Abstract

The present disclosure pertains to an in vitro method for the diagnostic classification of cancer based on the biological state of specific genomic sites. The disclosure provides a method that allows for a classification of a tumour sample obtained from a patient by analysing a multitude, preferably genome wide, collection of gene sites, combining the biological state of the analysed gene sites into a biological state pattern and comparing with pre-determined biological state patterns pertaining to different cancer types or tumour species. The disclosure is in particular useful for classifying cancer e.g. of the central nervous system, such as brain tumour samples and tumours of the spinal cord, since these are characterized by a large variety of distinct tumour species which have different prognostic values and require a developed treatment regime for each species in the clinical context. However, other cancers could similarly profit from the disclosure, for example sarcomas.

IPC Classes  ?

• G06N 20/20 - Ensemble learning
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G16B 40/20 - Supervised data analysis
• G16B 40/30 - Unsupervised data analysis
• G06F 9/50 - Allocation of resources, e.g. of the central processing unit [CPU]
• G06F 15/78 - Architectures of general purpose stored program computers comprising a single central processing unit
• G06N 20/10 - Machine learning using kernel methods, e.g. support vector machines [SVM]
• G06N 3/02 - Neural networks

Abstract

The present disclosure relates to a computer-implemented method for cancer diagnosis, comprising: a) selectively sequencing polymers of a biological sample according to at least one target gene site by translocating the polymers through nanopores of a nanopore sequencing system, including: (i) analyzing an initial nucleotide sequence of a first polymer of the biological sample while the first polymer is translocating through a nanopore of the nanopore sequencing system to determine whether the initial nucleotide sequence corresponds to the at least one target gene site; and (ii) continuing the sequencing of the first polymer to obtain measurement data of the first polymer only if the initial nucleotide sequence of the first polymer corresponds to the at least one target gene site; b) determining, based on the measurement data, a biological state of a nucleotide sequence of the first polymer corresponding to the at least one target gene site; and c) classifying a cancer using a classification algorithm based on the biological state of the nucleotide sequence of the first polymer, wherein the classification algorithm is trained based on the at least one target gene site and biological state data pertaining to cancer types.

IPC Classes  ?

• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 40/10 - Signal processing, e.g. from mass spectrometry [MS] or from PCR
• G16B 40/20 - Supervised data analysis

Abstract

The present invention relates to a method for attaching a 5'-nicotinamidnucleobasedinucleotide (NND)- capped nucleic acid sequence to a fusion protein or to a complex, comprising (a) contacting (i) a heterologous fusion protein which comprises a poly(peptide) of interest being fused to a tag, or (ii) a complex wherein a protein is under physiological conditions complexed with a tag with the 5'-NAD- capped nucleic acid sequence and an ADP-ribosyltransferase (ART) under conditions wherein the 5'- NND-capped nucleic acid sequence is covalently attached to the tag, wherein the tag comprises a recognition motif of the ART and preferably comprises or consists of (i) SEQ ID NO: 1 or a sequence being at least 80% identical thereto provided that the underlined Arg in the amino acid motif DVRPVRD (SEQ ID NO: 7) is conserved and preferably SEQ ID NO: 7 is conserved; (ii) SEQ ID NO: 2 ora sequence being at least 80% identical thereto provided that the underlined Arg in the amino acid motif DVRPVRD (SEQ ID NO: 7) is conserved and preferably SEQ ID NO: 7 is conserved; (iii) SEQ ID NO: 3 or a sequence being at least 80% identical thereto provided that the underlined Arg in the amino acid motif DVRPVRD (SEQ ID NO: 7) is conserved and preferably SEQ ID NO: 7 is conserved; (iv) SEQ ID NO: 4 or a sequence being at least 80% identical thereto provided that the underlined Arg in the amino acid motif LADGVEGYLRASEASRDRVE (SEQ ID NO: 8) is conserved and preferably SEQ ID NO: 8 is conserved; (v) SEQ ID NO: 5 or a sequence being at least 80% identical thereto provided that the underlined Arg in the amino acid motif LADGVEGYLRASEASRDRVE (SEQ ID NO: 8) is conserved and preferably SEQ ID NO: 8 is conserved; or (vi) SEQ ID NO: 6 or a sequence being at least 80% identical thereto provided that the underlined Arg in the amino acid motif LADGVEGYLRASEASRDRVE (SEQ ID NO: 8) is conserved and preferably SEQ ID NO: 8 is conserved.

IPC Classes  ?

• C12P 21/00 - Preparation of peptides or proteins
• C07K 1/107 - General processes for the preparation of peptides by chemical modification of precursor peptides
• C07K 19/00 - Hybrid peptides
• C12N 9/10 - Transferases (2.)
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides

Abstract

The present invention relates to a method of identifying a T-cell reactive to cells presenting a T-cell activating antigen (cancer-reactive T-cell), comprising (a) determining expression of at least one of CCL4, CCL4L2, CCL3, CCL3L1, and CXCL13 in T-cells from a sample of a subject; and (b) identifying a cancer-reactive T-cell based on the determination of step (a). The present invention also relates to a method of identifying a TCR binding to a cancer cell of a subject, said method comprising (A) identifying a cancer reactive T-cell according to the afore-said method (B) providing the amino acid sequences of at least the complementarity determining regions (CDRs) of the TCR of the cancer-reactive T-cell identified in step (A); and, hereby, (C) identifying a TCR binding to a cancer cell. The present invention further relates to further methods and cancer-reactive T-cells related thereto.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The invention relates to the use of a recombinant porcine adeno-associated virus (AAV) vector comprising a peptide-modified porcine AAV serotype 1 (AAVpo1) capsid in gene therapy of muscle and/or central nervous system (CNS) disorders, in particular neuromuscular diseases such as genetic neuromuscular diseases.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to conjugate compounds which comprise a peptide moiety (a) which is preferably a hydrophobic modified preS-derived peptide of hepatitis B virus or a respective cyclic peptide, and a NTCP substrate moiety (b), which is preferably a bile acid. The present invention further relates to pharmaceutical compositions comprising at least one conjugate compound. The present invention further relates to medical uses of said conjugate compounds and the pharmaceutical compositions, such as in the diagnosis, prevention and/or treatment of a liver disease or condition, and/or in the inhibition of HBV and/or HDV infection. The present invention further relates to methods of diagnosis, prevention and/or treatment of a said diseases and/or infections.

IPC Classes  ?

• C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• A61P 31/20 - Antivirals for DNA viruses

Abstract

The invention relates to a method for producing an osteotropic bone replacement material from a starting material which substantially has portlandite, calcium oxide, aragonite, calcite, and/or apatite. The starting material is introduced into an autoclave together with a strontium, fluorine, and/or gallium source. A phosphate source is introduced while using a starting material which substantially has portlandite, calcium oxide, aragonite, calcite, and/or apatite. Additionally, H2O is added into the autoclave as part of a solvent, and the pH value in the autoclave is set to a range above 7. The closed and filled autoclave is then heated for at least one hour and then cooled. The osteotropic bone replacement material produced in this manner is then cleaned of phosphorus, strontium, fluorine, and/or gallium source residue. The invention also relates to an osteotropic bone replacement material which substantially consists of apatite and in which strontium ions are incorporated into the crystalline lattice.

IPC Classes  ?

• A61L 27/12 - Phosphorus-containing materials, e.g. apatite
• C01B 25/32 - Phosphates of magnesium, calcium, strontium, or barium

Abstract

The present invention relates to pharmaceutical compositions with isolated and treated whole blood cells or Peripheral Blood Mononuclear Cells (PBMCs) as well as such pharmaceutical compositions for use in the prevention and / or treatment of organ or cell graft rejection in a human graft recipient.

IPC Classes  ?

• A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
• A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention relates to a method for diagnosing or prognosing cancer comprising determining in vitro cytosine methylation levels within marker genes and/or determining expression levels of miRNA markers.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The present invention relates to a polynucleotide comprising an expressible nucleic acid sequence encoding a relaxin family peptide receptor (RXFP) polypeptide for use in treatment and/or prevention of heart failure in a subject. The present invention further relates to a vector comprising the polynucleotide of the present invention for use in treatment and/or prevention of heart failure, as well as to host cells, RXFP agonists, kits and devices related thereto.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61K 38/22 - Hormones
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• C12N 15/861 - Adenoviral vectors

Abstract

The present invention relates to an adeno-associated virus (AAV) capsid polypeptide bonded to a binding peptide comprising an amino acid sequence RGDX1X2 X3 X4, with X1 to X4 being independently selected amino acids, for use in treating and/or preventing a muscular disease and/or in muscle regeneration. The present invention further relates to polynucleotides, host cells, adeno-associated virus (AAV) capsids, pharmaceutical compositions, uses, and methods related to said AAV capsid polypeptide.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• C07K 14/015 - Parvoviridae, e.g. feline panleukopenia virus, human parvovirus
• C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
• C12N 15/864 - Parvoviral vectors

Abstract

The present invention relates to a compound of formula (I), a pharmaceutical composition comprising or consisting of said compound, a kit comprising or consisting of said compound or pharmaceutical composition and use of the compound or pharmaceutical composition in the diagnosis or treatment of a disease characterized by overexpression of fibroblast activation protein (FAP).

IPC Classes  ?

• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

Abstract

The invention relates to recombinant adeno-associated virus (rAAV) virions for gene therapy, wherein the rAAV virions comprise a novel capsid protein. In particular,the invention relates to the use of such virions in gene therapy for the treatment of an arthritic disease, such as for example rheumatoid arthritis, or symptoms thereof, preferably by intraarticular administration.

IPC Classes  ?

• A61K 35/76 - Viruses; Subviral particles; Bacteriophages
• C12N 15/68 - Stabilisation of the vector

Abstract

A body fluid leakage detection aqueous composition, for use e.g. in intraoperative pancreatic fluid leakage detection. The composition comprises a gelling agent, increasing the viscosity of the composition, and buffering species, the composition thereby being buffered. The gelling agent is cross-linked a-glucan microspheres. Further, the composition comprises a pH-indicator. The pH of the composition is at least 0.1 pH units lower, or higher, than a pKa of the pH-indicator.

IPC Classes  ?

• A61K 49/00 - Preparations for testing in vivo

Abstract

The invention refers to a method for in vitro diagnosis of a severe infection comprising determining delta-like ligand 1 protein or a nucleotide sequence coding for delta-like ligand 1 protein in a biological sample wherein an elevated level of expression of delta- like ligand 1 protein or a nucleotide sequence coding for delta-like ligand 1 protein is indicative of a severe infection; and the use of delta-like ligand 1 protein as a biomarker for in vitro diagnosis of a severe infection such as sepsis.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Abstract

The present invention relates to a polynucleotide comprising (i) a sequence encoding an anti- CRISPR (Acr) polypeptide and (ii) an miRNA target sequence and to vectors and host cells related thereto. The present invention further relates to a kit comprising (I) a first polynucleotide comprising (i) a sequence encoding an anti-CRISPR (Acr) polypeptide and (ii) an RNA-interference (RNAi) target sequence; and a Cas nuclease or a second polynucleotide comprising an expressible gene encoding a Cas nuclease; (II) a first polynucleotide comprising (i) a sequence encoding an anti-CRISPR (Acr) polypeptide and (ii) an RNA- interference (RNAi) target sequence, said first polynucleotide further comprising an expressible gene encoding a first fragment of a Cas nuclease, and a second polynucleotide comprising an expressible gene encoding a second fragment of a Cas nuclease, wherein said first and second fragment of said Cas nuclease together reconstitute an active Cas nuclease; or (III) a first polynucleotide comprising (i) a sequence encoding an anti-CRISPR (Acr) polypeptide, (ii) an RNA-interference (RNAi) target sequence, and (iii) a sequence encoding a Cas nuclease; and a second polynucleotide comprising an expressible gene encoding an inhibitory RNA, preferably a siRNA or a miRNA hybridizing to said RNAi target sequence, more preferably a siRNA hybridizing to said RNAi target sequence. Further, the present invention relates to methods and uses related to the aforesaid means.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 9/22 - Ribonucleases
• C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• C07K 14/01 - DNA viruses

Abstract

The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding an IL-12 polypeptide, wherein said IL-12 polypeptide is an IL-12 fusion polypeptide comprising a p35 subunit of an IL-12 and a p40 subunit of an IL-12; to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.

IPC Classes  ?

• C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
• A61K 38/20 - Interleukins
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding a multispecific binding polypeptide, said multispecific binding polypeptide comprising a first binding domain binding to a surface molecule of an immune cell with antitumor activity, preferably a lymphocyte, more preferably a T cell or a dendritic cell, and a second binding domain binding to a tumor-associated antigen; to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.

IPC Classes  ?

• C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
• C12N 5/078 - Cells from blood or from the immune system
• A61K 35/76 - Viruses; Subviral particles; Bacteriophages
• A61P 35/00 - Antineoplastic agents
• 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
• C07K 16/46 - Hybrid immunoglobulins
• C12N 15/45 - Paramyxoviridae, e.g. measles virus, mumps virus, Newcastle disease virus, canine distemper virus, rinderpest virus, respiratory syncytial viruses
• C12N 15/62 - DNA sequences coding for fusion proteins
• C12N 15/86 - Viral vectors
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants

Abstract

The present invention relates to the multispectral imaging of samples, in particular of biological tissues. The invention further relates to a method for acquisition of fluorescence images and reflection images of an object (400) comprising the steps of alternatingly illuminating the object (400) with at least a first light and a second light, wherein the first light and the second light are spectrally shaped such that at least one light has several spectral regions of high light intensity separated by spectral region(s) of low light intensity, wherein the spectral regions of the first light and the second light with high intensity at least partially do not overlap and wherein at least one of the two lights has at least one region of low light intensity that is of longer wavelength to the neighboring region of high light intensity, and recording at least a first image of the object (400) and a second image of the object (400) while illuminating the object (400) with at least one of the lights wherein the light to be recorded as the first image is modified such, that at least one spectral region of high intensity of the second light is attenuated, and wherein the light to be recorded as the second image is modified such, that at least one spectral region of high intensity of the first light is attenuated.

IPC Classes  ?

• G01J 3/443 - Emission spectrometry
• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
• G01J 3/42 - Absorption spectrometry; Double-beam spectrometry; Flicker spectrometry; Reflection spectrometry
• A61B 1/04 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances

Abstract

The present invention relates to the multispectral imaging of samples, in particular of biological tissues. The invention further relates to a method for acquisition of fluorescence and reflectance images of an object (400) comprising the steps of alternatingly illuminating the object (400) with at least a first light having several spectral regions of high intensity, wherein the first light has at least one region of low intensity that is of longer wavelength to a region of high intensity, and at least a second light having at least one spectral region of high intensity, recording a first image of the object during illumination of the object with the first light and a second image of the object during illumination of the object with the second light using a common sensor array (200), wherein the light recorded by the sensor array (200) is attenuated in at least one of the spectral regions in which the first light has high intensities.

IPC Classes  ?

• G01N 21/64 - Fluorescence; Phosphorescence
• A61B 90/20 - Surgical microscopes characterised by non-optical aspects
• A61B 1/04 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
• A61B 1/06 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements
• G01N 21/55 - Specular reflectivity
• G01N 21/954 - Inspecting the inner surface of hollow bodies, e.g. bores

Abstract

In a diagnostic method for the prediction of tumor prognosis including the likelihood of formation of metastases or of relapse or local recurrence in tumor related diseases in a mammal and the provision of a therapy recommendation for a patient the enzyme activity of key enzymes of the energy metabolism is determined in fresh tumor tissue or fresh tumor cell mass after 24 hours incubation in a cell culture medium to reduce nutrition, drug and biopsy/surgery effects on the energy metabolism of the tissue slices or the cell mass, the quotients of enzyme activity of anaerobic enzymes are put in ratio to the enzyme activity of aerobic enzymes or vice versa, said ratio can be taken into account for prognosis of metastasis and a therapy recommendation.

IPC Classes  ?

• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer