202 results about "Nectin" patented technology

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 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 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.

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 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 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.

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 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.

Disclosed herein are polypeptides and polypeptide complexes that are capable of binding tumor cell antigens and effector cell antigens. In some embodiments, the polypeptides and polypeptide complexes bind the tumor cell antigens and the effector cell antigens in a tumor microenvironment.

To provide anti-claudin 18.2 and anti-4-1BB bispecific antibodies, and uses thereof.SOLUTION: There are provided bispecific and multi-specific antibodies that target both claudin 18.2 (CLDN18.2) and 4-1BB. These antibodies, in the absence of CLDN18.2-expressing cells, can bind to 4-1BB but are unable to activate 4-1BB signaling. In the presence of CLDN18.2-expressing cells, however, these antibodies can trigger CLDN18.2-dependent 4-1BB signaling, leading to potent immune response to the CLDN18.2-expressing tumor cells.SELECTED DRAWING: None

The present invention relates to an antibody-drug conjugate binding to Nectin-2 and use thereof, in which a mouse monoclonal antibody (m12G1 clone) and a chimeric anti-Nectin-2 antibody (chimeric 12G1; c12G1), which are capable of specifically targeting Nectin-2, have been prepared. The c12G1 antibody specifically bound to the C2 domain of human Nectin-2 with high affinity, but did not bind to mouse Nectin-2. Subsequently, an antibody-drug conjugate comprising a c12G1 antibody conjugated to DM1 was prepared, and as a result of examining the cytotoxic effect thereof on cancer cells in vitro and in vivo, c12G1-DM1 induced cell cycle arrest in the mitotic stage of Nectin-2-positive ovarian cancer cells, but not in Nectin-2-negative cancer cells. c12G1-DM1 induced approximately 100-fold cytotoxicity at IC50 in the range of 0.1-7.4 nM in ovarian cancer cells as compared to normal IgG-DM1, and c12G1-DM1 exhibited approximately 91% tumor growth inhibition in a mouse xenograft model transplanted with OV-90 cells. These results suggest that c12G1-DM1 can be effectively used as a potential therapeutic agent for Nectin-2-positive ovarian cancer.

Provided are a pharmaceutical composition containing an anti-Nectin-4 antibody drug conjugate and a use thereof. The provided pharmaceutical composition has good stability.

Multispecific antibodies that bind to an effector associated antigen (EAA), such as CD28, and a disease associated antigen (DAA), such as Nectin-4, are provided, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat disorders, such as cancer, where modulation of effector cell activity against target cells can be used as a treatment modality.

The present invention provides an antibody or an antigen-binding portion thereof that binds to Nectin-4. Also provided is an antibody-drug conjugate (ADC) including a drug moiety conjugated to the anti-Nectin-4 antibody or antigen-binding portion thereof. Also disclosed are methods of using the antibody or ADC for inhibiting cancer cell proliferation.

The application discloses application of butyric acid in preparation of a medicine for treating oral ulcer, and belongs to the field of biological medicine. The butyric acid plays a therapeutic effect by increasing expression of tight junction proteins in oral mucosa tissue, reducing inflammatory reaction and promoting healing of oral ulcer. The application uses butyric acid to treat oral ulcer, evaluates the curative effect of butyric acid and explores the corresponding internal mechanism. The results show that the butyric acid has obvious effect in treating oral ulcer caused by chemotherapy, and provide a scientific basis for clinical application of butyric acid.

A use of an anti-Nectin-4 antibody drug conjugate in the preparation of drugs for treating gynecological tumors.

The invention discloses a sheep female stem cell separation and in-vitro culture method, and relates to the technical field of biologication.According to the technical scheme, the sheep female stem cell separation and in-vitro culture method is characterized in that 0.25% pancreatin is adopted for digestion for 1 hour at the room temperature, mechanical cutting operation is combined, intercellular connexin can be effectively decomposed, and the survival rate of the sheep female stem cells is increased; the ovarian granular cells are quickly released. Medical alcohol and a culture medium containing double antibodies are used for cleaning ovaries for many times, so that the probability of bacterial and fungal contamination is remarkably reduced. A DPBS buffer solution preheated at 37 DEG C and a DMEM / F12 culture medium containing 10% of FBS are used in the whole process, and stress damage to cells caused by temperature shock is avoided. Complete granular cells and tissue fragments are efficiently separated through filtration and centrifugation, and the purity of a cell suspension is improved. The method is developed on the basis of ovaries of sheep, does not depend on feeder layer cells or a complex three-dimensional culture system, can be operated only by conventional laboratory equipment, and is suitable for research scenes with limited resources.