IPC Classes  ?

• G06F 1/20 - Cooling means
• H01L 23/46 - Arrangements for cooling, heating, ventilating or temperature compensation involving the transfer of heat by flowing fluids
• H01L 23/467 - Arrangements for cooling, heating, ventilating or temperature compensation involving the transfer of heat by flowing fluids by flowing gases, e.g. air
• H01L 23/473 - Arrangements for cooling, heating, ventilating or temperature compensation involving the transfer of heat by flowing fluids by flowing liquids
• H05K 7/20 - Modifications to facilitate cooling, ventilating, or heating

IPC Classes  ?

• A61K 31/13 - Amines, e.g. amantadine
• A61K 31/145 - Amines, e.g. amantadine having sulfur atoms, e.g. thiurams (N—C(S)—S—C(S)—N or N—C(S)—S—S—C(S)—N)Sulfinylamines (—N=SO)Sulfonylamines (—N=SO2)
• A61K 31/16 - Amides, e.g. hydroxamic acids
• A61P 7/06 - Antianaemics

Abstract

The subject matter described herein relates to methods of zNKT cell activation by the 7DW8- 5 glycolipid.

IPC Classes  ?

• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants

Abstract

Disclosed are systems and methods for motor control using piecewise affine modelling. An electronic controller may determine current values for a motor in a rotational reference frame. Each current value may be associated with a dimension of a set of dimensions of the rotational reference frame. The electronic controller may further determine, based on the current values, a flux linkage value for each of the set of dimensions of the rotational reference frame using a piecewise affine map. The electronic controller may further determine a target flux linkage value for each of the set of dimensions of the rotational reference frame. The electronic controller may then control a power switching network coupled between a power supply and the motor based on the flux linkage values and the target flux linkage values.

IPC Classes  ?

• H02P 6/34 - Modelling or simulation for control purposes
• H02P 21/06 - Rotor flux based control involving the use of rotor position or rotor speed sensors
• H02P 21/08 - Indirect field-oriented controlRotor flux feed-forward control
• H02P 21/10 - Direct field-oriented controlRotor flux feed-back control
• H02P 21/13 - Observer control, e.g. using Luenberger observers or Kalman filters
• H02P 21/14 - Estimation or adaptation of machine parameters, e.g. flux, current or voltage
• H02P 21/22 - Current control, e.g. using a current control loop
• H02P 21/24 - Vector control not involving the use of rotor position or rotor speed sensors
• H02P 21/26 - Rotor flux based control
• H02P 21/28 - Stator flux based control
• H02P 21/30 - Direct torque control [DTC] or field acceleration method [FAM]

Abstract

Provided herein are recombinant miniature swine without expression of endogenous porcine CD47 and SIRPA, but with the expression of human or humanized CD47 and human or humanized SIRPA under the same regulatory elements as the endogenous porcine CD47 and SIRPA. Also provided are cells, tissues, and organs derived from such recombinant miniature swine. Furthermore, provided herein are methods of transplanting a graft from a first donor of such recombinant miniature swine with or without bone marrow from a second donor of such recombinant miniature swine.

IPC Classes  ?

• A01K 67/027 - New or modified breeds of vertebrates
• A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants

Abstract

Methods and compositions for treating leukemia involving administering a therapeutically effective amount of an in¬ hibitor of indoleamine 2,3 dioxygenase (IDO1). The leukemia may be is acute myeloid leukemia or acute lymphoid leukemia. The inhibitor canbe a small molecule such as indiximod, epacadostat, BMS-986205, navoximod, PF-0684003, KHK2455 orLY3381916 or epacadostat. The inhibitor can be used alone or in conjunctions with other chemotherapeutic agents. IDO1 can also be inhibited using a CRISP-CAS system. The inhibitor canbe administered orally, intravenously, intramuscularly, topically, arterially, or subcutaneously.

IPC Classes  ?

• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• 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
• 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

Abstract

Anti-SARS-CoV-2 ?/?-polypeptides, pharmaceutical compositions containing the same, and methods to inhibit, treat, and ameliorate SARS-CoV-2 infections in mammals, including humans.

IPC Classes  ?

• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 31/14 - Antivirals for RNA viruses
• C07K 14/165 - Coronaviridae, e.g. avian infectious bronchitis virus

Abstract

The disclosed subject matter provides for genetically modified cells, e.g., fungal cells, that autonomously generates and/or secretes one or more skin therapeutics, and methods of use thereof. In certain embodiments, the present disclosure provides genetically-engineered fungal cells that generate and secrete growth factors, protease inhibitors, cytokines and/or chemokines and methods of use thereof, e.g., for treating skin conditions.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 36/06 - Fungi, e.g. yeasts
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• C12N 1/14 - Fungi Culture media therefor
• C12N 15/18 - Growth hormones
• C12N 15/19 - InterferonsLymphokinesCytokines
• C12N 15/81 - Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts

Abstract

The anionic manganese oxide nanoparticle nucleic acid scavengers are biodegradable anionic scavengers with low cytotoxicity, which are able to scavenge (bind) cell-free nucleic acids (e.g., extracellular ssRNA, dsRNA, and unmethylated DNA), providing treatment for various medical conditions. The main component of the scavenger is manganese oxide, which may be synthesized by using a manganese compound (e.g., manganese acetate) and an acid (e.g., tannic acid) at high temperature (e.g., 100-150°C). Synthesis may be performed by mixing a manganese compound and an acid in water forming a mixture, which is stirred, heated, and allowed to cool. The anionic manganese oxide nanoparticles are extracted from the cooled mixture. The typical size of the resultant nanomaterials ranges from 30 to 100 nm; the zeta potential of the as-prepared nanomaterials is about -20 mV. The nanoparticles have various uses, including administration to a subject to treat inflammation or to treat cancer.

IPC Classes  ?

• A61K 31/74 - Synthetic polymeric materials
• A61K 47/56 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
• A61K 47/59 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit

Abstract

A minimally invasive device, containing a pressure channel, camera, and optical fiber imaging probe, to measure the stiffness of tissues in vivo and ex vivo is disclosed. The device is inserted into a patient and navigated to a tissue of interest, where stiffness is evaluated by applying suction and measuring the elongation or by applying compression force and measuring the compression of the tissue. Biopsies can be taken for further analysis, or tissue can be removed using an ablation laser. Small fluorescent molecules or therapeutics can also be delivered for improved visualization and targeted treatment. As such, this technology may be used to evaluate the stiffness of biomaterials as well as tissues and organs that are difficult to access, allowing for simultaneous diagnosis, treatment, and excision of diseased tissues.

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• G01N 3/40 - Investigating hardness or rebound hardness
• G01N 33/483 - Physical analysis of biological material

Abstract

Provided herein are methods of xenotransplantation, for example, porcine to human transplantation. Also provided herein are extracellular vesicles ("EVs", e.g., exosomes) and compositions comprising the same, e.g. EVs expressing human CD47. Further provided herein are methods of making EVs and use thereof for xenotransplantation. In some aspects, the methods of xenotransplantation comprise steps of expressing human CD47 on xenografts.

IPC Classes  ?

• A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection

Abstract

Systems and methods for a high-efficiency power converter incorporating a half-bridge topology with one or more an additional upper capacitor and a drain-source capacitor. The converter includes DC voltage terminals and a DC link capacitor coupled across a positive and negative DC terminal of the DC voltage terminals. The converter further includes a power switching element pair including a high side switch and a low side switch coupled together at a midpoint node. The converter further includes an LC filter having a switch-side inductor, a lower capacitor coupled between a second end of switch- side inductor and the negative DC terminal; and an upper capacitor coupled between the second end of the switch-side inductor and the positive DC terminal. The converter may further include drain-source capacitors coupled across the drain and source terminals of the switches.

IPC Classes  ?

• H02M 1/02 - Circuits specially adapted for the generation of grid-control or igniter-control voltages for discharge tubes incorporated in static converters
• H02M 1/08 - Circuits specially adapted for the generation of control voltages for semiconductor devices incorporated in static converters
• H02M 1/084 - Circuits specially adapted for the generation of control voltages for semiconductor devices incorporated in static converters using a control circuit common to several phases of a multi-phase system
• H02M 1/12 - Arrangements for reducing harmonics from AC input or output
• H02M 1/14 - Arrangements for reducing ripples from DC input or output
• H02M 1/16 - Means for providing current step on switching, e.g. with saturable reactor

Abstract

Disclosed are implementations that include a power converter system including a non-isolated N-phase DC/AC power converter, for N = 1, with a DC voltage section and an N- phase AC voltage section, with the power converter including energy storage arrangements for each of three phases of the AC voltage section. The energy storage arrangements are commonly electrically coupled to the terminals of the DC voltage section. The system further includes a controller to control voltages at the energy storage arrangements, with the controller including one or more switching devices to control voltages at one or more terminals of the energy storage arrangements, and at least one model predictive control (MFC) module to generate control signaling, based on electrical operational characteristics of at least some of storage elements, to actuate the one or more switching devices to establish zero sequence voltage stabilization behavior at the terminals of the energy storage arrangements.

IPC Classes  ?

• H02M 7/02 - Conversion of AC power input into DC power output without possibility of reversal
• H02M 7/42 - Conversion of DC power input into AC power output without possibility of reversal
• H02M 7/53846 - Control circuits

Abstract

Disclosed are implementations that include a non-isolated power converter system comprising a filter including an inductor and a capacitor. The inductor of the filter includes a core portion and a winding portion. The core portion may include different shape core structures. The winding portion includes a winding embedded within a printed circuit board. The printed circuit board winding may include a litz wiring, and the printed circuit board having located thereon one or more of a controller or power switching elements.

IPC Classes  ?

• H02M 3/00 - Conversion of DC power input into DC power output
• H02M 7/02 - Conversion of AC power input into DC power output without possibility of reversal
• H05K 7/02 - Arrangements of circuit components or wiring on supporting structure

Abstract

Disclosed are implementations that include a power converter system and method including an N-phase power converter stage having to an alternating current (AC) side and a direct current (DC) side, with N > 1. The system and method further include an N-phase LC filter comprising one or more capacitors, wherein respective one or more neutral points of the one or more capacitors are electrically connected to a DC negative terminal of a DC source. A control system drives power switching elements of the N-phase power converter stage to convert received power and to output converted power. The control system drives the power switching elements using variable frequency soft switching at a frequency of at least 20 kHz. The power converter may have bidirectional operation to operate in a traction mode to drive a motor or a charging mode to charge a DC source.

IPC Classes  ?

• H02M 1/12 - Arrangements for reducing harmonics from AC input or output
• H02M 7/02 - Conversion of AC power input into DC power output without possibility of reversal
• H02M 7/42 - Conversion of DC power input into AC power output without possibility of reversal

Abstract

A method of preventing metastasis of a cancer in a patient in need thereof includes administering to the patient a therapeutically effective amount of ibudilast, or a pharmaceutical salt thereof.

IPC Classes  ?

• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61P 35/04 - Antineoplastic agents specific for metastasis

Abstract

The subject matter described herein relates to engineered monoclonal antibodies, derived from antibodies isolated from human patients, neutralizing a SARS-CoV-2 virus, its variants, or related coronaviruses.

IPC Classes  ?

• A61K 39/42 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum viral
• A61P 31/14 - Antivirals for RNA viruses
• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
• C12N 15/13 - Immunoglobulins
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression

Abstract

This disclosure describes a nucleic acid construct that contains sequences for an Endotope construct, a STAT1c, and miR142 target sites. In one example, disclosed is composition comprising an Endotope construct and a STAT1 construct including a nucleic acid sequence encoding a constitutively active STAT1 (e.g. STAT1c), wherein the Endotope and the STAT1 constructs each include miR142 target sites. In alternative examples, disclosed is a single construct that includes the Endotope construct and STAT1 construct along with miR142 target sites. The nucleic acid constructs can be packaged into polycationic molecules or liposome to create nanoparticles for efficient cell transfection.

IPC Classes  ?

• A61K 9/14 - Particulate form, e.g. powders
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
• A61P 37/02 - Immunomodulators
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
• C12N 5/078 - Cells from blood or from the immune system
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C12N 9/00 - Enzymes, e.g. ligases (6.)ProenzymesCompositions thereofProcesses for preparing, activating, inhibiting, separating, or purifying enzymes
• C12N 15/09 - Recombinant DNA-technology
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/12 - Genes encoding animal proteins
• C12N 15/13 - Immunoglobulins
• C12N 15/52 - Genes encoding for enzymes or proenzymes
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
• 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

Abstract

The present disclosure provides systems, kits, and methods provide systems and methods for recruiting one or more effector domains to a target nucleic acid and or modulating expression of a target gene in a cell utilizing an engineered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) system. More particularly, the present disclosure provides systems comprising: an engineered CRISPR-Cas system or one or more nucleic acids encoding the engineered CRISPR-Cas system, wherein the CRISPR-Cas system comprises: at least one Cas protein (e.g., Cas6, Cas7, Cas5, Cas8 and/or Cas12k); a guide RNA (gRNA) complementary to at least a portion of the target nucleic acid sequence; and, optionally, at least one transposon-associated protein (e.g., TniQ, TnsC, TnsA, and/or TnsB).

IPC Classes  ?

• A61K 38/46 - Hydrolases (3)
• C12N 9/22 - Ribonucleases
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

The present disclosure provides systems, kits, and methods for nucleic acid integration utilizing engineered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated transposon (CRISPR-Tn) system. More particularly, the present disclosure provides systems comprising: an engineered CRISPR-Tn system or one or more nucleic acids encoding the engineered CRISPR-Tn system, wherein the CRISPR-Tn system comprises at least one or both of: a) at least one Cas protein (e.g., Cas6, Cas7, Cas5, and/or Cas8); and b) one or more transposon-associated proteins (e.g., TnsA, TnsB, TnsC, TnsD, and/or TniQ). The present disclosure also provides systems, kits, and methods for nucleic acid integration in a eukaryotic cell.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression

Abstract

The present invention relates to an isolated nucleic acid molecule encoding a variant of sirtuin 6 (SIRT6) having at least 75% identity with sequence SEQ ID NO: 1, the variant having at least one mutation selected in the group comprising or consisting of a N308K substitution and a A313S substitution with respect to sequence SEQ ID NO: 1. The invention provides means for the regulation of ageing, and/or senescence, and/or lifespan in an individual. The invention further provides means for the repair of double strand breaks in a cell. Finally, the invention also provides means for the prevention and/or the treatment of an age-related disease.

IPC Classes  ?

• A61K 38/45 - Transferases (2)
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 9/10 - Transferases (2.)
• C12N 15/54 - Transferases (2)
• C12N 15/86 - Viral vectors

Abstract

The subject matter disclosed herein relates to a recombinant spike (S) protein from the B.1.351.2-7 variant of the SARS-CoV-2 virus, the DNA and RNA nucleotide sequences encoding the recombinant B.1.351.2-7 spike protein, and engineered antibodies that bind the B.1.351.2-7 spike protein and neutralize the B.1.351.2-7 virus.

IPC Classes  ?

• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 31/14 - Antivirals for RNA viruses
• C07K 14/165 - Coronaviridae, e.g. avian infectious bronchitis virus
• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses

Abstract

An exemplary system, method and computer-accessible medium for harmonizing neuromelanin (NM) data using combat directly on a NM database or using combat generated coefficients to harmonize future data can include, for example, receiving imaging information of a brain of the patient(s), from one MRI scanner, receiving imaging information of a brain of the patient(s), from a second MRI scanner and using combat to harmonize the data between scanners against a reference dataset. The Neuromelanin (NM) concentration of the patient(s) can then be determined based on the harmonized data. The NM concentration can be determined using a voxel-wise analysis procedure. The voxel-wise analysis procedure can be used to determine a topographical pattern(s) within a substantia nigra (SN) of the brain of the patient(s).

IPC Classes  ?

• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging

Abstract

The present invention provides a method of treating a subject afflicted with a substance use disorder (SUD) comprising administering to the subject an effective amount of a compound having the structure: [STRUCTURE], or a pharmaceutically acceptable salt or ester thereof, wherein A, X1, X2, Y1-Y6 and R1-R4 are as defined in the specification, so as to thereby treat the subject afflicted with the substance use disorder (SUD).

IPC Classes  ?

• 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
• A61P 25/00 - Drugs for disorders of the nervous system
• C07D 491/04 - Ortho-condensed systems
• C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings

Abstract

The present invention provides a pharmaceutical composition comprising the compound of any the present invention and a pharmaceutically acceptable carrier. The present invention provides a method for stabilizing TTR tetramers in a mammal comprising administering to the mammal an amount of a compound of the present invention or a composition of the present invention effective to stabilize TTR tetramers.

IPC Classes  ?

• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contractionDrugs for heart failure
• 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 27/02 - Ophthalmic agents
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• C07D 231/38 - Nitrogen atoms
• C07D 261/14 - Nitrogen atoms
• C07D 275/03 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings with hetero atoms or 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 to ring carbon atoms
• 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

Abstract

The present invention provides a compound having the structure: [STRUCTURE}, wherein D,E,F,X1, X2 and R1-R14 are as defined herein; a pharmaceutical composition comprising said compound and a pharmaceutically acceptable carrier; and a method of treating a subject afflicted with a substance use disorder, opioid withdrawal symptoms, a depressive disorder, a mood disorder, an anxiety disorder, Parkinson's disease, traumatic brain injury, a headache, a migraine, or of altering the psychological state or enhancing the effect of psychotherapy, comprising administering to the subject an effective amount of said compound or a pharmaceutically acceptable salt thereof.

IPC Classes  ?

• A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
• 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 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61P 25/00 - Drugs for disorders of the nervous system
• C07D 487/04 - Ortho-condensed systems
• C07D 491/04 - Ortho-condensed systems
• C07D 495/04 - Ortho-condensed systems

Abstract

A copper concentrate such as chalcopyrite is contacted with an aqueous solution includes acids and a reducing agent, such as vanadium (II) ions, chromium (II) ions, or tungstozincic acid (H6ZnW12O40). The aqueous solution reduces the copper in the copper concentrate, which can then dissolve into the solution for recovery therefrom, or precipitate out of solution as copper compounds or elemental copper for recovery in as a solid phase product. The solid phase product can then be isolated, dissolved, and further electrowinned to recover a copper product from the copper concentrate. Oxidized reducing agent can be recovered in an electrochemical device with ferrous iron reactants. Hydrometallurgical routes to convert copper concentrates to copper are potentially less expensive and less polluting than current pyrometallurgical processing and an advantageous response to environmental and economic pressures for increased copper production.

IPC Classes  ?

• C25B 1/01 - Products
• C25B 9/40 - Cells or assemblies of cells comprising electrodes made of particlesAssemblies of constructional parts thereof
• C25B 15/08 - Supplying or removing reactants or electrolytesRegeneration of electrolytes

Abstract

The subject matter disclosed herein relates to a method of treating glioblastoma (GBM) in a subject in need thereof, the method comprising determining one or more GBM subtypes in a GBM sample via a pathway -based classifier approach and administering to the subject a pharmaceutically effective amount of an agent capable of modifying the activity of the biological pathways associated with the one or more GBM subtypes.

IPC Classes  ?

• 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

Abstract

A microscope routes excitation light through a first set of optical components so the excitation light is projected into a sample and forms a sheet of excitation light at an oblique angle. The position of the sheet varies depending on an orientation of the scanning element. The first set of optical components routes detection light back to the scanning element, which routes the detection light into a second set of optical components. The second set of optical components forms an intermediate image plane that is imaged onto a detector. In some embodiments, a folding mirror is disposed between the first and second sets of optical components. In some embodiments, an optically transparent spacer covers the first objective and is configured to press against tissue being imaged. This spacer sets the working distance for the first objective to capture a particular range of depths within the tissue.

IPC Classes  ?

• G01N 21/64 - FluorescencePhosphorescence
• G02B 21/02 - Objectives
• G02B 21/04 - Objectives involving mirrors
• G02B 21/06 - Means for illuminating specimen
• G02B 26/10 - Scanning systems

Abstract

The invention described relates to the newly discovered ability of tumor internalizing arginylglycylaspartic acid (iRGD) peptides to alter the immune cell landscape in pancreatic ductal adenocarcinoma (PDAC) and other cancers. The iRGD peptides sensitize the cancer to immune checkpoint inhibitors, for example anti-PD-L1, anti-PD-L1. anti-PD-1, and anti-CTLA4 monoclonal antibodies to specifically deplete Tregs within the tumor, resulting in expansion of intratumoral CD8+ T cells (effector cells). This provides methods of treating cancers such as PDAC, preferably in synergistic combination with chemotherapy and immunotherapy, which leads to reduced tumor burden and prolonged survival.

IPC Classes  ?

• A61K 38/08 - Peptides having 5 to 11 amino acids
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
• A61P 35/04 - Antineoplastic agents specific for metastasis
• 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

Abstract

The system includes electrolyzers to generate acidic and alkaline effluent streams from saltwater. The electrolyzer include stacked pairs of porous anodes and cathodes that define feed channels into which reactants, e.g., hydrogen and brine, can be pumped to undergo an oxidation-reduction reaction. The porous cathode carries out the HER to generate H2, which floats upwards to the porous anode, where it is oxidized through the HOR. The reaction can thus progress in a self-maintaining manner. The HER creates an alkaline product stream with increased basicity, and the HOR an acidic product stream with increased acidity, compared to the inlet stream. Streams are pumped through the porous electrodes and the electrolyzer to sweep effluent through separate channels before they can combine. The alkaline product stream can have an alkalinity sufficient to drive metal ion precipitation in raw saltwater prior to feeding to the electrolyzer to reduce fouling/degradation of electrolyzer electrodes.

IPC Classes  ?

• C25B 1/34 - Simultaneous production of alkali metal hydroxides and chlorine, oxyacids or salts of chlorine, e.g. by chlor-alkali electrolysis
• C25B 1/50 - Processes
• C25B 9/17 - Cells comprising dimensionally-stable non-movable electrodesAssemblies of constructional parts thereof
• C25B 9/60 - Constructional parts of cells
• C25B 11/031 - Porous electrodes

Abstract

A neuromelanin sensitive magnetic resonance imaging ("MRI") technique, method and computer-accessible medium for measuring the extent of, providing a diagnosis of, monitoring the treatment of, assessing novel treatments for, or determining a prognosis related to one or more neurological conditions.

IPC Classes  ?

• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G16H 30/20 - ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
• G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing

Abstract

The present disclosure provides for systems and methods for modifying the epigenome of cells.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/79 - Vectors or expression systems specially adapted for eukaryotic hosts

Abstract

Described herein is a composition and method of preventing COVID-19 with lipid-peptide fusion antiviral therapy.

IPC Classes  ?

• A61K 31/56 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61K 47/10 - AlcoholsPhenolsSalts thereof, e.g. glycerolPolyethylene glycols [PEG]PoloxamersPEG/POE alkyl ethers
• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61P 31/14 - Antivirals for RNA viruses
• C07K 14/08 - RNA viruses

Abstract

The disclosure provides FOXO1 inhibitors having beneficial properties such as selectivity and metabolic stability. FOXO1 inhibitors are useful in the treatment of diabetes.

IPC Classes  ?

• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• C07C 403/14 - Derivatives of cyclohexane or of a cyclohexene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by doubly-bound oxygen atoms
• C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 487/04 - Ortho-condensed systems

Abstract

A method of treating a condition in a subject by improving the immune response of the subject comprising first determining the level of TCF1 in the subject to identify the subject as having an anti -PD- 1 responder phenotype or an anti-PD-1 non-responder phenotype, then administering an anti-PD-1 treatment to a subject having an anti-PD-1 responder phenotype or a metabolic inhibitor prior to ant-PD-1 treatment to a subject having an anti-PD-1 non/responder phenotype.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents
• A61P 37/02 - Immunomodulators
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

Methods and devices for positioning a nerve stimulation device on a subject are provided. Aspects are directed to methods of positioning a stimulation device on an anatomic target of a subject comprising positioning an alignment guide adjacent to at least a first alignment point associated with the anatomic target on the subject, wherein the alignment guide indicates a first target location on the anatomic target of the subject, and positioning the stimulation device at the first target location.

IPC Classes  ?

• A61N 1/04 - Electrodes
• A61N 1/36 - Applying electric currents by contact electrodes alternating or intermittent currents for stimulation, e.g. heart pace-makers

Abstract

Provided herein are recombinant miniature swine expressing human CD47 in a tissue specific fashion. Also provided are kidneys isolated from a miniature swine, wherein the glomeruli of the kidney express human CD47 at a level higher than the level of human CD47 expression in the tubules of the kidney. Furthermore, provided herein are methods of transplanting such swine kidneys with glomeruli-specific expression of human CD47 from recombinant miniature swine into human recipients. In certain aspects, provided herein are methods of transplantation comprising transplanting hematopoietic stem cells expressing human CD47 from a first donor animal (e.g., a miniature swine) and a kidney expressing human CD47 in the glomeruli from a second donor animal (e.g., a miniature swine) to a recipient (e.g., a human recipient).

IPC Classes  ?

• A01K 67/00 - Rearing or breeding animals, not otherwise provided forNew or modified breeds of animals
• A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
• A61K 35/22 - UrineUrinary tract, e.g. kidney or bladderIntraglomerular mesangial cellsRenal mesenchymal cellsAdrenal gland
• A61L 27/36 - Materials for prostheses or for coating prostheses containing ingredients of undetermined constitution or reaction products thereof
• A61N 1/30 - Apparatus for iontophoresis or cataphoresis

Abstract

The nanoparticulate system for delivering treating agents may be used, for example, for treating inflammation, or for treating cancer, such as oral cancer, and associated inflammation. The system used in this manner provides a solution to oral cancer and its associated metastasis by providing a targeted therapy to deliver chemotherapeutics. The nanoparticulate system is in the form of cholesterol-modified polyamidoamine-G3 nanoparticles (PAMAM-Chol NPs), which are used as a carrier for at least one drug. The at least one drug may include at least one cancer drug, at least one corticosteroid, at least one anabolic steroid, at least one hormone (natural or synthetic), and combinations thereof.

IPC Classes  ?

• A61K 47/62 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
• A61K 51/06 - Macromolecular compounds

Abstract

The subject matter disclosed herein relates to a method for determining dopamine function in a subject, the method comprising acquiring one or more neuromelanin-Magnetic Resonance Imaging (NM-MRI) scans of the subject's dopamine-associated brain region of interest.

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes Identification of persons

Abstract

The present subject matter relates to techniques for simultaneous blood-brain barrier opening and cavitation imaging. The disclosed system can include a transducer and a processor. The transducer can be configured to generate a plurality of focused transmits and simultaneously obtain a plurality of power cavitation images. The processor can be configured to control a parameter of the focused transmits, acquire the power cavitation images between each focused transmit, and generate a cavitation map based on the power cavitation images.

IPC Classes  ?

• A61B 8/08 - Clinical applications
• A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
• A61K 49/22 - Echographic preparationsUltrasound imaging preparations
• A61M 37/00 - Other apparatus for introducing media into the bodyPercutany, i.e. introducing medicines into the body by diffusion through the skin
• A61N 7/00 - Ultrasound therapy

Abstract

Bispecific antagonists of Retinol-Binding Protein 4, their preparation, and use in the treatment of common age-related comorbidities.

IPC Classes  ?

• A61K 31/402 - 1-aryl-substituted, e.g. piretanide
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 27/02 - Ophthalmic agents
• C07D 207/08 - 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 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 487/10 - Spiro-condensed systems

Abstract

Disclosed herein is a kit for detecting or quantifying a SARS-CoV-2 nucleocapsid phosphoprotein, including a first antibody, wherein a variable heavy chain domain comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, 5, 7, 11, 13, 15, 17, 19, and 21, and a variable light chain domain comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4, 6, 8, 12, 14, 16, 18, 20, and 22; and a second antibody, wherein a variable heavy chain domain comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 9 and 13, and a variable light hain domain comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 10 and 14.

IPC Classes  ?

• A61K 39/12 - Viral antigens
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 14/165 - Coronaviridae, e.g. avian infectious bronchitis virus

Abstract

The subject matter described herein relates to a method of regulating protein kinase activity by allosteric modifications such as prolyl hydroxylation.

IPC Classes  ?

• C12N 9/12 - Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
• C12Q 1/25 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving enzymes not classifiable in groups
• C12Q 1/26 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving oxidoreductase

Abstract

The disclosure relates to methods and compositions for preventing and/or treating an ocular disease. In particular, the disclosure relates to preventing and/or treating myopia with systemic or topical administration of fenoterol hydrobromide, which is a ?2-adrenergic receptor agonist, or a derivative thereof.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
• A61P 27/10 - Ophthalmic agents for accommodation disorders, e.g. myopia

Abstract

The disclosure relates to methods and compositions for preventing and/or treating an ocular disease. In particular, the disclosure relates to preventing and/or treating myopia with systemic or topical administration of trichostatin A, which is a histone deacetylase (HD AC) inhibitor, or a derivative thereof.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
• A61P 27/10 - Ophthalmic agents for accommodation disorders, e.g. myopia

Abstract

The disclosure relates to methods and compositions for preventing and/or treating an ocular disease. In particular, the disclosure relates to preventing and/or treating myopia with systemic or topical administration of fingolimod phosphate, which is a sphingosine-1- phosphate receptor modulator, or a derivative thereof.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• A61P 27/10 - Ophthalmic agents for accommodation disorders, e.g. myopia

Abstract

The disclosure relates to methods and compositions for preventing and/or treating an ocular disease. In particular, the disclosure relates to preventing and/or treating myopia with systemic or topical administration of berberine chloride, which is a berberidaceaen alkaloid, or a derivative thereof.

IPC Classes  ?

• 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 47/10 - AlcoholsPhenolsSalts thereof, e.g. glycerolPolyethylene glycols [PEG]PoloxamersPEG/POE alkyl ethers
• A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters

Abstract

. The disclosure relates to methods and compositions for preventing and/or treating an ocular disease. In particular, the disclosure relates to preventing and/or treating myopia with systemic or topical administration of S-methyl-L-thiocitrulline hydrochloride, which is a selective neuronal nitric oxide synthase (nNOS) inhibitor, or a derivative thereof.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/145 - Orthomyxoviridae, e.g. influenza virus
• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants

Abstract

Disclosed herein are methods of administering an agent targeting a lineage- specific cell-surface antigen, e.g., CD33 or EMR2, and a population of hematopoietic cells that are altered in the expression of the lineage- specific cell- surface antigen, e.g., CD33 or EMR2, for immunotherapy of hematological malignancies. Also disclosed herein are methods of administering an agent targeting more than one lineage-specific cell- surface antigen, and a population of hematopoietic cells that are altered in the expression of more than one lineage- specific cell-surface antigen, for immunotherapy of hematological malignancies. Cells comprising mutations in CD33, or EMR2, or more than one lineage- specific cell-surface antigen are also provided, as are methods of producing such cells using CRISPR-based base editor systems.

IPC Classes  ?

• A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells

Abstract

The disclosure relates to methods and compositions for preventing and/or treating an ocular disease. In particular, the disclosure relates to preventing and/or treating myopia with systemic or topical administration of levocabastine hydrochloride, which is a selective histamine HI -receptor antagonist, or a derivative thereof.

IPC Classes  ?

• A61K 9/06 - OintmentsBases therefor
• A61K 31/19 - Carboxylic acids, e.g. valproic acid
• A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
• A61P 27/02 - Ophthalmic agents
• A61P 27/10 - Ophthalmic agents for accommodation disorders, e.g. myopia
• C07C 255/60 - Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated

Abstract

The subject matter described herein relates to potent monoclonal and bispecific antibodies capable of neutralizing a SARS-CoV-2 viruses and methods of generating the antibodies.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 31/14 - Antivirals for RNA viruses
• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses

Abstract

Described herein is a composition and method of treating COVID-19 with lipid- peptide fusion antiviral therapy. Also described is a composition and method of treating Ebola with lipid-peptide fusion antiviral therapy.

IPC Classes  ?

• A61K 31/355 - Tocopherols, e.g. vitamin E
• C07K 14/08 - RNA viruses
• C07K 14/12 - Mumps virusMeasles virus

Abstract

Exemplary methods, compositions and uses thereof can be provided for preventing, reducing and/or treating loss of muscle function. In particular, e.g., it is possible to administer to a subject a pharmaceutical composition comprising a therapeutically effective amount of an agent that enhances Interleukin-6 (IL) release during exercise, and optionally a pharmaceutically acceptable carrier or excipient.

IPC Classes  ?

• A61K 38/00 - Medicinal preparations containing peptides
• A61K 38/22 - Hormones
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• C07K 14/575 - Hormones

Abstract

The present invention provides compositions and methods involving stable omega-3 diglyceride oil-in-water emulsions for acute therapy to treat and/or prevent tissue or organ injury. The compositions provide protection from cellular death, and find use in patients in need of neuroprotection. For example, the compositions find use in treating ischemia reperfusion injuries, such as ischemic stroke. The compositions further find use for treatment of traumatic injuries, such as traumatic brain injury or spinal cord injury, among others. The compositions have a large time window by which they are effective after onset of traumatic or ischemic injury (e.g., after onset of stroke), and may be administered in conjunction with other therapies.

IPC Classes  ?

• A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
• A61K 31/231 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds

Abstract

A biopolymer composition can be formed based, at least in part, on a recombinantly expressed protein, expressed from a DNA coding sequence of a source protein, and the recombinantly expressed protein can optionally comprise one or more tags that enhance the crosslinking capacity of the protein. It was determined that such biopolymer composition can be suitable for use to obtain, for example, a biodegradable textile that exhibits a functional characteristic associated with the recombinantly expressed protein.

IPC Classes  ?

• A61L 15/32 - Proteins, polypeptidesDegradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
• C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• C12N 9/14 - Hydrolases (3.)

Abstract

The present disclosure provides, inter alia, compounds to modulate GPX4 activity. Also provided are pharmaceutical compositions containing same compounds. Further provided are methods for treating or ameliorating the effects of a cancer in a subject, methods of modulating GPX activity in a subject, methods of inducing ferroptosis in a cell, and methods for treating or ameliorating the effects of a cancer in a subject using the compounds or composition in combination with other therapeutic agents.

IPC Classes  ?

• A61K 31/4035 - Isoindoles, e.g. phthalimide
• A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
• A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• A61K 31/426 - 1,3-Thiazoles
• A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• 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
• A61P 15/08 - Drugs for genital or sexual disordersContraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• 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 35/00 - Antineoplastic agents
• C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
• C07D 277/54 - Nitrogen and either oxygen or sulfur atoms
• C07D 295/192 - Radicals derived from carboxylic acids from aromatic carboxylic acids
• C07D 403/06 - 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 carbon chain containing only aliphatic carbon atoms
• C07D 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 455/02 - Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberineAlkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing not further condensed quinolizine ring systems
• C07D 487/04 - Ortho-condensed systems
• C07F 7/22 - Tin compounds

Abstract

The present disclosure relates to methods and compounds for reprogramming metabolism in one specific retinal and neuronal cell type leading to improved cell and tissue survival and function. In particular, the present disclosure relates to increasing PGC1?/Pgcl? or NRF2/Nrf2 or inhibiting HIF/Hif or KEAP1/Keap1 to reprogram metabolism and survival of cells in a variety of neurodegenerative conditions, and specifically those which cause blindness.

IPC Classes  ?

• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/12 - Genes encoding animal proteins
• C12N 15/86 - Viral vectors

Abstract

The present disclosure provides, inter alia, bivalent nanobody molecules and methods for treating or ameliorating the effects of a disease, such as long QT syndrome, or cystic fibrosis, in a subject, using the bivalent nanobody molecules disclosed herein. Also provided are methods of identifying and preparing nanobody binders that target proteins of interest.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• 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 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
• C07K 16/46 - Hybrid immunoglobulins
• C07K 19/00 - Hybrid peptides
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cellsLibraries contained in or displayed by vectors, e.g. plasmidsLibraries containing only microorganisms or vectors

Abstract

Compositions and methods for mitigating SVD mechanisms in BHV, including non-calcific SVD mechanisms, are provided.

IPC Classes  ?

• A61F 2/00 - Filters implantable into blood vesselsProstheses, i.e. artificial substitutes or replacements for parts of the bodyAppliances for connecting them with the bodyDevices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
• A61K 31/00 - Medicinal preparations containing organic active ingredients

Abstract

Provided herein are arylcyclohexylamine derivatives and their use in the treatment of psychiatric disorders.

IPC Classes  ?

• A61K 31/135 - Amines, e.g. amantadine having aromatic rings, e.g. methadone
• 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 31/4453 - Non-condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
• A61K 31/5375 - 1,4-Oxazines, e.g. morpholine
• A61P 25/22 - Anxiolytics
• A61P 25/24 - Antidepressants
• C07C 225/20 - Compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly-bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton
• 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 295/104 - 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 doubly bound oxygen or sulfur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings

Abstract

The present disclosure relates to methods and compositions for elevating and stabilizing retromer for treating and/or preventing Alzheimer's disease and other neurodegenerative disorders. Additionally, the disclosure relates to adenoviral based therapy for treating Alzheimer's disease (AD), and other neurodegenerative conditions such as Parkinson's Disease (PD), neuronal ceroid lipofuscinosis (NCL), and transmissible spongiform encephalopathies (TSEs or prion disease), multiple system atrophy (MSA), Down's syndrome, and hereditary spastic paraplegia, as well as tauopathies such as progressive supranuclear palsy (PSP), frontotemporal lobar dementia linked to chromosome 17q21-22 and its subtypes (FTLD-17/FTLD-Tau), Lewy Body Disease (LBD), amyotrophic lateral sclerosis (AES), frontal-temporal degeneration (FTD), ALS-FTD, and chronic traumatic encephalopathy (CTE).

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 15/86 - Viral vectors

Abstract

The present disclosure provides for transgenic swine, comprising one or more nucleotide sequences encoding one or more HLA I polypeptides and/or one or more HLA II polypeptides inserted into one or more native SLA loci of the swine genome, methods of making and methods of using. The present disclosure also provides for improved methods of making human immune system mice.

IPC Classes  ?

• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• C12N 15/873 - Techniques for producing new embryos, e.g. nuclear transfer, manipulation of totipotent cells or production of chimeric embryos

Abstract

A neuromelanin sensitive magnetic resonance imaging ("MRI") technique, method and computer-accessible medium for measuring the extent of, providing a diagnosis of, monitoring the treatment of, assessing novel treatments for, or determining a prognosis related to Parkinson's disease.

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G01N 33/00 - Investigating or analysing materials by specific methods not covered by groups
• G01N 33/53 - ImmunoassayBiospecific binding assayMaterials therefor
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• G01R 33/48 - NMR imaging systems

Abstract

Provided herein are compositions and methods of using Seneca Valley Virus (SVV) or a derivative thereof and an interferon type I (IFN-I) inhibiting agent comprising an mTOR inhibitor for treating a cancer in a subject. The disclosed methods particularly rely upon the expression level of an ANTXR1 and the expression level of IFN-I in the cancer from the subject. Also provided herein are methods for predicting the efficacy of an SVV treatment comprising IFN-I inhibiting agent.

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61P 35/00 - Antineoplastic agents
• C12N 15/36 - Hepadnaviridae
• C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora

Abstract

Systems and methods for associating single cell imaging data with RNA transcriptomics. Single cells are isolated into microwells with a microbead having oligonucleotides conjugated on its surface. Each oligonucleotide includes a cell identifying optical barcode that is unique to that bead and binding sequence for RNA capture after cell lysis. The system is configured for loading single cells into the microarray and for flowing cell lysis buffers and other reagents into the microarray for performing RNA library sample preparation. The system is also configured for lowing optical hybridization probes that are complementary to the cell identifying optical barcodes and optically labeled onto the microwell array and for obtaining images of the microwells in response to the probes. The system and unique cell identifying optical barcodes and complementary optical hybridization probes facilitate a link between phenotypic imaging of cells resident on the microwell array with single cell whole transcriptome sequencing.

IPC Classes  ?

• C12Q 1/6813 - Hybridisation assays
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms

Abstract

The invention provides a composition for use as a medicament, comprising cells of a recombinant microorganism capable of producing increased amounts of one or more of 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) and tryptamine (TRM) as compared to the non-recombinant microorganism from which it was derived. The composition finds use in preventing and/or treating TRM-; 5-HTP-, or 5-HT-related disorders of the central nerve system (CNS); enteric nervous system (ENS); gastro intestine (GI) and metabolism in a mammal, and may be orally administered to a mammal in need thereof. Additionally, a composition comprising cells of a recombinant microorganism capable of producing melatonin is provided for use as a medicament, such as for treatment of depression, dementia, cancer and sleep disorder.

IPC Classes  ?

• A61K 35/74 - Bacteria
• A61K 38/44 - Oxidoreductases (1)
• A61K 38/51 - Lyases (4)
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 25/00 - Drugs for disorders of the nervous system
• C12N 1/21 - BacteriaCulture media therefor modified by introduction of foreign genetic material
• C12N 9/02 - Oxidoreductases (1.), e.g. luciferase
• C12N 9/10 - Transferases (2.)
• C12N 9/78 - Hydrolases (3.) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
• C12N 9/88 - Lyases (4.)
• C12N 15/53 - Oxidoreductases (1)
• C12N 15/54 - Transferases (2)
• C12N 15/55 - Hydrolases (3)
• C12N 15/60 - Lyases (4)
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression

Abstract

Methods and devices for modifying sensory processing in a subject are provided. Aspects are directed to applying tonic vagus nerve stimulation to a subject for transient sensory processing modification. Devices for applying tonic vagus nerve stimulation when a subject is in need of sensory modification or on demand are also provided. The devices can be coupled with a prosthetic device for application to regions of the body in need of vagus nerve stimulation.

IPC Classes  ?

• A61N 1/02 - ElectrotherapyCircuits therefor Details
• A61N 1/05 - Electrodes for implantation or insertion into the body, e.g. heart electrode
• A61N 1/36 - Applying electric currents by contact electrodes alternating or intermittent currents for stimulation, e.g. heart pace-makers

Abstract

This invention relates to a method and a system of abating carbon dioxide (CO2) and/or hydrogen sulfide (H2S) in a geological reservoir. Water is pumped or transferred from a water source to an injection well. The gasses are merged with the water under conditions where the hydraulic pressure of the water is less or equal to the pressure of CO2 and/or H2S gas at the merging point. The water with dissolved CO2 and/or H2S is transfen-ed further downwardly with at a certain velocity, whereafter the dissolved CO2 and/or H2S is injected into the geological (e.g. geothermal) reservoir.

IPC Classes  ?

• B01D 53/52 - Hydrogen sulfide

Abstract

Methods for prophylactically treating a stress-induced affective disorder or stress-induced psychopathology in a subject are provided. Also provided are methods for inducing and/or enhancing stress resilience in a subject. In certain embodiments, an effective amount of an agonist of the serotonin 4 receptor (5-HT4R), or a pharmaceutically acceptable salt or derivative thereof, is administered to a subject prior to a stressor.

IPC Classes  ?

• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 31/401 - ProlineDerivatives thereof, e.g. captopril
• A61K 31/42 - Oxazoles

Abstract

The current disclosure provides for methods of promoting differentiation of pluripotent stem cells into thymic epithelial cells or thymic epithelial cell progenitors as well as the cells obtained from the methods, and solutions, compositions, and pharmaceutical compositions comprising such cells. The current disclosure also provides for methods of using the thymic epithelial cells or thymic epithelial cell progenitors for treatment and prevention of disease, generating organs, as well as other uses, and kits.

IPC Classes  ?

• A61K 35/26 - LymphLymph nodesThymusSpleenSplenocytesThymocytes
• A61P 37/02 - Immunomodulators
• C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
• C12N 5/078 - Cells from blood or from the immune system
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C12N 5/16 - Animal cells
• C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving viable microorganisms

Abstract

Various embodiments relate to a compound (represented by Formula I) or a pharmaceutically acceptable salt or tautomer thereof. The compound may selectively inhibit a Forkhead Box O1 (FOXO1) transcription factor. Various embodiments relate to methods comprising administering to a mammal having a disease or disorder associated with impaired pancreatic endocrine function, a therapeutically effective amount of the compound or a pharmaceutically acceptable salt or tautomer thereof. Various embodiments relate to methods for producing enteroendocrine cells that make and secrete insulin in a mammal, comprising administering to the mammal an effective amount of the compound or a pharmaceutically acceptable salt or tautomer thereof.

IPC Classes  ?

• A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/423 - Oxazoles condensed with carbocyclic rings
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/454 - 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 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 5/48 - Drugs for disorders of the endocrine system of the pancreatic hormones
• C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
• C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
• C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 471/04 - Ortho-condensed systems
• C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues

Abstract

An exemplary system, method, and computer-accessible medium for generating a Cartesian equivalent image(s) of a portion(s) of a patient(s), can include, for example, receiving non-Cartesian sample information based on a magnetic resonance imaging (MRI) procedure of the portion(s) of the patient(s), and automatically generating the Cartesian equivalent image(s) from the non-Cartesian sample information using a deep learning procedure(s). The non-Cartesian sample information can be Fourier domain information. The non-Cartesian sample information can be undersampled non-Cartesian sample information. The MRI procedure can include an ultra-short echo time (UTE) pulse sequence. The UTE pulse sequence can include a delay(s) and a spoiling gradient. The Cartesian equivalent image(s) can be generated by reconstructing the Cartesian equivalent image(s). The Cartesian equivalent image(s) can be reconstructed using a sampling density compensation with a tapering of over a particular percentage of a radius of a k-space, where the particular percentage can be about 50%.

IPC Classes  ?

• G06F 17/10 - Complex mathematical operations
• G06F 17/14 - Fourier, Walsh or analogous domain transformations
• G06F 17/16 - Matrix or vector computation
• G06T 3/20 - Linear translation of whole images or parts thereof, e.g. panning
• G16H 30/20 - ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS

Abstract

An exemplary system, method, and computer-accessible medium for generating a particular image which can be a quantitative image(s) of at least one section(s) of a patient(s) or (ii) a non-synthetic contrast image(s) of the section(s) of the patient(s), can include, for example, generating a first magnetic resonance (MR) signal and directing the first MR signal to patient(s), receiving a second MR signal from the patient(s) that can be based on the first MR signal, and generating the particular image(s) based on the second MR signal. The first MR signal can be a configured MR signal. The configured MR signal can be configured for a particular contrast. The first MR signal can have a constant signal intensity. The first MR signal can be generated based on a degree of a plurality of flip angles that maintains the constant signal intensity. A degree of flip angles can be selected for the first MR signal based on the particular contrast

IPC Classes  ?

• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G01R 33/42 - Screening
• G01R 33/44 - Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
• G01R 33/48 - NMR imaging systems
• G01R 33/54 - Signal processing systems, e.g. using pulse sequences
• G01R 33/563 - Image enhancement or correction, e.g. subtraction or averaging techniques of moving material, e.g. flow-contrast angiography

Abstract

In certain embodiments, the present systems and methods use Tn7-like transposons that encode CRISPR-Cas systems for programmable, RNA-guided DNA integration. For example, the CRISPR-Cas machinery directs the Tn7 transposon-associated proteins to integrate DNA downstream of a target site (e.g., a genomic target site) recognized by a guide RNA (gRNA).

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells

Abstract

Compounds and compositions comprising compounds that modulate histone acyl transferase (HAT). The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein as well as cancer by administering a compound that modulates HAT to a subject.

IPC Classes  ?

• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• C07C 235/64 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho- position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• C07D 213/69 - Two or more oxygen atoms
• C07D 213/75 - Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• C07D 235/18 - BenzimidazolesHydrogenated benzimidazoles with aryl radicals directly attached in position 2

Abstract

The present invention provides a composition which comprises a carrier and a compound having the structure: or a pharmaceutically acceptable salt or ester thereof. The present invention also relates to methods of using the compound to treat pain, depressive disorders, mood disorders, anxiety disorders, opioid use disorder, and opioid withdrawal symptoms.

IPC Classes  ?

• 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
• A61P 25/00 - Drugs for disorders of the nervous system
• C07D 459/00 - Heterocyclic compounds containing benz [g] indolo [2, 3-a] quinolizine ring systems, e.g. yohimbine16, 18-lactones thereof, e.g. reserpic acid lactone

Abstract

Disclosed herein are methods of administering an agent targeting a lineage-specific cell- surface antigen, e.g., CD33, and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen, e.g., CD33 for immunotherapy of hematological malignancies. Cells comprising mutations in CD33 are also provided, as are gRNAs targeting CD33.

IPC Classes  ?

• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• A61P 35/00 - Antineoplastic agents
• C12N 5/0789 - Stem cellsMultipotent progenitor cells
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/09 - Recombinant DNA-technology
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/12 - Genes encoding animal proteins
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression

Abstract

[00144] An exemplary system, method and computer-accessible medium for determining a dopamine function of a patient(s) can include, for example, receiving imaging information of a brain of the patient(s), determining a Neuromelanin (NM) concentration of the patient(s) based on the imaging information, and determining the dopamine function based on the NM concentration. The NM concentration can be determined using a voxel-wise analysis procedure. The voxel-wise analysis procedure can be used to determine a topographical pattern(s) within a substantia nigra (SN) of the brain of the patient(s). The topographical pattern(s) can include a pattern(s) of cell loss in the SN. The NM concentration can be based on a NM loss in the brain of the patient(s).

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G01R 33/48 - NMR imaging systems
• G01R 33/54 - Signal processing systems, e.g. using pulse sequences
• G01R 33/56 - Image enhancement or correction, e.g. subtraction or averaging techniques
• G06T 7/00 - Image analysis

Abstract

The present disclosure relates to making a hybrid pig-human thymic tissue and using the hybrid thymic tissue to induce tolerance in xenotransplantation. The hybrid thymic tissue can also be used for restoring or inducing immunocompetence in a recipient as well as restoring or promoting thymus-dependent ability for T cell progenitors to develop into mature functional T cells in a recipient.

IPC Classes  ?

• C12N 5/078 - Cells from blood or from the immune system
• C12N 5/0789 - Stem cellsMultipotent progenitor cells

Abstract

A method for treating pancreatic cancer in a subject in need thereof comprising, administering to the subject an effective amount of a tubulin polymerization inhibitor compound is described herein. More particularly, a method for treating pancreatic ductal adenocarcinoma in a subject in need thereof comprising, administering to the subject an effective amount of a substituted reverse pyrimidine tubulin polymerization inhibitor compound alone or in combination with other chemo-therapeutic agents is described herein.

IPC Classes  ?

• A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• A61P 35/00 - Antineoplastic agents

Abstract

Described herein are compositions and methods for treating a disease or disorder associated with PI3K signaling. For example, such compositions can include use of modulators of glucose metabolism, use of at least one kinase in the insulin-receptor/PI3K/AKT/mTOR pathway, and/or use of diet that influences the subject's metabolic state.

IPC Classes  ?

• A23L 33/20 - Reducing nutritive valueDietetic products with reduced nutritive value
• A61K 31/155 - Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (HN=C(OH)NH2), isothiourea (HN=C(SH)—NH2)
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 35/00 - Antineoplastic agents
• C07C 279/00 - Derivatives of guanidine, i.e. compounds containing the group the singly-bound nitrogen atoms not being part of nitro or nitroso groups

Abstract

The invention relates generally to a method of treatment for a human genetic disease, such as diseases characterized by unbalanced nucleotide pools, e.g., mitochondrial DNA depletion syndromes, and more specifically, thymidine kinase 2 (TK2) deficiency, using gene therapy. The gene therapy may involve administration of one or more constructs, such as a viral vector, containing a nucleic acid encoding a functional protein. The functional protein may correspond to a nuclear gene. For treatment of TK2 deficiency, the gene therapy may involve administration of one or more constructs, such as a viral vector, containing a nucleic acid encoding a functional TK2 enzyme. The treatment may also involve the administration of pharmacological therapy in conjunction with the gene therapy. The treatment protocols of the disclosure, such as those involving gene therapy alone or in combination with pharmacological therapy, can be used to treat, prevent, and/or cure various other disorders of unbalanced nucleoside pools, especially those found in mitochondrial DNA depletion syndrome.

IPC Classes  ?

• C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/117 - Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids

Abstract

The present invention provides, inter alia, a compound having the structure (I). Also provided are compositions containing a pharmaceutically acceptable carrier and one or more compounds according to the present invention. Further provided are methods for treating or ameliorating the effects of a disorder in a subject, methods of suppressing the toxicity of endoplasmic reticulum (ER) stress in a subject, methods of treating or ameliorating the effects of a disease involving axon degeneration in a subject, and methods for treating or ameliorating the effects of a neurodegenerative disease.

IPC Classes  ?

• C07D 209/20 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
• C07D 401/08 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing alicyclic rings
• 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

Abstract

Provided are chimeric polypeptides which modulate various cellular processes following cleavage of a force sensor cleavage domain, including non-Notch force sensor cleavage domains, induced upon binding of a specific binding member of the chimeric polypeptide with its binding partner. Methods of using force sensor cleavage domain-containing chimeric polypeptides to modulate cellular functions, including e.g., modulation (including induction or repression) of gene expression, are also provided. Nucleic acids encoding the subject chimeric polypeptides and associated expression cassettes and vectors as well as cells that contain such nucleic acids and/or expression cassettes and vectors are provided. Also provided, are methods of monitoring cell-cell signaling and method of treating a subject using the described components, as well as kits for practicing the subject methods.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 19/00 - Hybrid peptides
• C12N 5/22 - Human cells
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

The present disclosure relates to organic electrolyte solutions including organic electrolytes (e.g., aromatic imides, ferrocenes, spiro fused compounds, or cyclopropenium compounds), and redox flow batteries and systems including the same.

IPC Classes  ?

• H01G 11/56 - Solid electrolytes, e.g. gelsAdditives therein
• H01M 10/42 - Methods or arrangements for servicing or maintenance of secondary cells or secondary half-cells

Abstract

Methods and pharmaceutical compositions for treatment of amyloid deposition diseases using chimeric (e.g., mouse-human) antibody are disclosed, including a method for treating amyloid deposition diseases with cardiac involvement by administering pharmaceutical compositions comprising a chimeric anti-amyloid fibril antibody. The methods herein can improve myocardial function in patients diagnosed with light chain amyloid light chain amyloidosis (ALA) having a cardiac involvement in as little as three weeks after treatment.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 43/00 - Drugs for specific purposes, not provided for in groups

Abstract

A chimeric mouse-human antibody for treatment of amyloid deposition diseases, pharmaceutical compositions comprising the antibody, methods and materials for producing the antibody, and methods for treating an amyloid deposition disease using the antibody and the pharmaceutical composition.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 49/00 - Preparations for testing in vivo
• A61K 51/10 - Antibodies or immunoglobulinsFragments 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
• C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C07K 16/46 - Hybrid immunoglobulins
• C12N 15/13 - Immunoglobulins

Abstract

Pyrrolobenzodiazepines target alpha-4 and alpha-5 GABAA receptors for use in the treatment of airway hyperresponsiveness and inflammation in asthma. Compounds selectively partition to the peripheral compartment and have reduced CNS effects.

IPC Classes  ?

• A61K 31/5517 - 1,4-Benzodiazepines, e.g. diazepam condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• A61P 11/00 - Drugs for disorders of the respiratory system
• C07D 487/04 - Ortho-condensed systems
• C07D 487/14 - Ortho-condensed systems

Abstract

The invention provides pharmaceutical compositions and methods for treating cancer by administering a HAT modulator and a HDAC modulator to a subject. HAT modulators may be of formula (I),

IPC Classes  ?

• C07C 235/64 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho- position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• C07D 213/82 - AmidesImides in position 3

Abstract

Described are systems, methods, and devices relating to normothermic extracorporeal support of an organ, tissue, or bioengineered graft comprising cross-circulation (XC) perfusion for prolonged periods (days to weeks) via an XC perfusion circuit in connection with an extracorporeal host (e.g., animal, patient, organ transplant recipient) are disclosed. The XC perfusion circuit comprises auto-regulation of blood flow based on the trans-organ blood pressure difference between arterial and venous pressure. Recipient support enabled 36 h of normothermic perfusion that maintained healthy lungs with no significant changes in physiologic parameters and allowed for the recovery of injured lungs. Extended support enabled multiscale therapeutic interventions in all extracorporeal lungs. Lungs exceeded transplantation criteria.

IPC Classes  ?

• A01N 1/00 - Preservation of bodies of humans or animals, or parts thereof
• A01N 1/142 - Apparatus
• A01N 1/143 - Apparatus for organ perfusion
• A61J 1/00 - Containers specially adapted for medical or pharmaceutical purposes
• C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus
• C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor

Abstract

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, the treatment of ischemic injury, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, infections of the skin, peripheral vascular disease, stroke, asthma, and the like.

IPC Classes  ?

• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• A61P 25/00 - Drugs for disorders of the nervous system
• C07C 215/10 - Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with one amino group and at least two hydroxy groups bound to the carbon skeleton
• C07C 229/24 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid
• C07C 229/26 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one amino group bound to the carbon skeleton, e.g. lysine
• C07C 279/14 - Derivatives of guanidine, i.e. compounds containing the group the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
• C07C 279/26 - X and Y being nitrogen atoms, i.e. biguanides
• C07D 495/04 - Ortho-condensed systems
• C07H 5/06 - Aminosugars

Abstract

The present invention relates to methods for regulating prohormone convertase (PC1) and compounds and treatments which increase PC1 levels, for treating Prader-Willi Syndrome (PWS).

IPC Classes  ?

• A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• A61K 31/221 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having an amino group, e.g. acetylcholine, acetylcarnitine

Abstract

The present disclosure provides, in one embodiment, a method of treating or preventing an ID2 protein-related disease in a patient at risk of developing or having such a disease by administering to the patient a composition in an amount and for a time sufficient to increase degradation of HIFa in a cell affected by the ID2 protein-related disease in the patent and/or to decrease half-life of HIFa in the cell affected by the ID2 protein-related disease in the patient, as compared to an untreated cell affected by the ID2 protein-related disease.

IPC Classes  ?

• A61K 38/19 - CytokinesLymphokinesInterferons
• A61K 38/44 - Oxidoreductases (1)
• A61K 38/45 - Transferases (2)
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 9/12 - Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
• C12N 15/12 - Genes encoding animal proteins
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression

Abstract

Neutralizing antibodies that specifically bind to HIV-1 Env and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed.

IPC Classes  ?

• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses

Abstract

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

IPC Classes  ?

• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 14/725 - T-cell receptors
• 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 19/00 - Hybrid peptides
• C12N 5/078 - Cells from blood or from the immune system
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/09 - Recombinant DNA-technology
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

The invention relates generally to a pharmacological therapy for human genetic diseases, specifically those characterized by unbalance nucleotide pools, more specifically mitochondrial DNA depletion syndromes, and more specifically, thymidine kinase 2 (TK2) deficiency. The pharmacological therapy involves the administration of at least one deoxynucleoside, or mixtures thereof. For the treatment of TK2 deficiency, the pharmacological therapy involves the administration of either deoxythymidine (dT) or deoxycytidine (dC), or mixtures thereof. This administration of deoxynucleosides is applicable to other disorders of unbalanced nucleotide pools, especially those found in mitochondrial DNA depletion syndrome.

IPC Classes  ?

• A61K 31/7064 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
• A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• C07D 403/06 - 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 carbon chain containing only aliphatic carbon atoms

Abstract

The present invention relates to recombinant Glut1 adeno-associated viral vector (rAAV) constructs and related methods for restoring Glut1 expression in Glut1 deficient mammals. In certain embodiments, the rAAV further comprises a chicken ß-actin promoter wherein the rAAV is capable of crossing the blood-brain barrier (BBB). In certain embodiments, the present invention relates to a composition comprising any of the recombinant AAV's described herein. In certain embodiments, the present invention relates to a kit comprising a container housing comprising the composition described herein. In certain embodiments, the present invention relates to methods of restoring Glut1 transport in the BBB of a subject, comprising administering to the subject an effective amount of any of the recombinant AAV vectors described herein. In certain embodiments, the present invention relates to a method of treating Glut1 deficiency syndrome in a subject in need thereof.

IPC Classes  ?

• A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• 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

Abstract

The present invention provides a compound having the structure: wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl, wherein two or more of R1, R2, R3, R4, or R5 are other than H; R6 is H, OH, or halogen; and B is a substituted or unsubstituted heterobicycle, wherein when R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is H, R2 is CF3, R3 is H, R4 is CF3, and R5 is H, or R1 is C1, R2 is H, R3 is H, R4 is F, and R5 is H, or R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is CF3, R2 is F, R3 is H, R4 is H, and R5 is H, or R1 is C1, R2 is F, R3 is H, R4 is H, and R5 is H, then B is other than or a pharmaceutically acceptable salt thereof.

IPC Classes  ?

• 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 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61P 27/02 - Ophthalmic agents
• C07D 471/04 - Ortho-condensed systems
• C07D 487/04 - Ortho-condensed systems

Abstract

The present invention provides a compound having the structure (I) or a pharmaceutically acceptable salt or ester thereof.

IPC Classes  ?

• A61K 31/554 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• A61P 25/24 - Antidepressants
• C07D 281/02 - Seven-membered rings
• 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
• C07D 513/04 - Ortho-condensed systems