Abstract:
The present invention relates to formulations for administration of cannabis active agents, preferably, cannabis extracts. It provides a composition or kit comprising a plurality of cannabis active agents and a hyperbranched dendritic core-multishell-nanocarrier or core-shell nanocarrier, such as a hyperbranched dendritic polyglycerol nanocarrier, as well as corresponding pharmaceutical compositions and methods of preparing the same. Preferably, the cannabis active agents, e.g., THC and CBD, are stabilized by the nanocarrier, and their transdermal or transmucosal bioavailability is enhanced. The pharmaceutical compositions can be for use in treating a condition as a stand-alone pharmaceutical or an add-on pharmaceutical selected from the group comprising chronic pain, especially neuropathic pain, chronic inflammation, rheumatoid arthritis, diseases that are an expression of endocannabinoid deficiency, migraine, fibromyalgia, irritable bowel syndrome, Crohn's disease and ulcerative colitis, multiple sclerosis; nausea, vomiting, anxiety, Gilles-de-la-Tourette syndrome, Parkinson's disease, attention deficit disorder (ADD) post-traumatic stress disorder (PTSD) and sleep disorders, or as a potential antineoplastic therapeutic, as an add-on antiepileptic drug or for appetite stimulation.
Abstract:
The present invention relates to recombinant coagulation factors, in particular, recombinant Factor VIII (FVIII) proteins having an increased half-life. They comprise a heavy chain portion and a light chain portion of Factor VIII and at least two albumin binding domains, wherein at least one albumin binding domain is C-terminal to the heavy chain portion and at least one albumin binding domain is C-terminal to the light chain portion. If the protein is a single chain protein, the albumin binding domain(s) C-terminal to the heavy chain portion is/are N-terminal to the light chain portion. The protein of the invention may also be a de-immunized Factor VIII protein comprising specific point mutations at defined positions, which serve to reduce the immunogenicity, wherein the protein substantially retains its coagulant activity. The invention also relates to nucleic acids encoding the proteins of the invention, methods of producing them and pharmaceutical compositions comprising any of these, wherein the pharmaceutical composition preferably is for use in treatment of hemophilia A.
Abstract:
The present invention provides a composition comprising specific self-assembling peptides, which are capable of self-assembly at a pH below 7.5 and at least physiologic ionic strength, e.g., PI 1-4. PI 1-8, PI 1-14, PI 1-13, PI 1-12, PI 1-28, PI 1-29, PI 1-2, PI 1-5, PI 1-17, PI 1-19, PI 1-20, PI 1-12, PI 1-16, PI 1-18, PI 1-26 or PI 1-31 for use in treating an oral disease selected from the group consisting of gingivitis, periodontitis and/or peri-implantitis in a subject. Said composition may be used, after suitable cleaning procedures, for filling pockets formed adjacent to teeth in said diseases, which enhances tissue regeneration. The composition may be suitable for controlled release of an active agent, e.g., an antimicrobial or antibiotic agent. The invention also provides a kit suitable for said treatment further comprising self-assembling peptides suitable for forming a second layer on top of the first composition.
Abstract:
The invention relates to the field of immunology and immunotherapy, in particular, to adoptive T cell therapy of cancer utilizing T cell receptor (TCR)-engineered T cells. The invention provides novel methods and tools for identification and cloning of TCR, which are also applicable for identification of other receptors such as B cell receptors or antibodies. The invention provides immortalized cell lines able to induce subset specific (e.g. CD4 + or CD8 + specific) hybridization during co-culture, e.g., with primary lymphocytes of mice or men. The immortalized cells are engineered to express two mutated glycoproteins derived from the paramyxovirus family, namely hemagglutinin (H) and fusion (F) or a derivative thereof. H is a chimeric protein not able to bind to its natural ligands, fused to a targeting ligand capable of specifically binding to a specific cell surface antigen such as a lymphocytic subset-marking ligand (e.g. CD4 or CD8); fusion (F) mediates the fusion of cellular membranes of the immortalized cell line and cells, e.g., primary lymphocytes, H has bound to. The methods of the invention comprise preparing a hybridoma cell expressing a receptor, comprising steps of co-culturing a cell expressing a specific cell surface antigen and said receptor with the specific immortalized cells of the invention. The invention also relates to the hybridoma cells obtainable by said method.
Abstract:
The present invention relates to the field of diagnostic or analytic methods. In particular, the inventors teach that an Fc receptor for IgM heavy chains (FcμR), in particular, Faim 3/Toso or CD351, or a functional fragment thereof, which preferably comprises the Ig-like domain of Faim 3/Toso, may be used for in vitro quantification of IgM or IgA antibodies, preferably, IgM, in the form of immune complexes, i.e., complexes formed by antigen and specific antibody. These immune complexes may be formed by mixing an antigen with a sample comprising antibodies. A method for detection and quantification of IgA or IgM antibodies in the form of immune complexes is also provided. This can be useful for diagnosis of infections, e.g., with a virus.
Abstract:
The invention relates to a method for preparing a composition for treating a tooth lesion, said composition comprising peptides that are capable of undergoing self-assembly at a certain pH. The compositions of the invention are highly suitable for being used in the medical field, in particular for remineralising a tooth lesion such as a subsurface caries lesion.
Abstract:
The present invention relates to the field of blood products, in particular, to fibrinogen and fibrinogen drug products. The invention provides a fibrinogen drug product in dry, e.g., lyophilized form having a residual moisture content of 2-5% (w/w). The inventors have found that said moisture content is advantageous for viral inactivation by dry heat, which leads to a particularly virus-safe and stable product. The invention further provides a fibrinogen drug product in dry, e.g., lyophilized form, that has an especially low number of subvisible particles (SVPs), and a batch of such drug products. It suitable for reconstitution of 1 g of fibrinogen in water for injection to obtain a fibrinogen solution comprising 6000 or less SVPs having a size of 10-100 µm and 600 or less SVPs having a size of 25-100 µm. Methods of preparing the drug products of the invention are also disclosed, as well as these drug products for use in treatment of fibrinogen-deficiency.
Abstract:
The present invention relates to an ACE2 polypeptide lacking an N-linked glycosylation or comprising a truncated N-linked glyco- sylation, e.g., at an amino acid corresponding to Asn90 and/or Asn322 of SEQ ID NO: 1; its use in a treatment of a coronavirus infection and methods of manufacturing the ACE2 polypeptide.
Abstract:
The present invention relates to the field of gene therapy for the treatment of sensorineural hearing loss. In particular, the invention discloses a composition comprising a 3rd generation lentiviral vector pseudotyped with a viral envelope glycoprotein capable of binding to a receptor expressed in a cell of the inner ear for use in the treatment or prevention of sensorineural hearing loss, wherein said composition has a viral titer of at least 107TU/mL and is administered to the inner ear of a subject suffering from or in danger to undergo sensorineural hearing loss. The viral envelope glycoprotein is capable of binding to a receptor selected from the group consisting of the LDL-receptor and LDL-R family members, the SLC1 A5-receptor, the Pit1 /2-receptor and the PIRYV-G-receptor. Preferably, the viral glycoprotein is MARAV-G, COCV-G, VSV-G, VSV-G ts or PIRYV-G, most preferably, MARAV-G. The lentiviral vector further comprises a cargo sequence comprising, e.g. a protein-coding gene, a miRNA, an shRNA, a IncRNA or an sgRNA, wherein expression of said cargo sequence in the cell of the inner ear is capable of reducing, eliminating or preventing at least a symptom of sensorineural hearing loss in the subject. The invention further discloses a method for treating sensorineural hearing loss in a subject in need thereof.
Abstract:
The present invention relates to the field of nucleic acid sequencing at the single cell level, e.g., single-cell RNA sequencing (scRNA-seq). In particular, the invention provides a method of detecting nucleic acid in a fixated or non-fixated nucleic acid-containing compartment such as a eukaryotic cell or nucleus thereof, by hybridizing a plurality of single-stranded (ss)DNA oligonucleotide probes to complementary nucleic acid molecules within said compartment; removing ssDNA oligonucleotide probes from the compartment that have not specifically hybridized to nucleic acid; and identifying the ssDNA oligonucleotide probes specifically hybridized to nucleic acid molecules within said compartment by sequencing or amplification, thereby determining the corresponding nucleic acids present in said compartment. The method does not require a step of sequential ssDNA probe hybridization to the same target nucleic acid as a means for increased specificity or sensitivity, and preferably further does not require steps of RNA isolation and cDNA generation. The method of the invention has the potential to detect substantially every known and/or unknown nucleic acid species, in particular RNA, e.g., protein-encoding mRNAs as well as non-coding RNAs. The method further enables spatial mapping of detected nucleic acids, wherein the compartment is sectioned or dissociated into a single cell suspension prior to probe hybridization to obtain a collection of fractions and thus nucleic acid molecules are separated from each other depending on their localization or which cell type they belonged to. Spatial mapping of detected nucleic acids may be combined with the detection of at least one DNA locus, at least one protein, or with the analysis of chromatin condensation. The method of the invention is designated oligo-seq.