22 results about "HBsAg" patented technology

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.

According to the application of the E3 ligase UFL1 modified by the Especially in clearing the SHBs / HBsAg, the SHBs / HBsAg can be cleared by inhibiting the expression of the E3 ligase UFL1 modified by the Especially, so that the effect of treating HBV infection or HBV related diseases is achieved. The strategy of the invention is to directly target and remove the existing SHBs / HBsAg protein, and the action is more direct and rapid. According to the present invention, the inherent protein mass control system (proteasome pathway) of cells is utilized, such that the high biocompatibility and the low off-target toxicity can be provided; and the combination of the strategy and the existing antiviral drugs is expected to further significantly improve the functional cure rate of hepatitis B.

Provided are bispecific antibodies capable of specifically targeting both HBV surface antigen (HBsAg) and CD3 protein, and pharmaceutical compositions comprising them. In particular, provided are nucleic acid molecules encoding the bispecific antibodies or fragments thereof, and vectors comprising the nucleic acid molecules. Also provided are uses of the bispecific antibodies or fragments thereof, the nucleic acid molecules, and the vectors in the preparation of medicaments for preventing or treating HBV infection and other related diseases.

The invention relates to a bispecific antibody targeting HBsAg and DEC-205, and further relates to an antibody coupling medicine containing the antibody as well as a preparation method and application of the antibody coupling medicine.

Relates to the technical field of biology, in particular to a castrated HBsAg virus-like particle subunit vaccine and a preparation method thereof. The invention provides the GnRH-I-HBsAg recombinant protein which is high in purity and good in specificity. The vaccine prepared from the GnRH-I-HBsAg recombinant protein is high in antigen purity and good in safety, and has a good castration effect.

The application discloses application of a low-dose anti-PD-1 antibody in a limited course of treatment in treatment of hepatitis B. Anti-PD-1 antibody treatment is carried out on a chronic hepatitis B patient receiving nucleoside analogue or nucleotide analogue treatment, 100 mg is injected intravenously each time, once every three weeks, and the course of treatment is ended after 12 weeks or 24 weeks. The application blocks the combination of the PD-1 receptor highly expressed on the surface of T cells of the CHB patient with a ligand by blocking the CHB patient T cell surface high expression of the PD-1 receptor, thereby reversing the T cell exhaustion state, enhancing the HBV specific T cell immune response, and promoting HBsAg clearance. The application uses a limited course of treatment and a low-dose alpha PD-1 to enhance the HBV specific T cell immune response of the patient and promote the clearance of HBsAg while ensuring good safety. Compared with the traditional 48-week Peg-IFN alpha or several years or even decades of NAs treatment of the CHB patient, the 12-week or 24-week course of alpha PD-1 is shorter and has a smaller economic burden on the patient.

Provided are bispecific antibodies that may specifically target both HBV surface antigen (HBsAg) and CD3 protein and pharmaceutical compositions comprising the same. Particularly, provided are nucleic acid molecules encoding the bispecific antibodies or fragments thereof and vectors including the nucleic acid molecules. Also provided uses of the bispecific antibodies or fragments thereof and the nucleic acid molecules and the vectors in preparation of medicines for preventing or treating HBV infection and other related diseases.

The invention discloses a kit for quantitatively detecting an HBsAg-HBsAb immune complex and application of the kit. The kit provided by the invention is a detection kit based on an ELISA sandwich method, a novel double-antibody sandwich ELISA detection platform provided by the invention adopts an HBsAg specific mSA1 antibody as a capture carrier, and efficient solid phase coating is realized through specific binding of the HBsAg specific mSA1 antibody with HBsAg; meanwhile, an anti-human IgG-HRP conjugate is introduced as a detection antibody, and high-sensitivity and high-specificity quantitative detection of the HBsAg-HBsAb immune complex is realized by utilizing special epitopes of different subtypes of human IgG and the catalytic amplification effect of HRP. The detection kit disclosed by the invention provides a reliable tool for quantitatively detecting the HBsAg-HBsAb immune complex for clinical use.

The invention provides an application of combination of a recombinant oncolytic virus and a monoclonal antibody in preparation of a medicine for treating HBV positive liver cancer. The recombinant oncolytic virus is a recombinant attenuated vesicular stomatitis virus carrying an HBV HBsAg gene and a 4-1BBL gene (wherein the 51st amino acid M in the M gene of the virus is mutated into R). The curative effect of the recombinant oncolytic virus is proved in a tumor model, and the recombinant oncolytic virus can be used for preparing therapeutic vaccines for HBV positive tumors such as HBV positive liver cancer and HBV positive diffuse large B-cell lymphoma.

The invention discloses a cholestasis index-based liver cancer risk prediction model construction method, which comprises the following steps: collecting chronic HBV infected person data containing 16 parameters, carrying out desensitization, carrying out stratified random sampling to divide a data set, and carrying out two-stage screening to obtain HBsAg, ALT, ALP, GGT, PLT and AFP core features; after Min-Max Scaling processing, L1 regularization logistic regression is combined with grid search and 5-fold cross validation to construct the model, and the model constructed by the method is obviously superior to a traditional CU-HCC model and a REACH-B model, especially has higher recognition capability for early HBV-PLC, and can effectively reduce the missed diagnosis rate.

The invention provides siRNA for targeted degradation of hepatitis B viruses HBsAg and HBX mRNA, and relates to the technical field of biological medicines. A positive-sense strand of the siRNA comprises a base sequence as shown in SEQ ID NO. 1, and an antisense strand of the siRNA comprises a base sequence as shown in SEQ ID NO. 2; or, the positive-sense strand comprises the base sequence as shown in SEQ ID NO. 3, and the antisense strand comprises the base sequence as shown in SEQ ID NO. 4. The siRNA and the siRNA conjugate provided by the invention can significantly inhibit expression of HBsAg and HBX by targeting HBV, which indicates that the siRNA and the siRNA conjugate can be used as effective components for preparing anti-HBV drugs and for treating hepatitis B caused by HBV.

Provided are bispecific antibodies that may specifically target both HBV surface antigen (HBsAg) and CD3 protein and pharmaceutical compositions comprising the same. Particularly, provided are nucleic acid molecules encoding the bispecific antibodies or fragments thereof and vectors including the nucleic acid molecules. Also provided uses of the bispecific antibodies or fragments thereof and the nucleic acid molecules and the vectors in preparation of medicines for preventing or treating HBV infection and other related diseases.

Provided is a bispecific antibody targeting HBsAg and DEC-205; the invention further relates to an antibody-drug conjugate containing the antibody, a preparation method therefor, and the use thereof.

The invention discloses a preparation method and application of PD-L1mRNA targeting deoxyoligonucleotide carrying a CpG sequence, two PD-L1mRNA targeting ASO (named as P4 and P9) are designed and screened by taking a human PD-L1mRNA coding region conserved sequence and a mouse PD-L1mRNA coding region conserved sequence as a target region; cpG sequences are added to 3'ends of P4 and P9, and whether RCP4 and RCP9 can play an adjuvant role in improving the antibody level or inhibiting tumor growth in recombinant HBsAg vaccines and anti-kidney cancer vaccines or not is researched through in-vivo experiments. According to the invention, PD-L1mRNA targeting ASOs carrying a CpG sequence is innovatively designed as a novel adjuvant, the ASOs are used for inhibiting a PD-1 / PD-L1 signal channel and activating a TLR9 signal channel, meanwhile, an innate immune system and an adaptive immune system are activated, early activation and late response of CD8 < + > T cells are promoted, and the CD8 < + > T cells are effectively inhibited. Finally, the purpose of enhancing the immune effect of the antiviral vaccine and the immune effect of the anti-tumor vaccine is achieved. The implementation of the invention not only can provide a strategy for the development of novel vaccine adjuvants, but also lays a foundation for the development of effective antiviral vaccines and anti-tumor vaccines.

The invention discloses a three-antibody sandwich ELISA (enzyme-linked immuno sorbent assay) kit for quantitatively detecting HBsAg (hepatitis B surface antigen) and application of the kit. The invention provides a novel three-antibody sandwich ELISA (Enzyme-Linked Immunosorbent Assay) detection platform, which adopts an HBsAg specific mSA1 antibody as a capture carrier, and realizes efficient solid phase coating through specific binding of the HBsAg specific mSA1 antibody with HBsAg; meanwhile, a bridging antibody SA2G4 is introduced as a bridging molecule, so that the stability of the compound is enhanced; finally, an anti-human IgG4-HRP conjugate is adopted as a detection antibody, and high specificity of human IgG4 and the catalytic amplification effect of HRP are utilized, so that high-sensitivity and high-specificity quantitative detection of HBsAg is realized. According to the platform, the detection capacity of low-concentration HBsAg is remarkably improved, the detection limitation of mutant strains is effectively overcome, and a more reliable HBV infection diagnosis tool is provided for clinic.

The invention belongs to the field of medicinal chemistry, and discloses synthesis of a novel dimeric ursodesoxycholic acid-ASO conjugate. In order to reduce the off-target effect of an ASO drug, ASO is often coupled with GalNAc to improve the liver targeting ability of GalNAc in an animal body. Clinical research finds that after an ASO drug for treating HBV infection is coupled with GalNAc, the activity of the ASO drug is reduced compared with that of uncoupled ASO, HBV viruses enter hepatocytes through NTCP, and an NTCP inhibitor dimeric ursodesoxycholic acid derivative may become a brand-new bullet for delivering ASO to the HBV infected hepatocytes. The dimeric ursodesoxycholic acid is used as a target head of ASO targeted HBV virus infected hepatocytes, the dimeric ursodesoxycholic acid derivative and ASO are efficiently coupled by using a click reaction without copper catalysis to obtain a target compound, and the compound can inhibit the content of HBsAg in an HBV mouse and possibly generate the same inhibitory activity in a human body.

Disclosed in the present application are an immune-activating recombinant oncolytic virus and use thereof, relating to the field of biomedicine. A genome of the immune-activating recombinant oncolytic virus comprises a first nucleotide sequence for encoding an HBsAg molecule, a second nucleotide sequence for encoding an IL-15 molecule, and a third nucleotide sequence for encoding a sushi domain of IL-15Ra. According to the present application, by inserting the first nucleotide sequence for encoding the HBsAg molecule, the second nucleotide sequence for encoding the IL-15 molecule, and the third nucleotide sequence for encoding the sushi domain of IL-15Ra into the genome of the immune-activating recombinant oncolytic virus, the cure rate of tumors is improved while tumor recurrence is prevented.

The present disclosure is related to methods for treating chronic hepatitis B infection in a human having HBV / HIV coinfection. The methods comprise administering to a human having HBV / HIV coinfection a therapeutically effective amount of an antisense oligonucleotide (ASO), wherein the subject has a HBsAg baseline level of not greater than a threshold level.

The invention discloses an immune activation type recombinant oncolytic virus and application thereof, and relates to the field of biological medicine, the genome of the immune activation type recombinant oncolytic virus comprises a first nucleotide sequence used for coding HBsAg molecules, a second nucleotide sequence used for coding IL-15 molecules, and a third nucleotide sequence used for coding a sushi structural domain of IL-15Ra. The first nucleotide sequence for coding HBsAg molecules, the second nucleotide sequence for coding IL-15 molecules and the third nucleotide sequence for coding sushi structural domain of IL-15Ra are inserted into the immune activation type recombinant oncolytic virus genome, so that tumor recurrence is prevented while the tumor cure rate is increased.

The present disclosure relates to methods for treating humans suffering from chronic hepatitis B. The methods comprise administering to a human in need thereof a therapeutically effective amount of an antisense oligonucleotide (ASO), such as bepirovisenb, and a therapeutically effective amount of an interferon, wherein the human has an HBsAg baseline level that is not greater than a threshold level. The present disclosure further relates to specific dosing regimens.

The invention belongs to the technical field of biological medicines, and discloses an application of an RAB7 agonist in preparation of a medicine for treating MASLD, CHB or co-diseases thereof, and the RAB7 agonist activates Rab7 and simultaneously promotes HBV DNA and HBsAg degradation and autophagy-lysosome functions to realize double effects of targeted improvement of virus and metabolism at the same time. The technical problem that an existing treatment scheme cannot cooperatively regulate and control virus replication and metabolic disorder is solved, and an efficient and safe treatment strategy is provided for clinical refractory common diseases.

The invention belongs to the technical field of molecular detection, and discloses an antibody specifically bound with HBsAg protein, an antigen binding fragment of the antibody, a detection kit and application of the antibody. In the antibody specifically bound with HBsAg protein and the antigen binding fragment thereof provided by the invention, HCDR1-HCDR3 of a heavy chain variable region are respectively shown as SEQ ID NO: 1-3, LCDR1-LCDR3 of a heavy and light chain variable region are respectively shown as SEQ ID NO: 5-7, an antigen binding site with proper conformational flexibility and stability can be formed, a plurality of antigen epitopes such as 121 / 123 / 124 / 127 amino acids of the HBsAg protein can be identified, and the antigen binding fragment of the antibody specifically bound with HBsAg protein can be used for preparing the antigen binding fragment of the antibody specifically bound with HBsAg protein. The antibody and the antigen binding fragment thereof are endowed with the ability of specific recognition and combination of HBsAg proteins of various genotypes and mutant strains thereof, and the antibody and the antigen binding fragment thereof have huge application value in detection of high broad spectrum, high sensitivity and enough specificity of HBV.