This disclosure provides novel neutralizing and potent anti-SARS-CoV-2 antibodies, related nucleic acids, related cells, related kits, related compositions, and related methods or uses.
Embodiments of the present invention are directed to compositions and methods for anti-HIV (anti-CD4 binding site) potent VRC01-like (PVL) antibodies targeted to gp120 having an amino acid substitution at a residue in the anti-CD4 binding site PVL antibody that is equivalent to Phe43 in CD4, these antibodies having improved potency and breadth.
This disclosure is based, at least in part, on an unexpected discovery that novel combination therapies of an anti-CD40 antibody or antigen binding fragment thereof and an IL-15 polypeptide exhibit synergistic activity in inhibiting tumor growth than any of the monotherapies of the anti-CD40 antibody or antigen binding fragment thereof and the IL-15 polypeptide. Thus, the combination therapy as disclosed herein represents a surprisingly effective therapy for cancer treatment with a reduced risk of treatment-related toxicity.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A multiplexing module implements receiving a plurality of laser pulses from a pulsed laser source via an input coupler element; splitting each laser pulse into a plurality of beamlets; introducing a delay between adjacent beamlets of the plurality of beamlets; and outputting a plurality of beamlets associated with each respective laser pulse via an output coupler element, wherein the input coupler and the output coupler are separate elements of the multiplexing module.
The present invention provides biological markers which are molecular markers and predictive of brain pathology and clinical status and/or outcome in Parkinson's disease (PD). The invention provides genes, RNA and protein markers that are associated with, relevant to, or predictive of Parkinson's disease (PD), Parkinson's disease with dementia (PDD), Parkinson's disease with dyskinesia or Parkinson's disease duration. The present invention further provides methods, kits and markers for the identification and monitoring of disease and disease aspects in Parkinson's patients and their application as markers and targets in and for evaluating, monitoring and treatment of Parkinson's disease and relevant pathologies and conditions associated with or developing in Parkinson's disease.
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 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
6.
1-OXOISOINDOLIN-2-YL AMIDE ACTIVATORS OF VCP AND DERIVATIVES THEREOF
Compositions and methods for stimulating VCP activity and treating various degenerative diseases are disclosed. 1-oxoisoindolin-2-yl amides of the following formula (I) stimulate VCP activity and are therefore useful for treating various degenerative diseases.
N-(3-substituted thiazaheterocyclylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamides, N-(3-substituted thiazaheterocyclylidene)-1H-pyrrolo[2,3-b]pyridine-4-carboxamides and N-(3-substituted thiazaheterocyclylidene)-1H-pyrrolo[3,2-b]pyridine-1-carboxamides
N-(3-substituted thiazaheterocyclylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamides, N-(3-substituted thiazaheterocyclylidene)-1H-pyrrolo[2,3-b]pyridine-4-carboxamides and N-(3-substituted thiazaheterocyclylidene)-1H-pyrrolo[3,2-b]pyridine-1-carboxamides
wherein the ring designated Q or Q′ is a five-, six-, or seven-membered heterocycle containing one sulfur and one nitrogen are disclosed. The compounds activate Yap and inhibit Lats kinases. They are therefore useful for treating hearing loss.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/444 - 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 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
A61K 31/554 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
8.
EXPANDING AND IMPROVING NANOBODY REPERTOIRES: TARGETING SARS-COV-2
SEATTLE CHILDREN'S HOSPITAL DBA SEATTLE CHILDREN'S RESEARCH INSTITUTE (USA)
Inventor
Cross, Frederick R.
Rout, Michael P.
Chait, Brian T.
Aitchison, John D.
Fridy, Peter
Ketaren, Natalia
Mast, Fred
Olivier, Paul
Abstract
Provided are anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) VHH antibodies, and methods of making and using the VHH chain antibodies.
The invention provides a polypeptide containing at least one IgG Fc region, wherein said at least one IgG Fc region is glycosylated with at least one galactose moiety connected to a respective terminal sialic acid moiety by a α 2,6 linkage, and wherein said polypeptide having a higher anti-inflammatory activity as compared to an unpurified antibody.
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
A61K 39/00 - Medicinal preparations containing antigens or antibodies
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
C07K 16/06 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies from serum
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
The present invention provides compositions comprising mTOR inhibitors and their use for sensitizing cells to leptin and for treating or preventing diseases or disorders associated with leptin deficiency or leptin resistance.
Methods and compositions for treating SARS-CoV-2 and COVID-19 are disclosed. Sulfonamide-1H-pyrrole-2-carboxamides of the following formula inhibit the SARS-CoV-2 methyltransferase enzyme NSP14 and are therefore useful for treating SARS-CoV-2 and COVID-19.
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
Methods and compositions for treating SARS-CoV-2 and COVID-19 are disclosed. 1,3-indole propanamides of the following formula (I) inhibit the SARS-CoV-2 PLpro/NSP3 protein and are therefore useful for treating SARS-CoV-2 and COVID-19.
Methods and compositions for treating SARS-CoV-2 and COVID-19 are disclosed. Sulfone-1H-pyrrole-2-carboxamides of the following formula inhibit the SARS-CoV-2 PLpro/NSP3 protein and are therefore useful for treating SARS-CoV-2 and COVID-19.
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
The invention provides broadly neutralizing antibodies directed to epitopes of Human Immunodeficiency Virus, or HIV. The invention further provides compositions containing HIV antibodies used for prophylaxis, and methods for diagnosis and treatment of HIV infection.
The present invention discloses novel agents and methods for diagnosis and treatment of melanoma. Also disclosed are related arrays, kits, and screening methods.
A61K 31/195 - Carboxylic acids, e.g. valproic acid having an amino group
A61K 31/136 - Amines, e.g. amantadine having aromatic rings, e.g. methadone having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 31/265 - Esters, e.g. nitroglycerine, selenocyanates of carbonic, thiocarbonic or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07C 217/54 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
C07D 233/64 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
C07F 9/6506 - Five-membered rings having the nitrogen atoms in positions 1 and 3
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
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
17.
NEUTRALIZING ANTI- SARS-COV-2 ANTIBODIES AND METHODS OF USE THEREOF
This disclosure provides novel neutralizing anti-SARS-COV-2 antibodies or antigen-binding fragments thereof. The disclosed anti-SARS-COV-2 antibodies constitute a novel therapeutic strategy in protection from SARS-COV-2 infections.
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
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
18.
METHODS OF TREATING ADENOCARCINOMA WITH HUMAN MICROBIOTA DERIVED N-ACYL AMIDES
The presently claimed and described technology provides methods of treating adenocarcinoma in a subject by administering a genetically engineered cell expressing a human microbial N-acyl synthase (hm-NAS) gene, an hm-NAS gene, an N-acyl amide, or compositions thereof.
A volumetric imaging system implements obtaining raw image data of a sample volume of a sample material, the raw image data comprising light field data of the sample volume acquired using a microlens array disposed in front of a camera; and analyzing the raw image data using an image analysis pipeline configured to localize the objects of interest in the raw image data to obtain classified image data in which the objects of interest have been identified, the image analysis pipeline being configured to process the raw image data to improve signal extraction at depth in the scattering material to maximize localization accuracy.
G06T 7/262 - Analysis of motion using transform domain methods, e.g. Fourier domain methods
G06T 7/70 - Determining position or orientation of objects or cameras
G06V 10/26 - Segmentation of patterns in the image field; Cutting or merging of image elements to establish the pattern region, e.g. clustering-based techniques; Detection of occlusion
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
H04N 23/55 - Optical parts specially adapted for electronic image sensors; Mounting thereof
H04N 23/81 - Camera processing pipelines; Components thereof for suppressing or minimising disturbance in the image signal generation
Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermen
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
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
A multi-photon imaging system includes a laser module having a first channel for outputting a two-photon excitation laser pulse and a second channel for outputting a three-photon excitation laser pulse. The system further includes a first optical path for guiding the two-photon laser pulse from the first channel of the laser module and a second optical path for guiding the three-photon laser pulse from the second channel of the laser module. A microscope is also provided for simultaneously receiving the two-photon laser pulse from the first optical path and the three-photon laser pulse from the second optical path, and simultaneously, or with well controllable delays, delivering the two-photon laser pulse and the three-photon pulse to a target volume. The system further includes a photodetector configured to collect photons generated within the target volume in response to simultaneous excitation of the target volume by both the two-photon laser pulse and the three-photon laser pulse.
Described herein are methods and compositions for accurate detection of cancer using ultrasensitive immunoassays, e.g., digital ELISA, to detect open reading frame 1 protein (ORF1p), which is encoded by the LINE-1 retrotransposon, in biofluids.
The present invention provides methods of generating diverse chemical structures on DNA through Wittig olefination of novel on-DNA phosphorane ylides and Homer- Wadsworth-Emmons reaction of on-DNA β-keto phosphonates. The methods of this invention provide access to DNA-encode libraries (DELs) of diverse peptides, peptidomimetics, chalcone-based molecules, and the like.
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
A61K 47/50 - 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
A61K 47/51 - 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
24.
Neutralizing Anti-SARS-CoV-2 Antibodies and Methods of Use Thereof
This disclosure provides novel broadly neutralizing anti-SARS-CoV-2 antibodies or antigen-binding fragments thereof. The disclosed anti-SARS-CoV-2 antibodies constitute a novel therapeutic strategy in protection from SARS-CoV-2 infections.
This disclosure is based, at least in part, on an unexpected discovery that the novel nanobodies and variants thereof are able to specifically bind afucosylated or sialylated IgG Fc glycoforms. Glycosylation of the IgG Fc domain is a major determinant of the strength and specificity of antibody effector functions, modulating the binding interactions of the Fc with the diverse family of Fcγ receptors. These Fc glycan modifications, such as removal of the core fucose residue, are newfound clinical markers for predicting severity of diseases, such as diseases caused by dengue virus (DENV) or SARS-CoV-2. However, it remains challenging to accurately distinguish specific IgG glycoforms without costly and time-intensive methods. The novel glycol-specific nanobodies and variants thereof, as disclosed herein, can be used as rapid clinical diagnostics or prognostics to risk stratify patients with viral and inflammatory diseases.
C07K 16/42 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against immunoglobulins (anti-idiotypic antibodies)
A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
The present invention generally relates to compositions comprising a CRISPR based regulatory element comprising a barcode sequence that serves as a binding site for a Cas9/gRNA molecule and which alters expression of a downstream gene when bound by the Cas9/gRNA molecule.
C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
27.
COMPOSITIONS AND METHODS FOR SYNTHESIZING MULTI-INDEXED SEQUENCING LIBRARIES
Provided herein are methods for preparing a sequencing library from a plurality of single cells that includes nucleic acids having three index sequences, as well as methods for generating an RNA sequencing library from single cells that can be used to dissect the critical regulators of gene-specific transcription, splicing, and degradation in a massive-parallel manner. Also provided herein are compositions, such as oligonucleotide sets for generating the sequencing libraries and kits for preparing the sequencing libraries.
AFFINITY CAPTURING AND DIRECTLY DETERMINING STRUCTURES OF PROTEINS AND OTHER MATERIALS ON SUPERPARAMAGNETIC BEADS BY CRYO-ELECTRON MICROSCOPY SINGLE-PARTICLE ANALYSIS
Paramagnetic beads capture a biological target molecule for cryo-electron microscope imaging. Two spacer modules extend from a periphery of the paramagnetic beads comprising a first spacer module and a second spacer module. The first spacer module binds the beads and the second spacer module binds the first spacer module. A capture module is linked to an outer location of the second spacer module. The capture module includes capture proteins that are adapted to capture target molecules. A method is also provided of using cryo-electron microcopy and the magnetic particles to image a biological target molecule.
G01N 1/42 - Low-temperature sample treatment, e.g. cryofixation
G01N 23/2251 - Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups , or by measuring secondary emission from the material using electron or ion microprobes using incident electron beams, e.g. scanning electron microscopy [SEM]
G01N 33/551 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
The present disclosure provides biological markers which are molecular and cellular antecedents of rheumatoid arthritis (RA) flares. The present disclosure provides RNA and protein markers that can predict an RA flare one or two weeks prior to the flare. The present disclosure further provides blood circulating cells, particularly pre-inflammatory mesenchymal cells, which are cellular precursors and indicators of an impending RA flare. The present disclosure further provides methods, kits and markers for identification and monitoring of flares in RA patients and their application as markers and targets in and for treatment of rheumatoid arthritis and conditions induced or related to rheumatoid arthritis.
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
This disclosure provides novel neutralizing and potent anti-SARS-CoV-2 antibodies, related nucleic acids, related cells, related kits, related compositions, and related methods or uses.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C07K 16/08 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses
Provided herein are HIV immunogens and uses thereof for generating an immune response in a subject. This disclosure further provides a method for treating or preventing a human immunodeficiency type I (HIV-I) infection in a subject using the disclosed HIV immunogens and/or antibodies generated by any of the methods disclosed herein.
Provided herein are agonistic antibodies, or antigen binding portions thereof, that bind to human CD40. Such antibodies optionally comprise Fc regions with enhanced specificity for FcγRIIb. The invention also provides methods of treatment of cancer or chronic infection by administering the antibodies of the invention to a subject in need thereof.
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
33.
BROADLY NEUTRALIZING ANTIBODIES TO TICK-BORNE ENCEPHALITIS AND RELATED VIRUSES
This disclosure provides novel broadly neutralizing anti-tick-borne encephalitis virus (TBEV) antibodies. The disclosed anti-TBEV antibodies represent a novel therapeutic strategy for preventing or treating diseases or infections caused by various tick-borne flaviviruses, including TBEV.
Provided are compositions and methods for producing large repertoires of recombinant single domain antibodies with high affinities and specificities against any antigen. Included are methods for making and identifying single domain antibodies produced by camelids, the single domain antibodies themselves, modifications of the nanobodies, expression vectors encoding the nanobodies, cDNAs encoding the nanobodies, cells comprising the expression vectors and/or cDNA, and methods of making the single domain antibodies re-combinantly Antigen-specific single domain antibodies and antigen binding fragments thereof having a Kd for the antigen in a sub-micromolar range are provided. The use of Protein M in isolating Ag-specific HCAbs, and digesting the isolated HCAbs using IdeS protease, is an aspect of this disclosure.
Provided herein are HIV immunogens and uses thereof for generating an immune response in a subject. This disclosure further provides a method for treating or preventing a human immunodeficiency type I (HIV-I) infection in a subject using the disclosed HIV immunogens and/or antibodies generated by any of the methods disclosed herein.
The present invention provides methods, compositions, and articles of manufacture useful for the prophylactic and therapeutic amelioration and treatment of gram-positive bacteria, and related conditions. The present invention provides compositions and methods incorporating and utilizing cationic nonribosomal lipopeptide antibiotics represented by Formulae (I)-(VI) or derivatives or variants thereof.
The current disclosure is directed to antibodies which inhibit coronaviruses, methods of making such antibodies, and the uses of such antibodies for the treatment and prevention of infection caused by coronaviruses.
The present invention provides methods, compositions, and articles of manufacture useful for treatment of multidrug-resistant pathogens and related conditions. The present invention provides compositions and methods incorporating and utilizing cilagicin compounds or derivatives or variants thereof.
The invention provides broadly neutralizing antibodies directed to epitopes of Human Immunodeficiency Virus, or HIV. The invention further provides compositions containing HIV antibodies used for prophylaxis, and methods for diagnosis and treatment of HIV infection.
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/08 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
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
41.
METHODS FOR THE TREATMENT OF MYELOID DERIVED SUPPRESSOR CELLS RELATED DISORDERS
The invention features methods of treating disorders related to increased levels of myeloid derived suppressor cells such as cancer or infections. The disclosure also provides methods of treating cancer including combinations of LXRβ agonists and immunotherapies such as PD1 inhibitors, PDL1 inhibitors, and adoptive T-cell transfer therapy.
Seattle Children's Hospital d/b/a Seattle Children's Research Institute (USA)
Inventor
Chait, Brian T.
Rout, Michael P.
Aitchison, John
Mast, Fred David
Olivier, Jean Paul
Fenyo, David
Abstract
Single-domain antibodies that bind the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) spike protein are disclosed. The single-domain antibodies include binding domains that bind epitopes of the Spike ectodomain inside and outside the receptor binding domain. The single-domain antibodies can be used for multiple purposes including in the research, diagnosis, and prophylactic or therapeutic treatment of COVID-19.
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
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
A61K 51/10 - Antibodies or immunoglobulins; Fragments thereof
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 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
43.
METAGENOME-GUIDED BIOSYNTHESIS AND COMPOUNDS AND METHODS OF USE THEREOF
The present invention provides methods, compositions, and articles of manufacture useful for the prophylactic and therapeutic amelioration and treatment of gram-positive bacteria, and related conditions. The present invention provides compositions and methods incorporating and utilizing antibiotics represented by Formulae (I)-(IX) or derivatives or variants thereof.
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61K 31/055 - Phenols the aromatic ring being substituted by halogen
Disclosed herein are compositions and methods for detecting oligonucleotide molecules that can be ligated with high efficiency, and methods of using the oligonucleotides to tag DNA encoded libraries and to modify existing DNA encoded libraries to incorporate new functionalities. Also disclosed are compositions for increasing DNA solubility in non-aqueous solvents and assay systems for detecting compounds or conditions that increase the solubility or durability of DEL.
C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
C12Q 1/6837 - Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
This disclosure provides novel neutralizing and potent anti-SARS-CoV-2 antibodies, related nucleic acids, related cells, related kits, related compositions, and related methods or uses. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) produced a worldwide pandemic, infecting over 456 million people and responsible for over 6 million deaths. In the United States, the FDA authorized the use of three vaccines encoding prefusion-stabilized SARS15 CoV-2 spike: BNT162b2 from Pfizer-BioNtech, mRNA 1273 from Moderna, and an adenovirus based vaccine, Ad26.COV2.S from Janssen (1). While both mRNA-based vaccines were initially approved as two-dose primary vaccine regimens, the replication-incompetent adenovirus (Ad) 26 vector-based Ad26.COV2.S vaccine received FDA emergency authorization as a single-shot vaccine.
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 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/06 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies from serum
C07K 16/08 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses
47.
SEQUENCE SPECIFIC DEGRADATION OF SINGLE-STRANDED POLYNUCLEOTIDES WITH CARD1 NUCLEASE
Provided is an isolated or recombinantly expressed protein comprising the sequence of SEQ ID NO: 1 (CARD1), or an amino acid sequence that is at least 90% identical to the sequence of CARD1. Methods for producing and isolating the CARD1 protein are provided. Also provided are methods that include using CARD1, Cas1O and RNA obtained from a biological sample, and a guide RNA targeted to an RNA polynucleotide that may be in the biological sample, and determining whether or not the CARD1 cleaves a reporter ssDNA or reporter ssRNA that is added to the sample, to determine the presence or absence of the RNA polynucleotide. Kits for use in the assay are also provided.
NSERM(Institut National de la Santé la Recherche Médicale) (France)
Assistance Publique-Hôptiaux de Paris (APHP) (France)
Université Paris Cité (France)
Fondation Imagine (France)
Inventor
Casanova, Jean-Laurent
Abstract
The present invention provides methods, assays and kits for assessment of patients positive for SARS-CoV-2 infection and methods of diagnosis and treatment of COVID-19 disease and for assessment and evaluation of individuals prior to vaccination with live attenuated virus vaccines, particularly including yellow fever vaccines and COVID-19 vaccines, to assess risk for vaccine-associated disease and adverse events, and for evaluation, treatment and management of patients who develop vaccine-associated disease. The invention provides methods and assays for identification and characterization of inborn errors of type I interferon immunity and also auto-antibodies against Type I IFNs that are associated with severe COVID-19 disease or that are correlated and linked with vaccine-associated disease. The invention further provides methods of diagnosing and determining altered response to or susceptibility to SARS-CoV-2 infection or to live attenuated virus vaccines and for applicable and suitable treatment of COVID-19 disease or vaccine-associated disease.
This disclosure is based, at least in part, on an unexpected discovery that the novel nanobodies and variants thereof are able to specifically bind afucosylated or sialylated IgG Fc glycoforms. Glycosylation of the IgG Fc domain is a major determinant of the strength and specificity of antibody effector functions, modulating the binding interactions of the Fc with the diverse family of Fey receptors. These Fc glycan modifications, such as removal of the core fucose residue, are newfound clinical markers for predicting severity of diseases, such as diseases caused by dengue virus (DENV) or SARS-CoV-2. However, it remains challenging to accurately distinguish specific IgG glycoforms without costly and time-intensive methods. The novel glycol-specific nanobodies and variants thereof, as disclosed herein, can be used as rapid clinical diagnostics or prognostics to risk stratify patients with viral and inflammatory diseases, as well as therapeutics for patient treatment.
The present invention relates to anti-HIV antibodies. Also disclosed are related methods and compositions. HIV causes acquired immunodeficiency syndrome (AIDS), a condition in humans characterized by clinical features including wasting syndromes, central nervous system degeneration and profound immunosuppression that results in life-threatening opportunistic infections and malignancies. Since its discovery in 1981, HIV type 1 (HIV-1) has led to the death of at least 25 million people worldwide.
The present invention provides methods for rapid and efficient isolation and characterization of nucleic acid, particularly RNA, from small volume and self-collected samples, particularly saliva samples, to determine the presence or absence of infectious agent RNA, particularly viral RNA, particularly infectious viral RNA, particularly coronavirus. The invention provides methods for isolation and evaluation of infectious agent RNA from saliva samples, particularly viral agents, particularly coronavirus. The invention further provides methods and strategies for pooling samples and RNA to determine the presence or absence of infectious agent RNA, particularly viral RNA, particularly infectious viral RNA, particularly coronavirus, with regard to large numbers of samples at one time and in a single pooled test format.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
52.
ANTIBACTERIAL SYNTHETIC-BIOINFORMATIC NATURAL PRODUCTS AND USES THEREOF
The present invention relates to novel compounds and compositions thereof that are useful as antimicrobial agents. The present invention also relates to methods of generating said antimicrobial compounds and compositions thereof as well as methods for treating or preventing a bacterial infection using said compounds or compositions thereof. The present invention further discloses methods for preventing or reducing the growth or proliferation of microorganisms.
This disclosure provides anti-SARS-CoV-2 antibodies or antigen-binding fragments thereof targeting the N-terminal domain (NTD) of the spike (S) protein. The disclosed anti-SARS-CoV-2 antibodies or antigen-binding fragments thereof have broadly neutralizing activities against several SARS-CoV-2 variants of concern. The disclosed anti- SARS-CoV-2 antibodies represent a therapeutic strategy in protecting from SARS-CoV-2 infections.
The present invention provides methods for isolation and characterization of nucleic acid, particularly RNA, from small volume and self-collected samples, including fingerstick blood samples, swabs and saliva samples. The RNA derived is intact and of sufficient quality and quantity for RNA analysis, longitudinal RNA sequencing and global transcriptomic profiling.
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
55.
MARKERS AND CELLULAR ANTECEENTS OF RHEUMATOID ARTHRITIS FLARES
The present invention provides biological markers which are molecular and cellular antecedents of rheumatoid arthritis (RA) flares. The invention provides RNA and protein markers that can predict an RA flare one or two weeks prior to the flare. The invention further provides blood circulating cells, particularly pre-inflammatory mesenchymal cells, which are cellular precursors and indicators of an impending RA flare. The present invention further provides methods, kits and markers for identification and monitoring of flares in RA patients and their application as markers and targets in and for treatment of rheumatoid arthritis and conditions induced or related to rheumatoid arthritis.
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
56.
USE OF LYTIC POLYSACCHARIDE MONOOXYGENASES, ENZYMATIC COMPOSITION CONTAINING SAME, AND DEGRADATION METHOD FOR PLASTIC POLYMERS
The present disclosure relates to the novel activity of the enzymatic composition containing lytic polysaccharide monooxygenases (LPMOs) that are bacterial (Auxiliary Activity 10, AA10) and/or fungal (Auxiliary Activity 9, AA9) for degrading polyethylene terephthalate (PET) and related plastic polymers. The genes that encode KpLPMO10A (AA10) and AfLPMO9A (AA9) were isolated from Kitasatospora papulosa and Aspergillus fischeri microorganisms, respectively. Methods such as atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) detected alterations in the superficial chemical composition and morphology of the PET found in liquid bottles when treated with LPMOs. The gentle temperature conditions used during the LPMO-PET reaction suit the use of these enzymes to help canonical enzymes (PETases) deconstruct plastics, which is beneficial for the circular economy for PET.
Provided is an anti-CRISPR protein (AcrVIA1), which acts as an inhibitor of the nuclease of Cas13. Cas13 recognizes complementary viral transcripts to trigger the degradation of both host and viral RNA during the type VI CRISPR-Cas antiviral response. AcrVIA1 is provided as an isolated or recombinantly expressed protein comprising the sequence of SEQ ID NO:1, or derivatives thereof, expression vectors that encode the same sequence, and methods of making and using proteins that comprise the same sequence, or derivatives thereof, for inhibiting the function of Cas13 and/or protein complexes and/or ribonucleoprotein complexes that comprise Cas13. The disclosure further includes use of the described inhibitor protein in improved diagnostic assays that include Cas13. Inclusion of the inhibitor is expected to preclude a requirement to reverse transcribe and/or create cDNA amplifications of the particular RNA that is the subject of the analysis.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
58.
Highly active agonistic CD4 binding site anti-HIV antibodies (HAADS) comprising modified CDRH2 regions that improve contact with GP120
Embodiments of the present invention are directed to compositions and methods for anti-HIV (anti-CD4 binding site) potent VRC01-like (PVL) antibodies targeted to gp120 having an amino acid substitution at a residue in the anti-CD4 binding site PVL antibody that is equivalent to Phe43 in CD4, these antibodies having improved potency and breadth.
This disclosure provides modified B cells which produce heterologous antibodies and co-express cargo proteins. The modified B cells may be stimulated by binding of a cognate antigen to the heterologous antibodies. The B cells may be reduced or eliminated by contacting the heterologous antibody with an anti-idiotypic antibody. Methods of making, and using the modified B cells for prophylaxis and therapy for a variety of conditions are provided. The B cells are modified at an IgH locus, an IgK locus, and combinations thereof. Modified B cells maintain allelic exclusion.
Disclosed are compositions and methods for measuring olfactory sensitivity, olfactory resolution, and combinations thereof. Such measurements can be made during a single test, or over consecutive tests, which may be performed during a single testing period, such as in a single day, or over a series of testing periods. The tests may be performed by a health care professional, or may be conveniently self-administered by the user.
The present disclosure provides biological markers which are molecular and cellular antecedents of rheumatoid arthritis (RA) flares. The present disclosure provides RNA and protein markers that can predict an RA flare one or two weeks prior to the flare. The present disclosure further provides blood circulating cells, particularly pre-inflammatory mesenchymal cells, which are cellular precursors and indicators of an impending RA flare. The present disclosure further provides methods, kits and markers for identification and monitoring of flares in RA patients and their application as markers and targets in and for treatment of rheumatoid arthritis and conditions induced or related to rheumatoid arthritis.
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
62.
MARKERS AND CELLULAR ANTECEDENTS OF RHEUMATOID ARTHRITIS FLARES
The present disclosure provides biological markers which are molecular and cellular antecedents of rheumatoid arthritis (RA) flares. The present disclosure provides RNA and protein markers that can predict an RA flare one or two weeks prior to the flare. The present disclosure further provides blood circulating cells, particularly pre-inflammatory mesenchymal cells, which are cellular precursors and indicators of an impending RA flare. The present disclosure further provides methods, kits and markers for identification and monitoring of flares in RA patients and their application as markers and targets in and for treatment of rheumatoid arthritis and conditions induced or related to rheumatoid arthritis.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Provided are compositions and methods that concurrently generate DNA insertions at two different genomic loci. The compositions and methods include a modified Adeno Associated Virus that contains two sequences configured for insertion into two separate mammalian chromosome loci. The method includes electroporation ribonucleoproteins that contain a Cas enzyme and guide RNAs that coordinate the insertion. The method provide for producing concurrent knock-in insertions that replace endogenous coding sequences, and can be used for producing antibodies.
An optical system for the detection of skin disease, such as melanoma, acquires images of a lesion on a subject's skin at different wavelengths and utilizes a sweeping arm rotating about the lesion in a clock-like sweep to produce diagnostically relevant metrics and classifiers from the image data so as to enhance detection of the skin disease.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 5/1455 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value using optical sensors, e.g. spectral photometrical oximeters
A multiplexing module provided herein is configured to perform operations of receiving a plurality of laser pulses from a pulsed laser source; splitting each laser pulse into a plurality of beamlets; introducing a delay between each adjacent beamlet of the plurality of beamlets, such that the plurality of beamlets associated with a respective laser pulse of the plurality of laser pulses is distributed equally across a pulse repetition period associated with the pulsed laser source; changing a divergence of each subsequent beamlet of the plurality of beamlets associated with each respective laser pulse to introduce a distinguishing feature between each beamlet of the plurality of beamlet to cause each beamlet to focus on a different axial plane or lateral position of the sample; and outputting the plurality of beamlets associated with each respective laser pulse.
G02B 27/28 - Optical systems or apparatus not provided for by any of the groups , for polarising
G02F 1/01 - Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour
The present disclosure provides antibody-drug conjugates comprising (i) antibodies that specifically bind to Mer Tyrosine Kinase (MERTK) (e.g., human MERTK, or both human and mouse MERTK), and (ii) cytotoxic agents conjugated directly to the antibodies or conjugated to the antibodies via linkers, and compositions comprising such antibody-drug conjugates, wherein the antibodies contained in the antibody-drug conjugates agonize MERTK signaling of endothelial cells. The present disclosure also provides methods for treating cancer, by administering an antibody-drug conjugate that comprises (i) an antibody that specifically binds to MERTK and agonizes MERTK signaling of endothelial cells, and (ii) a cytotoxic agent conjugated directly to the antibody or conjugated to the antibody via a linker.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
N-(3-Substituted thiazol-2(3H)-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamides and N-(3-substituted oxazol-2(3H)-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamides
N-(3-Substituted thiazol-2(3H)-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamides and N-(3-substituted oxazol-2(3H)-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamides
N-(3-Substituted thiazol-2(3H)-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamides and N-(3-substituted oxazol-2(3H)-ylidene)-1H-pyrrolo[2,3-b]pyridine-3-carboxamides
are disclosed. The compounds activate Yap and inhibit Lats kinases. They are therefore useful for treating hearing loss.
The present invention provides methods, compositions, and articles of manufacture useful for treatment of multi drug-resistant pathogens and related conditions. The present invention provides compositions and methods incorporating and utilizing menaquinone-binding compounds or derivatives or variants thereof.
The invention provides a polypeptide containing at least one IgG Fc region region, said polypeptide having a higher anti-inflammatory activity and a lower cytotoxic activity as compared to an unpurified antibody and methods of production of such polypeptide.
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
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
70.
COMBINATION OF ANTI-CD40 ANTIBODY AND IL-15 FOR TREATING CANCER
This disclosure is based, at least in part, on an unexpected discovery that novel combination therapies of an anti-CD40 antibody or antigen binding fragment thereof and an IL-15 polypeptide exhibit synergistic activity in inhibiting tumor growth than any of the monotherapies of the anti-CD40 antibody or antigen binding fragment thereof and the IL-15 polypeptide. Thus, the combination therapy as disclosed herein represents a surprisingly effective therapy for cancer treatment with a reduced risk of treatment-related toxicity.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present invention provides phase separation sensors capable of targeting or associating with one or more biomolecular condensate or membraneless compartment in cells. The phase separation sensors comprise at least two domains wherein a first domain comprises one or more accessory protein or molecule and a second domain comprises an artificial client protein or intrinsically disordered sequence. The artificial client protein possesses intrinsic disorder and is capable of engaging in ultra-weak phase separation-specific interactions with one or more component protein or molecule in a biomolecular condensate. Methods and applications utilizing the sensors are provided including targeting, detecting, visualizing, manipulating, monitoring a biomolecular condensate and delivering one or more functional protein, label, drug or agent to a biomolecular condensate.
The presently claimed and described technology provides methods of treating an inflammatory disease or disorder of the gastrointestinal tract in a subject by administering a genetically engineered cell expressing a lectin, a modified lectin gene encoding a lectin, a lectin, or compositions thereof, wherein the lectin is a non-enzymatic protein comprising a carbohydrate-binding domain.
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
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula
Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula
Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula
inhibit ENL/AF9 YEATS and are therefore useful for treating leukemia.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The present disclosure relates to a neural ectodermal lineage cellular structure, and compositions and methods related thereto. In some embodiments, the disclosure provides a geometrically isolated neural ectodermal lineage cellular structure (neuruloid) including spatially segregated neuroepithelial cells, sensory placodes, neural crest cells, and epidermal cells having radial organization around a lumen within the neuroepithelial cells. The disclosure also provides methods directed to forming the neural ectodermal lineage cellular structure. The disclosure also provides methods and platforms directed to the neural ectodermal lineage cellular structure.
This disclosure provides novel neutralizing anti-SARS-CoV-2 antibodies or antigen-binding fragments thereof. The disclosed anti-SARS-CoV-2 antibodies constitute a novel therapeutic strategy in protection from SARS-CoV-2 infections.
A multiplexing module (200) implements receiving a plurality of laser pulses from a pulsed laser source via an input coupler element (KM1); splitting each laser pulse into a plurality of beamlets; introducing a delay between adjacent beamlets of the plurality of beamlets; and outputting a plurality of beamlets associated with each respective laser pulse via an output coupler element (M3), wherein the input coupler (KM1) and the output coupler (M3) are separate elements of the multiplexing module (200).
The present invention provides methods, compositions, and articles of manufacture useful for the prophylactic and therapeutic amelioration and treatment of gram-positive bacterial infections, including drug resistant bacterial infections, and related conditions, or inhibiting the growth of or killing a bacterial cell. The present invention provides compositions and methods incorporating and utilizing macolacin antibiotics or derivatives or variants thereof.
C07K 7/60 - Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation occurring through the 4-amino group of 2,4-diamino-butanoic acid
C12P 21/04 - Cyclic or bridged peptides or polypeptides, e.g. bacitracin
80.
COMPOSITIONS AND METHODS TO TREAT METASTATIC GASTROINTESTINAL CANCER
The present invention relates to agents and methods for treating gastrointestinal cancer (e.g., metastatic colorectal cancer) in a subject in need thereof. The method includes suppressing the enzymatic activity of DHODH and/or decreasing the level of creatine via suppression of creatine transporter channel SLC6a8 in the subject. In some embodiments, the suppression step can be carried out by administering to the subject a set of small molecule compounds.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
The presently claimed and described technology provides methods of treating adenocarcinoma in a subject by administering a genetically engineered cell expressing a human microbial N-acyl synthase (hm-NAS) gene, an hm-NAS gene, an N-acyl amide, or compositions thereof.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
A volumetric imaging system implements obtaining raw image data of a sample volume of a sample material, the raw image data comprising light field data of the sample volume acquired using a microlens array disposed in front of a camera; and analyzing the raw image data using an image analysis pipeline configured to localize the objects of interest in the raw image data to obtain classified image data in which the objects of interest have been identified, the image analysis pipeline being configured to process the raw image data to improve signal extraction at depth in the scattering material to maximize localization accuracy.
The invention relates to mutations and alterations in the inflammatory pathway, including IL-18BP and IL-10RB mutations, that are associated with the development of fulminant viral hepatitis following viral infection, such as following hepatitis virus infection. The invention relates to methods for treating or ameliorating viral hepatitis comprising administering IL-18BP, IL-18 antagonist, IFNγ antagonist or inhibitor, and/or IL-10RB or an IL-10 antagonist.
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/513 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
Provided are broadly neutralizing antibodies (bNAbs) and antigen binding fragments thereof that bind with specificity to epitopes expressed by Hepatitis B vims (HBV). The bNAbs target non-overlapping epitopes on the HBV S antigen (HBsAg). Pharmaceutical compositions that contain the bNAbs, or modified bNAbs, are provided. Combinations of the bNAbs are included, and are useful for prophylaxis and therapy of HBV infection, and for inhibiting development of HBV escape mutations in infected individuals. Expression vectors encoding the bNAbs and antigenic fragments of them are included, as are methods of making the bNAbs and antigenic fragments of them. HBV peptides for use as vaccines are provided, and include at least two non-overlapping epitopes from the HBsAg. Diagnostic reagents comprising the bNAbs or antigenic fragments thereof are provided, as are methods of detecting HBV and diagnosing HBV infection.
Antibodies to Zika virus (ZIKV) and dengue 1 virus (DENV1) are provided. The amino acid sequences of the antibodies may be modified. Methods for prophylaxis and/or therapy by administering the antibodies and combinations thereof are provided. Immunological detection methods using the antibodies are provided. Also provided are vaccine compositions which comprise peptides derived from ZIKV and DENV1.
The present disclosure relates to a method of inducing a neuroprotective state comprising administering a Bromodomain and Extra-Terminal motif (BET) inhibitor under conditions effective to induce a neuroprotective state. Also disclosed are methods of preventing and/or treating neurodegenerative disease, methods of reducing microglial inflammation, and methods of restoring microglial homeostasis, where the methods include administering a Bromodomain and Extra-Terminal motif (BET) inhibitor.
A61K 31/5517 - 1,4-Benzodiazepines, e.g. diazepam condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/444 - 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 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
A61K 31/538 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
87.
ANTIBODIES AND METHODS FOR TREATMENT OF VIRAL INFECTIONS
The present invention provides antibodies that are capable of activating dendritic cell maturation and/or inducing a protective CDS response. The disclosed antibodies can be used to treat or inhibit viral infections, including prophylaxis and treatment of influenza A infection. The invention also provides nucleic acids that encode and immortalized B cells and cultured plasma cells that produce such antibodies.
This disclosure provides novel broadly neutralizing anti-HIV antibodies and antigen-binding fragments thereof. The disclosed anti-HIV antibodies exhibited improved biophysical properties, e.g, reduced polyreactivity, prolonged half-life, while retaining broad and potent neutralization activity. The anti-HIV bNAb variants as disclosed constitute a novel therapeutic strategy for treating and/or preventing HIV infection.
This disclosure is based, at least in part, on an unexpected discovery that the novel nanobodies and variants thereof are able to specifically bind afucosylated or sialylated IgG Fc glycoforms. Glycosylation of the IgG Fc domain is a major determinant of the strength and specificity of antibody effector functions, modulating the binding interactions of the Fc with the diverse family of Fcγ receptors. These Fc glycan modifications, such as removal of the core fucose residue, are newfound clinical markers for predicting severity of diseases, such as diseases caused by dengue virus (DENV) or SARS-CoV-2. However, it remains challenging to accurately distinguish specific IgG glycoforms without costly and time-intensive methods. The novel glycol-specific nanobodies and variants thereof, as disclosed herein, can be used as rapid clinical diagnostics or prognostics to risk stratify patients with viral and inflammatory diseases.
Provided are compositions and methods for producing eukaryotic cells that comprise homozygous modifications. The modifications include homozygous insertions of a modified open reading frame (a “mORF”), and removable surface displayed epitopes that can be used for separating cells that contain the homozygous modifications by Fluorescence-activated cell sorting (FACS). The inserted mORFs are configured so that they are in frame with an endogenous open reading frame and their expression can be controlled by an endogenous promoter. The homozygous insertions are produced using specialized double stranded DNA repair templates and CRISPR-based approaches, which provide for insertion of the homozygous modified ORFs, surface expression of two different epitopes that are separated from the modified ORFs by ribosomal peptide skipping domains, and separation and isolation of cells that contain the homozygous insertions, with concurrent or sequential removal of the epitopes using recombinase-mediated approaches. Cells made using the compositions and methods are also provided.
This disclosure provides novel neutralizing anti-SARS-CoV-2 antibodies or antigen-binding fragments thereof. The disclosed anti-SARS-CoV-2 antibodies constitute a novel therapeutic strategy in protection from SARS-CoV-2 infections.
This disclosure provides novel neutralizing anti-SARS-CoV-2 antibodies or antigen- binding fragments thereof. The disclosed anti-SARS-CoV-2 antibodies constitute a novel therapeutic strategy in protection from SARS-CoV-2 infections.
Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both.
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
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
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermen
Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both.
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
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
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermen
e.g.,e.g., SARS-CoV-2 RNA replicons) that can be trans-packaged for single-cycle delivery into a wide array of cell types and recapitulate all major enzymatic activities of intracellular viral replication. As a low-containment platform, the disclosed RNA replicons are broadly amenable to molecular virology studies and drug development screening efforts.
Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both.
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
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
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermen
This disclosure provides novel broadly neutralizing anti-SARS-CoV-2 antibodies or antigen-binding fragments thereof. The disclosed anti-SARS-CoV-2 antibodies constitute a novel therapeutic strategy in protection against SARS-CoV-2 infections.
Tri-cyclyl nitrogen-containing heterocyclic compounds
Tri-cyclyl nitrogen-containing heterocyclic compounds
Tri-cyclyl nitrogen-containing heterocyclic compounds
are disclosed. The compounds are inhibitors of human cGAS in interferon-producing cell types. They are thus useful as therapeutic agents for treating cGAS-related autoimmune diseases in humans.
A UV-C decontamination apparatus is used to decontaminate PPEs, such as respiratory masks. The apparatus is formed from a 3D printing process which makes the manufacture and use widespread. The apparatus includes a 3D printed chamber and a lid for enclosing the chamber. At least one UV-C lamp is supported in the chamber. Activation of the lamp is designed to decontaminate the mask supported in the chamber from the lid. An electronic switch assembly permits activation of the lamp only upon locking closure of a lid to the chamber. In a further embodiment, the hook is rotatable on the lid so as to rotate the mask in the chamber upon lamp activation.
A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
A61K 31/20 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
A61K 35/747 - Lactobacilli, e.g. L. acidophilus or L. brevis
