C07C 279/18 - Derivatives of guanidine, i.e. compounds containing the group the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
Baylor Research Institute d/b/a Baylor Scott & White Research Institute (USA)
Baylor College of Medicine (USA)
The Regents of the University of California (USA)
Inventor
Goel, Ajay
Li, Wei
Xu, Jianfeng
Abstract
Provided herein are, inter alia, methods of detecting DNA methylation levels in patients at risk of developing a gastrointestinal cancer, methods of diagnosing a patient with a gastrointestinal cancer based on DNA methylation levels, methods of monitoring DNA methylation levels in patients at risk of developing a gastrointestinal cancer, and methods of treating patients having a gastrointestinal cancer.
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
3.
ADENO-ASSOCIATED VIRUS COMPOSITIONS AND METHODS OF USE THEREOF
Provided herein, inter alia, are compositions and methods related to correcting intron 22 inversion in the F8 gene using AAVHSC-mediated nuclease-free genome-editing.
BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (USA)
Inventor
Qin, Hong
Kwak, Larry W.
Abstract
Provided herein are T cells expressing a chimeric antigen receptor (CAR) targeted to B cell activating factor receptor (BAFF-R). The CAR targeted to BAFF-R (BAFF-R CAR) described herein includes a domain that binds BAFF-R. Methods of making and using the BAFF-R CAR are also provided.
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 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
Provided herein, inter alia, are methods for expanding a population of human group 2 innate lymphoid cells (ILC2), and methods of treating cancer in a subject including administering to the subject the population of expanded human ILC2. Further provided are genetically engineered human ILC2s including chimeric antigen receptors, and methods of treating cancer in a subject including administering to the subject the genetically engineered human ILC2.
Provided herein are, inter alia, viral compositions and methods of using the same. The viral compositions provided include, inter alia, therapeutically effective amounts of a chimeric poxvirus and are particularly useful for methods of treating cancer. The chimeric poxviruses provided herein may further include transgenes.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07C 233/81 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
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
Disclosed herein are methods of treating cancer by increasing mRNA m6A methylation level and/or decreasing mRNA m6A demethylation in cancer stem cells. The methods entail administering an effective amount of one or more therapeutic agents to the subject. The therapeutic agents include an agent that induces overexpression of METTL3, an agent that induces overexpression of METTL14, an agent that inhibits FTO, an agent that inhibits ALKBH5, and an agent that inhibits TLX. Also disclosed are pharmaceutical compositions for treating cancer, which compositions include one or more such therapeutic agents.
A61K 31/196 - Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
A61K 31/245 - Amino benzoic acid types, e.g. procaine, novocaine
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
Provided herein are, inter alia, antibody compounds comprising an anti-immune cell antibody (e.g., anti-CD3 antibody) covalently bound to a CS-1-binding antibody; immune cells bound to compounds comprising an anti-immune cell antibody (e.g., anti-CD3 antibody) covalently bound to a CS-1-binding antibody; humanized OKT3 antibodies; pharmaceutical compositions; and methods for treating cancer, such as multiple myeloma.
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
Provided herein are functionalized monoclonal antibodies (mAbs) including antibody fragments covalently linked to a peptide compound through a disulfide linkage. The disulfide linkage is between a cysteine in the Fab region of the antibody or fragment thereof and a thiol moiety of a side chain amino acid of the peptide compound. The covalently formed complexes including provided herein form highly stable and versatile drug delivery and diagnostic compositions.
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 31/4995 - Pyrazines or piperazines forming part of bridged ring systems
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 39/00 - Medicinal preparations containing antigens or antibodies
inter aliainter alia, to compositions comprising and methods making and using iPSC-derived macrophages expressing a chimeric antigen receptor (CAR) targeted one or more tumor antigens (e.g., prostate stem cell antigen (PSCA)).
45 - Legal and security services; personal services for individuals.
41 - Education, entertainment, sporting and cultural services
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Online social networking services in the field of cancer patient support Providing a website featuring non-downloadable publications in the nature of articles in the field of cancer treatment and cancer care and news and events related to cancer treatment and cancer care Providing a web site featuring technology that enables users to organize and conduct interactive discussions and online meetings in the field of cancer treatment and cancer care Providing a website featuring information about health and wellness, namely, cancer treatment, cancer support groups and advice relating to cancer
14.
METHODS FOR DETECTING DYSFUNCTIONAL NK CELLS IN LEUKEMIA PATIENTS
The Board of Trustees of the Leland Stanford Junior University (USA)
Inventor
Swaminathan, Srividya
Maecker, Holden
Kumar, Anil
Duault, Caroline
Taghi Khani, Adeleh
Abstract
Provided herein are, inter alia, methods for identifying dysfunctional natural killer (NK) cells in a subject with leukemia. Provided are methods for treating leukemia, including administering to the subject an effective amount of allogeneic NK cells.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
15.
METHODS OF PREVENTING, TREATING, OR REDUCING THE SEVERITY OF CORONAVIRUS DISEASE 2019 (COVID-19)
Disclosed are methods of preventing or treating COVID-19 caused by a coronavirus infection or variants thereof by administration to a subject in need thereof a synthetic MVA-based vaccine. Also disclosed are methods of preventing or treating a coronavirus infection, or increasing an immune response in a subject who has previously received a SARS-CoV-2 vaccine by administration to the subject or a booster dose of a synthetic MVA-based vaccine.
Provided herein, inter alia, are genetically-modified natural killer (NK) cells capable of expressing platelet-derived growth factor (PDGF) and/or platelet-derived growth factor receptor (PDGFR); pharmaceutical compositions comprising the genetically-modified natural killer (NK) cells; methods of treating cancer with the genetically-modified natural killer (NK) cells; and methods of expanding a population of NK cells using PDGF.
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Chan, Puiyee Agnes
Schork, Nicholas J.
Choi, Yongwook
Abstract
Methods, kits, and oligonucleotides used in the detection of coronavirus, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are disclosed. In some aspects, the oligonucleotides are primers or probes used in the described methods or kits. The nucleotide sequence of the oligonucleotide consists of 300 or less, 150 or less, or 40 or less continuous nucleotides from a nucleotide sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO: 5, or is a variant thereof. In some embodiments, the oligonucleotide is modified with an internal spacer or a detectable label. For example, the 5′ terminus is labeled with a fluorophore and the 3′ terminus is complexed to a quencher of fluorescence of said fluorophore. In some embodiments, the nucleotide sequence of the oligonucleotide further comprises a universal tail sequence.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
A truncated EGFR (tEGFR) cell surface molecule and its uses is provided herein. The tEGFR cell surface molecule includes an EGFR domain IV and does not include an EGFR domain III and may be used, inter alia, as an in vivo tracking marker for genetically modified human T cells. Furthermore, the tEGFR cell surface molecule has cellular depletion potential through mediated through specific anti-domain IV EGFR antibodies. Thus, the tEGFR cell surface molecules provided herein may, inter alia, be used as a non-immunogenic selection tool, tracking marker, a depletion tool or a suicide gene for genetically modified cells having therapeutic potential.
Disclosed herein are methods and compositions for alleviating resistance to chemotherapy in a subject using one or more therapeutic agents that perturb the interaction between integrin β4 (ITGB4) and paxillin (PXN), e.g., by inhibiting the expression of ITGB4, PXN, or both. Also disclosed is a combinational therapy for treating cancer with a chemotherapeutic agent such as cisplatin or carboplatin and an inhibitor of ITGB4, PXN or both, such as carfilzomib.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
20.
METHODS OF PREVENTING, TREATING, OR REDUCING THE SEVERITY OF COVID-19 IN IMMUNOCOMPROMISED BLOOD CANCER PATIENTS
Disclosed are methods of preventing or treating a coronavirus infection in a blood cancer patient having received a cellular therapy by administration of a synthetic MVA-based vaccine.
Provided herein are, inter alia, novel peptide compositions having multi-specific binding capabilities useful for therapeutic and diagnostic purposes. The peptide compositions provided herein are polypeptide conjugates including at least two ligand binding domains able to target (bind) two or more ligands (e.g., antigens) at the same time. The peptide compositions provided herein can be produced at very high yields and are therefore easy to manufacture.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
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
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
Provided herein are functionalized monoclonal antibodies (mAbs) including antibody fragments, including those where a Fab-binding molecule (Fab binding moiety) linked to a steric hindering molecule (steric hindering chemical moiety) is mechanically interlocked (e.g., through noncovalent conjugation) with the antibody or antibody fragment. Also provided are compositions that form highly stable and versatile drug delivery and diagnostic compositions.
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
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
42 - Scientific, technological and industrial services, research and design
43 - Food and drink services, temporary accommodation
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Promoting public awareness of the need for cancer prevention and the need for healthy diets; business administration of research in the field of health, diet, nutrition, cancer and cancer prevention; Hospital gift store services Downloadable electronic newsletters in the field of medical care, healthcare, disease and chronic illness information, cancer detection and treatment Newsletters in the field of medical care, healthcare, disease and chronic illness information, cancer detection and treatment; Publications, namely, magazines, brochures and printed matter, namely pamphlets, all in the field of medical care, healthcare, disease and chronic illness information, cancer detection and treatment Online non-downloadable electronic newsletters in the field of medical care, healthcare, disease and chronic illness information, cancer detection and treatment; Educational conferences and training programs in the field of health and cancer detection, treatment and research; providing classes and workshops to nurses and other care providers in the field of medical care, healthcare, disease and chronic illness information, cancer detection and treatment; Education in the nature of providing fellowship and residency programs, seminars, and conferences for physicians in the field of medical care, healthcare, disease and chronic illness information, cancer detection and treatment; training in the nature of educational research and clinical work for physicians in the field of medical care, healthcare, disease and chronic illness information, cancer detection and treatment Medical and scientific research, namely conducting clinical trials Providing temporary housing accommodations to patients and families Healthcare services; telemedicine services; telehealth services; medical consultation; medical services; Community Outreach services, namely providing counseling programs in the field of diet and nutrition; charitable services, namely providing care packages consisting primarily of personal care items, namely skincare products, wigs and makeup to individuals suffering from disease
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Analyzing and compiling business data for natural language and data processing technology, data services for analytics and presentation of data in the field of healthcare; Business data analysis related to collection and compilation of information into technology platforms and databases in the field of medicine and healthcare; collection and systematization of information into technology databases; database management; electronic data collection services for business purposes in the fields of medicine, healthcare and data analytics. Downloadable computer software using artificial intelligence for processing and analyzing medical data for healthcare, medical research, and healthcare organizations Providing temporary use of non-downloadable web application for healthcare and patients to log in to the system, share medical records, patient information, schedule appointments, request prescription refills, make payments for medical bills, communicate with healthcare workers and review lab results, accessible online and by means of mobile application; data acquisition and collection for data ingestion, data filtering, data organization, data indexing, data extraction, data cleansing, data standardization, data services, analytics and presentation of data for data enrichment in the field of healthcare; Clinical research and testing services in the fields of healthcare, drug development and research, biotech and medtech devices and products, clinical consultation in the field of healthcare, drug development and research and healthcare policy research and development services; managing, monitoring and coordinating clinical studies on human subjects for others; data mining; cloud computing featuring software for use in extracting, analyzing, standardizing and cleaning clinical, financial and operational data, for ensuring data quality, for modeling outcomes, for visualizing data and for database management in the fields of medicine and healthcare; providing healthcare data analytics and healthcare informatics for clinical, operational, financial and business purposes for healthcare providers, researchers and the biotech and medtech industry; providing temporary use of non-downloadable computer software using artificial intelligence algorithms and machine learning to support platforms for healthcare related information and data, including clinical outcomes, diagnostics and medical data, clinical and research testing, genetic and genome information, financial information, social and demographic information related to the fields of oncology, comorbidities and other chronic conditions and diseases; providing temporary use of non-downloadable computer software, namely, algorithms and computer programs supporting a platform for retrieving, analyzing, aggregating, cleansing, harmonizing, monitoring and displaying patient level healthcare information, providing temporary use of non-downloadable computer software, namely, algorithms and computer programs supporting a platform for identifying trends related to patient treatment; artificial intelligence as a service (AIAAS) service featuring software using artificial intelligence for Personalized Healthcare; Consultancy in the field of artificial intelligence technology; Software as a service (SAAS) services featuring software using artificial intelligence for Personalized Healthcare; Technical consulting in the field of artificial intelligence (AI) software customization; Technology consultation in the field of artificial intelligence; software as a service (SAAS) services featuring software using artificial intelligence for processing and analyzing medical data for healthcare, medical research, and healthcare organizations
25.
CLOSTRIDIUM BUTYRICUM COMPOSITIONS AND METHODS OF USING THE SAME
Provided herein, inter alia, are methods and compositions for the treatment of graft-versus-host disease. The compositions include Clostridium butyricum. Administration of Clostridium butyricum can enhance gut biodiversity and improve clinical outcome of a patient undergoing allogeneic hematopoietic stem cell transplantation.
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Huentelman, Matthew
Mcdaniel, Timothy
Naymik, Marcus
Abstract
The present disclosure relates to alternative methods of conducting standard blood chemistry tests, the methods typically comprising: extracting an RNA from a blood sample, determining a mRNA level of a predictive gene in the blood sample, and converting the mRNA level of the predictive gene into the blood test result of the target blood component. The present disclosure also relates to blood test for performing the proxy methods. The blood test includes a plasmid with at least an exon of a predictive gene, a reagent for detecting a mRNA level of the predictive gene, and a reagent for detecting a mRNA level of a housekeeping gene.
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
27.
T CELLS FOR EXPRESSION OF CHIMERIC ANTIGEN RECEPTORS AND OTHER RECEPTORS
Methods for preparing T cell populations useful for a variety of purposes requiring a highly active, long-lived T cell population. The T cell populations are enriched for: naïve T cells (TN), memory stem cells (TSCM) and central memory T cells (TCM). These cell populations can be derived from peripheral blood mononuclear cells (PBMC) by both: 1) depleting unwanted cell populations such as CD14 expressing myeloid cells and CD25 expressing cells; and 2) enriching for CD62L expressing memory and naïve T cells.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Sharma, Sunil
Soldi, Raffaella
Sampson, Samuel
Abstract
The present disclosure includes compounds and methods for treating a subject having a cancer, in particular. Ewing's Sarcoma. A method of treating Ewing's Sarcoma in a subject may comprise the steps of administering to the subject a therapeutically effective amount of a first pharmaceutical composition comprising SP-2577 and administering to the subject a therapeutically effective amount of a second pharmaceutical composition selected from the group consisting of Ruxolitinib, Dasatinib, Nilotinib, Imatinib, Bosutinib, and a drug targeting ABL2 pathway. The drug targeting ABL2 pathway may be an ABL2 knockdown drug, i.e., an ABL2 inhibitor.
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
Disclosed herein are programmable, conditionally activated small interfering RNA constructs (Cond-siRNAs) and methods of making and using the same as therapeutic agents. The Cond-siRNA comprises a sensor strand, a core strand, and a guide strand, which crossover to form a sensor duplex and a RNAi duplex attached to each other to form a single structure. Upon binding an input strand to the sensor strand, the Cond-siRNA is activated and releases RNAi targeting a desired gene.
Provided herein are, inter alia, antibodies capable of binding human and non-human primate (e.g., cynomolgus) CD3. The anti-CD3 antibodies provided herein including embodiments thereof may be used for therapeutic purposes, for example, as humanized anti-CD3 antibodies, or they may form part of bispecific antibodies. Further provided herein are, inter alia, non-CD3 binding antibodies that are derived from the anti-CD3 antibodies provided herein including embodiments thereof, and which due to the presence of amino acid substitutions have lost their ability to bind to CD3.
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
31.
MOLECULAR TAGGING METHODS AND SEQUENCING LIBRARIES
The Translational Genomics Research Institute (USA)
Inventor
Murtaza, Muhammed
De Las Nieves Perdigones Borderias, Maria
Abstract
The invention provides a tagged sequencing library and methods for tagging low abundance target sequences and generating a sequencing library for detecting low abundance target sequences.
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligationUse of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6853 - Nucleic acid amplification reactions using modified primers or templates
Provided herein, inter alia, are compositions and methods related to correcting mutations in the F8 gene using AAVHSC-mediated nuclease-free genome- editing.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Halperin, Rebecca
Craig, David
Abstract
A system is provided that considers allele fraction shifts as a function of copy number and clonal heterogeneity. The system leverages differences between allele frequencies to differentiate between somatic and normal variants in impure tumor samples. In solid tumors, stromal cells and infiltrating lymphocytes are typically interspersed among the tumor cells. The normal cell contamination in tumors can be leveraged to differentiate somatic from germline variants. We explicitly model allelic copy number and clonal sample fractions so that we can examine how these factors impact the power to detect somatic variants. The system models the copy number alterations, which can also affect the allele frequencies of both somatic and germline variants. The expected allele frequencies can be calculated. The expected allele frequencies for somatic and germline differ with tumor content for different copy number alterations.
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
G16B 20/40 - Population geneticsLinkage disequilibrium
Provided herein are, inter alia, compositions comprising chimeric antigen receptor (CAR)-engineered immune cells, methods of formulating, and methods useful for treating cancer and leukemia.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
35.
METHODS FOR LIGATION-FREE CHROMATIN CONFORMATION CAPTURE WITH HIGH THROUGHPUT SEQUENCING
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Barthel, Floris P.
Chen, Yi-An
Fukushima, Noelle
Mdegbu, Ogechukwu
Abstract
Methods are provided to capture telomere-associated DNA loci from chromatin. Chromatin was prepared from cultured cells by dual crosslinking using formaldehyde and EGS, followed by sonication. Biotinylated PNA probes were hybridized to the telomere DNA sequences, and serine protease was used to release the telomere-associated DNA sequences. The released DNA fragments in the supernatant were purified and subjected to library preparation for next-generation sequencing. The ligation-free chromatin capture and sequencing method enriches specific telomere-associated DNA loci to provide an accurate representation of chromatin interaction. Insights into the chromatin interactions occurring at telomeres are used to investigate the potential role of telomers in aging and age-related diseases.
Disclosed are vaccine compositions comprising a VLP comprising two or more EBV envelope glycoproteins and one or more T cell antigens and methods of preventing or treating EBV infections using the vaccine compositions. Also disclosed is an expression system or a single expression vector for co-expressing two or more EBV envelope glycoproteins simultaneously to generate a VLP vaccine. The expression system may include a single vector inserted with two or more nucleic acid sequences that encode two or more EBV envelope glycoproteins linked by one or more linking sequences such that the EBV envelope glycoproteins are co-expressed simultaneously.
Disclosed herein are, inter alia, compounds inhibiting activity of pseudouridine synthase (PUS) and methods of use thereof for treating PUS associated conditions or disorders.
C07C 233/76 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
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 31/4409 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
A61K 31/4418 - Non-condensed pyridinesHydrogenated derivatives thereof having a carbocyclic ring directly attached to the heterocyclic ring, e.g. cyproheptadine
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61P 35/02 - Antineoplastic agents specific for leukemia
C07C 237/22 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
C07D 213/68 - One oxygen atom attached in position 4
C07D 217/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
39.
METHODS OF INDUCING ORGAN TRANSPLANTATION IMMUNE TOLERANCE AND ASSOCIATED COMPOSITIONS AND METHODS
Described herein are methods and transplant compositions for promoting or inducing organ transplant tolerance and/or immune tolerance by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of PD-L1+ donor-derived CD4+ T-depleted bone marrow cells. In certain embodiments, the methods may also include transplanting an organ, such as a solid organ, into the recipient. The transplant compositions may comprise a therapeutically effective amount of PD-L1+ donor-derived CD4+ T-depleted bone marrow cells and a donor organ.
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/7056 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
Provided herein are, inter alia, antibodies (e.g. humanized antibodies, monoclonal antibodies, antibody fragments (e.g., scFvs) and antibody compositions (e.g., chimeric antigen receptors, bispecific antibodies), which bind herpesvirus entry mediator (HVEM) with high efficiency and specificity. The antibodies and antibody compositions provided herein include novel light and heavy chain domain CDRs and framework regions and are, inter alia, useful for diagnosing and treating cancer and other HVEM-related diseases.
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
Systems and methods are configured to determine an effective local dose for a treatment procedure. The systems and methods are configured to determine a mean dose of a particle and a particle density at least a portion of tumor and at least a portion of normal tissue, perform a microdosimetry simulation or calculation, using the mean dose and the particle density, and determine the effective local dose, based on the microdosimetry simulation or calculation. A treatment plan can be arrived at pursuant to such systems and methods.
G16H 20/40 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
G16H 50/50 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
42.
ASSAYS FOR CHARACTERIZATION OF EXTRACELLULAR VESICLES AND METHODS OF USING THE SAME
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
CITY OF HOPE (USA)
THE GENERAL HOSPITAL CORPORATION (USA)
Inventor
Talisman, Tijana
Jensen, Kendall
Saftics, Andras
Das, Saumya
Abstract
Disclosed herein, in certain embodiments, are methods for isolation and characterization of extracellular vesicles (EVs) subpopulations derived from one or more target tissues of interest using a novel assay that combines affinity capture of EVs, super‑resolution microscopy, transcriptomic analysis, and proteomic analysis.
Provided herein are, inter alia, nucleic acid compounds useful for targeting CTLA-4-expressing cells and modulating cell activity of the CTLA-4-expressing cells. The compositions provided herein may be part of pharamceutcial compositions and may be used for treatment of cancer, inflammatory diseases, infectious diseases or metabolic diseases.
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
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
44.
NATURAL KILLER CELLS ENGINEERED TO REDUCE OR ELIMINATE CBL-B AND USES THEREOF
Described herein are compositions comprising human natural killer (NK) cells engineered to reduce or eliminate Cbl-b and with or without a chimeric antigen receptor (CAR), methods of making such compositions, and methods of using such compositions (e.g., killing cancer cells, treating a subject having cancer or viral infection).
BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (USA)
Inventor
Qin, Hong
Kwak, Larry W.
Li, Jingxing
Huang, Kexin
Abstract
Provided herein are BAFF-R antibodies as well as compositions and methods of making and using the same. The antibodies provided herein are, inter alia, useful for the treatment of cancer and autoimmune diseases.
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
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
46.
SYSTEM, DEVICE AND METHOD FOR PRODUCTION OF BIOPRODUCT INCLUDING HIGH DENSITY CELL RESPIRATOR (HDCR) FOR INTENSIFIED PRODUCTION OF ADENO-ASSOCIATED VIRUSES (AAV) AND CELL-BASED PRODUCTION
A cell cultivation apparatus for cultivating microorganisms and growing cells at high density is provided. The apparatus includes a membrane comprising multiple surface features on a first side of the membrane for cell placement. The surface features comprising one or more compartments within which a cell can be located. The membrane includes a material that is at least partially permeable to gas. A second side of the membrane defines a gas region. The second side of the membrane is separated from the first side of the membrane by the membrane. The apparatus further includes a media region for receiving media. The compartments are configured to at least partially reduce media flow shear forces on one or more cells in the compartments. The surface features may be ridges, protrusions, fins, wells, and/or posts.
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
48.
AMPLICON-BASED APPROACH FOR DETECTING DIFFERENCES IN NON-HUMAN DNA FRAGMENTATION PATTERNS BETWEEN CANCER AND NON-CANCER SAMPLES
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Tomasetti, Cristian
Lahouel, Kamel
Kosakovsky Pond, Stephanie J.
Trent, Jeffrey
Wike, Candice L.
Zismann, Victoria L.
Bates, Kameron
Abstract
Disclosed herein is a method of detecting cancer by amplifying two or more regions of interest in the DNA; analyzing the amplified product to determine a length distribution of sequences of the amplified product; and comparing with the analogous length distribution of a control. A statically significant difference in distribution compared to the control DNA sample indicates detection of cancer. A set of primers for each amplicon is used for PCR, preferably the primers used have about 10-25 base pairs motif followed by 4-8 base pair kmer in the 5' to 3' direction and 4-8 base pair kmer in the 3' to 5' direction followed by an about 10-25 bp motif. The amplified product here often comprises a first amplicon with an average length of 35 to 45 base pairs and a second amplicon with an average length of 55 to 65 base pairs between the 5' to 3' and 3' to 5' primers.
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 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
Provided herein are, inter alia, Interleukin-1 receptor accessory protein (IL1RAP) antibodies, fragments and variants thereof as well as recombinant proteins including IL1RAP antibody regions are useful for treating IL1RAP-expressing cancers.
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 TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Tomasetti, Cristian
Lahouel, Kamel
Kosakovsky Pond, Stephanie J.
Trent, Jeffrey
Wike, Candice L.
Zismann, Victoria L.
Bates, Kameron
Abstract
Disclosed herein is a method of detecting cancer by amplifying two or more regions of interest in the DNA; analyzing the amplified product to determine a length distribution of sequences of the amplified product; and comparing with the analogous length distribution of a control. A statically significant difference in distribution compared to the control DNA sample indicates detection of cancer. A set of primers for each amplicon is used for PCR, preferably the primers used have about 10-25 base pairs motif followed by 4-8 base pair kmer in the 5' to 3' direction and 4-8 base pair kmer in the 3' to 5' direction followed by an about 10-25 bp motif. The amplified product here often comprises a first amplicon with an average length of 35 to 45 base pairs and a second amplicon with an average length of 55 to 65 base pairs between the 5' to 3' and 3' to 5' primers.
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 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
This disclosure relates to, inter alia, cells expressing both a chimeric antigen receptor (CAR) and membrane bound IL-12 and the use of these cells to target and treat cancers (e.g., solid tumors and cancers expressing CD19, CD22, BCMA, PSCA, HER2, TAG-72, and PSCA). The disclosure also relates to cells expressing a membrane bound IL-12.
A method for machine learning enabled mortality prognosis may include training, based on a set of labeled training samples, a mortality prognosis model to determine a risk of patient mortality within a given timeframe such as one week, two weeks, three weeks, one month, three months, six months, nine months, one year, 18 months, two years, three years, five years, and/or the like. The trained mortality prognosis model may be applied to determine, based on a health record of a patient, a risk of mortality for the patient within the given timeframe. A treatment plan for the patient may be determined based on the risk of mortality for the patient within the given timeframe. Related systems and computer program products are also provided.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 10/20 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for electronic clinical trials or questionnaires
53.
PCNA INHIBITORS AND EGFR INHIBITORS FOR CANCER TREATMENT
Described herein are, inter alia, methods of treating cancer using an EGFR-TK inhibitor and a PCNA inhibitor, and pharmaceutical compositions comprising an EGFR-TK inhibitor and a PCNA inhibitor.
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 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Sharma, Sunil
Soldi, Raffaella
Altin, John
Trent, Jeffrey
Abstract
The present disclosure includes compounds and methods for treating a subject having a disease such as cancer. A treatment method includes administering to the patient a therapeutically effective amount of one or more peptides corresponding to a tumor neoantigen or administering to the patient a therapeutically effective amount of one or more oligonucleotides each having a nucleic acid sequence that encodes a peptide corresponding to a tumor neoantigen. The tumor neoantigens may be identified from patient-specific tumor mutations in the patient's tumor cells.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
55.
CANCER TREATMENT BY TARGETING PROTEINS OR INTERACTIONS OF EPHRINB-RGS3-KIF20A-SEPT7 AXIS
A method of treating cancer in a subject by targeting at least one of KIF20A, SEPT7, RGS3 and EphrinB or disrupting protein-protein interaction in the EPHRINB-RGS3-KIF20A-SEPT7 axis. The method entails administering to the subject an RNA-based inhibitor such as an siRNA, shRNA, or miRNA or a peptide inhibitor which targets at least one of KIF20A, SEPT7, RGS3 and EphrinB or blocks the binding of KID20A to RGS3 and/or SEPT7 or the binding of EphrinB and RGS3.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
Provided herein are, inter alia, novel antibodies that specifically bind to domain IV of EGFR and are able to effectively induce antibody dependent cell mediated cytoxicity (ADCC) against EGFR-expressing cells. In embodiments, the immunoglobulin and the Fab of the antibodies provided herein bind domain IV of EGFR with differential affinity. Thus, the antibodies provided herein provide for highly specific antibody therapeutics without adverse effects.
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
Disclosed is a method of treating or preventing a CMV infection in a recipient of a hematopoietic cell transplant (HCT). The method entails administering an effective amount of a CMV Triplex vaccine composition to a donor and/or recipient of the hematopoietic cells.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
59.
Use of endogenous viral vaccine in chimeric antigen receptor T cell therapy
Provided herein are, inter alia, methods and compositions including T cells expressing (i) a recombinant CAR protein which includes a peptide binding site and is capable of specifically binding cancer-specific antigens and (ii) a T cell receptor specific for a viral antigen (e.g., a CMV pp65 protein). The engineered T cells provided herein may be used in combination with a viral vaccine (e.g. cytomegalovirus (CMV) Triplex Vaccine) to treat a variety of cancers. The methods described herein also permit in vivo expansion of CMV-specific CAR T cells, instead of or in addition to ex vivo expansion, avoiding excessive T cell exhaustion that results in some cases from ex vivo manufacturing.
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
WISCONSIN ALUMNI RESEARCH FOUNDATION (USA)
Inventor
Murtaza, Muhammed
Budhraja, Karan K.
Abstract
Fragmentation patterns observed in plasma DNA reflect chromatin accessibility in contributing cells. Since DNA shed from cancer cells and blood cells may differ in fragmentation patterns, we investigated whether analysis of genomic positioning and nucleotide sequence at fragment ends can reveal the presence of tumor DNA in blood and aid cancer diagnostics. Whole genome sequencing data from >2700 plasma DNA samples including healthy individuals and patients with 11 different cancer types were analyzed. Higher fractions of fragments with aberrantly positioned ends were observed in patients with cancer, driven by contribution of tumor DNA into plasma. Genome wide analysis of fragment ends using machine learning showed overall area under the receiver operative characteristic curve of 0.96 for detection of cancer. These findings remained robust with as few as 1 million fragments analyzed per sample, indicating that analysis of fragment ends is a cost-effective and accessible approach for cancer detection and monitoring.
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
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
inter aliainter alia, are stem cells including an exogenous immunostimulatory protein, where the stem cells have a nucleic acid encoding a viral vector that expresses the immunostimulatory protein, and where the viral vector is an oncolytic virus. The disclosure further provides methods for treating diseases and disorders, such as infectious diseases or cancer and pharmaceutical compositions thereof.
Novel adeno-associated virus (AAV) vectors in nucleotide and amino acid forms and uses thereof are provided. The isolates show specific tropism for certain target tissues, such as blood stem cells, liver, heart and joint tissue, and may be used to transduce stem cells for introduction of genes of interest into the target tissues. Certain of the vectors are able to cross tightly controlled biological junctions, such as the blood-brain barrier, which open up additional novel uses and target organs for the vectors, providing for additional methods of gene therapy and drug delivery.
A method for self-service cohort selection may include receiving one or more user inputs specifying one or more cohort selection criteria. A script for accessing a first data store storing a first dataset may be generated based on the one or more cohort selection criteria. The script may be executed to retrieve, from the first dataset in the first data store, a subset of data. A second dataset corresponding to the first subset of data retrieved from the first data store may be generated for storage at the second data store. A visual representation of at least a portion of the second dataset may be generated for display at the client device. Related systems and computer program products are also provided.
G16H 10/20 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for electronic clinical trials or questionnaires
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
Disclosed herein are methods of treating Canavan disease in a subject through restoring ASPA enzymatic activities in the subject by expressing exogenous wild type ASPA gene in the brain of the subject. Also disclosed are a process of producing neural precursor cells, including NPCs, glial progenitor cells and oligodendroglial progenitor cells, which express an exogenous wild type ASPA gene and the neural precursor cells produced by this process.
C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings
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
Described are immune cells (e.g., macrophages) expressing a chimeric antigen receptor or polypeptide targeted to a tumor cell antigen (e.g., CD19 or HER2) and a secondary protein or polypeptide that includes an inhibitor of the SIRPa and CD47 interaction (e.g., SIRPa, CV1-Fc, B6H12, or CC6C2).
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
Provided herein are, inter alia, viral compositions and methods of using the same. The viral compositions comprise a virus including a nucleic acid encoding a MUC16 promoter operably linked to an essential viral gene. The compositions provided herein are contemplated to be particularly useful for treating CA-125 expressing cancers.
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
68.
SYSTEMS, METHODS, AND DEVICES FOR ROTATING INSULIN ADMINISTRATION SITES
The Translational Genomics Research Institute (USA)
Inventor
Blanchard, John
Rangasamy, Sampathkumar
Abstract
An application running on a device to manage insulin site rotation may read a configuration file including a group, a plurality of sites in the group, and an image associated with the group. The application may detect an input selecting a site from the plurality of sites for administration of an insulin management device. The application may also set the selected site as unavailable for a predetermined duration in response to the input selecting the site. A log entry may be written to track usage of the site in response to the input selecting the site. A visual indicator on the selected site may show that the site is recently selected in response to detecting the input selecting the site within a predetermined duration. The insulin management device may be a pump, a syringe, or a glucose monitor.
G16H 20/17 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
69.
BI-SPECIFIC TARGETED CHIMERIC ANTIGEN RECEPTOR T CELLS
T cells expressing a chimeric antigen receptor and a T cell receptor specific for CMV (bi-specific T cells) are described as a methods for using such cells in immunotherapy. In the immunotherapy methods, the recipient can be exposed to a CMV vaccine in order to expand and/or stimulate the be-specific T cells.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
70.
METHODS FOR TREATING AND PREVENTING B CELL DISORDERS
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
A61K 31/7125 - Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
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
Nucleic acid molecules that include a nucleotide sequence encoding a chimeric antigen receptor (CAR) and a nucleotide sequence encoding a protease sensitive scFv, wherein the chimeric antigen receptor comprises: an scFv targeting a tumor antigen, a spacer, a transmembrane domain, a co-stimulatory domain, and a CD3 ζ signaling domain; and the protease-sensitive scFv and the scFv target the same tumor antigen are described.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
This disclosure features novel cell lines and related methods for producing human natural killer (NK) cells, compositions of the NK cells produced by these methods, and uses thereof.
Disclosed herein are, inter alia, inhibitors of protein arginine methyltransferase 9 and pharmaceutical compositions thereof, and methods comprising the use of protein arginine methyltransferase 9 inhibitors for the treatment of a protein arginine methyltransferase 9-modulated disease or disorder, such as a hematological cancer.
The disclosure provides, inter alia, compounds comprising a phosphorothioated CpG oligodeoxynucleotide linked to a DNA oligonucleotide that is hybridized to another DNA oligonucleotide that contain a constrained nucleotide, pharmaceutical compositions containing the compounds, and methods of treating cancer using the compounds.
C12N 15/117 - Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
75.
AUTOMATIC ANALYZER OF MULTIDIMENSIONAL CYTOMETRY DATA
Systems, methods, and computer readable storage mediums for performing multidimensional cytometry data analysis are described. The method includes filtering multidimensional cytometry data, based on a signal strength within each dimension of the plurality of dimensions, to select representative dimensions from the plurality of dimension, selecting an initial region within the representative dimensions of the multidimensional cytometry data. The initial region can include a bin with a maximum significance level. A significant region of the representative dimensions, presenting a response different from a reference response, can be determined by expanding the initial region to regions with a set significance. A display including the significant region of the representative dimensions of the multidimensional cytometry data can be generated.
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Kasibhatla, Srinivas Rao
Kaadige, Mohan
Thode, Trason
Sharma, Sunil
Weston, Alexis
Abstract
Compounds having activity as kinase inhibitors are provided. The compounds have Structure (I), or a stereoisomer, tautomer, or salt thereof, wherein, R1, R3, and m are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods of use of the same for treatment of diseases and disorders are also provided.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
77.
PHOSPHOROTHIOATE NUCLEIC ACID CONJUGATES INCLUDING DNA EDITING ENZYMES
Provided herein are, inter alia, complexes useful for editing (e.g., repairing, modifying) DNA in a cell in vitro and in vivo. The complexes provided herein include a DNA editing agent bound to a phosphorothioate nucleic acid through a chemical linker. The chemical linker (e.g., disulfide linker) may be a linker that dissociates once the complex has entered the inside of the cell, thereby releasing the DNA editing agent and allowing the DNA editing agent to access and edit a cellular target sequence. The complexes provided herein exhibit high transfection efficiency and editing efficacy and therefore provide for useful therapeutic and diagnostic tools.
Provided herein are, inter ilia, methods and compositions for the treatment of cancer. The methods include administering a combination of an anti-STAT3-Toll-like receptor 9 (TLR9)-binding conjugate and a checkpoint inhibitor. The anti-STAT3-Toll-like receptor 9 (TLR9)-binding conjugate provide herein may be a CpG moiety bound to an anti-STAT3 siRNA through a covalent linker and the checkpoint inhibitor may be an anti-CTLA4 antibody. Administration of a combined effective amount of the anti-STAT3-Toll-like receptor 9 (TLR9)-binding conjugate and the checkpoint inhibitor results in surprisingly increased anti-tumor efficacy and CDS T cell activity.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (USA)
Inventor
Han, Haiyong
Cridebring, Derek
Halder, Kuntal
Abstract
The disclosure concerns methods and kits of diagnosis of pancreatic cancer and monitoring disease burden in patients diagnosed with pancreatic cancer, the method comprising quantitative determination of the concentration of extracellular vesicles that are positive for one, two or three markers selected from thrombospondin-2 (THBS2), alkaline phosphatase placental-like 2 (ALPPL2), and macrophage migration inhibitory factor (MIF) in the patients' fluid samples.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Disclosed herein are CMV-specific CARs. In some embodiments. the present invention is directed to a method of treating, reducing, or inhibiting an infection by a cytomegalovirus in a subject, which comprises administering to the subject (a) an expression vector that encodes a CMV-specific CAR as described herein, or (b) one or more cells that are transduced with the expression vector.
Disclosed is a method of preventing or treating acute GVHD (aGVHD) such as gut aGVHD, steroid-resistant aGVHD, and steroid-resistant gut aGVHD in a subject receiving a hematopoietic cell transplantation (HCT) or autoimmune colitis by administering to the subject an effective amount of an anti-IL-22 antibody, an anti-IL-6 antibody, donor-type CX3CR1hi MNPs, donor-type NK cells, a ceacam-1 antagonist, an anti-Gr-1 antibody, or a combination thereof.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
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 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
82.
METHODS OF PREPARING AND EXPANDING TYPE I INNATE LYMPHOID CELLS AND THERAPEUTIC USES THEREOF
Provided herein are, inter alia, compositions comprising ex vivo expanded ILC1 cells, methods of preparing the compositions, and methods useful for treating cancer and leukemia.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 35/02 - Antineoplastic agents specific for leukemia
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/078 - Cells from blood or from the immune system
inter alia The highly selective antibodies provided may be used, inter alia, as diabetes diagnostics targeting immunogenic DRiP proteins on pancreatic beta cells.
Intracellular delivery of a genetic construct to immune cells including: obtaining a deterministic mechanoporation (DMP) platform that includes a substrate having a surface and a plurality of capture sites, each said capture site having a boundary shape at the surface adapted and configured to support thereon a cell, and each said capture site having a bottom and including a sub-micron-scale projection extending from the bottom toward the surface of the substrate, wherein said projection is adapted and configured to penetrate a cell membrane and/or wall of the cell, and wherein the substrate has a plurality of aspiration vias situated at the bottom of the capture sites; introducing the cells to the surface in a liquid media; capturing the cells within the capture sites by applying a first hydrodynamic force; applying a second hydrodynamic force on the captured cell and locally rupturing the membrane and/or wall of the cell with the projection, introducing the genetic construct into the cells, and releasing the porated cells from the capture sites. Also disclosed are methods of chimeric antigen receptor (CAR) T cell adoptive immunotherapy and T cell receptor (TCR) therapy.
A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61K 39/42 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum viral
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
Disclosed is a method of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation (HCT) by administering to the subject an effective amount of an anti-IL-2 antibody such as an anti-IL-2-JES6 antibody.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
The disclosure provides, inter alia, fusion proteins comprising a zinc finger domain and a transcriptional activator, nucleic acids, vectors, and exosomes that can be used to activate transcription in a cystic fibrosis transmembrane conductance regulator gene and treat cystic fibrosis.
A61K 35/42 - Respiratory system, e.g. lungs, bronchi or lung cells
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Provided herein, inter alia, are compositions including engineered NK cells and methods for preparing the same. The engineered NK cells provided herein include integrated nucleic acid sequences encoding Cas9 proteins (e.g. dCas9). The engineered NK cells are contemplated to be effective for treating and/or preventing cancer, particularly leukemia.
Provided herein are, inter alia, kits and methods for the detection SARS-CoV-2 in COVID-19 patients. The kits and methods provided herein are, interalia, useful for the rapid detection of SARS-CoV-2 and related variants in, for example, the saliva of COVID-19 patients.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
A method for treating a patient comprising: (a) providing a composition comprising a population of T cells expressing both a chimeric antigen receptor (CAR) and a T cell receptor specific for a cytomegalovirus (CMV) antigen; (b) administering the composition to the patient; and (c) administering to the patient a viral vector encoding: (i) CMV pp65 and (ii) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) either prior to or subsequent to administering the composition comprising a population of T cells to the patient is described.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
Provided herein are, inter alia, KIAA0930 inhibitors, pharmaceutical compositions, and methods for treating and preventing wasting syndromes, such as cancer cachexia.
C07K 14/35 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Mycobacteriaceae (F)
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
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
Provided herein, inter alia, are methods of treating colorectal cancer, diagnosing colorectal cancer, and monitoring colorectal cancer using biomarkers, such as miRNA, such as miR-513a- 5p, miR-628-3p, miR-193a-5p, miR-210, miR-4304, miR-194-3p, miR-4453, or a combination of two or more thereof.
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 1/6837 - Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
96.
OLIGONUCLEOTIDES CONTAINING 2'-DEOXY-2'FLUORO-BETA-D-ARABINOSE NUCLEIC ACID (2'-FANA) FOR TREATMENT AND DIAGNOSIS OF RETROVIRAL DISEASES
THE ROYAL INSTITUTION FOR THE ADVANCEMENT OF LEARNING/MCGILL UNIVERSITY (Canada)
Inventor
Rossi, John J.
Damha, Masad J.
Aishwarya, Veenu
Takahashi, Mayumi
Li, Haitang
Abstract
The disclosure relates to synthetic oligonucleotides that bind at least a portion of a dimerization initiation site (DIS) of a retrovirus genomic ribonucleic acid (RNA) molecule. In some aspects, the synthetic oligonucleotides include a 2′-deoxy-2′-fluoroarabinonucleotide (2′-FANA)-modified nucleotide sequence. In some embodiments, the 2′-FANA-modified nucleotide sequence inhibits dimerization of retroviral genomes (e.g., an HIV genome). Other embodiments include methods of inhibiting expression of a retrovirus using the synthetic oligonucleotide, and methods of treating or preventing a retroviral infection.
Disclosed herein are methods of treating Canavan disease in a subject through restoring ASPA enzymatic activities in the subject by expressing an exogenous functional ASPA gene in the brain of the subject. Also disclosed are a process of producing neural precursor cells, including NPCs, glial progenitor cells and OPCs, which express an exogenous functional ASPA gene and the neural precursor cells produced by this process.
Disclosed herein are high-density lipoprotein-like nanoparticles (HDL-NP) having a soft material core (e.g., a lipid-conjugated inorganic core) associated with hydrophobic therapeutic agents. In some embodiments, the HDL-NPs are targeted to scavenger receptor type B1 (SR-B1). In some embodiments, the hydrophobic therapeutic agents are chemotherapeutic agents. Also disclosed herein are methods for treating disorders such as cancer with the HDL-NPs.
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
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 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
99.
TARGETED CHIMERIC ANTIGEN RECEPTOR MODIFIED T CELLS FOR TREATMENT OF IL13RALPHA2 POSITIVE MALIGNANCIES
Chimeric antigen receptors targeted to IL-13Ra2 are described. The targeting domain is a IL13 variant having increased specificity for IL-13Ra2 relative to IL-13Ra1.
Provided herein are, inter alia, SARS-CoV-2 spike (S) proteins; nucleic acids and plasmids encoding the proteins; vaccines and pharmaceutical compositions comprising the proteins, nucleic acids, or plasmids; methods for treating or preventing COVID-19; and methods for increasing immunity or providing acquired immunity to SARS-CoV in a subject.