A device, kit, and method for aspirating graft tissue and delivering the graft tissue to a target delivery site. An injector comprises a cylinder and a plunger that is both linearly and rotatably advanceable and retractable within the cylinder. A kit comprises an injector, a cartridge, and a cartridge coupling element that connects the cartridge to the injector. The kit may also include a container that is configured to retain a cartridge and to facilitate connection between the injector and the cartridge. The container includes at least one fluid barrier that prevents spillage of storage solution from the container when the injector is at least partially inserted into the well of the container.
STING-dependent innate immune signaling pathway activators (STAVs) are delivered to antigen presenting cells in lipid nanoparticle formulations. The range of cancers amenable to STAV therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers STAV's into the Tumor MicroEnvironment (TME) to potently generate anti-tumor cytotoxic T cell activity. The range of cancers include melanomas and cutaneous T cell lymphomas. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APC's. Alternatively, the lipid nanoparticles can be introduced through direct inoculation.
C12N 15/117 - Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
3.
ENGINEERED MEGANUCLEASES THAT TARGET HUMAN MITOCHONDRIAL GENOMES
Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.
Hydrodynamic methods for conformally coating non-uniform size cells and cell clusters with biomaterials for implantation, thus preventing immune rejection or inflammation or autoimmune destruction while preserving cell functionality, are disclosed. Further disclosed are reagents, apparatus, and methods for conformally coating cells and cell clusters with hydrogels that are biocompatible, mechanically and chemically stable and porous, with an appropriate pore cut-off size.
Compositions and methods for detecting components of the inflammasome in a sample from a subject as markers for inflammasome-related diseases or disorders such as multiple sclerosis, stroke, mild cognitive impairment, Alzheimer's disease, age-related macular degeneration, NASH, inflammaging or traumatic brain injury. Methods of using such inflammasome markers to determine prognosis, direct treatment and monitor response to treatment for the subject with an inflammasome-related disease or disorder such as multiple sclerosis, stroke, mild cognitive impairment, Alzheimer's disease, age-related macular degeneration, NASH, inflammaging or traumatic brain injury are also described.
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 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
THE UNITED STATES GOVERNMENT AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS (USA)
Inventor
Mirsaeidi, Mehdi
Zhang, Chongxu
Schally, Andrew V.
Cai, Renzhi
Tian, Runxia
Abstract
The present disclosure is directed to a method of treating an inflammatory disorder, such as sarcoidosis, using a growth hormone-releasing hormone (GHRH) antagonist.
The compositions and methods described herein include methods and agents that inhibit inflammasome signaling in a mammal such as antibodies directed against inflammasome components used alone or in combination with extracellular vesicle uptake inhibitor(s) or other agents. Also described herein are compositions and methods of use thereof for treating viral-associated lung inflammation, for example lung inflammation associated with viral infections such as SARS-CoV-2.
Systems and methods for assessing, monitoring, or theranosing a condition or disorder based on a comparison of limb stability for one or more limbs of a subject from a baseline. The method includes placing two or more inertial measurement sensors on the limbs of the subject, acquiring baseline limb excursion data from the inertial measurement sensors while a patient is performing at least one of a static balance activity and a dynamic balance activity by tracking the relative displacement of the respective two or more inertial measurement sensors; acquiring post-injury limb excursion data after an injury from the inertial measurement sensors while a patient is performing at least one of a static balance activity and a dynamic balance activity; and determining the activity clearance index as a function of a comparison of the baseline limb excursion data compared to the post-injury limb excursion data.
A tissue processing chamber is disclosed. The tissue processing chamber includes at least one rotary blade housed within a tissue chamber and a drive shaft coupled to the rotary blades. Rotation of the drive shaft rotates the rotary'· blades and presses a tissue sample through a screen adjacent to the at least one rotary blade, wherein rotation of tire at least one rotary blade presses processed tissue through the screen. The tissue processing device also includes a collection chamber coupled to the tissue chamber configured to collect the processed tissue.
B02C 18/30 - Mincing machines with perforated discs and feeding worms
B02C 18/06 - Disintegrating by knives or other cutting or tearing members which chop material into fragments; Mincing machines or similar apparatus using worms or the like with rotating knives
B02C 18/08 - Disintegrating by knives or other cutting or tearing members which chop material into fragments; Mincing machines or similar apparatus using worms or the like with rotating knives within vertical containers
Ion booster for thrust generation. The invention pertains to electrical propulsion generated by the rapid acceleration of ions between asymmetrical electrodes. The invention is applicable for propulsion generation in atmospheric and space environments.
Quantification of symmetry and repeatability in limb motion for treating abnormal motion patterns. In the context of gait analysis, gait data may be acquired as signals from inertial sensors (e.g., gryoscopes). Each signal represents an angular velocity of a lower limb segment of a subject during ambulation. Each signal may be segmented into stride signals, and a gait metric may be calculated based on the stride signals. The gait metric may comprise a symmetry metric that represents a similarity of the stride signals across two signals acquired for at least one pair of contralateral limb segments. Additionally or alternatively, the gait metric may comprise a repeatability metric that represents a similarity of the stride signals within a signal. In other embodiments, other types of sensors may be used and/or motion data may be acquired and metrics calculated for other types of motions and/or for upper limb segments.
A61B 5/11 - Measuring movement of the entire body or parts thereof, e.g. head or hand tremor or mobility of a limb
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/103 - Measuring devices for testing the shape, pattern, size or movement of the body or parts thereof, for diagnostic purposes
A63B 21/00 - Exercising apparatus for developing or strengthening the muscles or joints of the body by working against a counterforce, with or without measuring devices
A63B 24/00 - Electric or electronic controls for exercising apparatus of groups
13.
GHRH ANTAGONISTS FOR USE IN A METHOD OF TREATING SARCOIDOSIS
Device for arterial puncture assistance. In an embodiment, the device comprises an upper component, lower component, and coupling mechanism that couples the lower component to the upper component. The upper component may comprise a platform configured to support a syringe. The lower component may comprise one or more finger holes, wherein each of the one or more finger holes is configured to receive a human finger therethrough, so as to enable contemporaneous stabilization of the lower component on the human finger and palpation of an arterial pulse by the human finger during an arterial puncture.
A61B 90/11 - Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups , e.g. for luxation treatment or for protecting wound edges for stereotaxic surgery, e.g. frame-based stereotaxis with guides for needles or instruments, e.g. arcuate slides or ball joints
A61B 17/00 - Surgical instruments, devices or methods, e.g. tourniquets
A steerable guide. In an embodiment, the steerable guide comprises a needle, a shaft, a spring housing, and a translational screw. The needle comprises a wire tube and a wire configured to curve the needle when retracted relative to the wire tube. The wire tube is connected to the distal end of the shaft, and the wire is connected to the distal end of the spring housing. The screw extends into a cavity within the shaft, and is configured to move along a longitudinal axis. A spring is positioned within the cavity, between the proximal end of the spring housing and the distal end of the screw. Thus, when the screw moves in the proximal direction while a position of the spring housing is fixed by the wire, the spring is compressed between the proximal end of the spring housing and the distal end of the translational screw.
A61M 25/06 - Body-piercing guide needles or the like
A61B 90/11 - Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups , e.g. for luxation treatment or for protecting wound edges for stereotaxic surgery, e.g. frame-based stereotaxis with guides for needles or instruments, e.g. arcuate slides or ball joints
A61B 18/22 - 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 beam being directed along or through a flexible conduit, e.g. an optical fibre; Hand-pieces therefor
16.
TREATMENT OF HEART DISEASE BY DISRUPTION OF THE ANCHORING OF PP2A
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY (USA)
Inventor
Kapiloff, Michael S.
Li, Jinliang
Abstract
The present invention provides a method of treating heart failure with reduced ejection fraction, by administering to a patient at risk of such damage, a pharmaceutically effective amount of a composition which inhibits the anchoring of PP2A to mAKAPß. This composition is preferably in the form of a viral based gene therapy vector that encodes a fragment of mAKAPß to which PP2A binds.
The present disclosure relates to methods of detecting and treating inherited neuropathy. In various aspects, the method comprises detecting the presence of a mutation in the sorbitol dehydrogenase (SORD) gene in a sample from a subject. In various embodiments, th SORD mutation is a DNA variant classified as pathogenic or likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) criteria.
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
C12N 9/04 - Oxidoreductases (1.), e.g. luciferase acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
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
18.
IMPROVED INHIBITORS OF THE NOTCH TRANSCRIPTIONAL ACTIVATION COMPLEX AND METHODS FOR USE OF THE SAME
Disclosed herein are inhibitors of the Notch transcriptional activation complex, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein can include compounds of Formula (I) and pharmaceutically acceptable salts thereof: Formula (I), wherein the substituents are as described.
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
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61P 9/00 - Drugs for disorders of the cardiovascular system
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
In certain embodiments, vision defect information may be generated via a dynamic eye-characteristic-based fixation point. In some embodiments, a first stimulus may be displayed at a first location on a user interface based on a fixation point for a visual test presentation. The fixation point for the visual test presentation may be adjusted during the visual test presentation based on eye characteristic information related to a user. As an example, the eye characteristic information may indicate a characteristic of an eye of the user that occurred during the visual test presentation. A second stimulus may be displayed during the visual test presentation at a second interface location on the user interface based on the adjusted fixation point for the visual test presentation. Vision defect information associated with the user may be generated based on feedback information indicating feedback related to the first stimulus and feedback related to the second stimulus.
A61B 3/113 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for determining or recording eye movement
A61B 3/00 - Apparatus for testing the eyes; Instruments for examining the eyes
A61B 3/14 - Arrangements specially adapted for eye photography
UNITED STATES GOVERNMENT AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS (USA)
UNIVERSITY OF MIAMI (USA)
Inventor
Jackson, Robert M.
Schally, Andrew V.
Cai, Renzhi
Cai, Xianyang Zhang
Wang, Haibo
Sha, Wei
Abstract
Described herein are compositions and methods for treating pulmonary fibrosis and cancer. The compositions include growth hormone releasing hormone peptides. The methods include reducing lung inflammation, lung scarring, reducing expression of T cell receptor complex genes as well as inhibiting tumor growth.
Systems, methods, and computer readable media for determining cognitive impairment (CI) in patients are provided herein. Various regional structural-functional parameters of the retina can serve as biomarkers for the detection of CI. The method can include forming a database including a quantification of retinal structure and retinal function of a plurality of eyes associated with a plurality of patients, providing a baseline cognitive impairment (CI) reference. The method can include determining a measure of functionality of neurons in the retina based on an electroretinogram (ERG) of a patient. The method can include determining a structural measure of the first retina based on a generalized dimension spectrum and singularity spectrum of the skeletonized retinal image, and a lacunarity parameter of the skeletonized retinal image. The method can include determining a level of cognitive impairment based on the structural and functional measures.
A61B 5/398 - Electrooculography [EOG], e.g. detecting nystagmus; Electroretinography [ERG]
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
A61B 3/00 - Apparatus for testing the eyes; Instruments for examining the eyes
A61B 3/12 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
22.
METHOD OF DETERMINING RESPONSIVENESS TO CELL THERAPY IN DILATED CARDIOMYOPATHY
The present disclosure is directed to methods for determining responsiveness to cell therapy in a subject suffering from a cardiovascular disorder (e.g., cardiomyopathy) and methods of treating subjects suffering from a cardiovascular disorder.
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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
A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
A61K 35/12 - Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
A device and method for preserving corneal graft tissue. In one embodiment, a device for preserving corneal graft tissue comprises: a first chamber; a second chamber; and a corneal graft tissue suspension assembly that is configured to retain and suspend the corneal graft tissue between the first chamber and the second chamber, the first chamber being fluidly isolated from the second chamber when the corneal graft tissue is graft tissue is retained and suspended within the corneal graft tissue suspension assembly. In one embodiment, a method includes filling a first chamber of a device with a first preservation medium and filling a second chamber of the device with a second preservation medium different than or the same as the first, a corneal graft tissue being located between the first and second chambers.
A61H 23/02 - Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms with electric or magnetic drive
In some embodiments, a set of eye images related to a subject may be provided to a prediction model. A first prediction may be obtained via the prediction model, where the first prediction is derived from a first eye image and indicates whether an eye condition is present in the subject. A second prediction may be obtained via the prediction model, where the second prediction is derived from a second eye image and indicates that the eye condition is present in the subject. An aspect associated with the first prediction may be adjusted via the prediction model based on the second prediction's indication that the eye condition is present in the subject. One or more predictions related to at least one eye condition for the subject may be obtained from the prediction model, where the prediction model generates the predictions based on the adjustment of the first prediction.
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
A61B 3/14 - Arrangements specially adapted for eye photography
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
The compositions and methods described herein include agents that inhibit inflammasome signaling in the mammal such as antibodies directed against inflammasome components used alone or in combination with extracellular vesicle uptake inhibitor(s). Also described herein are compositions and methods of use thereof for treating inflammasome related diseases or conditions.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 25/14 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
The present disclosure relates, in general, to recombinant viral vectors that stimulate STING (STimulator of INterferon Genes) activity and increase activity of immune cells.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
Disclosed herein are Notch transcriptional activation complex kinase ("NACK") inhibitors, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein include compounds of Formula (la) and pharmaceutically acceptable salts thereof: wherein the substituents are as described.
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
The disclosure provides a method of treating breast cancer, the method comprising administering to mammalian subject in need thereof an inhibitor of Receptor for Advanced Glycation End-product (RAGE). The disclosure further provides a method of inhibiting breast cancer metastasis, the method comprising administering to mammalian subject in need thereof an inhibitor of RAGE.
Devices for testing, identifying, and compensating for ocular pathologies affecting the vision of a patient are provided in the form of digital therapeutic corrective spectacles that provided personalized, customized visual field corrected/enhancement. The devices include wearable spectacles with one or more digital monitors that are used to recreate an entire visual field as a digitized corrected image or that include custom-reality glasses that can be used to overlay a visual scene with generated image to correct or enhance the visual field of the subject.
A61B 3/00 - Apparatus for testing the eyes; Instruments for examining the eyes
A61B 3/024 - Subjective types, i.e. testing apparatus requiring the active assistance of the patient for determining the visual field, e.g. perimeter types
A61B 3/113 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for determining or recording eye movement
The present invention provides compositions and methods for detecting components of the inflammasome in a sample from a subject as markers for brain injuries such as multiple sclerosis, stroke or traumatic brain injury. Methods of using such inflammasome markers to determine prognosis, direct treatment and monitor response to treatment for the subject with a brain injury such as multiple sclerosis, stroke, mild cognitive impairment or traumatic brain injury are also described.
The invention provides a method of treating or preventing pain in a subject in need thereof. The method comprising administering to the subject an expression vector comprising a nucleic acid sequence encoding carbonic anhydrase (10) or carbonic anhydrase (11) such that the nucleic acid is expressed to produce carbonic anhydrase (10) or carbonic anhydrase (11). Alternatively, the method comprising administering to the subject an expression vector comprising a nucleic acid sequence encoding a carbonic anhydrase (8) fragment such that the nucleic acid is expressed to produce the carbonic anhydrase (8) fragment.
The invention provides a method of increasing blood flow or perfusion in an ischemic tissue; inducing angiogenesis, neovascularization or revascularization; increasing skeletal muscle viability; promoting ischemic skin wound healing; treating or preventing gangrene; and/or treating CLI. In various aspects, the method comprises administering to a subject a hybrid adenoassociated virus (AAV) comprising a nucleotide sequence encoding an E-selectin, AAV serotype 2 (AAV2) inverted terminal repeats (ITRs), and a capsid from an AAV other than serotype 2. In various aspects, the method comprises administering to the subject a cell comprising an AAV comprising a nucleotide sequence encoding an E-selectin, AAV2 ITRs, and a AAV2 capsid.
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
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 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
35.
METHOD AND SYSTEM FOR THREE-DIMENSIONAL THICKNESS MAPPING OF CORNEAL MICRO-LAYERS AND CORNEAL DIAGNOSES
Techniques for improved diagnosis, treatment, and monitoring of corneal pathologies use enhanced mapping of the cornea or corneal regions, to develop three- dimensional mapping of corneal thickness, while retaining particular corneal micro-layer thickness data. Anterior and posterior surface identifications, along with surface apex determinations, are used for registration of segmentation of these micro-layers. 3D heat maps and bull's-eye maps are generated from resulting thickness date. The maps provided enhanced evaluation and diagnosis of a corneal pathologies, such as keratoconus, pellucid marginal degeneration, post-refractive surgery ectasia, keratoglobus, corneal transplant rejection and corneal transplant failed grafts, Fuchs dystrophy, corneal limbal stem cell deficiency, dry eye syndrome, and post-corneal collagen crosslinking evaluation.
A61B 3/12 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
36.
METHOD FOR MODULATING INFLAMMASOME ACTIVITY AND INFLAMMATION IN THE LUNG
The present invention provides compositions and methods for reducing inflammation in the lungs of a mammal that is afflicted by a condition that leads to inflammation in the lungs. The compositions and methods described herein include agents that inhibit inflammasome signaling in the mammal such as antibodies directed against inflammasome components used alone or in combination with extracellular vesicle uptake inhibitor(s).
Antibodies specific for secretogranin III (Scg3) are disclosed. Methods of using the antibodies, antigen -bin ding fragments thereof, or pharmaceutical compositions comprising the same in the treatment of diseases such as diabetic retinopathy, neovascular age-related macular degeneration, retinopathy of prematurity, and cancer, are also disclosed.
The present invention provides an expression vector, host cells, methods and kits for the treatment or prevention of a flavivirus infection in a subject.
The disclosure provides a method of forming carbon dots, including admixing carbon powder with sulfuric acid and nitric acid and heating the carbon powder mixture to reflux to oxidize the carbon powder. The method further includes isolating and purifying the carbon dots. The disclosure further provides applications of the carbon dots for diagnostic analysis (such as bone analysis), fibrillation inhibition, and drug delivery.
Kits and methods for detecting pathogens without the need for laboratory equipment are disclosed. The kits and methods described herein allow for near-room temperature amplification of pathogen polynucleotides in a biological sample in a one-compartment reaction vessel. The kits and methods may be used to detect any target nucleic acid, such as DNA or RNA from a bacterial, fungal, or viral pathogen.
C12Q 1/04 - Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
41.
INTERLEUKIN-2/INTERLEUKIN-2 RECEPTOR ALPHA FUSION PROTEINS AND METHODS OF USE
Various methods and compositions are provided which can be employed to modulate the immune system. Compositions include a fusion protein comprising: (a) a first polypeptide comprising Interleukin-2 (IL-2) or a functional variant or fragment thereof; and (b) a second polypeptide, fused in frame to the first polypeptide, wherein the second polypeptide comprises an extracellular domain of Interleukin-2 Receptor alpha (IL-2Ra ) or a functional variant or fragment thereof, and wherein the fusion protein has IL-2 activity. Various methods are provided for modulating the immune response in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the IL-2/IL-2Ra fusion protein disclosed herein.
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
A cell culture medium comprising adenosine triphosphate; a carrier protein; cholesterol, linoleic acid, and lipoic acid; glutathione; at least one nucleotide salvage pathway precursor base; phosphoethanolamine; selenium; transferrin; triiodothyronine; all-trans-retinoic acid (ATRA) and vitamin C; zinc, magnesium, and copper; an agent that increases intracellular cAMP; epidermal growth factor (EGF); hydrocortisone; insulin; and charcoal stripped fetal bovine serum, wherein said cell culture medium is substantially free, if not entirely free, of vitamin D, androgenic hormones, androgenic ligands, estrogenic hormones, estrogenic ligands, and/or androgenic receptors.
Disclosed herein are compositions and methods for determining a risk of cancer, such as head and neck squamous cell carcinoma, in a subject using a bodily fluid sample from the subject and assays for markers such as solCD44 and total protein. Also disclosed are methods of treating a subject based on said risk. Methods of determining the efficacy of a cancer treatment are also disclosed.
A novel classification system for breast cancer based on normal breast cell phenotypes and various expression levels of estrogen receptor (ER), androgen receptor (AR), and vitamin D receptor (VDR). The various categories of the classification system are associated with different survival rates and prognoses. The invention includes a method of classifying breast cancer comprises measuring the levels of ER, AR, and VDR in the cancerous tissue, and classifying the breast cancer into one of the above-noted categories according to expression levels. The invention includes a method of predicting the prognosis of breast cancer in a patient and a method of determining a treatment regimen for breast cancer depending on the category in which the breast cancer is classified. The invention includes a method of treating breast cancer according to the expression profile of ER, AR, and VDR detected in the cancerous tissue. Kits for detecting the same are also provided.
The present invention relates to the fields of medicine, cell biology, molecular biology and genetics. In particular, the present invention provides methods to isolate and purify microvesicles from cell culture supernatants and biological fluids. The present invention also provides pharmaceutical compositions of microvesicles to promote or enhance wound healing, stimulate tissue regeneration, remodel scarred tissue, modulate immune reactions, alter neoplastic cell growth and/or mobility, or alter normal cell growth and/or mobility. The present invention also provides compositions of microvesicles to be used as diagnostic reagents, and methods to prepare the compositions of microvesicles.
A61P 25/00 - Drugs for disorders of the nervous system
A61P 37/00 - Drugs for immunological or allergic disorders
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
A method of repairing diseased or dysfunctional pancreas or liver is provided. The method involves preparation of a suspension of stem cells and/or progenitor cells such as biliary tree stem cells, hepatic stem cells, pancreatic stem cells or their descendants, committed progenitor cells, from healthy tissue of the patient or of the biliary tree of a non-autologous donor and engrafting the cells into the wall of bile ducts near to the organ to be treated. The graft consists of stem cells or progenitors that are admixed with biomaterials and, optionally, with cytokines and/or native epithelial-mesenchymal cells appropriate for the maturational lineage stage of the cells to be engrafted. The cells are specifically introduced to the hepato-pancreatic common duct of the subject for treatment of pancreatic conditions or to the bile duct wall near to the liver for treatment of liver conditions and allowed to migrate to the pancreas or to the liver and expand and then rebuild part or the entirety of the diseased or dysfunctional organ.
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
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 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
47.
COMPOSITIONS AND METHODS FOR THE REGULATION OF T REGULATORY CELLS USING TL1A-IG FUSION PROTEIN
Compositions comprising TL1 A-lg fusion proteins and methods of their use, e.g., for the treatment of diseases and disorders associated with antigen-specific immune responses, are described. Also described are combination therapies that include the administration of a TNFRSF25 agonist and an interleukin (e.g., IL-2) and/or an mTOR inhibitor (e.g., rapamycin). In some embodiments, provided here is an isolated or recombinant nucleic acid comprising a polynucleotide sequence which encodes a fusion protein, the fusion protein comprising (a) a first polypeptide comprising a polypeptide sequence that specifically binds to Tumor Necrosis Factor Receptor Superfamily, Member 25 (TNFRSF25), and (b) a second polypeptide comprising an immunoglobulin (Ig) polypeptide; or a complementary polynucleotide sequence thereof.
The present invention provides novel markers of the severity of a central nervous system injury, such as spinal cord injury or traumatic brain injury, in a patient. In particular, protein components of inflammasomes in the cerebrospinal fluid that can be used to assess the severity of central nervous system injury in a patient are disclosed. Methods of using such protein biomarkers to determine a prognosis, direct treatment and rehabilitation efforts, and monitor response to treatment for a patient with a central nervous system injury are also described.
UNITED STATES OF AMERICA REPRESENTED BY THE DEPARMENT OF VETERANS AFFAIRS (USA)
Inventor
Schally, Andrew V.
Cai, Ren-Zhi
Zarandi, Marta
Abstract
The synthetic peptides have the sequence: [RrA\ A2, A6, A8, A11, A12, A15, A20, A21, A22, Nle27, A28, A29, A30]hGH-RH(1 -30)-R2 (SEQ ID NO: 1 ) wherein R1 is Ac, Tfa, or is absent, A1 is Tyr, Dat, or N-Me-Tyr, A2 is Ala, D-Ala, Abu, or D-Abu, A6 is Phe or Fpa5, A8 is Asn, Ala, Gin, Thr, or N-Me-Ala, A11 is Arg, His, or Har, A12 is Orn, or Lys(Me)2, A15 is Abu or Ala A20 is Arg, His, or Har, A21 is Orn, or Lys(Me)2, A22 is Leu, or Orn, A28 is Ser, or Asp, A29 is Arg, Har, Agm, D-Arg, or D-Har, A30 is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gin, D-GIn, Gin-Gab, D-Gln-Gab, or is absent, R2 is -NH2, -OH, -NHR2, -N(R2)2, or -OR2, in which R2 is any of C1-12 alkyl, C2-12 alkenyl, or C2-12 alkinyl, provided that if A29 is Agm then A30 and R2 are absent A1 is N-Me-Tyr only, and pharmaceutically acceptable salts thereof.
Methods and kits for diagnosing and determining prognosis of head and neck squamous cell carcinoma are described. An exemplary method for diagnosing head and neck squamous cell carcinoma (HNSCC) in a subject may comprise assaying a saliva sample from the subject for the presence of total protein, solCD44, and HPV, and using the combination of total protein, HPV, and CD44 levels in a multivariate analysis to determine a combined score, whereby an increase in score above a cut-off point distinguishes subjects with HNSCC, or an elevated risk of future occurrence thereof, from subjects without HNSCC or at low risk of future occurrence thereof.
Improved methods and systems for processing of solid tissue are described. The method may be performed manually or automatically. The system may have modules such as (i) a grossing module where a fresh tissue is sliced to prepare a tissue specimen, (ii) a hardening module that hardens the tissue specimen, (iii) an impregnating module that impregnates the tissue specimen that was hardened, and (iv) an embedding module that embeds a tissue specimen that was hardened and impregnated. Fresh (i.e., not fixed or frozen) tissue, which was excised to diagnose disease or to assess surgical treatment, is grossed to about 0.6 mm. Preferably, the hardening of fresh tissue is initiated, but not completed, during grossing by contact with a chemical admixture. Preferably, dry ice, a thermoelectric device, or a gas condenser cools a metal mold containing the embedded specimen. It is sectioned and then microscopically examined as an alternative to histologic examination of a frozen section to avoid the known problems of discordant and deferred diagnosis.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
53.
SYSTEM AND METHOD FOR EARLY DETECTION OF DIABETIC RETINOPATHY USING OPTICAL COHERENCE TOMOGRAPHY
A system for the imaging, processing and evaluation of tissues provides prognostic and diagnostic details regarding diseased tissue. A set of quantitative measures were developed and integrated in an image-base analysis software tool designed for OCT images. The system and methods in this invention is significant because it allows assessing the optical properties and struc-ture morphology differences between normal healthy subjects and diabetic patients with retinopathy up to ETDRS level 35 and without retinopathy.
A61B 3/10 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions
A61B 3/12 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
A system for the imaging, processing and evaluation of tissues provides prognostic and diagnostic details regarding diseased tissue. A set of quantitative measures were developed and integrated in an image-base analysis software tool designed for OCT images. The system and methods in this invention is significant because it allows assessing the optical properties and structure morphology differences between normal healthy subjects and diabetic patients with retinopathy up to ETDRS level 35 and without retinopathy.
A61B 3/12 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
55.
NOVEL N- AND C-TERMINAL SUBSTITUTED ANTAGONISTIC ANALOGS OF GH-RH
THE UNITED STATES OF AMERICA REPRESENTED BY THE UNITED STATES DEPARTMENT OF VETERAN'S AFFAIRS (USA)
Inventor
Schally, Andrew V.
Varga, Jozsef L.
Marta, Zarandi
Renzhi, Cai
Abstract
There is provided a novel series of synthetic analogs of hGH-RH(1-29)NH2 (SEQ ID NO: 96) and hGH-RH(1-30)NH2. Of particular interest are those carrying PhAc, N-Me-Aib, Dca, Ac- Ada, Fer, Ac-Anic, Me-NH-Sub, PhAc-Ada, Ac-Ada-D-Phe, Ac-Ada-Phe, Dca-Ada, Dca-Amc, Nac-Ada, Ada-Ada, or CH3{CH2)10-CO- Ada, at the N-Terminus and .beta.-Ala, Amc, Apa, Ada, AE2A, AE4P, .epsilon.-Lys(.alpha.-NH2), Agm, Lys(Oct) or Ahx, at the C- terminus. These analogs inhibit the release of growth hormone from the pituitary in mammals as well as inhibit the proliferation of human cancers through a direct effect on the cancer cells. The stronger inhibitory potencies of the new analogs, as compared to previously described ones, result from replacement of various amino acids.
Cell-based immunotherapy (e.g., immunization or vaccination) may be improved by frequent administration to a human subject of allogeneic cancer cells secreting a modified heat shock protein (e.g., gp96), depletion of B cells in the subject, or both. Antigen (e.g., epitope derived from neoantigen or tumor antigen of allogeneic or syngeneic cancer cells) may induce a spe-cific immune response in the subject. For example, the epitope bound in an immunogenic complex with the secreted heat shock protein may be obtained from allogeneic cancer cells coexpressing both secreted gp96 and antigen, or from syngeneic cancer cells of the subject expressing only antigen.
CoQlO has a stimulatory effect on fibroblasts and keratinocytes, increases ATP production, decreases pain. The formulations are useful for promoting acute wound healing, fatigue and treatment of acute and chronic pain.
It is an object of the invention to provide novel compositions and methods utilizing immunomodulating agents that can either stimulate or indirectly augment the immune system or in other cases have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used, among other things, to treat disease caused by asthma and chronic inflammation such as for example inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein are capable of inhibiting CD8 T cell-mediated cellular immune responses and can for example, mitigate organ or tissue rejection following a tissue transplantation. TNFR25 agonists disclosed herein represent biological response modifiers that alter the interaction between the body's cellular immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the cancer when given with tumor vaccines. TNFR25 specific immunotoxins disclosed herein are also capable of increasing the effectiveness of a chemotherapeutic regimen by depleting a cancer patient of naturally occurring immunosuppressive cells.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 51/10 - Antibodies or immunoglobulins; Fragments thereof
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
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
A system, method and apparatus for anatomical mapping utilizing optical coherence tomography. In the present invention, 3-dimensional fundus intensity imagery can be acquired from a scanning of light back-reflected from an eye. The scanning can include spectral domain scanning, as an example. A fundus intensity image can be acquired in real-time. The 3-dimensional data set can be reduced to generate an anatomical mapping, such as an edema mapping and a thickness mapping. Optionally, a partial fundus intensity image can be produced from the scanning of the eye to generate an en face view of the retinal structure of the eye without first requiring a full segmentation of the 3-D data set. Advantageously, the system, method and apparatus of the present invention can provide quantitative three-dimensional information about the spatial location and extent of macular edema and other pathologies. This three-dimensional information can be used to determine the need for treatment, monitor the effectiveness of treatment and identify the return of fluid that may signal the need for retreatment.
A61B 3/12 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
60.
TOPICAL CO-ENZYME Q10 FORMULATIONS AND METHODS OF USE
Topical formulations of CoQ10 reduce the rate of tumor growth in an animal subject. In the experiments described herein, CoQ10 was shown to increase the rate of apoptosis in a culture of skin cancer cells but not normal cells. Moreover, treatment of tumor-bearing animals with a topical formulation of CoQ10 was shown to dramatically reduce the rate of tumor growth in the animals.
Improved systems and methods for tissue processing are described here. The chemical process and the construction of the apparatus are simplified by using only two different solutions in two separate reaction modules. They are compatible with processing of tissue specimens for genetic analysis, histology, in situantibody binding and hybridization, archival preservation of morphology and nucleic acids, and combinations thereof.
patents
