532 results about "Interferon" patented technology

The present invention discloses a human serum albumin-targeting nanobody and its application. A variety of human serum albumin-targeting nanobodies that can be used to construct long-acting fusion protein drugs and their immune screening methods are disclosed. The antibody is composed only of the heavy chain variable region and can be fused and expressed with therapeutic proteins or polypeptide drugs such as interleukin, interferon, and tumor necrosis factor in an Escherichia coli expression system. The fusion protein has the activity of specifically binding to human serum albumin, has a relatively high affinity, can effectively extend the drug half-life, and does not affect the biological activity of the recombinant protein drug at the same time.

The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.

The invention discloses a grass carp gamma interferon fusion protein as well as a mutant, a coding gene and application thereof. In order to improve the expression quantity or expression efficiency of the grass carp gamma interferon, codon optimization and mutation are carried out on the coding gene of the grass carp gamma interferon to obtain the grass carp gamma interferon mutant. The fusion protein is further obtained by connecting the grass carp gamma interferon mutant with the C end of the grass carp ferritin heavy chain subunit of which the last 17 amino acids are removed through a connecting peptide. In order to further improve the antiviral activity of the fusion protein, the obtained fusion protein is subjected to single-point mutation, and the titer of the fusion protein is remarkably improved. The fusion protein is expressed by a silkworm cell eukaryotic expression system, and the fusion protein shows a conformation suitable for the interferon to play functions based on the ferritin self-assembly characteristic, so that the titer of the interferon in a host is effectively improved, and the in-vivo and in-vitro half-life period of the interferon is prolonged. The invention has application prospects in preparation of drugs or reagents for preventing or treating viral diseases of grass carp and the like.

The present invention relates, in part, to chimeric proteins comprising consensus interferon, or a variant thereof, and their use as therapeutic agents.

The invention discloses an immunosensor for detecting cytokine interferon gamma through electrochemiluminescence as well as a preparation method and application of the immunosensor. The immunosensor comprises a three-electrode system consisting of an immunoelectrode, a reference electrode and a counter electrode, the immunoelectrode is a VMSF modified electrode confined to cerium dioxide nano enzyme and platinum nano particles, and is obtained by covalently immobilizing an IFN-gamma antibody and closing a non-specific site; when the immunosensor is used for detection, a solution containing luminol is used as an electrolyte. The CeO2 and the PtNPs which are confined in the nano channel show a remarkable synergistic catalysis effect. Compared with direct modification on a plate electrode, CeO2-PtNPs has higher catalytic activity and stability. The sensor provided by the invention is used for INF-gamma detection, has the advantages of high sensitivity, low detection limit and wide detection range, does not need complex pretreatment and separation processes during detection, reduces the detection cost, is simple to operate, and is suitable for large-scale application.

The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.

The invention relates to a cyclopeptide inhibitor aiming at human STING (stimulating interferon gene) and application of the cyclopeptide inhibitor. The cyclic peptide can specifically bind to and inhibit activation of human STING. The invention also provides a nanoparticle delivery system for loading the cyclopeptide on a cationic polymer PBAE and an amphiphilic polymer pDMA-pEPEMA, and a preparation method of the nanoparticle delivery system. The cyclic peptide and the nanoparticles thereof can be used for preparing medicines for treating autoimmune diseases (such as systemic lupus erythematosus and the like) caused by excessive activation of the cGAS-STING signal pathway. Compared with the existing small molecule STING inhibitor, the cyclopeptide inhibitor provided by the invention has higher specificity, stability and inhibition effect.

Methods for interfering or controlling IFN induction, IFN production and / or IFN activity are disclosed, harnessing viral mechanisms for evading or suppressing host anti-viral immune reactions. These methods comprise administration of one or more viral messenger RNAs (mRNAs) coding for proteins or peptides that control or interfere with signal transduction upstream and / or downstream of IFN induction, thereby providing a means for preventing or treating diseases, disorders or conditions associated with increased IFN production, such as cancer, autoimmune diseases, inflammatory diseases and interferonopathies.

The invention relates to a recombinant expression cat interferon-omega gene and a preparation method and application thereof, the nucleotide sequence of the cat interferon-omega gene is as shown in SEQ ID NO.1, and the cat interferon-omega gene is obtained by introducing an Fc fusion fragment to the C terminal and / or N terminal of the natural gene sequence of the cat interferon-omega. XTEN or PAS is introduced to prolong a peptide fragment, and original glycosylation modification sites on a natural sequence are reserved. The method comprises the following steps: cloning a cat interferon-omega gene into an expression vector containing double promoters, further transfecting into a cell, carrying out stable cloning and screening, establishing a high-expression cell strain, and carrying out fermentation culture in a bioreactor. According to the invention, the cat interferon-omega gene is subjected to multiple modification and is efficiently expressed in a CHO-K1GS system, so that the protein yield, the stability and the half-life period are remarkably improved; the obtained fusion protein is high in purity and strong in activity, can obviously enhance immune response and protection effect when being matched with cat vaccines, and is good in safety.

The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human B7-H4 (and optionally cynomolgus monkey, mouse, and / or rat B7-H4) and compositions comprising such antibodies or antigen-binding fragments thereof. In a specific aspect, the antibodies or antigen-binding fragments thereof that specifically bind to human B7-H4 increase T cell proliferation, increase interferon-gamma production, and / or deplete B7-H4 expressing cells via ADCC activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4.

The invention discloses a nanoparticle for targeted protein degradation and a degradation method. The nanoparticles can enhance uptake of cells and effectively encapsulate specific antibodies for recognizing target proteins, and meanwhile, the interferon component can induce expression of TRIM family proteins in the cells. After ingestion into the cell, the antibody released by the nanoparticle can bind to the target protein and bind to the TRIM family protein to mediate degradation of the target protein. In this process, although the TRIM family protein is continuously consumed, the TRIM family protein can be compensated by the TRIM family protein expression induced by the particle of the invention, thereby maintaining efficient degradation.

The present disclosure relates to compositions and methods relating to interferon agonists and their engineered polypeptides. The engineered polypeptides have specificity to receptors in immune systems mediated by Type I interferon (IFN). The present disclosure also relates to methods and system for identifying surrogate agonists for cell surface receptors including dimeric and trimeric receptors.

The invention relates to the field of biological medicine and aquatic products, and discloses a grass carp IFNf interferon and truncated protein and application thereof in virus resistance or bacterium resistance. The applicant discovers the new subtype IFNf of the grass carp interferon for the first time, the protein coded by the new gene has an efficient antiviral effect, and the derived peptide AMP-G2 of the grass carp interferon has broad-spectrum antibacterial activity. The sensitivity of the grass carp interferon IFNf to grass carp reovirus (GCRV) infection is higher than that of other interferon, and the grass carp interferon IFNf shows obvious antiviral activity on the cellular level and can be used for preparing antiviral drugs. The interferon-derived peptide provided by the invention is a host natural peptide, is small in molecular weight and simple to synthesize, has a remarkable bactericidal effect on various bacteria and fungi, and can be used for preparing broad-spectrum antibacterial agents or antibacterial drugs.

The invention belongs to the technical field of biological medicine, and provides CKS1B serving as an immunotherapy response prediction biomarker and application of the CKS1B, and according to the application, CKS1B serves as an immunotherapy response marker, and a CKS1B inhibitor is combined with an active component to treat a model mouse. In-vitro cell experiments are adopted to evaluate the immunotherapy prediction effect of the CKS1B as a biomarker on esophageal squamous carcinoma, a Cks1b overexpression tumor mouse model, a homologous mouse model and a human immune reconstruction mouse model are established, and a CKS1B inhibitor is combined with active ingredients to treat the two models; results show that the CKS1B inhibitor combined with the active component can promote removal of esophageal squamous carcinoma cells by CD8 + T cells, inhibit interferon signal channels and antigen presentation, effectively recover immune response, inhibit tumor cell proliferation and significantly reduce tumor volume, so as to achieve the purpose of treating esophageal squamous carcinoma.

Provided are a fusion protein comprising recombinant porcine interferon λ1 and a use thereof, and a preparation method and use for the fusion protein. The fusion protein is formed by respectively linking porcine interferon λ1 to other fragments (such as porcine interferon γ) and / or porcine serum albumin (PSA) directly or indirectly by means of linker elements. The porcine interferon λ1 fusion protein can be prepared by using a mammalian cell expression system on the basis of genetic engineering technology. Compared with natural porcine interferon λ1, the provided recombinant porcine interferon λ1 fusion protein has a long half-life period and can be used for preparing drugs for preventing or treating porcine viral diseases.

An Interferon Gamma Inducible Protein 16 (IFI16) mutant gene and its use as a marker for predicting, diagnosing, or prognosticating risk or severity of chronic liver disease is described. As a result of performing genomic analysis on NAFLD and NASH patient groups, it was confirmed that the frequency of IFI16 single-nucleotide variants (SNVs) including rs2276404, rs73021847, rs7532207, and rs6940 was increased, and the expression of the IFI16 mutant gene was increased depending on the disease stage of liver disease. The IFI16 SNV was highly expressed in infiltrating macrophages, playing a role in macrophage-induced inflammatory processes, and the IFI16 variant bound more strongly to dsDNA than wild-type IFI16, exacerbating the impaired mitochondrial DNA-sensing response signaling of the IFI16-PYCARD-CASP1 pathway. Thus, the IFI16 mutant gene may be used for predicting, diagnosing, or prognosticating risk or severity of chronic liver disease.

The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer in patients in need thereof. The methods comprise administering to a patient in need a STING (stimulator of interferon genes) agonist, such as Compound No. 14, or a pharmaceutically acceptable salt thereof, in combination with one or more checkpoint inhibitors. Suitable checkpoint inhibitors include anti-PD-1 antibodies, anti-PD-L1 antibodies and anti-CTLA-4 antibodies. Also provided are medicaments for use in treating cancer. Compound No. 14 has the structure:

Provided is a Hunner-type interstitial cystitis therapeutic agent that can selectively inhibit IFN-γ without risk of biological contamination and can be stored at room temperature. Provided is a Hunner-type interstitial cystitis therapeutic agent or a reagent for test and research, comprising as an active ingredient a DNA oligonucleotide having a nucleotide sequence set forth in any of SEQ ID NO:1 to 3 and selectively binding to IFN-γ. A base, X, in the sequence of the DNA oligonucleotide having the nucleotide sequence set forth in SEQ ID NO: 3 is an artificially produced base, and the artificially produced base may be chemically modified with a low-molecular-weight compound, a medium-molecular-weight compound, a high-molecular-weight compound, a biopolymer, or a biocompatible polymer.

The invention discloses a cryptosporidium parvum AOX gene deleted strain as well as a construction method and application thereof, and the cryptosporidium parvum AOX gene deleted strain disclosed by the invention is obtained by editing an AOX gene of cryptosporidium parvum through a gene editing technology. According to the gene editing technology, the cryptosporidium parvum AOX gene is knocked out by using a CRISPR / Cas9 gene editing technology, so that a cryptosporidium parvum AOX gene deleted strain is obtained; the AOX gene is found to be related to insect toxicity for the first time, and the infection intensity of an AOX gene deleted insect strain in a gamma interferon gene knockout mouse body is remarkably reduced. Research shows that after the AOX gene is deleted from the wild type cryptosporidium parvum IIdA20G1 subtype strain, the strain has the advantage that the toxicity is obviously weakened, and can be used for preparing cryptosporidium parvum attenuated vaccines so as to prevent cryptosporidium parvum infection.

Disclosed in the present invention are an ultrasonic therapy system and use thereof. The ultrasonic therapy system comprises a host and a therapy head. The host comprises a signal module, a power supply module, an output module, and a matching module. The therapy head comprises a piezoelectric module and an amplitude transformer module. The length of the piezoelectric module and the length of the amplitude transformer module are half of the wavelength. The output frequency range of the ultrasonic therapy system conforms to the frequency range of ultrasonic waves output by bats. According to the present invention, low-frequency low-intensity ultrasonic acts on the immune system of an organism, and specific immune environments featuring high interferon α expression, strong immune response, enhanced autophagy, down-regulated inflammation level, etc., are formed in the organism. Therefore, the ultrasonic therapy system can be used to resist tumors and viruses, prevent and ameliorate inflammatory aging, prolong the lifespan, and treat autoimmune diseases.

The invention aims to provide a method for effectively separating and proliferating stem cells from peripheral blood. The composition according to the present invention comprises interferon-gamma (IFN-gamma) in order to enhance the adhesion of stem cells isolated from peripheral blood and thus improve the acquisition rate of stem cells. Therefore, the composition and the peripheral blood-derived stem cell isolation and culture method according to the present invention have been established for inducing progenitor cells differentiated into somatic cells that can be differentiated into various target tissues, and for preventing or treating diseases.

The present invention relates to anti-ILT7 antibodies. Antibodies capable of binding to IPC are obtained by using animal cells in which a cell membrane protein that binds to ILT7 is co-expressed as an immunogen. The antibodies of the present invention have high specificity, such that the antibodies can immunologically distinguish ILT7 from other ILT family molecules. The anti-ILT-7 antibodies of the present invention can bind to IPC and inhibit its activity. The activity of IPC can be inhibited by the anti-ILT-7 antibodies of the present invention, and interferon-related diseases can be treated or prevented. In the presence of IFNα, the expression of ILT7 in IPC can still be maintained. Therefore, in patients with various autoimmune diseases with increased IFNα production, an inhibitory effect of anti-ILT-7 antibodies on the activity of IPC can be expected.

The invention discloses a method for establishing a hemophagocytic syndrome in-vitro cell disease model, and belongs to the technical field of biology. Based on human PBMC construction, the reaction of a human immune system can be truly reflected, experimental result deviation caused by species difference in an animal model is avoided, and a more accurate model basis is provided for research of human diseases. In addition to T cell over-activation, the HLH model of the present application has a clear key feature of NK cell reduction, which is HLH, accompanied by up-regulation of cytokines such as interferon-gamma and IL-10. The establishment process of the model is rapid and efficient, the experimental period is remarkably shortened, a large number of samples or drugs can be rapidly screened, the research efficiency is improved, and the conversion process from basic research to clinical application is accelerated. The method can be used for researching various mechanisms related to the HLH, is beneficial to more comprehensive understanding of pathogenesis of the HLH, and provides a theoretical basis for developing preliminary screening of targeted drugs.

The invention relates to a biological preparation prepared from astragalus polysaccharide and application of the biological preparation. The biological preparation comprises the following components: traditional Chinese medicine components: 15-20g of an astragalus-codonopsis pilosula-lucid ganoderma co-extract, 10-15g of an astragalus-atractylodes macrocephala-Chinese yam co-extract, 8-12g of an astragalus-medlar-dendrobe co-extract, 6-10g of an astragalus-ginseng-polygala tenuifolia co-extract and 5-8g of an astragalus-coptis-kudzu vine root co-extract; the biological preparation comprises the following components: recombinant human interferon alpha-2b150-200IU, 0.03-0.05 mg of an anti-PD-1 antibody fragment, 0.08-0.1 [mu] g of a brain-derived neurotrophic factor (BDNF) and 0.05-0.1 mg of a glucagon-like peptide-1 (GLP-1) analogue, and by means of multi-target linkage, traditional Chinese medicine polysaccharide synergistic protection of the biological preparation, dynamic dosage regulation and the like, the treatment effect on complex diseases is improved, and the dosage and side effects of the biological preparation are reduced.

The present invention relates to a nucleic acid molecule capable of controlling innate immunity by RNA and, more specifically, to a short duplex hairpin RNA (sdhRNA) that binds to protein kinase R (PKR), which is activated upon recognition of RNA, thereby inhibiting the activity of PKR and suppressing PKR-mediated innate immunity and which, when introduced into the 3'-UTR of mRNA, can increase the expression level of an antigen. The sdhRNA motif according to the present invention inhibits the activity of protein kinase R (PKR) by binding to PKR activated by recognizing RNA. Therefore, when administered into cells in combination with exogenous RNA or as an insert into the 3'-UTR of mRNA, the sdhRNA motif exhibits the effect of reducing RNA-indued PKR activation, mitigating RNA-induced cell death, and downregulating the expression of interferon-stimulated gene (ISG) as well as improving the expression efficiency of a protein encoded by the mRNA. With the effects, the motif is applied to various RNA-based uses, for example, vaccines, in vivo / ex vivo gene therapeutic agents, and the like.

The invention discloses an engineered exosome for breaking through a pyroptosis immune starting and maintaining barrier as well as a preparation method and application of the engineered exosome. The exosome is constructed by loading an immune checkpoint inhibitor into a pre-stimulated exosome, and the exosome is derived from immune cells, high-expression interferon gamma and granzyme A. The expression of the tumor cell GSDMB is up-regulated by delivering the interferon gamma through the exosome, and the exogenous granzyme A cuts the GSDMB to trigger pyroptosis; meanwhile, an immune checkpoint inhibitor blocks a PD-1 / PD-L1 pathway in situ, T cell depletion is reversed, and release of endogenous granzyme A is promoted; the pyroptosis cells release antigens to activate the T cells, the activated T cells continuously secrete granzyme A / interferon gamma to form a cascade amplification effect, and the problem of double barriers existing in the pyroptosis immune cycle of granzyme A-GSDMB is solved. The engineered exosome can improve the infiltration degree of CD8 + T cells, and is suitable for treating tumors such as liver cancer and non-small cell lung cancer.

The present invention provides methods, compositions, systems, and kits comprising nano-satellite complexes and / or serum albumin carrier complexes, which are used for modulating antigen-specific immune response (e.g., enhancing anti-tumor immunity). In certain embodiments, the nano-satellite complexes comprise: a) a core nanoparticle complex comprising a biocompatible coating surrounding a nanoparticle core; b) at least one satellite particle attached to, or absorbed to, the biocompatible coating; and c) an antigenic component conjugated to, or absorbed to, the at least one satellite particle component. In certain embodiments, the complexes further comprise: d) a type I interferon agonist agent. In some embodiments, the serum albumin complexes comprise: a) at least part of a serum albumin protein, b) an antigenic component conjugated to the carrier protein, and c) a type I interferon agonist agent.

The application relates to the fields of biological medicine and aquaculture, and discloses a zebrafish IFNf interferon truncated protein and application thereof in antibiosis. The zebrafish interferon derivative peptide AMP-Z2 can specifically inhibit fungi. The interferon derivative peptide provided by the application is a host natural peptide, has small molecular weight, is simple to synthesize, has significant bactericidal effects on various bacteria and fungi, and can be used for preparing broad-spectrum antibacterial agents or antibacterial drugs.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APC's.