50 results about "Antibody block" patented technology

The present invention relates to a treatment of CCHFV infection, in particular CCFHV infection. Here, the inventors showed that antibody blocking LDL-R family at the surface of human cells could reduce CCHFV infection by 80%, such inhibition only occurred when blocking was performed prior to or at the time of infection though not at later time points. Furthermore, they found that incubation of viral particles with a soluble form of LDL-R could impair CCHFV infection. They found that ApoE antibodies could block CCHFV infectivity by up to 10-fold only when the viral particles were produced in cells that express ApoE. Thus, the present invention relates to an LDL-R family and / or an ApoE inhibitor for use in the prevention and / or the treatment of CCHFV infection in subjects in need thereof.

Provided are a fully human TSH receptor (TSHR) blocking monoclonal antibody for treating hyperthyroidism, and a preparation method therefor and a use thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and memory single B cells specifically recognizing a TSHR in the peripheral blood of patients having high titers of TSHR blocking antibody (TSH-stimulating blocking antibody, TBAb), performing in vitro cloning of antibody light and heavy chains and performing recombinant expression, and using hTSHR-CHO cells for antibody property screening and validation, to obtain a blocking monoclonal antibody specifically targeting human TSHR. The fully human TSHR blocking monoclonal antibody can specifically bind to the TSHR, has good inhibitory activity in vitro and in vivo experiments, and has broad application prospects in the development of treatment of Graves' diseases.

The invention belongs to the technical field of biology, and particularly relates to a swine monoclonal antibody of hog cholera virus Erns protein. The amino acid sequence of a heavy chain variable region of the swine monoclonal antibody is shown as SEQ ID NO: 1, the amino acid sequence of a heavy chain constant region of the swine monoclonal antibody is shown as SEQ ID NO: 2, the amino acid sequence of a light chain variable region of the swine monoclonal antibody is shown as SEQ ID NO: 3, and the amino acid sequence of the light chain constant region of the swine monoclonal antibody is shown as SEQ ID NO: 4. The full-length genes of the heavy chain and the light chain of the swine monoclonal antibody are obtained from a swine B cell specifically amplified by the same hog cholera virus Erns protein, the natural structure of an antibody molecule is reserved, affinity loss possibly caused by artificial recombination is avoided, and the swine monoclonal antibody has high affinity and specificity, and can be used for preparing the swine monoclonal antibody. And a precise molecular tool is provided for antigen structure analysis of the hog cholera virus Erns protein and establishment of a hog cholera diagnosis method. The monoclonal antibody is applied to a blocking ELISA detection method of the hog cholera virus Erns antibody, and the established Erns antibody blocking ELISA detection method is high in sensitivity and strong in specificity.

The invention belongs to the technical field of biology, and particularly relates to a hybridoma cell strain capable of secreting a clostridium perfringens ETX monoclonal antibody with neutralizing activity and application of the hybridoma cell strain. On the basis of natural toxin, an indirect ELISA (enzyme-linked immunosorbent assay) detection method is established by utilizing a non-toxic ETX single amino acid site protein mutant, and a series of hybridoma cell strains secreting an anti-clostridium perfringens ETX monoclonal antibody are screened; the hybridoma cell strain can stably and efficiently secrete a monoclonal antibody with neutralizing activity and a monoclonal antibody without neutralizing resistance respectively, and large-scale batch production can be realized. According to the present invention, the clostridium perfringens ETX monoclonal antibody is firstly utilized to establish the ETX antigen ELISA detection method, and the method has characteristics of simple sample operation, low cost, rapid reaction, strong specificity and the like, can provide the reference for the diagnosis of clostridium perfringens, and provides the basis for the research of the related vaccine potency test substitution method.

The invention discloses a thrombin-antithrombin III compound determination method, a blocking antibody, a detection antibody and a kit, the blocking antibody blocks the vicinity of the 274-site residue of the prothrombin nitrogen terminal, and the detection antibody is used as a capture antibody of a TAT compound and specially aims at the effect of thrombin close to the thrombin N terminal. When the closing antibody near the position behind the 274-site residue of the prothrombin nitrogen terminal is combined with the prothrombin antibody, the closing antibody can effectively prevent the detection antibody at the N terminal of the thrombin from combining with the prothrombin, but because the closing antibody near the position behind the 274-site residue of the prothrombin nitrogen terminal cannot combine with the thrombin, the closing antibody can effectively prevent the detection antibody at the N terminal of the thrombin from combining with the prothrombin. Therefore, the combination of the detection antibody at the N end of the thrombin to the thrombin is not influenced, and the TAT compound detection process is not interfered by high-concentration prothrombin in the plasma.

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 the treatment of locally advanced and metastatic muscle-invasive bladder cancers (MIBC). The present invention provides compositions to be used in immunotherapy of MIBC, especially in combination with an anti-PD-1 / PD-L1 / PD-L2 antibody-based therapy. The present invention also provides biomarkers of response to anti-PD-1 / PD-L1 / PD-L2 immune checkpoint blocking antibodies (ICBs), alone or together with anti-CTLA4 antibodies and / or chemotherapy, for best guiding their neoadjuvant use and avoid unefficient administration of potentially toxic drugs to patients with localized bladder cancers.

The invention provides antibodies and antigen-binding fragments thereof that recognize mesothelin (MSLN). In some embodiments, the antibodies bind to membrane-bound MSLN, but not to soluble MSLN. In some embodiments, the antibodies block the interaction between MSLN and MUC16. In some embodiments, the antibodies provide a means of treating mesothelin-positive cancer. In some embodiments, the antibodies are used to diagnose or image mesothelin-positive cancer.

Provided are a multispecific antibody and the use thereof. Specifically, provided is a multispecific antibody, which contains a first targeting domain that targets a chemokine (C-C motif) receptor 8 (CCR8) molecule highly expressed on the surface of a tumor-infiltrating regulatory T cell (Treg), and a second targeting domain that binds to VEGF and / or a third targeting domain that binds to PD-L1. Various functional domains of the CCR8-related multispecific antibody block a PD-1 / PD-L1 immunosuppressive pathway, etc. by means of killing the tumor-infiltrating Treg, so that a T cell is activated, and the generation of a tumor vessel is inhibited. Therefore, the CCR8-related multispecific antibody can be used as an effective therapeutic agent for tumor treatment.

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).

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 relates to a polyclonal antibody capable of specifically recognizing human and mouse FBXO45 proteins. The immunogen of the antibody is the 127th-143rd amino acid sequence (as shown in SEQ ID NO: 1) of the FBXO45 protein. The invention also provides an application of the FBXO45 protein polyclonal antibody. The antibody disclosed by the invention has high affinity and high specificity, can stably recognize human and mouse FBXO45 protein, and can be used for Western blot detection; the method is high in purity, low in background signal and suitable for scientific research and clinical development; a key tool is provided for researching the functional mechanism of the FBXO45 in lung cancer, COPD and other diseases; the polypeptide has the potential of developing diagnostic kits, functional blocking antibodies and drugs, and has good social and economic benefits.

Provided herein are compositions, methods, and kits for treating inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis, in a mammal in need thereof. The methods include administering to a subject with IBD a combination therapy comprising a therapeutically effective amount of a chemokine receptor 9 (CCR9) inhibitor compound and a therapeutically effective amount of an anti-IL-23 antibody. Kits comprising the CCR9 inhibitor compound and the anti-IL-23 antibody are also provided herein.

A method for phase separation-based modification of a chimeric antigen receptor, and the use thereof. It has been discovered that the intracellular domain of CD28 can undergo phase separation with the intracellular domains of Lck and PD-1 and regulate T cell activation, and upon researching the molecular mechanisms of CD28 / Lck and CD28 / PD-1 phase separation, it has been discovered that two mutations of the intracellular domain of CD28 inhibits phase separation thereof with PD-1 and do not affect phase separation thereof with Lck. Incorporating the intracellular domain of CD28 having the two mutations in CAR-T design facilitates CAR-T resistance to PD-1 inhibition, and the therapeutic efficacy may be further improved by joint use with PD-1 blocking antibodies.

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.

The present disclosure provides antigen binding proteins that specifically bind PD-1. The present disclosure further provides mouse anti-mouse PD-1 blocking antibodies, engineered cells, and methods of making and using the antigen binding proteins, anti-PD-1 antibodies, and cells of the disclosure. Aspects of the disclosure further relate to a polypeptide comprising any one of the complementary determining regions of the present disclosure.

The present application relates to an anti-PD-1 and OX-40 bifunctional antibody and a preparation method and application thereof. The bifunctional antibody comprises an antibody domain targeting PD-1 and an antibody domain targeting OX-40. The present application designs a novel anti-PD-1 / OX-40 bifunctional antibody, constructs a specific structure bifunctional antibody by using a PD-1 activating antibody and an OX-40 blocking antibody, and the whole synergizes, has high affinity to PD-1, can activate PD-1 activity and its signal pathway, has high affinity to OX40, can block OX40 / OX40L interaction and its signal transduction, inhibits T cell proliferation, inhibits CD25 or PD-1 positive CD4 + T cell production can be applied to the development of related drugs for treating inflammatory or autoimmune diseases.

Blocking antibodies against αMβ2 (CBP-α-αMβ2), αM (CBP-α-αM), α3 (CBP-α-α3), and anti-TGFβ as well as inhibitors of Talin2 reverse fibrosis in a mouse fibrosis model. Accordingly, aspects of the disclosure relate to inhibitors of Talin2 and inhibitors of the integrins αMβ2, αM, and α3. Aspects relate to a method for treating and / or reversing fibrosis in a subject comprising administering a composition comprising an inhibitor of Talin2 or a composition comprising a nucleic acid of the disclosure. Further aspects relate to a method for treating and / or reversing fibrosis in a subject comprising administering a composition comprising an antibody conjugate of the disclosure or a composition comprising an inhibitor or blocking agent of integrin α3, αM, αMβ2, or combinations thereof to the subject. Methods also include treating kidney fibrosis in a subject comprising administering a composition comprising an anti-TGFβ antibody operatively linked to an ECM-affinity peptide. The methods may be for reducing or decreasing the amount of existing fibrosis. The methods differ from traditional methods for treating fibrosis, since the current methods do not delay or inhibit the progression of fibrosis, but instead have shown to reverse, reduce, and / or decrease existing fibrosis. Accordingly, methods of the disclosure may be used in a manner that provides treatment to existing fibrosis rather than a prophylactic to prevent more fibrosis.

The invention discloses a coupling protein as well as a preparation method and application thereof. According to the preparation method disclosed by the invention, in-vitro self-coupling of the rotavirus VP8 protein and the norovirus VP1 protein is realized by utilizing a Spatier-Spytag system, the prepared coupled protein can induce a neutralizing antibody with higher titer aiming at the rotavirus, and the immunogenicity of the norovirus VP1 protein is not influenced; the immunized animal / human body can generate a high-titer specific IgG binding antibody, a serum blocking antibody and a neutralizing antibody aiming at the two viruses. The coupling protein has a wide application prospect in vaccines for resisting infant diarrhea viruses (norovirus and rotavirus).

The invention discloses an orf virus F1L protein monoclonal antibody as well as a blocking ELISA (enzyme-linked immunosorbent assay) detection kit and application thereof. Belongs to the technical field of biological detection. The kit comprises F1L protein expressed by baculovirus and an ORFV F1L protein monoclonal antibody marked by HRP (horse radish peroxidase). The ORFV F1L protein monoclonal antibody disclosed by the invention has the characteristics of strong specificity, high titer, stable property and the like, and is suitable for establishing an ORFV antibody blocking ELISA (Enzyme-Linked Immunosorbent Assay) kit. According to the invention, the HRP-labeled monoclonal antibody is used, so that non-specific reaction possibly introduced due to the use of an enzyme-labeled secondary antibody is reduced. The kit disclosed by the invention can be used for detecting a large batch of samples, has the advantages of low cost, simplicity, convenience, sensitivity, high specificity and the like, and provides an effective technical means for scientific prevention and control of the contagious pustular dermatitis of sheep.

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 present invention relates to a pharmaceutical composition for preventing or treating sicca syndrome, comprising a recombinant antisemaphorin 4D blocking antibody as an active ingredient.

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 present invention relates to methods and kits for reducing interference in immunoassays. In particular, the present invention belongs to the field of immunoassays for in vitro diagnostic applications and relates to the use of testing specific blocking antibodies for reducing interference caused by heterophilic antibodies or rheumatoid factors.

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.