37 results about "Blocking antibody" patented technology

The present invention relates to antibodies, and fragments thereof, that bind and inhibit CD73. The invention also relates to cells producing such compounds; methods of making such compounds, and antibodies, fragments, variants, and derivatives thereof; pharmaceutical compositions comprising the same; methods of using the compounds to diagnose, treat or prevent diseases, e.g., cancer.

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 invention belongs to the technical field of immunohistochemical detection, and discloses a modified composite sealing buffer solution as well as a preparation method and detection application thereof. The modified composite blocking buffer solution comprises a basic buffer system, a composite blocking agent, a nonionic detergent, an endogenous interferent blocking agent and an antibody stabilizer, wherein the basic buffer system provides a stable pH environment and ionic strength; the composite sealing agent firstly occupies a shielding site, and the background is lowered; the nonionic detergent destroys hydrophobic interaction, effectively elute and loosen adsorbed molecules, and promote dissolution of components with relatively strong hydrophobicity; the endogenous interferent blocker can be combined with a receptor firstly, so that non-specific combination of an antibody and the receptor is blocked, and the problem of specific background is solved; the antibody stabilizer can protect the activity of the detection reagent and maintain the stability, and the obtained modified composite sealing buffer solution and the kit thereof have the advantages of multiple cooperative sealing mechanisms, prospective blocking of endogenous interference, improvement of the stability, compatibility and high efficiency of the antibody and the like.

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).

Methods of improving PD-1 based immunotherapy in a subject suffering from a solid cancer, comprising decreasing bone morphogenetic protein 1 (BMP1) levels or function in T cells or in a tumor microenvironment (TME) or extracellular matrix (ECM) of the solid cancer are provided. Methods of treating a solid cancer comprising administering a PD-1 based immunotherapy and decreasing BMP1 levels or function in T cells or a TME or ECM of the solid cancer are also provided. Antibody drug conjugates comprising an anti-PDl blocking antibody and a BMP1 inhibiting small molecule or antibody or antigen binding fragment thereof small molecule inhibitor and pharmaceutical compositions for use in the methods of the invention are also provided.

The application discloses a pancreatic cancer immunotherapy drug composition for jointly targeting CD96 and PD-1, relates to the technical field of biological medicine, and comprises an anti-human CD96 blocking antibody and an anti-human PD-1 blocking antibody. By jointly blocking the double immune checkpoints of CD96 and PD-1, the pancreatic cancer immunotherapy drug composition presents a significant synergistic effect compared with single antibody treatment, can effectively enhance the killing activity of T cells on pancreatic cancer cells, reverses the immune suppression microenvironment of pancreatic cancer, and restores the anti-tumor immune response of the body. The in-vivo experimental results show that the drug composition can significantly inhibit the growth of transplanted tumors, reduce the tumor volume and the tumor weight, and the tumor inhibition effect is obviously better than that of a single drug group. The preparation has stable properties and simple administration, and provides a safe and effective new immunotherapy scheme with a conversion application prospect for clinically refractory pancreatic cancer.

This disclosure provides methods for treating Hodgkin lymphoma in a subject comprising nivolumab, a PD-1 blocking antibody, which inhibits immune-tumor attack in patients with relapsed or refractory Hodgkin lymphoma.

The present application relates to an activin receptor II antibody and a use. The activin receptor II antibody comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3. A mutation relative to CDRs of a parental antibody includes one or more selected from the following: a heavy chain CDR2 V54A mutation, a heavy chain CDR2 G56L mutation, a heavy chain CDR2 T58K mutation, a heavy chain CDR3 G99S mutation, a heavy chain CDR3 G99T mutation, a light chain CDR1 G24H mutation, a light chain CDR1 D28W mutation, a light chain CDR1 Y32F mutation, a light chain CDR2 P57E mutation, a light chain CDR3 S97A mutation, and a light chain CDR3 Y99N mutation. A balanced activin receptor II dual-blocking antibody that exhibits higher affinity for ActRIIA while not significantly reducing affinity for ActRIIB is obtained by screening.

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.

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 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.

The invention relates to the technical field of antibodies, and particularly provides an antibody specifically bound with African swine fever virus p34 protein or an antigen binding fragment thereof and application thereof. The antibody or the antigen binding fragment thereof comprises a heavy chain variable region as shown in SEQ ID NO.1 and a light chain variable region as shown in SEQ ID NO.3, and the antibody or the antigen binding fragment thereof can recognize ASFV p34 protein with high specificity. The invention also provides a nucleic acid molecule for coding the antibody or the antigen binding fragment thereof, an expression vector, a recombinant cell and other biological materials. The antibody or the antigen binding fragment thereof can be used for preparing an African swine fever virus detection product, particularly a blocking ELISA antibody detection kit, and the kit has the advantages of high sensitivity, strong specificity, simplicity and convenience in operation and the like, and is suitable for serological monitoring and diagnosis of ASFV. The invention provides an effective detection tool for prevention and control of African swine fever.

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).

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.

Recombinant blood group antigen-binding adhesin (BabA) can be used in a composition to raise humoral immune response i.e. antibodies, that target conserved structural epitopes in the fucosylated blood group antigen Lewis b (Leb) antigen binding domain in the blood group antigen-binding adhesin (BabA). Such broadly Leb-blocking antibodies can reduce the gastric mucosal attachment of Helicobacter pylori (H. pylori) to human gastric mucosa. This approach can be used for preventing and / or alleviating gastric disease in a subject diagnosed with H. pylori infection, said gastric disease chosen from gastroesophageal reflux disease, chronic active gastritis, peptic ulcer diseases, gastric ulcer disease, gastric cancer gastritis and gastric cancer, in particular gastric cancer. It also becomes possible to identify subjects that carry BabA positive H. pylori infections and subjects that are at risk of developing severe gastric disease, such as peptic ulcer diseases, gastric ulcer disease, gastritis with metaplasia and gastric cancer.

The application belongs to the technical field of biology and specifically relates to a SAT1 type foot-and-mouth disease virus monoclonal antibody 5G10, a kit and a detection method. The single-chain antibody 5G10 comprises a heavy chain variable region and a light chain variable region, the amino acid sequence of the heavy chain variable region is shown in SEQ ID No. 6, and the amino acid sequence of the light chain variable region is shown in SEQ ID No. 7. The titer is greater than 1:128000, the heavy chain is IgG1 type, and the light chain is lambda type. The antibody can specifically combine with VP1 recombinant protein of the SAT1 type foot-and-mouth disease virus and has high specificity. The application of the monoclonal antibody 5G10 in a foot-and-mouth disease virus SAT1 type blocking ELISA antibody detection method is provided, and convenient and effective technical reserves are provided for border port detection and animal serum antibody screening of the SAT type foot-and-mouth disease.

Provided are PD-1 - targeted IL-15 fusion proteins that do not compete with checkpoint blocking antibodies, including cytokine-based treatments and blockade of immune checkpoint proteins such as PD-1, two very promising approaches in cancer immunotherapy.SOLUTION: Fusion proteins comprising a variant IL-15 protein, fusion proteins comprising a variant anti-PD-1 antigen binding domain, and fusion proteins comprising a variant IL-15 protein and a variant anti-PD-1 antigen binding domain are provided. Also provided are nucleic acid molecules, expression vectors, host cells and methods for making such fusion proteins and the use of such fusion proteins in the treatment of cancer.SELECTED DRAWING: Figure 154C

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.

An antibody targeting CD19 antibody, methods of making and uses thereof. In particular, a novel antibody targeting CD19 antibody. Methods of making the monoclonal antibody. The monoclonal antibody is capable of binding CD19 antibody with high specificity and blocking the function of CD19 antibody.

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 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 belongs to the technical field of medicines, and discloses a method for promoting drug resistance of triple negative breast cancer bevacizumab by driving IGF2BP3 lactic acid modification through PARK7, and milk acylation modification (IGF2BP3-K76lac) of lysine at the 76th site of IGF2BP3 protein is a key driving factor of drug resistance of bevacizumab. The overexpression of the IGF2BP3-K76lac can obviously enhance the drug resistance of the bevacizumab, and the overexpression of the IGF2BP3-K76lac is verified in both in-vitro experiments and in-vivo models. From the perspective of a molecular mechanism, the milk acylation modification at the IGF2BP3K76 site can enhance the binding capacity of the IGF2BP3K76 site and m6A modified FSP1 mRNA, so that the expression level of FSP1 is up-regulated, and finally the cells are endowed with ferroptosis resistance. By blocking the IGF2BP3-K76lac, ferroptosis induced by bevacizumab can be remarkably enhanced, the antioxidant defense mechanism of an organism is destroyed, and tumor growth is inhibited. In addition, PARK7 functions as a milk acyltransferase, and enhances the binding ability of IGF2BP3-K76lac to promote the function thereof. And finally, the blocking antibody targeting IGF2BP3-K76lac is proved to have a synergistic effect with the bevacizumab, so that the sensitivity of the bevacizumab is effectively recovered.

The invention relates to the technical field of antibodies, and particularly provides an antibody specifically bound with African swine fever virus p62 protein and application. The antibody or the antigen binding fragment thereof comprises a heavy chain variable region with an amino acid sequence as shown in SEQ ID NO.1 and a light chain variable region with an amino acid sequence as shown in SEQ ID NO.3, p62 protein can be recognized with high specificity, and the blocking rate of the antibody reaches 90% or above. The antibody can exist in various forms such as a monoclonal antibody and a single-chain antibody, and biological materials such as coding nucleic acid, expression vectors and recombinant cells of the antibody can be produced on a large scale. Based on the antibody or the antigen binding fragment thereof, the antibody or the antigen binding fragment thereof can be used for preparing an African swine fever virus detection product, is especially suitable for constructing a blocking ELISA antibody detection kit with high sensitivity and strong specificity, and provides an effective tool for serological diagnosis and monitoring of African swine fever.

The application relates to the technical field of biology, and particularly provides an antibody specifically combined with a porcine circovirus type 3 Cap protein and products and applications thereof. The porcine circovirus type 3 Cap protein provided by the application is encoded by a sequence SEQ ID No. 1 or a degenerate sequence thereof, the antibody heavy chain variable region prepared by the application is SEQ ID No. 2, the light chain variable region is SEQ ID No. 4, and the two can be combined to prepare a porcine circovirus type 3 blocking ELISA antibody detection kit, so that the PCV3 infection state can be accurately evaluated.

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.