111 results about "TREM2" patented technology

The present disclosure provides compounds of Formula (I), useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 ("TREM2"). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a neurodegenerative disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

The present disclosure provides compounds of Formula (I), useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 ("TREM2"). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a neurodegenerative disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

The invention relates to the technical field of biological medicine, in particular to a functionalized targeted liposome and application thereof, and the functionalized targeted liposome comprises lipid and a targeted ligand, wherein the targeting ligand can be specifically combined with a TREM2 receptor. According to the lipidosome, the targeting ligand can be specifically combined with the TREM2 receptor, accurate targeting of cells with the surface containing the TREM2 receptor is achieved, it is ensured that the cells directly act on target cells, the accuracy of a delivered substance is further improved, and the lipidosome has the advantages of being targeting, high in stability, small in side effect and high in bioavailability. The functionalized targeted liposome can be applied to the development of drug carriers, pharmaceutical compositions and the like, and has wide application prospects, for example, the liposome is dynamically connected with hydrogel molecules through a borate bond to prepare a hydrogel pharmaceutical composition containing the functionalized targeted liposome, and the application prospect is wide. The liposome disclosed by the invention can respond to an inflammatory environment according to pH and ROS changes of a surrounding environment to release the liposome disclosed by the invention, targets cells with TREM2 receptors on the surfaces, namely microglial cells (with the TREM2 receptors on the surfaces) by virtue of the target ligands exposed on the surfaces, regulates the polarization state of the cells, inhibits the polarization of the cells to a pro-inflammatory M1 type and promotes the polarization of the cells to an anti-inflammatory M2 type, so that the anti-inflammatory effect of the liposome is improved. Therefore, the local microenvironment of the spinal cord injury part is improved, and nerve regeneration is promoted.

The present invention provides antibodies that bind to and stabilize human Triggering Receptor Expressed on Myeloid cells 2 (TREM2) protein and methods of using these antibodies.

The present invention relates to compounds useful for modulating Triggering Receptor Expressed on Myeloid Cells-2 (“TREM2”). The invention also relates to the compounds for use in treatment of conditions related to loss of function of TREM2, such as neurodegenerative diseases, and to pharmaceutical compositions comprising the compounds.

The present invention relates to compounds useful for modulating Triggering Receptor Expressed on Myeloid Cells-2 (“TREM2”). The invention also relates to the compounds for use in treatment of conditions related to loss of function of TREM2, such as neurodegenerative diseases, and to pharmaceutical compositions comprising the compounds.

The present invention relates to compounds useful for modulating Triggering Receptor Expressed on Myeloid Cells-2 ("TREM2"). The invention also relates to the compounds for use in treatment of conditions related to loss of function of TREM2, such as neurodegenerative diseases, and to pharmaceutical compositions comprising the compounds.

The present invention relates to compounds useful for modulating Triggering Receptor Expressed on Myeloid Cells-2 ("TREM2"). The invention also relates to the compounds for use in treatment of conditions related to loss of function of TREM2, such as neurodegenerative diseases, and to pharmaceutical compositions comprising the compounds.

The application relates to fused pyrimidinone derivatives of the general formula (I) which act as agonists of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) useful for the treatment of Parkinson's disease, rheumatoid arthritis, Alzheimer's disease, amyotrophic lateral sclerosis, Nasu-Hakola disease, frontotemporal dementia, multiple sclerosis, prion disease, and stroke.

The present disclosure provides a genetically modified mouse comprising a genomic nucleic acid encoding human APOE4, a genomic nucleic acid encoding mouse TREM2 modified to include a R47H substitution, and at least one genomic modification selected from the group consisting of: (a) a genomic nucleic acid encoding mouse ABCA7 modified to include an A 1541 G substitution; (b) a genomic nucleic acid encoding mouse APP modified to include G60IR, F606Y, and R609H substitutions; (c) a genomic nucleic acid encoding mouse PLCG2 modified to include a M28L substitution; (d) a genomic nucleic acid encoding mouse MTHFR modified to include a A262V substitution; (e) an inactivated Ceacaml allele; and (f) an inactivated II1rap allele. Methods of producing the genetically modified mouse and methods of using the genetically modified mouse are also provided.

The present disclosure provides compounds useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 ("TREM2"). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a neurodegenerative disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula I.

The invention relates to the field of in-vitro diagnostic reagents, in particular to application of a reagent for detecting TREM2 in preparation of a diagnostic kit for chronic kidney disease osteoporosis. The invention finds that the TREM2 signal channel is closely related to the common pathological background of chronic kidney disease and osteoporosis. Therefore, the TREM2 can be used as an expression characteristic and a molecular diagnosis marker in the chronic kidney disease-related osteoporosis, so that the chronic kidney disease-related osteoporosis can be subjected to early diagnosis. On the basis, the invention provides application of the TREM2 detection reagent in preparation of the chronic kidney disease osteoporosis diagnosis kit, and the application prospect is good.

The present disclosure is directed to compounds of Formula I and their use as TREM2 agonists for treatment and prevention of a neurodegenerative disorder associated with a loss of function of human TREM2. The disclosed TREM2 agonists may be useful for the treatment of Alzheimer's Disease and associated neurological conditions.

The invention relates to the technical field of biological medicine, and particularly discloses a macrophage membrane coated plateau encephaledema drug carrier and a preparation method and application thereof, and the macrophage membrane coated plateau encephaledema drug carrier is composed of a nanoparticle core and a macrophage membrane shell layer wrapping the core; the nanoparticle core comprises an ROS-responsive carrier material and carbon monoxide release molecules MnCO entrapped in the ROS-responsive carrier material; the content of phosphatidylserine in the shell layer of the macrophage membrane is not less than 5 mol% of the total phospholipid of the membrane. According to the invention, a bionic delivery system of ROS response type MnCO nanoparticles coated with a macrophage membrane is constructed, phosphatidylserine on the surface of the membrane is utilized to actively activate a microglial cell Trem2 receptor, a positive feedback cycle of targeting phagocytosis-CO release-Trem2 up-regulation is formed, and at the same time, fatty acid oxidative metabolism reprogramming is promoted by means of degraded membrane lipid, so that the biomimetic delivery system is used for preparing the ROS response type MnCO nanoparticles. And multi-mechanism synergistic efficient brain-targeted therapy is realized.

The present invention relates to compounds useful for modulating trigger receptor 2 ('TREM2') expressed on myeloid cells. The invention also relates to the use of said compounds in the treatment of conditions associated with loss of TREM2 function, such as neurodegenerative diseases, and to pharmaceutical compositions comprising said compounds.

To provide compounds useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 ("TREM2").SOLUTION: The present invention provides compounds of Formula (I). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a neurodegenerative disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).SELECTED DRAWING: None

The application discloses a polypeptide ligand for brain glioma diagnosis and preparation and application of a radioactive molecular probe. The polypeptide targeting a TREM2 protein has the amino acid sequence as shown in the following: HLRKLRKR. The targeted polypeptide designed by the application has the characteristics of small molecular weight, strong blood brain barrier penetration and strong TREM2 protein binding capacity. The radioactive nuclide labeled molecular probe prepared by the application has the characteristics of strong targeting and easy observation as a brain glioma imaging drug, and is convenient for clinical application. The application improves the diagnosis effect of brain glioma and provides a new idea for early discovery and early treatment of brain glioma.

The invention relates to a gene vector for CSF1R (Classical Sequence Factor 1R) related white matter encephalopathy as well as a construction method and application of the gene vector. The gene vector is AAV.MG1.1-Trem2. The gene vector disclosed by the invention can be used for increasing the expression content of the Trem2 of the microglial cells and compensating the dysfunction of the pathogenic gene CSF1R, so that the microglial cells can exert normal functions.

The present invention relates to the field of TREM2 receptor drug screening, and specifically proposes a rapid screening method for TREM2 receptor drugs. The method mainly comprises: (1) fusing a halogenated alkane dehalogenase to the inactive end of the TREM2 receptor to construct a TREM2 recombinant protein with a directional immobilization function; (2) covalently modifying a separation medium with 6-bromohexanoic acid to obtain a surface-modified separation medium; (3) fully mixing the TREM2 recombinant protein with the 6-bromohexanoic acid-modified separation medium, and incubating the mixture to allow the TREM2 receptor to be directionally modified on the surface of the separation medium. The resulting TREM2 recombinant protein immobilized complex is further used to prepare a TREM2 receptor chromatographic column, which can specifically identify its ligand based on retention time, thereby realizing rapid screening of TREM2 receptor-targeting compounds in complex systems such as traditional Chinese medicine.

The present invention relates to compounds of Formula (I) useful for modulating Triggering Receptor Expressed on Myeloid Cells 2 ("TREM2") expressed on myeloid cells. The present invention also relates to the use of the compounds for treating conditions associated with loss of function of TREM2, such as neurodegenerative diseases; and pharmaceutical compositions comprising the compounds.

The invention relates to the field of TREM2 receptor drug screening, and particularly provides a rapid screening method of TREM2 receptor drugs. The method mainly comprises the following steps: (1) fusing halogenated alkane dehalogenase subjected to specific mutation to an inactive terminal of a TREM2 receptor to construct a TREM2 recombinant protein with a directional immobilization function; (2) carrying out covalent modification on the separation medium by using 6-bromohexanoic acid to obtain a surface-modified separation medium; and (3) fully mixing the TREM2 recombinant protein with the 6-bromohexanoic acid modified separation medium, and carrying out incubation treatment, so that the TREM2 receptor is directionally modified to the surface of the separation medium. The obtained TREM2 recombinant protein immobilized complex is further used for preparing a TREM2 receptor chromatographic column, the TREM2 receptor chromatographic column can specifically recognize a ligand according to retention time, and rapid screening of TREM2 receptor targeted compounds in complex systems such as traditional Chinese medicine is achieved.

The present disclosure relates to antibodies that bind the extracellular domain of human TREM2 and the use of anti-TREM2 antibodies in therapy, prophylaxis, diagnosis, screening, and monitoring, including for increasing levels of soluble TREM2 (sTREM2) in serum and brain, increasing phagocytosis by microglia and / or macrophages, and developing treatments to address TREM2-mediated conditions that may benefit from enhanced phagocytosis by microglia and / or macrophages.

The present invention relates to compounds useful for modulating Triggering Receptor Expressed on Myeloid Cells-2 ("TREM2"). The invention also relates to the compounds for use in treatment of conditions related to loss of function of TREM2, such as neurodegenerative diseases, and to pharmaceutical compositions comprising the compounds.

Herein is reported an anti-TREM2 / A [beta] protein antibody comprising a first binding site that binds to human TREM2 and a second binding site that binds to human A [beta] protein, the first binding site comprising: a heavy chain variable domain comprising HVR-H1 of SEQ ID NO: 305, HVR-H2 of SEQ ID NO: 306 and HVR-H3 of SEQ ID NO: 307, and a light chain variable domain comprising HVR-L1 of SEQ ID NO: 309, HVR-L2 of SEQ ID NO: 310 and HVR-L3 of SEQ ID NO: 311 (TREM 23295), or a heavy chain variable domain comprising HVR-L1 of SEQ ID NO: 309, HVR-L2 of SEQ ID NO: 310 and HVR-L3 of SEQ ID NO: 311 (TREM 23295); the present invention relates to a single-chain variable domain comprising an HVR-H1 of SEQ ID NO: 329, an HVR-H2 of SEQ ID NO: 330, and an HVR-H3 of SEQ ID NO: 331, and a light chain variable domain comprising an HVR-L1 of SEQ ID NO: 333, an HVR-L2 of SEQ ID NO: 334, and an HVR-L3 of SEQ ID NO: 335 (TREM 23306); and a second binding site comprising: a heavy chain variable domain comprising HVR-H1 of SEQ ID NO: 09, HVR-H2 of SEQ ID NO: 10 and HVR-H3 of SEQ ID NO: 11, and in a light chain variable domain, HVR-L1 of SEQ ID NO: 13, HVR-L2 of SEQ ID NO: 14 and HVR-L3 of SEQ ID NO: 15 (A [beta] 8675).

The present disclosure provides an anti-TREM2 antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof specifically binds to TREM2, which is a hot target with potential to treat cancer and neurodegenerative diseases.

The present invention provides a method of treating a disease or disorder caused by and / or associated with ABCD1 dysfunction in a human patient, the method comprising administering to the patient in need thereof an effective amount of a compound that increases the activity of triggering receptor expressed on myeloid cells 2 (TREM2). In some embodiments, compound that increases the activity of TREM2 is an agonist of TREM2. In some embodiments, the agonist of TREM2 is a small molecule agonist of TREM2 or an antibody agonist of TREM2.