19 results about "Antibody block" patented technology

The invention relates to the technical field of biological medicines, and discloses a blocking antibody targeting CXCL6 and an application of the blocking antibody in preparation of antitumor drugs. The antibody or antigen-binding fragment thereof is capable of binding specifically to human CXCL6 protein with high affinity (e.g., Kd < = 1 nM). According to the invention, the specificity and high affinity of the antibody are verified by Western Blot, immunofluorescence, immunohistochemistry and surface plasmon resonance (SPR) technologies. Functional experiments show that the antibody can effectively block CXCL6-induced neutrophil chemotaxis, including in Transwell, a three-dimensional gel model and a zebra fish living body model. Besides, in a mouse MC38 colon cancer model, the antibody shows remarkable anti-tumor activity and can inhibit tumor growth driven by CXCL6. The invention also provides a pharmaceutical composition containing the antibody, and application of the antibody in preparation of drugs for preventing or treating diseases (such as inflammatory diseases, autoimmune diseases and cancers) related to abnormal expression or activity of CXCL6.

The present invention relates to an activatable transmembrane construct and an activatable degrader comprising the same, the activatable transmembrane construct comprising a cell penetrating portion, a cleavable portion and a shielding portion wherein the cell penetrating portion is selected from: a transmembrane peptide, an oligosaccharide peptide and any combination thereof, and / or the shielding portion is selected from a shielding peptide. The activatable transmembrane construct is connected with a target molecule binding part to form an activatable degradant. After the cleavable part is subjected to enzyme digestion, the cell penetrating part shielded by the shielding part is activated, so that the target molecule binding part connected with the cell penetrating part can be mediated to enter the cell to be degraded. After being connected with the activatable transmembrane construct, either a blocking antibody or a non-blocking antibody can achieve the effects of activating T cells and killing tumor cells, and the activatable transmembrane construct has additional benefits.

Provided are a set of fully human TSH receptor (TSHR)-blocking monoclonal antibodies targeting a CHK36 homolog cluster, a preparation method therefor, and an application thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and single memory B cells that specifically recognize TSHR in peripheral blood of a patient with a high titer of TSH-blocking antibodies (TBAb), performing in vitro cloning of antibody light and heavy chains and performing recombinant expression, and using hTSHR-CHO cells to perform screening and validation of antibody properties to obtain a blocking monoclonal antibody that specifically targets human TSHR. The fully human TSH receptor-blocking monoclonal antibodies specifically bind to a TSHR, and effectively block signal transduction after a TSH binds to a receptor, inhibit the synthetic secretion of thyroid hormones, and significantly reduce and inhibit TSHR expression and fibrosis in orbital fibroblasts of effector cells associated with thyroid-related ocular diseases. The fully human TSH receptor-blocking monoclonal antibodies have broad application prospects in the treatment of Graves' disease (GD) and other diseases caused by hyperthyroidism, such as thyroid eye disease (TED).

The invention discloses a preparation method and application of a Taq DNA polymerase monoclonal antibody based on structural domain analysis, which are specifically different from a traditional method using full-length Taq polymerase as an immunogen (the method generally cannot generate a functional blocking antibody due to a hidden epitope which is difficult to approach). According to the invention, by adopting a structure-oriented and domain-specific strategy, the exposure of epitopes related to active sites is remarkably enhanced, and a novel antigen Taq-P protein is developed. Based on the antigen, a high-specificity inhibitory monoclonal antibody is prepared, and the antibody is expected to become a core component of a high-performance hot start PCR reagent. According to the invention, a novel and generalizable mode is established for the development of a core diagnostic reagent, a key raw material is provided for gene detection and molecular diagnosis, and a valuable methodological framework is contributed to the development of propulsor engineering and biotechnology reagents.

Provided are a group of fully human thyrotropin receptor (TSHR) (TSH receptor, TSHR) blocking monoclonal antibodies belonging to a SH1 homocluster, a preparation method therefor, and a use thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and individual memory B cells, which specifically recognize TSHR, from peripheral blood of a patient having a high TSH receptor blocking antibody (TBAb) titer, cloning antibody light and heavy chains in vitro, followed by recombinant expression, and performing antibody characteristic screening and verification by using hTSHR-CHO cells, thereby obtaining blocking monoclonal antibodies that specifically target human TSHR. The fully human TSH receptor blocking monoclonal antibodies can specifically bind to TSHR, thereby enabling effective blockage of signal transduction after TSH binds to the receptor, inhibiting the synthesis and secretion of thyroid hormones, and significantly reducing and suppressing the expression of TSHR and fibrosis in orbital fibroblasts, the effector cells in thyroid-related eye diseases. The present invention has broad application prospects in the treatment of Graves' diseases and diseases caused by hyperthyroidism, such as thyroid eye diseases.

The application discloses a preparation method and application of a dual-immune checkpoint inhibitor modified glycosyl nanoparticle, relates to the technical field of biological medicine, and comprises (a) a core-shell structure nano carrier formed by self-assembly of amphiphilic quaternary ammonium chitosan oligosaccharide, wherein the nano carrier is loaded with a dabrafenib; (b) a PD-1 / PD-L1 pathway blocking polypeptide AUNP-12, which is coupled to the surface of the nano carrier through a covalent bond; and (c) a CTLA-4 pathway blocking antibody alpha-CTLA-4, which is coupled to the surface of the nano carrier through a Schiff base reaction; wherein the amphiphilic quaternary ammonium chitosan oligosaccharide is composed of a hydrophilic quaternary ammonium chitosan oligosaccharide segment, a hydrophobic vitamin E succinate segment and an enzyme-sensitive polypeptide GPLGVRGDG connecting the two segments and capable of being specifically cut by matrix metalloproteinase 2; the dual-immune checkpoint inhibitor modified glycosyl nanoparticle provided by the application has good biological tissue compatibility, and the dual-immune checkpoint inhibitor modified glycosyl nanoparticle (LTHAC) has strong killing effect and targeting capacity on B16F10 melanoma cells with high expression of PD-L1 and abnormal activation of a MAPK pathway.

The invention discloses an ROS responsive antibody nano-drug conjugate as well as a preparation method and application thereof, and belongs to the field of biological medicines. The conjugate comprises a nano-drug carrier, a TIM-3 blocking antibody and a VISTA blocking antibody, wherein the nano-drug carrier is encapsulated with a first chemotherapeutic drug and a second chemotherapeutic drug which can be subjected to cascade reaction, and the TIM-3 blocking antibody and the VISTA blocking antibody are covalently connected to the surface of the carrier through ROS responsive linkers. After reaching a tumor site, the conjugate can respond to a high-level ROS release antibody of a tumor microenvironment, synchronously block TIM-3 and VISTA immune checkpoints, and relieve immunosuppression; the carried chemotherapeutic drug is subjected to cascade reaction in tumor cells to induce immunogenic death and release tumor antigens and danger signals. Tumor cascade killing and antibody effective blocking synergism can effectively remodel an immunosuppression microenvironment, activate and enhance anti-tumor immune response, and realize efficient tumor killing. The conjugate has the advantages of precise targeting, synergistic interaction and good biological safety, and provides a new strategy for tumor immunotherapy.

The present application relates to an activatable cell-penetrating construct comprising a cell-penetrating moiety, a cleavable moiety and a masking moiety, wherein the cell-penetrating moiety is selected from the group consisting of a cell-penetrating peptide, an oligosaccharide peptide and any combination thereof, and / or the masking moiety is selected from a masking peptide. The activatable cell-penetrating construct forms an activatable degrader when linked to a target molecule-binding moiety. After the cleavable moiety is cleaved by an enzyme, the cell-penetrating moiety masked by the masking moiety is activated, thereby enabling the target molecule-binding moiety linked thereto to enter intracellular degradation. After being linked to the activatable cell-penetrating construct of the present application, whether it is a blocking antibody or a non-blocking antibody, the effect of activating T cells and killing tumor cells can be achieved, which has additional benefits.

This invention discloses a monoclonal antibody targeting zebrafish TNFRSF17 protein and its applications. The amino acid sequences of CDR1, CDR2, and CDR3 of the heavy chain of the monoclonal antibody are shown in SEQ ID NO. 1 to SEQ ID NO. 3, respectively; the amino acid sequences of CDR1, CDR2, and CDR3 of the light chain of the monoclonal antibody are shown in SEQ ID NO. 4 to SEQ ID NO. 6, respectively. This antibody exhibits excellent specificity, no cross-reactivity with other members of the zebrafish TNFRSF family, low background signal, and nanomolar-level high affinity for zebrafish TNFRSF17 protein, ensuring its effectiveness in various sensitive detection and functional intervention applications. The antibody prepared in this invention can also be used as a functional blocking antibody to dynamically intervene in this signaling pathway in live zebrafish, showing promising application prospects.

The invention discloses a double-antibody blocked Taq DNA polymerase as well as a construction method and application thereof. The Taq DNA polymerase is blocked by a Taq DNA polymerase monoclonal antibody and a thermosensitive fusion nano antibody; the thermosensitive fusion nano antibody is composed of a heat-labile protein tag and a nano antibody capable of being specifically combined with a Taq DNA polymerase 5 '-3' polymerization active structural domain. The preparation method of the double-antibody closed Taq DNA polymerase comprises the following steps: constructing a thermosensitive fusion nano antibody and purifying the thermosensitive fusion nano antibody; and co-incubating the purified thermosensitive fusion nano antibody and a commercial monoclonal antibody with Taq DNA polymerase according to a ratio to realize double-antibody blocking. The double-antibody closed Taq DNA polymerase prepared by the invention has the advantages of low cost, higher fluorescence signal value and amplification efficiency in real-time fluorescent quantitative PCR, high sensitivity, high specificity and the like, and is suitable for conventional PCR and real-time fluorescent quantitative PCR amplification.

This invention belongs to the field of biotechnology, specifically relating to a classical swine fever virus E. rns A porcine monoclonal antibody against a protein. The amino acid sequence of the heavy chain variable region of the porcine monoclonal antibody is shown in SEQ ID NO:1, the amino acid sequence of the heavy chain constant region is shown in SEQ ID NO:2, the amino acid sequence of the light chain variable region is shown in SEQ ID NO:3, and the amino acid sequence of the light chain constant region is shown in SEQ ID NO:4. The full-length genes of the heavy and light chains of this porcine monoclonal antibody are derived from the same classical swine fever virus E. rns Obtained through protein-specific amplification in porcine B cells, this antibody retains its native structure, avoiding the affinity loss that may occur with artificial recombination. It exhibits high affinity and specificity, making it a suitable candidate for classical swine fever virus E1. rns This provides a precise molecular tool for elucidating the antigenic structure of the protein and establishing diagnostic methods for classical swine fever. The monoclonal antibody was then applied to the classical swine fever virus E... rns In the antibody blocking ELISA detection method, the established E rns Antibody blocking ELISA detection method has high sensitivity and specificity.

The application provides a kit for detecting AChR blocking antibodies, a detection method and application, and belongs to the technical field of medical detection. The application provides a compound for detecting AChR blocking antibodies instead of alpha-BGT. Compared with alpha-BGT, the compound is non-toxic, cheap, easy to obtain, and can still detect AChR blocking antibodies after high-temperature treatment. The application also provides a method for detecting AChR blocking antibodies by using the compound. The compound does not need to be labeled with radioactive iodine or other substances, thereby reducing the cost, avoiding the influence of radioactive substances on the environment and the harm to experimenters, and being green and environmentally friendly. The compound can also be incubated with a serum sample at the same time, thereby shortening the detection time and improving the detection efficiency.

The invention provides a blocking type GIPR antibody, an antigen binding fragment thereof, an antibody conjugate and application of the antibody conjugate in preparation of drugs. The GIPR antibody and the antigen binding fragment thereof have relatively high affinity to GIPR protein, and are combined with the GIPR protein expressed on the surface of a cell to block the activity of the GIP activated cell; the GIPR antibody has relatively good cell internalization activity, pharmacokinetic studies show that the GIPR antibody and the antigen binding fragment thereof show relatively good stability in a mouse body, and AUC0-t can be up to 15033.01 hou * [mu] g / mL at most. An antibody conjugate prepared from the GIPR antibody shows the activity of stably and lastingly reducing the weight of an experimental animal model, and has a wide application prospect.

This invention belongs to the field of biomedical detection technology, and relates to a semi-quantitative nano-selenium chromatography test strip for detecting T4, T3, or TSH, and its preparation method. The test strip is extremely sensitive to humidity; if exposed to a humid environment for more than 5 minutes during storage and transportation, the test strip will become damp, significantly affecting the chromatography process and leading to erroneous test results. The improved stepwise labeling and post-mixing process employed in this invention, through physical separation of competing steps, ensures the optimized labeling and functional purity of both the specific antibody and the blocking antibody, fundamentally eliminating false positives caused by defects in probe preparation. The prepared test strip exhibits no cross-reactivity, excellent specificity, accurate T3 index localization, superior stability, and a long shelf life, meeting the requirements for commercial storage and transportation.

Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-α v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-α v2 polypeptide, or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-α polypeptide, an extracellular domain of a mouse SIRP-α polypeptide, an extracellular domain of a human SIRP-β polypeptide, and / or an extracellular domain of a human SIRP-γ polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-α polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-α polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

The invention discloses an anti-idiotypic antibody of aflibercept and application of the anti-idiotypic antibody. The anti-idiotype antibody comprises a heavy chain variable region and a light chain variable region; the heavy chain variable region comprises a heavy chain complementarity determining region HCDR1-3 of which the amino acid sequences are respectively shown as SEQ ID NO: 3-5; the light chain variable region comprises LCDR1-3 of which the amino acid sequences are respectively as shown in SEQ ID NO: 6-8. The anti-idiotypic antibody is a blocking antibody, has high binding force and high specificity of the aflibercept, can be used for detecting the content of the aflibercept medicine in a sample, plays an important role in pharmacokinetic and pharmacodynamic analysis of the aflibercept medicine, and has a good application prospect.

Provided are a group of SH23 homologous cluster fully-human thyrotropin receptor (TSH receptor, TSHR)-blocking monoclonal antibodies, a preparation method therefor and the use thereof. The method comprises the following steps: by means of flow cytometry, sorting plasma cells and memory single B cells that specifically recognize TSHR from the peripheral blood of a patient with a high TSH receptor-blocking antibody (TSH-stimulating blocking antibody, TBAb) titer, performing in-vitro cloning of light and heavy chains of the antibody, performing recombination and expression, and carrying out antibody property screening and verification by using TSHR-CHO cells to obtain a blocking monoclonal antibody that specifically targets human TSHR. The fully-human TSH receptor blocking monoclonal antibodies can specifically bind to TSHR, can effectively block the signal transduction after TSH binds to a receptor, and have good inhibitory activity in in vitro and in vivo experiments, and therefore have broad application prospects in the treatment of diseases, such as Graves' disease (GD) and hyperthyroidism-induced diseases, such as thyroid eye disease (TED).

The invention provides a one-step screening method for rapidly screening the affinity and the blocking function of the candidate antibody at low cost and high throughput. The method comprises the following specific steps: constructing an antibody gene to be screened in an expression vector, transfecting the vector into cells for expression, optionally using a high-concentration LiCl cell lysis solution to lyse the cells expressing the antibody in the cells, fully curing the antibody in a cell lysis supernatant or a cell culture supernatant by using a BLI sensor, immersing the sensor into an antigen so that the sensor is fully combined with the antibody, and detecting the antibody in the cell lysis supernatant by using the BLI sensor. After balancing, immersing into receptor protein for competitive experiment, and calculating the affinity constant of the antibody and the antigen and the efficiency of blocking the combination of the receptor and the antigen according to the detection signal of the sensor. According to the method, the tedious step of antibody purification in traditional screening is omitted, and the accuracy and the sensitivity which are the same as those of the purified antibody determination affinity and the blocking activity can be achieved; and step-by-step detection of traditional antibody affinity determination and function determination is combined, and the affinity and blocking efficiency data of the antibody can be obtained through one experiment. Meanwhile, the invention discloses a cell lysis solution formula, sample types of the method are expanded to comprise intracellular expression antibodies, BLI is used for determining the affinity of the antibodies and antigens in lysis cell supernatant, and the sensitivity of the cell lysis solution formula is equivalent to that of purified antibodies.