253 results about "Nectin" patented technology

The invention discloses a method for simulating a tumor blood vessel growth process. The method comprises the following steps: constructing a two-dimensional discrete coordinate system based on a tumor two-dimensional model, and defining a blood vessel index function for describing unit grid attributes of unit grids; updating the cell number, the oxygen concentration, the fibronectin concentration and the growth factor concentration of each unit grid every preset time t; predicting the movement direction of the blood vessel tip in the t time period according to the fibronectin concentration and the growth factor concentration; calculating a first predicted extension distance and a second predicted extension distance according to the motion direction in the current t time period and the motion direction in the last t time period; and updating the unit grid attribute of each unit grid in the two-dimensional discrete coordinate system according to the movement direction in the t time period, the blood vessel existence time of the blood vessel tip and the movement extension distance calculated by the blood vessel tip. The oxygen concentration and the number of cells are incorporated into the tumor blood vessel growth model, and accurate simulation prediction of the tumor blood vessel growth process is achieved.

An anti-Nectin-4 single-domain antibody and the use thereof. Provided are a single-domain antibody specifically targeting Nectin-4, and amino acid sequences of a framework region FR and a complementarity-determining region CDR of a VHH chain thereof. The anti-Nectin-4 single-domain antibody can bind to a Nectin-4 antigen. An antibody-drug conjugate and a multi-specific antibody targeting the Nectin-4 target prepared by means of using the single-domain antibody have an excellent activity and high therapeutic efficacy.

The invention provides a probe for cell senescence analysis and a preparation method and application thereof, and belongs to the technical field of cell detection. The invention discloses a probe for cell aging analysis. The probe comprises fusion protein formed by fibronectin RGD and fluorescent protein, the fibronectin RGD is a polypeptide fragment containing an amino acid sequence as shown in SEQ ID NO: 1. The probe is fixed on a solid-phase carrier and then co-incubated with cells to be detected, the condition of senescent cells can be analyzed and judged by detecting the intensity of a fluorescence signal, the purpose of rapid analysis is achieved, the analyzed cells can be recycled and then continuously cultured, the detection cost is low, and the probe is suitable for large-scale popularization and application in the market.

The present invention relates to a novel antibody and antibody fragment specifically binding to Nectin-4, and a composition containing the antibody or the antibody fragment. In addition, the present invention relates to a nucleic acid encoding the antibody or the antibody fragment thereof, a host cell containing same, and a related use. Further, the present invention relates to therapeutic and diagnostic uses of the antibody and the antibody fragment.

The present invention relates to a heterotandem bicyclic peptide complex which comprises a first peptide ligand, which binds to Nectin-4, conjugated via a linker to two second peptide ligands, which bind to CD137. The invention also relates to the use of said heterotandem bicyclic peptide complex in preventing, suppressing or treating cancer.

The invention provides application of G3BP1 in preparation of a medicine for protecting barrier function integrity of vascular endothelial cells, and belongs to the technical field of biological medicine manufacturing. The invention provides application of G3BP1 in preparation of a medicine for protecting barrier function integrity of vascular endothelial cells. The present invention relates to G3BP1 that ensures the sustained expression of key adherent junction proteins (VE-cadherin, p120) by directly binding to and stabilizing the mRNA of these proteins; meanwhile, the G3BP1 is combined with the MYD88mRNA to promote the degradation of the MYD88mRNA, so that a permeability-promoting MYD88-ARNO-ARF6 signal channel is inhibited, especially under the condition of an inflammation period. Therefore, the G3BP1 regulates and maintains the integrity of the vascular barrier through double transcription, and a new treatment strategy is provided for damage repair of the functional integrity of the vascular endothelial cell barrier.

The invention provides a Nectin-4 targeting bicyclic peptide compound as shown in a formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof as a nuclide ligand, and belongs to the field of medicines. The invention also provides a complex containing the bicyclic peptide compound, the bicyclic peptide compound is further connected with radionuclide, a pharmaceutical composition containing the complex, and application of the complex and the pharmaceutical composition in preparation of drugs for preventing, treating, treating and / or alleviating cancers. # imgabs0 #

The invention belongs to the technical field of biological medicines, and relates to a protein degradation system based on polyamide-amine dendrimers as well as a preparation method and application of the protein degradation system. The protein degradation system is of a nano-particle structure, and the nano-particle structure comprises silicon dioxide nano-particles and a polyamide-amine type dendritic polymer layer coating the surfaces of the silicon dioxide nano-particles. An MDM2 protein ligand, a GLUT1 protein ligand and an E3 ubiquitin enzyme ligand are connected to the polyamide-amine dendritic polymer layer through chemical bonds. The protein degradation system provided by the invention can be used for synergistically degrading the MDM2 protein and the GLUT1 protein. The synergistic degradation strategy not only can effectively inhibit proliferation and energy metabolism of tumor cells, but also can significantly enhance the stability of the p53 protein. By recovering the normal function of the p53 protein, the growth of tumor cells is further inhibited, and a new strategy is provided for tumor treatment.

The invention relates to the technical field of biological medicines, and particularly discloses a dimer bicyclic peptide nuclide ligand and application thereof. The dimer bicyclic peptide nuclide ligand disclosed by the invention has a structure as shown in a formula I: # imgabs0 # formula I. The dimer bicyclic peptide nuclide ligand disclosed by the invention can be prepared into a nuclide probe targeting Nectin-4 after being labeled by radionuclide, the dimer bicyclic peptide nuclide ligand is good in radiation stability and ideal in pharmacokinetics, a tumor overexpressed by the Nectin-4 is high in uptake of the dimer bicyclic peptide nuclide ligand, and the tumor and muscle uptake ratio and in-vivo metabolic performance are good.

To provide peptide ligands, and peptide complexes comprising the peptide ligands conjugated to a second peptide.SOLUTION: The present invention provides a peptide ligand that binds to Nectin-4 present on a cancer cell, or a pharmaceutically acceptable salt thereof, the peptide ligand comprising a polypeptide comprising at least three reactive groups separated by at least two loop sequences, and a molecular scaffold that forms covalent bonds with the reactive groups of the polypeptide, such that at least two polypeptide loops are formed on the molecular scaffold, wherein the polypeptide is a modified derivative of a specific sequence.SELECTED DRAWING: None

The invention discloses a cell adhesion protein Nectin-4 targeted bicyclic peptide fluorescent probe and a preparation method thereof, the probe provided by the invention can be used for accurate detection of recurrent tumors and metastatic lymph nodes, and the probe is applied to rapid pathology and fluorescent surgical navigation in an operation. The method has the advantages of high signal-to-background ratio, high specificity and long imaging time window.

The present invention discloses a novel coronavirus nano-vaccine with targeted synergistic effect, belonging to the field of vaccines. The active ingredient of the vaccine is a fusion protein, which includes the amino acid sequence of the RBD domain of the novel coronavirus. The N-terminus of the amino acid sequence of the RBD domain is connected to XCL1 through a flexible linker GSG, and the C-terminus of the RBD domain sequence is connected to the Ferritin protein through a flexible linker GSG. The purified XCL1-RBD-Ferritin can be assembled into nanoparticles of 24-mers, improving the efficiency of RBD antigen in activating DCs, especially DC1s, thereby efficiently initiating humoral and cellular immune responses.

The invention belongs to the field of biological medicine, and particularly relates to an artificially synthesized polypeptide P2 and application thereof in resisting herpes virus infection. According to the invention, a polypeptide P2 of key amino acid residues (77N, 80I, 82N, 84N, 85N and 129F) combined with virus glycoprotein gD in a specific targeting host cell surface receptor Nectin-1 is designed and obtained through an RFdiffusion algorithm; the polypeptide P2 can significantly inhibit PRV infection, and has no significant cytotoxicity; the polypeptide P2 can be used for remarkably down-regulating PRV UL42 protein expression and gB mRNA (messenger Ribonucleic Acid) level; based on the conservative property of Nectin-1 in a herpes virus invasion mechanism, the polypeptide P2 can also be used for inhibiting infection of other herpes viruses (such as HSV-1 and HSV-2), and an important strategy is provided for developing novel anti-herpes virus drugs.

The invention discloses an application of a compound in preparation of a medicine for protecting pulmonary vascular endothelial cells, and relates to the technical field of medicines, the application of the compound in preparation of the medicine for protecting the pulmonary vascular endothelial cells comprises the compound, and the compound is used as an active component of the medicine. The compounds are useful as inhibitors of OSM causing barrier damage to endothelial cells; the compound is used for inhibiting OSM-induced vascular endothelial cell permeability increase in drugs. The compound is used for improving the reduction of vascular epithelial cell membrane electrical impedance caused by OSM in medicines, so that the integrity of a cell barrier is protected; the compound is used for up-regulating vascular endothelial cadherin expression and reducing vascular endothelial permeability in medicines, and repairing vascular endothelial barrier damage caused by OSM. The compound can reverse the reduction of OSM-induced endothelial adhesion connexin and protect the damage of an endothelial barrier, and has a remarkable application prospect in medicines for protecting pulmonary vascular endothelial cells.

Provided are anti-Claudin-6 antibodies (e.g., VHH domain antibodies), and a chimeric antigen receptor (CAR) that binds to Claudin-6 comprising same in an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Immune effector cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

The present disclosure provides Nectin-4 antibody drug conjugates (ADCs) comprising exatecan and pharmaceutical compositions thereof, and methods of using the ADCs for the treatment of cancer.

The invention discloses a Nectin-4 targeted nucleic acid aptamer nuclide diagnosis and treatment integrated probe, and relates to the field of biotechnology and diagnosis and treatment integration and treatment, and the diagnosis and treatment integrated probe comprises a Nectin-4 targeted nucleic acid aptamer, a nuclide chelating ligand and a nuclide for marking; wherein the Nectin-4 targeting nucleic acid aptamer has a base sequence as shown in any one of SEQ ID NO.1-3, or has a base sequence of which the homology with the base sequence as shown in any one of SEQ ID NO.1-3 is more than 80%. The diagnosis and treatment integrated probe prepared by the invention can be applied to PET / CT diagnosis and internal irradiation radioactive therapy, on one hand, non-invasive visual molecular imaging of Nectin-4 receptor protein overexpression tumors is realized, and on the other hand, radioactive therapy of malignant bladder cancer is further realized; the probe is good in specific targeting effect and high in tumor uptake and has a diagnosis and treatment integrated function.

The present invention relates to an isolated antibody or antigen-binding fragment specifically binding to the Nectin-4 protein, and a multispecific antibody containing the isolated antibody or antigen-binding fragment specifically binding to the Nectin-4 protein. The present invention also relates to a nucleic acid encoding the isolated antibody or antigen-binding fragment specifically binding to the Nectin-4 protein and the multispecific antibody, a host cell containing the isolated antibody or antigen-binding fragment specifically binding to the Nectin-4 protein and the multispecific antibody, and a method for preparing the isolated antibody or antigen-binding fragment specifically binding to the Nectin-4 protein and the multispecific antibody. Furthermore, the present invention relates to the diagnostic, preventive and / or therapeutic use of the isolated antibody or antigen-binding fragment specifically binding to the Nectin-4 protein and the multispecific antibody.

Disclosed herein are VH-only single domain binders that target claudin 18.2 (CLDN18.2) and chimeric antigen receptors (CARs) that contain the same, engineered T cells containing the CLDN18.2-targeting CARS, and methods of treating cancer (e.g., gastric cancer or pancreatic cancer) using the CAR-T cells.

The invention discloses a monoclonal antibody 5B11 for recognizing an extracellular domain of peste des petits ruminants virus H protein and application of the monoclonal antibody 5B11, and belongs to the technical field of monoclonal antibodies. According to the invention, PPRV-H-185 protein with an amino acid sequence as shown in SEQ ID NO.1 is used for immunizing a mouse, a monoclonal antibody 5B11 with a neutralizing effect is prepared, a heavy chain variable region of the monoclonal antibody 5B11 comprises CDR1-3 with an amino acid sequence as shown in SEQ ID NO.7-9, and a light chain variable region of the monoclonal antibody 5B11 comprises CDR1-3 with an amino acid sequence as shown in SEQ ID NO.12-14. Experimental results show that the monoclonal antibody can be combined with a virus, so that the virus loses the ability of combining an epithelial cell H protein receptor Nectin-4 and a lymphocyte H protein receptor SLAM, and the virus is prevented from invading cells. The invention provides a new biological material for detection and prevention of peste des petits ruminants virus, and has a good clinical application prospect.

Provided herein are polypeptides and conjugates thereof, including radionuclide conjugates, useful in compositions and methods of treating, diagnosing, monitoring, and / or imaging a disease, disorder, or condition associated with expression of one or more targets, including Nectin-4.

The present disclosure relates to a method for improving the quality of glycosylated antibody drug conjugates (DAR distribution, stability, etc.) using activated carbon. Specifically, the present disclosure employs hydrophobic interaction chromatography (HIC) column, protein A chromatography, activated carbon stirring, and buffer exchange, alone or in series, to remove free glycosyltransferases. As a result, the purity of the glycosylated antibody drug conjugates is improved, and the degradation of the antibody drug conjugates is prevented. Ultimately, the drug substance (DS) of OBI-902 (anti-TROP2 antibody drug conjugate) and OBI-904 (anti-Nectin-4 antibody drug conjugate) is further determined.

This invention relates to mini-binding proteins targeting Nectin-4, their drug conjugates, and their applications. The present invention has screened and obtained a class of mini-binding proteins specifically targeting Nectin-4, whose amino acid sequences include any one of SEQ ID Nos. 1-6. This application further conjugates the mini-protein conjugates with the microtubule inhibitor VcMMAE to generate mini-protein drug conjugates (MPDCs), which can target and kill Nectin-4 positive tumor cells.

The invention discloses an antibody targeting to Nectin-4 and an application of the antibody. The antibody targeting Nectin-4 comprises at least one immunoglobulin single variable structural domain, the immunoglobulin single variable structural domain comprises CDR1, CDR2 and CDR3, the amino acid sequence of the CDR1 is INVMG, the amino acid sequence of the CDR2 is TITSGGSTNYADSVKG, and the amino acid sequence of the CDR3 is DRMDGSIWYDY. The antibody provided by the invention has strong binding force with the Nectin-4 antigen, and has the advantages of strong tumor targeting, fast tumor enrichment and long retention.

Provided herein are antibodies or antigen-binding fragments thereof targeting Nectin-4. Also provided herein are the uses and methods of the antibodies or antigen-binding fragments thereof, or the antibody-drug conjugates in treating cancers.

The present invention relates to use of expression vectors and other compounds in methods to disrupt the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, uncoupling the nucleus from its linkage to the cytoskeleton, resulting in amelioration of diseases caused by one or more Lmna mutations, so-called laminopathies. More particularly, the invention relates to the expression of dominant negative SUN domain protein and / or dominant negative KASH domain protein to disrupt, for example, the LINC complex in cardiomyocytes for suppressing disease progression in dilated cardiomyopathy (DCM).

The present disclosure provides conjugates of anti-Nectin-4 antibodies or antigen binding fragments thereof to a myeloid cell agonist, compositions comprising the conjugates, and methods of treating cancer with the conjugates. The present disclosure also provides for anti-Nectin-4 antibodies or antigen binding fragments thereof and method for using the antibodies or antigen binding fragments thereof in treating cancer.

The invention relates to the technical field of biology, in particular to a method for improving affinity of a nano antibody based on computer-aided design. According to the method, a series of bioinformatics tools for nano antibody affinity maturation are investigated and researched in literatures, and part of databases, servers and software are optimized to construct a set of computer-aided design (CAD) nano antibody affinity improvement method by evaluating the operability and the improvement effect of the tools. In order to verify the effectiveness and universality of the method, based on the method, a high-affinity mutant nano antibody is virtually screened out of an Anti-Nectin-4 camel source nano antibody NBNT-1 and an Anti-PD-L1 shark source nano antibody NBNT4 screened in a synthetic library through model construction, model evaluation, site prediction, molecular docking, structural analysis, mutation prediction and mutation evaluation. Traditional in-vitro affinity maturation methods, such as error-prone PCR, are low in screening efficiency, large in randomness introduced by mutation, long in experimental period, large in workload and difficult to accurately optimize the affinity of target molecules. According to the method, various defects of a traditional in-vitro affinity maturation method are overcome, and the success rate and efficiency of affinity maturation are improved.

The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of Nectin-4.The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by Nectin-4.

The invention discloses an oral drug delivery system with a double-emulsion structure and application of the oral drug delivery system in preparation of drugs for treating premature ovarian insufficiency, and belongs to the technical field of biological medicines. The oral drug delivery system comprises droplet particles formed by wrapping an MSCs conditioned culture medium with an oil-phase solvent, and exosomes uniformly distributed on the outer surfaces of the droplet particles, so that a double-emulsion structure is formed. Water-soluble MSC-CM is wrapped by a water-in-oil-in-water method to form a double-emulsion structure, so that water-soluble protein enters a human body to be absorbed in an oral manner. The MSC-CM composite has good structural stability and viscoelasticity, the particle size range is about 10-50 microns, contact with intestinal epithelial cells can be increased, meanwhile, the skeleton of the intestinal epithelial cells can be changed, expression of tight junction protein of the intestinal epithelial cells can be lowered, tight junction barriers of the intestinal epithelial cells can be opened, and therefore the bioavailability of MSC-CM is improved, and the MSC-CM composite has a good application prospect. The effect of treating the POI is achieved.