366 results about "Hepatitis B" patented technology

The invention discloses an anti-human hepatitis B e antigen monoclonal antibody and application thereof, and relates to the technical field of hepatitis B detection. In a heavy chain variable region of the monoclonal antibody, an amino acid sequence of a complementarity determining region CDR1-3 is as shown in SEQ ID NO.1-3 or has at least 95% of homology with the sequence as shown in SEQ ID NO.1-3; in the light chain variable region, amino acid sequences of complementary determining regions CDR1 and CDR3 are shown as SEQ ID NO.4 and SEQ ID NO.5 or have at least 95% of homology with the sequences shown as SEQ ID NO.4 and SEQ ID NO.5, and an amino acid sequence of a complementary determining region CDR2 is FAS. The monoclonal antibody provided by the invention can well recognize a natural hepatitis B e antigen, and the titer of a supernatant cultured by a B cell can reach 1: 10000, so that the monoclonal antibody can be completely applied to detection research of the human hepatitis B e antigen. The chemiluminescence reagent prepared by using the monoclonal antibody has the advantages of high specificity, strong anti-interference capability, high detection sensitivity, good stability and the like, almost has no leak detection, and can replace an imported reagent.

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.

Provided are a double-gap modified oligonucleotide and the use thereof in resisting hepatitis B viruses and hepatitis D viruses. In particular, provided is a compound, or pharmaceutically acceptable salts, hydrates or solvates thereof, wherein (a) the compound is a double-gap modified oligonucleotide, the oligonucleotide having a sequence as shown in SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4 or SEQ ID NO. 5; (b) the double-gap modification refers to that each nucleoside portion in the oligonucleotide is modified in the manner as shown in formula (I); and (c) internucleoside linkages of the oligonucleotide are unmodified or modified internucleoside linkages. The double-gap modified oligonucleotide has remarkably improved antiviral activity. Pl＞SI-P2-S2-P3 (I)

The invention provides a terahertz wave band sensing chip for detecting hepatitis B and H9N2 and application thereof, at least one terahertz wave band sensing unit structure, and each terahertz wave band sensing unit structure comprises a first double-hollow cylinder and a second double-hollow cylinder which are arranged on a quartz substrate at an interval, the first double-hollow cylinder and the second double-hollow cylinder are double-hollow cylinders prepared from a silicon material, the radius ratio of double hollow parts of the second double-hollow cylinder is different from the radius ratio of double hollow parts of the first double-hollow cylinder, and quasi-BIC is realized through asymmetry of the first double-hollow cylinder and the second double-hollow cylinder. High Q factors as high as 1674 and 2244 are provided respectively, and the sensitivities are as high as 110 GHz / RIU and 85 GHz / RIU respectively.

The present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-L1 or the PD-1 / PD-L1 interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

Provided herein are methods for administering a hepatitis B virus surface antigen (HBsAg) to subjects with chronic hepatitis B to distinguish between responder subjects who respond to the HBsAg administration with an increase in an HBV antibody levels and non‑responder subjects, and treating chronic hepatitis B in the responder subjects with an HBV therapy. Methods of excluding non-responder subjects from a clinical study are also provided.

This invention discloses a monoclonal antibody against human hepatitis B e antigen and its application, relating to the field of hepatitis B detection technology. In the heavy chain variable region of the monoclonal antibody, the amino acid sequences of the complementarity-determining regions (CDR1-3) are as shown in SEQ ID NO. 1-3 or have at least 95% homology with the sequences shown in SEQ ID NO. 1-3; in the light chain variable region, the amino acid sequences of the complementarity-determining regions (CDR1 and CDR3) are as shown in SEQ ID NO. 4 and 5 or have at least 95% homology with the sequences shown in SEQ ID NO. 4 and 5, and the amino acid sequence of the complementarity-determining region (CDR2) is FAS. The monoclonal antibody provided by this invention can effectively recognize natural hepatitis B e antigen, and the titer of the supernatant from B cell culture can reach 1:10000, making it fully applicable to the detection and research of human hepatitis B e antigen. The chemiluminescent reagent prepared using the monoclonal antibody described in this invention has advantages such as high specificity, strong anti-interference ability, high detection sensitivity, and good stability, with almost no missed detections, and can replace imported reagents.

The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

The present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-L1 or the PD-1 / PD-L1 interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

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.

The invention provides a construction method and system of a chronic hepatitis B liver tissue inflammation grading prediction model and application. The construction method of the chronic hepatitis B liver tissue inflammation grading prediction model comprises the following steps: S1, screening out a plurality of patients which are diagnosed as chronic hepatitis B through liver tissue biopsy pathology and have clear liver tissue inflammation grading according to inclusion and exclusion standards, and collecting clinical data and serum samples of the patients; s2, performing serum protein N-carbohydrate chain fingerprint spectrum difference analysis on the serum samples of the patients with different ALT levels by adopting an N-carbohydrate fingerprint spectrum technology; s3, on the basis of conventional biochemical indexes and / or N-sugar markers, constructing liver tissue inflammation grading evaluation models under different ALT levels by adopting a binary logistic regression analysis method; and S4, respectively evaluating and selecting the model with the optimal efficiency as a chronic hepatitis B liver tissue inflammation grading prediction model. The chronic hepatitis B liver tissue inflammation grading method can be used for quickly, accurately and noninvasively grading the chronic hepatitis B liver tissue inflammation.

The invention belongs to the field of biological medicines, and particularly relates to an antigen-antibody compound for enhancing immune response of hepatitis B patients as well as a preparation method and application of the antigen-antibody compound. The antigen-antibody compound preparation prepared from the HBsAg and the anti-HBsAg monoclonal antibody is superior to an antigen-antibody compound preparation prepared from a polyclonal antibody in the aspect of continuously inducing the immune response of a chronic hepatitis B patient, and an antigen-antibody compound for inducing the immune response of the hepatitis B patient is developed for the first time; in the compound, the hepatitis B surface antigen is combined with the anti-HBsAg monoclonal antibody, and the compound formed by the hepatitis B surface antigen and the anti-HBsAg monoclonal antibody in a certain mass ratio can induce immune response of chronic hepatitis B patients and can also prevent and / or treat chronic hepatitis B.

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 immune effect drugs, and discloses a dendritic cell albumin suspension and a preparation method and application thereof.The preparation method of the dendritic cell albumin suspension includes the following steps that isolated mononuclear cells PBMC are collected, and matured DCs are cultured in a laminar flow purification laboratory; loading the multi-valence hepatitis B virus antigen epitope peptide on the DC; and the DC cell albumin suspension is prepared. The CTL immune effect excited by the DC can effectively remove HBV viruses in an integrated state in liver cells, so that the conditions of patients with hepatitis B and cirrhosis are reversed until HBV antigens are negative, and the conditions are relieved fundamentally; in the immune response excited by DC, the effector CTL cells immediately play a role in clearing HBV viruses, and the memory T lymphocytes play a role in clearing HBV viruses in vivo for a long time, so that the condition of hepatitis B is continuously reversed. Reagents used in the DC culture process are completely localized. The cost is greatly reduced and is obviously lower than that of foreign countries, and popularization is facilitated; china gets rid of the history of long-term dependence on imported anti-hepatitis B viruses.

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 a G quadruplex ligand and entecavir combined drug in resisting HBV (hepatitis B virus) infection, and relates to the technical field of HBV treatment drugs. The invention determines that a G quadruplex sequence and a G quadruplex structure exist in an HBV genome, G quadruplex ligands TMPyP4 and BRACO19 can be combined with the HBV G quadruplex structure and inhibit transcription and translation of HBV, and TMPyP4 and existing clinical drug ETV combined medication have obvious synergistic effect, which indicates that the HBV G quadruplex can be used as a new drug target for resisting virus infection. The results of the invention can provide new tools and ideas for clinical prevention and treatment of hepatitis B, especially have broad prospects in the aspects of development, clinical application and the like of anti-hepatitis B drugs and vaccines, and can also be directly applied to the field of scientific research or guide the development of inhibitors for inhibiting HBV life cycle. The invention has important application value for obtaining new anti-HBV drug targets and screening new drugs.

The invention provides a Mongolian medicine composition for treating hepatitis B and a preparation method of the Mongolian medicine composition. The composition is prepared from the following components in parts by weight: 75 to 85 parts of saffron, 75 to 85 parts of trogopterus dung, 65 to 75 parts of gardenia jasminoides, 45 to 55 parts of cortex phellodendri, 45 to 55 parts of dianthus chinensis, 55 to 65 parts of gypsum, 55 to 65 parts of scabiosa, 55 to 65 parts of calamine, 55 to 65 parts of caulis akebiae, 25 to 35 parts of rhizoma coptidis, 25 to 35 parts of fructus gardeniae, 25 to 35 parts of calomel, 25 to 35 parts of bunge corydalis herb, 45 to 55 parts of elecampane, 45 to 55 parts of rose and 55 to 65 parts of calculus bovis factitius. The Mongolian medicine composition for treating hepatitis B is prepared from multiple raw materials, meanwhile, the added coptis chinensis and rose flowers are treated through a specific extraction mode and a specific fermentation mode, and the prepared Mongolian medicine composition for treating hepatitis B has an excellent hepatitis B treatment effect.

The invention discloses thymus dependent lymphocyte antigen epitope peptide of hepatitis B virus antigen and application, and belongs to the field of medical immunology and infectious pathology. The thymus dependent lymphocyte antigen epitope peptide of the hepatitis B virus antigen is characterized in that the amino acid sequence of the epitope peptide comprises any one or more of the following: SPTVWLSVI; an LPLLPIFFCL (low-performance liquid chromatography- CPTVQASKL, and CPTVQASKL; an LPSDFFPSI (Liquefied Peptide The amino acid sequence is an amino acid sequence obtained by removing or replacing a single amino acid of the amino acid sequence. The epitope peptide disclosed by the invention can be specifically combined with cytotoxic thymus dependent lymphocytes to stimulate the cytotoxic thymus dependent lymphocytes to activate, proliferate and differentiate, so that the immune effect of resisting the hepatitis B virus is exerted; the antigen peptides can be used for preparing therapeutic and prophylactic vaccines for hepatitis B virus infection, can also be used for preparing detection reagents for detecting hepatitis B virus specific cytotoxic thymus dependent lymphocytes, and have potential application value in prevention, treatment and diagnosis of hepatitis B.

Use of a compound in the treatment of liver diseases. Experimental results show that the compound has a relatively high liver-tissue-targeting property, very low toxicity to liver primary cells and high liver safety, has significant efficacy on liver diseases such as viral hepatitis (e.g., hepatitis B) and liver cancers (including primary liver cancers and metastatic liver cancers), and has relatively good physicochemical properties, metabolic stability, bioavailability and safety, thus having very good drug development prospects.

The invention discloses application of a compound in treatment of liver diseases. Experimental results show that the compound has relatively high liver tissue targeting property, very low toxicity to liver primary cells, high liver safety and obvious curative effects on liver diseases such as viral hepatitis (such as hepatitis B), liver cancer (including primary liver cancer and metastatic liver cancer) and the like; in addition, the compound also has better physicochemical properties, metabolic stability, bioavailability and safety, and has a very good drug development prospect.

The present disclosure relates to antibodies, and antigen binding fragments thereof, that can bind to the antigenic loop region of hepatitis B surface antigen (HBsAg) and can neutralize infection of both hepatitis B virus (HBV) and hepatitis delta virus (HDV). The present disclosure also relates to epitopes to which the antibodies and antigen binding fragments bind, as well as to fusion proteins that comprise the antigen binding fragments, and to nucleic acids that encode and cells that produce such antibodies and antibody fragments. In addition, the present disclosure relates to the use of the antibodies and antibody fragments of the present disclosure in the diagnosis, prophylaxis and treatment of hepatitis B and hepatitis D.

The invention provides a polypeptide for activating cellular immunity in chronic hepatitis B and application of the polypeptide, and belongs to the technical field of biological medicine. A polypeptide library is designed and synthesized on the basis of a preS1 structural domain for coding HBV large HBsAg, a full-length core protein Core, a polymerase protein fragment rich in T cell epitopes and an mRNA-PreS1CPX holoantigen sequence (as shown in SEQ ID NO.1) of full-length X protein HBX, and peptide fragments capable of activating T cell immunity are screened by utilizing ELISPOT and flow cytometry. Experimental results show that the polypeptide sequences as shown in SEQ ID NO.2-15 can promote HBV antigen specific immune response by stimulating CD8 + T lymphocytes to secrete IFN-gamma, so that immune activation treatment of hepatitis B is realized.

The present application relates to derivatives of STOPS™ antiviral compounds having enhanced helicity, wherein the compounds are S-antigen transport inhibiting oligonucleotide polymers. This application further relates to processes for making the compounds and methods of using them to treat diseases and conditions. In some embodiments, the diseases and conditions are related to hepatitis B and / or hepatitis D.

Disclosed herein are compositions and methods for the treatment of hepatitis B infection, including chronic hepatitis B (CHB).

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 discloses an antibody-drug conjugate and a preparation method and application thereof, in particular, a conjugate of an anti-PD-L1 antibody and a TLR7 and / or TLR8 agonist and a pharmaceutical composition, preparation method and application thereof. The present invention obtains a modified anti-PD-L1 antibody with a mutant cysteine ​​by gene editing, which basically retains the structure of the original antibody and can be used for the construction of an antibody-drug conjugate. Through anti-tumor experiments, it was found that the obtained antibody-drug conjugate has better activity, such as strong anti-tumor activity, can significantly improve the survival rate of tumor-bearing animals, and has significantly reduced toxicity, less burden on the body of experimental animals, greatly reduces the minimum effective dose of small molecule drugs when used alone, expands its therapeutic window, and is expected to be used in the development of therapeutic drugs for various diseases (such as tumors, viral diseases such as hepatitis B, etc.), with good application prospects and value.

A drug conjugate includes a structure shown by the following formula: Z-(linker-[R]m)n. In the formula, Z is a drug compound, R is a sugar, and m and n are independently an integer from 1 to 6. The drug compound Z is a hepatitis virus targeting drug, a hepatitis B virus (HBV) drug, an inhibitor of apoptosis protein (IAP) antagonist, a multidrug resistance (MDR) inhibitor, or analogues, precursors, prodrugs, derivatives thereof.