37 results about "Hepatitis b viral" patented technology

The present application relates to the technical field of knowledge graph, in particular to a multi-task hepatitis B drug screening method and system based on knowledge graph assistance, comprising the following steps: based on hepatitis B virus genotype sequence data recorded over time, patient drug use records and drug sensitivity. In the present application, multi-dimensional dynamic time series data such as virus genotype sequence data, patient drug use records and drug sensitivity are integrated, the interaction events between entities are marked by time stamp, the dynamic characteristics such as virus variation track and drug efficacy change are embedded in the graph node attributes, so that the knowledge representation can reflect the time dependence in the real scene. Based on biological pathway annotation information and protein interaction data, the hyperedge connection multi-entity set is defined, the limitation of traditional knowledge graph which only supports binary relationship is expanded, the drug combination and multi-target synergistic mechanism are explicitly modeled, and the misjudgment of combination effect caused by the simplification of interaction relationship is avoided.

The present disclosure relates to a ribavirin derivative-embedded double-stranded siRNA analogue, a conjugate comprising the same, and salts and uses thereof. The double-stranded siRNA analogue, the conjugate comprising the same, and the salts thereof of the present disclosure can effectively inhibit multiple viral indicators such as hepatitis B virus DNA, pgRNA, S antigen, E antigen, etc., and provide an effective and feasible method for the treatment of hepatitis B.

The invention discloses a traditional Chinese medicine composition for treating fatty liver and reducing hepatitis B virus load. The traditional Chinese medicine composition is prepared from the following raw material medicines: prepared rehmannia root, rhizoma polygonati (processed), radix asparagi, schisandra chinensis, hawthorn leaf, glossy privet fruit, oriental wormwood, radix curcumae, illicium verum and salvia miltiorrhiza. According to the technology of the invention, liver treatment is a preparation based on compatibility of traditional Chinese medicine syndrome differentiation in which liver, spleen and kidney are treated at the same time, fat in the liver can be effectively removed, damage of hepatitis B virus to the liver can be reduced, hepatitis B virus reproduction can be effectively inhibited, the load of hepatitis B virus can be reduced, and multiple curative effects of liver treatment, liver nourishing and liver protection can be realized; the traditional Chinese medicine composition is superior to other treatment medicines and treatment technologies for fatty liver in modern medicine. The method can be widely applied to the fields of medicines, functional foods, health-preserving and health-care products, common foods and beverages and the like.

Provided herein are non-naturally occurring variants of the hepatitis B virus (HBV) Core protein, the HBV polymerase N-terminal domain, and the HBV polymerase C-terminal domain, as well as immunogenic fragments thereof. Fusion proteins comprising the HBV variants fused to a herpes simplex virus (HSV) glycoprotein (gD) sequence, as well as methods of using the fusion proteins, are also provided.

The utility model relates to a convenient-to-titrate hepatitis B virus five-item detection kit, which solves the technical problem that the dropping position is easy to be inaccurate when the existing detection kit detects dropping buffer solution, and comprises a sample adding hole, slots arranged on the side wall of a detection card body are symmetrically arranged on two sides of the sample adding hole, and the slots are arranged on the side wall of the detection card body. The detection card body is provided with a plurality of slots, the slots are detachably matched with arched limiting plates in a sliding manner, the inner sides of the lower ends of the limiting plates are fixedly provided with inserting blocks matched with the slots, the limiting plates are provided with limiting holes corresponding to the sample adding holes, and integrated disposable buffer solution devices are inserted into the limiting holes. After the limiting plate is inserted into the detection card body, a limiting foundation for subsequently dropwise adding a buffer solution can be fixed, and after a buffer solution device is arranged, the accuracy of dropwise adding the buffer solution can be improved, the buffer solution can be accurately dropwise added, meanwhile, the waste of the buffer solution is avoided, the buffer solution is saved, and only a small amount of buffer solution needs to be prepared.

This invention belongs to the field of affinity membrane and bioseparation technology, and provides a cellulose-based affinity membrane for hepatitis B virus (HBV), its preparation method, and its application. The affinity membrane consists of a base membrane and an affinity ligand immobilized on the base membrane. The base membrane is a carboxylated cellulose filter membrane or a carboxylated modified cellulose filter membrane. The affinity ligand is a biomolecule that specifically recognizes HBV surface antigen. The carboxyl groups of the base membrane and the amino groups of the affinity ligand are linked by amide bonds. Unreacted carboxyl groups on the base membrane are blocked by a blocking reagent. The carboxyl content of the base membrane is 400-1000 μmol / g, the pore size is 400-1000 nm, and the porosity is 30%-60%. The application refers to the use of the above-mentioned affinity membrane in the specific clearance of HBV from HBV-positive plasma. This invention can achieve efficient and specific clearance of HBV from plasma, maximally preserving the activity and function of normal plasma components, and improving the feasibility of industrial application.

The application discloses a monoclonal antibody against hepatitis B virus e antigen and a preparation method and application thereof, and relates to the field of hepatitis B antigen detection. Specifically, the antibody provided by the application has HCDR1-3 as shown in SEQ ID NO: 1, 2 and 3 respectively, and LCDR1-3 as shown in SEQ ID NO: 4, 5 and 6 respectively. The provided antibody can specifically recognize human hepatitis B e antigen. The positive coincidence rate, the negative coincidence rate and the total coincidence rate of a detection reagent constructed using the antibody and the Abbott control reagent are all 100%. Compared with an existing antibody 3A3, the stability and the repeatability of detection are significantly improved, and the early detection rate of the reagent kit has important value.

Provided in the present application are a glycosylated fusion protein, a nucleic acid molecule, an expression vector, a host cell and the use thereof. A first aspect of the present application provides the glycosylated fusion protein, comprising a murine Fc variant and a hepatitis B virus antigen, wherein the murine Fc variant is obtained by performing amino acid mutation and non-mammalian glycosylation modification on a murine Fc fragment, the murine Fc variant comprises at least one of alanine at position 223, alanine at position 228, alanine at position 230, leucine at position 330, and glutamic acid at position 332, the glycosylation modification does not comprise sialic acid modification, and the positions are numbered according to the EU numbering system. The fusion protein can bind to DC cells and activate DC cells, and thus promote the proliferation and activation of specific T cells.

Provided are a pharmaceutically acceptable salt, a crystal form and a preparation method of a TLR7 / 8 agonist compound of formula I, a pharmaceutical composition containing the pharmaceutically acceptable salt, and a medical use of the pharmaceutically acceptable salt, which can be used for preparing drugs for preventing or treating Toll-like receptor 7 / 8 (TLR7 / 8) related diseases, such as a new therapeutic agent for human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection and cancer.

The invention belongs to the field of biological medicines, and relates to a pharmaceutical composition and application thereof in preparation of medicines for preventing and treating hepatitis B virus. Comprising a nucleic acid drug and a carrier for loading the nucleic acid drug, the carrier can specifically target liver Kupffer cells, the nucleic acid drug is mRNA, and a gene sequence for coding the mRNA comprises nucleotide sequences shown as SEQ ID NO: 1 and SEQ ID NO: 2. The pharmaceutical composition provided by the invention can specifically activate Notch signal channels of Kupffer cells, and can play a role in treating and preventing hepatitis B; meanwhile, the anti-HBV effect of the pharmaceutical composition depends on the participation of Kupffer cells, and the pharmaceutical composition becomes a potential novel strategy for clinical treatment of chronic hepatitis B.

This invention relates to a fusion antigen mRNA molecule, which encodes a protein comprising at least two of the following: hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein Core, hepatitis B X antigen protein HBxAg, and hepatitis B preS1 antigen protein PreS1, preferably comprising hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein, and hepatitis B PreS1 antigen protein, denoted as sHBsAg-Core-PreS1, and its amino acid sequence is shown in SEQ ID No. 17; the above-mentioned fusion antigen mRNA molecule can be prepared into an mRNA-LNP vaccine composition and used to treat chronic hepatitis B virus infection. The preferred sHBsAg-Core-PreS1 mRNA-LNP of this invention can normally express and present each encoded target antigen in vivo, and achieve cross-presentation, cross-activation and enhanced expression, inducing target antigen-specific humoral and cellular immune responses. It can also effectively overcome immune tolerance in a mouse model of chronic hepatitis B, and has excellent antiviral and immunotherapeutic effects. Compared with existing related therapeutic HBV mRNA-LNP vaccines, it effectively improves the immune tolerance breakthrough threshold, providing a candidate vaccine and a new immunotherapy strategy for the immunotherapy of patients with chronic HBV infection.

The invention discloses a molecular imprinting colorimetric sensor for detecting hepatitis B virus as well as a preparation method and application of the molecular imprinting colorimetric sensor. The sensor takes an aminated zeolite imidazate framework material (ZIF-8-NH2) with peroxidase-like activity as a catalytic core, after surface double-bond functionalization, a molecularly imprinted polymer (MIPs) layer is constructed on the surface through a free radical polymerization reaction by taking the aminated zeolite imidazate framework material as a carrier and taking HBV as a template molecule. According to the sensor, after HBV is specifically recognized and captured through MIPs, the catalytic efficiency of ZIF-8 on hydrogen peroxide is changed, then the generation amount of hydroxyl radicals is regulated and controlled, and finally visual and quantitative detection of HBV is achieved through the color fading reaction of the hydroxyl radicals and chromogenic dye crystal violet. The sensor prepared by the invention has the advantages of high sensitivity, strong specificity, low cost, simplicity and convenience in operation, rapidness in detection and the like, and can be used for rapid screening and on-site instant detection of hepatitis B viruses.

A composition for treating chronic hepatitis B infection, comprising mRNA encoding a hepatitis B viral antigen, the mRNA being encapsulated in a lipid nanoparticle (LNP).

The application discloses a recombinant virus-like nanoparticle for immunotherapy of gastric cancer and application thereof. The recombinant virus-like nanoparticle is a chimeric recombinant virus-like nanoparticle formed by self-assembly of a fusion protein HBC-CLDN18.2 of a hepatitis B virus core protein and CLDN18.2 tight junction protein. The application uses genetic engineering technology to truncate the C-terminal end of a natural hepatitis B virus core antigen, and mutate cysteine residues at positions 48 and 107 into serine, so that the hepatitis B virus core antigen can self-assemble into a virus-like nanoparticle with strong stability. The virus-like nanoparticle is used as a carrier, a B cell epitope peptide (tight junction protein CLDN18.2) of a gastric cancer tumor-related antigen is inserted into an immunodominant site of the carrier, so that the humoral immune response against gastric cancer is enhanced. Two T cell epitope peptides of the heterologous hepatitis B virus core antigen are used to replace T cell epitope peptides on the carrier, so that the cellular immune response against gastric cancer is enhanced, and strong antitumor effect and immune memory effect are shown.

The application discloses a hepatitis B surface antigen specific B cell receptor gene knock-in mouse model, and establishes a hepatitis B virus surface antigen (HBsAg) specific B cell receptor (BCR) gene knock-in mouse model, wherein 70-90% of B cells of the mouse can specifically recognize HBsAg, and differentiate into germinal center B cells and plasma cells. Therefore, the model can be used for basic research on hepatitis B antiviral humoral immune response and tolerance mechanism, and can also be used for application research on development of drugs and vaccines for breaking HBsAg immune tolerance. In summary, the establishment of the model lays a solid foundation for development of a functional cure immune means for hepatitis B.

The application discloses a primer probe combination for detecting hepatitis B virus, a detection product and application thereof, and relates to the technical field of hepatitis B virus detection. The primer probe combination comprises a forward primer HBV-FP, a reverse primer HBV-RP and a detection probe HBV-Probe. The nucleotide sequence of the forward primer HBV-FP is shown as SEQ ID NO. 1, the nucleotide sequence of the reverse primer HBV-RP is shown as SEQ ID NO. 2, and the nucleotide sequence of the detection probe HBV-Probe is shown as SEQ ID NO. 3. The 5' end of the detection probe HBV-Probe is coupled with a first fluorescent group, and the 3' end is connected with a quenching group. The detection system, the detection product and the detection method provided by the primer probe combination have good specificity, strong specificity, good linearity, good repeatability, high sensitivity and wide application prospect.

Provided are a ribavirin derivative-embedded double-stranded siRNA analog, a conjugate comprising the same, and a salt and use thereof. The provided double-stranded siRNA analog, the conjugate comprising the same, and the salt thereof can effectively inhibit multiple viral indicators such as hepatitis B virus DNA, pgRNA, S antigen, E antigen, etc., and provide an effective and feasible method for the treatment of hepatitis B.

Provided herein are methods for treating chronic hepatitis B (CHB) infections in human subjects. In some embodiments, the methods involve administering a lipid nanoparticle carrying an epigenetic-modifying DNA targeting system composed of polynucleotides for targeting repression of total Hepatitis B Viral (HBV) transcripts. Also provided is a lipid nanoparticle carrying the polynucleotides.

The invention discloses a nano antibody targeting a hepatitis B surface antigen and application of the nano antibody. The nano antibody has an amino acid sequence as shown in SEQ ID NO: 1-5, and has high affinity to HBsAg. The nano antibody not only can effectively neutralize hepatitis B virus, but also can enter cells to realize'multi-link and all-directional 'inhibition of virus life cycle, including inhibition of virus RNA transcription, protein expression, nucleocapsid assembly, DNA replication and particle secretion, and can significantly down-regulate HNF4alpha, Sp1 and other key transcription factors in host hepatocytes. The antibody can be efficiently expressed in a prokaryotic or eukaryotic system. The PEGylated derivative (such as Nb1-PEG40) can prolong the half-life period, and shows stronger effects of clearing serum HBsAg and inhibiting liver virus replication in an HBV infected mouse model. The invention provides a new strategy and drug candidate for hepatitis B treatment.

The invention relates to the technical field of biological medicine, in particular to fusion protein and application thereof in preparation of products for treating or preventing hepatitis B virus. PreS1 is used as a core antigen component and modified IgM is used as a basic skeleton to obtain a preS1-IgM monomer, then J chain connection is performed to obtain fusion protein, the fusion protein is used as an active component to construct the therapeutic vaccine, anti-preS1 antibody response can be effectively stimulated, and Th1 / Th2 immune response can be synergistically activated. Experiments show that serum HBsAg, HBV DNA and intrahepatic virus antigen levels of a chronic HBV infection model can be remarkably reduced by using the vaccine alone, and serological conversion of part of animals is realized; when the compound is combined with entecavir, the compound shows an excellent synergistic effect. According to the vaccine, the treatment effect is remarkably improved, meanwhile, remarkable liver injury is not caused, and an innovative immunotherapy with prevention and treatment functions is provided for chronic hepatitis B treatment.

The invention discloses a nano antibody targeting a hepatitis B core antigen as well as a coding gene and application thereof, and relates to the technical field of biological medicines. The nano antibody comprises an amino acid sequence as shown in any one of SEQ ID NO: 1 to SEQ ID NO: 5, and can be specifically combined with HBcAg. The invention also relates to a coding nucleic acid, an expression vector, a host cell and a preparation method of the nano antibody, and application of the nano antibody in preparation of anti-hepatitis B virus drugs and diagnostic reagents. Experiments show that the nano antibody has high affinity of targeting HBcAg, can combine and destroy hepatitis B virus nucleocapsid assembly and inhibit secretion of virus proteins such as HBsAg, HBeAg and the like, and thus has good anti-hepatitis B virus activity.

The present application relates to the technical field of biological medicine, and particularly relates to a fusion protein and application thereof in preparation of a product for treating or preventing hepatitis B virus. The present application takes preS1 as a core antigen component and takes an improved IgM as a basic skeleton to obtain a preS1-IgM monomer, and then connects the preS1-IgM monomer through a J chain to obtain a fusion protein. The fusion protein is taken as an active component to construct a therapeutic vaccine, which can effectively stimulate an anti-preS1 antibody response and synergistically activate a Th1 / Th2 immune response. Experiments show that the vaccine alone can significantly reduce the serum HBsAg, HBV DNA and intrahepatic virus antigen levels of a chronic HBV infection model, and realize seroconversion of part of the animals. When the vaccine is used in combination with entecavir, a remarkable synergistic effect is exhibited. The vaccine significantly improves the therapeutic effect without causing significant liver damage, and provides an innovative immunotherapy with both prevention and treatment functions for chronic hepatitis B treatment.

The invention discloses 2-deoxy-2-fluoro-4-azido-N-hydroxycytidine shown as a formula (F4) as well as a preparation method and application of the 2-deoxy-2-fluoro-4-azido-N-hydroxycytidine. Compared with the prior art, the 2-deoxy-2-fluoro-4-azido-N-hydroxycytidine (F4) and the phosphate prodrugs (F6 and F12) thereof provided by the invention show relatively strong cell viability to HepG2 / 2.2. 15 cells capable of continuously and stably expressing HBV (Hepatitis B Virus), the cell viability can reach a nanomole level, and the 2-deoxy-2-fluoro-4-azido-N-hydroxycytidine (F4) and the phosphate prodrugs (F6 and F12) thereof can be used for remarkably inhibiting HBV DNA (Deoxyribonucleic Acid) replication to serum and liver of a hepatitis B virus model mouse; the compound has a liver targeting property and has a good application prospect in the aspect of treating HBV (Hepatitis B Virus). The development of the medicine lays a foundation for the research of fluorine-containing nucleoside analogues. And (F4).

An immunomodulatory nanoparticle vaccine carrier protein and its application. This invention uses duck hepatitis B virus core antigen (DHBc) as a base, fuses and expresses the SpyCatcher003 sequence to construct DHBc-SpyCatcher (DHBc-SC) virus-like particles with self-assembly capability, and efficiently expresses them in *E. coli*. When DHBc-SC virus-like particles are mixed with heterologous monomeric antigens containing SpyTag, they can spontaneously couple to form virus-like particles displaying the heterologous antigen, significantly enhancing the immunogenicity of the heterologous antigen.

The application provides a glycosyl-modified fusion protein, a nucleic acid molecule, an expression vector, a host cell and application. The first aspect of the application provides a glycosyl-modified fusion protein, comprising a murine Fc variant and a hepatitis B virus antigen, wherein the murine Fc variant is obtained by amino acid mutation and non-mammalian glycosylation modification on a murine Fc fragment; the murine Fc variant comprises at least one of alanine at position 223, alanine at position 228, alanine at position 230, leucine at position 330 and glutamic acid at position 332; the glycosylation modification does not comprise sialic acid modification; and the position numbering is according to the EU numbering system. The fusion protein can bind to DC cells, activate DC cells and promote the proliferation and activation of specific T cells.

The utility model relates to the technical field of medical instruments, in particular to a hepatitis B virus adsorption device. The device comprises an adsorption assembly and a mounting assembly, the adsorption assembly comprises a circulation pipe body, a filtering sub-assembly detachably arranged in the circulation pipe body and a pair of installation connectors symmetrically arranged at the upper end and the lower end of the circulation pipe body and used for being communicated with the two hemodialysis pipes respectively. The mounting assembly comprises a pair of mounting shells which are symmetrically buckled on the left side and the right side of the circulating pipe body, a pair of clamping sub-assemblies which are symmetrically arranged on the opposite side faces of the two mounting shells left and right, and a fixing sub-assembly which is arranged between the mounting shells and the circulating pipe body and is used for fixing the mounting pipe body; each clamping sub-assembly comprises a pair of clamping plates which are symmetrically and rotationally arranged at the upper end and the lower end of the mounting shell; arc-shaped parts are arranged at the ends, away from each other, of the two clamping plates in each clamping sub-assembly. According to the device, the situation that the communicating position of the hemodialysis tube and the mounting connector is bent in the adsorption process, and blood passing is affected is avoided as much as possible.

The invention relates to the field of immunology, and particularly discloses a TCR combination for recognizing hepatitis B virus antigens and application, the TCR combination for recognizing hepatitis B virus antigens comprises a plurality of separated TCRs, the plurality of separated TCR combinations for recognizing hepatitis B virus antigens form four TCR groups, and the four TCR groups comprise a first TCR group, a second TCR group, a third TCR group and a fourth TCR group; wherein the first TCR group specifically recognizes a first antigen epitope, and the amino acid sequence of the first antigen epitope is as shown in SEQ ID NO: 1; the second TCR group specifically recognizes a second antigen epitope, and the amino acid sequence of the second antigen epitope is as shown in SEQ ID NO: 2; the third TCR group specifically recognizes a third antigen epitope, and the amino acid sequence of the third antigen epitope is as shown in SEQ ID NO: 3; the fourth TCR group specifically recognizes a fourth antigen epitope, the amino acid sequence of the fourth antigen epitope is as shown in SEQ ID NO: 4, and an important means can be provided for treatment of TCR-T immune cells infected by hepatitis B virus.

The invention discloses a novel N4-acyl substituted-2 '-deoxy-2'-fluoro-4 '-azido cytidine derivative and pharmaceutical application thereof, the novel N4-acyl substituted-2'-deoxy-2 '-fluoro-4'-azido cytidine derivative has a structure of a general formula (b): in the formula, R1 is H, F or CH3; r2 = H, N3 or C2H; and R3 is C0-C10 straight chain or branched chain saturated and unsaturated alkane, C6-C12 aromatic alkane or C3-C6 heterocyclic alkane. N4-acyl substituted-2 '-deoxy-2'-fluoro-4 '-azide cytidine derivatives are synthesized by modifying the 4-amino group of a compound a, and the compounds have anti-hepatitis B virus and anti-tumor activity; the preparation method is feasible; the compound has a good application prospect when being applied to drugs for treating viruses and tumors.

Provided herein are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas / guide RNA (gRNA) systems, for the transcriptional repression of Hepatitis B viral (HBV) genes to promote a cellular phenotype that leads to the reduction of HBV infection. In some embodiments, the epigenetic-modifying DNA-targeting systems bind to or target a target site of at least one gene or regulatory element thereof in a Hepatitis B viral DNA sequence in cell. In some aspects, the provided systems relate to the transcriptional repression of one or more Hepatitis B viral gene and / or regulatory element thereof. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in repressing Hepatitis B viral replication and expression in connection with Hepatitis B infections.

The invention is applicable to the technical field of biological medicines, and provides a single-antigen or multi-antigen mRNA vaccine for preventing or treating hepatitis B virus infection and application thereof. The protein coded by mRNA comprises a fusion protein (Pan-HLA-DR-epitope-preS1-Fc) formed by fusing a hepatitis B virus surface antigen and / or a hepatitis B virus front surface antigen 1 with a pan-HLA-DR binding epitope and a human IgG1 Fc segment. After mRNA is wrapped into a delivery system through lipid nanoparticles, a single-antigen or multi-antigen mRNA vaccine is prepared. The mRNA vaccine preparation can specifically enhance humoral immune response and cellular immune response aiming at hepatitis B virus surface antigen and / or hepatitis B virus front surface antigen 1, and can be used for preventing and treating hepatitis B; all the components in the mRNA vaccine preparation can be widely obtained, the vaccine cost is effectively reduced, the vaccine yield is increased, and good practical application value is achieved.