Presented is an airway organ bioreactor apparatus, and methods of use thereof, as well as bioartificial airway organs produced using the methods, and methods of treating subjects using the bioartificial airway organs. The bioreactor comprises: an organ chamber: an ingres line connecting the organ chamber and a reservoir system and comprising an arterial line, a venous line and a tracheal line; an egress line connecting the chamber and the reservoir system, pumps in ingress and egress lines; a controller to control fluid exchange; a chamber pressure sensor connected to the organ chamber.
The present disclosure relates to methods and compositions for enhanced assessment of exogenous polynucleotide and/or polypeptide-mediated transcriptional perturbations at high throughput and single cell/droplet levels of resolution. In embodiments, nucleic acid fusions of exogenous polynucleotide(s) and associated target transcript(s) are produced within individually sequestered or discretely identifiable cells/lysates and analyzed for exogenous polynucleotide mediated perturbations across a vast population of droplets/cells within individual reactions. Kits for performance of the methods are also provided.
The invention provides a molecular classifier and a targeted sequencing assay for use in characterization and treatment of diffuse large B-cell lymphoma.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A system and a method is provided for assessing motion of a biological tissue of a subject including one or more superficial biological layers and a targeted biological layer. A perturbation unit provide an optical perturbation to the one or more superficial biological layers. An optical signal generator transmits optical signals at one or more near-infrared wavelengths. An optical signal receiver acquires a set of optical signal data preceding, during, or following the optical perturbation at a first acquisition time relative to the optical perturbation. A signal processor determines, using the set of optical signal data, a set of optical characteristics and separates, using the set of optical characteristics, a target optical signal. The signal processor generates a report indicative of a movement of the targeted biological tissue within the subject. The movement of the targeted biological layer is calculated using the target optical signal.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/1455 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using optical sensors, e.g. spectral photometrical oximeters
Disclosed herein are nanoparticles that include one or more cyclodextrin moieties crosslinked by a linker. The cyclodextrin moieties can complex therapeutic (e.g., anticancer) agents, and can be used to treat diseases such as cancer.
A61K 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
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
6.
METHOD AND APPARATUS FOR TISSUE GRAFTING AND COPYING
Exemplary embodiments of apparatus and method for obtaining one or more portions of biological tissue (“micrografts”) to form grafts are provided. For example, a hollow tube can be inserted into tissue at a donor site, and a pin provided within the tube can facilitate controlled removal of the micrograft from the tube. Micrografts can be harvested and directly implanted into an overlying biocompatible matrix through coordinated motion of the tube and pin. A needle can be provided around the tube to facilitate a direct implantation of a micrograft into a remote recipient site or matrix. The exemplary apparatus can include a plurality of such tubes and pins for simultaneous harvesting and/or implanting of a plurality of micrografts. The harvested micrografts can have a small dimension, e.g., less than about 1 mm, which can promote healing of the donor site and/or viability of the harvested tissue.
Systems and methods are provided for generating a statistical parameter representing a state of a surgical procedure from sensor data. Sensor data representing a time period. is received from a sensor. Numerical features representing the time period are generated from the sensor data. Each of a plurality of long short term memory units are updated according to the plurality of numerical features via a message passing process. The long short term memory units are connected to form a graph, with a first set of the long short term memory units representing a plurality of nodes of the graph and a second set of the long short term memory units representing a plurality of hyperedges of the graph. A statistical parameter representing a state of the surgical procedure for the time period is derived from an output of one of the long short term memory units and provided to a user.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G16H 40/63 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation
The disclosure features methods for inhibiting RAS proteins, e.g., RAS proteins that have acquired resistance to one or more RAS inhibitors. The disclosure also methods for the treatment of cancer.
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A system for determining intestinal potential difference. The system includes a measurement probe including a measurement tube having a measurement lumen which houses a measurement electrode therein, a measurement fluid delivery system in fluid communication with the measurement lumen, the measurement fluid delivery system being configured to deliver an electrically-conductive fluid into the measurement lumen such that the electrically-conductive fluid is electrically coupled to the measurement electrode, and the measurement lumen including an outlet at a distal end thereof through which the electrically-conductive fluid exits the measurement lumen and contacts an intestinal tissue of a subject to provide electrical coupling between the measurement electrode and the intestinal tissue; a controller coupled to the measurement electrode configured to measure a potential difference between tire measurement electrode and a reference electrode electrically coupled to the subject.
The subject matter disclosed herein is generally directed to pathogenic Th1 cells whose phenotype is dependent on IL-23R signaling. Th1 cell specific therapeutic targets and gene programs are disclosed herein. In particular, inhibition of CD160 reduces Th1 cell pathogenicity.
Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the residence articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the residence article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the residence article may be configured to control drug release e.g., with zero-order drug kinetics with no potential for burst release for weeks to months. In some embodiments, the residence articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the residence article includes dimensions configured for transesophageal retrieval. In some cases, the residence articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).
The disclosure features antagonistic TNFR superfamily polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the downstream signaling of TNFR superfamily members. The antibodies and antigen-binding fragments thereof can be used to treat a wide variety of cancers, infectious diseases, autoimmune disorders, obesity, type 2 diabetes, neurological disorders, and osteoporosis.
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
14.
METHODS AND COMPOSITION FOR THE TREATMENT OF AUTISM SPECTRUM DISORDER
Disclosed herein are methods and compositions useful for the treatment of Autism Spectrum Disorder (ASD). The methods and compositions include combination therapy with probiotics and oxytocin (OXT), resulting in a therapeutic synergy that exerts beneficial effects on ASD symptoms. The methods and compositions provide improvements in several measurable parameters including but not limited to: measured clinical index for ASD core symptoms, gut microbiome profile, and levels of OXT and inflammatory markers in the blood.
THE GENERAL HOSPITAL CORPORATION d/b/a MASSACHUSETTS GENERAL HOSPITAL (USA)
Inventor
Gray, Nathanael S.
Haggarty, Stephen J.
Cai, Quan
Zhang, Tinghu
Telo Baptista Lima Da Silva, Maria Catarina
Ferguson, Fleur M.
Abstract
Provided herein are bifunctional compounds that bind tau protein and/or promote targeted ubiquitination for the degradation of tau protein. In particular, provided are compounds that can bind tau protein, a protein whose aggregation is implicated in a variety of neurodegenerative disease (e.g., tauopathies), and can promote its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon), which can ubiquitinate tau protein, marking it for proteasomal degradation. Also provided are radiolabeled forms of the bifunctional compounds, pharmaceutical compositions comprising the bifunctional compounds, methods of detecting and/or diagnosing neurological disorders, methods of detecting and/or diagnosing pathological aggregation of tau protein (e.g., in the central nervous system), methods of treating and/or preventing neurological disorders, and methods of promoting the degradation of tau protein by E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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
A61K 31/437 - 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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
The present application relates to novel methods for preventing, slowing the progression of, or treating nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), and/or liver fibrosis, and/or reducing the risks of liver cancer in subjects, such as HIV-infected subjects, using a GHRH molecule, e.g., trans-3-hexenoyl-GHRH(1-44)-NH2, or a pharmaceutically acceptable salt thereof. The subjects may have particular pathological features such as liver fibrosis, a hepatic fat fraction (HFF) of at least about 10%, serum alanine aminotransferase (ALT) levels of at least about 30 U/L, and/or a NAFLD Activity Score (NAS) of at least 4 or 5.
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
18.
Image-seq: A New Technology for Spatially-Resolved Single-Cell RNA Sequencing
A system and method for image-guided cell isolation from a region of interest of a subject is disclosed. The system and method include imaging the subject using optical microscopy to identify the region of interest in a target anatomy, inserting a micropipette into the region of interest under guidance of the optical microscopy, and aspirating at least one cell of a target population of cells in the region of interest under guidance of the optical microscopy. The method further includes analyzing the at least one cell aspirated from the region of interest.
A61B 10/02 - Instruments for taking cell samples or for biopsy
A61B 18/20 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
A61B 90/20 - Surgical microscopes characterised by non-optical aspects
A method for the systemic delivery of a polypeptide within a subject is provided by creating genetically modified skin cells via topical introduction of a genetically engineered virus which delivers a nucleic acid encoding a therapeutic polypeptide for expression by the skin cells, wherein the expressed therapeutic polypeptide is secreted by the skin cells and is introduced into the circulatory system of the subject.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
Antibodies, and antigen-binding fragments thereof, that specifically bind to bone morphogenetic protein-9 (BMP9) are provided. Embodiments include uses, and associated methods of using the antibodies, and antigen-binding fragments thereof.
Described herein are methods of treating neuron inflammation conditions, for example, Alzheimer's disease, Parkinson's disease, Huntington's disease, ischemic stroke, and prion disease, comprising administering a therapeutically effective amount of cromolyn or a cromolyn derivative compound.
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 9/00 - Medicinal preparations characterised by special physical form
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 311/22 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
C07D 311/24 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
The present invention provides compositions and methods for treating cancer in a human. The invention includes a chimeric receptor which comprises an CD64 binding domain, a transmembrane domain, and a CD3zeta signaling domain.
This disclosure provides a method for substantially increasing the concentration of cfDNA in a patient. By injecting a patient with lipid and/or polymer nanoparticles, agents that bind cfDNA, or inhibit deoxyribonucleases prior to collection of a sample of cfDNA, e.g., by way of a liquid biopsy, major pathways for the degradation of cfDNA are temporarily blocked, permitting transient accumulation of cfDNA. This strategy has the potential to dramatically enhance the quality of detection achieved by downstream cfDNA e analytical applications, such as sequencing applications.
A system and method for measuring and monitoring blood pressure is provided. The system includes a wearable device and a tonometry device coupled to the wearable device. The Tonometry device is configured to compress a superficial temporal artery (STA) of a user. A sensor pad is attached to the wearable device adjacent the tonometry device. A blood pressure sensor is integrated within the sensor pad for continuous, unobtrusive blood pressure monitoring.
The subject matter disclosed herein is generally directed to genetic variants associated with local adiposity traits and metabolic disease. Embodiments disclosed herein provide genetic variants associated with local adiposity traits obtained by adjusting adiposity traits for BMI and height. Embodiments disclosed herein also provide genes linked to variants and associated with the local adiposity traits. The local adiposity traits are associated with metabolic disorders. In example embodiments, variants indicate risk for a metabolic disorder and can be used to determine treatment. In example embodiments, genes associated with local adiposity traits and/or variants can be targeted therapeutically. In example embodiments, a risk for a metabolic disorder can be determined by detecting one or more risk variants associated with a local adiposity trait.
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
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
27.
SYSTEM AND METHOD FOR HIGH-RESOLUTION, HIGH-SPEED CAPSULE ENDOMICROSCOPY
A probe for performing endomicroscopy, including: a light source; a waveguide coupled to the light source; a diffraction grating, the waveguide directing light from the light source to the diffraction grating; and a lens having a first aspheric surface and a second biconic surface, diffracted light from the diffraction grating being directed into the aspheric surface of the lens and being emitted from the biconic surface of the lens towards a transparent cylindrical surface of the probe.
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. endoscopes; Illuminating arrangements therefor
A61B 1/04 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
Described herein are methods for diagnosing and monitoring subjects with diseases associated with aberrant splicing, based upon detecting properly spliced isoforms and mis-spliced isoforms in a urine sample from the subject.
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
C12Q 1/6865 - Promoter-based amplification, e.g. nucleic acid sequence-based amplification [NASBA], self-sustained sequence replication [3SR] or transcription-based amplification system [TAS]
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
29.
Methods for Detecting Site-Specific and Spurious Genomic Deamination Induced by Base Editing Technologies
The technology described herein is directed to methods of determining oligonucleotide sequences, e.g. by enriching target sequences prior to sequencing the sequences.
Systems and methods are provided for provided for automatic evaluation of a human embryo. An image of the embryo is obtained and provided to a neural network to generate a plurality of values representing the morphology of the embryo. The plurality of values representing the morphology of the embryo are evaluated at an expert system to provide an output class representing one of a current quality of the embryo, a future quality of the embryo, a likelihood that implantation of the embryo will be successful, and a likelihood that implantation of the embryo will result in a live birth.
The present application relates to polypeptides which are integrin antagonists. Methods of preparing the integrin antagonists and methods of treating diseases and disorders associated with abnormal levels and/or expression of one or more integrins are also provided.
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
In some embodiments, devices, systems, and methods for advancing and positioning tethered capsule microendoscopes are provided. In some embodiments, a device for capsule endomicroscopy is provided, comprising: a tether having a proximal end and distal end; an optical fiber disposed within the tether; a tube enclosing at least a portion of the tether, the tube having a proximal end and a distal end, a diameter of the tube being larger than the diameter of the tether; a housing coupled to the distal end of the tether and the distal end of the tube; and an optical element disposed within the housing, the optical element being optically coupled to the distal end of the optical fiber and configured to direct light received from the optical fiber toward a periphery of the housing.
A61B 1/04 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
A61B 1/00 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
A61B 1/07 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements using light-conductive means, e.g. optical fibres
A61B 1/273 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor for the upper alimentary canal, e.g. oesophagoscopes, gastroscopes
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
34.
CHIMERIC ANTIGEN RECEPTOR T CELLS TARGETING THE TUMOR MICROENVIRONMENT
The invention provides methods and compositions for use in treating cancer, which advantageously may be achieved by targeting of the tumor microenvironment.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
35.
Genome editing approaches to treat Spinal Muscular Atrophy
Described herein are methods and compositions for treating subjects with spinal muscular atrophy (SMA) using CRISPR editing of exon 7 and/or intron 7 of SMN2.
Provided herein are methods of intracellular delivery of a substance to one or more cells. The methods include providing a substrate defining a micro-channel in fluid communication with a first chamber and optionally in fluid communication with a second chamber, the micro-channel having a hydraulic diameter that is less than a hydraulic diameter of the first and second chambers; and driving a cell suspension through the micro-channel, thereby: i) causing the one or more cells to be stretched along a direction of flow and ii) inducing a formation of one or more temporary pores in a membrane of the one or more cells, wherein the cell suspension comprises the one or more cells, a polymer, and the substance. Also provided are systems for the intracellular delivery of a substance to one or more cells.
Disclosed herein are RNA methyltransferase inhibitors and methods of using and making the same. The inhibitors may be used in a method for the treatment of a subject in need of a treatment for a cancer by administering an effective amount of the RNA methyltransferase inhibitor and an effective amount of a DNA damaging agent to the subject.
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/502 - Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
One aspect of the invention provides a method of ovarian protection by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). Ovarian protection can be an induced arrest of folliculogenesis to preserve fertility. In some embodiments, ovarian protection is oncoprotection, the protection of the ovarian function during a cytotoxic treatment, e.g., chemotherapy. Another aspect of the invention relates to a method of treating PCOS, the method comprising administering to a female subject a composition comprising recombinant MIS protein.
Novel cromolyn analogs useful as imaging agents for detecting atherosclerotic plaques and for treating atherosclerosis and Alzheimer's Disease, and methods of making the cromolyn analogs, are disclosed. The cromolyn analogs have the general formula:
Novel cromolyn analogs useful as imaging agents for detecting atherosclerotic plaques and for treating atherosclerosis and Alzheimer's Disease, and methods of making the cromolyn analogs, are disclosed. The cromolyn analogs have the general formula:
Novel cromolyn analogs useful as imaging agents for detecting atherosclerotic plaques and for treating atherosclerosis and Alzheimer's Disease, and methods of making the cromolyn analogs, are disclosed. The cromolyn analogs have the general formula:
wherein X is OH, C1-C6 alkoxyl; Y and Z are independently selected from a C1-C6 alkyl, C1-C6 alkoxyl, halogen, un-substituted or C1-C6 substituted amine, 18F, 19F, or H; and n is 1, 2 , or 3; and wherein for structure (I), if n are both 1 and Y and Z are both H and X is OH.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
C07D 311/24 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
The present disclosure provides bioorthogonal linkers and reagents, including trans-cyclooctene (“TCO”)- and tetrazine (“Tz”)-containing compounds. In a general aspect, the present disclosure provides reagents, conjugates, and bioactive molecules containing a trans-cyclooctene (“TCO”) fragment. Examples of TCO fragments include: Formulae (I) and (II).
The present disclosure provides bioorthogonal linkers and reagents, including trans-cyclooctene (“TCO”)- and tetrazine (“Tz”)-containing compounds. In a general aspect, the present disclosure provides reagents, conjugates, and bioactive molecules containing a trans-cyclooctene (“TCO”) fragment. Examples of TCO fragments include: Formulae (I) and (II).
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
The present invention provides methods and compositions based on a non-naturally occurring nucleic acid construct encoding a fusion protein for quantitating levels of secretion in a single cell which may comprise a protein sequence which may comprise a cytoplasmic domain, a transmembrane domain and a vesicular domain, wherein the vesicular domain may comprise a protein tag sequence, wherein upon expression of the fusion protein by a cell, the fusion protein localizes to the membrane of a secretory vesicle such that the protein tag localizes to the lumen of the secretory vesicle, and wherein the protein tag binds to a cell-impermeable marker; whereby upon secretion of the contents of the secretory vesicle, the protein tag is exposed to the cell-impermeable marker, the fusion protein is recycled back into the cell, and the single cell becomes labeled with the marker relative to the amount of secretion.
The invention provides compositions and methods useful in characterizing and/or treating classical Hodgkin's Lymphoma and/or primary mediastinal B-cell lymphoma (PMBL). In embodiments, the characterization is carried out using a biological sample comprising circulating tumor DNA (ctDNA) from a subject.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
43.
PROBIOTICS COMPOSITIONS AND METHOD OF USING THE SAME TO ENHANCE GROWTH AND SOCIAL FUNCTION IN CHILDREN
Disclosed herein are methods and compositions useful for the treatment of subjects suffering from Prader-Willi Syndrome (PWS). The methods include administering compositions comprising probiotics, such as Lactobacillus reuteri (L. reuteri) and Bifidobacterium animalis subsp. lactis (B. lactis) to subjects in need thereof.
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
44.
PANCREATIC DUCTAL ADENOCARCINOMA SIGNATURES AND USES THEREOF
Described herein are pancreatic ductal adenocarcinoma (PDAC) signatures and methods of detecting the same in a sample from heterogeneity-score a subject. Also described herein, are methods of methods of diagnosing, prognosing, and/or treating PDAC in a subject that can include detecting one or more of the PDAC signatures.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
45.
METHODS AND SYSTEMS FOR NON-CONTACT CONSTRUCTION OF AN INTERNAL STRUCTURE
The present disclosure includes system, methods, and kits relating to creating a second structure with a plurality of first structures at a target site inside or adjacent to a host object. The methods include the step of generating a field that non-invasively penetrates into the host object. The methods further include the step of positioning a first portion of the plurality of first structures at the target site using a force corresponding to the field. Additionally, the methods include the step of linking the first portion of the plurality of first structures with one another and/or the host object at the target site to form the second structure.
A61M 37/00 - Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
A method of treating and preventing viral infection in a subject comprising administering an effective amount of one or more inhibitors of folate or one-carbon metabolism pathways to the subject.
A61K 31/4412 - Non-condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
A61K 31/4162 - 1,2-Diazoles condensed with heterocyclic ring systems
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/198 - Alpha-amino acids, e.g. alanine, edetic acid (EDTA)
A61K 31/4418 - Non-condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic ring directly attached to the heterocyclic ring, e.g. cyproheptadine
A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Described herein are compositions comprising, and methods for using, biocompatible cold slurries and methods of administering the same to provide reversible inhibition of peripheral nerves in a subject in need thereof.
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61K 31/245 - Amino benzoic acid types, e.g. procaine, novocaine
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 47/18 - Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
48.
METHODS AND COMPOSITIONS FOR IN SITU MACROMOLECULE DETECTION AND USES THEREOF
The present disclosure relates to compositions and methods for detecting nucleic acid sequences (e.g., coding and non-coding RNAs; nuclear/genomic DNA; mtDNA; pathogen nucleic acids, etc.) in a tissue sample, specifically providing improved matrices and matrix-employing methods for performance of nucleic acid capture and amplification in a tissue sample in situ and/or in a manner that retains spatial location information for captured nucleic acids (including nucleic acid-associated macromolecules).
A system for awake functional magnetic resonance imaging (fMRI) of an animal subject includes an RF coil apparatus and a tunnel apparatus. The RF coil apparatus includes an RF coil configured to be implanted on the animal subject, a head post coupled to the RF coil and comprising a housing and a circuit board positioned within the housing, and a connector coupled to the circuit board. The tunnel apparatus includes a first end having an opening, a second end, a slot positioned on a top side of the tunnel apparatus and configured to movably receive the head post of the RF coil apparatus, and an inner region configured to receive the animal subject and allow the animal subject to move from the first end to the second end.
G01R 33/34 - Constructional details, e.g. resonators
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
A61B 5/0205 - Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
50.
APPARATUS, METHODS AND COMPUTER-ACCESSIBLE MEDIA FOR IN SITU THREE-DIMENSIONAL RECONSTRUCTION OF LUMINAL STRUCTURES
An apparatus for determining a shape of a luminal sample including: a catheter including a lens, the catheter disposed within a strain-sensing sheath such that the lens rotates and translates; a structural imaging system optically coupled to the catheter; a strain-sensing system optically coupled to the catheter; and a controller coupled to the strain-sensing system and the structural imaging system. The controller determines: a first position of the catheter relative to the luminal sample at a first location within the strain-sensing sheath; a second position of the catheter relative to the luminal sample at a second location within the strain-sensing sheath; a first strain of the strain-sensing sheath at the first location; a second strain of the strain-sensing sheath at the second location; a local curvature of the luminal sample relative to the catheter; a local curvature of the catheter; and a local curvature of the luminal sample.
A first layer, a first spacer layer, and a second layer of a semiconductor wafer can be etched to produce a plurality of columnar structures extending from the substrate layer and including a first optical cavity situated about the first gain medium, a second optical cavity situated about the second gain medium, and a first spacer region contacting the first gain medium and the second gain medium. Also, a photonic microparticle formed from a layered semiconductor wafer and of a columnar structure having a first optical cavity situated about a first gain medium, a second optical cavity situated about a second gain medium, and a first spacer region contacting the first gain medium and the second gain medium. The first optical cavity and the second optical cavity in the photonic microparticle are each capable of generating laser light with a distinct spectral peak when energetically excited.
The present application provides compounds that modulate the activity of one or more salt inducible kinases (SIKs). Pharmaceutical composition and methods of treating diseases associated with abnormal expression and/or activity of one or more SIKs are also provided.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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
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
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 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
53.
CHOLESTEROL REDUCING COMPOSITIONS AND METHODS OF USE THEREOF
Microbes expressing cholesterol oxidoreductase (COR) proteins, methods of engineering the microbes expressing COR proteins, compositions and methods of using the microbes are provided.
A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
A61K 9/00 - Medicinal preparations characterised by special physical form
C12N 15/70 - Vectors or expression systems specially adapted for E. coli
C12N 9/04 - Oxidoreductases (1.), e.g. luciferase acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
C12Q 1/26 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
The present disclosure provides methods of anchoring active molecules on the surface of a cell, methods of anchoring at least two active molecules on the surface of a cell, and methods of enhancing an immune response to a target cell in a human.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
C07H 15/12 - Acyclic radicals, not substituted by cyclic structures attached to a nitrogen atom of a saccharide radical
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
The present invention relates to use of the compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof in the manufacture of a medicament or pharmaceutical composition for preventing, treating or lessening POD,
The present invention relates to use of the compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof in the manufacture of a medicament or pharmaceutical composition for preventing, treating or lessening POD,
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
56.
MODULATING HEMATAOPOIESIS AND MYLEOID CELL PRODUCTION
The invention features a method of treating a disease or disorder in a subject, the method comprising administering a therapeutically effective amount of a 5′-tiRNA to treat the disease or disorder in the subject.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
57.
COMPOSITIONS AND METHODS COMPRISING ENERGY ABSORBING MATERIALS FOR FOLLICULAR DELIVERY
The present invention provides compositions comprising energy (e.g., light) absorbing submicron particles (e.g., nanoparticles comprising a silica core and a gold shell) and methods for delivering such particles via topical application. This delivery is facilitated by application of mechanical agitation (e.g. massage), acoustic vibration in the range of 10 Hz-20 kHz, ultrasound, alternating suction and pressure, and microjets.
Described herein are methods and assays relating to the presence and/or level of circulating tumor cells (CTCs). These CTC-Cs represent a highly metastatic subpopulation of CTCs. In some embodiments, the methods and assays described herein relate to the treatment of cancer.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
59.
Antibodies and Single-Chain Variable Region Proteins Recognizing Click Products
The present disclosure is directed, at least in part, to click-product binding molecules for recognition of templated assembly products defined by bioorthogonal click groups. Such molecules can be used for therapeutic and diagnostic purposes, including kits for the same.
Disclosed herein are RNA methyltransferase inhibitors and methods of using the same. The inhibitors may be used in a method for the treatment of a subject in need of a treatment for a cancer by administering an effective amount of an RNA methyl-transferase inhibitor to the subject.
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
Systems and methods are provided for neurostimulation timed relative to respiratory activity. Neurostimulation may be delivered to the spinal cord, the vagus nerve, and/or branches of the vagus nerve to provide therapeutic outcomes by controlling or adjusting stimulation based on pulmonary activity. In particular, the systems and methods use a detecting device to detect respiratory activity over time. Specific points in the respiratory signal are identified where central autonomic nuclei may be more receptive to afferent input and a stimulator is instructed to provide neurostimulation to at least one auricular branch of a vagus nerve, or to a cervical branch of the vagus nerve, or to a spinal cord of the subject. In this regard, the neurostimulation is advantageously correlated to the detected respiratory activity providing improved therapeutic outcomes.
Korea Advanced Institute of Science and Technology (Republic of Korea)
Inventor
Lee, Hakho
Im, Hyungsoon
Bae, Nam Ho
Lee, Seok Jae
Lee, Kyoung Gyun
Kim, Kwang Hee
Roh, Kil Sun
Abstract
Methods, systems, and apparatus, for a sensor-chip device for performing analysis on target substances. In one aspect, the sensor-chip assembly includes a chip body including a substrate, at least one metal layer formed on the substrate, and nanoholes formed in the metal layer, a base having an accommodating portion for accommodating the chip body, and a fixing member fixing the chip body accommodated in the accommodating portion by being coupled to the base.
The present disclosure provides methods of metabolically labeling cells to provide a substrate for assembly of desired molecules, and to bifunctional compounds used in such methods.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
Next Generation Sequencing (NGS)-based methods using Methylation Sensitive Restriction Enzymes (MSREs) for methylation analysis of DNA, e.g., circulating tumor DNA.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
Systems and methods for shielded fluid transfer are provided. A fluid transfer shield is provided to facilitate transferring fluid from a first container to a secondary container. The fluid transfer shield includes a shield having an exterior and defining an interior space, a first port extending from the exterior of the shield, the first port configured to be fluidly coupled to the first container, and a second port extending opposite the first port and into the interior space of the shield so that the shield laterally surrounds the second port, the second port configured to be fluidly coupled to the secondary container. A passageway is provided that extends between the first port and the second port to fluidly couple the first container and the secondary container when the first container is fluidly coupled to the first port and the secondary container is fluidly coupled to the second port.
Drug-inducible, tunable, and multiplexable Clustered Regularly Interspaced Short Palindromic Repeats from Prevotella and Francisella 1 (Cpf1)-based activators, and methods of use thereof.
Exemplary methods and devices can be provided for harvesting a plurality of small tissue pieces, e.g., having widths less than about 1 mm or 0.5 mm, using one or more hollow needles. A fluid can be flowed through a conduit past the proximal ends of the needles to facilitate removal of the tissue pieces from the needle lumens, and can maintain the tissue pieces in a controlled and protective liquid environment. A filter can be used to extract and collect the tissue pieces from the liquid, or the tissue pieces can be deposited directly onto a porous dressing. Such tissue pieces can be used as microscopic grafts, which can be applied directly to a wound site or provided on a substrate or dressing, or stored for later use. Such microscopic grafts can promote tissue regrowth and wound healing, or can be applied to a scaffold to grow new tissue.
A61B 10/02 - Instruments for taking cell samples or for biopsy
A61M 1/00 - Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
Disclosed herein is a nanosensor of miRNA activity in a target cell, and methods of use, for detection and diagnostic applications. The nanosensor comprises a delivery particle comprising an iron oxide crystal coated with a polymer, and a sensor oligonucleotide covalently attached to the polymer. The sensor oligonucleotide comprises a seed region, comprising a nucleic acid sequence that is completely complementary to the target miRNA and comprises a cleavage site which can be engaged and cleaved by the target miRNA. The senor oligonucleotide also comprises two non-seed regions that each flank the seed region and are each comprised of a nucleic acid sequence that is complementary to the target miRNA to promote hybridization of the sensor oligonucleotide to the target miRNA, and members of a quencher-fluorophore pair. The quencher fluorophore pair members respectively flank the cleavage site and are separated by a distance that permits significant quenching of emitted fluorescent signal.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C12Q 1/6818 - Hybridisation assays characterised by the detection means involving interaction of two or more labels, e.g. resonant energy transfer
70.
METHODS FOR IDENTIFYING DRIVERS OF IMMUNE RESPONSES USING MOLECULAR EXPRESSION SIGNATURES OF IMMUNOMODULATING AGENTS
The present disclosure provides methods for determining signatures of immune responses to immunomodulating agents in cells and in tissues. Also provided herein are computational methods for deconvoluting gene expression profiling data. Further provided herein are methods for treating a disease or disorder (e.g, proliferative diseases such as cancer, autoimmune diseases such as rheumatoid arthritis and psoriasis, allergies, etc.) in a subject comprising administering one or more immunomodulating agents to drive an immune response, in combination with a treatment for the disease or disorder (e.g, an anti-cancer therapy, an anti-viral therapy, a vaccination, etc.).
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
71.
Bifunctional Compounds And Methods Of Using The Same
The present disclosure provides bifunctional compounds and methods of labeling a cell having an azide-modified sugar on its surface by contacting the cell with a bifunctional compound.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 211/32 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
72.
Engineered CRISPR-Cas9 Nucleases with Altered PAM Specificity
Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.
The present disclosure relates to magnetic resonance imaging (MRI) using biochemically responsive imaging probes that can be used in, for example, non-invasive pH mapping in cancer and/or diseases characterized by aberrant metabolism using contrast enhanced MRI.
An injectable nanoparticular formulation and method of use thereof for treating non-compressible hemorrhage or internal bleeding has been developed. The formulation includes two interactive components, one a targeting nanoparticle with a polypeptide sequence that binds to a cell present at a site of injury, and the other a crosslinking nanoparticle with a bioorthogonal click-crosslinking group.
Provided herein are therapeutic nanoparticles including a radiolabel, a chelator that is covalently linked to the therapeutic nanoparticle and to the radiolabel, and a nucleic acid molecule that is covalently linked to the therapeutic nanoparticle. The therapeutic nanoparticle has a diameter between about 10 nanometers (nm) to about 30 nm, and the therapeutic nanoparticle is magnetic. Also provided are pharmaceutical compositions containing these therapeutic nanoparticles. Also provided herein are methods of decreasing cancer cell invasion or metastasis in a subject having a cancer and methods of treating a metastatic cancer in a lymph node in a subject that require the administration of these therapeutic nanoparticles to a subject. Also provided herein are methods of detecting, diagnosing, and/or monitoring a metastatic cancer tissue in a subject. Also provided herein are methods of preparing these therapeutic nanoparticles.
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
A61P 35/04 - Antineoplastic agents specific for metastasis
In some embodiments, systems, methods, and media for multiple reference arm spectral domain optical coherence tomography are provided which, in some embodiments, includes: a sample arm coupled to a light source; a first reference arm having a first path length; a second reference arm having a longer second path length; a first optical coupler that combines light from the sample arm and the first reference arm; a second coupler that combines light from the sample arm and the second reference arm; and an optical switch comprising: a first input port coupled to the first optical coupler; a second input coupled to the second coupler via an optical waveguide that induces a delay at least equal to an acquisition time of an image sensor; and an output coupled to the image sensor.
Provided herein are microfluidic platforms and methods of use thereof for generating, tracking, monitoring, and analyzing thousands of droplets per second for interactions between two or more particles, such as cells, encapsulated in individual droplets, wherein the individual droplets are uniquely identified by specific ratios of multiple different optical barcodes and at least one sequence barcode per droplet.
The present application relates to methods, reagents and kits for the assessment of the severity of nonalcoholic fatty liver disease (NAFLD) in a patient over time, and/or of the likelihood that a subject suffers from NAFLD. The methods, reagents and kits are based on the determination of the levels of VEGFA, TGFB1, and/or CSF1 in a biological sample, such as a plasma sample, from the subject. The methods, reagents and kits may be used, for example, for assessing the progression of NAFLD in a patient and/or the response of the patient to therapy.
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
80.
COMPOSITIONS AND METHODS FOR TUMOR CHARACTERIZATION
The invention provides methods for characterizing microsatellite instability in biological samples and for selecting a treatment for a subject having a neoplasia.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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
81.
TARGETING XIST AND RNA METHYLATION FOR X REACTIVATION THERAPY
Described herein are compositions of one or more inhibitors of XIST RNA and inhibitors of RNA methylation. Also described are methods of using said compositions, or said inhibitors separately, to activate expression of one or more alleles in a cell—e.g., an inactive X-linked allele, an epigenetically silenced allele, or a hypomorphic allele. For example, described herein are methods for reactivating genes on the inactive X chromosome that include administering both of an inhibitor of XIST RNA (e.g., an inhibitory nucleic acid, such as an antisense oligonucleotide (ASO), e.g., locked nucleic acid (LNA), that targets XIST RNA), and an inhibitor of RNA methylation, e.g., a small molecule or an inhibitory nucleic acid, such as an antisense oligonucleotide (ASO), e.g., shRNA, or siRNA, that targets an RNA encoding a factor involved in RNA methylation, e.g., an m6a protein.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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
82.
Methods and Compositions for Reducing Immunosupression by Tumor Cells
The General Hospital Corporation d/b/a Massachusetts General Hospital (USA)
Inventor
Wucherpfennig, Kai W.
Dranoff, Glenn
Zhou, Penghui
Shaffer, Donald
Hacohen, Nir
Cantor, Harvey I.
Alvarez Arias, Diana
Abstract
The present disclosure provides, in part, methods of discovering immunotherapy targets in vivo, therapeutic compositions (e.g., shRNA, immunoresponsive cells expressing shRNA and/or a chimeric antigen receptors (CAR)), and methods of use thereof.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
Provided herein are methods for treating cancer and for selecting a cancer treatment based on the expression of Stag2/3 proteins and/or the presence of mutations in the genes encoding Stag2/3 proteins.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
Described are antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and/or myeloid-derived suppressor cells (MDSCs), to expand T effector cell populations or function, and to reduce the proliferation of, or directly kill, tumor cells, such as tumor cells that express TNFR2 antigen. The polypeptides, such as antibodies and antigen-binding fragments thereof, are TNFR2 antagonists, such as dominant TNFR2 antagonists. The polypeptides can be used to suppress the T-reg- or MDSC-mediated deactivation of tumor reactive T lymphocytes, expand populations of tumor-reactive cytotoxic T cells, and/or to directly kill TNFR2+ tumor cells. The antagonistic TNFR2 polypeptides described herein can be used to treat a wide variety of cancers and infectious diseases.
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 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
87.
Ice Nucleation Formulations for Cryopreservation and Stabilization of Biologics
A platform for creating engineered tissues includes a vascular tube that defines a vascular diameter and is configured to receive vascular system seed cells, a non-vascular tube that defines a non-vascular tube diameter and is configured to receive organ system seed cells, and a barrier formed between the vascular tube and the non-vascular tube.
Methods of bulk cryopreservation of C. parvum oocysts by vitrification using high aspect ratio cryopreservation devices are disclosed. Cryopreserved oocysts exhibit high viability, maintain infectivity in vitro, and are infectious to interferon-γ knockout mice. The course of the infection is comparable to that observed with unfrozen oocysts.
Provided herein are methods for inducing an anti-tumor immune response and/or treating cancer comprising treating tumor tissue of the subject with energy to induce fractional tissue damage in combination with one or more checkpoint molecule modulating agents.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61B 18/20 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
The present disclosure provides systems and method for medical ice slurry production. In particular, systems and methods are provided for medical ice slurry production that enable an end user to produce and deliver a sterile medical ice slurry at the point of care.
Systems and methods for tracking sympathetic-driven arousal state (SDAS) including nociception under anesthesia is described herein. The method includes obtaining heart rate variability and electrodermal activity of a subject. Point process models are generated for the heart rate variability and the electrodermal activity. A multimodal approach is implemented to determine a state space framework based on these point process models. SDAS can be estimated using the state space framework. In some implementations, an anesthesiologist can modify the dosage of drugs administered to the subject based on this estimation.
The present invention provides triazolone compounds of general formula (I):
The present invention provides triazolone compounds of general formula (I):
The present invention provides triazolone compounds of general formula (I):
in which R1, R2, R3, R4, and R5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment and prophylaxis of diseases, in particular hyperproliferative disorders, as a sole agent or in combination with other active ingredients.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Methods of the invention encompass delivery of nucleic acid sequences encoding ABCD1 for the treatment of X-linked Adrenoleukodystrophy (X-ALD), e.g., for Adrenomyeloneuropathy (AMN).
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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
95.
BONE MARROW MICROFLUIDIC DEVICES AND METHODS FOR PREPARING AND USING THE SAME
The present disclosure relates to a microfluidic devices and methods for culturing bone marrow cells. Aspects include methods of preparing microfluidic devices and culturing bone marrow cells with the microfluidic devices. In some aspects, a method includes providing a microfluidic device having an upper chamber, a lower chamber, and a porous membrane separating the upper chamber from the lower chamber. The method further includes seeding walls of the lower chamber and a bottom surface of the membrane with endothelial cells. The method further includes providing a matrix within the upper chamber. The matrix includes fibrin gel and bone marrow cells. The method further includes filling or perfusing the upper chamber with a media.
Diffusion-weighted data are acquired with an MRI system. From the diffusion-weighted data, a comprehensive diffusion tensor distribution (CDTD) is generated. The provides a proportional weighting, at the voxel level, of different diffusion tensors that could describe the water diffusion occurring in the voxel. The CDTD provides insight into tissue microstructure without making assumptions about the structure of a diffusion tensor used to characterize diffusion occurring in tissues of interest. Water pool images, corresponding to different subsets of diffusion tensors in the CDTD, may be generated to assess different components of water diffusion in tissue. Classification images can also be generated from the CDTD to depict different clusters of voxels having similar distributions of diffusion tensors.
A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
97.
LIPID SUPPRESSION IN MAGNETIC RESONANCE IMAGING USING MULTI-COIL LOCAL B0 FIELD CONTROL
Lipid suppression in magnetic resonance imaging (“MRI”) is provided on a slice-by-slice basis using tailored local field control that is configured for lipid control for each slice in a planned slice prescription. Only those lipid voxels that fall within the bandwidth of the concurrent RF excitation pulse are targeted. Switched B0 offset fields are used to improve lipid suppression pulse performance by pushing water and lipids apart in the frequency domain. Multi-coil B0 shim arrays with rapidly switchable output currents that can be turned on during the lipid suppression pulse may be used. A convex optimization may be used to jointly solve for the shim currents and the lipid suppression pulse center frequency and bandwidth to optimize lipid suppression while minimizing water signal loss.
The present application provides a compound of Formula (I): A-L-B (I), or a pharmaceutically acceptable salt thereof, wherein A, L, and B are as described herein. Compositions comprising the compounds of Formula (I) (and optionally a fluorescent probe) are also provided, as well as the methods of (i) using the compound of formula (I) for identifying a misfolding-prone or an aggregating-prone protein in a sample, (ii) determining concentration of a misfolding-prone or an aggregating-prone protein in a sample, (iii) imaging an organ or tissue comprising a misfolding-prone or an aggregating-prone protein in a subject, (iv) diagnosing or monitoring treatment of a disease or condition associated with a misfolding-prone or an aggregating-prone protein in a subject, and (v) diagnosing a disease or condition characterized by accumulation of misfolding-prone or aggregation-prone peptides or proteins in a blood of a subject.
The present invention provides a system and method for performing a single-scan rest-stress cardiac measurement. In one aspect, the system includes a positron emission tomography (PET) imaging system, a source of a first PET radiotracer for administration to a subject, a source of a second PET radiotracer for administration to a subject, and a processor. The processor has non-transient computer readable media programmed with instructions to obtain PET images of the subject administered with the radiotracer. Furthermore, the computer readable media is programmed with instructions to process the PET images with a non-steady-state, multi-compartment parametric model. An output of the non-steady-state, multi-compartment parametric model is a measure of myocardial blood flow for both a rest state and a stress state of the subject.
This invention relates to polycomb-associated RNAs, libraries and fragments of those RNAs, inhibitory nucleic acids and methods and compositions for targeting RNAs, and methods of use thereof.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
patents
