83 results about "TREM2" patented technology

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 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 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 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.

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.

The present invention provides a method of treating a disease or disorder caused by and / or associated with CSF1R 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.

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 invention provides a protein or antibody capable of binding to human TREM2, the protein or antibody comprises an Ig light chain variable region and an Ig heavy chain variable region, the amino acid sequence of the light chain variable region is an amino acid sequence of SEQ ID NO: 1, or an amino acid sequence with one or two amino acid residue substitutions compared with SEQ ID NO: 1, and the amino acid sequence of the heavy chain variable region is an amino acid sequence with one or two amino acid residue substitutions compared with SEQ ID NO: 1. And the amino acid sequence of the heavy chain variable region is an amino acid sequence of SEQ ID NO: 2, or an amino acid sequence with one or two amino acid residue substitutions compared with SEQ ID NO: 2.

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 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.

Nucleic acids encoding triggering receptor expressed on myeloid cells 2 (TREM2) and that can be used in gene therapy are described, as are expression constructs, vectors, and methods of using them for the treatment of TREM2-associated diseases and disorders, particularly neurological disorders such as Alzheimer's disease (AD), adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), or Nasu-Hakola disease (NHD).

Described herein are chimeric antigen receptors (CARs) comprising an extracellular domain comprising a portion of an anti-triggering receptor expressed on myeloid cells 2 (TREM2) scFv for targeting macrophages expressing TREM2. Methods for producing and utilizing cells comprising the CAR are further provided herein.