The invention is in the field of regenerative medicine and provides compositions and methods for treating cancer and/or infections in patients. The invention provides cells, preferably immune cells, genetically engineered to enforce expression of PHGDH, and expression constructs, vectors and methods for preparing and using the same.
The invention relates to a biologically produced nucleic acid sequence comprising two or three primary nucleic acid sequence parts of SARS-COV-2 and not more than three secondary nucleic acid sequence parts, wherein a secondary nucleic acid sequence part encodes an amino acid sequence having the function of a SARS-COV-2 amino acid sequence encoded by ORF3a, ORF6, ORF7a or ORF8. The invention further relates to a host cell or a kit for producing the nucleic acid of the invention, a vector encoding the nucleic acid of the invention and products that can be obtained by the expression of the nucleic acid of the invention such as virus envelopes. The invention further relates a pharmaceutical composition comprising the nucleic acid of the invention or products derived thereof, preferably for use in the prevention of SARS-COV-2.
The present intention relates to compound comprising the general structure P-L-J-E, wherein P is a phosphoinositide 3-kinase (PI3K) binding moiety that binds class 1 phosphoinositide 3-kinase (PI3K), L is a linker with a linker length of 12 to 21 atoms, J is a junction selected from (formula I), (formula II) and (formula III), wherein R7133 alkyl; E is an E3 ubiquitin ligase binding moiety that binds cereblon, J is a junction selected from (formula IV), (formula I), (formula II) and (formula III), R7133 alkyl; and SP is chosen in such way that the length of the linker L is 12 to 21 atoms.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH (Switzerland)
UNIVERSITÄT BASEL (Switzerland)
Inventor
De Geyter, Christian M.H.R.
Gill, Mark E.
Peters, Antoine Hendrik Felix Marie
Abstract
The present invention provides a method for assessing male fertility by assessing the DNA accessibility in the spermatozoa of a population of spermatozoa from mammalian semen from a subject. The present invention also provides a method of selecting a population of spermatozoa from a subject, wherein the fertility of the population is assessed by assessing the DNA accessibility in the spermatozoa of the population. In addition, the present invention provides a method of in vitro fertilization comprising the step of selecting a population of spermatozoa from a subject by assessing the DNA accessibility in the spermatozoa of spermatozoa populations from the subject.
The present invention is directed to compounds, compositions, uses and methods useful in the prevention or treatment of urinary infections, in particular E. coli infections and in particular recurrent urinary infections.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/593 - 9,10-Secocholestane derivatives, e.g. cholecalciferol, vitamin D3
A61K 31/7004 - Monosaccharides having only carbon, hydrogen and oxygen atoms
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 36/73 - Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
09 - Scientific and electric apparatus and instruments
35 - Advertising and business services
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Software, downloadable Software as Medical Devices (SaMD),
downloadable applications for use with mobile devices. Collection, systematization and input of information in
databases, analysis and evaluation of data in a central
file. Scientific and technological services as well as research
and design services relating thereto; industrial analysis
and research services; design and development of computers
and software; development and testing of computing methods,
algorithms and software; design and development of medical
technology, scientific research services for medical
purposes; provision of information with respect to medical
and scientific research in the field of pharmaceutical
products, clinical trials. Health services, medical services, provision of medical
information; medical care and analysis services relating to
patient treatment; disease diagnosis services.
7.
NOVEL PROTEINS AND NUCLEIC ACID SEQUENCES AND USE THEREOF IN THE PROPHYLAXIS AND/OR TREATMENT OF CONGENITAL MUSCULAR DYSTROPHIES
The present invention relates to a modified recombinant agrin protein or a fragment thereof and a recombinant chimeric laminin-nidogen protein or a fragment thereof, to nucleic acid sequences encoding these proteins, to vectors comprising these nucleic acid sequences, to compositions comprising these proteins and to uses of these proteins in the prophylaxis and/or treatment of congenital muscular dystrophies, in particular (laminin-α2) LAMA2-related muscular dystrophy.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The current invention relates to nucleic acid expression vectors such as therapeutic viruses, or mRNA vaccines, encoding catalytic fucosidase moieties for use in treating cancer. Further aspects of the invention relate to fusion proteins comprising a catalytic fucosidase moiety, and beneficial therapeutic combinations of the above with administration of a sialidase, and/or a checkpoint inhibitor agent.
THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS (USA)
UNIVERSITÄT BASEL (Switzerland)
Inventor
Burke, Martin, D.
Syntrivanis, Leonidas-Dimitrios
Tiefenbacher, Konrad
Abstract
The present disclosure relates to methods of making cyclic terpenoids through substrate-controlled catalysis taking place in the presence of a supramolecular capsule.
The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD117 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD52 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
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
12.
HAFNIUM (IV) OXIDE NANOPARTICLES AND AQUEOUS COMPOSITIONS THEREOF
The invention relates to a hafnium (IV) oxide (HfO2) nanoparticle nanocrystal comprising or having a diameter equal or less than (≤) 15 nm, stabilized by a plurality of dispersant molecules attached to its surface. The dispersant molecules comprise of a catechol or gallol surface adsorption moiety and an oligo (ethyleneglycol) moiety. The invention further relates to a composition of such nanoparticles in stable colloidal suspension at physiological pH, and the use of the composition in medical treatment and diagnostic applications, particularly to enhance radiotherapy and as an X ray contrast agent. In yet another aspect, the invention provides a method for manufacturing compositions and nanoparticles according to the invention.
A61K 47/54 - 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
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Collection, systematization and input of information in databases, analysis and evaluation of data in a central file. Software, downloadable Software as Medical Devices (SaMD), downloadable applications for use with mobile devices. Scientific and technological services as well as research and design services relating thereto; industrial analysis and research services; design and development of computers and software; development and testing of computing methods, algorithms and software; design and development of medical technology, scientific research services for medical purposes; provision of information with respect to medical and scientific research in the field of pharmaceutical products, clinical trials. Health services, medical services, provision of medical information; medical care and analysis services relating to patient treatment; disease diagnosis services.
09 - Scientific and electric apparatus and instruments
37 - Construction and mining; installation and repair services
42 - Scientific, technological and industrial services, research and design
Goods & Services
Scientific, optical, measuring, signaling and checking apparatus and instruments; digital panel meters; electric measuring apparatus; electric control, testing and monitoring apparatus; probes for testing integrated circuits; printed circuit testing apparatus, measuring instruments, probes for scientific use; cryogenic measuring instruments for testing components of semiconductors and quantum computers; quantum computers; scientific apparatus, software; computer scanning software. Installation, maintenance and repair of electric and electronic measuring and testing apparatus and instruments. Scientific and technological services and research and development services relating thereto; design and development of computers and programs for computers; engineering; testing of apparatus in the field of electrical engineering for certification purposes; quality control testing; software engineering; quantum computing; scientific research, testing and analysis services; analysis and testing services relating to electrical engineering apparatus; development and testing services in the field of engineering; technical measuring and testing services; conducting of scientific studies; conducting of scientific experiments; preparation of scientific reports; calibration (measuring); testing of computer hardware and software.
The present invention relates to recombinant Gram-negative bacterial strains and the use thereof for delivery of heterologous proteins into eukaryotic cells.
C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/24 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
C12N 15/70 - Vectors or expression systems specially adapted for E. coli
C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving viable microorganisms
16.
PROBE SUPPORT STRUCTURE FOR A MICROMETER-SCALE AND/OR NANOMETER-SCALE MEASURING DEVICE
The invention relates to a probe support structure for a small-scale measuring device, particularly a micrometer-scale or nanometer-scale measuring device, more particularly for a scanning magnetometry device using nitrogen-vacancy (NV) magnetic imaging comprising a probe unit (18) designed for scanning a sample, a holder (1) comprising a probe end (2) carrying the probe unit (18) and a connecting end (3) for connection to the measuring device, and a driving field coupling structure comprising a first coupling lead and a second coupling lead separated from each other between the probe end (2) and the connecting end (3) of the holder (1). At least one longitudinal side of the holder (1) carries the coupling structure, wherein at least a first surface (6) and a second surface (7) of at least one longitudinal side of the holder (1) are separated from each other between the probe end (2) and the connecting end (3) and connected to each other at the probe end (2). The first coupling lead (15) covers the first surface (6) and the second coupling lead (16) covers the second surface (7). The holder (1) can comprise a through hole (10) at the probe end (2) for a driving field through the through hole (10) to provide optical access.
09 - Scientific and electric apparatus and instruments
35 - Advertising and business services
41 - Education, entertainment, sporting and cultural services
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Software, software used for running applications; electronic
agendas. Collection, systematization and input of data in a database;
analysis and evaluation of data in a central file. Education; training; entertainment; sporting and cultural
activities; education and further education. Consultant services with respect to computer hardware and
software design, development and use; design, development
and programming of software; pharmaceutical research and
development services; computer-aided scientific research
services. Pharmacy dispensary services; preparation of prescriptions
by pharmacists; services provided by consultants in the
medical, medicinal and pharmaceutical field.
18.
HYBRID TRIBLOCK COPOLYMER MEMBRANE COMPOSITIONS AND METHODS FOR NANOPORE SEQUENCING
This application discloses hybrid lipid bilayer compositions that include a phospholipid, a triblock copolymer, and a molecule with a pore connecting the two sides of the bilayer, and the use of these lipid bilayer compositions in electrochemical cells for nanopore-based nucleic acid detection techniques, such as nanopore Sequencing-by-Expansion (Nano-SBX) and nanopore Sequencing-by-Synthesis (Nano-SBS) methods.
A manipulating device (1) for manipulating an object comprises a body unit (3), a camera (5) and a work tool (4). The work tool (4) comprises a base (41) and at least one manipulating member (42) elastically movable relative to the base and having an object contact section (4241). The manipulating device defines a field of view of the camera. The object contact section (4241) of the at least one manipulating member (42) of the work tool (4) is in the field of view of the camera (5).
B25J 15/10 - Gripping heads having finger members with three or more finger members
B25J 15/12 - Gripping heads having finger members with flexible finger members
B25J 19/00 - Accessories fitted to manipulators, e.g. for monitoring, for viewingSafety devices combined with or specially adapted for use in connection with manipulators
The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1X2 and X3 are N; Y is N or CH; R1 and R2 are independently of each other (iii) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fhioroalkyl, C1-C2alkoxy, C1-C2alkoxyC1-C3alkyl, CN, or C(0)0-C1-C2alkyl; or R3 and R4 form together a bivalent residue —R5R6- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2—, —CH2—NH—CH2—, or any of the structures wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence Ci-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3 alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue —R8R9— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2— or —O—CH2CH2-0-; with the proviso that at least one of R1 and R2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.
The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1X2 and X3 are N; Y is N or CH; R1 and R2 are independently of each other (iii) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fhioroalkyl, C1-C2alkoxy, C1-C2alkoxyC1-C3alkyl, CN, or C(0)0-C1-C2alkyl; or R3 and R4 form together a bivalent residue —R5R6- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2—, —CH2—NH—CH2—, or any of the structures wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence Ci-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3 alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue —R8R9— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2— or —O—CH2CH2-0-; with the proviso that at least one of R1 and R2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.
The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1X2 and X3 are N; Y is N or CH; R1 and R2 are independently of each other (iii) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fhioroalkyl, C1-C2alkoxy, C1-C2alkoxyC1-C3alkyl, CN, or C(0)0-C1-C2alkyl; or R3 and R4 form together a bivalent residue —R5R6- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2—, —CH2—NH—CH2—, or any of the structures wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence Ci-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3 alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue —R8R9— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2— or —O—CH2CH2-0-; with the proviso that at least one of R1 and R2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.
The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1X2 and X3 are N; Y is N or CH; R1 and R2 are independently of each other (iii) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fhioroalkyl, C1-C2alkoxy, C1-C2alkoxyC1-C3alkyl, CN, or C(0)0-C1-C2alkyl; or R3 and R4 form together a bivalent residue —R5R6- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2—, —CH2—NH—CH2—, or any of the structures wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence Ci-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3 alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue —R8R9— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2— or —O—CH2CH2-0-; with the proviso that at least one of R1 and R2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
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
C07D 417/14 - 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 three or more hetero rings
C07D 451/02 - Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamineCyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropaneCyclic acetals thereof
C07D 451/14 - Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamineCyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantaneCyclic acetals thereof
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A mesenchymal stem/stromal (MSC) cell line, in particular a human mesenchymal stem cell (hMSC), capable of chondrogenic differentiation when cultured in a chondrogenic medium, comprising a first transgene comprising a first nucleic acid sequence encoding for a preferably mammalian immortalizing enzyme under control of a first promoter sequence operable in said mesenchymal cell and a second transgene comprising a second nucleic acid sequence encoding a preferably mammalian bone morphogenic protein under control of a second promoter sequence operable in said mesenchymal cell.
The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD33 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present invention relates to adenovirus-associated virus comprising an influenza-derived neuraminidase transgene, used alone or together with an immune checkpoint inhibitor to treat a patient diagnosed with a solid cancer.
The present invention relates to a process of manufacturing 2,3,5-tri- methylhydroquinone from a mixture of mesitol and 2,3,6-trimethylphenol (=2,3,6- TMP). This process offers a highly interesting and commercial interesting way of producing α-tocopherol.
C07C 37/07 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by conversion of non-aromatic six-membered rings or of such rings formed in situ into aromatic six-membered rings, e.g. by dehydrogenation with simultaneous reduction of C=O group in that ring
C07C 37/16 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms by condensation involving hydroxy groups of phenols or alcohols or the ether or mineral ester group derived therefrom
C07C 37/14 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms by addition reactions, i.e. reactions involving at least one carbon-to-carbon unsaturated bond
C07C 39/07 - Alkylated phenols containing only methyl groups as alkyl groups, e.g. cresols, xylenols
C07C 45/64 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by introduction of functional groups containing oxygen only in singly bound form
C07C 49/713 - Unsaturated compounds containing a keto group being part of a ring containing hydroxy groups a keto group being part of a six-membered ring
C07C 46/06 - Preparation of quinones by oxidation giving rise to quinoid structures of at least one hydroxy group on a six-membered aromatic ring
C07C 50/02 - Quinones with monocyclic quinoid structure
C07C 409/14 - Peroxy compounds the —O—O— group being bound between a carbon atom, not further substituted by oxygen atoms, and hydrogen, i.e. hydroperoxides the carbon atom belonging to a ring other than a six-membered aromatic ring
25.
METHOD FOR IDENTIFYING PI3 KINASE-ALPHA INHIBITORS
The invention relates to a method of identifying selective covalently binding inhibitors by using a reversibly inhibiting scaffolds modified by a warhead comprising a fast-reacting Michael acceptor moiety and a linker of different length, determining kinact, and replacing the warhead of the covalently binding inhibitor with the highest kinact by a warhead comprising a moderately reacting Michael acceptor.
Kinase-targeted covalent inhibitors are usually irreversibly targeting noncatalytic cysteines in the ATP-binding site. These compounds are designed by directly introducing an electrophile on a reversible-inhibitor scaffold. Our invention relates to novel triazine compounds, containing chemical reactive groups (warheads), targeting a solvent exposed cysteine at >10 Å from the core reversible inhibitor. A variety of novel linkers have been designed and used to link the warhead with the reversible scaffold. We disclose a novel chemical space for drug-like covalent modifiers of phosphoinositide 3-kinase alpha (PI3Kα), an enzyme frequently altered in human malignancies. The invention relates to novel covalent inhibitors showing higher in vitro affinity, cellular potency and improved metabolic stability (rat liver microsomes). The compounds of the invention could be exploited as therapeutic agents and chemical probes useful for modulating cellular activities such as signal transduction, proliferation, differentiation and cell death.
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
The present disclosure relates to antibodies and antibody fragments that are specific for CD45. The antibodies are improved humanized versions of a murine antibody. In addition to a sophisticated humanization campaign, the antibodies were also engineered to remove several detrimental motifs within the CDR region without losing any beneficial properties. The antibodies are useful for the treatment of diseases associated with CD45.
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
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
28.
TRIAZINE DERIVATIVE AS REVERSIBLE AND IRREVERSIBLE COVALENT INHIBITORS OF PI3K
Our invention relates to novel triazine compounds, containing chemical reactive groups (warheads) and behaving as reversible and irreversible covalent inhibitors. Linkers have been introduced to target a solvent exposed, distal cysteine at >10 Å from the core reversible inhibitor. Different exit vectors have been investigated to modulate inhibitor intrinsic reactivity and efficiency in covalent bond formation. We disclose novel, optimized covalent modifiers of phosphoinositide 3-kinase alpha (PI3Kα), an enzyme frequently altered in human malignancies. The compounds of the invention could be exploited as therapeutic agents and chemical probes useful for the investigation of the role of PI3K isoforms in cancer and metabolism, and for treatment of PI3Kα-driven cancers and malformations.
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A radiopeptide is provided which comprises (a) a radionuclide, wherein the radionuclide is terbium-161, (b) a chelator coordinating terbium-161, and (c) a peptide or peptide analogue, which is a somatostatin receptor (SSTR) antagonist. The radiopeptide is suitable for use in the treatment of tumor diseases.
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 51/12 - Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes
A medical endodevice (1) for an intervention inside a body cavity (54) of a body of a human or animal being (5), comprising an elongated liaising structure (2; 29), an intervention tool (7), a positioning unit (3), a decoupling structure and at least two expandable members (62). The elongated liaising structure (2; 29) has a distal end (211; 2119) arrangeable in the body cavity (54) and a proximal end arrangeable outside the body while the distal end (211; 2119) is in the body cavity (54). The intervention tool (7) is arranged to manipulate a target tissue inside the human or animal body, wherein the intervention tool (7) is arranged at the distal end (211; 2119) of the liaising structure (2; 29). The positioning unit (3) has a moving formation (32) arranged to dislocate the intervention tool (7) relative to the target tissue. The decoupling structure is arranged to decouple the positioning unit (3) once it is arranged in the body cavity (54). The at least two expandable members (62) are mounted to the positioning unit (3) and configured to fix the positioning unit (3) in the body cavity (54) when being expanded.
A61B 1/00 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopesIlluminating arrangements therefor
A61B 17/22 - Implements for squeezing-off ulcers or the like on inner organs of the bodyImplements for scraping-out cavities of body organs, e.g. bonesSurgical instruments, devices or methods for invasive removal or destruction of calculus using mechanical vibrationsSurgical instruments, devices or methods for removing obstructions in blood vessels, not otherwise provided for
A device is disclosed for modelling a blood labyrinth barrier of a human ear that includes a first fluid channel and a second fluid channel, and a membrane separating the first and second fluid channels. The membrane has a luminal side in the first fluid channel and an abluminal side in the second fluid channel, endothelial cells attached to the luminal side of the membrane, pericytes attached to the abluminal side of the membrane, and perivascular macrophage-type melanocytes arranged in the second fluid channel. A method of preparing such device is also disclosed. As well, a device with two fluid channels and a membrane as described above is disclosed, wherein the endothelial cells, pericytes and perivascular macrophage-type melanocytes are arranged in two fluid containers.
The invention relates to a quantum spin-based optical sensor system (1) for measuring a characteristic quantity in magnetometry or gyroscopy, the system (1) comprising the following components: - a crystal (2) comprising a photoluminescent color-center (20) having a defect-axis (200) along an axis of symmetry of the color-center (20), wherein the color-center (20) comprises a defect-atom (21) arranged on the defect-axis (200), wherein the defect-atom (21) exhibits a nuclear spin that is polarizable with light (100), and wherein the color-center (20) exhibits a nuclear spin-dependent photoluminescence characteristic, - a light source (3) configured and arranged to excite the color-center (20) with light (100), - a detector (4) configured and arranged to record a photoluminescence signal (101) emitted from the color-center (20), a field-generating device (5) configured and adapted to generate a static magnetic field, wherein a magnetic field vector (500) of the generated magnetic field at the crystal (2) encloses an angle (θ ) with the defect-axis (200) with a magnitude in the range of 0.1° or greater.
G01R 33/032 - Measuring direction or magnitude of magnetic fields or magnetic flux using magneto-optic devices, e.g. Faraday
G01R 33/26 - Arrangements or instruments for measuring magnetic variables involving magnetic resonance for measuring direction or magnitude of magnetic fields or magnetic flux using optical pumping
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07D 215/54 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
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 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
35.
TARGETING SNX9 RESCUES RECOMBINANT T CELL IN ADOPTIVE THERAPY
A first aspect of the invention relates to a nucleic acid agent capable of downregulating or inhibiting the expression or biological activity of SNX9 in a target cell, wherein the nucleic acid agent is selected from an antisense oligodeoxynucleotide, an siRNA, a miRNA and a shRNA. A second aspect of the invention relates to a nucleic acid vector capable of expressing the nucleic acid agent in a target cell, particularly in a transgenic T cell. Another aspect of the invention relates to a preparation of T cells with suppressed, inhibited or abrogated SNX9 expression. Any of the above aspects are provided for use in treatment of a condition characterized by or associated with exhaustion of T cell function, particularly cancer immunotherapy, more particularly in the context of cancer immunotherapy that benefits from the prevention of T cell exhaustion.
A microinvasive surgery device (10) comprising a body element (20), a tube component (30) having a proximal portion (340) and a distal portion (330), wherein the proximal portion of the tube component (30) is connected to the body element (20), a plurality of tools (40) each having an operative portion (4210) to contact a target and a proximal portion (4270), a magazine (50) having a plurality of chambers (520) each configured to receive one of the plurality of tools (40), and a tool (40) interchange mechanism (60) configured to activate one of the plurality of tools (40) by advancing the one of the plurality of tools (40) from its chamber (520) of the magazine (50) through the tube component (30) to the distal portion (330) of the tube component (30) and mounting the forwarded tool (40) to the distal portion (330) of the tube component (30), and to deactivate the one of the plurality of tools (40) by demounting the tool (40) from the distal portion (330) of the tube component (30) and retracting the demounted one of the tools (40) from the distal portion (330) of the tube component (30) through the tube component (30) into its chamber (520) of the magazine (50). The tool interchange mechanism (60) has a selection structure to select one of the plurality of tools (40) in the magazine (5; 50) to be activated. The microinvasive surgery device (10) further comprises a power supply arrangement (70) configured to provide electricity to the proximal portion of one of the tools, when being mounted to the distal portion (330) of the tube component (30). Each of the plurality of tools (40) is configured either to transmit electricity through the proximal portion (4270) of one of the tools (40) to the operative portion (4210) or to electrically isolate the proximal portion (4270) of one of the tools (40) so that no electrical transmission to the operative portion (4210) is possible, when being mounted to the distal portion (330) of the tube component (30).
A61B 17/29 - Forceps for use in minimally invasive surgery
A61B 18/12 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, diastereoisomer, enantiomer, polymorph, racemic mixture, solvate or isomers and mixtures thereof. The invention further relates to a process for the stereoselective preparation of such compounds. The compound of formula (I) can be used as a medicament, in particular for inhibiting coronin 1 expression in the induction of immunosuppression or in the treatment and/or prevention of a disease or disorder selected from the group consisting of transplant rejection, autoimmune diseases, inflammatory diseases, infectious diseases, and lymphoproliferative disorders. The present invention further relates to a vector comprising a coronin 1 promoter element, wherein in a vertebrate genome, said coronin 1 promoter element starts directly upstream from a transcription starting site (TSS) of a coronin 1 gene and spans a sequence stretch of at least about 700 bp in said genome. The present invention further relates to a method using said vector for identifying immunomodulatory compounds that alter the coronin 1 promoter activity. The present invention further relates to BRD3 as an upstream target responsible for driving the coronin-1 expression and activity in immune cells, and relates to compounds, in particular compound of formula (I), that selectively target bromodomains of BRD3 and thereby deplete coronin 1 levels.
C07D 215/54 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
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 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
The invention relates to the treatment and prevention of diseases and conditions associated with EBV infection. In particular, the invention is directed to the use of an IDO1 inhibitor for the treatment and prevention of diseases and conditions associated with EBV infection. The invention also relates to methods for predicting the risk of developing a disease or condition associated with EBV infection.
A61P 31/22 - Antivirals for DNA viruses for herpes viruses
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
The present invention relates to the photooxidation of 2,4,6-trimethyl-phenol to yield 4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one using methylene blue as photosensitizer in a solvent mixture of water and alcohols using light of the high wavelength range of the visible spectrum. This process allows 5 obtaining 4-hydroxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one and 2,3,5-trimethyl-hydroquinone in high yields and selectivity from 2,4,6-trimethylphenol.
The present invention concerns a computer implemented method of reconstructing a digital image (50) of an electromagnetic source (10) using a neural network (20) comprising the steps of receiving an electromagnetic signal (11) acquired by an electromagnetic sensor (12) sensing said electromagnetic source (10), providing the electromagnetic signal (11) as input into a neural network (20) parametrized by a set of parameters (θ) for determining an estimated electromagnetic source vector (21) associated to the electromagnetic signal, determining a loss function (30), minimizing the loss function (30) by feed-forwarding the neural network (20) until a stop criterion is met so as to obtain an optimal electromagnetic source vector (40), reconstructing a digital image (50) of the electromagnetic source (10) based on the optimal electromagnetic source vector (40), characterized in that determining the loss function (30) comprises computing an estimated electromagnetic signal (31) based on the estimated electromagnetic source vector (21), the loss function (30) depending on the estimated electromagnetic signal (31). The present invention also concerns a system for reconstructing a digital image of an electromagnetic source from electromagnetic imaging data comprising: at least one electromagnetic sensor (12) for sensing an electromagnetic signal (11), means for carrying out the computer implemented method described above so as to obtain a digital image (50) of the electromagnetic source (10).
The invention relates to a pharmaceutical composition capable of protecting a patient from disease caused by a pathogenic strain of a bacterium, that displays a wild type surface antigen. It comprises a probiotic component comprising a live avirulent bacterial strain of said pathogen, which displays a variant of said surface antigen, said variant being capable of escaping binding by immunoglobulins capable of specifically recognizing the wild-type surface antigen. The composition further comprises a vaccine component of an inactivated vaccine strain of said bacterium, which displays said wild type surface antigen.
An endodevice is disclosed with tension control. The endodevice includes a back end unit with an endoscopic unit coupled thereto. The back end unit includes first and second sensor elements, wherein the first sensor element is arranged between a drive member and a first spring element and the second sensor element is arranged between another end of the first spring element and a first tendon coupler. Each of the first and second sensor elements are configured to generate a sensor signal wherein the first sensor element, the second sensor element and the drive member are connected to a control unit. The control unit is configured to obtain sensor signals from the first sensor element and the second sensor element and to compute a deflection of the first spring element on the basis of the sensor signals obtained from the first sensor element and the second sensor element.
A61B 1/00 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopesIlluminating arrangements therefor
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
The present invention relates to a hemostatic elastin-like polypeptide comprising a glutamine embedded in a Q-block sequence and, optionally, a lysine embedded in a K-block sequence. Under physiological setting, the Q-block sequence and the K-block sequence are recognized by human transglutaminase factor XIIIa and crosslinked with fibrin networks. The present invention also relates to the medical use of the polypeptide, to a nucleic acid sequence encoding the polypeptide, to an expression vector comprising the nucleic acid sequence, and to a cell comprising the nucleic acid sequence or the expression vector.
The present disclosure relates to antibodies and antibody fragments that are specific for CD117. The antibodies are improved versions of state-of-the art antibodies. In addition to a sophisticated humanization campaign, the antibodies were also engineered to remove several detrimental motifs within the CDR region without losing any beneficial properties. The antibodies are useful for the treatment of diseases associated with CD117.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
46.
LFA-1 SIGNALLING MEDIATOR FOR USE IN CANCER THERAPY
The present invention relates to an LFA-1 signalling mediator with moderate LFA-1 stabilization properties for use in cancer immunotherapy or a composition for use in cancer immunotherapy comprising an immune system modulator, wherein the immune system modulator enhances the immune response against cancer, and an LFA-1 signalling mediator with moderate LFA-1 stabilization properties wherein the LFA-1 signalling mediator selectively and significantly enhances the anti-cancer immune response. The composition may comprise a carrier for target delivery of the composition.
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
Described herein is a method of isolating a T cell that expresses a T cell receptor capable of binding specifically to an antigen presented by a cancer cell in association with an MR1 molecule. The method comprises the steps of (a) providing a preparation of T cells, (b) contacting the preparation with cancer cells expressing MR1 protein; (c) isolating a T cell that is specifically reactive to said cancer cells. The invention further relates to a method of preparing a T cell preparation expressing select MR1 recognizing T cell receptors from transgene expression vectors, the use of such T cell preparations in treatment of cancer, and to collections of MR1 reactive T cell receptor encoding nucleic acids and cells.
SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE (Switzerland)
UNIVERSITÄT BASEL (Switzerland)
Inventor
Jennings, Michael P.
Day, Christopher J.
Pluschke, Gerd
Abstract
This disclosure relates generally to the use of compounds that inhibit binding of Plasmodium cysteine-rich protective antigen (CyRPA) to glycans of cells that are susceptible to infection by Plasmodium pathogens, including glycans terminating with α2-6-linked sialic acid, in methods, compositions and kits for inhibiting the interaction of a Plasmodium pathogen to Plasmodium-binding glycan-expressing cells, including α2-6-linked sialic acid-expressing cells such as erythrocytes, and for treating or inhibiting the development of malaria.
A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A bruxism detection device (1) comprises an earplug body (2) designed to be positioned in an ear canal (3) of a user; a sound sensing transducer (4) mounted to the earplug body (2) such that the sound sensing transducer (4) is directed towards a tympanic membrane (5) of the user when the earplug body (2) is positioned in the ear canal (3) of the user; and a processing unit connected (6) to the sound sensing transducer (4) such that a sound signal detected by the sound sensing transducer (4) is receivable by the processing unit (6). The processing unit (6) is configured to evaluate the sound signal received from the sound sensing transducer (4) to detect sound associated to tooth grinding. Further, the processing unit (6) is configured to evaluate the sound signal received from the sound sensing transducer (4) to detect sound associated to jaw clenching.
The invention relates to a method for classifying a tissue sample obtained from mammary carcinoma. The method comprises determining a stiffness value for each of a plurality of points on said tissue sample, resulting in a stiffness distribution, and assigning said sample to a breast cancer subtype and nodal status based on said stiffness distribution.
The invention relates to a method for device-independent quantum key generation and distribution between a first and a second receiver, the method comprising the steps of:
a) Generating an entangled information pair, comprising two entangled quantum moieties that have at least one quantum state entangled with each other, such as a polarization,
b) Transmitting a first entangled quantum moiety of the two entangled quantum moieties to the first receiver (A) and a second entangled quantum moiety of the two entangled quantum moieties to the second receiver (B), and measuring the quantum states of the entangled moieties with a set of selected detection settings chosen randomly at each receiver
c) In a modification step, assigning each measurement value b1 measured with a detection setting B1 a complementary value
b
1
∗
according to a noise-probability p, wherein the noise-probability p is larger than 0 and lower than 1, such that a modified plurality of measurement values
b
1
˜
is obtained,
d) Generating a final shared quantum key from the modified plurality measurements values
b
1
˜
and from a plurality of measurement values a0 measured with a detection setting A0 at the first receiver (A).
The present invention relates to a single photon source, comprising: a microcavity arranged between a concave first minor and a semiconductor heterostructure forming a planar second minor, wherein the microcavity supports an optical mode, a quantum dot embedded in the semiconductor heterostructure and facing the first minor, and a laser light source configured to provide laser light in the microcavity to excite the quantum dot to emit single photons exiting the microcavity.
H01S 5/34 - Structure or shape of the active regionMaterials used for the active region comprising quantum well or superlattice structures, e.g. single quantum well [SQW] lasers, multiple quantum well [MQW] lasers or graded index separate confinement heterostructure [GRINSCH] lasers
H01S 5/10 - Construction or shape of the optical resonator
H01S 5/04 - Processes or apparatus for excitation, e.g. pumping
H01S 5/183 - Surface-emitting [SE] lasers, e.g. having both horizontal and vertical cavities having only vertical cavities, e.g. vertical cavity surface-emitting lasers [VCSEL]
The disclosure provides, in various embodiments, methods of treating fungal infections in subjects in need thereof, methods of attenuating virulence of fungi (e.g., in subjects in need thereof), and methods of inhibiting formation of fungal biofilms on surfaces (e.g., living or inert surfaces) with mucin glycans, tautomer, stereoisomer and/or pharmaceutically acceptable salts thereof. The disclosure further provides, in various embodiments, mucin glycan compositions, such as synthetic mucin glycans and defined mucin glycan compositions.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 47/54 - 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 invention is in the field of regenerative medicine and provides compositions and methods for treating cancer and/or infections in patients. The invention provides cells, preferably immune cells, genetically engineered to enforce expression of PHGDH, and expression constructs, vectors and methods for preparing and using the same.
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified 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
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
The invention is in the field of regenerative medicine and provides compositions and methods for treating cancer and/or infections in patients. The invention provides cells, preferably immune cells, genetically engineered to enforce expression of PHGDH, and expression constructs, vectors and methods for preparing and using the same.
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified 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
The invention relates to a method to obtain a preparation of nano plasma membrane vesicles (nPMVs), comprising the steps: providing eukaryotic cells; exposing the eukaryotic cells to conditions leading to vesiculation of the eukaryotic cell, leading to shedding of vesicles from the cell; separating vesicles to yield a cell culture supernatant comprising vesicles; extruding said cell culture supernatant through a filter membrane characterized by pores of 30nm to 400nm diameter; removing the vesiculation agent; to obtain a preparation of nano plasma membrane vesicles. The invention further relates to a preparation of nano plasma membrane vesicles, obtained by the method according to the invention.
The disclosure provides, in various embodiments, methods of treating fungal infections in subjects in need thereof, methods of attenuating virulence of fungi (e.g., in subjects in need thereof), and methods of inhibiting formation of fungal biofilms on surfaces (e.g., living or inert surfaces) with mucin glycans, tautomer, stereoisomer and/or pharmaceutically acceptable salts thereof. The disclosure further provides, in various embodiments, mucin glycan compositions, such as synthetic mucin glycans and defined mucin glycan compositions.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A radiopeptide is provided which comprises (a) a radionuclide, wherein the radionuclide is terbium-161, (b) a chelator coordinating terbium-161, and (c) a peptide or peptide analogue, which is a somatostatin receptor (SSTR) antagonist. The radiopeptide is suitable for use in the treatment of tumor diseases.
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 51/12 - Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes
CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS (CHUV) (Switzerland)
UNIVERSITÄT BASEL (Switzerland)
Inventor
Abid, Karim
Grouzmann, Eric
Fani, Melpomeni
Mansi, Rosalba
Grand-Guillaume-Perrenoud, Joana
Abstract
The present invention relates to compositions comprising a P13K/Akt/mTOR inhibitor, and a radiopharmaceutical, whose cellular uptake is upregulated upon inhibition of P13K/Akt/mTOR, as well as to pharmaceutical compositions and kits of parts comprising the same. Instant compositions, pharmaceutical compositions and kits of parts are particularly useful in therapy and diagnosis, in particular of neuroendocrine tumours. The present invention further relates to P13K/Akt/mTOR inhibitors for use in diagnosis and therapy.
A61K 31/436 - 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 oxygen as a ring hetero atom, e.g. rapamycin
A61K 31/4738 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
The present invention relates to a modified recombinant agrin protein or a fragment thereof and a recombinant chimeric laminin-nidogen protein or a fragment thereof, to nucleic acid sequences encoding these proteins, to vectors comprising these nucleic acid sequences, to compositions comprising these proteins and to uses of these proteins in the prophylaxis and/or treatment of congenital muscular dystrophies, in particular (laminin-α2) LAMA2-related muscular dystrophy.
The present invention relates to a modified recombinant agrin protein or a fragment thereof and a recombinant chimeric laminin-nidogen protein or a fragment thereof, to nucleic acid sequences encoding these proteins, to vectors comprising these nucleic acid sequences, to compositions comprising these proteins and to uses of these proteins in the prophylaxis and/or treatment of congenital muscular dystrophies, in particular (laminin-2) LAMA2-related muscular dystrophy.
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61P 13/00 - Drugs for disorders of the urinary system
A61K 36/00 - Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
A61K 36/73 - Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
The present invention is directed to compounds, compositions, uses and methods useful in the prevention or treatment of urinary infections, in particular E. coli infections and in particular recurrent urinary infections.
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
The present invention relates to recombinant virulence attenuated Gram-negative bacterial strains and its use in a method of treating cancer in a subject.
C07K 14/24 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD45 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
A61P 35/02 - Antineoplastic agents specific for leukemia
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD45 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD117 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The invention relates to a method to determine a homology directed repair (HDR) event within a eukaryotic cell, wherein the cell expresses a first isoform of a surface protein, which is different from a second isoform of said surface protein with regard to an amino acid marker. The method comprises the steps of inducing a DNA double strand break, providing a HDR template DNA construct comprising the amino acid marker corresponding to the second isoform of the surface protein and subsequently determining the expression of the first or second isoform of said surface protein on said cell, wherein expression of the second isoform indicates a successful HDR event. The invention also relates to a method for editing a genomic location of interest within a eukaryotic cell, and to a method of selectively depleting or enriching an edited cell in a composition of non-edited and edited cells.
The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD117 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
A radiopeptide is provided which comprises (a) a radionuclide, wherein the radionuclide is terbium-161, (b) a chelator coordinating terbium-161, and (c) a peptide or peptide analogue, which is a somatostatin receptor (SSTR) antagonist. The radiopeptide is suitable for use in the treatment of tumor diseases.
A61K 51/12 - Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 9/00 - Medicinal preparations characterised by special physical form
The invention relates to a hafnium (IV) oxide (HfO2) nanoparticle nanocrystal comprising or having a diameter equal or less than (?) 15 nm, stabilized by a plurality of dispersant molecules attached to its surface. The dispersant molecules comprise of a catechol or gallol surface adsorption moiety and an oligo(ethyleneglycol) moiety. The invention further relates to a composition of such nanoparticles in stable colloidal suspension at physiological pH, and the use of the composition in medical treatment and diagnostic applications, particularly to enhance radiotherapy and as an X ray contrast agent. In yet another aspect, the invention provides a method for manufacturing compositions and nanoparticles according to the invention.
22) nanoparticle nanocrystal comprising or having a diameter equal or less than (≤) 15 nm, stabilized by a plurality of dispersant molecules attached to its surface. The dispersant molecules comprise of a catechol or gallol surface adsorption moiety and an oligo(ethyleneglycol) moiety. The invention further relates to a composition of such nanoparticles in stable colloidal suspension at physiological pH, and the use of the composition in medical treatment and diagnostic applications, particularly to enhance radiotherapy and as an X ray contrast agent. In yet another aspect, the invention provides a method for manufacturing compositions and nanoparticles according to the invention.
The present invention relates to a method for automatically determining an optimal individual dosing regimen of at least one drug for a patient suffering from a known disease, the optimal individual dosing regimen being optionally subject to at least one clinical constraint, wherein the method comprises the steps of: providing a mathematical model adapted to model a progression of said disease and an effect of the at least one drug on the progression of the disease, the model comprising individual model parameters associated with the patient; utilizing an empirical Bayesian estimation to automatically and numerically estimate the individual model parameters of the mathematical model utilizing patient data associated with the patient; automatically calculating an optimal individual dosing regimen for the mathematical model by solving an optimal control problem based on a desired progression of the disease, the estimated individual model parameters, and an initial guess for the dosing regimen; and adjusting the optimal individual dosing regimen to optionally account for at least one clinical constraint to yield the optimal individual dosing regimen subject to said at least one clinical constraint.
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 50/50 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
75.
METHOD, SYSTEM AND COMPUTER PROGRAM FOR COMPUTATION OF OPTIMAL INDIVIDUAL DOSING REGIMEN, PARTICULARLY SUBJECT TO CLINICAL CONSTRAINTS
The present invention relates to a method for automatically determining an optimal individual dosing regimen of at least one drug for a patient suffering from a known disease, the optimal individual dosing regimen being optionally subject to at least one clinical constraint, wherein the method comprises the steps of: providing a mathematical model adapted to model a progression of said disease and an effect of the at least one drug on the progression of the disease, the model comprising individual model parameters associated with the patient; utilizing an empirical Bayesian estimation to automatically and numerically estimate the individual model parameters of the mathematical model utilizing patient data associated with the patient; automatically calculating an optimal individual dosing regimen for the mathematical model by solving an optimal control problem based on a desired progression of the disease, the estimated individual model parameters, and an initial guess for the dosing regimen; and adjusting the optimal individual dosing regimen to optionally account for at least one clinical constraint to yield the optimal individual dosing regimen subject to said at least one clinical constraint.
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 50/50 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
76.
A CLASS IIA HDAC INHIBITOR AND DECITABINE TO TREAT MYOPATHY
The present invention relates to a pharmaceutical composition comprising a class Ila HDAC inhibitor characterised by a trifluoromethyloxadiazole group and/or 5-Aza-2-deoxycytidine for use in treating myopathy.
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/706 - 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
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
A radiopeptide is provided which comprises (a) a radionuclide, wherein the radionuclide is terbium-161, (b) a chelator coordinating terbium-161, and (c) a peptide or peptide analogue, which is a somatostatin receptor (SSTR) antagonist. The radiopeptide is suitable for use in the treatment of tumor diseases.
A diamond scanning element, especially for an imaging application, includes a support and a pillar extending from the support. The pillar has a longitudinal axis and the pillar includes a tip with a tapered lateral section with a, preferably constantly, increasing curvature. The tip includes a sensor element, which is a defect, and a flat end facet extending toward the axis with a gradient of less than 10%.
C30B 33/04 - After-treatment of single crystals or homogeneous polycrystalline material with defined structure using electric or magnetic fields or particle radiation
G01Q 60/54 - Probes, their manufacture or their related instrumentation, e.g. holders
A radiopeptide is provided which comprises (a) a radionuclide, wherein the radionuclide is terbium-161, (b) a chelator coordinating terbium-161, and (c) a peptide or peptide analogue, which is a somatostatin receptor (SSTR) antagonist. The radiopeptide is suitable for use in the treatment of tumor diseases.
The invention relates to a method for modulating an interaction between an MR1 polypeptide and an MR1-specific T cell receptor molecule, whereby a MR1 polypeptide is contacted with a MR1 ligand compound that is a nucleobase adduct product reflecting a state of metabolic distress of a cell.
The invention relates to a method for modulating an interaction between an MR1 polypeptide and an MR1-specific T cell receptor molecule, whereby a MR1 polypeptide is contacted with a MR1 ligand compound that is a nucleobase adduct product reflecting a state of metabolic distress of a cell.
The invention further relates to the use of compounds identified as MR1 ligands in vaccination or modulation of an MR1-restricted immune response.
The invention relates to a biologically produced nucleic acid sequence comprising two or three primary nucleic acid sequence parts of SARS-CoV-2 and not more than three secondary nucleic acid sequence parts, wherein a secondary nucleic acid sequence part encodes an amino acid sequence having the function of a SARS-CoV-2 amino acid sequence encoded by ORF3a, ORF6, ORF7a or ORF8. The invention further relates to a host cell or a kit for producing the nucleic acid of the invention, a vector encoding the nucleic acid of the invention and products that can be obtained by the expression of the nucleic acid of the invention such as virus envelopes. The invention further relates a pharmaceutical composition comprising the nucleic acid of the invention or products derived thereof, preferably for use in the prevention of SARS-CoV-2.
The invention relates to a biologically produced nucleic acid sequence comprising two or three primary nucleic acid sequence parts of SARS-CoV-2 and not more than three secondary nucleic acid sequence parts, wherein a secondary nucleic acid sequence part encodes an amino acid sequence having the function of a SARS-CoV-2 amino acid sequence encoded by ORF3a, ORF6, ORF7a or ORF8. The invention further relates to a host cell or a kit for producing the nucleic acid of the invention, a vector encoding the nucleic acid of the invention and products that can be obtained by the expression of the nucleic acid of the invention such as virus envelopes. The invention further relates a pharmaceutical composition comprising the nucleic acid of the invention or products derived thereof, preferably for use in the prevention of SARS-CoV-2.
The invention relates to the use of an agent for use in treatment of Pityriasis rubra pilaris (PRP). The agent is selected from a ligand capable of specifically binding to, and inhibiting the physiological activity of, interleukin-1, and a nucleic acid agent capable of down-regulating or inhibiting the physiological activity of interleukin-1. In particular embodiments, the invention relates to the use of anakinra in treatment of PRP, particularly therapy-refractive PRP.
A mesenchymal stem/stromal (MSC) cell line, in particular a human mesenchymal stem cell (hMSC), capable of chondrogenic differentiation when cultured in a chondrogenic medium, comprising a first transgene comprising a first nucleic acid sequence encoding for a preferably mammalian immortalizing enzyme under control of a first promoter sequence operable in said mesenchymal cell and a second transgene comprising a second nucleic acid sequence encoding a preferably mammalian bone morphogenic protein under control of a second promoter sequence operable in said mesenchymal cell.
The present invention relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD123 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
86.
DISCERNIBLE CELL SURFACE PROTEIN VARIANTS FOR USE IN CELL THERAPY
The present invention relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD123 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
87.
MR1 LIGANDS AND PHARMACEUTICAL COMPOSITIONS FOR IMMUNOMODULATION
The present invention relates to ligands specifically presented by MR1 molecules to MR1-specific T cells. These ligands are derivatives or analogues of nucleic acid forming bases, particularly ribonucleoside and deoxyribonucleoside adducts occurring in eukaryotic cells under certain conditions. The invention further relates to pharmaceutical preparations and methods for use of such ligands in treatment and research. The invention further relates to pharmaceutical preparations provided with the aim of modulating presentation of MR1 ligands in clinical situations where such modulated presentation of MR1 ligands is of clinical benefit.
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
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
Anti-Siglec-9 antibody molecules or binding fragments thereof are disclosed. These Anti-Siglec-9 antibody molecules or binding fragments can be used to treat cancer, acute or chronic hepatitis B.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
The invention relates to a cleaning head (3) of a toothbrush, said cleaning head comprising a first cleaning head segment (4a) and a second cleaning head segment (4b), the first cleaning head segment (4a) being positioned so as to be adjustable to a rotational position and/or so as to be adjustable to an angle with respect to the second cleaning head segment (4b), a joint (5) for adjusting the predefined angle and/or the rotational position of the first cleaning head segment (4a, 4b) with respect to the second being positioned between the first and the second cleaning head segment (4a, 4b), the cleaning head having at least two holding plates (6, 7) each comprising a cleaning side, in particular comprising cleaning elements, each one of the at least two holding plates (6, 7) being fixed to one cleaning head segment (4a or 4b), and the tensile force for removing the holding plate (6, 7) from the associated cleaning head segment (4a or 4b) being at least 1 N.
Device and method for comminution or inactivation of circulating tumor cells (CTC) or tumor cell clusters (CTCC) from a tumor-affected organ or organ part, wherein it is proposed that in the venous drain of the tumor-affected organ or organ part a pump (2) with a pressure-increasing section and a pressure-reducing throttle (13) is arranged and is operated at the output side in its design point given by volumetric flow (Q) and pumping pressure (p) according to the volumetric flow and the blood pressure of the venous drain of the tumor-affected organ or organ part. Circulating tumor cells (CTC) and tumor cell clusters (CTCC) are thus comminuted and inactivated to thus reduce the risk of metastasis formation in cancerous diseases.
A61M 60/135 - Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient’s body implantable via, into, inside, in line, branching on, or around a blood vessel inside a blood vessel, e.g. using grafting
A61M 60/523 - Regulation using real-time patient data using blood flow data, e.g. from blood flow transducers
A61M 60/531 - Regulation using real-time patient data using blood pressure data, e.g. from blood pressure sensors
A61M 60/31 - Medical purposes thereof other than the enhancement of the cardiac output for enhancement of in vivo organ perfusion, e.g. retroperfusion
A61M 60/237 - Non-positive displacement blood pumps including a rotating member acting on the blood, e.g. impeller the blood flow through the rotating member having mainly axial components, e.g. axial flow pumps
The present application relates to arenavirus particles containing a genome engineered such that an arenaviral open reading frame (“ORF”) is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. The arenavirus particles described herein are genetically stable and provide high-level transgene expression. In certain embodiments, the arenavirus particles are tri-segmented. In particular, described herein is a nucleotide sequence comprising one or more ORFs comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. Also described herein is an arenavirus particle containing a genome engineered such that an arenaviral ORF is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. Also described herein is an arenavirus genomic or antigenomic segment engineered such that the transcription thereof results in one or more mRNA transcripts comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. The arenavirus particles described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.
The present application relates to arenavirus particles containing a genome engineered such that an arenaviral open reading frame ("ORF") is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. The arenavirus particles described herein are genetically stable and provide high-level transgene expression. In certain embodiments, the arenavirus particles are tri-segmented. In particular, described herein is a nucleotide sequence comprising one or more ORFs comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. Also described herein is an arenavirus particle containing a genome engineered such that an arenaviral ORF is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. Also described herein is an arenavirus genomic or antigenomic segment engineered such that the transcription thereof results in one or more mRNA transcripts comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. The arenavirus particles described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.
The invention relates to a HLA-B57 open conformer or a HLA-B57 Fc fusion protein for use in the treatment or prevention of cancer. The Fc open conformer comprises or consists of a first and a second monomer, and each monomer comprises a HLA-B57 chain. The Fc fusion protein further comprises a protein stabilizing polypeptide sequence and optionally an amino acid linker. Further aspects of the invention provide combination medicaments comprising the HLA-B57 Fc open conformer and immune checkpoint inhibitors and/or checkpoint agonist agents. Furthermore, the invention relates to the use of HLA-B57 open conformer as an immunomodulator, particularly in diseases where modulation of diverse immune cell components (e.g. cytotoxic CD8+T cells, Tregs) is a therapeutic strategy, e.g. infectious diseases.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/74 - Major histocompatibility complex [MHC]
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61P 25/00 - Drugs for disorders of the nervous system
95.
MR1 RESTRICTED T CELL RECEPTORS FOR CANCER IMMUNOTHERAPY
The invention relates to a method of isolating a T cell that expresses a T cell receptor capable of binding specifically to an antigen presented by a cancer cell in association with an MR1 molecule. The method comprises the steps of (a) providing a preparation of T cells, (b) contacting the preparation with cancer cells expressing MR1 protein; (c) isolating a T cell that is specifically reactive to said cancer cells.
The invention relates to a method of isolating a T cell that expresses a T cell receptor capable of binding specifically to an antigen presented by a cancer cell in association with an MR1 molecule. The method comprises the steps of (a) providing a preparation of T cells, (b) contacting the preparation with cancer cells expressing MR1 protein; (c) isolating a T cell that is specifically reactive to said cancer cells.
The invention further relates to a method of preparing a T cell preparation expressing select MR1 recognizing T cell receptors from transgene expression vectors, the use of such T cell preparations in treatment of cancer, and to collections of MR1 reactive T cell receptor encoding nucleic acids and cells.
To account for the anatomical variability of the round window, and its surrounding bony structure, and ensure the safety of the delicate round window membrane (RWM) and structures in the cochlea closely adjacent to the RWM, the disclosure provides devices and methods that safely and effectively couple the motion of a variety of actuators to the RWM.
Our invention relates to novel triazine compounds, containing chemical reactive groups (warheads) and behaving as reversible and irreversible covalent inhibitors. Linkers have been introduced to target a solvent exposed, distal cysteine at > 10 Å from the core reversible inhibitor. Different exit vectors have been investigated to modulate inhibitor intrinsic reactivity and efficiency in covalent bond formation. We disclose novel, optimized covalent modifiers of phosphoinositide 3-kinase alpha (PI3Kα), an enzyme frequently altered in human malignancies. The compounds of the invention could be exploited as therapeutic agents and chemical probes useful for the investigation of the role of PI3K isoforms in cancer and metabolism, and for treatment of PI3Kα-driven cancers and malformations.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61P 37/00 - Drugs for immunological or allergic disorders
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
98.
TRIAZINE DERIVATIVE AS REVERSIBLE AND IRREVERSIBLE COVALENT INHIBITORS OF PI3K
Our invention relates to novel triazine compounds, containing chemical reactive groups (warheads) and behaving as reversible and irreversible covalent inhibitors. Linkers have been introduced to target a solvent exposed, distal cysteine at > 10 Å from the core reversible inhibitor. Different exit vectors have been investigated to modulate inhibitor intrinsic reactivity and efficiency in covalent bond formation. We disclose novel, optimized covalent modifiers of phosphoinositide 3-kinase alpha (PI3K?), an enzyme frequently altered in human malignancies. The compounds of the invention could be exploited as therapeutic agents and chemical probes useful for the investigation of the role of PI3K isoforms in cancer and metabolism, and for treatment of PI3K?-driven cancers and malformations.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
99.
TRIAZINE DERIVATIVE AS COVALENT INHIBITORS OF PI3K
Kinase-targeted covalent inhibitors are usually irreversibly targeting noncatalytic cysteines in the ATP- binding site. These compounds are designed by directly introducing an electrophile on a reversible-inhibitor scaffold. Our invention relates to novel triazine compounds, containing chemical reactive groups (warheads), targeting a solvent exposed cysteine at > 10 Å from the core reversible inhibitor. A variety of novel linkers have been designed and used to link the warhead with the reversible scaffold. We disclose a novel chemical space for drug-like covalent modifiers of phosphoinositide 3-kinase alpha (PI3Kα), an enzyme frequently altered in human malignancies. The invention relates to novel covalent inhibitors showing higher in vitro affinity, cellular potency and improved metabolic stability (rat liver microsomes). The compounds of the invention could be exploited as therapeutic agents and chemical probes useful for modulating cellular activities such as signal transduction, proliferation, differentiation and cell death.
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 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61P 25/00 - Drugs for disorders of the nervous system
A61P 37/00 - Drugs for immunological or allergic disorders
A61P 35/02 - Antineoplastic agents specific for leukemia
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
100.
METHOD FOR IDENTIFYING PI3 KINASE-ALPHA INHIBITORS
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
