region outside of the fixed biological sample as in step b; followed by registering and normalization step e.
G06T 3/4053 - Scaling of whole images or parts thereof, e.g. expanding or contracting based on super-resolution, i.e. the output image resolution being higher than the sensor resolution
19.
USE OF 3'-OXYMETHYLENE ALKYL DISULFIDE PROTECTED NUCLEOTIDES FOR ENZYMATIC DNA AND RNA SYNTHESIS
This invention is about enzymatic synthesis of nucleic acids using 3′-O—(CH2SSR) protected reversible nucleotide terminators. The nucleotide base of the protected nucleotide may consist of natural or non-natural (e.g. 7-de-aza G and 7-de-aza A), or mixture thereof. The base of the nucleotides can be modified with a linker carrying carboxylic acid (—CO2H). amine (—NH2), thiol (—SH). hydroxymethyl (—CH2OH), propargy lamine. alkyne group etc. for subsequent modification and labeling. Such nucleotide substrates can be incorporated into the single strand, template free nucleic acid or into the templated DNA hybrid. And in later step the 3′-O—CH2SSR 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.
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
17 - Rubber and plastic; packing and insulating materials
Goods & Services
(1) 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.
(2) 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.
(3) 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.
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.
22.
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 protein having an antigen binding domain specific for FolRl. Specific binding of the target was shown in several different applications. Depending on the application the protein of the present invention may comprise additional structural features and/or domains. Depending on the structural features the protein having an antigen binding domain specific for FolRl may be e.g. a chimeric antigen receptor, protein drug conjugate, Bispecific T cell engager (BITE) or a detection reagent.
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
A61K 39/00 - Medicinal preparations containing antigens or antibodies
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
24.
METHODS TO IMPROVE 3D PRINTING USING TWO-COLOR POLYMERIZATION
A dual-color photoinitiator-mediated 3D printing process comprising the photopolymerization of at least one monomer at a desired spatial position on an object plane (1) in a liquid comprising the least one monomer and at least one photo initiator system capable of initiating photopolymerization of the at least one monomer by providing one or more first light beams and a second light beam having different wavelengths to the desired spatial position thereby activating the at least one photo initiator system and wherein the first and second light beams are movable relative to the desired spatial position characteriyed in that the first light beam is provided in form of a light sheet to the object plane (1).
B29C 64/124 - Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified
B29C 64/273 - Arrangements for irradiation using laser beamsArrangements for irradiation using electron beams [EB] pulsedArrangements for irradiation using laser beamsArrangements for irradiation using electron beams [EB] frequency modulated
B29C 64/277 - Arrangements for irradiation using multiple radiation means, e.g. micromirrors or multiple light-emitting diodes [LED]
The present invention provides an in-vitro method that allows to assess specificity as well as tissue cross reactivity of novel binders. i.e. antigen recognizing moieties such as antibodies or antigen binding fragments thereof, wherein said binders may be beneficially used in e.g. CAR T cell therapy.
The invention is directed to a method to incorporate barcode sequences onto biomolecules to obtain spatial location and sequence information of a target sequence of at least one m-RNA strand on a tissue sample. It uses light-directed in situ spatial deprotection and ligation of barcodes added to target molecules in desired ROIs for ex situ NGS analysis.
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
30.
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.
33.
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
34.
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
36.
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
39.
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
A61K 40/11 - T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cellsLymphokine-activated killer [LAK] cells
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
42.
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
48.
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 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 (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
53.
BIOLOGICAL CONJUGATES HAVING AN PHOTOGENERATED ACIDIC OR BASIC RELEASABLE DETECTION MOIETY ON TOP OF BIOLOGICAL TISSUES
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
59.
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 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) Chemical additives for use in the manufacture of fungicides and insecticides used in science, agriculture, horticulture and forestry; chemical preparations for use in photography; unprocessed artificial resins, unprocessed plastics; manures; fire extinguishing compositions; tempering and soldering preparations; chemical substances for preserving foodstuffs; synthetic resin adhesives for industrial purposes
(2) Scientific, optical and measuring apparatus and instruments, namely, laboratory apparatus and instruments for the separation, analysis, processing and cultivation of biological material, namely, biological microscopes; image scanners; computer hardware for data processing; computer software for use in operating medical equipment for use in the separation, analysis, processing and cultivation of biological tissue, bone marrow, cells, and blood; all the aforesaid for analysis of biological material (1) Scientific and technological services and research and design services, namely, scientific research and design of medical and laboratory equipment for others; industrial analysis and research services, namely, medical research laboratory services and laboratory research in the fields of biology and medicine; design and development of computer hardware and software for analysis of biological material.
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Reagents for medical diagnostic purposes; reagents featuring magnetic beads, antibody reagents, all being for medical or veterinary purposes; buffer solutions and reagents for use with medical apparatus, namely, separation apparatus, analysing apparatus, reactors and imaging apparatus for medical diagnostic purposes; reagents for processing biological material, namely, tissues, bone marrow, cells, blood and components thereof, all being for medical or veterinary purposes; diagnostic preparations and reagents for medical and veterinary use; cell culture media for medical and veterinary purposes; pharmaceutical preparations for cellular therapy for treating cancer and autoimmune disorders; chemical, biological and biochemical preparations used for therapeutic purposes, namely, in-vitro diagnostic (ivd) preparations for medical use; diagnostic reagents for medical or veterinary purposes
65.
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.
71.
EX-SITU SEQUENCING OF RCA PRODUCT GENERATED IN-SITU
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.
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).
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 namely, biological tissue cultures, diagnostic preparations for in vitro testing for scientific use; chemical preparations for use in separation processes for biological materials, namely, tissue, bone marrow, cells, blood; chemical reagents for use in genetic research, namely, reagents for cell separation, 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 for use in genetic research, namely, reagents for the fragmentation, processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of biological material, namely, tissue, bone marrow, cells and blood; chemical reagents with magnetic beads for use in genetic research; antibody reagents for scientific purposes; buffer solutions and chemical reagents for use with laboratory instruments, especially fragmentation or separation instruments, analysis instruments, reactors and imaging instruments; in vitro diagnostic reagents for scientific purposes; cell culture media and contrast agents for in-vivo imaging, all for scientific purposes; chemical reagents for use in genetic research in the fields of biological treatment processes and in the biotechnology industry.
(2) Scientific, optical and measuring apparatus and instruments, namely, laboratory apparatus and instruments for the separation, analysis, processing and cultivation of biological material, namely, biological microscopes; computer software for use in operating medical equipment for use in the separation, analysis, processing and cultivation of biological tissue, bone marrow, cells, and blood; scientific, electrical and electronic laboratory instruments for conducting enzymatic reactions, namely, spectrophotometers for laboratory use; laboratory devices, namely, flow cytometer for measuring physical and chemical properties of cells and other particles in suspensions; tissue fragmentation machines for scientific purposes and research, namely, for conducting tissue biopsy; tissue fragmentation vessels being test tubes for scientific purposes and research; sterile bags for laboratory use for transporting liquid or solid samples for use in cryopreservation; test tubes for cryopreservation for laboratory use; apparatus and instruments for scientific purposes, namely, magnetic separators and optical microscopes for scientific purposes.
(3) Magnetic cell separators for medical purposes; medical tubing; blood collection bags for medical purposes, sheets for medical use, medical tubing and needleless connectors for cryopreservation; dialysis machines; parts and components of dialysis machines; blood transfusion apparatus; blood drawing apparatus; parts and components of blood transfusion and blood drawing apparatus; tissue fragmentation machines for medical use, namely, for conducting tissue biopsy; medical instruments for general examination; surgical instruments.
74.
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
75.
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, medical and veterinary preparations, namely, diagnostic preparations for clinical laboratory use for the purpose of early recognition and characterization of diseases; clinical diagnostic reagents, contrast media for in vivo imaging, and diagnostic agents for the preparation of contrast media for in vivo imaging, all for medical and veterinary purposes; chemical, biochemical and diagnostic reagents for the processing, separation, isolation, enrichment, depletion, detection, screening, analysis and counting of biological tissue, bone marrow, cells, and blood, diagnostic reagents with magnetic beads, and antibody reagents, all the foregoing for medical or veterinary purposes; cell culture media for the processing of biological material, especially tissue, bone marrow, cells, blood and its components, all for medical laboratory use and veterinary research; blood culture media, cell culture media, and clinical diagnostic reagents for medical and veterinary purposes; diagnostic preparations for clinical laboratory use; cryopreservation cell freezing media for medical and veterinary purposes, contrast agents for diagnostic ultrasound imaging all for medical and veterinary purposes; pharmaceutical products, for the cellular therapy, namely, pharmaceutical products for the treatment of cancer, immunologic diseases, namely, autoimmune diseases, immunologic deficiency syndromes, bacterial skin infections, fungal skin infections, viral skin infections, parasitic skin infections and neurological diseases, namely, Alzheimer's, Huntington's Disease, cerebral palsy and cardiovascular diseases; chemical, biological and biochemical products for therapeutic and diagnostic purposes, namely, diagnostic preparations made from chemicals and biochemicals for medical purposes for the treatment of cancer and biological preparations for the therapeutic treatment of cancer, immunologic diseases, namely, autoimmune diseases, immunologic deficiency syndromes, bacterial skin infections, fungal skin infections, viral skin infections, parasitic skin infections and neurological diseases, namely, Alzheimer's, Huntington's Disease, cerebral palsy and cardiovascular diseases; contrast agents for magnetic resonance imaging; sanitary preparations for medical purposes for the treatment of autoimmune diseases, immunologic deficiency syndromes, bacterial skin infections, fungal skin infections, viral skin infections, parasitic skin infections; medical and surgical plasters, plasters as materials for dressings; material for stopping teeth, dental wax; all purpose disinfectants for use with medical instruments; preparations for destroying vermin; fungicides, herbicides.
(2) Scientific, optical and measuring apparatus and instruments, namely, laboratory apparatus and instruments for the separation, analysis, processing and cultivation of biological material, namely, biological microscopes; scientific, electrical and electronic laboratory instruments for conducting enzymatic reactions, namely, spectrophotometers for laboratory use; laboratory equipment, namely, cytometer for measuring physical and chemical properties of cells and other particles in suspensions.
(3) Apparatus for magnetic cell separation for medical purposes, namely, magnetic columns for laboratory use, medical drainage and transfusion tubing, medical diagnostic apparatus in the nature of columns for cell analysis for medical purposes, medical sacks, bags, surgical sterile sheets, tubes and tubing connectors for medical, scientific and biotechnological purposes, namely, for tissue and blood collection for cryopreservation, apparatus and instruments for medical, biotechnological and scientific purposes, namely, medical instruments for general examination, spare structural parts for the aforesaid goods; dialysis machines for medical use; apheresis machines for medical use; surgical apparatus, namely, surgical instruments; dental instruments; medical apparatus and instruments, namely, medical instruments for apheresis; artificial limbs, eyes and teeth; suture materials.
77.
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
80.
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
86.
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
92.
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
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
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 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.
