990 results about "High avidity" patented technology

The invention relates to the technical field of biological medicines, and particularly discloses an anti-human CD3 rabbit recombinant monoclonal antibody as well as a preparation method and application thereof. The antibody obtains anti-CD3 immune response by immunizing a rabbit, is obtained by combining single B cell sorting, gene cloning and a mammalian cell expression system, and has high affinity and good specificity. The antibody can effectively recognize CD3 positive T cells in human peripheral blood and can be applied to the fields of flow cytometry, immunohistochemistry, T cell function research and the like. Experimental results show that the antibody has the advantages of high titer, strong fluorescence signal, low background and the like, and is superior to the traditional murine anti-CD3 antibody. Amino acid sequences of light chain and heavy chain variable regions of the antibody are further obtained, and controllability and repeatability of antibody expression are achieved. The antibody has important scientific research value and industrial application prospect, and is suitable for various scenes such as T cell marker detection, immune state evaluation, immunotherapy auxiliary research and the like.

The invention belongs to the field of antibodies, and particularly relates to an anti-NMP22 monoclonal antibody as well as a preparation method and application thereof. The invention provides CDR sequences of a heavy chain variable region and a light chain variable region of an anti-NMP22 antibody, the antibody can specifically recognize nuclear matrix protein 22 (NMP22), has high affinity and high specificity to the protein, can be applied to diagnosis of diseases related to abnormal urine nuclear matrix protein 22 level, and especially can be applied to clinical diagnosis of bladder cancer.

The present application provides anti-B7-H3 monoclonal antibodies, in particular, high affinity B7-H3 humanized monoclonal antibodies having cross-activity with humans, cynomolgus monkeys and mice, as well as nucleic acids encoding the antibodies, vectors comprising the nucleic acids, and host cells comprising the nucleic acids or vectors. Also disclosed are pharmaceutical compositions and conjugates comprising the antibodies, as well as uses of the antibodies.

The invention relates to an anti-CD3 nano antibody, an anti-CD38 antibody and a bispecific antibody containing the anti-CD3 nano antibody and the anti-CD38 antibody. According to the invention, an anti-CD3 nano antibody and an anti-CD38 monoclonal antibody are excavated and prepared, humanized design is carried out to obtain antibodies with high affinity and specificity, and different configurations of bispecific T cell conjugation antibodies targeting CD3 and CD38 are further designed, so that the CD3 and CD38 dual-specificity T cell conjugation antibodies are obtained. The antigen binding activity, the T cell-mediated tumor cell killing effect and the T cell proliferation and activation function of the antibody are systematically evaluated in vitro, and experimental results show that the T cell conjugation antibody can effectively recruit and activate T cells and has a remarkable killing effect on CD38 positive tumor cells, and it is further verified that the antibody has remarkable in-vivo anti-tumor activity and has a good application prospect. Therefore, the polypeptide has high affinity, good pharmacological characteristics and development potential.

The invention belongs to the technical field of biological detection, and particularly relates to a monoclonal antibody combination for detecting measles virus nucleoprotein and application of the monoclonal antibody combination. The combination is composed of monoclonal antibodies 5E2 and 5G9 and can efficiently and specifically recognize measles virus nucleoprotein, amino acid sequences of complementary determining regions (CDR) of heavy chain and light chain variable regions of the combination are clear and are shown as SEQ ID NO.1-12 respectively, high specificity and high affinity of the antibodies are guaranteed, the antibody combination can effectively capture and detect target antigens, and the antibody combination can be used for detecting measles virus nucleoprotein. The risk of non-specific binding and cross reaction is obviously reduced. The combination shows excellent sensitivity and specificity in detection platforms such as colloidal gold immunochromatography, and provides a stable and reliable biological recognition tool for rapid and accurate detection of measles viruses.

The invention discloses a novel coronavirus neutralizing antibody, a detection kit and application of the novel coronavirus neutralizing antibody. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR12 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR12 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR12 to S-Trimer and RBD under 2-fold and 300-fold dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR12 has high affinity and dilution stability and is suitable for clinical large-dose administration.

The present invention discloses a nucleic acid aptamer that specifically recognizes DEHP and its application, and belongs to the field of environmental safety biotechnology. The nucleic acid aptamer is any one of the following: (1) a single-stranded DNA sequence such as a nucleotide sequence shown in SEQ ID No.10; (2) a sequence that uses the nucleotide sequence shown in SEQ ID No.10 as a core sequence, is extended or shortened on both sides or on one side, and has the same function as the nucleotide sequence described in (1). The present invention is based on Capture‑SELEX technology, and after 10 rounds of repeated screening, a nucleic acid aptamer SEQ ID No.10 that can bind to DEHP with high affinity and high specificity is finally obtained. The nucleic acid aptamer is applied to the DEHP detection of actual samples, which has important application prospects for the analysis and detection of DEHP in blood samples, cell samples, food and drinking water.

The invention discloses a novel coronavirus neutralizing antibody, a detection kit and application of the novel coronavirus neutralizing antibody. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR75 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR75 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR75 to S-Trimer and RBD under 2-fold and 300-fold dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR75 has high affinity and dilution stability and is suitable for clinical large-dose administration.

The invention discloses a deep mutation scanning method based on protein-protein interaction in bacterial cells and a binding affinity prediction method. In the invention, split dCas9 proteins (SEQ ID NO.1 and SEQ ID NO.2) are respectively subjected to fusion expression with a receptor and a ligand with binding affinity to be detected, and are combined with a toxic sgRNA guide sequence (SEQ ID NO.3), and when PPI occurs, a toxic dCas9: sgRNA complex is formed to inhibit bacterial growth, so that a PPI affinity size signal is converted into a bacterial cell generation speed signal, and the signal can be quantified into a copy number value through next-generation sequencing. The invention further designs a deep learning binding affinity prediction model, high-affinity sequences can be screened from theoretical mutation space, the workload and cost of experimental verification are remarkably reduced, and a reliable basis is provided for subsequent protein function optimization and design.

The invention provides an ORM1 and CEA protein antibody, a combination of the ORM1 and CEA protein antibody and an application of the ORM1 and CEA protein antibody in colorectal cancer diagnosis, and aims to effectively solve the problems of low affinity and specificity and poor stability of the existing antibody by optimizing the immunogen sequences of ORM1 and CEA, screening a monoclonal antibody with high affinity and high specificity, screening the optimal ORM1 and CEA antibody and combining the optimal ORM1 and CEA antibody. The kit has a wide detection range, shows an extremely high collaborative diagnosis value during combined detection, remarkably improves the diagnosis efficiency of early colorectal cancer, and has an important clinical application value.

The invention discloses a novel coronavirus neutralizing antibody GR46, a detection kit and application of the novel coronavirus neutralizing antibody GR46. The amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region of the neutralizing antibody is shown as SEQ ID No.2. The antibody with mature affinity is screened through bioinformatics analysis of a single B cell, the antibody screening process is optimized by combining single cell RNA sequencing, VDJ rearrangement analysis and somatic cell hypermutation research, blindness of a traditional method is avoided, and the accuracy and effectiveness of antibody screening are improved. According to the neutralizing antibody GR46 provided by the invention, a heavy chain variable region and a light chain variable region of the neutralizing antibody GR46 can be specifically combined with an RBD structural domain of the SARS-CoV-2 and an S-Trimer structural domain of an Omicro variant, so that a broad-spectrum neutralizing effect on the SARS-CoV-2 virus and the variant thereof is realized. The binding activity of the antibody GR46 to S-Trimer and RBD under 2-time and 300-time dilution conditions is obviously superior to that of other antibodies, which indicates that the antibody GR46 has high affinity and dilution stability and is suitable for clinical large-dose administration.

The present invention discloses a nucleic acid aptamer binding to CD5 protein, the sequence of which is shown in SEQ ID NO.1 to SEQ ID NO.6, and by improving the screening conditions, a nucleic acid aptamer with small molecular weight, stable chemical properties, easy storage and labeling, which can bind to CD5 protein with high affinity, is screened and obtained. The aptamer is measured by surface plasmon resonance (SPR) and dot hybridization experiments to have high affinity and high specificity, and can be used in detection, diagnosis, imaging and treatment, and has broad application prospects.

The invention discloses a monoclonal antibody H2 specifically bound with a lung cancer marker CYFRA21-1 and application, and relates to the technical field of biological medicines. The method comprises the following steps: firstly, screening from a Tomlinson I + J phage library by utilizing a phage display technology to obtain a lung cancer marker CYFRA21-1 monoclonal antibody H2, and the antibody has a heavy chain complementary determining region and a light chain complementary determining region which are formed by novel amino acid sequences and can be specifically combined with CYFRA21-1 protein; the monoclonal antibody H2 of the lung cancer marker CYFRA21-1 has the characteristics of high affinity, high specificity, stability and the like, and the monoclonal antibody H2 of the lung cancer marker CYFRA21-1 not only can efficiently and accurately detect the concentration of CYFRA21-1 protein, but also can be used for immunostaining of lung cancer tumor cells and lung cancer tissues in pathological diagnosis, and has important significance for detecting the concentration of CYFRA21-1.

The invention belongs to the technical field of biological medicine and molecular biology, and particularly relates to a single-chain antibody targeting NRP1, a CAR-T cell and application of the single-chain antibody and the CAR-T cell in fibrosis treatment. Four types of high-affinity single-chain antibodies targeting mouse NRP1 antigens are obtained by immunizing mice, the single-chain antibodies are applied to second-generation CAR, T cells of mouse spleen sources are infected after virus packaging, and CAR-T cells are constructed. The CAR-T cells of the targeted NRP1 can be used for effectively killing NRP1 positive cells. In-vivo experiments show that the CAR-T cells can inhibit the growth of NRP1 positive tumor cells. The CAR-T cell can improve the mouse liver fibrosis condition, collagen in the mouse liver is reduced through treatment, and the molecular level of fibrosis markers SMA and NRP1 is reduced, it is indicated that the CAR-T cell recognizes and eliminates activated HSCs through targeting NRP1, and the fibrosis degree is reduced.

The present application is directed to methods and compositions that are useful for reducing the number of myeloid-derived suppressor cells (MDSC), tumor associated macrophages (TAM), or both in a subject. The methods include administering an antigen binding protein that binds to an antigen expressed by MDSC and / or TAM, or administering a modified T cell or NK-92 cell that expresses an antigen binding protein that binds to an antigen expressed by MDSC and / or TAM, or a combination of both, to a subject. For example, the antigen binding protein can bind to CD33 expressed by MDSC and / or TAM. The methods and compositions are useful for treating a disease associated with MDSC and / or TAM infiltration into a tissue or tumor.

The invention relates to genetically encoded fusion proteins comprised of a capture component that binds a target with high affinity and a peptide polymer, such as elastin-like polypeptides, that display phase behavior and can be used for purification. The invention further relates to methods for optimizing capture fusion proteins for individual biologic targets such that phase separation occurs under desirable conditions, such as at room temperature, lower concentrations of salt, and / or at suitable pH ranges and optimized capture domains and polypeptides with phase behavior that have been identified by the optimization methods.

The invention relates to the technical field of antibodies, in particular to an anti-African swine fever virus p30 protein monoclonal antibody and application thereof, and the anti-African swine fever virus p30 protein monoclonal antibody can be specifically combined with African swine fever virus p30 protein. The anti-ASFV p30 protein monoclonal antibody is prepared by immunizing a BALB / c mouse through an immunological method, and the antibody is high in specificity, titer and affinity and can be applied to immunological detection or antibody detection kits.

The invention discloses a nano antibody capable of specifically recognizing staphylococcus aureus as well as a preparation method and application of the nano antibody. A ribosome display technology is adopted, a nano antibody pair with a good pairing effect is screened out through construction of a nano antibody display library, three rounds of high-throughput screening and ELISA verification, and the nano antibody pair is used for in-vivo detection of actual pathogenic bacteria in combination with an immunochromatography technology. The nano antibody disclosed by the invention shows high affinity, high specificity and achievable detection limit when being combined with staphylococcus aureus, has the advantages of good stability, low cost and the like compared with a monoclonal antibody, can be produced on a large scale, and has a wide application prospect in the field of staphylococcus aureus detection and analysis.

The invention belongs to the technical field of biological medicine, and particularly relates to a T cell receptor capable of recognizing KRAS G12V antigen oligopeptide, a compound, a pharmaceutical composition and application. The T cell receptor can be used for recognizing a KRAS G12V-HLA-A * 11: 01 compound with high affinity; the T cell receptor is an alpha-beta heterodimer consisting of an alpha chain and a beta chain; the amino acid sequence of the alpha chain is as shown in SEQ ID NO.10, or an amino acid sequence with at least 90% of sequence identity with the alpha chain; the amino acid sequence of the beta chain is as shown in SEQ ID NO.14, or has an amino acid sequence with at least more than 90% of sequence identity with the beta chain. The T cell receptor provided by the invention can be used for preparing medicines for treating tumors or other immune diseases.

The present invention discloses a hs-TnI detection method based on quantum dot microspheres, which directly reacts a sample with a first solution containing antibody 1 and a second solution containing antibody 2 to generate a sandwich structure complex of antibody 1-antigen-antibody 2, and the antigen and antibody react in a reaction cup, incubate at a constant temperature, and the reaction time is longer, and the reaction is more sufficient, which is conducive to the improvement of detection sensitivity. At the same time, during chromatography, with the high affinity of streptavidin and biotin, the complex obtained by the reaction can be better captured on the T line, so that the reaction can be made more sensitive, and the detection time is also faster relative to the existing reagent strips. Further, combined with the advantages of high sensitivity and wide linear range of quantum dot microspheres, detection repeatability (CV) is better, CV is increased from the traditional 15wt% to within 8wt%, and the detection sensitivity is as high as 2pg / ml, while the linear range is 2-30000pg / ml, and full coverage is achieved for low-concentration and high-concentration samples.

The invention relates to a method for screening a human-mouse cross MR1 restriction high-affinity TCR (T cell receptor) by using a phage display technology, and relates to the technical field of T cell receptors. According to the invention, a phage display technology is utilized to prepare an MAIT cell single-chain T cell receptor (scTCR) phage library, the scTCR phage library is subjected to biological elutriation through an MR1 / 5-OP-RU tetramer, and Phage-ELISA identifies that TCR6 clone (TCR6) has specific binding with human and mouse MR1 / 5-OP-RU and has higher affinity compared with other clone.

Disclosed are a preparation method and application of a single-chain antibody fragment targeting SARS-COV-2 nucleocapsid protein, aiming to provide a single-chain antibody fragment with high affinity and strong specificity. The present disclosure obtains three single-chain antibody fragments targeting SARS-COV-2 nucleocapsid protein through construction of a nanobody phage library and phage screening technology. The single-chain antibody fragment consists of a heavy chain variable region, a 15aa connecting peptide, and a light chain variable region connected in sequence, and has an amino acid sequence shown in SEQ ID NO: 1-SEQ ID NO: 3. The single-chain antibody fragment in the present disclosure has excellent binding performance and specificity with the SARS-COV-2 nucleocapsid protein, can be applied to a variety of immunoassay platforms of the SARS-COV-2, and has broad application prospects in the field of SARS-COV-2 detection.

The present invention discloses CLDN18.2-targeting antibodies, bispecific antibodies and use thereof. The CLDN18.2-targeting antibody is a single-domain heavy-chain antibody that has high affinity for tumor cells endogenously expressing CLDN18.2 and can induce high endocytic activity. The bispecific antibody can target CLDN18.2 and CD3 and retains the binding effect of an Fc to an FcRn; meanwhile, a mutant Fc is preferred so as to reduce the binding to an FcgR and thus the activation of non-specific T cells caused by the cross-linking of an FcgR. The CD3-terminus activity is optimized so that the release of common cytokines in CRS, such as IL6 and TNFα can be reduced.

The present invention relates to an antigenic peptide targeting FLT3-D835 mutation and its application in tumor immunotherapy. Specifically, the present invention provides an antigenic peptide for eliciting an immune response targeting FLT3-D835 mutation. Compared with the lack of affinity between the wild-type polypeptide and HLA-A * 02:01 molecule, the antigenic peptide of the present invention has high affinity for HLA-A * 02:01 molecule. The present invention also provides the application of the antigenic peptide of the present invention. The antigenic peptide of the present invention has good immunogenicity, can activate specific immune responses, and has important clinical significance for targeting the clearance of leukemia cells, stabilizing the remission state of AML patients, and prolonging the disease-free survival time.

The present invention provides isolated monoclonal antibodies that specifically bind LAG-3, and have optimized functional properties compared to previously described anti-LAG-3 antibodies, such as antibody 25F7 (US 2011 / 0150892 A1). These properties include reduced deamidation sites, while still retaining high affinity binding to human LAG-3, and physical (i.e., thermal and chemical) stability. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided, as well as immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies. The present invention also provides methods for detecting LAG-3, as well as methods for treating stimulating immune responses using an anti-LAG-3 antibody of the invention. Combination therapy, in which the antibodies are co-administered with at least one additional immunostimulatory antibody, is also provided.

The invention belongs to the technical field of biological medicine, and relates to a small-molecule near-infrared fluorescent probe SHP-PP and a preparation method and application thereof.The small-molecule near-infrared fluorescent probe SHP-PP is composed of a targeted SHP2 recognition group, a linking group and a fluorophore Py5, keeps high affinity to SHP2, can specifically mark SHP2 in living cells, and can be used for detecting the SHP2 in the living cells. According to the present invention, the probe has characteristics of high sensitivity, high protein selectivity, maximum reduction of interference of other proteins, excellent optical property, imaging requirement meeting, maximum emission wavelength in the near-infrared region, large Stokes displacement reaching 200 nm, high signal-to-noise ratio, stable fluorescence signal, and low phototoxicity, and can be used for the preparation of the fluorescent probe, such that the probe has characteristics of high signal-to-noise ratio, stable fluorescence signal, and low phototoxicity.

Prostate-specific membrane antigen targeted high-affinity agents for endoradiotherapy of prostate cancer are disclosed.

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 discloses a nano antibody 1B4 of targeted serum albumin and long-acting application of the nano antibody 1B4, and belongs to the technical field of antibody engineering. The nano antibody 1B4 of the targeted serum albumin, disclosed by the invention, contains a specific complementary determining region (CDR): CDR-H1 as shown in SEQ ID NO.2 (SGYMA), CDR-H2 as shown in SEQ ID NO.3 (AISTTSRFTYYADDVKG), and CDR-H3 as shown in SEQ ID NO.4 (GPYISWPLQLYEYKD, so that the nano antibody 1B4 of the targeted serum albumin can be specifically combined with the serum albumin with high affinity. Based on the characteristics, the nano antibody 1B4 can effectively prolong the in-vivo half-life period of polypeptide, protein or antibody drugs fused with the nano antibody 1B4, the treatment effect and practicability of related biological medicine products are remarkably improved, and the nano antibody 1B4 is particularly suitable for development of long-acting polypeptide, protein and antibody drugs.

The invention relates to an anti-GPC3 protein nano antibody and application thereof. The amino acid sequence of the complementarity determining region CDR1 of the nano antibody comprises a sequence shown in SEQ ID NO.1, the amino acid sequence of the complementarity determining region CDR2 comprises a sequence shown in SEQ ID NO.2, and the amino acid sequence of the complementarity determining region CDR3 comprises a sequence shown in SEQ ID NO.3. The brand-new anti-GPC3 protein nano antibody is excavated, can specifically recognize and combine with GPC3 protein, has high affinity and small molecular weight, can be effectively applied to detection of GPC3 protein and diagnosis and treatment of GPC3 protein related diseases, and provides reference for development and development of new products for diagnosis and treatment of GPC3 protein related diseases.