Abstract: The present invention relates to the field of genetic engineering, in particular, to a transposon-based transfection kit suitable for transfection of primary cells, such as T cells, comprising mRNA encoding a transposase, or reagents for generating mRNA encoding said transposase, as well as minicircle DNA comprising the transposon. The invention also relates to a nucleic acid, preferably, a DNA minicircle, comprising a transposon, wherein the transposon encodes a protein and at least one miRNA, wherein the sequences encoding the miRNA are located in an intron and expression of the protein and the miRNA is regulated by the same promoter. The invention also provides a population of cells obtainable with the method of the invention. Methods of transfection are also provided, as well as medical use, e.g. in immunotherapy, in particular, in adoptive T cell therapy or T cell receptor (TCR) or chimeric antigen receptor (CAR) gene therapy.

Abstract: The present invention pertains to antigen recognizing constructs against tumor specific proteasome splicing variants. The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for tumor cells carrying antigenic epitopes generated by proteasome peptide splicing of tumor specific antigens. The TCRs of the invention, and antigen binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of proliferative diseases, preferably for the treatment of cancer. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Abstract: A method of treating a medical disorder associated with the presence of pathogenic B cells expressing B cell maturation antigen (BCMA), the method comprising administering to a subject an isolated antibody or antibody fragment comprising specific VH and VL domain complementary determining region (CDR) sequences, wherein the antibody or fragment thereof specifically binds an epitope of the extracellular domain of CD269 (BCMA).

Abstract: The present invention relates to the field of immunotherapy, in particular adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer. The invention provides a nucleic acid encoding at least one T cell receptor alpha chain construct and/or TCR beta chain construct of a TCR construct capable of specifically binding to an epitope from NY-ESO-1 (also designated CTAG-1) in complex with a human MHC, wherein the TCR alpha chain construct and/or the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having at least 90% sequence identity to an amino acid selected from SEQ ID NO: 1-20. The invention provides TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC I, and, for the first time, TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC II molecules, and thus enables a combined adoptive T cell therapy with both recombinant CD4+ and re-combinant CD8+ T cells.

Abstract: The invention relates to a xanthine derivative defined by chemical formula I or a salt thereof, its use as a medicament, especially for use in the treatment of serotonin-related diseases or disorders, and a pharmaceutical preparation comprising the xanthine derivative. The novel xanthine compounds are capable of inhibiting tryptophan hydroxylases (TPH) involved in the biosynthesis of serotonin and are effective in influencing the serotonin level in the body.

Abstract: The invention relates to antibodies or antibody fragments that bind CD269 (BCMA), thereby disrupting the interaction between CD269 and its native ligands (BAFF and APRIL), and their use in the treatment of plasma cell-mediated diseases such as multiple myeloma and autoimmune diseases.

Abstract: An antisense oligonucleotide comprising a sequence targeted to the 3? untranslated region (3? UTR) of the TNFAIP3 (A20) transcript and its use as a medicament, for example in the treatment of cancer or an autoimmune disease.

Abstract: The invention relates to a xanthine derivative defined by chemical formula I or a salt thereof, its use as a medicament, especially for use in the treatment of serotonin-related diseases or disorders, and a pharmaceutical preparation comprising the xanthine derivative. The novel xanthine compounds are capable of inhibiting tryptophan hydroxylases (TPH) involved in the biosynthesis of serotonin and are effective in influencing the serotonin level in the body.

Abstract: The present invention relates to the field of analysis of the three-dimensional structure of the genome, i.e., for genome architecture mapping (GAM). The invention provides a method of determining spatial proximity of a plurality of nucleic acid loci in a compartment such as the cell nucleus, by exploiting their co-segregation amongst fractions of that compartment, identified upon separation of the nucleic acid loci from each other depending on their localization in the compartment to obtain a collection of fractions, e.g., by cryo-sectioning or cryo-milling the compartment; determining the presence or absence of the plurality of loci in the fractions; and determining the co-segregation of the plurality of loci. Co-segregation may then be analysed with statistical methods to determine spatial proximity. The method can be used e.g., for determining physical distance between a plurality of loci; and mapping loci and/or genome architecture, e.g.

Abstract: The present invention pertains to novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, which specifically bind to the melanoma associated antigen (MAGE) A1. The constructs of the invention are particularly useful for the diagnosis, prevention or therapy of tumorous diseases which are characterized by the specific expression of the MAGE-A1 antigen. Furthermore provided are nucleic acids, vectors and host cells—such as CD4 or CD8 positive T cells—which encode, comprise or present the antigen recognizing constructs of the invention. The invention thus provides new means for immune therapy, specifically adoptive T cell therapy, for treating cancer.

Abstract: The invention relates to a xanthine derivative defined by chemical formula I or a salt thereof, its use as a medicament, especially for use in the treatment of serotonin-related diseases or disorders, and a pharmaceutical preparation comprising the xanthine derivative. The novel xanthine compounds are capable of inhibiting tryptophan hydroxylases (TPH) involved in the biosynthesis of serotonin and are effective in influencing the serotonin level in the body.

Abstract: The invention relates to a xanthine derivative defined by chemical formula I or a salt thereof, its use as a medicament, especially for use in the treatment of serotonin-related diseases or disorders, and a pharmaceutical preparation comprising the xanthine derivative. The novel xanthine compounds are capable of inhibiting tryptophan hydroxylases (TPH) involved in the biosynthesis of serotonin and are effective in influencing the serotonin level in the body.

Abstract: The invention relates to humanized antibodies or antibody fragments that bind CD269 (BCMA), thereby disrupting the interaction between CD269 and its native ligands (BAFF and APRIL), and their use in the treatment of plasma cell-mediated diseases such as multiple myeloma and autoimmune diseases.

Abstract: The invention pertains to a means for downregulating or inhibiting or mislocalizing CAR in a cardiac cell for treating/curing a patient who has suffered or is predisposed to suffering a myocardial infarction (MI) or preventing myocardial infarction or complications thereof.

Abstract: The present invention refers to hyperactive variants of a transposase of the transposon system Sleeping Beauty (SB). The invention further refers to corresponding nucleic acids producing these variants, to a gene transfer system for stably introducing nucleic acid(s) into the DNA of a cell by using these hyperactive variants of a transposase of the transposon system Sleeping Beauty (SB) and to transposons used in the inventive gene transfer system, comprising a nucleic acid sequence with flanking repeats (IRs and/or RSDs). Furthermore, applications of these transposase variants, the transposon, or the gene transfer system are also disclosed such as gene therapy, insertional mutagenesis, gene discovery (including genome mapping), mobilization of genes, library screening, or functional analysis of genomes in vivo and in vitro. Finally, pharmaceutical compositions and kits are also encompassed.

Abstract: The invention relates to a xanthine derivative defined by chemical formula I or a salt thereof, its use as a medicament, especially for use in the treatment of serotonin-related diseases or disorders, and a pharmaceutical preparation comprising the xanthine derivative. The novel xanthine compounds are capable of inhibiting tryptophan hydroxylases (TPH) involved in the biosynthesis of serotonin and are effective in influencing the serotonin level in the body.

Abstract: The present invention refers to hyperactive variants of a transposase of the transposon system Sleeping Beauty (SB). The invention further refers to corresponding nucleic acids producing these variants, to a gene transfer system for stably introducing nucleic acid(s) into the DNA of a cell by using these hyperactive variants of a transposase of the transposon system Sleeping Beauty (SB) and to transposons used in the inventive gene transfer system, comprising a nucleic acid sequence with flanking repeats (IRs and/or RSDs). Furthermore, applications of these transposase variants, the transposon, or the gene transfer system are also disclosed such as gene therapy, insertional mutagenesis, gene discovery (including genome mapping), mobilization of genes, library screening, or functional analysis of genomes in vivo and in vitro. Finally, pharmaceutical compositions and kits are also encompassed.

Abstract: The invention relates to method for cultivating stem cells in vitro, comprising the following steps: providing a sample comprising stem cells and cultivating the stem cells by subjecting the sample to a treatment for a first period of time. The treatment is carried out under hypothermic conditions having a defined temperature and a defined atmosphere, wherein the temperature does not exceed 15° C. and the atmosphere has an oxygen content not exceeding 21% (v/v). Thereby, the first period of time is 4 days to 4 weeks.

Abstract: The invention relates to humanized antibodies or antibody fragments that bind CD269 (BCMA), thereby disrupting the interaction between CD269 and its native ligands (BAFF and APRIL), and their use in the treatment of plasma cell-mediated diseases such as multiple myeloma and autoimmune diseases.

Abstract: A peptide having an ED50 of less than 500 nm, in particular 10 nM to an antibody which recognizes an epitope on an extracellular ?1 loop 2 or ?2 loop1 of a human adrenoceptor wherein the antibody's binding to the epitope results in an increase of ?-secretase activity, an increased release of ?-amyolid molecules and/or cellular dysfunction of cerebral blood vessel cells, glia cells or neurons, wherein the ED50 value is measured by bioassay.