Abstract

The present invention relates to a combination therapy of an IGF1R inhibitor together with an Akt inhibitor for the treatment of cancer, such as colorectal cancer, ovarian cancer, and endometrial cancer.

IPC Classes  ?

• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61P 35/00 - Antineoplastic agents

Abstract

A method of processing detected images comprises obtaining measurement data comprising at least one image generated based on a signal captured by a detector, theat least one image comprising a plurality of data values, each data value being associated with a spatial location having a distance to the detector. A first segmentation comprises first segmentation values, each first segmentation value being associated with the spatial location having the distance. A second segmentation comprises second segmentation values, each second segmentation value being associated with the spatial location having the distance. Weights are based on the distances of the spatial locations to the detector. The first segmentation values compared to the second segmentation values obtains comparison results associated with the spatial locations. A quantification of a difference between the first segmentation and the second segmentation based on the weights and the comparison results is calculated.

IPC Classes  ?

• G06T 7/11 - Region-based segmentation
• G06T 7/143 - SegmentationEdge detection involving probabilistic approaches, e.g. Markov random field [MRF] modelling

Abstract

The present invention is in the field of triacylglyccrol synthesis. In particular the invention relates to the identification of DIESL as a new triacylglycerol synthase. The invention also relates to the identification of TMX1 as a negative regulator of DIESL mediated triacylglycerol synthesis. Screening assays for identifying agents that modulate the activity of DIESL and/or of TMX1, or that modulate the interaction between DIESL and TMX1 are also provided.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• A01K 67/0276 - Knock-out vertebrates
• C12N 9/90 - Isomerases (5.)
• C12P 7/6445 - Glycerides
• C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
• C12Q 1/533 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving isomerase

Abstract

Provided are methods involved in assessing homologous recombination deficiency (HRD) status in a patient having ovarian cancer based on the determination of copy number variations (CNVs) in a genomic locus. Furthermore methods for predicting a patient's response to an anti-cancer therapy and thus to the identification of ovarian cancer patients likely to respond to a particular cancer treatment regime based on their HRD status are provided.

IPC Classes  ?

• G16B 20/10 - Ploidy or copy number detection
• G16H 20/10 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
• G16H 40/67 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation

Abstract

Described herein is a method of treating or preventing cancer in a subject wherein the cancer has functional suppression of CDS1, the method comprising administering a therapeutically effective amount of a CDS2 inhibitor to the subject Also described are methods for predicting whether a subject having cancer, wherein the cancer has functional suppression of CDS1, is likely to respond to treatment with a CDS2 inhibitor; as well as methods of selecting, and identifying and treating a subject likely to respond to treatment with a CDS2 inhibitor. Also disclosed are methods of screening for a compound for use in treatment of cancer.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• 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 an inducer of senescence, in combination with a short-lived, selective Death Receptor 5 (DR5) agonist, for use in a method of treating a patient suffering from a tumor. The invention further relates to a pharmaceutical composition, comprising a short-lived, selective Death Receptor 5 (DR5) agonist and, optionally, an inducer of senescence. The invention further relates to methods of treating a patient having a tumor, and to a selective, short-lived DR5 agonist, for use in a method of selectively killing senescent cells, including senescent cancer cells.

IPC Classes  ?

• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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

Abstract

A personalized implant for bone replacement comprises an implant body as a reconstruction of a bone portion. The implant body comprises a closed cavity and a solid impervious layer of material defining an outside surface of the implant body exposed to an exterior of the implant. The solid impervious layer fully encloses the closed cavity inside the implant body. The closed hollow interior can comprise an open support structure to reinforce the solid outside layer.

IPC Classes  ?

• A61F 2/28 - Bones
• A61F 2/30 - Joints

Abstract

A first surgical instrument cooperates with a second surgical instrument. The first instrument comprising a needle having a form of a hollow shaft comprising an outer wall around an inner cavity, an interior of the needle providing a space for positioning the second surgical instrument coaxially to the needle at least partly inside the needle and movable with respect to the needle in an axial direction of the needle. A tissue analysis device comprising an analysis sensor to analyse non-removed tissue at a distal tip of the needle. The tissue analysis device is configured to provide a sensor signal representative of an analysed characteristic of the tissue, in particular for the presence of unhealthy tissue or cancer cells within the tissue.

IPC Classes  ?

• A61B 10/02 - Instruments for taking cell samples or for biopsy
• A61B 10/00 - Instruments for taking body samples for diagnostic purposesOther methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determinationThroat striking implements
• A61B 17/32 - Surgical cutting instruments
• A61B 34/20 - Surgical navigation systemsDevices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis
• A61B 34/30 - Surgical robots

Goods & Services

Pharmaceutical, medical and medicinal preparations; medical substances; pharmaceutical preparations and substances for the treatment of cancer.

Goods & Services

(1) Pharmaceutical, medical and medicinal preparations; medical substances; pharmaceutical preparations and substances for the treatment of cancer.

Goods & Services

Pharmaceutical, medical and medicinal preparations; medical substances; pharmaceutical preparations and substances for the treatment of cancer.

Abstract

A hand-held device (100) has a housing (200). The housing (200) comprises a first compartment (210) containing at least one first optical coupler (212) configured to transmit a light signal into an elongated optical component (300), at least one second optical coupler (213) configured to receive a light signal from the elongated optical component (300), an optical sensor (410) optically connected to the at least one second optical coupler (213), and configured to detect the received light signal, a processor (420) configured to generate a parameter based on a signal generated by the optical sensor (410).. The housing further comprises a second compartment (220) containing a placeholder (222) configured to receive at least a placement member (302) of the elongated optical component (300).

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• A61B 10/02 - Instruments for taking cell samples or for biopsy
• G01J 3/02 - SpectrometrySpectrophotometryMonochromatorsMeasuring colours Details

Abstract

The current invention relates to the identification of specific T cells, antigen-presenting cells (APC) and/or tumor cells in T cell clusters identified in a sample obtained from a subject having cancer or being suspected of having cancer. The T cells and/or APC identified with the current invention are useful in the treatment of cancer, in particular in the subject from which the sample was obtained, for example in adoptive T cell therapy (ACT), for example but not limited to TIL therapy. The TCR from the T cells identified with the current invention may be used in preparing engineered T cells that are likewise useful in the treatment of cancer.

IPC Classes  ?

• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61P 35/00 - Antineoplastic agents
• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C12N 5/0784 - Dendritic cellsProgenitors thereof
• C12N 5/09 - Tumour cells

Abstract

This invention pertains in general to the production of biologicals using genetically modified cells, including genetically modified immune cells. The engineered cell, for example T cell, comprises a receptor, for example a chimeric antigen receptor, capable of receiving an activating signal, for example binding with an antigen. The cell further comprises a chimeric protein comprising a docking domain that is able to bind to the receptor and thereby inhibits signal transduction that is normally induced when the receptor receives the activating signal. The chimeric protein further comprises a drug-regulated protein stability domain. The cell further comprises an inducible promoter operably linked to a nucleic acid encoding a protein of interests (for example, a biological), wherein the inducible promoter is induced when the receptor receives an activating signal in the absence of the chimeric protein. A drug capable of regulating the drug-regulated protein stability domain regulates stability and levels of the chimeric protein, and therewith production of the biological.

IPC Classes  ?

• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• 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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C12N 15/86 - Viral vectors

Abstract

An image processing method comprises dividing (605) a plurality of pixels of an image into a first subset of pixels and a second subset of pixels. The image intensity of each pixel in the first subset is decomposing (606) using a variance of an image intensity of the pixels in a local neighbourhood of each pixel, to obtain at least one image property of each pixel in the first subset. Said at least one image property is spatially interpolated (607) to obtain said at least one image property in respect of at least one pixel in the second subset of pixels. The method further comprises decomposing (608) the image intensity of said at least one pixel in the second subset of pixels using the interpolated at least one image property of said at least one pixel in the second subset of pixels.

IPC Classes  ?

• G06T 5/00 - Image enhancement or restoration

Abstract

This invention relates to a method of measuring gene promotor activity and a training data set consisting of promoter activity measurements for each of a plurality of DNA fragments. The invention also relates to a computer-implemented method for predicting gene promoter activity; and computer-readable storage medium or a computer program comprising computer-executable instructions which when executed by a computing system, are capable of causing the computing system to perform the method. The invention also relates to a computer-implemented method for training a deep learning (DL) model to predict gene promoter activity and the resulting trained model. Lastly, the invention also relates to various uses of the computer-implemented method for predicting gene promoter activity including predicting the effect of a carcinogenic mutation in a genome.

IPC Classes  ?

• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C40B 40/06 - Libraries containing nucleotides or polynucleotides, or derivatives thereof
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 25/00 - ICT specially adapted for hybridisationICT specially adapted for gene or protein expression
• G16B 40/20 - Supervised data analysis

Abstract

A tumor sensor system having an implantable probe and an auxiliary device, the probe having at least one sensor configured to generate an electric signal in response to a physical stimulus, the at least one sensor having a position sensor configured to sense a signal from a position tracking system, the sensed signal indicative of a position of the probe in a space, the position sensor having at least one electromagnetic sensor configured to cooperate with an external electromagnetic field generator, and the at least one electromagnetic sensor is configured to detect a property of the electromagnetic field and send it as an electric signal to the processing circuit, at least one antenna for data communication by means of inductive communication, an energy harvesting coil, and transmitting the data via the at least one antenna to the auxiliary device.

IPC Classes  ?

• A61B 34/20 - Surgical navigation systemsDevices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis
• A61B 5/06 - Devices, other than using radiation, for detecting or locating foreign bodies

Abstract

The invention relates to methods of producing at least one out-of-frame peptide of 5-40 amino acid residues by a cell, and to methods of identifying said at least one out-of-frame peptide. The invention further relates to the identified out-of-frame peptides, and epitopes and polyepitopes encompassing at least one of said out-of-frame peptides, and to a nucleic acid molecule encoding at least one of said out-of-frame peptides. The invention further relates to methods of inducing an immune response against at least one out-of-frame peptide, method of treating an individual suffering from a tumor, comprising providing said individual with at least one out-of-frame peptide, and to a pharmaceutical composition, comprising at least one out-of-frame peptide. The invention additionally relates to a kit for detecting expression of at least one out-of-frame peptide, and to methods of typing an individual for presence or absence of a cell that expresses at least one out-of-frame peptide.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
• C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans

Abstract

This invention pertains in general to therapy using pre-treated T cells and/or vesicles secreted by these T cells. In particular there is provided for the use of such pre-treated T cells and/or vesicles secreted by these T cells as a medicament. The pre-treated T cells and/or vesicles secreted by these T cells are useful in the treatment of various conditions including cancer. In particular the pre-treated T cells and/or vesicles secreted by these T cells are useful in therapy that is aimed at preventing adverse effects such as neuropathy that is normally induced by the use of antimitotic agents such as taxanes and vinca alkaloids. The invention also pertains to a method of producing the pre-treated T cells and/or vesicles secreted by these T cells of the invention.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
• A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system

Abstract

A surgical forceps comprises a first jaw (101) and a second jaw (102), the first jaw (101) and the second jaw (102) being configured to be rotated relative to each other around an axis of rotation (104). A position sensor (105) is capable of sensing a first orientation with respect to a first axis (106) and a second orientation with respect to a second axis (107) different from the first axis (106), wherein the first axis (106) and the second axis (107) are orthogonal to the axis of rotation (104). The surgical forceps comprises a stapler (108) for stapling a tissue grasped by the surgical forceps (100) and a cutter (103) for cutting the tissue grasped by the surgical forceps (100) along a line.

IPC Classes  ?

• A61B 17/072 - Surgical staplers for applying a row of staples in a single action, e.g. the staples being applied simultaneously
• A61B 17/068 - Surgical staplers
• A61B 17/295 - Forceps for use in minimally invasive surgery combined with cutting implements
• A61B 18/14 - Probes or electrodes therefor
• A61B 34/00 - Computer-aided surgeryManipulators or robots specially adapted for use in surgery
• A61B 34/20 - Surgical navigation systemsDevices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis

Abstract

The present invention relates to a P2Y purinoceptor 2 (P2RY2) activity modulator for use in T cell immunotherapy. The present invention further relates to a polynucleotide encoding a P2RY2 activity modulator and to a host cell comprising the P2RY2 activity modulator for use in T cell immunotherapy. Furthermore, the present invention relates to a method of identifying 5 a subject amenable to T cell immunotherapy comprising (A) determining in a sample of said subject the activity of P2RY2; (B) comparing the activity determined in step (A) to a reference; and identifying a subject amenable to T cell immunotherapy based on the comparison of step (B), as well as to a method for identifying a P2RY2 activity modulator, said method comprising (I) contacting a host cell with a candidate compound suspected to be a P2RY2 activity 10 modulator; (II) determining B7-H3 activity in said host cell; (III) comparing the B7-H3 activity determined in step (II) to a control; and (IV) identifying a P2RY2 activity modulator based on the comparison in step (III).

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
• A61P 35/00 - Antineoplastic agents
• A61P 37/00 - Drugs for immunological or allergic disorders

Abstract

This invention provides compositions of (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, checkpoint kinase 1 (“CHK1”) inhibitor, B-cell lymphoma-extra large (“BCL-xL”) inhibitor, BCL-xL proteolysis-targeting chimera (“BCL-xL PROTAC”), pan-BCL inhibitor or ataxia telangiectasia and Rad3-related (“ATR”) inhibitor. This invention further provides methods for treating cancer or for preventing, inhibiting, or reducing risk of metastasis of a cancer, such as colorectal cancer, cholangiocarcinoma, pancreatic cancer or ovarian cancer, using (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, CHK1 inhibitor, BCL-xL inhibitor, BCL-xL PROTAC, pan-BCL inhibitor or ATR inhibitor.

IPC Classes  ?

• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

This invention pertains in general to novel zinc finger degron sequences wherein the zinc finger degron comprises at least one non-natural zinc finger domain in the form of a hybrid composed of a first portion from a first zinc finger and a second portion form a second zinc finger, preferably wherein the first portion comprises a beta-hairpin of a first zinc finger and the second portion comprises an alpha-helix of a second zinc finger. In a preferred embodiment the degron tag comprises a further, second, non-natural hybrid zinc finger domain.

IPC Classes  ?

• C12N 15/62 - DNA sequences coding for fusion proteins
• 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
• C12N 9/10 - Transferases (2.)

Abstract

A system for image reconstruction comprises a memory for storing data and instructions and a processor system. The system obtains measured data y defined in a dual space, the measured data relating to a primal space. The system determines dual parameters defined in the dual space based on the measured data and primal parameters defined in the primal space based on back- projection of the dual parameters. The system updates the primal parameters and the dual parameters, by obtaining auxiliary dual parameters by forward-projecting the primal parameters, applying a dual-space learned invertible operator to the dual parameters, based on the auxiliary dual parameters, obtaining auxiliary primal parameters by back-projecting the dual parameters, and applying a primal-space learned invertible operator to the primal parameters, based on the auxiliary primal parameters. The system determines an image in the primal space based on the updated primal parameters.

IPC Classes  ?

• G06T 11/00 - 2D [Two Dimensional] image generation

Abstract

This invention provides compositions of (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, checkpoint kinase 1 ("CHK1") inhibitor, B-cell lymphoma-extra large ("BCL-xL") inhibitor, BCL-xL proteolysis-targeting chimera ("BCL‑xL PROTAC"), pan-BCL inhibitor or ataxia telangiectasia and Rad3-related ("ATR") inhibitor. This invention further provides methods for treating cancer or for preventing, inhibiting, or reducing risk of metastasis of a cancer, such as colorectal cancer, cholangiocarcinoma, pancreatic cancer or ovarian cancer, using (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, CHK1 inhibitor, BCL-xL inhibitor, BCL‑xL PROTAC, pan-BCL inhibitor or ATR inhibitor.

IPC Classes  ?

• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/4995 - Pyrazines or piperazines forming part of bridged ring systems

Abstract

A heat and moisture exchanger, comprises a rigid monolithic body (101). The rigid monolithic body (101) comprises a circumferential wall (102); and a structure of interconnected elements (106) surrounded by the circumferential wall (102). The structure (106) is open to fluid communication through the structure (106) between a first side (114) of the structure and a second side (115) of the structure (106) opposite the first side (114) of the structure (106). The circumferential wall (102) extends from the first side (114) to the second side (115) of the structure (106). The heat and moisture exchanger (100) is open on both of the first side (114) and the second side (115) of the structure (106), to allow fluid communication between the structure (106) and an exterior of the heat and moisture exchanger (100) on both sides (114, 115).

IPC Classes  ?

• A61M 16/10 - Preparation of respiratory gases or vapours
• A61M 16/16 - Devices to humidify the respiration air

Abstract

A heat and moisture exchanger, comprises a rigid monolithic body (101). The rigid monolithic body (101) comprises a circumferential wall (102); and a structure of interconnected elements (106) surrounded by the circumferential wall (102). The structure (106) is open to fluid communication through the structure (106) between a first side (114) of the structure and a second side (115) of the structure (106) opposite the first side (114) of the structure (106). The circumferential wall (102) extends from the first side (114) to the second side (115) of the structure (106). The heat and moisture exchanger (100) is open on both of the first side (114) and the second side (115) of the structure (106), to allow fluid communication between the structure (106) and an exterior of the heat and moisture exchanger (100) on both sides (114, 115).

IPC Classes  ?

• A61M 16/10 - Preparation of respiratory gases or vapours
• B33Y 10/00 - Processes of additive manufacturing
• B33Y 80/00 - Products made by additive manufacturing
• F28D 21/00 - Heat-exchange apparatus not covered by any of the groups
• B22F 3/11 - Making porous workpieces or articles
• B22F 10/20 - Direct sintering or melting

Abstract

Fluid injection device for injecting a fluid behind a tympanic membrane of a patient, comprising: a hollow needle having a needle tip with a fluid outlet at a distal end thereof, the needle tip being configured for piercing the tympanic membrane of the patient; a container for storing the fluid to be injected behind the tympanic membrane, the container being arranged in fluid communication with the hollow needle; characterised, in that the hollow needle comprises an elongated venting aperture in an outer wall thereof, the elongated venting aperture being positionable at an inner side of an ear membrane of the patient as well as at an outer ide of said ear membrane when injecting fluid, so as to allow excess fluid on the inner side of said membrane to flow through the elongated venting aperture, to the outer side of said membrane.

IPC Classes  ?

• A61M 31/00 - Devices for introducing or retaining media, e.g. remedies, in cavities of the body
• A61F 11/00 - Methods or devices for treatment of the ears or hearing sense Non-electric hearing aidsMethods or devices for enabling ear patients to achieve auditory perception through physiological senses other than hearing senseProtective devices for the ears, carried on the body or in the hand

Abstract

The present invention is in the field of triacylglycerol synthesis. In particular the invention relates to the identification of DIESL as a new triacylglycerol synthase. The invention also relates to the identification of TMX1 as a negative regulator of DIESL mediated triacylglycerol synthesis. Screening assays for identifying agents that modulate the activity of DIESL and/or of TMX1, or that modulate the interaction between DIESL and TMX1 are also provided.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• C12P 7/64 - FatsFatty oilsEster-type waxesHigher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl groupOxidised oils or fats
• C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
• G01N 33/573 - ImmunoassayBiospecific binding assayMaterials therefor for enzymes or isoenzymes

Abstract

The current invention relates to a chimeric polypeptide, a nucleic acid encoding such chimeric polypeptide, a cell comprising such chimeric polypeptide of nucleic acid, preferably a T cell, a CAR T cell, NK cell or a CAR NK cell, and method of treatment using such cell, polypeptide of nucleic acid in the treatment of cancer, in particular in immune cell therapy. The chimeric polypeptide according to the invention allows for the reversible and dose dependent control of T cell and NK cell function (cytokine release, cytotoxicity).

IPC Classes  ?

• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C07K 14/725 - T-cell receptors
• 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
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants

Abstract

The invention relates to a cellular protein comprising a phenylalanine residue that replaces a tryptophan residue that is encoded by the cell's genome, to methods of identifying said cellular protein, and to a T cell epitope comprising 8-22 amino acid residues of said cellular protein. The invention further relates to a polyepitope comprising 2-50 individual T cell epitopes, a nucleic acid molecule encoding the T cell epitope, a T-cell receptor (TCR) that specifically recognizes the T cell epitope, and a pharmaceutical composition comprising the T cell epitope. The invention further relates to methods of inducing an immune response in an individual and to methods of treating an individual suffering from a tumor.

IPC Classes  ?

• A61K 38/04 - Peptides having up to 20 amino acids in a fully defined sequenceDerivatives thereof
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C07K 7/04 - Linear peptides containing only normal peptide links
• C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
• C12N 5/09 - Tumour cells

Abstract

Generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

IPC Classes  ?

• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61P 35/04 - Antineoplastic agents specific for metastasis
• A61P 37/04 - Immunostimulants

Abstract

Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL). Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).

IPC Classes  ?

• C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 295/192 - Radicals derived from carboxylic acids from aromatic carboxylic acids
• C07D 405/12 - 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 two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 401/04 - 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 directly linked by a ring-member-to-ring- member bond
• C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• 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
• C07D 403/12 - 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 linked by a chain containing hetero atoms as chain links

Abstract

Generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

IPC Classes  ?

• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61P 35/04 - Antineoplastic agents specific for metastasis
• A61P 37/04 - Immunostimulants

Abstract

The current invention relates to the treatment of cancer. In particular the invention relates to modulating the anti-tumor immunity in a cancer patient. The disclosed invention is in particular useful in the treatment of so-called cold tumors and/or in tumors that are resistant to or acquired resistance to treatment with immune checkpoint modulators. Compounds for use in the disclosed treatment, combinations and methods of treatment are provided.

IPC Classes  ?

• A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents

Abstract

Provided are methods involved in assessing homologous recombination deficiency (HRD) status in a patient having ovarian cancer based on the determination of copy number variations (CNVs) in a genomic locus. Furthermore methods for predicting a patient's response to an anti-cancer therapy and thus to the identification of ovarian cancer patients likely to respond to a particular cancer treatment regime based on their HRD status are provided.

IPC Classes  ?

• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• 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 current invention relates to a combination therapy comprising administering the antimitotic agent ABT-751 to a subject and delivering ionizing radiation to the same subject for the treatment of a brain tumor. Provided is for ABT-751 and ionizing radiation for use in such treatments.

IPC Classes  ?

• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

A monitoring device for monitoring a hypocortiolism patient, the monitoring device comprising: - a needle for penetrating a skin of the patient, and - an analysis module fluidly connected with the needle, the analysis module comprising: o a first sensor, for measuring an inflammation level representative for the patient; and/or o a second sensor, for measuring a stress level representative for the patient; and wherein the monitoring device is configured to automatically trigger a notification in response to the first sensor measuring an inflammation level exceeding a first pre-defined threshold and/or in response to the second sensor measuring a stress level exceeding a second pre-defined threshold.

IPC Classes  ?

• A61M 5/142 - Pressure infusion, e.g. using pumps
• A61M 5/172 - Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters electrical or electronic
• A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value

Abstract

In a method to determine a patient (radiation) dose distribution (13), it is provided to calculate, from a measured signal (7) of a detector (6) placed behind a region of interest, a dose distribution (11) for a patient-shaped water equivalent phantom (12) and to compute from this a patient dose distribution (13) that takes into account inhomogeneities of a matter distribution of the patient (4).

IPC Classes  ?

• A61N 5/10 - X-ray therapyGamma-ray therapyParticle-irradiation therapy

Abstract

A personalized implant (100) for bone replacement comprises an implant body (101) as a reconstruction of a bone portion. The implant body comprises a closed cavity (106) and a solid impervious layer (105) of material defining an outside surface of the implant body exposed to an exterior of the implant. The solid impervious layer fully encloses the closed cavity inside the implant body. The closed hollow interior can comprise an open support structure to reinforce the solid outside layer.

IPC Classes  ?

• A61B 17/80 - Cortical plates
• A61F 2/28 - Bones
• A61B 17/17 - Guides for drills
• B33Y 80/00 - Products made by additive manufacturing
• A61C 8/00 - Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereonDental implantsImplanting tools
• A61B 17/56 - Surgical instruments or methods for treatment of bones or jointsDevices specially adapted therefor

Abstract

A blood collection device for the self-collection of a blood sample by a user, wherein, a base element has a width of more than 1.75 in and including an upstanding wall which defines a receive opening, the upstanding wall having a height of less than 1.75 in; a collection container is configured for placement in said receive opening in a substantially upright orientation; the finger portion comprising a blood collection hole that provides a fluid channel between the collection container and the finger portion; wherein at least the base element is a separate part, configured to be shipped in a de-assembled state with respect to the other parts of the blood collection device, wherein the blood collection device is configured to be assembled by a user after receiving said blood collection device.

IPC Classes  ?

• A61B 5/15 - Devices for taking samples of blood

Abstract

This invention pertains to a CD4/IL-2 biomarker that predicts response to treatment with one or more immune checkpoint inhibitors. The invention further pertains to treatment of a patient having a tumor and that has been determined to be negative for the CD4/IL-2 biomarker. Also provided is a kit for determining the CD4/IL biomarker that predicts response to treatment with one or more immune checkpoint inhibitors.

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

Described herein is sodium thiosulfate (STS) for use in preventing or reducing hearing loss in patients receiving platinum-based drugs, for example as chemotherapy to treat cancer. The invention further relates to STS gel compositions suitable for administering to the middle ear of a patient in need thereof, particularly a patient receiving platinum-based drugs.

IPC Classes  ?

• A61K 33/04 - Sulfur, selenium or telluriumCompounds thereof
• A61K 9/06 - OintmentsBases therefor
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
• A61K 33/243 - PlatinumCompounds thereof
• A61P 27/16 - Otologicals

Goods & Services

Cells for medical use; small molecule titratable switches for medical use. Platform as a service (PaaS) for technologies based on small molecule titratable switches for cell therapies; research and development in the field of molecules, switches and cells. Medical treatment involving small molecule titratable switches; cell therapy.

Goods & Services

Cells for medical use; small molecule titratable switches for medical use. Platform as as service (PaaS) for technologies based on small molecule titratable switches for cell therapies; research and development in the field of molecules, switches and cells. Medical treatment involving small molecule titratable switches; cell therapy.

Abstract

The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor

Abstract

The invention relates to a method of treating a patient suffering from a carcinoma, especially a hepatocellular carcinoma. The methods of the invention employ a specific combination of two protein kinase inhibitors, comprising lenvatinib and an Epidermal Growth Factor Receptor (EGFR) inhibitor. The invention further relates to a pharmaceutical preparation comprising lenvatinib and an EGFR inhibitor, a kit of parts, comprising lenvatinib and an EGFR inhibitor, and to the use of the pharmaceutical preparation or the kit of parts in a method of treating a patient suffering from a hepatocellular carcinoma.

IPC Classes  ?

• A61K 31/47 - QuinolinesIsoquinolines
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/4706 - 4-Aminoquinolines8-Aminoquinolines, e.g. chloroquine, primaquine
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents

Goods & Services

(1) Human blood cells for medical use; human blood cells for the treatment and prevention of cancer; stem cells for medical use; stem cells for the treatment and prevention of cancer; small molecule titratable switches for medical use, namely, anti-cancer preparations. (1) Platform as a Service (PaaS) featuring computer software platforms for the development of cancer prevention treatments based on small molecule titratable switches for cell therapies; research in the field of molecules, switches and cells for the development of cancer treatment and diagnostics. (2) Medical treatment of cancer and autoimmune diseases involving small molecule titratable switches; stem cell therapy services.

Goods & Services

Cells for medical use; small molecule titratable switches, namely cells for medical use Platform as a Service (PaaS) featuring computer software platforms for use in creating technologies based on a small molecule titratable switches for cell therapies; research and development in the field of molecules, switches and cells Medical treatment of cancer and autoimmune diseases involving small molecule titratable switches; stem cell therapy services

Goods & Services

Cells for medical use; small molecule titratable switches, namely cells for medical use Platform as a Service (PaaS) featuring computer software platforms for use in creating technologies based on a small molecule titratable switches for cell therapies; research and development in the field of molecules, switches and cells Medical treatment of cancer and autoimmune diseases involving small molecule titratable switches; stem cell therapy services

Goods & Services

(1) Human blood cells for medical use; human blood cells for the treatment and prevention of cancer; stem cells for medical use; stem cells for the treatment and prevention of cancer; small molecule titratable switches for medical use, namely anti-cancer preparations. (1) Platform as a Service (PaaS) featuring computer software platforms for the development of cancer prevention treatments based on small molecule titratable switches for cell therapies; research in the field of molecules, switches and cells for the development of cancer treatment and diagnostics. (2) Medical treatment of cancer and autoimmune diseases involving small molecule titratable switches; stem cell therapy services.

Abstract

A tumor sensor system comprising an implantable probe and an auxiliary device, the probe comprising at least one sensor configured to generate an electric signal in response to a physical stimulus, wherein the at least one sensor comprises a position sensor configured to sense a signal from a position tracking system wherein the sensed signal is indicative of a position of the probe in a space, wherein the position sensor comprises at least one electromagnetic sensor configured to cooperate with an external electromagnetic field generator, wherein the at least one electromagnetic sensor is configured to detect a property of the electromagnetic field and send it as an electric signal to the processing circuit, at least one antenna for data communication by means of inductive communication, an energy harvesting coil, and transmitting the data via the at least one antenna to the auxiliary device.

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• A61B 6/00 - Apparatus or devices for radiation diagnosisApparatus or devices for radiation diagnosis combined with radiation therapy equipment
• A61B 5/06 - Devices, other than using radiation, for detecting or locating foreign bodies
• A61B 5/07 - Endoradiosondes
• A61B 5/0538 - Measuring electrical impedance or conductance of a portion of the body invasively, e.g. using a catheter
• A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value

Abstract

The invention relates to an inducer of senescence, in combination with a short-lived, selective Death Receptor 5 (DR5) agonist, for use in a method of treating a patient suffering from a tumor. The invention further relates to a pharmaceutical composition, comprising a short-lived, selective Death Receptor 5 (DR5) agonist and, optionally, an inducer of senescence. The invention further relates to methods of treating a patient having a tumor, and to a selective, short- lived DR5 agonist, for use in a method of selectively killing senescent cells, including senescent cancer cells.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole

Abstract

The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

IPC Classes  ?

• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• A61P 35/00 - Antineoplastic agents
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes

Abstract

The invention relates to methods for tumor marker analysis comprising providing a genomic DNA sample from tumor cells of a patient, preselecting a chromosomal region on the genomic DNA comprising at least part of a potential structural variant (SV); and sequencing the genomic region to characterize the potential SV. The invention further relates to methods for detecting minimal residual disease, monitoring treatment response and tumor progression in a patient by employing the SV, and to personalized therapy based on the identity of the SV.

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 methods of producing at least one out-of-frame peptide of 5-40 amino acid residues by a cell, and to methods of identifying said at least one out-of-frame peptide of 5-40 amino acid residues. The invention further relates to the identified out-of-frame peptides of 5-40 amino acid residues, and epitopes and polyepitopes encompassing at least one of said out-of-frame peptides, and to a nucleic acid molecule encoding at least one of said out-of-frame peptides. The invention further relates to methods of inducing an immune response against at least one out-of-frame peptide, method of treating an individual suffering from a tumor, comprising providing said individual with at least one out-of-frame peptide, and to a pharmaceutical composition, comprising at least one out-of-frame peptide. The invention additionally relates to a kit for detecting expression of at least one out-of-frame peptide, and to methods of typing an individual for presence or absence of a cell that expresses at least one out-of-frame peptide.

IPC Classes  ?

• C07K 14/435 - 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

Abstract

A surgical forceps comprises a first jaw (101) and a second jaw (102), the first jaw (101) and the second jaw (102) being configured to be rotated relative to each other around an axis of rotation (104). A position sensor (105) is capable of sensing a first orientation with respect to a first axis (106) and a second orientation with respect to a second axis (107) different from the first axis (106), wherein the first axis (106) and the second axis (107) are orthogonal to the axis of rotation (104). The surgical forceps comprises a stapler (108) for stapling a tissue grasped by the surgical forceps (100) and a cutter (103) for cutting the tissue grasped by the surgical forceps (100) along a line.

IPC Classes  ?

• A61B 17/072 - Surgical staplers for applying a row of staples in a single action, e.g. the staples being applied simultaneously
• A61B 34/20 - Surgical navigation systemsDevices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis
• A61B 90/57 - Accessory clamps
• A61B 17/00 - Surgical instruments, devices or methods
• A61B 90/00 - Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups , e.g. for luxation treatment or for protecting wound edges

Abstract

The invention relates to a combination of a FGFR inhibitor and an EZH2 inhibitor for use in a method of treating a patient suffering from a BRCA1-associated protein 1 (BAP1) negative cancer. The invention further relates to a pharmaceutical preparation, comprising a FGFR inhibitor and an EZH2 inhibitor, to the use of said pharmaceutical preparation in a method of treating BAP1-negative cancer, to methods of identifying a patient with cancer, who is eligible for treatment with a combination of a FGFR inhibitor and an EZH2 inhibitor, and to a mouse model for mesothelioma.

IPC Classes  ?

• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A01K 67/027 - New or modified breeds of vertebrates

Abstract

The invention relates to the field of medicine and medicinal chemistry, more in particular to the design, manufacture and use of anti-cancer drugs that can be activated by an external stimulus that can be applied in a spatiotemporal fashion. Provided herein is a compound having the chemical structure or a pharmaceutically acceptable salt thereof.

IPC Classes  ?

• C07D 405/12 - 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 two hetero rings linked by a chain containing hetero atoms as chain links
• A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation

Abstract

Fluid injection device for injecting a fluid behind a tympanic membrane of a patient, comprising: - a hollow needle having a needle tip with a fluid outlet at a distal end thereof, the needle tip being configured for piercing the tympanic membrane of the patient; - a container for storing the fluid to be injected behind the tympanic membrane, the container being arranged in fluid communication with the hollow needle; characterised, in that the hollow needle comprises an elongated venting aperture in an outer wall thereof, the elongated venting aperture being positionable at an inner side of an ear membrane of the patient as well as at an outer side of said ear membrane when injecting fluid, so as to allow excess fluid on the inner side of said membrane to flow through the elongated venting aperture, to the outer side of said membrane.

IPC Classes  ?

• A61M 5/158 - Needles
• A61F 11/00 - Methods or devices for treatment of the ears or hearing sense Non-electric hearing aidsMethods or devices for enabling ear patients to achieve auditory perception through physiological senses other than hearing senseProtective devices for the ears, carried on the body or in the hand
• A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
• A61M 5/46 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests having means for controlling depth of insertion

Abstract

The invention relates to a method for increasing the efficiency of introducing a mutation using CRISPR/Cas technology. More specifically, the method is directed to preventing the occurrence of re-cutting after successful introduction of the desired mutation by introducing an inactive guide RNA. The invention further relates to use of the method in therapy and kits comprising components for carrying out the method.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

Method of activating dysfunctional T cells, determining responsiveness of a subject having a tumor to an immune checkpoint inhibition are provided. Also provided is an agent capable of inhibiting a target gene or expression product thereof for use in treating a subject having a tumor. Additionally or alternatively provided is an immune checkpoint inhibitor and an agent capable of inhibiting a target gene or expression product thereof for use in treating a subject having a tumor.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The current invention relates to the treatment of cancer. In particular the invention relates to modulating the anti-tumor immunity in a cancer patient. The disclosed invention is in particular useful in the treatment of so-called cold tumors and/or in tumors that are resistant to or acquired resistance to treatment with immune checkpoint modulators. Compounds for use in the disclosed treatment, combinations and methods of treatment are provided.

IPC Classes  ?

• A61K 39/085 - Staphylococcus
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
• A61P 35/00 - Antineoplastic agents

Abstract

Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).

IPC Classes  ?

• C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 295/108 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulfur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
• C07D 401/04 - 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 directly linked by a ring-member-to-ring- member bond
• 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
• C07D 403/12 - 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 linked by a chain containing hetero atoms as chain links
• C07D 405/12 - 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 two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61P 35/00 - Antineoplastic agents
• A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine

Abstract

The present invention relates to TWEAK-receptor agonists for use in the treatment of a cancer, wherein the TWEAK-receptor agonist is combined with immunotherapy of the cancer. The TWEAK-receptor agonist preferably is a multivalent ligand that causes clustering of TWEAK-receptors at the cell surface. A suitable TWEAK-receptor agonist is an agonistic anti-Fn14 antibody. The TWEAK-receptor agonist and immunotherapy be can further be combined with a SMAC mimetic in the treatment of cancer. The TWEAK-receptor agonist is useful, optionally in combination with a SMAC mimetic, to prevent resistance of a cancer to immunotherapy and/or to treat a cancer comprising tumor cells that are resistant to immunotherapy.

IPC Classes  ?

• C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• A61P 35/00 - Antineoplastic agents
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 38/00 - Medicinal preparations containing peptides

Abstract

The invention pertains to a compound that induces aberrant splicing in a tumor cell for use in the treatment of cancer, wherein in the treatment, the compound is combined with an immune checkpoint therapy. A preferred compound is a sulphonamide, preferable an aryl-sulphonamide. The invention further pertains to a diagnostic method to identifyi a subject that benefits from immune checkpoint therapy, comprising a step of detecting the presence of a mutated splicing factor in a tumor sample.

IPC Classes  ?

• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/404 - Indoles, e.g. pindolol
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• 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

Abstract

The current invention relates to a combination therapy comprising administering the antimitotic agent ABT-751 to a subject and delivering ionizing radiation to the same subject for the treatment of a brain tumor. Provided is for ABT-751 and ionizing radiation for use in such treatments.

IPC Classes  ?

• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
• A61P 35/00 - Antineoplastic agents

Abstract

Combined ultrasensitive sequencing of matched white blood cells and cell free DNA (cfDNA) identified bona fide tumor-specific alterations that predict clinical outcome after preoperative treatment and resection.

IPC Classes  ?

• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding

Abstract

A blood collection device for the self-collection of a blood sample by a user, wherein, - a base element has a width of more than 32 mm and including an upstanding wall which defines a receive opening, the upstanding wall having a height of less than 32 mm; - a collection container is configured for placement in said receive opening in a substantially upright orientation; - the finger portion comprising a blood collection hole that provides a fluid channel between the collection container and the finger portion; wherein at least the base element is a separate part, configured to be shipped in a de-assembled state with respect to the other parts of the blood collection device, wherein the blood collection device is configured to be assembled by a user after receiving said blood collection device.

IPC Classes  ?

• A61B 5/15 - Devices for taking samples of blood

Abstract

The current invention relates to a chimeric polypeptide, a nucleic acid encoding such chimeric polypeptide, a cell comprising such chimeric polypeptide of nucleic acid, preferably a T cell, a CAR T cell, NK cell or a CAR NK cell, and method of treatment using such cell, polypeptide of nucleic acid in the treatment of cancer, in particular in immune cell therapy. The chimeric polypeptide according to the invention allows for the reversible and dose dependent control of T cell and NK cell function (cytokine release, cytotoxicity).

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 14/725 - T-cell receptors
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression

Abstract

The invention relates to a method of treating a patient suffering from a carcinoma, especially a hepatocellular carcinoma. The methods of the invention employ a specific combination of two protein kinase inhibitors, comprising lenvatinib and an Epidermal Growth Factor Receptor (EGFR) inhibitor. The invention further relates to a pharmaceutical preparation comprising lenvatinib and an EGFR inhibitor, a kit of parts, comprising lenvatinib and an EGFR inhibitor, and to the use of the pharmaceutical preparation or the kit of parts in a method of treating a patient suffering from a hepatocellular carcinoma.

IPC Classes  ?

• A61K 31/47 - QuinolinesIsoquinolines
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents

Abstract

The current invention relates to a chimeric polypeptide, a nucleic acid encoding such chimeric polypeptide, a cell comprising such chimeric polypeptide of nucleic acid, preferably a T cell, a CAR T cell, NK cell or a CAR NK cell, and method of treatment using such cell, polypeptide of nucleic acid in the treatment of cancer, in particular in immune cell therapy. The chimeric polypeptide according to the invention allows for the reversible and dose dependent control of T cell and NK cell function (cytokine release, cytotoxicity).

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C07K 14/725 - T-cell receptors

Abstract

A surgical instrument is disclosed to remove tissue, in particular unhealthy tissue or tissue containing cancer cells, from a body and to analyse the removed tissue. A tissue removal device is arranged at a distal end of the surgical instrument, wherein the distal part of the surgical instrument comprises a movable part, for example a bendable part, to adjust a position and/or orientation of the tissue removal device with respect to a proximal end of the surgical instrument, wherein movement of the movable part can be controlled by an operator. A discharge channel is connected to the tissue removal device for discharge of removed tissue. A tissue analysis device comprises an analysis sensor to analyse non-removed tissue in front of the tissue removal device, wherein the tissue analysis device is configured to provide a sensor signal representative for an analysed characteristic of the tissue.

IPC Classes  ?

• A61B 10/02 - Instruments for taking cell samples or for biopsy
• A61B 34/30 - Surgical robots

Abstract

The invention relates to a combination of an activator of glucocorticoid receptor (GR) and an inhibitor of insulin like growth factor 1 (IGF1) signaling, for use as a medicament. The invention further relates to a kit of parts and to a pharmaceutical composition comprising an activator of GR and an inhibitor of IGF1 signaling, preferably for use in a method of treating a cancer.

IPC Classes  ?

• A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

The invention relates to methods for typing an individual suffering from a colorectal lesion, or suspected of suffering therefrom, based on a set of biomarkers. The invention further relates to methods of assigning treatment to an individual having a high risk colorectal adenoma, and to a kit comprising reagents for directly or indirectly determining a level of expression of the biomarkers.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The current invention relates to use of oral disodium pyrophosphate for preventing and/or reducing tissue calcification, particularly soft tissue calcification, and/or diseases or disorders characterized by low plasma PPi levels, as, e.g., occurs in chronic kidney disease (CKD), end- stage renal disease (ESRD), generalized arterial calcification of infancy (GACI), Pseudoxanthoma elasticum (PXE), Arterial Calcification Due to Deficiency of CD73 (ACDC), Ehlers-Danlos syndrome, arteriosclerosis obliterans, venous calcifications, crystal deposition disorders, calcification resulting from neurological disorders, calcinosis universalis, calcinosis circumscripta, scleroderma, dermatomyositis, systemic lupus erythematosus, hyperparathyroidism, neoplasms, milk-alkali syndrome, hypervitaminosis D, tumoral calcinosis, hypophosphatemic rickets, ossification of the posterior longitudinal ligament of the spine, myocardial ischemia, joint calcification, heterotropic ossification of traumatized muscle, angioid streaks, diabetes mellitus type II, cardiovascular disorder, calciphylaxis, calciphylaxis secondary to chronic kidney disease, calcific uremic arteriolopathy or atherosclerosis.

IPC Classes  ?

• A61K 33/42 - PhosphorusCompounds thereof
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• 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
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
• A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• A61P 19/08 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
• A61P 17/00 - Drugs for dermatological disorders
• A61P 37/02 - Immunomodulators

Abstract

Described herein is sodium thiosulfate (STS) for use in preventing or reducing hearing loss in patients receiving platinum-based drugs, for example as chemotherapy to treat cancer. The invention further relates to STS gel compositions suitable for administering to the middle ear of a patient in need thereof, particularly a patient receiving platinum-based drugs.

IPC Classes  ?

• A61K 33/04 - Sulfur, selenium or telluriumCompounds thereof
• A61P 43/00 - Drugs for specific purposes, not provided for in groups
• A61P 27/16 - Otologicals

Abstract

ex vivoex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

IPC Classes  ?

• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• C12N 5/0775 - Mesenchymal stem cellsAdipose-tissue derived stem cells

Abstract

The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

IPC Classes  ?

• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells

Abstract

The invention relates to a combination of a FGFR inhibitor and an EZH2 inhibitor for use in a method of treating a patient suffering from a BRCA1-associated protein 1 (BAP1) negative cancer. The invention further relates to a pharmaceutical preparation, comprising a FGFR inhibitor and an EZH2 inhibitor, to the use of said pharmaceutical preparation in a method of treating BAP1-negative cancer, to methods of identifying a patient with cancer, who is eligible for treatment with a combination of a FGFR inhibitor and an EZH2 inhibitor, and to a mouse model for mesothelioma.

IPC Classes  ?

• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

Method of activating dysfunctional T cells, determining responsiveness of a subject having a tumor to an immune checkpoint inhibition are provided. Also provided is an agent capable of inhibiting a target gene or expression product thereof for use in treating a subject having a tumor. Additionally or alternatively provided is an immune checkpoint inhibitor and an agent capable of inhibiting a target gene or expression product thereof for use in treating a subject having a tumor.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

IPC Classes  ?

• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• C12N 5/07 - Animal cells or tissues
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• A61P 35/00 - Antineoplastic agents
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

Provided are methods for predicting the responsiveness (predictive assays) of a gastrointestinal cancer patient or stratifying said patient into a responder or non-responder to a chemotherapy treatment comprising: 1) 5-flurouracil or capecitabine in combination with irinotecan or 2) irinotecan only or 3) 5-fluorouracil alone. Also provided are methods of treating a gastrointestinal cancer patient using the predictive assay of the invention. The methods of the invention can be advantageously used to decide on or assign the best treatment option(s) to a gastrointestinal cancer patient, to prevent exposing said patient to the unnecessary side effects associated with a treatment which will prove to be ineffective at a later stage, and/or to reduce the financial burden associated with ineffective cancer treatment options.

IPC Classes  ?

• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The invention relates to methods for determining the cellular composition of a tumor based on bulk mRNA sequencing, and to methods for constructing a reference library comprising single-cell sequencing data for use in the method for determining the cellular composition, as well as methods for predicting recurrence free survival or optimal treatment strategy based on the cellular composition of a tumor.

IPC Classes  ?

• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• 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 field of medicine and medicinal chemistry, more in particular to the design, manufacture and use of anti-cancer drugs that can be activated by an external stimulus that can be applied in a spatiotemporal fashion. Provided herein is a compound having the chemical structure or a pharmaceutically acceptable salt thereof.

IPC Classes  ?

• A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
• A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting 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 31/37 - Coumarins, e.g. psoralen
• C07D 405/12 - 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 two hetero rings linked by a chain containing hetero atoms as chain links
• A61P 35/00 - Antineoplastic agents

Abstract

high cells and populations of such cells. The invention further relates to methods for classifying an individual suffering from cancer and typing a tumor sample as well as for determining the etiology of autoimmune diseases.

IPC Classes  ?

• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The present invention relates to TWEAK-receptor agonists for use in the treatment of a cancer, wherein the TWEAK-receptor agonist is combined with immunotherapy of the cancer.The TWEAK-receptor agonist preferably is a multivalent ligand that causes clustering of TWEAK- receptors at the cell surface. A suitable TWEAK-receptor agonist is an agonistic anti-Fn14 antibody. The TWEAK-receptor agonist and immunotherapy be can further be combined with a SMAC mimetic in the treatment of cancer. The TWEAK-receptor agonist is useful, optionally in combination with a SMAC mimetic, to prevent resistance of a cancer to immunotherapy and/or to treat a cancer comprising tumor cells that are resistant to immunotherapy.

IPC Classes  ?

• 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
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants

Abstract

The present invention relates to TRAF2inhibitorsfor use in the treatment of a cancer, wherein the TRAF2inhibitor is combined with immunotherapy of the cancer and/or a SMAC mimetic.The TRAF2 inhibitor is preferably combined with immune checkpoint therapy of the cancer, more preferably in combination with a SMAC mimetic.

IPC Classes  ?

• 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
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants

Abstract

The present invention relates to the field of cancer, more particularly to the field of immunotherapy and gene signatures. Provided are two specific and distinct gene signatures, namely a Response Immune Signal (RIS) gene signature and a Stromal Immune Signal (SIS) gene signature, which can be used as biomarkers to accurately predict the response of a cancer subject to treatment with a PD-1 antagonist (e.g., PD-1 antibody) and/or a CTLA-4 antagonist (e.g., CTLA-4 antibody). In particular, it was found that the RIS and SIS gene signatures of the invention may be used in combination to predict the response of a cancer subject to treatment with a combination therapy consisting of a PD-1 antagonist (e.g., PD-1 antibody) and a CTLA-4 antagonist (e.g., CTLA-4 antibody). The gene signatures of the invention may be advantageously used in methods for treating cancer, such as melanoma, and to help devise treatment strategies best suited to individual patients (e.g., to achieve personalized therapy, and spare patients from undesired side effects, e.g., toxicity).

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 the field of cellular senescence and cancer therapy, more particularly to combination therapies and use thereof for the treatment of various cancers (e.g. liver cancer). Provided are combination therapy compositions comprising a CDC7 inhibitor compound, an mTOR inhibitor compound, and kit thereof, for use in the treatment of divers cancers (e.g. liver cancer, lung cancer, non-small lung cancer, colon cancer, and others), as well as for use in methods of treatment of a cancer subject (e.g. liver cancer subject) as taught herein. Also provided are methods for selecting a cancer subject suitable for treatment with the combination therapy composition of the invention.

IPC Classes  ?

• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to the field of biomarker development for cancer immunotherapy with PD-1 inhibitor compounds and/or PD-L1 inhibitor compounds. Provided are assays for quantifying PD-1 expression (i.e. immunostaining intensity) in cells present in a tumor sample (i.e. intratumoral cells), which are advantageously used to identify a unique sub-population of intratumoral cells referred to herein as PD-1 T cells, which serves as a biomarker for cancer immunotherapy with PD-1 inhibitor compounds and/or PD-L1 inhibitor compounds alone or in combination with other therapeutic agents (e.g. CTLA-4 inhibitor compound, e.g. ipilimumab). The present invention also provides methods of selecting a human subject diagnosed with cancer (e.g. non-small cell lung cancer (NSCLC)) suitable for immune checkpoint therapy with agents such as PD-1 inhibitors (e.g. nivolumab) and/or PD-L1 inhibitors (e.g. atezolizumab) alone or in combination with other therapeutic agents (e.g. CTLA- 4 inhibitor compound, e.g. ipilimumab), methods for predicting responsiveness to immune checkpoint therapy with agents such as PD-1 inhibitors and/or PD-L1 inhibitors, and method of treatment of a human subject diagnosed with cancer using PD-1 inhibitors and/or PD-L1 inhibitors alone or in combination with other therapeutic agents (e.g. CTLA-4 inhibitor compound, e.g. ipilimumab).

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

A surgical instrument is disclosed to remove tissue, in particular unhealthy tissue or tissue containing cancer cells, from a body and to analyse the removed tissue. A tissue removal device is arranged at a distal end of the surgical instrument, wherein the distal part of the surgical instrument comprises a movable part, for example a bendable part, to adjust a position and/or orientation of the tissue removal device with respect to a proximal end of the surgical instrument, wherein movement of the movable part can be controlled by an operator. A discharge channel is connected to the tissue removal device for discharge of removed tissue. A tissue analysis device comprises an analysis sensor to analyse non-removed tissue in front of the tissue removal device, wherein the tissue analysis device is configured to provide a sensor signal representative for an analysed characteristic of the tissue.

IPC Classes  ?

• A61B 10/00 - Instruments for taking body samples for diagnostic purposesOther methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determinationThroat striking implements
• A61B 10/02 - Instruments for taking cell samples or for biopsy
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons

Abstract

The invention is concerned with use of oral inorganic pyrophosphate for preventing and/or reducing tissue calcification, particularly soft tissue calcification, and/or diseases or disorders characterized by low plasma PPi levels, as, e.g., occurs in chronic kidney disease (CKD), end-stage renal disease (ESRD), generalized arterial calcification of infancy (GACI), Pseudoxanthoma elasticum (PXE), Arterial Calcification Due to Deficiency of CD73 (ACDC), Ehlers-Danlos syndrome, arteriosclerosis obliterans, venous calcifications, crystal deposition disorders, calcification resulting from neurological disorders, calcinosis universalis, calcinosis circumscripta, scleroderma, dermatomyositis, systemic lupus erythematosus, hyperparathyroidism, neoplasms, milk-alkali syndrome, hypervitaminosis D, tumoral calcinosis, hypophosphatemic rickets, ossification of the posterior longitudinal ligament of the spine, myocardial ischemia, joint calcification, heterotropic ossification of traumatized muscle, angioid streaks, diabetes mellitus type II, cardiovascular disorder, or atherosclerosis.

IPC Classes  ?

• A61K 33/42 - PhosphorusCompounds thereof
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells

Abstract

The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells

Abstract

The current invention relates to a fast, flexible and efficient method to generate MHC multimers loaded with a desired peptide, by using temperature-mediated peptide exchange. The method may be used at the same time in parallel for different desired peptides. In the method conditional peptides are used that form stable peptide-MHC complexes at low temperatures, but dissociate when exposed to a defined elevated temperature. The resulting conditional MHC I complexes and multimers can be loaded with peptides of choice.

IPC Classes  ?

• C07K 14/74 - Major histocompatibility complex [MHC]
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses

Abstract

In a method and apparatus, a property of an optically diffuse medium including a first optical absorber having a first concentration and a second optical absorber having a second concentration is determined. A surface area of the medium is imaged at multiple wavelengths around an isosbestic wavelength of the first absorber and the second absorber. A reflectance spectrum of the medium at the surface area at the multiple wavelengths is determined. A derivative of the determined reflectance spectrum around the isosbestic wavelength is determined. From the derivative, a concentration ratio of the first concentration and the second concentration is estimated.

IPC Classes  ?

• G01N 21/31 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
• G01N 33/02 - Food
• G01N 33/12 - MeatFish
• G01N 21/47 - Scattering, i.e. diffuse reflection
• G01N 21/49 - Scattering, i.e. diffuse reflection within a body or fluid
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• G01J 3/42 - Absorption spectrometryDouble-beam spectrometryFlicker spectrometryReflection spectrometry
• G01J 3/28 - Investigating the spectrum
• G01J 3/12 - Generating the spectrumMonochromators

Abstract

The present invention relates to active agents or compounds as well as pharmaceutical compositions comprising said compounds, which are capable of reducing or inhibiting or blocking the enzymatic activity of the glutaminyl-peptide cyclotransferase (QPCT) protein, the glutaminyl-peptide cyclotransferase-like protein (QPCTL) protein, or combinations thereof or are capable of reducing or inhibiting the expression of QPCT gene, the QPCTL gene, or combinations thereof. Also provided are methods for screening or selecting for said compounds. The present invention further relates to a pharmaceutical composition comprising a first active agent for use in a method of treating a condition in a subject that would benefit from reducing the signaling or the binding between SIRPa and CD47 in the subject (e.g. cancer), wherein the method of treating comprises reducing expression or enzymatic activity of QPCTL, QPCT, or combinations thereof in the cell with CD47 on the surface. The compounds and pharmaceutical compositions of the invention may be particularly useful for treating a subject suffering from a disease or condition involving the CD47-SIRPa signaling axis such including e.g., various cancer types, atherosclerosis, fibrotic diseases, and infectious diseases.

IPC Classes  ?

• A61K 31/417 - Imidazole-alkylamines, e.g. histamine, phentolamine
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• 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
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The invention relates to methods for typing a sample of an individual suffering from a colorectal cancer, or suspected of suffering therefrom. A preferred sample is stool. The invention further relates to methods for determining a level of expression of at least two extracted protein expression molecules in stool,, based on the quantified reaction products, and to methods of assigning treatment to an individual that was typed as suffering from colorectal cancer according to the invention.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The invention relates to methods for typing a sample of an individual suffering from a colorectal cancer, or suspected of suffering therefrom. A preferred sample is stool. The invention further relates to methods for determining a level of expression of at least two extracted protein expression molecules in stool,, based on the quantified reaction products, and to methods of assigning treatment to an individual that was typed as suffering from colorectal cancer according to the invention.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer