52 results about "TREM2" patented technology

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 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.

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 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 invention relates to a fusion polypeptide for diabetes wound repair and a pharmaceutical composition thereof, and discloses a sequence design and a preparation method of the fusion polypeptide FP-DW01-Chol, and a temperature-sensitive hydrogel composition containing the polypeptide and MitoQ. The fusion polypeptide contains a TREM2 agonist domain, an AGE-RAGE blocking domain, an MMP9 recognition cleavage site, an Angiopoietin-2 mimic peptide fragment and a cholesterol modification terminal, and can activate anti-inflammatory polarization of macrophages, block a chronic inflammation pathway and respond to a wound enzyme environment to release an angiogenesis promoting fragment. The pharmaceutical composition takes poloxamer 407 / 188 as a temperature-sensitive carrier, realizes cooperative delivery of polypeptide and MitoQ, and has the advantages of slow release, skin retention and stability. In-vitro and db / db mouse model experiments prove that the composition can remarkably promote high-glucose damaged cell activity recovery, inhibit inflammatory factor release, accelerate wound closure, promote angiogenesis and tissue remodeling, provides a multi-mechanism synergistic and local long-acting treatment scheme for diabetic refractory wounds, and has important clinical transformation value.

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 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 application relates to the technical field of biological medicine, in particular to a functionalized targeted liposome and application thereof, comprising: lipids and a targeting ligand; wherein the targeting ligand can specifically bind to a TREM2 receptor. The liposome of the present application can specifically bind to the TREM2 receptor by means of the targeting ligand, realize precise targeting of cells containing the TREM2 receptor on the surface, ensure direct action on target cells, and further improve the precision of delivered substances. The liposome has targeting property, high stability, small side effects, and can be applied to the development of drug carriers, pharmaceutical compositions, etc., and has a wide application prospect. For example, the liposome of the present application is dynamically connected with a hydrogel molecule by a borate ester bond to prepare a hydrogel pharmaceutical composition containing the functionalized targeted liposome of the present application. The hydrogel pharmaceutical composition can release the liposome of the present application according to the change of pH and ROS in the surrounding environment in response to an inflammatory environment, and target cells containing the TREM2 receptor on the surface, i.e. microglial cells (having the TREM2 receptor on the surface), by virtue of the targeting ligand exposed on the surface, and regulate the polarization state of the cells, inhibit the polarization of the cells to the pro-inflammatory M1 type, and promote the polarization of the cells to the anti-inflammatory M2 type, thereby improving the local microenvironment of the spinal cord injury site and promoting nerve regeneration.

This invention provides an antibody that binds to and stabilizes the trigger receptor 2 (TREM2) protein expressed in human myeloid cells. [Solution] The present invention provides a nucleic acid molecule or a set of nucleic acid molecules encoding an anti-TREM2 antibody or its antigen-binding fragment, comprising three heavy chain complementarity-determining regions (HCDR1, HCDR2, and HCDR3) and three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3) containing specific amino acid sequences, as defined by the Kabat numbering system, Chothia numbering system, IMGT numbering system, and combined numbering system. Furthermore, the present invention provides a vector containing the nucleic acid molecule, cells containing the vector, and a method for producing an anti-TREM2 antibody or its antigen-binding fragment, comprising culturing the cells.

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 invention discloses a double-drug co-delivery lipidosome and a preparation method and application thereof, and belongs to the technical field of biological medicine and nano-drug delivery, the surface of the double-drug co-delivery lipidosome is modified with Angiopep-2 and COG1410, riluzole is loaded, the Angiopep-2 mediates the lipidosome to cross a blood brain barrier, the COG1410 excites a TREM2 pathway to enhance microglial cell mediated A beta removal, and the riluzole is loaded on the lipidosome. Riluzole inhibits glutamic acid release and promotes removal, so that neuronal hyperactivity is reduced; the preparation method of the liposome comprises the following steps: lipid dissolution, hydration, membrane extrusion and gel column purification. The invention also provides an application of the double-drug co-delivery liposome in medicines for treating Alzheimer's disease, provides a composite nano-drug system with cross-BBB capability, A beta removal and neuroprotection, and overcomes the limitation of the existing therapy.

This invention discloses a method for restoring TREM2 in the preparation of diabetic nephropathy using luteolin. + This invention relates to the application and research methods of macrophage functional drugs, and pertains to the field of biomedical technology. Through the technical solution of this invention, luteolin is used for the intervention of diabetic nephropathy, achieving the effect of regulating TREM2. + Targeted regulation of the key pathological link of macrophage dysfunction; by increasing TREM2 + The number and functional status of macrophages are improved, enhancing their ability to eliminate apoptotic cells, reducing the level of renal tissue cell apoptosis and immune inflammatory damage; thereby alleviating the progression of kidney damage in diabetic nephropathy.

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 disclosure relates to a bicyclic fused-ring (for example, pteridine, pyridopyrimidine, pyridopyrazine, quinazoline, naphthyridine, or quinoxaline) derivative or a pharmaceutically acceptable salt thereof inducing activation of a triggering receptor expressed on myeloid cells 2 (TREM2), a pharmaceutical composition including the same, and a use thereof. The bicyclic fused-ring derivative or a pharmaceutically acceptable salt thereof may be useful in treatment and prevention of TREM2-mediated neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Huntington's disease and Nasu-Hakola disease.

The present invention discloses an application of TREM2hi macrophages in preparation of drugs for treating cardiac dysfunction, and belongs to the technical field of medicine. The present invention discloses for the first time that there is a kind of macrophage subsets for high expression of a triggering receptor expressed on myeloid cells-2 in cardiac derived macrophages, which has a strong function of recognizing and reducing mitochondrial damage and plays an important role in maintaining a cardiac metabolic balance. Therefore, the TREM2hi macrophages have important application value in treatment of the cardiac dysfunction.

The present application relates to the field of in vitro diagnostic reagents, and particularly relates to the use of a reagent for detecting TREM2 in the preparation of a chronic kidney disease osteoporosis diagnostic kit. The present application finds that the TREM2 signaling pathway is closely related to the common pathological background of chronic kidney disease and osteoporosis. Therefore, TREM2 can be used as an expression feature and a molecular diagnostic marker in chronic kidney disease-related osteoporosis, thereby enabling early diagnosis of chronic kidney disease osteoporosis. Based on this, the present application provides the use of a reagent for detecting TREM2 in the preparation of a chronic kidney disease osteoporosis diagnostic kit, which has a good application prospect.

This invention discloses the application of AM80 agonists and the retinoic acid signaling pathway in the treatment of autism spectrum disorder, belonging to the field of pharmaceutical technology. This invention provides the use of AM80 or its pharmaceutically acceptable salts in the preparation of drugs for treating ASD. Experiments have demonstrated that AM80 can significantly improve social impairment and repetitive stereotyped behaviors in ASD model rats. Its mechanism of action is as follows: AM80, as a RARα agonist, can upregulate the activity of the RA / RARα signaling pathway, thereby promoting the transcription and expression of the downstream target molecule TREM2. Elevated TREM2 can correct the abnormal activation of microglia (reducing their number, improving their morphology, and promoting their conversion from pro-inflammatory M1 to anti-inflammatory M2) and improve synaptic pruning function (regulating the expression of synaptic proteins such as SYN-1, PSD95, and Gephyrin). This invention provides new drug candidates and targets for the treatment of ASD.

The present disclosure provides methods of using a small molecule TREM2 agonist or a pharmaceutically acceptable salt thereof to treat Alzheimer's Disease in a human subject.

The invention provides a head and neck squamous cell carcinoma prognosis prediction model based on a characteristic macrophage subset and a construction method of the head and neck squamous cell carcinoma prognosis prediction model, and belongs to the technical field of biomedicine. According to the invention, an immune spectrum of LN metastatic HNSCC is firstly established, single cell sequencing identification is utilized, then a TREM < 2 + > TAMs cell population with significant prediction value for HNSCC prognosis is identified by combining microarray data, multiple immunofluorescence, an in-vitro co-culture technology and the like, and a mechanism that TREM < 2 + > TAMs induces CD8 < + > T cell depletion through an SPP1-CD44 signal axis to promote HNSCC LN metastasis is clarified. Then, single-factor COX regression and LASSO regression are jointly used, a random forest algorithm is introduced, modeling is carried out in microarray sample data based on a TREM2 + TAMs feature gene set, and the established model can accurately predict prognosis after head and neck squamous cell carcinoma immunotherapy.

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.