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

Aspects of the present disclosure include polymeric structures (e.g., microneedles) having a lattice microstructure composed of one or more lattice cell units. Polymeric structures according to certain embodiments have repeating lattice cell units that are formed by high resolution continuous liquid interface production. Aspects also include systems for making polymeric structures having a lattice microstructure. Systems according to certain embodiments include a micro-digital light projection system having a light beam generator component and a light projection monitoring component and a liquid interface polymerization module having a build elevator and a build surface configured for generating the polymeric lattice microstructure from a polymerizable composition positioned therebetween. Methods for making polymeric structures having a lattice microstructure with the subject systems are also provided. Patches having an array of polymeric microneedles for applying to a skin surface of a subject are also described. In some embodiments, patches include microneedles that contain an active agent compound (e.g., an immunogenic active agent). Methods for applying the patches to the skin surface of a subject are also described.

IPC Classes  ?

• A61M 37/00 - Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
• A61L 31/06 - Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• A61L 31/16 - Biologically active materials, e.g. therapeutic substances

Abstract

A method is provided for treating cancer in an individual, the method comprising culturing patient derived tumor organoids (PDO) with cognate immune cells with or without the presence of one or more direct or indirect T cell activating agents; expanding T cells following activation; and administering the activated T cells to the individual.

IPC Classes  ?

• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C12N 5/07 - Animal cells or tissues
• C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives 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

Abstract

The present disclosure provides a CAR comprising a tumor antigen binding domain, a transmembrane domain, and an intracellular domain comprising an intracellular signaling domain of an interleukin-9 receptor alpha (IL9Ra), and modified cell(s), i.e., immune cell(s) or precursor cell(s) thereof, engineered to express the CAR. Also provided are methods and uses of the modified cells, e.g., for treating at least one sign and/or symptom of cancer. Related nucleic acids, vectors, and pharmaceutical compositions are also provided.

IPC Classes  ?

• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• 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

Abstract

The present disclosure provides chimeric cytokine receptors comprising an intracellular signaling domain of an interleukin-9 receptor alpha (IL9Ra). The present disclosure also provides modified cell(s), i.e., immune cell(s) or precursor cell(s) thereof, wherein the cell(s) are engineered to express a) interleukin-9 receptor alpha (IL9Ra), or a chimeric cytokine receptor disclosed herein; and b) a chimeric antigen receptor (CAR). The present disclosure further provides a vector (e.g., an oncolytic adenoviral vector) comprising a nucleic acid sequence encoding a cytokine, as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof. Also provided are modified immune cell(s) or precursor cell(s) thereof which are engineered to express a chimeric antigen receptor (CAR), wherein expression of Cullin 5 in the cell(s) is reduced and/or eliminated. Also provided are methods and uses of the modified cells, e.g., for treating at least one sign and/or symptom of cancer. Related nucleic acids, vectors, and pharmaceutical compositions are also provided.

IPC Classes  ?

• C07K 14/715 - Receptors; Cell surface antigens; Cell surface determinants for interferons
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C07K 14/71 - Receptors; Cell surface antigens; Cell surface determinants for growth regulators

Abstract

The present disclosure generally relates to, inter alia, recombinant cells capable of expressing polypeptides, e.g., chimeric antigen receptors (CARs) that can be used for logic gating ( e.g., NOT-gating) to specifically target and eliminate some types of cells ( e.g., cancer cells). The disclosure also provides recombinant cells capable of expressing polypeptides such as inhibitory chimeric antigen receptors (iCARs), either alone or in combination as Boolean logic NOT gates, as well as pharmaceutical compositions containing the cells or the polypeptides for use in treating various conditions, such as diseases (e.g., cancers). The present description provides a composition containing an inhibitory chimeric antigen receptor (iCAR) polypeptide capable of reducing activation of an, activating chimeric antigen receptor (aCAR) polypeptide.

IPC Classes  ?

• 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 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• A61K 35/12 - Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells

Abstract

Methods and devices for vector-based targeting of the human central thalamus (CT) to guide deep brain stimulation (DBS) are disclosed. In some examples, electrode(s) each with a plurality contacts are provided. A three-dimensional orientation of a dominant axis of a central lateral nucleus dorsal tegmental tract medial component (CL/DTTm) fiber bundle of a human subject is determined. The contacts of the electrode(s) are positioned in the subject's CT fibers in substantial alignment with the three-dimensional orientation. An electrical stimulus is applied to the contacts to selectively activate the CT fibers. The positioning and the applying are carried out to maximize activation of a central lateral nucleus and medial dorsal tegmental tract fiber pathway in the subject and to minimize activation of a centromedian-parafascicularis fiber pathway in the subject. Methods and devices for surgical planning involving for vector-based targeting of the human CT to guide DBS are also disclosed.

IPC Classes  ?

• A61N 1/05 - Electrodes for implantation or insertion into the body, e.g. heart electrode
• A61N 1/20 - Applying electric currents by contact electrodes continuous direct currents
• A61N 1/36 - Applying electric currents by contact electrodes alternating or intermittent currents for stimulation, e.g. heart pace-makers

Abstract

The present disclosure generally relates to, inter alia, a class of chimeric switch receptors containing an endodomain of an IL-9 receptor, engineered to modulate transcriptional regulation in a ligand-dependent manner. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating gene expression, modulating an activity of a cell, and/or for the treatment of various health conditions or diseases.

IPC Classes  ?

• C12N 15/62 - DNA sequences coding for fusion proteins
• C12N 5/0781 - B cells; Progenitors thereof
• C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
• C12N 5/0784 - Dendritic cells; Progenitors thereof
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 35/00 - Antineoplastic agents
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C07K 14/71 - Receptors; Cell surface antigens; Cell surface determinants for growth regulators
• C07K 14/715 - Receptors; Cell surface antigens; Cell surface determinants for interferons
• C07K 19/00 - Hybrid peptides
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression

Abstract

The present disclosure provides recombineering-editing systems using CRISPR and recombination enzymes as well as methods, vectors, nucleic acid compositions, and kits thereof. The methods and systems provide means for altering target DNA, including genomic DNA in a host cell.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

Currently, more than 60% of the U.S. population is overweight, and close to 40% is obese. Obesity is considered to be an epidemic. Obesity is not just characterized by an increase in body mass, but it also comes with a range of physiological changes. As a result, obese and ovenweight people are at a higher risk for developing life-threatening conditions such as cardiovascular diseases, diabetes and many types of cancers. Herein are methods, compositions and kits for enhancing immune cell mediated cancer treatment in overweight and obese individuals.

IPC Classes  ?

• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61P 3/00 - Drugs for disorders of the metabolism
• A61P 35/00 - Antineoplastic agents
• 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

Skin graft methods are provided. Aspects of the methods include applying a skin graft to a wound in combination with a mechanotransduction blocker, such as a pharmacological mechanotransduction blocker, e.g., a focal adhesion kinase inhibitor. Also provided are compositions and kits for use practicing methods of the invention.

IPC Classes  ?

• A61L 27/36 - Materials for prostheses or for coating prostheses containing ingredients of undetermined constitution or reaction products thereof
• A61K 35/36 - Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61L 15/42 - Use of materials characterised by their function or physical properties
• A61L 15/44 - Medicaments
• A61L 15/60 - Liquid-swellable gel-forming materials, e.g. super-absorbents
• A61L 27/52 - Hydrogels or hydrocolloids
• A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

Abstract

Methods, systems, and devices, including computer programs encoded on a computer storage medium are provided for measuring and displaying subject motion information during procedures which require remote subject monitoring. The system uses a mobile device with depth sensor capabilities, data processing capabilities and artificial intelligence (AI) predictive models to provide motion information. The system motion information can be used to measure the period of time a subject performed deep-inspiration breath hold (DIBH) and for training the subject to achieve a DIBH of at least 20 seconds.

IPC Classes  ?

• A61B 5/113 - Measuring movement of the entire body or parts thereof, e.g. head or hand tremor or mobility of a limb occurring during breathing
• G06T 7/20 - Analysis of motion

Abstract

The present invention relates to the field of yeast fermentations. More particularly, the invention relates to mutant alleles useful to engineer industrially relevant traits in yeast.

IPC Classes  ?

• C12N 1/16 - Yeasts; Culture media therefor
• A61K 36/06 - Fungi, e.g. yeasts
• C12N 15/80 - Vectors or expression systems specially adapted for eukaryotic hosts for fungi
• C12P 7/16 - Butanols
• C12P 7/54 - Acetic acid

Abstract

Provided herein are recombinant circular RNA (circRNA) molecules comprising an internal ribosome entry site (IRES) operably linked to a protein-coding nucleic acid sequence. The IRES may be, for example, a Type I IRES, such as a viral IRES. In some embodiments, the IRES is a synthetic IRES, such as an IRES comprising an aptamer. Methods of producing a protein in vitro or in vivo using the recombinant circRNA molecules are also provided.

IPC Classes  ?

• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides

Abstract

Gastrostomy tubes and systems and methods for implanting them are provided. In one example, the gastrostomy tube includes an elongate tubular member including a first end sized for introduction into the patient's mouth, a second end including an expandable member or other bumper, and a feeding lumen extending between the first and second ends. A bolster is connectable around the first end after the first end has been directed from within the patient's stomach through intervening tissue and extends from the patient's skin and the bumper is placed against the wall of the stomach. An adapter is connectable to the bolster after the first end and excess material of the tubular member beyond the bolster has been separated, the adapter including a connector for removably connecting to a feeding tube.

IPC Classes  ?

• A61J 15/00 - Feeding-tubes for therapeutic purposes

Abstract

A shock absorbing device is disclosed comprising a first collapsible chamber having a first reservoir space, a first wall configured to receive an impact force, and a first orifice configured to eject a fluid from the first reservoir space in reaction to the impact force; and a second collapsible chamber having a second reservoir space, a second wall configured to receive at least a portion of the impact force, a second orifice in communication with the first orifice and the second reservoir space, and at least one ejection orifice in communication with the second reservoir space and configured to eject the fluid from the second reservoir space in reaction to the said received at least a portion of the impact force.

IPC Classes  ?

• A42B 3/12 - Cushioning devices
• F16F 9/06 - Springs, vibration-dampers, shock-absorbers, or similarly-constructed movement-dampers using a fluid or the equivalent as damping medium using both gas and liquid

Abstract

Devices, systems, and methods are provided for relieving peripheral nerve pain in a subject. In one example, the device includes a surface configured for placement against a subject's skin, an imaging element on the housing configured to transmit signals from the surface into the subject's body and receive reflected signals from the body, and one or more transducer elements configured to deliver focused ultrasound from the surface into the body. A controller is coupled to the imaging element to process the reflected signals to identify a target nerve within the body and coupled to the one or more transducer elements to control delivery of the focused ultrasound to the target nerve to relieve pain.

IPC Classes  ?

• A61B 8/00 - Diagnosis using ultrasonic, sonic or infrasonic waves
• A61B 8/08 - Detecting organic movements or changes, e.g. tumours, cysts, swellings
• A61B 18/00 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
• A61B 18/04 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
• A61N 7/00 - Ultrasound therapy
• A61N 7/02 - Localised ultrasound hyperthermia

Abstract

Methods are provided herein for vaccine development, characterization and validation. Using the response signatures disclosed herein, methods are provided for optimization, selection and benchmarking of vaccines, including adjuvants for vaccines. The methods include a prediction of response durability, e.g. the longevity of an antibody response, for a candidate vaccine or vaccine adjuvant; and assessment of similarity to a benchmark reference vaccine.

IPC Classes  ?

• A61K 49/00 - Preparations for testing in vivo
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations

Abstract

A sequencer for automated in situ sequencing of volumetric tissue samples is provided. In particular, an automated volumetric in situ sequencing device capable of operating on multiple samples in parallel is provided. Methods of fabrication and use of the sequencer are also provided.

IPC Classes  ?

• B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
• B01L 7/00 - Heating or cooling apparatus; Heat insulating devices

Abstract

Provided herein are devices, methods, and systems for next-generation volumetric in situ sequencing of nucleic acids in cells in intact tissue. In particular, methods are provided for improving robustness across sample types, including for thin and thick tissue volumes, and increasing the efficiency and specificity of target labeling for volumetric combinatorial in situ sequencing.

IPC Classes  ?

• C12Q 1/6841 - In situ hybridisation
• C12Q 1/682 - Signal amplification
• G01N 33/52 - Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper

Abstract

Processes and materials to detect cancer, transplant rejection, or fetal genetic abnormalities from a biopsy are described. In some cases, nucleic acid molecules, such as cell-free nucleic acids, can be sequenced, and the sequencing result can be utilized to detect sequences indicative of a neoplasm, transplant rejection, or fetal genetic abnormality. Detection of somatic variants occurring in phase and/or insertions and deletions (indels) can indicate the presence of cancer, transplant rejection, or fetal genetic abnormalities in a diagnostic scan, and a clinical intervention can be performed.

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
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection

Abstract

The present disclosure relates to glyconucleic acids, such as glycoRNA and glycoDNA described herein. Provided are glycosylated ribonucleic acid (glycoRNA)-related methods and compositions.

IPC Classes  ?

• A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound

Abstract

Disclosed herein is a method of reducing Miro1 level in a cell, the method comprising contacting the cell with an effective amount of a T-type calcium channel antagonist.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• C07D 249/16 - Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems

Abstract

Provided are methods of selecting for cells that comprise two or more separate expression constructs. In certain embodiments, the methods comprise contacting a population of cells with two or more separate expression constructs under conditions in which the two or more expression constructs are delivered to cells of the population of cells. The two or more separate expression constructs comprise a first expression construct that encodes a fusion protein comprising a selection marker, a protein localization tag, and a protease cleavage site disposed between the selection marker and the protein localization tag. The second expression construct encodes a protein required for cell surface expression of the selection marker. Such methods further comprise selecting for cells exhibiting cell surface expression of the selection marker. Related cells, compositions, kits and therapeutic methods are also provided.

IPC Classes  ?

• C12N 9/50 - Proteinases
• C12N 15/09 - Recombinant DNA-technology
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C12N 15/79 - Vectors or expression systems specially adapted for eukaryotic hosts
• C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

Methods of use, pharmaceutical formulations, and labeled versions of compounds are provided of compounds that penetrate the blood-brain barrier and influence the balance of excitatory versus inhibitory neurotransmission by enantiomer selective modulation of glutamate and GABA metabolism. In some embodiments, a glutamatergic false neurotransmitter is S-2-methylglutamate (S-2MeGlu). In some embodiments a GABAergic false neurotransmitters is R-4 aminopentanomic acid (4APA) or S-4 aminopentanomic acid (S-4APA), with high penetration of the blood brain barrier and low toxicity, therein providing useful pharmacologic or imaging agents.

IPC Classes  ?

• A61K 31/198 - Alpha-amino acids, e.g. alanine, edetic acid (EDTA)

Abstract

Photovoltaic retinal prosthesis is provided with optically configurable confinement of electrical field. A video stream is projected onto a retinal implant. An array of photovoltaic pixels is configured to provide retinal stimulus responsive to the video stream. The photovoltaic pixels have a common return electrode. Each pixel has an active electrode that is coupled to retinal tissue via a capacitive interface or a faradaic interface. Each pixel includes photodiode(s) connected in series between the common return electrode and the corresponding active electrode. The projected video stream is configured based on a source video stream such that one or more pixels of the retinal implant that will be dark in a next frame of the projected video stream are optically preconditioned (pre-charged) by the projected video stream during the previous frame to become sufficiently conductive to act as transient local return electrodes during the next frame of the projected video stream.

IPC Classes  ?

• A61F 2/16 - Intraocular lenses
• A61F 9/08 - Devices or methods enabling eye-patients to replace direct visual perception by another kind of perception
• 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

Methods and formulations of treatment for menstrual complications, gestational complications, and to prolong gestation are described. Treatments include administration of a compound related to regulation of gestational progress or uterine contractions.

IPC Classes  ?

• A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• A61P 5/24 - Drugs for disorders of the endocrine system of the sex hormones
• A61P 5/34 - Gestagens
• C07J 7/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of two carbon atoms

Abstract

Aspects of the present disclosure include bispecific molecules. The bispecific molecules comprise a cell-targeting moiety and a glycan-binding moiety. According to some embodiments, the cell-targeting moiety is a cancer cell-targeting moiety or an immune cell-targeting moiety. In certain embodiments, the glycan-binding moiety comprises the sialoglycan-binding domain of a lectin, non-limiting examples of which are sialic acid-binding immunoglobulin-like lectins (Siglecs). The bispecific molecules may take a variety of forms including heterodimeric molecules, fusion proteins, conjugates, and the like. Compositions, kits and methods of using the bifunctional molecules, e.g., for therapeutic purposes, are also provided.

IPC Classes  ?

• A61K 31/00 - Medicinal preparations containing organic active ingredients
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans

Abstract

Embodiments herein describe systems and methods to generate a surgical risk score. Various embodiments obtaining multi-omics data from an individual, such as genomics, transcriptom ics, and proteomics. In certain embodiments, a machine algorithm is used to generate the surgical risk score based on the multi-omics data. In further embodiments, clinical data is further used in the determination of the surgical risk score.

IPC Classes  ?

• A61B 17/17 - Guides for drills

Abstract

Engineered T cell receptor (TCR) sequences, cells expressing such sequences and methods of use thereof are provided. The engineered receptors are mutagenized in vitro, and selected for target activation potency in combination with selection for a pMHC affinity that is sufficiently low to reduce off-target cross-reactivity. In some embodiments the engineered TCR recognizes the tumor associated antigen (TAA), human MAGE-A3

IPC Classes  ?

• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
• C07K 14/725 - T-cell receptors

Abstract

Provided herein, inter alia, are methods and compositions for assembling oligonucleotide fragments in vivo. The methods bypass inefficient cloning methods and the requirement for expensive enzymes. The methods may further be used to assemble long fragments of DNA. The methods may be used to generate variant libraries and combinatorial libraries and may be used to trace biological processes. Also provided herein, inter alia, are methods for in vivo DNA barcoding of oligonucleotide sequences. Methods provided herein are contemplated to produce unique barcode-oligonucleotide fusion sequences for identifying and isolating the oligonucleotide sequences, e.g., from a mixture. Accordingly, also provided are methods of identifying an oligonucleotide from a mixture of oligonucleotides.

IPC Classes  ?

• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

The invention regards a method for electrochemical ammonia synthesis, comprising the steps of: - providing an electrolysis cell having a cathode, - contacting the cathode with a source of cations, preferably lithium cations, a source of nitrogen, a source of oxygen, and a source of protons, wherein the oxygen source provides a predefined oxygen concentration, and - subjecting the cell to a potential and current load, whereby ammonia is synthesized.

IPC Classes  ?

• C25B 1/27 - Ammonia
• C25B 9/17 - Cells comprising dimensionally-stable non-movable electrodes; Assemblies of constructional parts thereof

Abstract

Methods of delivering one or more imaging or diagnostic substance(s) to the brain in a subject.

IPC Classes  ?

• A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
• A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment

Abstract

Methods are provided herein for modulating the epigenome of immune cells by administration of an immunostimulatory composition comprising adjuvants, e.g. vaccine adjuvants, to stimulate broad and persistent innate immunity against pathogens unrelated to antigens present in the composition.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
• A61P 35/00 - Antineoplastic agents
• A61P 37/04 - Immunostimulants

Abstract

The present disclosure provides methods for determining the presence of at least one biomolecule in a sample. The present disclosure further provides methods for determining the presence of a coronavims antibody in a sample.

IPC Classes  ?

• G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
• C07K 1/13 - Labelling of peptides
• G01N 33/53 - Immunoassay; Biospecific binding assay; Materials therefor
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Abstract

Provided are modified microorganisms, such as live recombinant commensal bacteria, that express a non-native antigen, or are surface-labeled with a non-native antigen, and methods of using the modified microorganisms to induce an antigen-specific immune response to the non-native antigen. The modified microorganism can be used to induce a regulatory T cell immune response to the heterologous antigen to treat an autoimmune disease in a subject in need thereof, or can be used to induce an effector T cell immune response to the heterologous antigen to treat an infectious disease or proliferative disease in a subject in need thereof.

IPC Classes  ?

• A61K 35/74 - Bacteria
• A61K 35/744 - Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs

Abstract

Provided are methods of analyzing a capillary microsample obtained from a subject. In certain embodiments, the methods comprise assessing a test mixture for one or more capillary microsample analytes, wherein the test mixture comprises the capillary microsample diluted into a stabilizing buffer comprising isopropanol, ethanol, methanol, or a combination thereof. Such methods further comprise analyzing capillary microsample nucleic acids purified from the test mixture. According to some embodiments, analyzing the capillary microsample nucleic acids comprises genotyping the subject. Methods of determining one or more alleles of a subject are also provided, as are kits that find use in practicing the methods of the present disclosure.

IPC Classes  ?

• G01N 21/01 - Arrangements or apparatus for facilitating the optical investigation
• G01N 21/76 - Chemiluminescence; Bioluminescence

Abstract

The present disclosure provides methods of improving the structure and/or function of a joint tissue of a subject by administering to the subject an amount of a 15-PGDH inhibitor effective to inhibit 15-PGDH activity and/or reduce 15-PGDH levels in the subject. The methods described herein are useful for treating joint dysfunction and/or degeneration associated with aging, injury, disease, disorder, and/or condition.

IPC Classes  ?

• A61K 31/557 - Eicosanoids, e.g. leukotrienes
• A61K 31/5575 - Eicosanoids, e.g. leukotrienes having a cyclopentane ring, e.g. prostaglandin E2, prostaglandin F2-alpha
• A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• A61P 19/04 - Drugs for skeletal disorders for non-specific disorders of the connective tissue

Abstract

Provided herein are novel azopodophyllotoxin analog compounds, pharmaceutical compositions comprising them, and their use as inhibitors of Y box protein 1 (YB1 or YBX1) in treatments for conditions including gynecological, breast, bladder, kidney, head and neck, neuronal, and prostate cancers, lymphomas, and leukemias. Methods of their use in sensitizing resistant cancers to treatment with anticancer agents and radiation are also provided.

IPC Classes  ?

• A61K 31/435 - 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
• 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
• C07D 215/00 - Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems

Abstract

Process for making a composite oxide according to the formula x·Li2Ni1-y1-y2Mny1M1y2O3·(1-x)·LiNi1-zM2zO2 wherein x is in the range of from 0.01 to 0.5, z is in the range of from zero to 0.5, M1 is selected from Ti, Zr, Sn, Ge, Ta, Nb, Sb, W, and Mo, and combinations of at least two of the foregoing, M2 is at least one of Co, Al, Mg, Fe, or Mn, or a combination of at least two of the foregoing, 0.1 ? y1 ? 0.75, zero ? y2 ? 0.05, said process comprising the following steps: (a) providing a particulate hydroxide, oxide or oxyhydroxide of TM where TM has the general formula x·Ni1-y1-y2Mny1M1y·(1-x)Ni1-zM2z, or the respective species without M1 and/or M2, (b) adding a source of lithium, (c) treating the mixture obtained from step (b) thermally under an atmosphere comprising oxygen in two steps: (c) heating the mixture obtained from step (b) to 680 to 800°C in an atmosphere containing in the range of from 10 to 100 vol-% oxygen, and, (e) heating the intermediate from step (c) to 450 to 580°C in an atmosphere containing at least 90 vol-% oxygen.

IPC Classes  ?

• H01M 4/131 - Electrodes based on mixed oxides or hydroxides, or on mixtures of oxides or hydroxides, e.g. LiCoOx
• H01M 4/505 - Selection of substances as active materials, active masses, active liquids of inorganic oxides or hydroxides of manganese of mixed oxides or hydroxides containing manganese for inserting or intercalating light metals, e.g. LiMn2O4 or LiMn2OxFy
• H01M 4/525 - Selection of substances as active materials, active masses, active liquids of inorganic oxides or hydroxides of nickel, cobalt or iron of mixed oxides or hydroxides containing iron, cobalt or nickel for inserting or intercalating light metals, e.g. LiNiO2, LiCoO2 or LiCoOxFy
• C01D 15/02 - Oxides; Hydroxides

Abstract

A two-component hydrogel matrix system is provided, which system is useful in a variety of cell growth uses, including without limitation three-dimensional culture systems. The components comprise modified hyaluronic acid (HA); and modified elastin-like proteins (ELP). Variables of HELP, including for example, matrix stiffness, matrix stress relaxation rate, and cell-adhesive-ligand concentration, can be independently and quantitatively specified.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/70 - Web, sheet or filament bases
• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61K 38/39 - Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups

Abstract

Methods of modulating transcription of a target gene in a cell (which may be in vitro or in vivo) are provided. Aspects of the methods employ a transcription factor-chemical inducer of proximity (TF-CIP) system to modulate, e.g., enhance or reduce, transcription of a target gene in a cell. Embodiments of the methods include providing in a cell a chemical inducer of proximity (CIP) which links a first endogenous anchor transcription factor that binds to a promoter of the target gene and a second endogenous transcription modulating factor (e.g., a transcription factor or transcription repressor), wherein CIP mediated linkage of the anchor transcription factor and transcription modulating factor modulates transcription of the target gene in the cell. Also provided are compositions that find use in practicing methods of the invention.

IPC Classes  ?

• A61K 38/00 - Medicinal preparations containing peptides
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 35/00 - Antineoplastic agents
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

The present disclosure generally relates to, inter alia, methods, kits, and systems for the diagnosis and/or treating various health conditions, such as proliferative disorders (e.g., cancers), associated with a decreased level or a loss of CD58 expression or molecular alterations in CD58 activity.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12Q 1/6886 - 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
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

Methods are provided for the prevention and treatment of vascular inflammation. The methods comprise administering to a human subject an effective dose of an agent that specifically binds to CD47, and reduces one or more indicia of vascular inflammation.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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

Compositions and methods are provided for inhibiting or treating the progression of inflammatory diseases by administration to an individual of an effective dose of a combination of active agents comprising or consisting essentially of a selective histamine H1 receptor antagonist; in combination with a second agent that provides for reduction of pain, inflammation, alteration of inflammatory lipids, and the like.

IPC Classes  ?

• A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• 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

Abstract

The present invention relates to methods for identifying guide RNAs for use in site-directed RNA editing. In particular, the present invention relates to a high-throughput screening method for identifying guide RNAs effective for site directed A-to-I RNA editing, and methods of use for the identified guide RNAs.

IPC Classes  ?

• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

Compositions and methods are provided relating to NR1 ES-derived neural stem cells. The cells are useful in methods of treatment for an adverse neurologic conditions, including without limitation stoke.

IPC Classes  ?

• A61K 35/30 - Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• C12N 5/0793 - Neurons
• C12N 5/0797 - Stem cells; Progenitor cells
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

Compositions and methods are provided for detection of dynamic loci in a genome. The methods may utilize microfluidic platforms and functionalized polymer matrices to allow determination of mechanisms of cell-type-specific, programmed genomic heterogeneity.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6869 - Methods for sequencing
• C40B 40/06 - Libraries containing nucleotides or polynucleotides, or derivatives thereof

Abstract

Systems and methods for neuronavigation in accordance with embodiments of the invention are illustrated. Targeting systems and methods as described herein can generate personalized stimulation targets for the treatment of mental conditions. In many embodiments, direct stimulation of a personalized the stimulation target indirectly impacts a brain structure that is more difficult to reach via the stimulation modality. In various embodiments, the mental condition is major depressive disorder. In a number of embodiments, the mental condition is suicidal ideation.

IPC Classes  ?

• A61N 2/00 - Magnetotherapy
• A61N 2/02 - Magnetotherapy using magnetic fields produced by coils, including single turn loops or electromagnets

Abstract

The disclosure pertains to methods for modifying empathy in a subject, such as a human, by modulating type 2 theta oscillations in a brain region of the subject. The methods include increasing empathy in a subject, such as a human, by increasing type 2 theta oscillations in a brain region of the subject, thereby increasing empathy in the subject. The human subject may have a psychiatric or neurological condition that causes suboptimal empathy. Modulating type 2 theta oscillations in a brain region of a subject can be accomplished by optogenetic treatment, electric stimulation of a brain region, administration of a pharmaceutical drug, or a combination thereof. Also provided are systems for performing the methods disclosed herein.

IPC Classes  ?

• A61N 1/36 - Applying electric currents by contact electrodes alternating or intermittent currents for stimulation, e.g. heart pace-makers
• A61N 1/40 - Applying electric fields by inductive or capacitive coupling

Abstract

Compositions and methods are provided for the achievement of organ and tissue transplantation and autoimmune tolerance using the infusion of living and/or deceased donor hematopoietic cells. The methods provided herein provide for conditioning with a plurality of doses of total lymphoid irradiation (TLI), and a single, very low dose of TBI (svldTBI), referred to herein as "TLI-svldTBI-ATG" or "TLI-svldTBI" depending on whether ATG is included. The combination of svldTBI and TLI specifically targets non-lymphoid-tissue resident memory immune cells. An in vitro manipulated donor cell composition is provided for use with the conditioning regimen, in which specific ratios of CD34+ and other hematopoietic stem cell and precursor cell populations are combined with defined doses of CD3+ T cells, and/or purified regulatory T cells (Treg) cells, invariant natural killer (iNK-T) cells, and/or CD8+ memory T cells.

IPC Classes  ?

• A61K 35/28 - Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes

Abstract

Many embodiments provide the formation of active Pd sites upon steam treatment. Steam treatment of Pd catalysts can improve redox combustion reaction efficiencies. Several embodiments provide the formation of twin boundaries under steam treatment can improve catalytic activities of nanoparticle catalysts.

IPC Classes  ?

• B01J 35/02 - Solids
• B01J 23/42 - Platinum
• B01J 23/44 - Palladium

Abstract

Provided is a conformation-specific antigen binding domain (ABD) specific for the Hedgehog receptor Patched1, which may be provided in the form of a nanobody. This nanobody potently activates the Hedgehog pathway in vitro and in vivo by stabilizing an alternative conformation of a Patched1 "switch helix". This ABD or nanobody is water soluble, i.e. does not require lipid modifications for its activity, facilitating mechanistic studies of Hedgehog pathway activation and therapeutic use.

IPC Classes  ?

• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
• C12N 15/09 - Recombinant DNA-technology
• C12N 15/13 - Immunoglobulins

Abstract

Provided herein are Cas proteins and guide RNA molecules engineered to exhibit increased activity in eukaryotic cells. The provided Cas proteins and RNA molecules are particularly useful for applications where modulation of eukaryotic nucleic acids with relatively small molecules is advantageous. Also provided are nucleic acids and vectors encoding the disclosed Cas proteins and guide RNA molecules, pharmaceutical compositions including the Cas proteins and guide RNA molecules, and methods for using the disclosed materials.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C07K 14/00 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• C07K 19/00 - Hybrid peptides
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

Provided are fusion proteins including an amino acid sequence of an ectodomain of Spike protein of a coronavirus, such as SARS-CoV-2, joined to an amino acid sequence of a ferritin subunit polypeptide. Nanoparticles including such fusion proteins, with surface-exposed trimers of the ectodomain of the Spike protein of the coronavirus, are also provided. Also provided are nucleic acids and vectors encoding the fusion proteins, cells containing such nucleic acid and vectors, immunogenic compositions including the fusion proteins, the nanoparticles, or the vectors, as well as corresponding methods and kits.

IPC Classes  ?

• A61K 39/12 - Viral antigens
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 31/12 - Antivirals
• A61P 31/14 - Antivirals for RNA viruses
• C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof

Abstract

The invention therefore provides methods of treating a respiratory disease characterized by mucus hyper-secretion comprising administering to a human patient in need of such treatment a gamma secretase inhibitor (GSI), wherein the administration of a GSI is effective in reducing mucus in such patient's lungs or inhibiting mucus accumulation in said patient's lungs. In some embodiments, the methods of the invention are effective in treating a respiratory disease selected from the group consisting of cystic fibrosis, chronic obstructive pulmonary disease, primary ciliary dyskinesis, chronic bronchitis, asthma, idiopathic and secondary bronchiectasis, bronchiolitis obliterans, idiopathic pulmonary fibrosis and other fibrotic lung disorders, respiratory infection including exacerbations in chronic respiratory disorders, and mucus accumulation in response to acute infection. Methods of the invention further include methods of treating cystic fibrosis wherein a GSI is administered to a patient being administered or in need of a CFTR modulator, wherein the mucus in such patient's lungs is reduced or mucus accumulation in such patient's lungs is inhibited.

IPC Classes  ?

• A61K 31/00 - Medicinal preparations containing organic active ingredients

Abstract

Multiparametric analysis is performed at the single cell level of biological samples obtained from an individual during pregnancy to obtain a determination of changes in the interactome, integrating metabolome, immunome and proteome features during pregnancy that are predictive of time to onset of labor.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

The invention is directed to novel sBCMA variants and sBCMA variant - Fc fusion proteins, polynucleotides encoding the sBCMA variants and/or sBCMA variant - Fc fusion proteins, methods of making the sBCMA variants and/or sBCMA variant - Fc fusion proteins, and methods of using compositions comprising the sBCMA variants and/or sBCMA variant - Fc fusion proteins, for example, in treating diseases such as tumors/cancers, immunoregulatory disorders, etc.

IPC Classes  ?

• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals

Abstract

The present disclosure provides methods and compositions for treating SCID-X1 in subjects, comprising genetically modifying cells from the subjects ex vivo by integrating a full-length, codon-optimized IL2RG cDNA at the endogenous IL2RG locus.

IPC Classes  ?

• A61K 35/28 - Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• C12N 5/0789 - Stem cells; Multipotent progenitor cells
• C12N 15/861 - Adenoviral vectors
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

Methods for treating cancer using combination therapy with an anti-coagulant and a B-Raf inhibitor and/or a mitogen-activated protein kinase (MEK) inhibitor are disclosed. The anti-coagulant may be a direct inhibitor of thrombin or an indirect inhibitor of thrombin, such as an inhibitor of factor Xa, factor XIa, or other coagulation factors.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

Provided herein are chimeric transmembrane receptor polypeptides configured to oligomerize upon recognition of an extramembrane signal. The receptors include an extramembrane domain, a transmembrane domain, and an intramembrane domain configured to induce activation of one or more intramembrane signal pathways upon oligomerization of the receptor. The provided receptors are particularly useful for engineered cell therapies. Also provided are systems and host cells including the disclosed receptors, and methods for using the disclosed materials.

IPC Classes  ?

• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 35/00 - Antineoplastic agents
• C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies

Abstract

Provided herein, inter alia, are complexes comprising nanoparticles attached to viral proteins or nucleic acids encoding said viral proteins. Methods for making and using said complexes are provided. Compositions including the complexes are contemplated to be useful for treating and/or preventing viral infections.

IPC Classes  ?

• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
• A61P 37/04 - Immunostimulants
• C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
• C07K 14/08 - RNA viruses
• C07K 14/165 - Coronaviridae, e.g. avian infectious bronchitis virus

Abstract

Methods are provided for the isolation and analysis of circular DNA from complex samples, based on the topology of the DNA molecule. A sample comprising DNA species is combined with a chaotropic dense salt solution. A fraction containing the circular DNA of interest is isolated and dialyzed to remove excess salt. In some embodiments salt gradients are generated by ultracentrifugation in the absence of intercalating dyes, e.g. ethidium bromide; and in the absence of protease digestion. The circular DNA thus isolated is substantially pure, e.g. greater than about 75%, greater than about 80%, greater than about 90%, greater than about 95% of DNA in the isolated fraction is comprised of circular DNA.

IPC Classes  ?

• C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C40B 40/00 - Libraries per se, e.g. arrays, mixtures

Abstract

There are provided herein, inter alia, complexes, compositions and methods for a vaccine for COVID-19. The cell-penetrating complexes provided herein may include a nucleic acid non- covalently bound to a cationic amphipathic polymer, the cationic amphipathic polymer including a pH-sensitive immolation domain. The cell-penetrating complexes provided herein are, inter alia, useful in vaccines, wherein the vaccine includes a ribonucleic acid including a sequence encoding a viral protein, a nucleic acid adjuvant and a cationic amphipathic polymer provided herein including embodiments thereof.

IPC Classes  ?

• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
• C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
• A61K 39/12 - Viral antigens
• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
• A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
• 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 31/12 - Antivirals
• A61P 37/04 - Immunostimulants
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells

Abstract

The present disclosure generally relates to, inter alia, recombinant immune cells that have been engineered to express elevated levels of one or more glucose transporters, and particularly relate to engineered immune cells exhibiting increased glycolytic flux and/or enhanced effector functions. Also provided are methods for generating a population of engineered immune cells with enhanced effector function, pharmaceutical compositions the same, as well as methods and kits for the prevention and/or treatment of a health condition in subjects in need thereof.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals

Abstract

Provided are cis-binding Siglec agonists. In certain embodiments, the cis-binding Siglec agonists comprise a scaffold bearing Siglec ligands, and a membrane-tethering domain. Also provided are compositions, e.g., pharmaceutical compositions, comprising any of the cis-binding Siglec agonists of the present disclosure. Methods of agonizing Siglec activity, e.g., in an individual in need thereof, are also provided. Kits comprising the cis-binding Siglec agonists, as well as methods of making the cis-binding Siglec agonists, are also provided.

IPC Classes  ?

• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C07K 14/735 - Fc receptors
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans

Abstract

Systems and methods for decoding intended symbols from neural activity in accordance with embodiments of the invention are illustrated. One embodiment includes a brain- computer interface, comprising a processor, a neural signal recorder implanted into a brain of a user, and a memory, where the memory comprises an application capable of directing the processor to provide the user with a set of options, where each option is selectable by a respective time-varying gesture, obtain neural signal data from the neural signal recorder, estimate a gesture from the neural signal data using a model, and select an option from the set of options associated with the gesture. In many embodiments, the gestures available are distance maximized.

IPC Classes  ?

• A61N 1/36 - Applying electric currents by contact electrodes alternating or intermittent currents for stimulation, e.g. heart pace-makers
• A61M 5/172 - Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters electrical or electronic

Abstract

The present disclosure provides methods and compositions for treating lysosomal storage disorders in subjects, comprising genetically modifying cells from the subjects ex vivo by integrating therapeutic transgenes into the CCR5 locus.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 5/0789 - Stem cells; Multipotent progenitor cells
• A61K 35/28 - Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 9/22 - Ribonucleases
• C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
• C12N 15/56 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. amylase, galactosidase, lysozyme
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
• C12N 15/864 - Parvoviral vectors
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

Provided herein are recombinant circular RNA (circRNA) molecules comprising an internal ribosome entry site (IRES) operably linked to a protein-coding nucleic acid sequence. The IRES includes at least one RNA secondary structure element; and a sequence region that is complementary to an 18S ribosomal RNA (rRNA). Methods of producing a protein in a cell using the recombinant circRNA molecules are also provided.

IPC Classes  ?

• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
• C12N 15/117 - Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
• C12N 15/67 - General methods for enhancing the expression

Abstract

Systems and methods are provided for altering the shape of a target tissue structure of a subject, e.g., a nasal septum or other nasal tissue that include securing a first end of a shaping element to tissue adjacent the structure; manipulating the tissue to alter a shape of the structure; and applying a force to the shaping element to maintain the altered shape of the structure.

IPC Classes  ?

• A61B 17/24 - Surgical instruments, devices or methods, e.g. tourniquets for use in the oral cavity, larynx, bronchial passages or nose; Tongue scrapers
• A61F 2/00 - Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
• A61F 2/18 - Internal ear or nose parts, e.g. ear-drums

Abstract

Provided are innovative compositions for tethering blocking an inactivating of airborne respiratory infectious viruses. The compositions comprise bispecific proteins with two different antigen binding regions (ABR), which are typically configured as immunoglobulin "single variable domains" (ISV). A first ISV binds to a surface protein found on an airborne infectious virus. A second ISV binds to a mucin protein, e.g. a mucin protein present on ocular, nasopharyngeal, tracheal and/or oral surfaces of a mammal. The two ISV are joined by a polypeptide linker.

IPC Classes  ?

• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
• C07K 16/46 - Hybrid immunoglobulins

Abstract

The present disclosure relates generally to compositions and methods for modulating signal transduction mediated by interleukin-10 (IL-10). In particular, the disclosure provides novel IL-10 polypeptide variants with altered binding affinity to interleukin-10 receptor subunit beta (IL-10Rb). Also provided are compositions and methods useful for producing such IL-10 polypeptide variants, as well as methods for modulating IL-10-mediated signaling, and/or for the treatment of conditions associated with the perturbation of signal transduction mediated by IL-10.

IPC Classes  ?

• A61K 38/00 - Medicinal preparations containing peptides
• A61K 38/16 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• A61K 38/20 - Interleukins
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
• C07K 14/00 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses

Abstract

Provided herein are compositions comprising a calcineurin inhibitor and a nonsteroidal anti-inflammatory drug (NSAID) and related methods of administering such compositions for preventing post-ERCP pancreatitis (PEP).

IPC Classes  ?

• A61K 38/13 - Cyclosporins
• A61K 9/02 - Suppositories; Bougies; Bases for suppositories or bougies
• A61K 31/405 - Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• A61L 31/16 - Biologically active materials, e.g. therapeutic substances
• A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes

Abstract

Methods are provided for non-invasively determining the expression of genes of interest by inference and the use thereof in cancer classification and stratification for treatment. The methods are based on an integrated analytic method, where a single biomarker is derived from promoter fragment entropy (PFE) and analysis of nucleosome depleted regions (NDR) depth. In some embodiments the methods use only noninvasive blood draws, and robustly identify which patients will achieve durable clinical benefit from immune checkpoint inhibition, what the cancer subtype classification is and/or what the tumor burden is. In an embodiment, the methods further comprise selecting a treatment regimen for the individual based on the analysis.

IPC Classes  ?

• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• G16B 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation

Abstract

Provided herein are compositions, systems, and methods for the generation, identification, and characterization of effector domains for activating and silencing gene expression. In particular, high throughput systems are provided to discover and characterize effector domains.

IPC Classes  ?

• C12N 9/64 - Proteinases derived from animal tissue, e.g. rennin
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• G01N 33/53 - Immunoassay; Biospecific binding assay; Materials therefor
• G01N 33/567 - Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagent utilising isolate of tissue or organ as binding agent

Abstract

Provided are protease inhibitor compounds that find use in treating or preventing coronavirus disease. In some embodiments, the coronavirus disease is COVID-19. Also provided are compositions and kits comprising the compounds, as well methods of using the compounds to treat or prevent coronavirus disease. Methods of assessing inhibition of coronavirus protease activity by an agent are also provided.

IPC Classes  ?

• C07K 5/083 - Tripeptides the side chain of the first amino acid being acyclic, e.g. Gly, Ala
• A61K 38/05 - Dipeptides
• A61K 38/06 - Tripeptides
• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
• A61P 31/14 - Antivirals for RNA viruses
• C07K 5/078 - Dipeptides the first amino acid being heterocyclic, e.g. Pro, His, Trp

Abstract

Described herein is a microfluidic chip comprising a first channel in fluid communication with an adjacent second channel through a opening, wherein the height of the first channel and the second channel are chosen to generate sufficient surface tension at the opening such that a liquid injected into the first channel or the second channel is substantially confined within the first channel or the second channel, respectively, or that flow of the liquid therebetween is controlled, the surface tension producing a non-physical microfluidic barrier that limits or selectively controls passage of the liquid. Also described are in vitro microphysiological systems that use such microfluidic chips in modeling the structure and functions of human organs, such as a blood-brain barrier, and studying in vivo-like physiological responses of such organs to various investigative or therapeutic agents.

IPC Classes  ?

• B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
• B01J 19/00 - Chemical, physical or physico-chemical processes in general; Their relevant apparatus
• C12M 1/00 - Apparatus for enzymology or microbiology
• C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus
• C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means

Abstract

A polyacrylamide-based copolymer reduces or prevents aggregation of biologic molecules including proteins, peptides, and nucleic acids, and lipid-based vehicles such as liposomes, lipid nanoparticles, polymerosomes, and micelles, in aqueous formulations at hydrophobic interfaces, thereby increasing the thermal stability of the molecules in the formulation. Methods and compositions comprising the copolymer and a protein or the copolymer and insulin can be used for treating conditions including diabetes.

IPC Classes  ?

• C12N 11/08 - Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer

Abstract

The present disclosure relates generally to compositions and methods for modulating signal transduction mediated by interleukin-12 and interleukin-23. In particular, the disclosure provides novel variants of interleukin-12 subunit p40 with reduced binding affinity to IL- 12RPß1. Also provided are compositions and methods useful for producing such IL-12p40 polypeptide variants, as well as methods for modulating IL-12p40-mediated signaling, and/or for the treatment of conditions associated with perturbations of signal transduction mediated by IL- 12p40.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 37/02 - Immunomodulators

Abstract

Process for making a mixed oxide according to the formula Li1+xTM1-xO2 wherein x is in the range of from 0.1 to 0.2 and TM is a combination of elements according to general formula (I) (NiaCobMnc)1-dM1d (I) wherein a is in the range of from 0.30 to 0.38, b being in the range of from zero to 0.05, c being in the range of from 0.60 to 0.70, and d being in the range of from zero to 0.05, M1 is selected from Al, Ti, Zr, W, Mo, Nb, Ta, Mg and combinations of at least two of the forego-ing, a + b + c = 1, said process comprising the following steps: (a) providing a particulate hydroxide, oxide or oxyhydroxide of manganese, nickel, and, optionally, at least one of Co and M1, (b) adding a source of lithium, (c) calcining the mixture obtained from step (b) thermally under an atmosphere comprising 0.05 to 5 vol.-% of oxygen at a maximum temperature the range of from 650 to 1000°C.

IPC Classes  ?

• C01G 53/00 - Compounds of nickel

Abstract

The present disclosure relates generally to compositions and methods for modulating signal transduction mediated by interleukin-22 (IL-22). In particular, the disclosure provides novel IL-22 polypeptide variants with altered binding affinity to interleukin- 10 receptor subunit beta (IL-10Rß). Also provided are compositions and methods useful for producing such IL-22 polypeptide variants, as well as methods for modulating IL-22-mediated signaling, and/or for the treatment of conditions associated with the perturbation of signal transduction mediated by IL-22.

IPC Classes  ?

• C07K 14/54 - Interleukins (IL)
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 35/00 - Antineoplastic agents

Abstract

Methods are provided for the efficient differentiation of hPSCs into HSC-like cells and endothelial cells in defined, monolayer conditions solely using extracellular signals to guide differentiation. The instant disclosure also provides methods of screening for cellular responses of the generated hematopoietic stem cells, endothelial cells and derivatives thereof. Treatment methods making use of the generated hematopoietic stem cells and endothelial cells are also provided. The instant disclosure also provides systems, compositions, and kits for practicing the methods of the disclosure.

IPC Classes  ?

• C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
• C12N 5/0735 - Embryonic stem cells; Embryonic germ cells
• C12N 5/077 - Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells
• C12N 5/0775 - Mesenchymal stem cells; Adipose-tissue derived stem cells

Abstract

Formulations of anti-CD47 antibodies having a pharmacologically acceptable concentration and stable shelf life are provided.

IPC Classes  ?

• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• A61K 47/10 - Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• A61K 47/12 - Carboxylic acids; Salts or anhydrides thereof
• A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells

Abstract

Adaptive graft assemblies and methods of manufacture and implantation are provided herein. In particular, such grafts can be 3D printed and can be defined as standard designs or patient-specific, external sheaths customized for specific vein graft dimensions following minimally/non-invasive vein mapping and computational modeling. The external sheath may include one or more layers of various biomaterials to produce customized biomechanical properties. The external sheath may be made to elute specific bioactive drugs allowing for pharmacologic prevention of adverse remodeling in addition to mechanical support. These customizable features may be tailored for each patient individually depending on specific medical history, including hypertension, diabetes, smoking history, anatomy or any pertinent patient attribute. These methods protect vascular grafts, specifically venous grafts, from immediate exposure to arterial pressure that can induce adverse remodeling and graft failure, thereby providing a precision medicine solution to cardiovascular bypass surgery.

IPC Classes  ?

• A61F 2/06 - Blood vessels
• A61F 2/07 - Stent-grafts
• A61B 17/11 - Surgical instruments, devices or methods, e.g. tourniquets for closing wounds, or holding wounds closed, e.g. surgical staples; Accessories for use therewith for performing anastomosis; Buttons for anastomosis
• A61F 2/04 - Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
• A61L 27/04 - Metals or alloys
• A61L 27/56 - Porous or cellular materials
• A61L 27/58 - Materials at least partially resorbable by the body

Abstract

Methods of inhibiting a respiratory virus, (i.e., a virus associated with a respiratory condition, e.g., influenza A, influenza B, RSV, etc.) in a sample are provided. Aspects of the methods include contacting a sample comprising viral RNA (vRNA) having a target motif with an effective amount of an agent that specifically binds the target motif to inhibit the respiratory virus. Also provided are methods of treating or preventing respiratory virus infection in a subject. Also provided are compounds and pharmaceutical compositions comprising an oligonucleotide sequence complementary to a target vRNA region that find use in the subject methods.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 31/16 - Antivirals for RNA viruses for influenza or rhinoviruses
• C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof

Abstract

Methods are described herein for facilitating tissue regeneration in humans and other large organisms, and kits therefor. Application of an inhibitor of focal adhesion kinase (FAK) to injured tissue may reduce fibrosis and/or scarring during the wound healing process. Patient care for a large number of fibrotic diseases which affect organ function may be ameliorated by such treatment. Kits for application of the FAK inhibitor may include a hydrogel formulation encapsulating the FAK inhibitor.

IPC Classes  ?

• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61K 31/33 - Heterocyclic compounds
• A61K 31/51 - Thiamines, e.g. vitamin B1
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 17/00 - Drugs for dermatological disorders
• A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

Abstract

The present disclosure provides recombineering-editing systems using CRISPR and recombination enzymes as well as methods, vectors, nucleic acid compositions, and kits thereof. The methods and systems provide means for altering target DNA, including genomic DNA in a host cell.

IPC Classes  ?

• C12N 15/09 - Recombinant DNA-technology
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C07K 14/195 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
• C07K 19/00 - Hybrid peptides
• C12N 9/22 - Ribonucleases
• C12N 9/78 - Hydrolases (3.) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C12N 15/62 - DNA sequences coding for fusion proteins
• C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

Methods of reversing hyperglycemia and suppressing diabetes onset in a patient at risk of developing type 1 diabetes are provided. In particular, a vector system comprising a first expression cassette encoding BCL2 associated X apoptosis regulator (BAX) and a hypermethylated second expression cassette encoding a secreted glutamic acid decarboxylase 65 (sGAD55) are administered to the patient to induce a tolerogenic response.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 15/117 - Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• C12N 9/10 - Transferases (2.)

Abstract

Variant IL-2 proteins and uses thereof are provided. In some embodiments, the IL-2 variant proteins have greater potency for activation of IL-2 signaling pathways in cells lacking CD25 expression, relative to wild-type IL-2.

IPC Classes  ?

• A61K 38/20 - Interleukins
• A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• A61K 47/62 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid

Abstract

Success in generating or curtailing seizures is related to their onset time, with inhibition proving less effective on earlier-onset afterdischarges. To identify targets for intervention, fMRI or simultaneous fMRI-LFP is used to map the seizure network of afterdischarges initiated from the dorsal and ventral hippocampus.

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
• G16H 30/20 - ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• A61H 33/00 - Bathing devices for special therapeutic or hygienic purposes
• A61N 5/06 - Radiation therapy using light
• G01R 33/48 - NMR imaging systems

Abstract

Processes and materials to protect nucleic acid molecules are described. Processes and materials to detect neoplasms from a biopsy are described. Processes and materials to build a sequencing library are described. Cell-free nucleic acids can be sequenced and the sequencing result can be utilized to detect sequences derived from a neoplasm.

IPC Classes  ?

• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 38/44 - Oxidoreductases (1)

Abstract

Processes and materials to detect neoplasms from a biopsy are described. Processes and materials to build a sequencing library are described. Processes and material to perform targeted sequencing are described. Processes and materials to mitigate confounding sources are described. Cell-free nucleic acids can be sequenced and the sequencing result can be utilized to detect sequences derived from a neoplasm.

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
• C12Q 1/6813 - Hybridisation assays
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• C40B 40/06 - Libraries containing nucleotides or polynucleotides, or derivatives thereof
• C40B 50/06 - Biochemical methods, e.g. using enzymes or whole viable microorganisms
• C40B 70/00 - Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or barcodes

Abstract

An ablation catheter for treating electrical rhythm disorders includes an array of sensor electrodes to detect electrical signals to determine a location of a target region for treatment. If the catheter is not optimally positioned at the target region, a controller uses the detected signals to guide movement of the catheter towards the target region. Once proper positioning is ascertained, the controller activates ablation components within the catheter to deliver energy to modify tissue at the target region.

IPC Classes  ?

• A61B 5/0245 - Measuring pulse rate or heart rate using sensing means generating electric signals
• G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
• G16H 20/00 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
• A61B 5/024 - Measuring pulse rate or heart rate
• A61B 18/14 - Probes or electrodes therefor

Abstract

Disclosed are chimeric antigen receptors comprising a CD2 co-stimulatory domain that retain function against CD58- and CD58low tumor cells, and CD2 co-stimulatory receptors that promote CAR function against CD58- and CD58low tumor cells.

IPC Classes  ?

• C12N 15/11 - DNA or RNA fragments; Modified forms thereof

Abstract

Compositions and methods are provided relating to FOXP3 gene edited hematopoietic cells, include hematopoietic stem and progenitor cells, lymphoid progenitor cells, and CD4+ T cells. The gene edited cells are useful in cellular therapy to restore normal immune functions and promote immune tolerance. In particular, CD4edFOXP3 T cells, which may be differentiated from FOXP3 gene edited hematopoietic progenitor cells, can physiologically express functional FOXP3 and exert normal immune responses as effector T cells or have immune suppressive characteristics as naturally occurring Treg cells.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals

Abstract

A method for synthesizing furan-2, 5-dicarboxylate (FDCA2-) is provided. Furan-2-carboxylate is provided with an inorganic base in the form of an inorganic base salt, wherein the furan-2-carboxylate and the inorganic base salt form a mixture. A CO2 gas is provided to the mixture. The mixture is heated to a temperature to at least partially melt the mixture, wherein the heating of the mixture causes the synthesizing of a MxFDCA solid, wherein MxFDCA denotes a salt comprising furan-2,5-dicarboxylate (FDCA2-) and cation M+ and/or M2+, where x is a number between 1 and 2, inclusive. The mixture containing furan-2-carboxylate is mechanically agitated, wherein the mechanically agitating breaks up the MxFDCA solid.

IPC Classes  ?

• C07C 51/02 - Preparation of carboxylic acids or their salts, halides, or anhydrides from salts of carboxylic acids
• C07C 51/15 - Preparation of carboxylic acids or their salts, halides, or anhydrides by reaction of organic compounds with carbon dioxide, e.g. Kolbe-Schmitt synthesis
• C07D 307/68 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Abstract

Wearable nystagmus detection devices are provided. The wearable device comprises first and second sensors configured to sense eye movement of the subject, and circuitry operably coupled to the sensors and configured to detect horizontal and vertical eye movements based on signals from the first and second sensors and/or a transmitter configured to transmit signals sensed by the first and second sensors to remote circuitry configured to receive signals transmitted by the transmitter and to detect horizontal and vertical eye movement based on signals from the first and second sensors. Also provided are systems and kits that include the devices, as well as methods for using devices and systems to monitor eye movement of a subject. The devices, systems, methods and kits find use in a variety of different applications.

IPC Classes  ?

• A61B 3/113 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for determining or recording eye movement
• A61B 5/103 - Measuring devices for testing the shape, pattern, size or movement of the body or parts thereof, for diagnostic purposes

Abstract

It is shown that ventral hippocampal kindling results in functional reorganization of the ventral hippocampal excitatory circuits. Most pronounced is the connectivity to the medial prefrontal cortex, with increased volume of activation on fMRI and increased amplitude of activation on electrophysiology. There is evidence of increased anxiety following kindling. Methods are provided for simultaneous LFP-fMRI to image single seizures. Imaging the spatiotemporal dynamics of individual seizures enables characterization of propagation patterns of focal and secondary-generalized seizures, that provide for targeted intervention.

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
• A61B 5/24 - Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
• A61N 1/36 - Applying electric currents by contact electrodes alternating or intermittent currents for stimulation, e.g. heart pace-makers

Abstract

Provided herein are methods and compositions for increasing blood-brain barrier permeability in a subject to enhance blood-brain barrier drug transport and methods and composition for identifying agents that regulate blood-brain barrier permeability.

IPC Classes  ?

• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61K 38/16 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• A61P 25/00 - Drugs for disorders of the nervous system
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

Disclosed herein are ladder polymers comprising fused aromatic and non-aromatic rings. Also disclosed are the manufacture and use of these ladder polymers, e.g., in separation membranes, such as membrane for gas separation.

IPC Classes  ?

• C08G 61/12 - Macromolecular compounds containing atoms other than carbon in the main chain of the macromolecule
• B01D 71/62 - Polycondensates having nitrogen-containing heterocyclic rings in the main chain
• B01D 71/64 - Polyimides; Polyamide-imides; Polyester-imides; Polyamide acids or similar polyimide precursors
• C08G 73/10 - Polyimides; Polyester-imides; Polyamide-imides; Polyamide acids or similar polyimide precursors