113 results about "Hepatitis b viral" patented technology

The invention relates to the technical field of knowledge maps, in particular to a multi-task hepatitis B drug screening method and system based on knowledge map assistance, and the method comprises the following steps: based on hepatitis B virus genotype sequence data recorded along with time, patient drug use records and drug sensitivity. According to the method, virus genotype sequence data, patient drug use records, drug sensitivity and other multi-dimensional dynamic time sequence data are integrated, interaction events between entities are marked through timestamps, and virus variation tracks, drug curative effect changes and other dynamic characteristics are embedded into atlas node attributes; and the knowledge representation can reflect the time dependence in a real scene. A hyperedge connection multi-entity set is defined based on biological pathway annotation information and protein interaction data, the limitation that only a binary relation is supported in a traditional knowledge graph is expanded, a drug combination and multi-target synergistic effect mechanism is explicitly modeled, and misjudgment of the combination effect caused by simplification of the interaction relation is avoided.

The invention relates to the field of immunology, and particularly discloses a TCR combination and application thereof, the TCR combination is used for recognizing HBV antigen epitopes, the TCR combination comprises a plurality of separated TCRs, the plurality of separated TCRs form two TCR groups, and the two TCR groups comprise a first TCR group and a second 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 first TCR group specifically recognizes a first antigen epitope, the second TCR group specifically recognizes a second antigen epitope, the amino acid sequence of the second antigen epitope is shown as SEQ ID NO: 2, the second antigen epitope respectively and correspondingly recognizes different antigen epitopes, the hepatitis B virus specific TCR and the epitope thereof are screened out, and an important means can be provided for treatment of TCR-T immune cells infected by hepatitis B virus.

The invention discloses a virus-like structure nano adapter and application thereof, on the basis of hepatitis B virus core protein Uniprot P03146 of which nucleic acid binding domains at 145-183 sites of a C tail end are removed, CBP as shown in SEQ ID NO.01 is respectively inserted into a spike part and an N tail end of the hepatitis B virus core protein Uniprot P03146. The invention is constructed based on collagen combined polypeptide CBP designed by bionic decorrin, aims to imitate the interaction between natural decorrin and collagenous fiber, can efficiently cross over corneal epithelium barrier and repair corneal stroma in a non-photo-crosslinking manner, and solves the limitation of existing clinical treatment.

The invention relates to the field of immunology, and particularly discloses a hepatitis B virus specific TCR combination and application, the hepatitis B virus specific TCR combination is used for recognizing HBV antigen epitopes, the hepatitis B virus specific TCR combination comprises a plurality of separated TCRs, the plurality of separated TCRs form two TCR groups, and the two TCR groups comprise a first TCR group and a second 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 first TCR group specifically recognizes a first antigen epitope, the second TCR group specifically recognizes a second antigen epitope, the amino acid sequence of the second antigen epitope is shown as SEQ ID NO: 2, the second antigen epitope respectively and correspondingly recognizes different antigen epitopes, the hepatitis B virus specific TCR and the epitope thereof are screened out, and an important means can be provided for treatment of TCR-T immune cells infected by hepatitis B virus.

The invention relates to the technical field of biological medicines, in particular to a vaccine for treating or preventing hepatitis B virus infection. The vaccine comprises a hepatitis B surface antigen and a composite adjuvant, wherein the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21, and the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21; the nucleotide sequence of the CpG oligodeoxynucleotide is as shown in SEQ ID NO. 1. According to the vaccine provided by the invention, an HBsAg antibody can be generated in a normal mouse body, and HBV in an HBV-carrier mouse can be effectively eliminated, so that the vaccine has the effect of treating or preventing hepatitis B virus infection. According to the vaccine provided by the invention, two adjuvants, namely CpG oligodeoxynucleotide and saponin QS-21, are adopted, so that the vaccine can be used for synergistically activating an immune effect, enhancing the activation of B cells and permanently transforming into plasma cells, and meanwhile, the vaccine can be used for resisting immune tolerance of T cells, realizing the removal of hepatitis B viruses and realizing functional cure of clinical hepatitis B treatment.

The invention discloses an application of a combination of entecavir, an ASO drug, an mRNA therapeutic vaccine and / or interferon in preparation of drugs for treating chronic hepatitis B. Entecavir and interferon have an antiviral effect, the ASO drug reduces hepatitis B surface antigen titer, and the mRNA therapeutic vaccine is high in immunization speed, so that the entecavir, ASO drug, mRNA therapeutic vaccine and / or interferon combination can inhibit virus replication, and can be used for treating chronic hepatitis B. The composition strikes hepatitis B virus from multiple angles and multiple levels, achieves a good, lasting and non-rebound antiviral effect, and can cure hepatitis B to a certain extent.

Disclosed are antibodies to anti-hepatitis B surface antigen (HBsAg) (especially humanized antibodies), nucleic acid molecules encoding same, methods for preparing same, and pharmaceutical compositions containing same. The antibodies have higher affinity for HBsAg at neutral pH than at acidic pH, thereby significantly enhancing the virus clearance efficiency and prolonging the virus inhibition time. The antibodies and the pharmaceutical compositions can be used for preventing and / or treating HBV infections or diseases related to HBV infections (e.g., hepatitis B), for neutralizing the virulence of HBV in a subject (e.g., a human), for reducing the serum level of HBV DNA and / or HBsAg in the body of the subject, or for activating the humoral immune response of the subject (e.g., a chronic HBV infected or chronic hepatitis B patient) against HBV.

The invention belongs to the technical field of biological medicines, and particularly relates to an mRNA vaccine for preventing or treating hepatitis B virus infection and application of the mRNA vaccine. The mRNA vaccine comprises mRNA for coding hepatitis B virus surface antigen or / and hepatitis B virus core associated antigen or / and hepatitis B virus front surface antigen 1 fusion IgG Fc segment protein, and the mRNA is wrapped by lipid nanoparticles to form a delivery system to be prepared into the mRNA vaccine. The vaccine preparation can specifically enhance humoral immune response and cellular immune response aiming at hepatitis B virus surface antigen or / and hepatitis B virus core related antigen or / and hepatitis B virus front surface antigen, and can be used for preventing and treating hepatitis B. All the components in the vaccine preparation can be widely obtained, the vaccine cost is effectively reduced, the vaccine yield is increased, and therefore the vaccine preparation has good practical application value.

The present disclosure provides methods for treating HBV infection using combination therapies, and related kits and compositions for use. The components of the combination therapies include an inhibitor of HBV gene expression or an agent that reduces HBV antigenic load, and an anti-HBV antibody.

The invention discloses an application of TFPI2 in preparation of an anti-hepatitis B virus drug. Through in-depth study, it is found for the first time that overexpressed TFPI2 can significantly inhibit the replication ability of HBV on the cellular level and the animal level, and the expression level of HBV DNA and HBV RNA and the secretion level of HBsAg and HBeAg are reduced. Besides, mechanism analysis finds that overexpression TFPI2 promotes degradation of hepatitis B virus X protein (HBx), the half-life period of the HBx protein is remarkably shortened, and finally the HBV replication ability is damaged. Based on the research results, the application of the TFPI2 in chronic viral hepatitis B is provided for the first time, and candidate treatment targets and backup protein drugs are provided for clinical treatment of chronic hepatitis B patients.

2'-Fluoro-6'-methylene-carbocyclic adenosine (FMCA, 21) and its phosphoramidate prodrug (FMCAP, 31) have demonstrated potential anti-HBV activity against both adefovir- resistant as well as lamivudine-resistant double (rtL180M / rtM204V) mutant hepatitis B virus (HBV). In addition, in vitro, these molecules have reinstated a significant activity against lamivudine / entecavir triple mutants (L180M+S202G+M204V). This invention is directed to compounds, pharmaceuticals and methods of treating HBV infections, especially including infections caused by resistant and multiple resistant HBV. Pursuant to the present invention, a complete structure-activity relationship (SAR) of 2'-fluoro-6'-methylene-carbocyclic derived nucleos(t)ides has been evaluated and that analysis is presented herein. Pursuant to the present invention, the synthesis and antiviral evaluation of purine and pyrimidine-derived nucleosides have been reported against wild-type and various HBV mutants. Guanosine analog (FMCG, 25) demonstrated an EC50 value of 0.217μM and cytosine analog (FMCC, 41) expressed a potent EC50 value of 0.0025 μM compared to entecavir (EC50 = 0.0029) against wild-type HBV. Additionally, FMCC (41) maintains its antiviral potency against various HBV mutants. Furthermore, chiral pure FMCAP Sp (34) isomer demonstrated an EC50 value of 1.3 nM and was more potent against several HBV mutants than entecavir.

The application discloses a low-cost hepatitis B (HBV) virus nucleic acid rapid detection method based on a functionally modified paper base, and can realize rapid detection of HBV virus nucleic acid.The method comprises the following steps: (1) pre-amplifying HBV virus nucleic acid to obtain Texas red-labeled nucleic acid; (2) capturing and enriching the Texas red-labeled nucleic acid by using a functionally modified paper base; and (3) performing signal detection.The functionally modified paper base is modified with a fusion protein containing a TR512 polypeptide.The protein functionally modified paper base is simple in preparation, fast in nucleic acid detection time and low in detection cost.

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 invention provides anti-HBV compounds, pharmaceutically acceptable compounds or stereoisomers thereof, and preparation methods and uses for treating, eradicating or inhibiting HBV infection or for alleviating liver injury caused by HBV infection, and so on.

Provided are a combination comprising a drug for treating hepatitis B and an antiviral agent, and a use thereof. The drug for treating hepatitis B comprises a nucleic acid or nucleic acid combination (e.g., an mRNA combination) encoding an antigen of hepatitis B virus. The combined use of the drug for treating hepatitis B and the antiviral agent can significantly reduce the number of liver HBV Core positive cells in an infected subject, greatly improve the HBV-specific T cell response level in the subject, and shows no obvious rebound of HBsAg after drug withdrawal.

A method for detecting hepatitis B virus comprising a step of bringing a sample into contact with an antibody which binds to a surface antigen protein of hepatitis B virus, and a lectin. The surface antigen protein of hepatitis B virus may be an S protein, and the lectin may be wheat germ agglutinin. The detection method may involve an ELISA measurement and may be used for testing, prophylaxis, or planning treatment of hepatitis B virus, and for screening medicines.

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 provides preparation of a novel mRNA vaccine and application of the novel mRNA vaccine in a medicine composition for treating hepatitis B virus diseases. Specifically, the invention provides a chronic hepatitis B infection therapeutic mRNA vaccine, which comprises mRNA for coding a large protein (L protein) region of hepatitis B virus surface antigen, and simultaneously comprises two mRNA for respectively coding a middle protein (M protein) region of hepatitis B virus surface antigen and a small protein (S protein) region, or comprises mRNA for coding the small protein (S protein) region. The mRNA therapeutic vaccine provided by the invention can break the immune tolerance state in chronic hepatitis B infection, and has the potential of functionally curing chronic hepatitis B infection clinically.

This invention relates to compositions, methods, strategies, and treatment modalities related to the epigenetic modification of hepatitis B virus (HBV) genes.

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 present invention relates to the field of biotechnology and discloses a nucleic acid targeting hepatitis B virus and its uses. The nucleic acid of the present invention can effectively inhibit the replication of hepatitis B virus in vitro and in vivo. By applying the RNA interference technology of the nucleic acid of the present invention, specific degradation of HBV mRNA is triggered through targeting, thereby inhibiting the protein expression and virus replication of HBV. It has the advantages of strong specificity, small side effects, and long-lasting drug effect, and also provides a new treatment method for completely clearing HBV genes and curing hepatitis B.

The invention relates to the technical field of antigen detection, and provides a hepatitis B virus surface antigen detection device, which comprises a detection table and a door body, the top of the detection table is provided with a first built-in cavity, and the interior of the detection table below the first built-in cavity is provided with a second built-in cavity. By arranging a fixing structure, a test tube with a to-be-detected reagent is moved between spring pieces to be pressed downwards, the test tube can be clamped under the action of the spring pieces, the test tube is prevented from displacing in a fixing cylinder, at the moment, a clamping block is moved into a movable groove, and under the elastic force action of a second reset spring, the test tube can be clamped in the movable groove. A clamping block is moved into a clamping groove, a test tube is pressed, a reset plate and a fixing cylinder are separated from each other, under the elastic force action of a first reset spring, the reset plate drives the test tube to move upwards through a spring piece, the test tube is conveniently taken out, and the function that the device is convenient to fix is achieved; therefore, the applicability of the hepatitis B virus surface antigen detection device in use is improved.

This invention relates to compositions, methods, strategies, and treatment modalities related to the epigenetic modification of hepatitis B virus (HBV) genes.

The present invention relates to a dual-target double-stranded RNA for treating hepatitis B, and a pharmaceutical composition. The dual-target double-stranded RNA comprises a first double-stranded RNA and a second double-stranded RNA, wherein one of the first double-stranded RNA and the second double-stranded RNA targets the hepatitis B virus (HBV) life cycle, and the other targets a host immune target PD-L1. The double-stranded RNA can simultaneously target the dual targets of HBV and host immune PD-L1, which can inhibit HBV replication while activating human immunity, and is therefore expected to bring about a clinical functional cure.

The invention discloses an efficient production process of an umbilical cord mesenchymal stem cell preparation in the field of stem cells, which comprises the following steps: S101, collection and separation of umbilical cord mesenchymal stem cells: under a sterile condition, separating Walton's jelly by adopting a tissue block culture method, taking out an umbilical cord from an umbilical cord bottle, transferring the umbilical cord into a sterile culture dish, and reserving a sample of a protective solution in the umbilical cord bottle for sterile detection; washing the umbilical cord with normal saline, cutting off two ends of the umbilical cord, discarding the umbilical cord, segmenting the umbilical cord for about 3-4cm, washing to remove blood, umbilical cord veins, two arteries and amniotic membranes, collecting the Walton's jelly, and transferring the Walton's jelly into a 50ml centrifugal tube; adding a small amount of the culture medium, cutting the Walton's gum into pieces with a size of about 1mm < 3 > by using scissors, and centrifugally washing for two times by using normal saline; the preparation produced by the invention is negative in detection of hepatitis B virus, hepatitis C virus, human immunodeficiency virus, syphilis antibody, cytomegalovirus and mycoplasma, and is high in extraction efficiency and convenient to popularize.

The invention discloses a bipyrimidine heterocyclic compound and a preparation method and application thereof, the bipyrimidine heterocyclic compound has a structure as shown in a formula (I), and the invention also provides a pharmaceutical composition containing the compound or a stereoisomer, a medicinal salt, a hydrate, a solvate or a crystal thereof. The invention also discloses application of the compounds in preparation of drugs for treating hepatitis B virus infection, and particularly the compounds can be used as PAPD5 / 7 enzyme inhibitors and hepatitis B RNA non-stabilizers for treating hepatitis B viruses. The compound provided by the invention has the characteristics that the concentration of hepatitis B surface antigen and hepatitis B DNA and RNA can be remarkably reduced, and the probability of functional healing of hepatitis B can be remarkably improved by clinically combining with nucleoside drugs, oligonucleotide drugs / PD-L1 compounds 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 invention provides an antibody for HBV genotyping, a product and a preparation method and application thereof, and relates to the field of hepatitis B virus detection. The invention provides an antibody B11 for HBV genotype typing, the antibody B11 can simultaneously recognize B genotype and C genotype of HBV, the antibody comprises a heavy chain and a light chain, the amino acid sequence of the heavy chain is as shown in SEQ ID NO.15, and the amino acid sequence of the light chain is as shown in SEQ ID NO.17; the invention further provides a colloidal gold immunochromatography kit based on the B11 antibody, the colloidal gold immunochromatography kit can be directly used for serum sample detection, the procedure of hepatitis B virus typing diagnosis is simplified, and the detection accuracy is high.

Provided in the present invention are a preparation of a new mRNA vaccine, and the use thereof in a pharmaceutical combination for treating the hepatitis B virus disease. Specifically, provided in the present invention is a therapeutic mRNA vaccine against chronic hepatitis B infection, which vaccine contains an mRNA encoding a large protein (L protein) region of a hepatitis B virus surface antigen, and also contains two mRNAs respectively encoding a middle protein (M protein) region of the hepatitis B virus surface antigen and encoding a small protein (S protein) region thereof, or contains an mRNA encoding the small protein (S protein) region. The therapeutic mRNA vaccine of the present invention can break the immune tolerance state in chronic hepatitis B infection, and has the potential to functionally cure chronic hepatitis B infection clinically.