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
G01N 33/566 - ImmunoassayBiospecific binding assayMaterials therefor using specific carrier or receptor proteins as ligand binding reagent
2.
SYSTEM AND METHOD FOR PROTEIN CORONA SENSOR ARRAY FOR EARLY DETECTION OF DISEASES
G01N 15/02 - Investigating particle size or size distribution
G01N 27/00 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
G01N 27/26 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variablesInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by using electrolysis or electrophoresis
G01N 27/60 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrostatic variables
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
3.
AUTOMATED EVALUATION OF QUALITY ASSURANCE METRICS FOR ASSISTED REPRODUCTION PROCEDURES
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G16H 40/20 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the management or administration of healthcare resources or facilities, e.g. managing hospital staff or surgery rooms
4.
ELECTROPHILIC REACTIVE LINKERS FOR LABELING OF POLYPEPTIDES AND METHODS OF USE THEREOF
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
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
7.
TREATMENT OF SOLID TUMORS WITH IMPLANTABLE POLYMERS WITH SMALL MOLECULES OR CELLS
A61K 9/52 - Sustained or differential release type
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61K 47/60 - 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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61M 31/00 - Devices for introducing or retaining media, e.g. remedies, in cavities of the body
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
10.
BIFUNCTIONAL CHIMERIC MOLECULES FOR LABELING OF KINASES WITH TARGET BINDING MOIETIES AND METHODS OF USE THEREOF
A61P 31/06 - Antibacterial agents for tuberculosis
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
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
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
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 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
13.
PLATINUM COMPLEXES, RELATED COMPOSITIONS, AND USES THEREOF IN CYANIDE COUNTERMEASURES
KLRB1 binding agents (in particular anti-KLRB1 antibodies and antigen binding portion thereof) and compositions thereof, as well as therapeutic methods of using the agents, e.g., for depleting cells or inhibiting cells or activating cells (in particular, Th17, Th17.1, ex-Th17, Tc17, MAIT, iNKT, peTh2, ILC2, ILC3, NK cells, and/or neoplastic T or NK cells in vivo), for the treatment of autoimmune disease, allergic diseases, transplant rejection, hematologic malignancies, and cancer
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
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
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
16.
COMPOSITIONS FOR LOCAL THERAPY DELIVERY TO BRAIN TUMORS AND METHODS
Compositions for local delivery of a drug to an intracranial region, such as brain tissue or a brain tumor. Methods for locally delivering drug or therapy to an intracranial region. Compositions may include a hydrogel in which a chemotherapy drug or immunotherapy drug is dispersed. Kits that include compositions or solutions that may be combined to form compositions.
Provided herein are recombinant antibodies and antigen-binding fragments thereof useful for binding to and inhibiting carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Also provided are methods of using the disclosed CEACAM1 antibodies and antigen-binding fragments thereof for reducing T-cell tolerance and for the treatment of cancer and infection.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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
18.
USE OF MICROVESICLE SIGNATURES IN THE IDENTIFICATION AND TREATMENT OF RENAL DISORDERS
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
19.
COMPANION DIAGNOSTIC FOR HUMAN CEACAM1 DIRECTED THERAPEUTIC AGENTS
Provided herein are methods and compositions for determining if a subject diagnosed with a CEACAM1-related disease or disorder is administered a CEACAM1 antibody or antigen-binding agent as a treatment.
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
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
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
20.
GENERATION OF BROWN ADIPOCYTES FROM HUMAN PLURIPOTENT STEM CELLS
Provided herein are methods of generating Gata6-positive brown adipose progenitor cells, and brown adipose cells and tissue therefrom. Additionally, provided herein are methods of generating UCP1 positive organoids. Generally, the methods include a step of culturing brown adipose progenitor cells in a medium containing an FGF signaling pathway activator, a BMP signaling pathway activator, a TGFβ activator, a Wnt inhibitor, and a thyroid hormone receptor activator.
The present disclosure relates to chimeric small molecules, which find utility as modifiers of target substrates according to the formula A-L1-E-B or A-L1-E-L2-B, wherein A is a kinase binding moiety; B is a target binding moiety; L1 and L2 are each a linker; and E is an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post-translational modifications to targets that are not the natural substrate of the kinase; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.
C07D 233/58 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
The present disclosure provides methods of suppressing the activation of microglial cells, methods of ameliorating or treating the neurological effects of cerebral ischemia or cerebral inflammation, and methods of ameliorating or treating specific diseases that affect the CNS by nasally administering an anti-CD3 antibody.
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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
23.
SINGLE MOLECULE ASSAYS FOR ULTRASENSITIVE DETECTION OF ANALYTES
The invention provides ultrasensitive methods for detection and quantification of target analytes in samples. The methods can be multiplexed to allow simultaneous detection and quantification of multiple target analytes. The methods can achieve an attomolar limit of detection. The invention also provides related compositions and kits.
The present disclosure relates to bifunctional chemical conjugation molecules, which find utility as modifiers of target substrates. The present disclosure includes multifunctional compounds comprising an enzyme binding moiety, a chemical linker moiety, and a target binding moiety, which may further include an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post- translational modifications to proteins that are not the natural substrate of the enzyme. Diseases or disorders may be treated or prevented with molecules of the present disclosure.
C07D 473/26 - Heterocyclic compounds containing purine ring systems with an oxygen, sulfur, or nitrogen atom directly attached in position 2 or 6, but not in both
The disclosure relates to antibodies, or antigen-binding fragments thereof, that specifically bind to killer cell lectin-like receptor G1 (KLRG1). Such antibodies, or antigen-binding fragments thereof, are useful for various therapeutic or diagnostic purposes, including treatment of cancers and to increase the effectiveness of vaccines.
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
Disclosed are compositions including a pharmaceutical agent assembled with a lipid composition, wherein the lipid composition comprises a lipidoid having structural Formula (I) or a pharmaceutically acceptable salt thereof, wherein Ra, Rb1, Rb2, Rb3, Rb4, n1 and n2 are as described herein.
An indwelling catheter surveillance system which can detect and distinguish a clean catheter system from one with bacterial colonization and from one with bacterial infection. This is done using a micro-spectroscopy system placed on the outside of an indwelling catheter's drainage tube with analysis being facilitated using machine learning algorithms. This system is based on the ability to leverage the analysis of bacteria and biomarkers in liquid bio samples at the patient's bedside, in real time to deliver a mobile, continuous, point of care, disposable and cost-effective solution. This represents a feasible and scalable system for resolving the problem of infections in indwelling catheter systems.
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value
A61B 5/1473 - Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
A61B 90/30 - Devices for illuminating a surgical field, the devices having an interrelation with other surgical devices or with a surgical procedure
Described herein are methods and compositions for treating gliomas such as pediatric low grade glioma. In some embodiments, a herein described method of treating pediatric low grade glioma comprises administering to a subject in need thereof (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A), or a pharmaceutically acceptable salt thereof. In some embodiments, Compound A or a pharmaceutically acceptable salt thereof is administered in an amount that is equivalent to about 400 mg/m2 to about 600 mg/m2 of Compound A per week. In some embodiments, the subject is less than 20 years of age.
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
Described herein are methods and kits for diagnosing and treating minimal change disease, and for identifying subjects for eligibility or treatment before kidney transplant, based on the presence of circulating anti-nephrin autoantibodies.
Systems and methods are provided for fully automated screening for aneuploidy in a human embryo. An image of the embryo is obtained at an associated imager and provided to a neural network to generate a first clinical parameter. A set of at least one parameter representing one of biometric parameters of one of a patient receiving the embryo, an egg utilized to produce the human embryo, a sperm used to create the embryo, a sperm donor who provided sperm used to create the embryo, and an egg donor who provided the egg is retrieved, and a second clinical parameter is generated from the set of at least one parameter at a predictive model. A composite parameter, representing a likelihood of aneuploidy in the embryo, is generated from the first clinical parameter and the second clinical parameter.
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
31.
DETERMINING LOCATIONS IN REPRODUCTIVE CELLULAR STRUCTURES
Systems and methods are provided for determining a clinical parameter representing the location of interest within a reproductive cellular structure. An image of the reproductive cellular structure is obtained and provided to a neural network to generate the clinical parameter. The clinical parameter is stored on a non-transitory computer readable medium.
Systems and methods are provided for medical image classification of images from varying sources. A set of microscopic medical images are acquired, and a first neural network module configured to reduce each of the set of microscopic medical images to a feature representation is generated. The first neural network module, a second neural network module, and a third neural network module are trained on at least a subset of the set of microscopic medical images. The second neural network module is trained to receive a feature representation associated with an image of the microscopic images and classify the image into one of a first plurality of output classes. The third neural network module is trained to receive the feature representation, classify the image into one of a second plurality of output classes based on the feature representation, and provide feedback to the first neural network module.
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
G06V 10/774 - Generating sets of training patternsBootstrap methods, e.g. bagging or boosting
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
33.
SINGLE MOLECULE ASSAYS FOR ULTRASENSITIVE DETECTION OF BIOMOLECULES
Provided herein are assays that provide digital measurement methods to detect proteins and other biomolecules, e.g., at low- to mid-attomolar concentrations.
The present disclosure relates to methods of identifying and treating kidney rejection in a subject comprising analyzing microvesicular RNA, cell-free DNA or the combination of microvesicular and cell-free DNA.
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 disclosure relates to methods for treating tumors. In particular, the disclosure relates to a method of treating a tumor by magnetic resonance image-guided radiation therapy in a subject in need thereof, said method comprising the steps of: (i) administering an efficient amount of high-Z element containing nanoparticles having both contrast enhancement for magnetic resonance imaging and radiosensitizing properties for radiation therapy, in a subject in need thereof, and, (ii) exposing said subject to magnetic resonance image-guided radiation therapy by means of a MR-Linac, wherein said high-Z element containing nanoparticles are nanoparticles containing an element with an atomic Z number higher than 40, preferably higher than 50, and said nanoparticles have a mean hydrodynamic diameter below 20 nm, for example between 1 and 10 nm, preferably between 2 and 8 nm.
A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
A61K 47/69 - 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 49/18 - Nuclear magnetic resonance [NMR] contrast preparationsMagnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
The present invention is directed to methods and compositions for treating Glioblastoma multiforme (GBM). The risk of developing therapy resistant GBM may be assessed by detecting the presence of ABCB5 in the GBM cells. Therapeutic interventions utilizing an ABCB5 blockade to sensitize the GBM cells to therapeutic agents such as temozolomide are provided.
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
37.
SELECTIVE MODULATION OF TRANSFORMING GROWTH FACTOR BETA SUPERFAMILY SIGNALING VIA MULTI-SPECIFIC ANTIBODIES
Compositions and methods for selective targeting of BMP/TGF? signaling using heteromeric complexes, preferably comprising single chain variable domain (scFv) antibodies (Abs) targeting the extracellular domains of BMP type I and type II receptors.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present disclosure relates to multifunctional chemical conjugation molecules, which find utility as modifiers of target substrates. The present disclosure includes multifunctional compounds comprising a localizing moiety, a chemical linker moiety, an activator moiety, a first orienting adaptor interconnecting the chemical linker moiety on one end to the activator moiety, and optionally a second orienting adaptor interconnecting the chemical linker molecule on a different end to the localizing moiety. Molecules according to the present invention find use making post-translational modifications to macromolecules that are not the natural substrate of the activator moiety. Diseases or disorders may be treated or prevented with molecules of the present disclosure.
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
The present application relates to sequences that enhance permeation of immunotherapy agents across the blood brain barrier (BBB), compositions comprising the sequences, and methods of use thereof to treat brain cancer, e.g., glioblastoma (GBM). Further disclosed are a number of potential targeting peptide sequences identified that enhance permeation through the BBB, when inserted into the capsid of an adeno-associated virus (AAV).
A system and method is provided for controlling physiological-noise in functional magnetic resonance imaging using raw k-space data to extract physiological noise effects. The method can identify these effects when they are separable and directly reflects the artefactual effects on fMRI data, without the need for external monitoring or recording devices and to be compensated for via rigorous statistical analysis modeling of such noise sources. The physiological fluctuations may be treated as global perturbations presented around the origin point in a k-space 2D slice. Each k-space 2D slice may be acquired at a very short repetition time with an effective sampling rate to sample cardiac and respiratory rhythms through proper reordering and phase-unwarping techniques applied to the raw k-space data.
A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
G01R 33/56 - Image enhancement or correction, e.g. subtraction or averaging techniques
G01R 33/563 - Image enhancement or correction, e.g. subtraction or averaging techniques of moving material, e.g. flow-contrast angiography
G01R 33/565 - Correction of image distortions, e.g. due to magnetic field inhomogeneities
The present disclosure provides compositions, methods, and kits that enable the in situ growth of polymers on or within a subject. In some aspects, the tissue-active monomers, including monomers comprising macromolecules, provide a broad set of material choices for synthetic tissue barriers. In additional aspects, the compositions, methods, and kits are useful for treating or preventing a disease or disorder.
In the various aspects and embodiments, this disclosure provides genetic, pharmacological, and mechanical stimuli for transitioning endothelial cells to hemogenic endothelial (HE) cells, and for transitioning HE cells to HSCs, including HSCs that comprise a significant level of LT-HSCs. The disclosure further provides methods for expanding HSCs using the genetic, pharmacological, and mechanical stimuli.
Systems and methods are provided for assigning a quality parameter to a reproductive cellular structure. An image of the reproductive cellular structure is obtained. The image of the reproductive cellular structure is provided to a neural network to generate a value representing a morphology of the reproductive cellular structure. The value is compared to a predefined standard to provide a quality assurance metric representing one of a medical personnel, a facility, a growth medium, and an identity of the reproductive cellular structure.
Systems and methods for patient monitoring and repositioning are provided. The system includes a mattress with a cell array and a base board array to receive the cell array. The cell array includes a plurality of individually height- adjustable cells each having sensor surface configured to sense at least one biomarker of the patient while lying on the mattress. The system also includes a main unit in communication with each cell of the cell array through the base board array. The main unit is configured to receive data from each of the cells, including measurements of the at least one biomarker, and independently control a height of each of the cells.
Binding polypeptides (e.g., antibodies and antigen-binding fragments thereof) that specifically bind one or more species of soluble, AD brain-derived synaptotoxic amyloid beta (?ß) without binding to classical monomeric, protofibrillar or fibrillar ?ß, are provided. Pharmaceutical compositions comprising binding polypeptides that specifically bind one or more species of soluble, synaptotoxic ?ß are provided. Methods of making binding polypeptides that specifically bind one or more species of soluble, synaptotoxic ?ß are provided. Methods of treating Alzheimer's disease using binding polypeptides that specifically bind one or more species of soluble, synaptotoxic ?ß are provided. Methods of reducing one or more symptoms of Alzheimer's disease using binding polypeptides that specifically bind one or more species of soluble, synaptotoxic ?ß are provided.
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
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
The present disclosure provides, among other things, human codon-optimized sequences encoding presenilin 1, and methods for using the sequences in gene therapy to treat neurodegenerative diseases including, but not limited to Alzheimer's disease, frontotemporal dementia, frontotemporal lobar degeneration, Pick's disease, Lewy body dementia, memory loss, and cognitive impairment including mild cognitive impairment (MCI).
A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene 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
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
Methods and compositions for the treatment of conditions associated with pharyngeal airway muscle collapse while the subject is in a non-fully conscious state, e.g., sleep apnea and snoring, comprising administration of (i) a norepinephrine reuptake inhibitor (NRI) and (ii) a non myorelaxing hypnotic and/or 5-HT2A inverse agonist or antagonist.
A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
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
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61P 25/00 - Drugs for disorders of the nervous system
48.
HUMANIZED AND AFFINITY-MATURED ANTI-CEACAM1 ANTIBODIES
Provided herein are recombinant antibodies and antigen-binding fragments thereof useful for binding to and inhibiting carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Also provided are methods of using the disclosed CEACAM1 antibodies and antigen-binding fragments thereof for reducing T-cell tolerance and for the treatment of cancer.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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
49.
AUTOMATIC DETERMINATION OF A BIOLOGICAL CONDITION OF A SUBJECT FROM FERNING PATTERNS
A system comprises: an optical assembly comprising at least one lens and having an associated axis; a microfluidic device comprising a channel to hold a fluid sample from a subject and a reservoir for receiving the fluid sample, the channel being configured to receive a smearing block that spreads a thin film of the fluid sample across the channel, and the microfluidic device being configured to engage with a housing such that the channel is aligned with the axis of the optical assembly; a camera aligned with the axis of the optical assembly; a processor; and a non-transitory computer readable medium storing executable instructions for providing at least one image captured at the camera to a computer vision model implemented as a convolutional neural network comprising: a plurality of convolutional layers to determine if there is a ferning pattern representative of a biological condition of the subject in the at least one image.
A61B 10/00 - Instruments for taking body samples for diagnostic purposesOther methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determinationThroat striking implements
G01N 21/01 - Arrangements or apparatus for facilitating the optical investigation
G01N 33/483 - Physical analysis of biological material
G01N 33/487 - Physical analysis of biological material of liquid biological material
Systems and methods are provided for provided for automatic evaluation of sperm morphology. An image of a semen sample is obtained, and at least a portion of the image is provided to a convolutional neural network classifier. The convolutional neural network classifier evaluates the portion of the image to assign to the portion of the image a set of likelihoods that the portion of the image belongs to a plurality of output classes representing the morphology of sperm within the portion of the image. A metric is assigned to the semen sample based on the likelihoods assigned by the convolutional neural network.
A system comprises: a camera that produces an image of a semen sample; an image processor that segments the image to provide a plurality of image tiles, the image processor locating individual sperm within a representation of the image generated via a template matching process in which a cross-correlation between a template representing at least a portion of a sperm and each of a plurality of locations on the image is computed and locations having a cross-correlation output above a threshold value are selected and generating a plurality of image tiles from the image according to the locations of the individual sperm; and a convolutional neural network that evaluates a subset of the plurality of image tiles and assigns, to each of the image tiles, respective likelihoods that sperm within the image tile belongs to each of a set of at least one of a plurality of image output classes representing the morphology of sperm within the image tile.
The invention relates to antibodies, or antigen-binding fragments thereof, that specifically binds to killer cell lectin-like receptor G1 (KLRG1). Such antibodies, or antigen-binding fragments thereof, are useful for various therapeutic or diagnostic purposes including treatment of cancers and to increase the effectiveness of vaccines.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
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 invention is based on the development of artificial targeting sequences that enhance permeation of agents into cells and across the blood brain barrier, compositions comprising the sequences, and methods of use thereof. Provided herein is an AAV comprising a capsid protein comprising a targeting sequence and a transgene, preferably a therapeutic or diagnostic transgene. Further, provided herein are methods of delivering a transgene to a cell, the method comprising contacting the cell with an AAV or fusion protein described herein.
The systems and methods described herein determine metrics of cardiac performance via a mechanical circulatory support device and use the cardiac performance to calibrate, control and deliver mechanical circulatory support for the heart. The systems include a controller configured to operate the device, receive inputs indicative of device operating conditions and hemodynamic parameters, and determine vascular performance, including vascular resistance and compliance, and native cardiac output. The systems and methods operate by using the mechanical circulatory support device (e.g., a heart pump) to introduce controlled perturbations of the vascular system and, in response, determine heart parameters such as stroke volume, vascular resistance and compliance, left ventricular end diastolic pressure, and ultimately determine native cardiac output.
The systems and methods described herein determine metrics of cardiac or vascular performance, such as cardiac output, and can use the metrics to determine appropriate levels of mechanical circulatory support to be provided to the patient. The systems and methods described determine cardiac performance by determining aortic pressure measurements (or other physiologic measurements) within a single heartbeat or across multiple heartbeats and using such measurements in conjunction with flow estimations or flow measurements made during the single heartbeat or multiple heartbeats to determine the cardiac performance, including determining the cardiac output. By utilizing a mechanical circulatory support system placed within the vasculature, the need to place a separate measurement device within a patient is reduced or eliminated. The system and methods described herein may characterize cardiac performance without altering the operation of the heart pump (e.g., without increasing or decreasing pump speed).
Disclosed are compounds that activate excitatory amino acid transporter 2 (EAAT2), as well as methods of using these compounds to treat or preventing diseases, disorders, and conditions associated with glutamate excitotoxicity.
A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
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 401/06 - 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 carbon chain containing only aliphatic carbon atoms
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 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 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
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
In some aspects and embodiments, the invention provides methods for making hematopoietic stem cells, including for HSCT. The method comprises providing a cell population comprising hemogenic endothelial (HE) or endothelial cells, and increasing activity or expression of DNA (cytosine-5-)-methyltransferase 3 beta (Dnmt3b) and/or GTPase IMAP Family Member 6 (Gimap6) in the HE and/or endothelial cells under conditions sufficient for stimulating formation of HSCs.
C07D 403/00 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group
C12M 1/00 - Apparatus for enzymology or microbiology
C12N 5/02 - Propagation of single cells or cells in suspensionMaintenance thereofCulture media therefor
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
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
The present disclosure provides, among other things, methods for using presenilin based gene therapy to treat neurodegenerative dementia including, but not limited to Alzheimers disease, frontotemporal dementia, frontotemporal lobar degeneration, Picks disease, Lewy body dementia, memory loss, and cognitive impairment including mild cognitive impairment (MCI).
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene 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
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
Provided herein are methods of treating or reducing the risk of a cardiovascular disease using a lipid lowering agent (e.g., statin and/or PCSK9 inhibitor) and an anti-inflammatory agent (e.g., a pro-inflammatory cytokine inhibitor). Further provided herein are methods of predicting the recurrence rate of a subject who has received or is undergoing therapy for a cardiovascular disease with a lipid lowering agent on the basis of the C-reactive protein (CRP) level in the subject. In some embodiments, the recurrence rate can be reduced using an anti-inflammatory agent.
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Gastric resident electronics, devices, systems, and related methods are generally provided. Some embodiments comprise administering (e.g., orally) an (electronic) resident structure to a subject (e.g., a patient) such that the (electronic) resident structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before exiting said location internal to the subject. In some embodiments, the resident structure is a gastric resident electronic. That is to say, in some embodiments, the resident structure is configured for relatively long gastric residence and comprises an electronic component. In some embodiments, the structures and components described herein may comprise one or more components configured for the delivery of an active substance(s) (e.g., a pharmaceutical agent) to the subject. In some embodiments, the device has a modular design, combining an electronic component(s) with materials configured for controlled and/or tunable degradation/dissolution to determine the time at which (gastric) residence is lost and the device exits the location internal to the subject. For example, in some embodiments, the resident structure comprises an electronic component and one or more additional components associated with the electronic component such that the resident structure is configured to be retained at a location internal to a subject for greater than or equal to 24 hours.
An automated system and method is provided for biotype extraction and biomarker discovery from task-based fMRI imaging data. The system and method may include automatically mapping a localizome, such as a task-condition/contrast/population-specific brain functional localizome, based on fMRI data and automatically selecting and sorting brain regions or brain nodes to produce a subset of functional brain regions or brain nodes. A report may then be generated indicating that the subject has a particular brain circuit pattern of activity and connectivity associated with one or more symptoms of the given mental disorder, treatments, or associated with normal brain functions, based upon the extracted biosignatures by searching for the optimal multivariate classifier with least dimensionality in the brain functional localizome. These biosignatures and biomarkers that reveal hidden, implicit, and latent brain circuit patterns provoked by fMRI tasks, can also provide for the development of non-invasive diagnostics and targeted therapeutics in neuropsychiatric diseases.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
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
The present invention provides methods of suppressing the activation of microglial cells, methods of ameliorating or treating the neurological effects of cerebral ischemia or cerebral inflammation, methods of ameliorating or treating specific diseases that affect the CNS by administering an anti-CD3 antibody.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/00 - Drugs for disorders of the nervous system
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
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, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell.
C07K 14/74 - Major histocompatibility complex [MHC]
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving viable microorganisms
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C40B 20/04 - Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
Provided is a self-righting article, comprising an outer shell, a spring at least partially encapsulated within the outer shell, a support material associated with the spring such that the support material maintains at least a portion of the spring under at least 5% compressive strain under ambient conditions, and a tissue interfacing component operably linked to the spring, wherein the self-righting article comprises a monostatic body due to a center of mass of the article and/or the shape of the article, such that the article has a single stable resting position. The self-righting article is useful as a general platform for delivery of a wide variety of pharmaceutical drugs and sensors or to take a biopsy, without the need for an endoscopy.
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
A61M 31/00 - Devices for introducing or retaining media, e.g. remedies, in cavities of the body
65.
SELF-RIGHTING SYSTEMS, METHODS, AND RELATED COMPONENTS
Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self- righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject). In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component is associated with a self-actuating component. For example, the self- righting article may comprise a self-actuating component configured, upon exposure to a fluid, to release the tissue interfacing component from the self-righting article. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent (e.g., for delivery to a location internal to a subject).
A61J 3/07 - Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
A61K 9/00 - Medicinal preparations characterised by special physical form
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
A61M 5/14 - Infusion devices, e.g. infusing by gravityBlood infusionAccessories therefor
Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self- righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject). In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component is associated with a self-actuating component. For example, the self- righting article may comprise a self-actuating component configured, upon exposure to a fluid, to release the tissue interfacing component from the self-righting article. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent (e.g., for delivery to a location internal to a subject).
Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self- righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject). In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component is associated with a self-actuating component. For example, the self- righting article may comprise a self-actuating component configured, upon exposure to a fluid, to release the tissue interfacing component from the self-righting article. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent (e.g., for delivery to a location internal to a subject).
A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
A61M 5/20 - Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
A61M 31/00 - Devices for introducing or retaining media, e.g. remedies, in cavities of the body
Components with relatively high loading of active pharmaceutical ingredients are generally provided. In some embodiments, the component (e.g., a tissue interfacing component) comprises a solid therapeutic agent and a supporting material wherein the solid therapeutic agent is present in the component in an amount of 510 wt% versus the total weight of the tissue interfacing component. Such components may be useful for delivery of API doses. Advantageously, in some embodiments, the volume reduction required to deliver the required API dose as compared to a liquid formulation permits the creation of solid needle delivery systems for a variety of drugs in a variety of places/tissues (e.g., tongue, GI mucosal tissue, skin) and/or reduces and/or eliminates external force application to inject a drug solution through the needle's small opening. In some cases, a physiologically relevant dose may be present in a single tissue interfacing component (e.g., having a relatively high API loading).
Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject). In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component is associated with a self-actuating component. For example, the self- righting article may comprise a self-actuating component configured, upon exposure to a fluid, to release the tissue interfacing component from the self-righting article. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent (e.g., for delivery to a location internal to a subject).
A61J 3/07 - Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
A61K 9/00 - Medicinal preparations characterised by special physical form
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
A61M 5/14 - Infusion devices, e.g. infusing by gravityBlood infusionAccessories therefor
Methods and compositions for the treatment of conditions associated with pharyngeal airway muscle collapse while the subject is in a non-fully conscious state, e.g., sleep apnea and snoring, comprising administration of a norepinephrine reuptake inhibitor (NRI) and a muscarinic receptor antagonist.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61K 31/7008 - Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
71.
NOVEL ALK2 INHIBITORS AND METHODS FOR INHIBITING BMP SIGNALING
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
THE BRIGHAM AND WOMEN'S HOSPITAL, INC. (USA)
Inventor
Yu, Paul B.
Huang, Wenwei
Sanderson, Philip Edward
Jiang, Jian-Kang
Shamim, Khalida
Zheng, Wei
Huang, Xiuli
Tawa, Gregory
Lee, Arthur
Alimardanov, Asaf
Huang, Junfeng
Abstract
The present invention provides small-molecule inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. These compounds and compositions may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds and compositions may also be used to treat subjects with Sjogren's syndrome, or diffuse intrinsic pontine glioma (DIPG).
A61K 31/4355 - 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 oxygen as a ring hetero atom
A61K 31/4365 - 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 having sulfur as a ring hetero atom, e.g. ticlopidine
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/438 - 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 the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 19/08 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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
Tissue explants of the gastrointestinal tract are provided. Methods of making and using the tissue explants are also provided, along with substrates designed for the tissue explants described.
The present disclosure provides methods for assaying a biological sample, comprising: a) contacting the biological sample with a plurality of particles comprising different particle types to permit biomolecules of the biological sample to bind to the plurality of particles and form coronas around the plurality of particles, wherein the coronas corresponding to the different particle types (i) differ based on particle type, and (ii) comprise overlapping and distinct proteins; b) separating at least a subset of the plurality of particles comprising the coronas from the biological sample by removing the subset of the plurality of particles thereby producing a subset of proteins from the biological sample; c) assaying the subset of proteins of (b) with an instrument to detect, in the subset, proteins in the biological sample at concentrations across a dynamic range comprising at least 6 orders of magnitude.
Provided herein are nanoparticle compositions (e.g., nanoparticle compositions comprising high atomic number ions) that are useful for imaging diseases in a subject as well as radiosensitizing a disease in a subject (e.g., radiosensitizing a cancer in the subject). Methods of imaging a subject, methods of treating cancer, and processes of preparing the nanoparticle compositions are also provided.
A61K 49/08 - Nuclear magnetic resonance [NMR] contrast preparationsMagnetic resonance imaging [MRI] contrast preparations characterised by the carrier
A61K 49/18 - Nuclear magnetic resonance [NMR] contrast preparationsMagnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
75.
COMPOSITIONS AND METHODS FOR TREATING PULMONARY VASCULAR DISEASE
UNIVERSITY OF PITTSBURGH-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION (USA)
THE BRIGHAM AND WOMEN'S HOSPITAL, INC. (USA)
Inventor
Chan, Stephen Y.
Bertero, Thomas
Abstract
Provided herein are compositions and methods for treating pulmonary vascular disease in a subject comprising administering to the subject a therapeutically effective amount of a YAP/TAZ inhibiting composition and/or a GLS1 inhibiting composition.
A61K 31/409 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having four such rings, e.g. porphine derivatives, bilirubin, biliverdine
A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
A61P 11/00 - Drugs for disorders of the respiratory system
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
76.
SELF-ASSEMBLED GELS FOR CONTROLLED DELIVERY OF BIOLOGICS AND LABILE AGENTS
Gels are formed based on generally recognized as safe (GRAS) low molecular weight amphiphilic molecules in a self-assembly process with limited or no heating. A selective range of ratios between an organic solvent and water, or an aqueous solution, in the medium, allows for the GRAS low molecular weight amphiphiles to form a homogeneous self-supporting gel encapsulating agents to be delivered under very mild conditions. Proteins including enzymes, antibodies, and serum albumin are loaded in the self-assembled gels to provide sustained and/or responsive delivery. The encapsulated proteins retain at least 70%, 80%, or 90% of their activity over days in various storage conditions.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC. (USA)
UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. (USA)
THE BRIGHAM AND WOMAN'S HOSPITAL, INC. (USA)
Inventor
Yang, Jenny Jie
Hu, Jian
Brown, Edward
Moremen, Kelly
Abstract
Described herein are compounds that can bind CaSR and/or a CaSR extracellular domain and formulations thereof. Also described herein are methods of inhibiting CaSR and/or treating a disease or disorder associated with a mutation in CaSR by administering a compound or formulation thereof described herein. Also described herein are assays that can be used to identify compounds that can bind an extracellular domain of CaSR.
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
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
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
G01N 33/566 - ImmunoassayBiospecific binding assayMaterials therefor using specific carrier or receptor proteins as ligand binding reagent
Described herein are methods for treating fibrosis, e.g., kidney fibrosis, using agents that target Secreted Modular Calcium-binding protein 2 (SMOC2).
The present invention provides compositions and methods for repair and reconstruction of defects and injuries to the cornea. The composition comprises a methacryloyl-substituted gelatin, a visible light activated photoinitiator, and a pharmaceutically acceptable carrier, wherein the methacryloyl-substituted gelatin comprises methacrylamide substitution and methacrylate substitution, and the ratio of methacrylamide substitution to methacrylate substitution in the methacryloyl-substituted gelatin is between 80:20 and 99:1. The composition can be used, in combination with exposure to visible light, for treatment of an eye, for example, for repair and reconstruction of defects and injuries to the cornea.
Methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4) agonists, and methods of use of the HSCs in transplantation are provided. Specifically, the methods comprising providing a population cells comprising hemogenic endothelial (HE) cells, contacting the HE cells with an amount of an agonist of Trpv4; and/or subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Further disclosed are methods of treating malignant or non-malignant hematologic, metabolic, or immune disorders comprising administering to a subject a therapeutically effective amount of HSCs obtained by the methods.
A non-covalently assembled hydrogel or organo-gel composition with serum stability is described. Low molecular weight (<2,500 Da), generally regarded as safe (GRAS), materials assemble in the presence of a stabilizing agent at an appropriate molar percentage, forming hydrogel or organo-gel with nanostructures that resist disassembly or destabilization in serum for an extended period of time. The composition is used to deliver one or more therapeutic, prophylactic, or diagnostic agents, allowing for controlled release in response to biological stimuli such as enzymes and a greatly improved dosing efficacy.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
A system and method for generating biological products. In some aspects, the system includes a first substrate having formed therein a plurality of inlet channel extending substantially along a longitudinal direction, and a second substrate having formed therein a plurality of outlet channel corresponding to the plurality of inlet channel and extending substantially along the longitudinal direction, the second substrate configured to releasably engage the first substrate. The system also includes a permeable membrane, arranged between the substrates, forming microfluidic pathways between respective inlet and outlet channels and configured to selectively capture biological source material capable of generating biological products, wherein at least one channel is tapered transversally to control a pressure differential profile regulating perfusion through the permeable membrane.
Compositions and methods for the radiological and immunotherapeutic treatment of cancer are provided. Metallic nanoparticles conjugated with an immunoadjuvant are dispersed within a biodegradable polymer matrix that can be implanted in a patient and released gradually. The implant may be configured as, or be a component of, brachytherapy spacers and applicators, or radiotherapy fiducial markers. The composition may be combined with marginless radiotherapy, allowing for lower doses of radiation and enhancing the immune response against cancer, including at non-irradiated sites.
Systems and methods are provided for evaluating the quality of a semen sample at a mobile device. An assembly includes an optical assembly with at least one lens and a housing configured to engage with the mobile device such that an axis of the optical assembly is substantially aligned with a camera of the mobile device. The optical assembly is contained within the housing. A microfluidic chip includes a reservoir to hold the semen sample. The microfluidic chip engages with the housing such that the reservoir is aligned with the axis of the optical assembly.
Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a second generation oncolytic virus rQNestin34.5v2 with less toxicity that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of glioblastoma, as well as other cancers.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
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
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
87.
TREATMENT OF CANCER WITH ANTI-LAP MONOCLONAL ANTIBODIES
Described herein are compositions and methods relating to LAP-binding agents, including, for example, anti-LAP antibodies, and to their use in methods of treatment of cancer. LAP-binding agents affected both systemic and intra-tumor immunity and were shown effective to treat a broad spectrum of cancer types.
Methods of treatment are provided herein, including administration of a population cells modified to enforce expression of an E-selectin and/or an L-selectin ligand, the modified cell population having a cell viability of at least 70% after a treatment to enforce such expression.
A population of neural stem cells (NSCs) that expresses an Hematopoietic CellE-/L-selectin Ligand (HCELL) for use in treatment of multiple sclerosis in a subject, wherein the subject has E-selectin expression on endothelial cells within the neural tissue.
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
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
Residence structures, systems, articles, and related methods are provided. In one embodiment, there is provided a gastric residence structure comprising: a loadable polymeric component; an elastic polymeric component; and a separate linker component, said linker connecting the loadable polymeric component with the elastic polymeric component; wherein the gastric residence structure is configured to be folded and physically constrained during administration and is configured to assume an open retention shape upon removal of a constraint, wherein change between the folded shape and the open retention shape is mediated by the elastic polymeric component that undergoes elastic deformation when the residence structure is in the folded shape and recoils when the gastric residence structure assumes the open retention shape, and wherein said linker degrades, dissolves, disassociates, or mechanically weakens in a gastric environment which results in loss of retention shape integrity and passage out of a gastric cavity.
Residence devices as well as their related methods of manufacture and use are generally provided. In some embodiments, a residence device includes a plurality of self-assembling structures that assemble in vivo to form an aggregate structure. Each structure of the plurality of structures includes a first side and a first attachment point that attaches to a second attachment point on another structure of the plurality of structures. The aggregate structure may be sized and shaped to maintain an in vivo position relative to an internal orifice of a subject. The attachment between the first and second attachment points may degrade after a period of time.
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61M 31/00 - Devices for introducing or retaining media, e.g. remedies, in cavities of the body
The present invention relates to 2-amino-4-arylpyrimidine and 2-amino-4- aryltriazine compounds such as compounds of formula (I) as inhibitors of heat shock protein 90 (Hsp90) family of chaperone proteins. The invention also features pharmaceutical compositions and kits that include the compounds and compositions of the invention. The invention further relates to the medical use of these compounds and compositions for the treatment of a disorder in a subject such as a disorder caused by the action of Hsp90 (Hsp90). For example, the disorder can be a neurodegenerative disorder. (see formula I)
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 239/70 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
C07D 251/16 - Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
C07D 405/10 - 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 carbon chain containing aromatic rings
Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.
BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY (USA)
Inventor
Demirci, Utkan
Ghiran, Ionita
Tasoglu, Savas
Davis, Ronald W.
Steinmetz, Lars
Durmus, Naside Gozde
Tekin, Huseyin Cumhur
Abstract
Magnetic cell levitation and cell monitoring systems and methods are disclosed. A method for separating a heterogeneous population of cells is performed by placing a microcapillary channel containing the heterogeneous population of cells in a magnetically-responsive medium in the disclosed levitation system and separating the cells by balancing magnetic and corrected gravitational forces on the individual cells. A levitation system is also disclosed, having a microscope on which the microcapillary channel is placed and a set of two magnets between which the microcapillary channel is placed. Additionally, a method for monitoring cellular processes in real-time using the levitation system is disclosed.
A system and method for sorting sperm is provided. The system includes a housing and a microfluidic system supported by the housing. The system also includes an inlet providing access to the microfluidic system to deliver sperm to the microfluidic system and an outlet providing access to the microfluidic system to harvest sorted sperm from the microfluidic system. The microfluidic system provides a flow path for sperm from the inlet to the outlet and includes at least one channel extending from the inlet to the outlet to allow sperm delivered to the microfluidic system through the inlet to progress along the flow path toward the outlet. The microfluidic system also includes a filter including a first plurality of micropores arranged in the flow path between the inlet and the outlet to cause sperm traveling along the flow path to move against through the filter and gravity to reach the outlet.
In some aspects, the invention teaches pharmaceutical compositions that include a TGF-beta ligand trap, and methods of using a TGF-beta ligand trap to treat, prevent, or reduce the progression rate of pulmonary hypertension (PH). The invention also provides methods of using a TGF-beta ligand trap to treat, prevent, or reduce the progression rate of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, right ventricular hypertrophy, diseases associated with excessive TGF-beta signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using a TGF-beta ligand trap to reduce right ventricular systolic pressure in a subject.
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
A61P 9/00 - Drugs for disorders of the cardiovascular system
Pre-polymers for use as tissue sealants and adhesives, and methods of making and using thereof are provided. The pre-polymers have flow characteristics such that they can be applied through a syringe or catheter but are sufficiently viscous to remain in place at the site of application and not run off the tissue. The pre-polymers are also sufficiently hydrophobic to resist washout by bodily fluids. The pre-polymers are stable in bodily fluids; that is the pre-polymer does not spontaneously crosslink in bodily fluids absent the presence of an intentionally applied stimulus to initiate crosslinking. Upon crosslinking, the adhesive exhibits significant adhesive strength in the presence of blood and other bodily fluids. The adhesive is sufficiently elastic that it is able to resist movement of the underlying tissue. The adhesive can provide a hemostatic seal. The adhesive is biodegradable and biocompatible, causing minimal inflammatory response.
A61L 15/22 - Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS (USA)
THE BRIGHAM AND WOMEN'S HOSPITAL, INC. (USA)
Inventor
Frank, Markus H.
Frank, Natasha Y.
Orgill, Dennis P.
Murphy, George F.
Abstract
The present invention is directed to wound healing scaffolds cografted with a population of stem cells, wherein the population of stem cells are ABCB5+ stem cells. The scaffolds are, for instance, collagen glycosaminoglycan scaffolds.
A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.
Adhesive articles containing microtopography, such as microprotrusions, and a coating of adhesive glue, such an adhesive having known toxicity and/or tissue reactive functional groups are described herein. The articles described herein contain a substrate, a plurality of micro features, and an adhesive, such as an adhesive glue. The articles described herein exhibit a 90° pull off adhesion of at least about 1.5 N/cm2. The articles described herein can contain less adhesive than when the adhesive is used alone without microtopography and yet exhibit equivalent adhesive strength with little or no toxicity or other adverse side effects (e.g., exothermic reaction).
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