The present disclosure relates generally to T cells, e.g., CAR T cells, which have been engineered to express immunomodulatory factors in a tumor-site specific manner. The engineered T cells and pharmaceutical compositions comprising the engineered T cells exhibit improved therapeutic efficacy and reduced toxicity when used for the treatment of cancer. In other embodiments contemplated herein, the present disclosure relates to genome editing systems for engineering T cells to express immunomodulatory factors in a tumor-site specific manner.
The present invention generally relates to T cells that are modified to enhance the efficiency of adoptive cellular therapy by modulating dendritic cell activity, a composition comprising modified T cells, vectors and methods for the treatment of cancer comprising administering modified T cells. In particular, the present invention provides modified T cells for use in adoptive cellular therapies for the treatment of solid tumours.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
The present disclosure relates generally to lipid nanoparticles (LNPs) and compositions comprising the same, and their use in delivery of agents, such as nucleic acid-based therapeutics, in particular to transfection recalcitrant cells and/or to lung tissue.
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
A61P 11/00 - Drugs for disorders of the respiratory system
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
4.
METHODS FOR THE ANALYSIS OF GENE EXPRESSION AND USES THEREOF
The present disclosure relates generally to methods for the analysis of gene expression. In particular, the methods of the present disclosure are based on the measurement of gene expression from fragments of cell-free DNA (cfDNA), which is useful in non-invasive methods for monitoring disease status in cancer patients and in methods for the treatment of cancer patients.
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
The present disclosure provides a crRNA comprising a spacer sequence that is capable of hybridizing to a target RNA sequence, wherein the target RNA sequence is within at least one hepatitis B virus (HBV) transcript, wherein the HBV transcript is selected from the group consisting of pre-core mRNA (pcRNA), pre-genomic RNA (pgRNA), pre-S mRNA, S mRNA, and X mRNA. In some embodiments, there is also provided RNA editing systems comprising the crRNAs disclosed herein, pharmaceutical compositions comprising the crRNAs or RNA editing systems disclosed herein, and methods for the treatment of a HBV infection using the crRNAs or RNA editing systems disclosed herein.
RGS16RGS1RGS2CLUCLU. In some embodiments, there is provided pharmaceutical compositions comprising the engineered T cell disclosed herein, and methods for the treatment of cancer using the engineered T cell disclosed herein. The present disclosure also provides genome editing systems, and methods for enhancing the function of a T cell using the genome editing systems disclosed herein.
THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC. (USA)
WOMEN'S HEALTH INTEGRATED RESEARCH CENTER, INOVA HEALTH SYSTEM (USA)
PETER MACCALLUM CANCER INSTITUTE (Australia)
Inventor
Bateman, Nicholas, W.
Abulez, Tamara
Conrads, Thomas, P.
Maxwell, George, L.
Pandey, Ahwan
Garsed, Dale
Bowtell, David
Abstract
Disclosed herein is a method of treating cancer in a subject in need thereof, comprising classifying a tumor from the subject as a homologous recombination deficient (HRD) tumor and administering a therapeutically effective amount of at least one DNA damage repair inhibitor to the subject when the tumor is classified as an HRD tumor. Also disclosed herein are methods of classifying a tumor as an HRD or HRP tumor and kits for use in classifying a tumor as an HRD or HRP tumor.
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 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
8.
CONDUCTOMETRIC SENSOR FOR DETECTING A NUCLEIC ACID AND A METHOD FOR THE DETECTION THEREOF
ROYAL MELBOURNE INSTITUTE OF TECHNOLOGY (Australia)
PETER MACCALLUM CANCER INSTITUTE (Australia)
Inventor
Ahmed, Taimur
Perera, Ganganath
Walia, Sumeet
Bhaskaran, Madhu
Sriram, Sharath
Fox, Stephen
Fellowes, Andrew
Abstract
The invention provides a sensor for detecting a nucleic acid, comprising: a substrate; a pair of terminal electrodes disposed on the substrate in mutually spaced apart and opposing relation; and a sensing element, between and in electrical contact with the pair of terminal electrodes, wherein the sensing element comprises: (i) a semiconducting portion of the substrate, wherein a conduction path between the terminal electrodes passes through the semiconducting portion; and (ii) an oligonucleotide on a surface of the semiconducting portion, the oligonucleotide being complementary to the nucleic acid to be detected, wherein hybridisation of the nucleic acid with the oligonucleotide leads to a change in resistance of the sensor.
The present disclosure relates generally to methods for the treatment of cancer with an immune checkpoint inhibitor. The present disclosure further relates to methods for the stratification of patients with cancer for treatment with an immune checkpoint inhibitor, and kits comprising one or more reagents or devices for use in performing the methods disclosed herein.
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 35/04 - Antineoplastic agents specific for metastasis
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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
10.
A METHOD OF PREPARING CELLS FOR ADOPTIVE CELL THERAPY
The present disclosure relates generally to methods for preparing T cell populations for adoptive cell therapy. In particular, disclosed herein are methods for preparing a population of T cells enriched for central memory T cells relative to effector T cells. The present disclosure further relates to populations of T cells enriched for central memory T cells prepared according to the methods described herein, and the use of populations of T cells enriched for central memory T cells for the treatment of cancer.
The present disclosure relates generally to fusion proteins comprising a truncated transforming growth factor beta receptor 2 (TGFBRII) and one or more intracellular co-stimulatory domains.
The present application is directed to bispecific polypeptides comprising a first domain binding an antigen on an antigen presenting cell (ARC) and a second domain binding an antigen on an immune cell expressing a chimeric antigen receptor (CAR). Nucleic acids, vectors and host cells used in producing the polypeptide of the invention are also disclosed. Compositions comprising the bispecific polypeptides and methods of treating cancer and stimulating activation and expansion of immune cells in vivo and in vitro are also disclosed.
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 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
e.g.e.g.e.g.e.g., a population of modified T cells). In particular embodiments, the modified T cells described herein are useful for the treatment of cancer or viral infections.
Processes for the synthesis of [8944 from [8944]4-salt are provided. The [8944 can be reacted with biomarker targeting agents to produce 89Zr labelled radiopharmaceuticals. The 89Zr labelled radiopharmaceuticals find use in, for example, non-invasive molecular imaging.
The disclosure provides methods of treating solid tumors with a combination of tucatinib, or salt or solvent thereof, and an anti-PD-1 antibody, or an antigen-binding fragment thereof. The disclosure also provides methods of treating solid tumors with a combination of tucatinib, or salt or solvent thereof, and an anti-PD-L1 antibody, or an antigen-binding fragment thereof.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present invention generally relates to methods of activating cells via the inhibition of PTP1B and PTPN2 for use in therapy. For example, the invention relates to preparing cells ex vivo for use in immunotherapy, particularly cancer immunotherapy. More specifically, the invention relates to methods for the preparation of leukocytes, particularly T cells, exhibiting cytotoxic properties for use in adoptive cell transfer. The invention also relates to cells and compositions including them for cancer immunotherapy. The invention also relates to methods of immunotherapy, particularly cancer immunotherapy.
The present disclosure relates generally to (CRISPR) RNA (crRNA) for the precision silencing of transcripts. In some embodiments, the crRNA are enriched for guanosine (G) nucleotides at key spacer positions, which is useful in enhancing the silencing efficacy of otherwise inefficient crRNA, thereby expanding the targeting spectrum of Cas13 endonucleases, e.g., Cas13b and Cas13d. In other embodiments, the crRNA comprise a spacer sequence having at least one nucleotide mismatch relative to the target RNA sequence, wherein the target RNA sequence is a wild-type transcript and/or a variant transcript (e.g., a transcript comprising a single nucleotide variant (SNV)). The present disclosure also provides RNA editing systems comprising the crRNA described herein in complex a Cas13 effector protein and a target RNA sequence, methods for the selective targeting of transcripts encoding proteins that are difficult to target, or are not amenable to pharmacological targeting, e.g., oncogenic fusion transcripts or oncogenic transcripts comprising single nucleotide variant(s), and methods for the design and selection of potent crRNA.
Provided herein are compounds of Formula (I) that are dual inhibitors of kinases and bromo-domain proteins. The disclosure also relates to pharmaceutical compositions containing such compounds, methods for using such compounds in the treatment of cancers, particularly, the treatment of multiple myeloma cancers, and to related uses.
Centre National de la Recherche Scientifique (CNRS) (France)
Institut National de la Santé et de la Recherche Médicale (INSERM) (France)
Institut Curie (France)
Peter MacCallum Cancer Institute (Australia)
Inventor
Rodriguez, Raphaël
Dawson, Mark
Garciaz, Sylvain
Caneque Cobo, Tatiana
Abstract
The invention relates compound of formula (I), enantiomers, mixture of enantiomers, diastereoisomers and mixture of diastereoisomers thereof: wherein W, X, Y and Z are as defined, for use in the treatment of Acute Myeloid Leukemia (AML).
The invention relates compound of formula (I), enantiomers, mixture of enantiomers, diastereoisomers and mixture of diastereoisomers thereof: wherein W, X, Y and Z are as defined, for use in the treatment of Acute Myeloid Leukemia (AML).
A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 35/02 - Antineoplastic agents specific for leukemia
The present invention relates to compounds and methods for the targeted delivery of diagnostic/therapeutic radionuclides to cancer tissue. In particular, the present invention relates to the targeted delivery of diagnostic/therapeutic radionuclides to cholecystokinin-2 receptor positive cancers and to methods for the diagnosis and treatment of cancer.
The present disclosure relates generally to T cells, e.g., CAR T cells, which have been engineered to express immunomodulatory factors in a tumor-site specific manner. The engineered T cells and pharmaceutical compositions comprising the engineered T cells exhibit improved therapeutic efficacy and reduced toxicity when used for the treatment of cancer. In other embodiments contemplated herein, the present disclosure relates to genome editing systems for engineering T cells to express immunomodulatory factors in a tumor-site specific manner.
ROYAL MELBOURNE INSTITUTE OF TECHNOLOGY (Australia)
PETER MACCALLUM CANCER INSTITUTE (Australia)
Inventor
Ahmed, Taimur
Perera, Ganganath
Walia, Sumeet
Bhaskaran, Madhu
Sriram, Sharath
Fox, Stephen
Fellowes, Andrew
Abstract
The invention provides a sensor for detecting a nucleic acid, comprising: a substrate; a pair of terminal electrodes disposed on the substrate in mutually spaced apart and opposing relation; and a sensing element, between and in electrical contact with the pair of terminal electrodes, wherein the sensing element comprises: (i) a semiconducting portion of the substrate, wherein a conduction path between the terminal electrodes passes through the semiconducting portion; and (ii) an oligonucleotide on a surface of the semiconducting portion, the oligonucleotide being complementary to the nucleic acid to be detected, wherein hybridisation of the nucleic acid with the oligonucleotide leads to a change in resistance of the sensor.
G01N 27/12 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon absorption of a fluidInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon reaction with a fluid
H01L 21/62 - Manufacture or treatment of semiconductor devices or of parts thereof the devices having no potential barriers
The present disclosure relates generally to methods for the analysis of gene expression. In particular, the methods of the present disclosure are based on the measurement of gene expression from fragments of cell-free DNA (cfDNA), which is useful in non-invasive methods for monitoring disease status in cancer patients and in methods for the treatment of cancer patients.
The disclosure provides methods of treating solid tumors with a combination of tucatinib, or salt or solvant thereof, and an anti-PD-1 antibody, or an antigen-binding fragment thereof. The disclosure also provides methods of treating solid tumors with a combination of tucatinib, or salt or solvant thereof, and an anti-PD-Ll antibody, or an antigen-binding fragment 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
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
The present application is directed to bispecific polypeptides comprising a first domain binding an antigen on an antigen presenting cell (ARC) and a second domain binding an antigen on an immune cell expressing a chimeric antigen receptor (CAR). Nucleic acids, vectors and host cells used in producing the polypeptide of the invention are also disclosed. Compositions comprising the bispecific polypeptides and methods of treating cancer and stimulating activation and expansion of immune cells in vivo and in vitro are also disclosed.
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 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 39/00 - Medicinal preparations containing antigens or antibodies
26.
NITROGEN-CONTAINING ANALOGS OF SALINOMYCIN FOR USE IN ACUTE MYELOID LEUKEMIA
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) (France)
INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) (France)
INSTITUT CURIE (France)
PETER MACCALLUM CANCER INSTITUTE (Australia)
Inventor
Rodriguez, Raphaël
Dawson, Mark
Garciaz, Sylvain
Caneque Cobo, Tatiana
Abstract
The invention relates compound of formula (I), enantiomers, mixture of enantiomers, diastereoisomers and mixture of diastereoisomers thereof: wherein W, X, Y and Z are as defined, for use in the treatment of Acute Myeloid Leukemia (AML).
A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61P 35/02 - Antineoplastic agents specific for leukemia
The present invention generally relates to T cells that are modified to enhance the efficiency of adoptive cellular therapy by modulating dendritic cell activity, a composition comprising modified T cells, vectors and methods for the treatment of cancer comprising administering modified T cells. In particular, the present invention provides modified T cells for use in adoptive cellular therapies for the treatment of solid tumours.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
Provided herein are compounds of Formula (I) that are dual inhibitors of kinases and bromo-domain proteins. The disclosure also relates to pharmaceutical compositions containing such compounds, methods for using such compounds in the treatment of cancers, particularly, the treatment of multiple myeloma cancers, and to related uses.
The present invention generally relates to methods of activating cells for use in therapy. For example, the invention relates to preparing cells ex vivo for use in immunotherapy, particularly cancer immunotherapy. More specifically, the invention relates to methods for the preparation of leukocytes, particularly T cells through PTP1B inhibition, exhibiting cytotoxic properties for use in adoptive cell transfer. The invention also relates to cells and compositions including them for cancer immunotherapy. The invention also relates to methods of immunotherapy, particularly cancer immunotherapy.
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
30.
METHODS OF ACTIVATING CYTOTOXIC LEUKOCYTES USING PTP1B AND PTPN2 INHIBITORS
The present invention generally relates to methods of activating cells via the inhibition of PTP1B and PTPN2 for use in therapy. For example, the invention relates to preparing cells ex vivo for use in immunotherapy, particularly cancer immunotherapy. More specifically, the invention relates to methods for the preparation of leukocytes, particularly T cells, exhibiting cytotoxic properties for use in adoptive cell transfer. The invention also relates to cells and compositions including them for cancer immunotherapy. The invention also relates to methods of immunotherapy, particularly cancer immunotherapy.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
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
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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 31/662 - Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
31.
BISPECIFIC POLYPEPTIDES FOR ENGAGEMENT OF CAR EXPRESSING IMMUNE CELLS WITH ANTIGEN PRESENTING CELLS AND USES 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 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
The present invention generally relates to T cells that are modified to enhance the efficiency of adoptive cellular therapy by modulating dendritic cell activity, a composition comprising modified T cells, vectors and methods for the treatment of cancer comprising administering modified T cells. In particular, the present invention provides modified T cells for use in adoptive cellular therapies for the treatment of solid tumours.
The present invention generally relates to methods of activating cells for use in therapy. For example, the invention relates to preparing cells ex vivo for use in immunotherapy, particularly cancer immunotherapy. More specifically, the invention relates to methods for the preparation of leukocytes, particularly T cells through PTP1B inhibition, exhibiting cytotoxic properties for use in adoptive cell transfer. The invention also relates to cells and compositions including them for cancer immunotherapy. The invention also relates to methods of immunotherapy, particularly cancer immunotherapy.
The present invention relates generally to a method of detecting a risk of the progression from a pre-invasive neoplasia of the glandular epithelium. More particularly, the present invention provides a method of detecting a risk of the progression from a pre-invasive breast neoplasia by screening for the level of expression of Stefin A in the myoepithelial cells. The method of the present invention is useful in a range of applications including, but not limited to, assessing a neoplastic condition, monitoring the progression of such a condition, predicting the likelihood of a subject progressing to a more advance disease state or informing decisions in relation to the design of treatment schedules.
G01N 31/00 - Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroupsApparatus specially adapted for such methods
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for 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
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present invention relates generally to a method of prognosing the survival of a patient with a breast neoplasm, more particularly a patient with a breast neoplasm which is estrogen receptor-/progesterone receptor-/HER-2-(“triple-negative”). The method of the present invention more particularly provides a method for prognosing breast cancer patient survival, in particular risk of metastatic spread, by screening for IRF9 expression. In a related aspect, the present invention provides a method of therapeutically or prophylactically treating patients with a triple-negative breast neoplasm, in particular those patients with triple-negative breast neoplasia which is characterised by a poor survival prognosis, still more particularly a high risk of metastatic spread, by upregulating type I IFN levels.
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
The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection). Preferred compounds of the invention are those of Formula II, as follows:
and pharmaceutically acceptable derivatives thereof.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 235/20 - Two benzimidazolyl-2 radicals linked together directly or via a hydrocarbon or substituted hydrocarbon radical
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 235/18 - BenzimidazolesHydrogenated benzimidazoles with aryl radicals directly attached in position 2
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
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
37.
METHODS OF TREATING BREAST CANCER AND REAGENTS THEREFOR
This disclosure relates to RNA interference (RNAi) reagents for treatment of breast cancer, compositions comprising same, and use thereof to treat individuals suffering from breast cancer as a monotherapy or in combination with a chemotherapeutic agent. In particular, the present disclosure relates to microRNAs (miRNAs) which affect viability of breast cancer cells.
An isolated T cell that is modified to express: a. at least one functional exogenous non-T cell receptor (TCR) that comprises a chimeric antigen receptor (CAR) comprising an antigen binding domain attached to at least one signalling domain; and b. at least one functional exogenous adenosine receptor, wherein the resulting CAR T cell is suitable for use in the treatment of cancer.
This disclosure relates to RNA interference (RNAi) reagents for treatment of neuroblastoma, compositions comprising same, and use thereof to treat individuals suffering from neuroblastoma as a monotherapy or in combination with a chemotherapeutic agent. In particular, the present disclosure relates to microRNAs (miRNAs) which affect viability of neuroblastoma cells.
The present disclosure relates generally to methods of treatment and the classification of subjects that will respond to such methods of treatment. In particular, the present disclosure provides a means to classify subjects who will respond to RNA Polymerase I (Pol I) inhibitor therapy and the treatment of subjects with a Pol I inhibitor or a treatment regimen comprising a Pol I inhibitor.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
The present disclosure provides combination therapy of a bromodomain inhibitor and an immune modulator (e.g., an immune check point inhibitor). The combination of the bromodomain inhibitor and the immune modulator may be useful in treating or preventing cancer in a subject. In certain embodiments, the subject has an intact immune system. The combination of the bromodomain inhibitor and the immune modulator is expected to be synergistic.
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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 31/495 - 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 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
A method, system and processing system for assessing a risk of an individual developing a breast cancer phenotype. The method (300) includes determining, in a biological sample from a human subject, an absence of an identified pathogenic mutation to the BRCA-1 and BRCA-2 genes (310). In response to a successful determination, the method (300) includes determining in the biological sample a presence or absence of risk alleles of common allelic variants associated with a breast cancer phenotype at a plurality of independent loci (320). A polygenic risk score for the human subject can then be calculated based upon the presence or absence of the risk alleles and using case data indicative of women who developed breast cancer (330) which did not carry the pathogenic mutation to the BRCA-1 and BRCA-2 genes. A high polygenic risk score indicates a higher risk for developing a breast cancer phenotype.
The present disclosure relates generally to a biomarker of disease, more particularly a biomarker of gastric cancer, including agents, methods and protocols for the diagnosis, prognosis and treatment of gastric cancer, wherein the biomarker is secreted frizzled related protein 4 (SFRP4).
Adelaide Research & Innovation PTY LTD (Australia)
Peter Maccallum Cancer Institute (Australia)
Inventor
Mccoll, Shaun Reuss
Comerford, Ian
Harata-Lee, Yuka
Smyth, Mark
Abstract
The present disclosure relates to the prevention and/or treatment of metastatic cancer. Certain example embodiments of the present disclosure provide a method for preventing and/or treating a metastatic cancer in a subject. The method comprises administering to the subject a therapeutically effective amount of an inhibitor of a chemokine receptor CCX-CKR.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
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
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
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
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
45.
Perforin inhibiting benzenesulfonamide compounds, preparation and uses thereof
C07D 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 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
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 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 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
The present invention relates to antibodies and antigen-binding fragments thereof that bind RYK, in particular human RYK and their use in regulating RYK-associated activities. Specifically there is provided an isolated monoclonal antibody or antigen- binding fragment or derivative thereof that specifically binds to the extracellular domain of human RYK, in particular, the antibody or antigen-binding fragment thereof, binds specifically to the WIF domain of human RYK. Preferably, the antibodies of the present invention modulate RYK-associated activity, which includes RYK mediated signal transduction activity and modulation of the interaction of Wnts with RYK and, preferably, modulate Wnt induced signaling. In particular, the antibodies inhibit the binding of Wnt5a and inhibit Wnt induced phosphorylation of Dishevelled (Dvl) 2 and/or Dvl3 proteins.
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
47.
METHODS AND PRODUCTS FOR PREVENTING AND/OR TREATING METASTATIC CANCER
ADELAIDE RESEARCH & INNOVATION PTY LTD (Australia)
PETER MACCALLUM CANCER INSTITUTE (Australia)
Inventor
Mccoll, Shaun Reuss
Comerford, Ian
Harata-Lee, Yuka
Smyth, Mark
Abstract
The present disclosure relates to the prevention and/or treatment of metastatic cancer. Certain example embodiments of the present disclosure provide a method for preventing and/or treating a metastatic cancer in a subject. The method comprises administering to the subject a therapeutically effective amount of an inhibitor of a chemokine receptor CCX-CKR.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
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 15/11 - DNA or RNA fragmentsModified forms thereof
48.
PERFORIN INHIBITING BENZENESULFONAMIDE COMPOUNDS, PREPARATION AND USES THEREOF
Compounds of formula (la) and pharmaceutically acceptable salts, solvates, and hydrates thereof and related methods of modulatin perforin activity on a cell: wherein Ring A is selected from a 6-10 membered aryl, 5-6 membered cycloalkyi, 5-6 membered heteroaryl or 5-6 membered heterocyclyl, wherein the heteroaryl and heterocyclyl rings comprise at least one heteroatom selected from N, O or S; and wherein the aryl, cycloalkyi, heteroaryl or heterocyclyl rings are optionally substituted with 1 to 3 substituents selected from halo, nitro, -C1-Cealkyl, -C1-Ceaminoalkyl, -C1-C6hydroxyalkyl, -haloC1-C6alkyl, -C1- C6alkoxyl, -haloC1-C
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 409/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic 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 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
Methods of treatment or prevention of a cancerous or pre-cancerous condition, of slowing or preventing growth of a cancerous condition, of stimulating a cell-mediated immune response, stimulating a Th1 helper T cell response against a pathogen in a mammal and of treating or preventing inflammatory diseases or disorders that involve administration of N-methyl pyrrolidone (NMP) or a physiologically acceptable salt, solvate, tautomer or prodrug thereof are provided. Also provided are formulations of an active agent.
A01N 43/36 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61K 47/00 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient
A61K 31/4015 - 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 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection). Preferred compounds of the invention are those of Formula II, as follows:
and pharmaceutically acceptable derivatives thereof.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 235/20 - Two benzimidazolyl-2 radicals linked together directly or via a hydrocarbon or substituted hydrocarbon radical
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 235/18 - BenzimidazolesHydrogenated benzimidazoles with aryl radicals directly attached in position 2
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
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
CD73 may be used as a prognostic marker to detect the recurrence of triple negative breast cancer in patients who have undergone a cancer therapy, in particular a chemotherapy based treatment. There is provided a method for diagnosing or predicting the recurrence of triple negative breast cancer in a subject who has undergone a cancer therapy, the method the comprising (i) obtaining a triple negative breast cancer cell sample from the subject; and (ii) detecting CD73 activity or expression in a cell of the sample, wherein increased activity or expression of CD73 in the cell, when compared to a normal breast tissue cell, indicates that the subject has or is at risk of developing recurrent triple negative breast cancer. There is also provided a method for predicting the efficacy of a triple negative breast cancer therapy in a subject comprising: (i) administering a cancer therapy to the subject; (ii) obtaining a triple negative breast cancer cell sample from the subject; and (iii) detecting CD73 activity or expression in a cell of the sample, wherein decreased activity or expression of CD73 in the triple negative breast cancer cell, when compared to a triple negative breast cancer cell of the same type prior to therapy, indicates that the therapy is efficacious.
Methods of treatment or prevention of a cancerous or pre-cancerous condition, of slowing or preventing growth of a cancerous condition, of stimulating a cell-mediated immune response, stimulating a Th1 helper T cell response against a pathogen in a mammal and of treating or preventing inflammatory diseases or disorders that involve administration of N-methyl pyrrolidone (NMP) or a physiologically acceptable salt, solvate, tautomer or prodrug thereof are provided. Also provided are formulations of an active agent.
A61K 31/4015 - 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 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection). Preferred compounds of the invention are those of Formula (II), as follows: wherein W represents -N(R1R2) where R1 and R2 are not both hydrogen and where they may together form a 5, 6 or 7 membered ring structure, -NHN(R1R2), NHR3N(R1R2), -NHR3OR2, -N(R3)R3OR2, -N(R1)R3OR3OR3, OR3NR1R2, -OR3 or W represents piperidyl, piperazinyl, morpholinyl, thiomorpholinyl or diazepanyl each of which may be optionally substituted by C1 to C4 alkyl, C2 to C4 alkenyl, -N(CO)N(R1R2), -N(CO)OR1, -N(CO)OR3OH, -(CO)NR1R2, -R3(CO)NR1R2, -R3OR1, -OR1, -N(R1R2) OR -NH-; R1 and R2 are the or different and are selected from hydrogen, C1 to C4 alkyl or C2 to C4 alkenyl; group or chain; Z is the same or different and represents N or CH; Z' is the same or different and represents N or C; X represents CH, N or NH, where ⃜⃜ is a double bond when X is CH or N and a single bond when X is NH; X' represents N or NH, wherein when X is CH or N X' is NH and wherein X and X' are different and further where ≃≃≃is a double bond when X' is N and a single bond when X' is NH; Q represents H, alkoxyl, -NR1R2, F or Cl; Q1 is absent when Z' is N and when Z' is C it represents H, alkoxyl, -NR1R2, F or Cl; A represents a five to ten membered single or multiple ring structure with heterocyclic N or O located at the ortho position, said ring including optional double bonds, substitutions and/or other heteroatoms and pharmaceutically acceptable derivatives thereof.
The present invention provides novel compounds of the Formula (I), pharmaceutical compositions comprising such compounds and methods for using such compounds as agents or drugs for inhibiting perforin activity and for treating a subject at risk of or susceptible to a disease or disorder, or having a disease or disorder associated with undesirable perforin activity.
A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
C07D 333/16 - Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07D 333/18 - Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
A61K 31/5355 - Non-condensed oxazines containing further heterocyclic rings
C07D 233/86 - Oxygen and sulfur atoms, e.g. thiohydantoin
A61K 31/5415 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
C07D 307/89 - Benzo [c] furansHydrogenated benzo [c] furans with two oxygen atoms directly attached in positions 1 and 3
55.
METHOD OF DETECTING RADIATION EXPOSURE AND ADVERSE TOXICITY THERETO
The present invention relates generally to an array of nucleic acid molecules, the nucleic acid expression profiles of which are indicative of cellular exposure to radiation, in particular ionizing radiation. In a related aspect, the present invention provides an array of nucleic acid molecules, the nucleic acid expression profiles of which are indicative of susceptibility to adverse radiation toxicity. More particularly, the methods of the present invention are directed to detecting genes, the expression levels or alternative splicing of which are indicators of exposure to radiation and/or susceptibility to adverse radiation toxicity. Accordingly, the present invention provides a valuable means of screening individuals to determine, inter alia, their inadvertent exposure to ionizing radiation or the predisposition of a patient to exhibit susceptibility to adverse radiation toxicity, thereby indicating that an alternative treatment regime should be pursued.
TECHNION RESEARCH & DEVELOPMENT FOUNDATION LTD (Israel)
Inventor
Bomzon, Ze'Ev, Wayne
Russell, Sarah, May
Gu, Min
Herschtal, Alan, Gerald
Abstract
A method of automatic cell function classification, comprising obtaining a sequence of images of a sample area in which at least one cell is located, processing the sequence of images to determine objects in each of the images, classifying the objects in each of the images to identify cell objects based on which of the objects resemble cells, determining properties of the identified cell objects across the sequence of images to determine behaviour of each cell object, and classifying one or more cell functions of each identified cell object based on the determined properties.
The present invention provides a method of evaluating DNA methylation in a sample. The method comprises (i) reacting the DNA with an agent that differentially modifies methylated cytosine and non-methylated cytosine to produce modified DNA, (ii) amplifying the modified DNA by methylation specific PCR to produce amplified DNA, and (iii) subjecting the amplified DNA to melting analysis. In the method the methylation specific primers are selected such that the sequence between the primers includes a region of known sequence variation and/or at least one cytosine nucleotide.
The invention relates to radioprotectors of formula (I), processes for their preparation and their use in protecting biological materials from radiation damage. In diagnostic and therapeutic radiology, particularly in cancer radiotherapy, the radioprotectors of the present invention may be used to protect certain normal tissues or structures from radiation damage. The radioprotectors of formula (I) may also have uses in decreasing the effects of irradiation in non-medical scenarios, both civil and military.
The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection). Preferred compounds of the invention are those of Formula (II), as follows: wherein W represents -N(R1R2) where R1 and R2 are not both hydrogen and where they may together form a 5, 6 or 7 membered ring structure, -NHN(R1R2), NHR3N(R1R2), -NHR3OR2, -N(R3)R3OR2, -N(R1)R3OR3OR3, OR3NR1R2, -OR3 or W represents piperidyl, piperazinyl, morpholinyl, thiomorpholinyl or diazepanyl each of which may be optionally substituted by C1 to C4 alkyl, C2 to C4 alkenyl, -N(CO)N(R1R2), -N(CO)OR1, -N(CO)OR3OH, -(CO)NR1R2, -R3(CO)NR1R2, -R3OR1, -OR1, -N(R1R2) OR -NH-; R1 and R2 are the or different and are selected from hydrogen, C1 to C4 alkyl or C2 to C4 alkenyl; group or chain; Z is the same or different and represents N or CH; Z' is the same or different and represents N or C; X represents CH, N or NH, where ?? is a double bond when X is CH or N and a single bond when X is NH; X' represents N or NH, wherein when X is CH or N X' is NH and wherein X and X' are different and further where ???is a double bond when X' is N and a single bond when X' is NH; Q represents H, alkoxyl, -NR1R2, F or Cl; Q1 is absent when Z' is N and when Z' is C it represents H, alkoxyl, -NR1R2, F or Cl; A represents a five to ten membered single or multiple ring structure with heterocyclic N or O located at the ortho position, said ring including optional double bonds, substitutions and/or other heteroatoms and pharmaceutically acceptable derivatives thereof.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61P 39/00 - General protective or antinoxious agents
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
61.
PERFORIN INHIBITING BENZENESULFONAMIDE COMPOUNDS, PREPARATION AND USES THEREOF
The present invention relates to compounds that inhibit perforin activity and uses thereof as tools for biological studies or as agents or drugs for immunosuppressive therapies. In particular, the present invention relates to benzenesulfonamide compounds such as compounds of formula (W):whereinRing A is optionally substituted phenyl;L is a linker selected from branched or unbranched C1-C4 alkylene, -S(O)2-NH-, -C(O)-NH-,-NH-C(O)-NH-, -S(O)2-NH-C(O)-NH-, -S(O)2-NH-C(O)-, -C(O)-NH-C(S)-NH- and -CH=CH-;X is N-R1;R1 is H or C1-C6 alkyl optionally substituted with hydroxyl or halo;n is 1;m is 0-2; X1 and X2 are independently CH or N, andwhen X1 is CH, X2 is N; orwhen X1 is N, X2 is CH; andR8 is an optional substituent attached to a C atom selected from Cl, F, CF3, OCF3, C1-C3alkyl, C1-C3alkoxy, or NJJ, wherein each J is independently selected from hydrogen or C1-C3alkyl.
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 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 409/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 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
62.
BISPECIFIC POLYPEPTIDES FOR ENGAGEMENT OF CAR EXPRESSING IMMUNE CELLS WITH ANTIGEN PRESENTING CELLS AND USES THEREOF
The present application is directed to bispecific polypeptides comprising a first domain binding an antigen on an antigen presenting cell (ARC) and a second domain binding an antigen on an immune cell expressing a chimeric antigen receptor (CAR). Nucleic acids, vectors and host cells used in producing the polypeptide of the invention are also disclosed. Compositions comprising the bispecific polypeptides and methods of treating cancer and stimulating activation and expansion of immune cells in vivo and in vitro are also disclosed.
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
63.
METHODS OF TREATING CANCER WITH A COMBINATION OF TUCATINIB AND AN ANTI-PD-1/ANTI-PD-L1 ANTIBODY
The disclosure provides methods of treating solid tumors with a combination of tucatinib, or salt or solvant thereof, and an anti-PD-1 antibody, or an antigen-binding fragment thereof. The disclosure also provides methods of treating solid tumors with a combination of tucatinib, or salt or solvant thereof, and an anti-PD-Ll antibody, or an antigen-binding fragment thereof.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
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
64.
CONDUCTOMETRIC SENSOR FOR DETECTING A NUCLEIC ACID AND A METHOD FOR THE DETECTION THEREOF
ROYAL MELBOURNE INSTITUTE OF TECHNOLOGY (Australia)
PETER MACCALLUM CANCER INSTITUTE (Australia)
Inventor
Ahmed, Taimur
Perera, Ganganath
Walia, Sumeet
Bhaskaran, Madhu
Sriram, Sharath
Fox, Stephen
Fellowes, Andrew
Abstract
The invention provides a sensor for detecting a nucleic acid, comprising: a substrate; a pair of terminal electrodes disposed on the substrate in mutually spaced apart and opposing relation; and a sensing element, between and in electrical contact with the pair of terminal electrodes, wherein the sensing element comprises: (i) a semiconducting portion of the substrate, wherein a conduction path between the terminal electrodes passes through the semiconducting portion; and (ii) an oligonucleotide on a surface of the semiconducting portion, the oligonucleotide being complementary to the nucleic acid to be detected, wherein hybridisation of the nucleic acid with the oligonucleotide leads to a change in resistance of the sensor.
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6834 - Enzymatic or biochemical coupling of nucleic acids to a solid phase
G01N 27/12 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon absorption of a fluidInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body in dependence upon reaction with a fluid
H01L 21/62 - Manufacture or treatment of semiconductor devices or of parts thereof the devices having no potential barriers
The present invention relates to compounds and methods for the targeted delivery of diagnostic/therapeutic radionuclides to cancer tissue. In particular, the present invention relates to the targeted delivery of diagnostic/therapeutic radionuclides to cholecystokinin-2 receptor positive cancers and to methods for the diagnosis and treatment of cancer.
