Described herein are methods for predicting treatment response to glutamate modulating agents, selecting treatment comprising glutamate modulating agents, for, and treating subjects with glutamate modulating agents, in subjects with autism spectrum disorder (ASD).
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
A61P 43/00 - Drugs for specific purposes, not provided for in groups
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 analytical applications, such as sequencing applications.
C08L 101/12 - Compositions of unspecified macromolecular compounds characterised by physical features, e.g. anisotropy, viscosity or electrical conductivity
G01N 33/551 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
3.
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.
IL-2 agents that comprise IL-2 variants are disclosed as well as methods, compositions, and uses thereof. The IL-2 agents described herein can be used to treat and/or prevent various disorders and conditions.
The disclosure features in some aspects methods for identifying subjects with constitutional mismatch repair deficiency (CMMRD), a mismatch repair deficiency (MMD) cancer, a polymerase proofreading deficiency (PPD) cancer, and/or a MMD&PPD cancer. The disclosure also features in some aspects methods for predicting response of a subject to immunotherapy.
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
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
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
6.
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
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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
7.
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.
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
C07D 211/60 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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
8.
KITS, REAGENTS AND METHODS FOR THE ASSESSMENT OF LIVER DISEASES
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.
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
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
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 70/60 - ICT specially adapted for the handling or processing of medical references relating to pathologies
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
10.
BCG VACCINATIONS FOR PREVENTION OF COVID-19 AND OTHER INFECTIOUS DISEASES
The invention relates, in part, to a method for the prophylactic treatment of a coronavirus infection in a human adult subject comprising administering at least two doses of a Bacillus Calmette-Guerin (BCG) vaccine to the subject, wherein the subject is a type I diabetic.
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.
12.
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.
Aspects of the disclosure relate to compositions and methods for treating hereditary hearing loss and/or vision loss, for example, due to Usher syndrome, Type 3A. In some embodiments, the disclosure provides a recombinant adeno-associated virus comprising: (i) an AAV-S capsid protein, and (ii) an isolated nucleic acid comprising a transgene (e.g., a transgene for expressing a clarin-1 protein). The present disclosure also provides methods of treating hereditary hearing loss and/or vision loss (e.g., Usher Syndrome, Type 3A) using the same.
C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07K 14/015 - Parvoviridae, e.g. feline panleukopenia virus, human parvovirus
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
Disclosed are methods of identifying a cross-modal feature from two or more spatially resolved data sets, the method including: (a) registering the two or more spatially resolved data sets to produce an aligned feature image including the spatially aligned two or more spatially resolved data sets; and (b) extracting the cross-modal feature from the aligned feature image.
The present invention relates to a homogeneous, time resolved, Förster resonance energy transfer (TR-FRET)-based method for detection of SARS-CoV-2, SARS CoV-1, and MERS-CoV antibodies in a patient fluid sample.
G01N 33/542 - Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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.
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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 31/4545 - 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
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
17.
INTESTINAL ALKALINE PHOSPHATASES AND METHODS OF USE IN INHIBITING LIVER FIBROSIS
Enhanced virus-like particles (eVLPs), comprising a membrane comprising a phospholipid bilayer with one or more virally-derived glycoproteins on the external side; and a cargo disposed in the core of the eVLP on the inside of the membrane, wherein the eVLP does not comprise an exogenous gag/pol protein, and methods of use thereof for delivery of the cargo to cells.
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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
Tunneling nanotube (TNT) cells, comprising a TNT promoting factor (TPF); and a biomolecule cargo overexpressed by the TNT cell, and methods of use thereof for delivery of the biomolecule cargo from TNT cells to neighboring cells.
Disclosed are bispecific compounds (degraders) that target ?-synuclein protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat neurodegenerative diseases.
THE GENERAL HOSPITAL CORPORATION - DBA MASS GENERAL HOSPITAL (USA)
Inventor
Al'Khafaji, Aziz
Blainey, Paul
Babadi, Mehrtash
Garimella, Kiran V
Hacohen, Nir
Smith, Jonathan Theodore
Abstract
The present disclosure relates to compositions and methods for nucleic acid sequencing, and specifically, at least in certain aspects, provides methods and compositions for enhancing the efficacy, throughput and/or yield of known long-range sequencing platforms, by providing chimeric arrays of input sequences. Such arrays of component nucleic acid sequence elements can be prepared via methods that minimize introduction of bias. The application of the current methods to obtain isoform sequencing information, e.g., from patient samples is specifically also provided, as are methods for mitochondrial lineage tracing that employ the instant chimeric amplicon sequencing processes. Methods and systems for array nucleic acid sequence processing and interpretation are also provided.
UNITED STATES GOVERNMENT AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS (USA)
MASSACHUSETTS INSTITUTE OF TECHNOLOGY (USA)
THE GENERAL HOSPITAL CORPORATION D.B.A MASSACHUSETTS GENERAL HOSPITAL (USA)
Inventor
Rasalingam, Ravi
Ward, Tarsha
Roche, Ellen T.
Venegas, Jose
Abstract
An oral appliance and method for treating a sleep disorder in a subject are disclosed. The appliance includes, among other elements, a palatal overlay element that engages a portion of the dorsal surface of the subject's tongue, stabilizing the tongue in a superior direction toward the hard palate. The method generally involves stabilizing the dorsal surface of a subject's tongue in a superior direction toward the subject's hard palate.
Methods, systems, compositions and strategies for the use of ARMM-mediated delivery of molecules (e.g., biological molecules, small molecules, proteins, and nucleic acids (e.g., DNA, RNA), DNA plasmids shRNA, mRNA) to cells of the nervous system (e.g., central nervous system and peripheral nervous system).
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
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
Methods for the use of glutathione trisulfide (GSSSG) in neuroprotection, e.g., in neurodegenerative diseases and to reduce the risk of ischemic injury. The methods can be used, e.g., to reduce risk of injury to brain, spinal cord, and peripheral nerves from ischemia or low blood flow states possibly caused by surgery, trauma, and other conditions that decrease/impair blood flow and or oxygen delivery to the nervous system.
C07K 5/093 - Tripeptides the side chain of the first amino acid containing more carboxyl groups than amino groups, or derivatives thereof, e.g. Asp, Glu, Asn
25.
FREQUENCY-COMB GENERATION BASED ON ELECTRO-OPTIC PHASE-CODE MODE-LOCKING FOR CIRCULAR-RANGING OCT
A source for providing electromagnetic radiation within a particular spectral range, including: a ring-shaped optical resonator for circulating a plurality of wavelength bands including: a first optical phase modulator, a first chromatic dispersion device, a second optical phase modulator, a multi-line spectral domain filter, a second chromatic dispersion device, and an optical amplifier; a controller coupled to the first optical phase modulator and the second optical phase modulator which is configured to drive the first optical phase modulator with a first waveform and the second optical phase modulator with a second waveform, the first chromatic dispersion device being configured between the first optical phase modulator and the second optical phase modulator to provide chromatic dispersion so as to subject each of the plurality of wavelength bands to a respective plurality of different time delays, the first optical phase modulator and the second optical phase modulator being configured to create spectral broadening by the first optical phase modulator of each of the plurality of wavelength bands and spectral recovery by the second optical phase modulator of a particular wavelength band of the plurality of wavelength bands by modulating a first phase using the first optical phase modulator driven by the first waveform and, after a particular time delay, modulating a second phase using the second optical phase modulator driven by the second waveform comprising an inverse of the first waveform, the particular time delay being determined so as to create spectral recovery for the particular wavelength band of the plurality of wavelength bands, the multi-line spectral domain filter being configured to provide multi-line spectral filtering with narrow bandwidths in order to induce power loss for each of the plurality of wavelength bands except for the particular wavelength band, the second chromatic dispersion device being configured to provide chromatic dispersion compensation to an output of the multi-line spectral domain filter in order to compensate a group delay dispersion within the optical resonator and match a roundtrip frequency for each of the plurality of wavelength bands, and the first and second waveforms being configured to create a periodic phase modulation for recovery of the plurality of wavelength bands at a frequency that is an integer multiple of a roundtrip frequency of the optical resonator.
G01K 11/32 - Measuring temperature based on physical or chemical changes not covered by group , , , or using changes in transmittance, scattering or luminescence in optical fibres
G02B 6/293 - Optical coupling means having data bus means, i.e. plural waveguides interconnected and providing an inherently bidirectional system by mixing and splitting signals with wavelength selective means
H01S 3/106 - Controlling the intensity, frequency, phase, polarisation or direction of the emitted radiation, e.g. switching, gating, modulating or demodulating by controlling devices placed within the cavity
26.
TARGETED DEGRADERS OF ABERRANT TAU BASED ON THE PET TRACER PBB3
Disclosed are bispecific compounds (degraders) that target tau protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat neurodegenerative and neuropsychiatric diseases associated with aberrant tau.
Systems and methods are provided for performing a hair transplant using a hair transplant device. The hair transplant device comprises an extraction unit including a coring needle configured to extract at least one hair follicle from a donor site, an implanting unit removably coupled to the extraction unit, the implanting unit including a splitting needle configured to create an opening in a recipient site, a housing coupled to the extraction unit, and a user interface extending from the housing and moveable relative to the housing. The user interface includes a pin movable within the coring needle relative to the housing.
Provided herein are compounds useful as imaging agents. Exemplary compounds provided herein are useful as myeloperoxidase imaging agents using magnetic resonance or nuclear imaging techniques. Methods for preparing the compounds provided herein and diagnostic methods using the compounds are also provided.
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
29.
SYSTEMS, METHODS, AND MEDIA FOR MULTIPLE BEAM OPTICAL COHERENCE TOMOGRAPHY
Systems, methods, and media for multiple beam optical coherence tomography are provided which, in some embodiments, include: a light source; a splitter that outputs a fraction of light to various waveguides; optical components that receive light from the waveguides and direct the light as beams that simultaneously impinge a sample at different lateral positions, and collect backscattered light from the lateral positons; another splitter that outputs a fraction of light to waveguides of a reference arm as reference light samples; a mixer that receives the backscattered light samples and the reference light samples, and combines each backscattered sample with a corresponding reference sample such that the mixer outputs fringes; and a detector that receives the fringes, and outputs OCT signals, each indicative of a structure of the sample at a respective lateral position.
The present disclosure presents nanoparticle compositions for use in the treatment, prevention, or imaging of a disease (e.g., cancer), methods of treating, preventing, or imaging a disease in a subject in need thereof with the nanoparticle compositions, and methods of preparing the nanoparticle compositions of the disclosure. The nanoparticle compositions can include a magnetic nanoparticle ferric chloride, ferrous chloride, or a combination thereof, and a dextran coating functionalized with one or more amine groups.
An apparatus, including: an electromagnetic radiation source producing radiation for illuminating a sample located at an optical path depth, the electromagnetic radiation source providing the radiation to the sample to facilitate determining the optical path depth within the sample: an interferometer including: a reference arm a first portion of the radiation is delivered to, a sample arm to which a second portion of the radiation is delivered, a first optical subsystem coupled to the sample arm to interrogate the sample with the radiation delivered to the sample arm and to collect backscattered radiation from the sample, and a second optical subsystem coupled to the reference arm and the first optical subsystem to generate interference fringes between the collected backscattered radiation and the radiation delivered to the reference arm; and a data collection and processing system configured to compute the optical path depth of the sample from the received interference fringes.
Provided herein are floating hydrogel droplet culture methods that enable scaling of stem cell derived alveolar epithelial cell (AEC) expansion to numbers compatible with large animal or human whole lung engineering, as well as molds for generating the droplets and methods of use thereof.
The technology described herein is directed to compositions comprising components of multi-compoent CALs or CARs, e.g., a TCR recognition domain; and one or both of: (a) an intracellular signaling domain; and (b) a first-type protein interaction domain. Further provided herein are methods for treating or preventing an autoimmune disease, a transplant rejection, or graft versus host disease.
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 provides a method of treating, preventing, or lessening postoperative cognitive dysfunction (POCD) in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of a compound of Formula I or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof,
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
36.
COMPOSITIONS AND METHODS FOR PULMONARY SURFACTANT-BIOMIMETIC NANOPARTICLES
Compositions and methods comprising Pulmonary Surfactant (PS)-biomimetic nanoparticles are disclosed. Specifically, the disclosure is related to a composition comprising a nanoparticle with an average size of 200-400 nm, including a plurality of pulmonary surfactant biomimetic molecules, wherein the nanoparticle is negatively charged; and one or more cargo molecules that are enveloped by the nanoparticle, wherein the cargo molecule has a molecular weight up to 1200 Da.
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.
The disclosure provides various aspects and embodiments of methods of, and compositions for use in methods of, treating age-related physiological alterations (e.g., those associated with age-related diseases or disorders) and/or treating or delaying the onset of age-related frailty in a subject. The methods include administering an AP-based agent or composition (e.g., a bovine intestinal alkaline phosphatase).
A61K 9/00 - Medicinal preparations characterised by special physical form
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 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
Provided herein are self-assembling pharmaceutical compositions comprising a heat shock protein fused to a biotin-binding protein, wherein the biotin-binding protein is non- covalently bound to a biotinylated component (e.g, tumor cell, tumor antigen, virus or viral antigen). The self-assembling pharmaceutical compositions may further comprise an immunotherapy (e.g, anti-PD-1 antibody). In addition, methods of using these pharmaceutical compositions to prevent and/or treat cancer, or to induce an immune response are provided. Methods of using the self-assembling pharmaceutical compositions in combination with an immunotherapy (e.g., anti-PD-1 antibody) are also provided.
Human-derived virus-like particles (heVLPs), comprising a membrane comprising a phospholipid bilayer with one or more HERV-derived envelope proteins on the external side; one or more HERV-derived GAG proteins in the heVLP core, and a cargo molecule, e.g., a biomolecule and/or chemical cargo molecule, disposed in the core of the heVLP on the inside of the membrane, wherein the heVLP does not comprise a gag protein, except for gag proteins that are encoded in the human genome or gag proteins that are encoded by a consensus sequence that is derived from gag proteins found in the human genome, and methods of use thereof for delivery of the cargo molecule to cells.
The invention provides antibodies, antibody-drug conjugates, bispecific T cell engagers (BiTEs), and chimeric antigen receptors (CARs) that target transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Such antibodies, antibody-drug conjugates, BiTEs, and CARs can be used, e.g., in methods for treating a cancer (e.g., multiple myeloma), an autoimmune disorder (e.g., characterized by a high titer of antibodies contributing to the disorder), or a plasma cell disease disorder (e.g., plasma cell dyscrasias) in a subject in need thereof.
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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).
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
Methods and compositions for preventing or treating cognitive decline associated with dementia and/or mild cognitive impairment and/or neurodegeneration using antibodies, peptides, fusion proteins, or genome editing systems that modulate HSPG/heparin binding affinities of ApoE.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
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
The present disclosure provides targeted T-cell engaging agents (TEAC) and antibody tumor-targeting assembly complexes (ATTAC) for targeting to cancer. The TEAC or ATTAC described herein may have, for example, longer half-life or comprise multiple components in a single agent.
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
A61K 39/00 - Medicinal preparations containing antigens or antibodies
45.
GHRH OR ANALOGUES THEREOF FOR USE IN TREATMENT OF HEPATIC DISEASE
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., frans-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.
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
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
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
47.
ENGINEERED ADENO-ASSOCIATED (AAV) VECTORS FOR TRANSGENE EXPRESSION
Engineered AAV vectors for transgene expression, e.g., in the CNS, PNS, inner ear, heart, or retina, and methods of use thereof. Also provided are methods for discovering new engineered AAV vectors that mediate transgene expression in desired cell types.
Systems and methods are provided for intraoperative real-time clinical decision support. A system includes a processor, a non-transitory computer readable medium, storing executable instructions, and an output device. An interface is configured to receive a first set of patient data in real-time from at least one sensor monitoring vital signals of a patient during a surgical procedure and a second set of patient data in real-time from an anesthesia machine during the surgical procedure. An input interface receives an indicator representing at least an identity of a therapeutic to be administered to the patient. A machine learning model determines from the indicator, the first set of patient data, and the second set of patient data if an alert should be provided to a user. The output device provides the alert to the user if the machine learning model determines that the alert should be provided.
A61M 21/02 - Other devices or methods to cause a change in the state of consciousness; Devices for producing or ending sleep by mechanical, optical, or acoustical means, e.g. for hypnosis for inducing sleep or relaxation, e.g. by direct nerve stimulation, hypnosis, analgesia
A61M 31/00 - Devices for introducing or retaining media, e.g. remedies, in cavities of the body
49.
NOVEL SMALL MOLECULE INHIBITORS OF TEAD TRANSCRIPTION FACTORS
The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.
A61K 31/136 - Amines, e.g. amantadine having aromatic rings, e.g. methadone having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
A61K 31/196 - Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
A61K 31/245 - Amino benzoic acid types, e.g. procaine, novocaine
A61K 31/351 - 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 not condensed with another ring
A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
A61K 31/40 - 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
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
C07C 229/58 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho- position having the nitrogen atom of at least one of the amino groups further bound to a carbon atom of a six-membered aromatic ring, e.g. N-phenyl-anthranilic acids
C07C 229/60 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in meta- or para- positions
C07C 237/40 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
C07C 311/44 - Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
C07C 317/36 - Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atoms of the amino groups bound to hydrogen atoms or to carbon atoms
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 207/04 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
C07D 211/06 - 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
C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07D 235/06 - Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
C07D 239/47 - One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
C07D 277/42 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07D 295/155 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
C07D 309/14 - Nitrogen atoms not forming part of a nitro radical
Compositions and methods for the treatment of benign nervous system tumors including schwannomas using attenuated Salmonella typhimurium and optionally one or more checkpoint inhibitors.
The present disclosure provides technologies relating to treatment of nausea and/or vomiting, and in some embodiments relates in particular to induced (e.g., chemotherapy-induced) nausea and/or vomiting. Alternatively, or additionally, in some embodiments, provides technologies relating to treatment or prevention of one or more feeding disorders (e.g., anorexia nervosa). Also provided herein are therapeutic compositions for oral delivery comprising a therapeutically effective amount of a C50 carotenoid compound, and a pharmaceutically acceptable carrier.
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/08 - Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
A61P 25/00 - Drugs for disorders of the nervous system
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
The present invention provides methods and compositions for stable genetic modification of immune cells. The genetic modifications can be used to produce immune cells for therapeutic or diagnostic purposes.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
Compositions, methods and kits are described for stabilizing cells and biological samples, allowing for storage and transportation of stabilized cells and biological samples. Cells can be stabilized in whole blood or fractionated blood. Isolated cells can also be stabilized.
The invention, in general, features a method of treating a neurodegenerative disease (such as amyotrophic lateral sclerosis) or a traumatic brain injury in a subject (e.g., a human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of isolated B cells (such as autologous or allogeneic or xenogeneic B cells).
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
55.
ANTI-EPHRIN-B2 BLOCKING ANTIBODIES FOR THE TREATMENT OF FIBROTIC DISEASES
Methods and compositions for treating organ fibrosis using antibodies or antigen-binding fragments thereof that bind to and block the soluble Ephrin B2 ectodomain.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61K 39/395 - Antibodies; Immunoglobulins; Immune 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
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
56.
PEPTIDE TAGS FOR LIGAND INDUCED DEGRADATION OF FUSION PROTEINS
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
Described herein are compounds and methods of treating or imaging a disease or disorder, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, ischemic stroke, and prion disease, comprising administering a therapeutically effective amount of a cromolyn ester.
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
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
Immunotolerant engineered human tissue constructs are provided that are suitable for implantation into subjects. In some embodiments, the immunotolerance is controllable by an inducible system. Methods of making and using the immunotolerant engineered tissue constructs are provided.
A61F 2/00 - Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
RNA targeting proteins are utilized to provide a robust massively multiplexed CRISPR-based diagnostic by detection in droplets with attomolar sensitivity. Detection of both DNA and RNA with comparable levels of sensitivity at nanoliter volumes can differentiate targets from non-targets based on single base pair differences, with applications in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, and sensitive genotyping.
Described herein are methods and compositions for treating a liver disease. Aspects of the invention relate to administering to a subject an agent that inhibits WISP1. Another aspect of the invention relates to administering to a subject a HSC that expresses and agent that inhibits WISP1.
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
A61P 19/04 - Drugs for skeletal disorders for non-specific disorders of the connective tissue
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
61.
COMPOSITIONS AND METHODS FOR IMMUNE CHECKPOINT INHIBITION
Therapeutic compositions and methods for treating cancer, e.g., pancreatic cancer, that use nanoparticles linked to inhibitory nucleic acids, e.g., siRNAs, targeting an immune checkpoint molecule, e.g., programmed cell death 1 ligand 1 (PD-L1).
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 49/18 - Nuclear magnetic resonance (NMR) contrast preparations; Magnetic resonance imaging (MRI) contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
The present disclosure relates to a method of treating at least one condition selected from Cytokine Release Syndrome (CRS), Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), cancer-related cognitive impairment, Infusion Reaction Syndrome (IRS), Capillary Leak Syndrome (CLS), Tumor Lysis Syndrome (TLS), Macrophage Activation Syndrome (MAS), Systemic Inflammatory Response Syndrome (SIRS), Immune Reconstitution Inflammatory Syndrome (IRIS), Graft-Versus-Host Disease (GVHD), Acute Respiratory Distress Syndrome (ARDS), sepsis, Ebola, avian influenza, smallpox, Systemic Inflammatory Response Syndrome (SIRS), and Immune-related Adverse Events Syndrome (IrAES) in a subject in need thereof, comprising administering a mast cell stabilizer or a compound of Formula I or Formula II: Formula I, Formula II, wherein R1 is halogen, OH, or -OC(O)C1-5alkyl R2 and R3 are each independently selected from CO2R4 or CH2OR5; R4 is Li, Na, K, H, C1-5alkyl, or -CH2CO(C1-5alkyl); and R5 is H or C(O)(C1-5alkyl), or a pharmaceutically acceptable salt thereof.
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
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
63.
COMPOSITIONS AND METHODS FOR DETECTING ANTIBIOTIC RESPONSIVE MRNA EXPRESSION SIGNATURES AND USES THEREOF
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/04 - Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C40B 40/06 - Libraries containing nucleotides or polynucleotides, or derivatives thereof
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.
A61K 39/395 - Antibodies; Immunoglobulins; Immune 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 application relates to compounds 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 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 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 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
A61K 31/428 - Thiazoles condensed with carbocyclic rings
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 31/4439 - 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 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
C07D 209/42 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
A system can deliver a specific amount of energy to a target region of a patient's body by scanning an energy beam over a precise path. The system can include a beam-path determination unit that defines the path and a duration for an energy beam to deliver a dose and/or a fluence of energy to the target region of the patient's body of the shape and/or the size. The system can also include an energy delivery system comprising an energy source that projects the energy beam for the duration and director device that directs (or scans) the energy beam along the path to deliver the dose and/or the fluence to the target region to achieve the dose profile and/or the fluence profile.
A61B 18/18 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
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 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.
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
C07K 7/64 - Cyclic peptides containing only normal peptide links
A method including: scanning a sample over a period of time using an electro-magnetic radiation source, the period of time including a first time period and a second time period, a sample portion of the electro-magnetic radiation source being directed to the sample in a sample arm of an optical interferometric system, and a reference portion of the electro-magnetic radiation source being directed to a reference arm of the optical interferometric system; applying, using a phase modulator, a phase shift comprising a first phase shift and a second phase shift to at least one of the reference portion or the sample portion of the electro-magnetic radiation source, the first phase shift being applied during the first time period and the second phase shift being applied during the second time period, the second phase shift having a difference of 90 degrees from the first phase shift; acquiring in-phase data based on a first interference between first backscattered electro-magnetic radiation during the first time period and the at least one of the reference portion or the sample portion subjected to the first phase shift; acquiring quadrature data based on a second interference between second backscattered electro-magnetic radiation during the second time period and the at least one of the reference portion or the sample portion subjected to the second phase shift; and determining a complex interference signal based on the in-phase data and the quadrature data.
The present disclosure provides antibody tumor-targeting assembly complexes (ATTACs) for selectively activating desired immune cells in 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
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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
70.
POWDERED FORMULATIONS OF CROMOLYN SODIUM AND .ALPHA.-LACTOSE
The present disclosure is directed to a composition comprising micronized cromolyn sodium, a-lactose, and a salt of fatty acid, wherein the a-lactose has a particle size distribution of D90 of 45-70 µm, D50 of 10-35 µm, and D10 of 2-13 µm. The present disclosure is also directed to a method of treating Alzheimer's disease, amyloidosis-associated condition (AAC), traumatic brain injury, Huntington's disease, atherosclerosis, cytokine release syndrome (CRS), dementia, head injury, infection, neuroinflammation, prion disease, stroke, amyotrophic lateral sclerosis (ALS), Parkinson's disease, or asthma using the composition.
A61K 9/72 - Medicinal preparations characterised by special physical form for smoking or inhaling
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 47/12 - Carboxylic acids; Salts or anhydrides 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
71.
CHIMERIC ANTIGEN RECEPTORS TARGETING CD37 AND CD19
The invention provides bispecific chimeric antigen receptors (CARs) targeting CD37 and CD19, as well as related molecules, immune cells including the same, compositions thereof, and their methods of use. The invention further provides methods for treating a disease or disorder, e.g., a 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
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
C12N 15/62 - DNA sequences coding for fusion proteins
72.
METHODS AND COMPOSITIONS FOR CHIMERIC ANTIGEN RECEPTOR TARGETING CANCER CELLS
THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL (USA)
THE GENERAL HOSPITAL CORPORATION (USA)
Inventor
Dotti, Gianpietro
Ferrone, Soldano
Hudson, Hannah Reid
Dukhovlinova, Elena
Ferrone, Cristina
Wang, Xinhui
Abstract
The present invention provides a chimeric antigen receptor (CAR) that recognizes CSPG4 as well as methods of use in the treatment of diseases and disorders.
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
C12N 5/078 - Cells from blood or from the immune system
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 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
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
A cell-scaffold device includes at least one channel network including an inlet, a plurality of channels include a parent channel having an end portion communicating with the inlet and another end portion communicating with a first bifurcation, forming two child channels. Each child channel has an end portion communicating with a respective end portion of the first bifurcation and another end portion communicating with a second bifurcation, forming two grand-child channels from each child channel. Each grand-child channel has an end portion communicating with a respective end portion of the second bifurcation and another end portion. The other end portion of the grand-child channel either forms an outlet or a third child channel in communication with the grand-child channel. Each forming of grand-child channels defines a generation of the fractal structure. The devices are of use as scaffolds for seeding, growing, and maintaining cells implanted in and/or on the device.
The present invention relates to an engineered CCCTC-binding factor (CTCF) variant including at least one amino acid residue in at least one zinc finger that differs in sequence from the amino acid sequence of a wild-type CTCF, where the engineered CTCF variant binds to a mutant CTCF binding sequence (CBS) with a higher affinity than wild-type CTCF, the mutant CBS including at least one nucleotide base that differs in sequence from the nucleotide sequence of a consensus CBS, where the at least one amino acid residue that differs in sequence from the amino acid sequence of a wild-type CTCF is selected from the group consisting of the amino acid residues at the position(s) -1, +1, +2, +3, +5, and +6 of any of ZF7, ZF6, ZF5, ZF4, and ZF3 of the engineered CTCF variant.
The present invention provides methods and compositions for increasing tumor antigenicity by increasing the level of expression of phosphoneoantigens in cells (e.g., restoring the expression of a phosphoneoantigen on the surface of a cancer cell). The invention also provides methods and compositions for enhancing recognition of phosphoneoantigens by immune cells.
Methods and compositions for performing highly sensitive in vitro assays to define substrate preferences and off-target sites of nucleic-acid binding, modifying, and cleaving agents.
The present disclosure relates to pharmaceutical compositions including a compound derived from a parent compound having a hydroxyl or amino moiety, wherein the hydroxyl in the parent compound is presented as an ester in the compound or the amino in the parent compound is presented as an amide in the compound, and their use to prevent or treat neurological disease.
C07C 233/22 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 31/223 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of alpha-amino acids
A61K 31/4045 - Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
C07C 217/60 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
C07C 219/28 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton having amino groups bound to acyclic carbon atoms of the carbon skeleton
79.
COMBINATION THERAPIES FOR THE TREATMENT OF AMYOTROPIC LATERAL SCLEROSIS AND RELATED DISORDERS
Described herein are methods of treating neuron inflammation conditions, for example, amyotropic lateral sclerosis and prion disease, comprising administering a therapeutically effective amount of a combination of cromolyn or a cromolyn derivative compound and an anti-inflammatory agent.
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
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
80.
MICROFLUIDIC SYSTEMS AND METHODS TO DENUDE MAMMALIAN OOCYTES
Microfluidic systems are configured to process liquid samples that include cumulus-oocyte complexes (COCs), such as raw follicular fluid, in an automated and continuous manner to produce oocytes separate or "denuded" from surrounding cumulus cells. The systems include a substrate and a channel that can have two or more sub-channels. Each channel includes an inlet, an outlet, and one or more stages arranged in series. Each of the stages includes one or more expansion units and one or more constriction units. At least one stage includes constriction units having jagged internal surfaces, e.g., teeth, that help remove the cumulus cells from the COCs.
The technology described herein relates to methods and compositions to prevent or treat vascular disease by targeting the epigenetic regulation of gene expression of vascular smooth muscle cell cytoskeletal 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
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
A61P 9/00 - Drugs for disorders of the cardiovascular system
The invention provides methods and compositions for use in treating cancer, which advantageously may be achieved by targeting of a tumor microenvironment. The invention provides chimeric antigen receptors (CARs) that target a tumor microenvironment. In one aspect, the invention features an immune cell engineered to express: (a) a chimeric antigen receptor (CAR) polypeptide including an extracellular domain including a first antigenbinding domain that binds to a first antigen and a second antigen-binding domain that binds to a second antigen; and (b) a bispecific T cell engager (BiTE), wherein the BiTE binds to a target antigen and a T cell antigen. In another aspect, the invention features a pharmaceutical composition including the immune cell. In another aspect, the invention features a method of treating a cancer in a subject in need thereof, the method comprising administering the immune cell.
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 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
84.
COMPOSITIONS AND METHODS FOR IMPROVING MITOCHONDRIAL FUNCTION
Described herein are methods for producing and utilizing T cells comprising chimeric antigen receptors (CAR) comprising two or more extracellular domains, each comprising a portion of the extracellular domain of a Tumor Necrosis Factor (TNF) superfamily receptor ligand, e.g., A PRoliferation- Inducing Ligand (APRIL). The CARs described herein are capable of targeting, e.g., B cell maturation antigen (BCMA) and/or transmembrane activator and CAML interactor (TACI). Additionally, the CAR T cells of this present invention overcome resistance to anti-BCMA targeted therapies and utilize dimerizing and trimerizing transmembrane domains for optimal function. Further, this invention is related to methods of treating cancer (e.g., multiple myeloma (MM)), plasma cell diseases or disorders, autoimmune diseases or disorders, or transplant rejection.
Described herein are methods and compositions for the treatment of cancer. Aspects include administering (1) an agent that inhibits activity of a CBM signalosome complex, or (2) a cell engineered to have reduced CBM signalosome complex levels to a subject having cancer. In various embodiment, the methods further comprise administering second therapeutic, for example, a checkpoint inhibitor or anti-cancer therapy, to the 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
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
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
Compositions comprising (i) lactate oxidase (LOX) and Catalase (CAT), preferably in a 1:1 molar ratio; or (ii) a fusion polypeptide comprising both LOX and CAT, e.g., LOXCAT, and methods of use thereof for reducing blood lactate levels, increasing blood pyruvate levels, and/or decreasing blood lactate/pyruvate ratio in a subject.
A61K 47/62 - 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 a protein, peptide or polyamino acid
A61P 7/08 - Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
Methods of delivering cromolyn to a patient in need thereof, methods of treating amyloid-associated conditions and inflammatory or allergic lung diseases, and packs and kits comprising cromolyn are described.
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 9/72 - Medicinal preparations characterised by special physical form for smoking or inhaling
The invention provides herein engineered regulatory T cells (Tregs), compositions thereof, and their methods of use. The Tregs described herein can be engineered to include, e.g., a chimeric antigen receptor (CAR), conferring increased stability, specificity, and immunosuppressive activity towards a target antigen. Furthermore, Tregs can also be engineered to reduce T cell cytotoxicity functions. Also provided are methods of suppressing immune response against a specific target antigen using the engineered Tregs described herein.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.
C07K 14/195 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
C07K 14/315 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
Systems and methods are provided for measuring the mechanical properties of ocular tissue, such as the lens or corneal tissue, for diagnosis as well as treatment monitoring purposes. A laser locking feedback system is provided to achieve frequency accuracy and sensitivity that facilitates operations and diagnosis with great sensitivity and accuracy. Differential comparisons between eye tissue regions of a patient, either on the same eye or a fellow eye, can further facilitate early diagnosis and monitoring.
Methods and devices for evaluating coagulation are described, including methods and devices for detecting an anticoagulant agent or a coagulation abnormality. In various embodiments, the methods and devices of the invention measure coagulation of a sample in response to a gradient of one or more coagulation factors. These responses can be evaluated to accurately profile coagulation impairments of the sample, including the presence of anticoagulant medication. In various embodiments, the invention provides point-of-care or bedside testing with a convenient, microfluidic device that can be used by minimally trained personnel.
The invention is directed to a composition comprising cromolyn sodium and ibuprofen, wherein the cromolyn sodium is micronized and the cromolyn sodium and ibuprofen are present in a weight ratio of 1:1-2. In one embodiment, the ibuprofen is passed through a sieve, such as a 300 µm sieve and to methods of making the same.
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.
SCREENING PLATFORM TO IDENTIFY THERAPEUTIC DRUGS OR AGENTS FOR TREATMENT OF ALZHEIMER'S DISEASE
Disclosed are methods and compositions for screening candidate substances for the prevention or treatment of neurodegenerative disorders such as Alzheimer's disease. The disclosure also relates to identifying the mechanisms of action for known or suspected Alzheimer's disease drugs and generally to compositions and methods for modulating the function of cells expressing CD33.
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
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 GENERAL HOSPITAL CORPORATION, D/B/A MASSACHUSETTS GENERAL HOSPITAL (USA)
Inventor
Gray, Nathanael S.
Haggarty, Stephen J.
Cai, Quan
Telo Baptista Lima Da Silva, Maria Catarina
Zhang, Tinghu
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.
THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL (USA)
THE GENERAL HOSPITAL CORPORATION (USA)
Inventor
Dotti, Gianpietro
Ferrone, Soldano
Du, Hongwei
Wang, Xinhui
Ferrone, Cristina
Abstract
The present invention provides a chimeric antigen receptor (CAR) that recognizes B7-H3 (CD276), as well as methods of use in the treatment of diseases and disorders.
Described herein are methods for producing and utilizing T cells comprising chimeric antigen receptors (CAR) comprising an extracellular domain that binds CD79b, or CD79b and CD 19. Further, this invention is related to methods of treating cancer, plasma cell diseases or disorders, or autoimmune diseases or disorders.
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 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
The present disclosure provides a blood vessel model including: a pair of channel members, mutually opposing each other, each of which includes an opposing face in which a respective microchannel is formed; and a porous membrane that includes plural through-holes penetrating in a thickness direction, that is disposed between the opposing faces of the pair of channel members, and that partitions between the microchannels, wherein the porous membrane is provided with a vascular endothelial cell layer so as to cover one face facing one of the microchannels, an average opening diameter of the through-holes is from 1 µ?? to 20 µm, and an opening coverage ratio of the through-holes is from 30% to 70%.
A living tissue model device includes: a first liquid compartment storing a liquid composition; a second liquid compartment storing a liquid composition; and a cell layered body disposed between the first liquid compartment and the second liquid compartment, as a partition between both compartments. A vascular wall model includes: a porous membrane having a honeycomb structure; a vascular endothelial cell layer disposed on one face of the porous membrane; and a smooth muscle cell layer, or a mesenchymal stem cell layer, disposed on another face of the porous membrane. A vascular wall model device includes: a first liquid compartment storing a liquid composition; a second liquid compartment storing a liquid composition; and a vascular wall model disposed between the first liquid compartment and the second liquid compartment, as a partition between both compartments. Applications of these models or model devices are also provided.
C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
C12N 5/077 - Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells
C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus
C12M 3/04 - Tissue, human, animal or plant cell, or virus culture apparatus with means providing thin layers
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
C12N 11/00 - Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
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