55 results about "Toll" patented technology

The present invention relates to a flagellin fusion protein and the use thereof, and, more specifically, to a fusion protein comprising a human IgG4 Fc variant and the use thereof using toll-like receptor 5 (TLR5) stimulation activity, wherein the human IgG4 Fc variant has mutation preventing a Fab-arm exchange.

Compounds and pharmaceutical compositions useful to treat cancer (e.g., lymphoma), neurodegenerative diseases, and autoimmune disorders include (1) a first nucleic acid sequence capable of binding to a transcription factor, for example, a signal transducer and activator of transcription (STAT) factor, such as STAT3, (2) a second nucleic acid sequence capable of binding a Toll-like receptor protein, for example, a CpG oligodeoxynucleotide, and (3) a ubiquitin ligase binding compound capable of binding a ubiquitin ligase protein, for example, a compound that is capable of binding a cereblon protein, such as lenalidomide, pomalidomide, or thalidomide.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.

The present invention relates to oligonucleotides that inhibit Toll-like receptor 7 (TLR7) and / or Toll-like receptor 8 (TLR8) or enhance TLR8 and uses thereof.

A Toll-like receptor (TLR) is an indispensable component of an innate immune system and plays a key role in identifying and coping with microbial pathogens. TLR7, TLR8, and TLR9 are located in the endosome-lysosome compartment within the cell and then exclusively used to detect nucleic acids of a microorganism after the microorganism is swallowed and reaches the endosome compartment. The biological importance of the TLR agonists lies in that they can be used as powerful tools for studying innate immune responses, developing vaccines and potential therapeutic applications. In addition, TLR agonists have been explored for use as immunotherapy, while these TLR antagonists can be used as new pathogenic nodes in the context of different autoimmune diseases. Therefore, the agonists and antagonists of the endosomal TLR have therapeutic significance in different clinical backgrounds. The previous study on 8-oxo adenines shows that the C-6-site-NH2 group is extremely important for the recognition of agonistic active sites and the subsequent induction of interferon (IFN). The present invention explores the ability of a hydrogen-substituted 8-oxopurine derivative that does not contain an essential C-6 amine group. The C-6 amino group in the 8-oxopurine derivative is substituted by hydrogen (H), providing an exciting opinion for regulating the endosome TLRs (Toll-Like Receptors). The ability of 8-oxopurine derivatives to modulate the endosomal TLR has been reported, which derivatives are related / interrelated to various substitutions at N-7, N-9 and C-2, all derivatives containing hydrogen at C-6. Structure 1

To provide a compound of insect origin exhibiting high immunostimulatory activity.SOLUTION: There is provided a polymer compound that is polyethylene glycol or a derivative thereof having an ability to bind to a Toll-like receptor 4.SELECTED DRAWING: None

Provided is an adjuvant composition comprising a glycoarchaeol and at least one immunostimulant selected from a Toll-like receptor (TLR) agonist and a saponin. The glycoarchaeol and / or immunostimulant may be present as a pharmaceutically acceptable salt. The adjuvant composition may be comprised together with an antigen in an immunogenic composition, such as a vaccine composition, which may be for use to induce an immune response in a subject. Further provided is use of the immunogenic composition to induce an immune response in a subject, particularly an immune response that comprises both a cell-mediated response and a humoral response.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.

The present disclosure relates to the use of compound (I) and any of its salts for the treatment of a neoplasm characterized by high expression of toll-like receptor 4 (TLR4) in the tumor or its microenvironment, associated with at least one of the pathophysiological complications including immunosuppression, angiogenesis, fibrosis, or metastasis.

The invention belongs to the field of medicinal chemistry and pharmacology, and relates to application of a novel glycolipid TLR2 agonist 13-C in preparation of vaccine adjuvants and anti-tumor treatment. The compound is excellent in human TLR2 agonist activity, EC50 reaches 2.2 nM, and the compound is simple in structure, easy to prepare and excellent in solubility and has industrial application potential. In a B16-OVA tumor model, the antibody induction capacity of the compound is superior to that of a positive control drug Diprovocim, and the anti-tumor activity of the compound is more remarkable; in addition, PD-L1 expression of tumor tissue can be effectively down-regulated, and a synergistic anti-tumor effect is generated with a PD-L1 monoclonal antibody Atezolizumab. Besides, 13-C and a vaccine adjuvant QS-21 are combined for use, so that a synergistic enhancement effect is achieved, the antibody titer induced by a vaccine can be remarkably improved, antibody subtypes are enriched, meanwhile, cellular immunity and humoral immunity response of an organism are stimulated, and the effect of dual immune activation is achieved.

Disclosed herein are compounds that are Toll-like receptor (TLR) agonist, conjugates comprising these compounds and cell targeting moiety, pharmaceutical compositions thereof, method of activating toll-like receptors 7 and / or 8 and method for the treatment of diseases or disorders mediated by toll-like receptors 7 and / or 8, in particular viral infections and proliferative disorders, such as cancer.

Some aspects of the present disclosure are generally related to injectable compositions, for example, for intratumoral drug delivery. In some embodiments, the injectable composition comprises a polymer configured to undergo a solution-gel transition when heated from room temperature to at or around body temperature, allowing for the injection of the injectable composition as a liquid with subsequent gelation to retain the composition at the injection location. In some embodiments, the injectable compositions may be capable of encapsulating radio-opaque label and / or a hydrophobic immunoadjuvant (e.g., imiquimod) at a concentration of greater than or equal to 0.5 mg / mL. Accordingly, some aspects of the present disclosure are related to the radio-opaque label facilitating visualization of the injectable composition during injection and / or the retention of the injectable composition at the injection location, allowing for localized and extended-release of the immunoadjuvant. Still other aspects are generally directed to related methods, kits, or the like.

The invention provides an establishment method and application of a Zika virus infectious animal model, and belongs to the technical field of biology. According to the invention, ZIKV is inoculated to Toll-like receptor-deleted animals, such that the ZIKV challenging animal model is obtained. After the animal is inoculated with ZIKV, obvious ZIKV load can be detected in blood, liver, spleen, reproductive organ and brain tissue of the animal, moreover, the spleen is obviously swollen, the liver tissue has punctiform necrotic lesion, the splenosome is obviously reduced, and the mRNA level of inflammation related indexes Ccl5, Cxcl1, Isg15 and Isg56 is obviously up-regulated, which indicates that the ZIKV challenge model disclosed by the invention is successfully constructed; the method can be used in related researches such as ZIKV infection mechanism, vaccine research and development, anti-ZIKV drug research and development and the like.

The application discloses a targeted acne-removing composition suitable for sensitive skin and a preparation method and application thereof. The targeted acne-removing composition comprises lysozyme, a first extract and a second extract in a mass ratio of 1:(0.1-10):(0.1-5). The first extract comprises guaiacum extract and myrtle fruit extract. The second extract comprises sophora flavescens extract and angelica sinensis extract. The targeted acne-removing composition containing lysozyme, the first extract and the second extract in specific mass ratios can inhibit the activity of propionibacterium acnes, down-regulate the expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), and achieve efficient acne removal, and has the mild property and can be suitable for sensitive skin.

This application relates generally to toll like receptor modulator compounds and pharmaceutical compositions which, among other things, modulate toll-like receptors (e.g. TLR8), and methods of making and using them.

The invention relates to a CpGODN molecule and an application thereof. According to the CpG adjuvant, by optimizing a core CpG motif (such as 5 '-GACGTT-3') and a flanking sequence thereof, the activation efficiency of a Toll-like receptor 9 (TLR9) is remarkably improved. In order to further enhance the stability and the targeting property of the CpG adjuvant, the CpG oligonucleotide is subjected to phosphorothioate modification, and the CpG adjuvant shows excellent immune activation ability in both in-vitro and in-vivo experiments, can significantly enhance the immunogenicity of vaccines, overcomes the species effect, has a good stimulation effect on both mouse and human lymphocytes, and can be used for preparing the immunopotentiator. The compound has a remarkable synergistic effect with an aluminum adjuvant, realizes relatively balanced cell humoral immune response, and has a wide application prospect in the field of vaccine development.

The present disclosure relates to methods of selecting, designing or modifying oligonucleotides so that they inhibit cyclic GMP-AMP synthase (cGAS), Toll-Like Receptor 3 (TLR3) Toll-Like Receptor 7 (TLR7), Toll-Like Receptor 8 (TLR8) and / or 5 Toll-Like Receptor 9 (TLR9), or potentiate Toll-Like Receptor 8 (TLR8). Additionally, the present disclosure resides in methods of selecting, designing or modifying oligonucleotides such that they exhibit reduced cGAS inhibitory activity.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid (RP) and one or more sequences of micro-interfering ribonucleic acid (miRNA). When the RP interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a toll-like receptor. In some embodiments of the present disclosure, the toll-like receptor is TLR3.

The present invention relates to a Toll-like receptor 5 gene conditional overexpression animal model. Specifically, the present invention provides a method for preparing a non-human model animal with conditional overexpression of the TLR5 gene, wherein Cas9mRNA and gRNA are obtained by in vitro transcription; a homologous recombination vector (donor vector) is constructed, wherein the vector comprises a 5' homology arm, a TLR5 gene expression cassette and a 3' homology arm, wherein the TLR5 gene expression cassette is a silent expression cassette, and under induction conditions, the silent expression cassette is converted into an activated TLR5 gene expression cassette. Cas9mRNA, gRNA and the homologous recombination vector are injected into a fertilized egg in vitro to obtain an injected fertilized egg. The injected fertilized egg is regenerated into a TLR5 gene conditional overexpression animal model. The animal model of the present invention has broad application prospects in antiviral, antibacterial immunity, antitumor immunity, diagnosis and treatment of inflammatory bowel disease, etc.

The invention discloses Toll gene dsRNA and application thereof in improving the effect of abamectin in preventing and treating diaphorina citri. The invention provides a technical scheme for preventing and treating diaphorina citri through combined use of dsRNA of a targeted DcToll gene and abamectin, specifically, the DcToll gene of the diaphorina citri is silenced, the immune response of the diaphorina citri is inhibited, and the potential tolerance of the diaphorina citri to abamectin can be reduced. The method provided by the invention is expected to realize the synergistic interaction of immunosuppression and chemical agents, provides a new technical thought for improving the control effect of abamectin and delaying the development of resistance, and is beneficial to the realization of pesticide reduction and synergism.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.

The present invention relates to the interdisciplinary field of pharmaceutical chemistry and immunology, and discloses a Toll-like receptor 4 immunostimulator and its application, an antiviral vaccine molecule, and its preparation method and application. The Toll-like receptor 4 immunostimulator is a compound represented by formula (1) and a pharmaceutically acceptable salt thereof, wherein m is an integer of 0-21, n is 0 or 1, o is an integer of 0-10, and p is an integer of 1-25; X and Y are each independently an oxygen element, a nitrogen element, or a carbon element; D is an oxygen element or a sulfur element; and any two of A, B, and C are ‑CH2OH, and the remaining one is ‑CH2NH2, ‑COOH, ‑CH2OH, ‑CH2SH, ‑CF3, ‑CHF2, ‑CH2F, ‑CH2OCH3, ‑CH2NH‑, ‑CH2N3‑, ‑CH2O‑, ‑CH2S‑, or ‑C(O)‑. The Toll-like receptor 4 immunostimulator of the present invention can be used as a vaccine adjuvant, and the antiviral vaccine molecule prepared has a simple structure and is easy to prepare and store.

The present application provides a novel series of small molecular immune agonists of Toll-like receptor 7, having a structure represented by Formula I. The present application further provides use of the immune agonist for activating and amplifying immune cells and lymphocytes, and for preparing an immunomodulatory drug, an immune anti-tumor small molecule drug, and an immune anti-tumor macromolecular drug.

The invention provides a high-sensitivity in-vitro pyrogen detection method, which is characterized in that on the basis of an in-vitro pyrogen detection method (reporter gene method), a transgenic cell which expresses a Toll-like receptor and transfects an NF-kB reaction element and a luciferase gene is used for detecting a pyrogen, the pyrogen is combined with the Toll-like receptor on the surface of the cell to activate an NF-kB signal channel, and the NF-kB reaction element and the luciferase gene are converted into the NF-kB signal channel. Therefore, the expression of luciferase is activated.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.

Methods of modulating an immune response for the treatment of cancer includes compositions which comprise chimeric molecules with an anti-CD47 binding domain and an immunomodulatory agent.

The present invention relates generally to the field of immunomodulation and more specifically to compounds that exhibit Toll-like receptor 4 (TLR4) agonist activity. The invention provides novel compounds capable of stimulating or promoting an immune response, thereby offering potential therapeutic applications. In particular, the compounds may be useful in methods of promoting and / or maintain gastrointestinal health, as well as treating or preventing gastrointestinal diseases, such as IBD and colitis.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.