186 results about "Claudin" patented technology

Provided are an anti-CLDN18.2 antibody or an antigen-binding fragment thereof, a derivative comprising said antibody or antigen-binding fragment thereof, a pharmaceutical composition, and related use of said antibody or antigen-binding fragment thereof for treating, diagnosing and detecting cancers.

The invention belongs to the field of biological medicines, and particularly discloses application of uridine in preparation of medicines for preventing and treating ulcerative colitis, including application of uridine in preparation of medicines for preventing and treating ulcerative colitis in acute stage, application of uridine in preparation of medicines for preventing and treating ulcerative colitis in remission stage and the like. Uridine can improve the symptoms of DSS-induced acute experimental colitis model mice, has a good treatment effect, and improves the weight of the model mice; experimental results indicate that a high-dose group of uridine has a good treatment effect, the mechanism and specificity of uridine up-regulate expression and activity of colon local SIRT1 protein, further inhibit phosphorylation activation of an NF-kappa B signal channel, regulate secretion of inflammatory factors and expression of tight junction protein, repair intestinal mucosal barrier while moderately regulating immunity, and improve the immunity of a human body. The systemic inflammatory response is effectively relieved.

The invention belongs to the technical field of biological medicine, and discloses application of cornu cervi degelatinatum extract in strengthening a skin barrier. The cornu cervi degelatinatum extract disclosed by the invention can promote proliferation of HacaT cells and expression of tight junction protein Claudin-1, also has better capabilities of removing hydroxyl free radicals, DPPH free radicals and superoxide anions and an effect of promoting wound healing, and can protect a skin mechanical barrier and promote barrier injury repair. The cornu cervi degelatinatum extract has a good application prospect in preparation of drugs for promoting wound healing and products related to strengthening and toughening skin barriers, and resource development and utilization of cornu cervi degelatinatum are enriched.

Provided herein anti-human claudin 6 (CLDN6) and anti-human C5 antibodies.

The present invention relates to bispecific antibodies against claudin 18.2 and CD3, pharmaceutical compositions comprising said bispecific antibodies, and related uses in the treatment of cancer.

Provided are combination therapies that include an inhibitor of PD-1 or PD-L1 and an antibody-drug conjugate targeting claudin 18.2.

Antibodies and compositions against Claudin 6 and uses thereof are provided.

The invention discloses application of fraxinellone as a cGAS-STING signal channel inhibitor in preparation of a medicine for treating inflammatory bowel disease, and belongs to the technical field of biological medicine. Aiming at the problem that the specific action mechanism between fraxinellone and the inflammatory bowel disease is not clear, the invention researches the specific action mechanism of fraxinellone for exerting the treatment and protection effects on the inflammatory bowel disease from the in-vivo and in-vitro aspects. Results show that the FRA can significantly inhibit the increase of the ROS level of IEC-6 cells caused by LPS, improve the mitochondrial membrane potential, significantly improve the pathological characteristics of DSS-induced mouse weight loss, DAI index increase, red, swollen and shortened colon, damaged colon tissue structure and the like, and inhibit the expression level of inflammatory factors. According to the present invention, it is found that the FRA can up-regulate the TJ tight junction protein and recover the intestinal barrier function by regulating the expression of cGAS-STING signal channel related proteins such as cGAS, STING, p-TBK1, NF-kappa B and the transcriptional level of mRNA, such that the IBD treatment effect is provided, and the basic basis is provided for the development of the new IBD treatment drug or strategy.

The application discloses a use of a solute carrier family 25A33 gene in preparation of a medicament for treating presbycusis, and the use is achieved by enhancing SLC25A33 expression on an endolymphatic vascular stripe, by maintaining mitochondrial function stability of pericyte cells around the vascular stripe, by reducing active oxygen free radical (ROS) generation, and by blocking TGFbeta / SMAD pathway-mediated pericyte differentiation, so as to protect the integrity of the blood labyrinth barrier. Animal experiments show that overexpression of SLC25A33 can significantly reduce the hearing threshold of a presbycusis model mouse, protect the structure of the blood labyrinth barrier, and improve the expression of tight junction proteins, and the SLC25A33 gene has the potential to treat presbycusis.

The present application provides a nanobody targeting Claudin18.2 and a nucleic acid sequence encoding the same. The present application also provides a multispecific antibody, a chimeric antigen receptor, an antibody conjugate comprising the Claudin18.2 nanobody, a pharmaceutical composition and a kit comprising the same, and the use of the same in the diagnosis / treatment / prevention of diseases associated with Claudin18.2 expression.

The present invention provides a method of constructing a library of binder scaffolds (library of protein scaffolds) comprising the steps a) providing an initial polypeptide, wherein said initial polypeptide comprises or consists of a polypeptide having at least 90% identity to SEQ ID NO:1, and b) introducing diversity into copies of said initial polypeptide to form the binder scaffold library (protein scaffold library).

Described herein are methods for inhibiting a solid tumor expressing claudin-6 in a human subject, comprising administering to the human subject an effective amount of a composition comprising conjugates of a CLDN6-specific antigen-binding protein covalently bound to heterologous moieties comprising structural formula (I):whereina first plurality of the conjugates are bound to four heterologous moieties comprising structural formula (I);at least about 95% of the first plurality of conjugates are structurally homogenous; andthe effective amount is in a range of about1.0 mg of conjugate / kg weight of the subject to 10 mg of conjugate / kg weight of the subject.

The invention discloses a manganese-based nano-enzyme composite material as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) preparing Mn3O4-PVP from Mn3O4 NPs and PVP10, and then loading the Mn3O4-PVP into a ZIF-8 structure in the process that Zn < 2 + > and 2-MI react to form ZIF-8, so as to obtain Mn3O4-coated ZIF-8 NPs; (2) covering the surface of the Mn3O4 ZIF-8 with HA through ion coordination, and synthesizing MZH; and (3) carrying out clathration on MZH through ES100, and synthesizing MZH coated ES100. By inhibiting a TLR4 / NF-kappa B pathway, activating an Nfr2 / Keap1 pathway and increasing expression of intestinal tight junction protein, mouse colitis induced by DSS is resisted, and symptoms of the mouse colitis are relieved.

The present invention relates to CLAUDIN-6 conjugate dosing for cancer treatment. Described herein are methods for inhibiting a Claudin-6 expressing solid tumor in a human subject comprising administering to the human subject an effective amount of a composition comprising a CLDN6 specific antigen binding protein covalently bonded to a heterologous moiety comprising structural formula (I), wherein a first plurality of the conjugates are bonded to four heterologous moieties comprising structural formula (I); at least about 95% of the first plurality of conjugates are structurally uniform; and the effective amount is in the range of about 1.0 mg conjugate / kg body weight of the subject to 10 mg conjugate / kg body weight of the subject.

The present invention relates to a strain of Lactobacillus johnsonii N5 and its application in preventing and treating enteritis and diarrhea. Lactobacillus johnsonii N5), was deposited in the China Center for Type Culture Collection on February 10, 2023, with the deposit number CCTCC NO: M2023104. The Lactobacillus johnsonii N5 was isolated from the fecal microorganisms of piglets resistant to heat stress-induced diarrhea. This Lactobacillus johnsonii N5 has the effect of alleviating enteritis and diarrhea, which is specifically reflected in: significantly enhancing the expression of intestinal epithelial tight junction proteins and cytoprotective heat shock protein 70, improving the immune balance of animal intestinal T cells, enhancing immune tolerance, and reducing the degree of intestinal inflammation and the occurrence of diarrheal diseases in animals. Therefore, Lactobacillus johnsonii N5 has a significant effect in preventing and treating diarrhea and related intestinal inflammatory diseases.

The application discloses a phytosterol and phytosterol ester complex agent and application thereof, wherein the complex agent comprises phytosterol and phytosterol ester with a mass ratio of 1:10. The application aims to improve the water solubility and bioavailability of phytosterol, realize synergistic effect by compounding phytosterol and phytosterol ester, interfere with the lipid acquisition of coccidia from multiple targets, up-regulate the expression of cecal tight junction protein to repair the intestinal barrier, inhibit the release of serum and cecal pro-inflammatory factors to relieve inflammatory reaction, regulate the expression of genes related to lipid synthesis and fatty acid oxidation to remodel lipid metabolism homeostasis, and then effectively inhibit the growth and development of coccidia, and significantly improve the growth performance of broilers infected with coccidia.

Disclosed in the present invention are a CLDN18.2-targeting nanobody, and a preparation method therefor and the use thereof. Specifically disclosed are CLDN18.2-targeting nanobodies having amino acid sequences of SEQ ID NOs: 2, 4 and 20, respectively, and the uses thereof. The nanobody of the present invention has a high affinity and a good specificity, can bind to a CLDN18.2 antigen, has an anti-tumor activity, and cannot bind to other CLDN family members. The nanobody has few toxic and side effects, and thus can be prepared into a prophylactic and therapeutic drug for a Claudin 18.2 target-related disease, a diagnostic drug, a detection or in-vivo imaging product for a Claudin 18.2 protein, etc.

The present invention provides anti-claudin 18.2 nanobodies or their binding fragments. The antibody exhibits good specificity, and immune effector cells targeting claudin 18.2 prepared using the antibody show good therapeutic efficacy in treating or improving diseases with positive claudin 18.2 expression.

Provided herein are Claudin 18.2 binding agents and chimeric antigen receptors (CARs) that comprise Claudin 18.2 binding molecules that specifically bind to Claudin 18.2, and the immune cells, such as CAR-T cells, that comprise these Claudin 18.2 specific CARs.Also provided are the methods for producing and using Claudin 18.2 specific CARs and Claudin 18.2 binding agents, and the immune cells that comprise Claudin 18.2 specific CARs.

The invention discloses asterias amurensis glucan as well as a preparation method and application thereof, and belongs to the technical field of biological medicine, the asterias amurensis glucan is obtained by combining an enzymolysis method with anion exchange column chromatography and gel column chromatography purification, the main chain structure of the asterias amurensis glucan is 1, 4-linked alpha-D-glucose, and the main chain structure of the asterias amurensis glucan is 1, 4-linked alpha-D-glucose. A terminal alpha-D-glucose branch chain is arranged at the O-6 position of a main chain, and meanwhile, a small amount of mannose and galactose are contained. Moreover, it is proved for the first time that the asterias amurensis glucan can serve as an intestinal barrier protective agent, and oxidative damage, caused by H2O2, of intestinal epithelial cells is improved by up-regulating an Nrf2 signal channel and tight junction protein. Therefore, the asterias amurensis glucan prepared by the invention has a huge potential of being developed into medicines and health-care products for protecting intestinal tracts.

The invention discloses a probiotic which is derived from human milk and has the effects of resisting oxidation, resisting inflammation, protecting tissues and protecting intestinal barriers and application of the probiotic. Lactobacillus paracasei DPUMW-M14-9 is preserved in the general microbiological center of the China Committee for Culture Collection of Microorganisms, and the preservation number is CCTCC M 20252990. The strain has the characteristics of acid resistance, bile resistance, strong oxidation resistance, high surface hydrophobicity, self-aggregation capability and the like. The lactobacillus paracasei DPUMW-M14-9 can effectively adhere to epithelial cells, promote cell proliferation and regulate and control the process of a cell cycle. The bacterial strain can be used for inhibiting proinflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) induced by lipopolysaccharide (LPS) and repairing tight junction proteins (ZO-1, Occludin and Claudin-1) at the same time, so that the integrity of epithelial cells is enhanced.

This application relates to antibody-drug conjugates and their use.

The present disclosure provides antigen-binding proteins which bind to Claudin-6 (CLDN6). In various aspects, the antigen-binding proteins bind to Extracellular Loop 2 (EL2) of the extracellular domain of CLDN6. Related polypeptides, nucleic acids, vectors, host cells, and conjugates are further provided herein. Kits and pharmaceutical compositions comprising such entities are moreover provided. Also provided are methods of making an antigen-binding protein and methods of treating a subject having cancer.

The present invention provides Claudin-6-specific immunoreceptors (T cell receptors and artificial T cell receptors (chimeric antigen receptors; CARs)) and T cell epitopes which are useful for immunotherapy.

The invention discloses recombinant lactobacillus casei for expressing sialyltransferase ST6GALNAC1, and belongs to the technical field of genetic engineering and microorganisms. The recombinant bacterium is obtained by cloning an ST6GALNAC1 gene to a pPG612 vector and electrically transforming the ST6GALNAC1 gene into lactobacillus casei ATCC393. Experiments show that the engineering bacterium can significantly enhance glycosylation modification of intestinal mucoprotein MUC2, improve expression of tight junction proteins (ZO-1, Occludin and Claudin-1), inhibit activation of a p38 / MAPK inflammation pathway and regulate an intestinal flora structure, so that intestinal injury and systemic inflammatory response caused by salmonella are effectively relieved. The invention provides a strain basis and technical support for developing a novel oral microecological preparation.

The invention belongs to the technical field of medicine and pharmacy, and particularly relates to application of an AP1B1 allosteric activator of ethyl gallate. In the invention, AP1B1 is a beta 1 subunit (AP1B1) of a linking factor associated protein complex 1 (AP-1), and is an essential component for assembling a functional AP-1B complex. The ethyl gallate is used as an allosteric activator of AP1B1 and is specifically combined with an allosteric pocket of the AP1B1 to induce the AP1B1 to generate conformational change, so that the vesicle transportation function of an AP1B complex is activated, and the substrate-side membrane protein sorting capacity is recovered. A target dependence experiment verifies that the effect of ethyl gallate on promoting tight junction protein ZO-1 expression and membrane localization in AP1B1 knocked-down Caco-2 cells is remarkably weakened, and it is prompted that the intestinal barrier protection function of ethyl gallate depends on AP1B1. The invention provides a new strategy for developing medicines for treating intestinal barrier injury related diseases.

The present disclosure provides an anti-claudin-6 antibody (e.g., a VHH domain antibody) and a chimeric antigen receptor (CAR) that binds to claudin-6. The chimeric antigen receptor includes an anti-claudin-6 antibody 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 application discloses a nanobody targeting Claudin 18.2 and an application thereof, and belongs to the technical field of molecular biology. In view of the unique advantages of the nanobody in the prior art, the application provides a nanobody targeting Claudin 18.2, wherein the amino acid sequence of the nanobody is shown as SEQ ID NO. 1; the nanobody has strong affinity to 293T-Claudin 18.2 positive cells and can be combined with the Claudin 18.2 protein expressed on the cell surface. The nanobody targeting Claudin 18.2 provided by the application can be prepared by large-scale expression of an in-vitro engineering bacterium, can be applied to preparation of a protein detection antibody or a therapeutic antibody, can be used for in-vitro and in-vivo detection of tumor tissues expressing Claudin 18.2, and has important commercial value in clinical disease diagnosis and treatment.

The invention discloses an application of a solute carrier family 25A33 gene in preparation of a medicine for treating senile deafness, which is characterized in that SLC25A33 expression on inner ear vascular lines is enhanced, the mitochondrial function stability of vascular periripple cells is maintained, the production of reactive oxygen species (ROS) is reduced, and pericyte differentiation mediated by a TGF (Transforming Growth Factor) beta / SMAD pathway is blocked, so that the senile deafness is inhibited, and the senile deafness is inhibited. Therefore, the integrity of the blood lost barrier is protected. Animal experiments show that overexpression of the SLC25A33 can significantly reduce the hearing threshold of an age-related deafness model mouse, protect the structure of a blood labyrinth barrier and improve the expression of tight junction protein, and the SLC25A33 gene has the potential of treating age-related deafness.

The invention belongs to the technical field of gene engineering, and provides Hsp60 receptor targeted recombinant lactobacillus plantarum as well as a construction method and application thereof, lactobacillus plantarum is taken as a host, pPG612 is taken as an expression vector, and CsgB gene or CsgF gene is expressed. The two engineering probiotics can express target protein and can be stably expressed on the surfaces of thalli, the AB.9 intestinal epithelial cells can be effectively adhered, and the adhesion and invasion of the A.veronii to the AB.9 cells can be inhibited. And secondly, the engineering probiotics LP-pPG-CsgB and LP-pPG-CsgF can promote the proliferation of dendritic cells, T lymphocytes and B lymphocytes, and improve the IgT secretion of intestinal mucus. The engineering bacteria can be competitively combined with an intestinal epithelial cell Hsp60 receptor, down-regulate p65 expression, inhibit NF-kappa B signal channel activation, regulate intestinal tight junction protein redistribution and down-regulate proinflammatory factor expression through a TLR4 / TLR5 dependent NF-kappa B signal channel, and the engineering bacteria can increase the abundance of effective microbial communities in the intestinal tract of the snakeheaded fish, so that the growth of the snakeheaded fish is promoted, and the growth of the snakeheaded fish is promoted. And the flora can transfer, mediate and activate immune response through a feeding environment.