93 results about "Affinity binding" patented technology

The present invention provides a combination of (i) an immune checkpoint modulator and (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, for use in therapeutic treatment of a cancer disease. The T-cell redirecting multifunctional antibody comprises (a) a specificity against a T cell surface antigen; (b) a specificity against a cancer- and / or tumor-associated antigen; and (c) a binding site for human FcγRI, FcγRIIa and / or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and / or FcγRIII than to human FcγRIIb.

The present disclosure relates HER2 antibodies and to the de novo design of structure-based design targeted antibodies. According to the current disclosure, computer-implemented methods of designing an antibody sequences that will bind the HER2 with significant affinity at a target receptor epitope are disclosed. The method utilizes artificial intelligence (Al) and machine learning (ML) models that are trained to predict improved biomolecule (e.g., antibody or antibody fragments) binding sequences or other desirable properties using known biomolecule / binding partner complexes. A designed HER2 antibody is generated by replacing matching residues with different residues such that a predicted affinity is increased.

In alternative embodiments, provided are chimeric, synthetic or recombinant antibodies (Ab) against the human homologous box NKX-2. 1 (also known as NK2 homologous box 1, or thyroid transcription factor 1 (TTF-1)) protein, including articles of manufacture and kits comprising them, and methods of making and using them, including, for example, their use in the detection or diagnosis and treatment of cancer. In alternative embodiments, an anti-NKX-2. 1 (TTF-1) antibody provided herein is used with an agent for determining whether NKX-2. 1 (TTF-1) expression or activity is present, reduced or deleted; or the sensitivity of the specific binding of the Ab or the antigen (Ag) binding fragment or protein (ABP) or the monomer or dimer ABP provided by the invention with the squamous cell carcinoma cells is lower than the sensitivity of the specific binding with the adenocarcinoma cells (or binding with lower affinity), so that false positives of the squamous cell carcinoma are less, and the positive recognition of the lung adenocarcinoma is better.

The invention relates to the technical field of immune carrier microspheres, in particular to an immune carrier microsphere constructed by individualized MHC-II combined polypeptide, a vaccine and application of the immune carrier microsphere and the vaccine. A core comprises microspheres constructed by a plurality of MHC-II binding polypeptides, sequences of the MHC-II binding polypeptides are obtained based on HLA gene typing results of an inoculator, and each HLA gene corresponds to at least one high-affinity MHC-II binding polypeptide; a shell is a glucan with sulfydryl or other polymer coating layer, and sulfydryl is used as a coupling group to be connected with an antigen to construct the vaccine. The method has the advantages that competition is avoided, inhibition is generated, a better immune effect is achieved, antibodies of high-titer carrier molecules are not generated, and cross reaction side effects are avoided. The carrier molecular diversity is reduced; side effects are avoided. And antibody immunity and cellular immunity functions are generated. The particle size of the microspheres is controllable, and the immunologic function can be achieved without adjuvants. The preparation process is simple to operate and good in repeatability.

The invention discloses a monoclonal antibody targeting all CD45 subtypes and application of the monoclonal antibody, and belongs to the field of monoclonal antibody preparation. The hybridoma cell strain capable of stably secreting all anti-human CD45 subtype antibodies is successfully obtained by stably expressing short and long molecular subtypes of human CD45 extracellular regions in L929 mouse fibroblasts, immunizing BALB / c mice with L929 cells expressing the two molecular subtypes of human CD45, and fusing splenocytes with SP20 myeloma cells after the serum titer reaches the standard. And the monoclonal antibody targeting all subtypes of CD45 is obtained. The monoclonal antibody provided by the invention shows a high-affinity binding characteristic with all human CD45 molecular subtypes, has important application value in the aspect of human CD45 molecular detection, and can be used as a therapeutic antibody in the fields of tumor immunotherapy, autoimmune disease treatment, transplant rejection resistance and the like.

The invention belongs to the technical field of antibodies, and particularly relates to an antibody and an antibody pair for resisting human IL-12 / IL-23p40 protein, and application of the antibody and the antibody pair. The antibody is a first antibody or a second antibody, amino acid sequences of light chains CDR1-3 of the first antibody are respectively shown as SEQ ID NO.3-5, and amino acid sequences of heavy chains CDR1-3 of the first antibody are respectively shown as SEQ ID NO.8-10; the amino acid sequences of light chains CDR1-3 of the second antibody are respectively as shown in SEQ ID NO.13-15, and the amino acid sequences of heavy chains CDR1-3 of the second antibody are respectively as shown in SEQ ID NO.18-20. The two antibodies disclosed by the invention have specific recognition and high-affinity binding capacities on recombinant and natural human IL-12 / IL-23p40 protein, and have important practical values in the fields of immunodiagnosis and immunotherapy taking p40 as a target spot.

The invention provides an adsorption material and a preparation method and application thereof, the adsorption material comprises a carrier and an endotoxin affinity binding ligand, the endotoxin affinity binding ligand comprises a recombinant C factor protein, and the carrier and the recombinant C factor protein are connected through a spacer arm; wherein the carrier comprises at least one of resin, chitosan, cellulose, agarose and glucan; the spacer arm comprises at least one of modified polyethylene glycol, polyvinyl pyrrolidone, polymethylacrylic acid-2-hydroxyethyl ester, polyvinyl alcohol, polyacrylic acid, hexamethylenediamine, divinyl sulfone and glutaraldehyde, and at least one end of the modified polyethylene glycol is provided with carboxyl, aldehyde or amino. The adsorption material provided by the invention can efficiently adsorb endotoxin, has the characteristics of low toxicity risk and excellent blood compatibility, and can improve the safety of blood purification.

The invention discloses a bipeptide modified bionic nano-vesicle as well as a preparation method and application thereof, and belongs to the field of biological medicines. The dipeptide modified bionic nano-vesicle comprises nano-particles formed by PLGA (poly (lactic-co-glycolic acid)), and the nano-particles are loaded with a medicine with a nerve protection or nerve repair effect; the surface of the nanoparticle is coated with a macrophage membrane for expressing RVG peptide and T7 peptide. The bipeptide modified bionic nano-vesicle simultaneously presents T7 peptide and RVG peptide through an engineered macrophage membrane, the T7 peptide is combined with a blood-brain barrier transferrin receptor through high affinity to realize efficient brain entry, astrocytes in the brain are specifically recognized by virtue of the RVG peptide, accurate recognition and delivery of target cells in a focus area are realized, and the bipeptide modified bionic nano-vesicle has a good application prospect. Meanwhile, the natural inflammation tropism and immune escape ability of a macrophage membrane are reserved, and the problems that a traditional drug delivery system is low in targeting precision, and cross-barrier distribution and intracerebral distribution are difficult to cooperate are solved.

The present invention is referred to a method for production of a pharmaceutical composition, said composition comprises: A) naturally secreted exosomes from normal human embryonic lung fibroblast cells (MRC-5 cell line), wherein said exosomes comprise a lipophilic and / or hydrophilic active substance, said method comprises the following steps in the following order: a) separation of exosomes by ultrafiltration, b) collection of exosomes by membrane-based affinity binding method, c) loading of exosomes with active substance, or B) artificial exosomes, wherein said exosomes comprise a lipophilic and / or hydrophilic active substance, said method is a microfluidic method and said method comprises the following steps in the following order: a) extraction of lipids from a cell line of normal human embryonic lung fibroblast cells (MRC-5 cell line) to obtain a lipid film, b) resuspending of the lipid film in an organic solvent and mixing with the aqueous phase in a microfluidics device to obtain exosomes, wherein the aqueous phase comprises Tween 20 and wherein in the microfluidics device I) the flow rate ratio of the organic phase to the flow rate of the aqueous phase (flow rate ratio, FRR) is set from 1:5 to 1:3, ii) the organic phase flow rate (OPFR) is preferably set at 200 pL / min or 400 pL / min and ill) the aqueous phase flow rate (APFR) is preferably set at 100 pL / min or 1000 pL / min, c) purification of the obtained exosomes using size exclusion chromatography, d) loading of the exosomes with active substance, e) purification of the obtained exosomes using size exclusion chromatography to remove the unloaded drug.

The invention relates to the technical field of immune carriers, in particular to immune carrier microspheres loaded with individualized MHC-II binding polypeptide and vaccine preparation and application of the immune carrier microspheres loaded with the individualized MHC-II binding polypeptide. The core microsphere is loaded with individualized MHC-II binding polypeptide, the sequence of the MHC-II binding polypeptide is obtained by predicting and screening based on an HLA genotyping result, and each HLA allele corresponds to at least one high-affinity MHC-II binding polypeptide; and the shell is a glucan or other polymer coating layer. The preparation method has the advantages that the T epitope and the B epitope are separately subjected to immune competitive inhibition inside and outside the microspheres, so that a better immune effect is obtained. The antibody avoids cross reaction side effects; carrier molecule diversity is reduced, and side effects caused by T cell over-activation are avoided; th1 epitopes and Th2 epitopes can be contained in the microspheres, so that antibody immunity and T cell immunity functions are generated; the particle size of the microspheres is controllable, and the immunologic function can be achieved without adjuvants.

The invention belongs to the technical field of biological medicine, and particularly relates to a small molecule compound for resisting porcine circovirus type 2 and application thereof. By predicting the binding area of the PCV2 Cap protein and the gC1qR protein and performing screening such as high-throughput molecular docking by taking the predicted binding area as a docking pocket, the invention finds that the small-molecule compound W29 can be bound with the predicted binding area of the PCV2 Cap protein and the gC1qR protein in a high affinity manner, and cell tests verify that the small-molecule compound W29 can effectively inhibit PCV2 replication and can inhibit PCV2 replication. The small molecule compound W29 is low in cytotoxicity and high in safety. Therefore, the small molecule compound W29 can be used as a candidate compound of a novel anti-PCV2 drug, is excellent in safety and has a potential application prospect.

A device for intermittent monitoring of a biomolecule in a human body, and use thereof. The device includes a device casing, a microneedle array including an array of needles configured to extract interstitial fluid from a user, a microfluidic system defining a fluidic channel including a biomolecule debonding agent, wherein the fluidic channel is in fluidic communication with the microneedle array and configured to facilitate flow of the extracted interstitial fluid therethrough, and an assay system in fluidic communication with the microfluidic system. The assay system includes an affinity binding agent capable of generating an indication of a level of one or more biomolecules present in the extracted interstitial fluid. The microneedle array, the microfluidic system, and assay system are disposed within the device casing.

The invention relates to bispecific antigen binding proteins (ABP), such as bispecific antibodies, that bind with a first antigen binding site to both leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1) and LILRB2 while not binding to, or binding with significantly less affinity to, leukocyte immunoglobulin-like receptor subfamily A (LILRA). The bispecific ABP of the invention bind with a second antigen binding site to immune checkpoint (molecules) such as PD-1 or PD-L1. The bispecific ABP of the invention can also inhibit the interaction between LILRB1 and / or LILRB2 and a natural ligand of ULRB receptors (e.g. interacting proteins, such as HLA-G) on immune cells and the inhibition of such interaction can reduce immune cell suppression and thereby support anti-infection and anti-tumour immune responses in a subject suffering from such diseases. Bispecific molecules combining LILRB1 / 2 antagonism with inhibition of immune checkpoints, such as the inhibition of the PD-1 / PD-L1 axis, is specifically useful in the treatment of proliferative disorders. Also provided are methods of reducing the immune suppression of cells involved with a cell-mediated immune response, and / or methods for treating infective- and / or proliferative diseases, using an LILRB1 and / or LILRB2 antigen binding protein such as an antibody binding to both LILRB1 and / or LILRB2, as well as certain related aspects including detection, diagnostic and screening methods.

The invention discloses a method for rapidly screening and identifying an alpha-glucosidase inhibitor from stevia rebaudiana by combining a magnetic MOF immobilized enzyme technology with an ultra-high performance liquid chromatography-time-of-flight mass spectrometry technology. The method is based on an immobilized enzyme technology, screening of the alpha-glucosidase inhibitor in stevia rebaudiana is carried out by means of the affinity binding effect of active small molecules and enzyme and the magnetic separation characteristic of magnetic MOF immobilized alpha-glucosidase, and structural identification of an active compound is carried out by applying an ultra-high performance liquid chromatography-time-of-flight mass spectrometry technology. And finally, verifying the in-vitro alpha-glucosidase inhibitory activity of the screened active compound, and simulating the binding information of the two compounds by means of a molecular docking technology. The method provided by the invention has the characteristics of rapidness, high efficiency, accuracy, easiness in separation from a reaction system and reutilization of the target receptor immobilized alpha-glucosidase, is suitable for screening the alpha-glucosidase inhibitor from complex systems such as traditional Chinese medicines and natural products, and has a wide application prospect.

The present invention relates to antibodies that bind to IgE and their use in the treatment of autoimmune diseases, particularly Bullous Pemphigoid (BP) and Chronic Spontaneous Urticaria (CSU). The anti-IgE antibodies comprise a variant Fc domain that binds to the Fc receptor FcRn with increased affinity relative to a wild-type Fc domain. The anti-IgE antibodies may comprise a variant Fc domain comprising the amino acids Y, T, E, K, F and Y at EU positions 252, 254, 256, 433, 434 and 436, respectively, wherein the variant Fc domain binds to human FcRn with increased affinity relative to a wild-type human IgG Fc domain.

This invention provides improved compositions and methods for mRNA display libraries for the rapid production of stable recombinant high-affinity binders. [Solution] A composition, method, and use of recombinant viruses and / or recombinant viral vectors encoding distinct antibodies or antibody fragments prepared from a highly diverse nucleic acid library are disclosed. Preferably, the recombinant virus is a genetically modified low immunogenic virus, for example, an E2b deletion adenovirus. The highly diverse nucleic acid library is (1)V H -CDR1 / 2 sublibrary, (2) multiple V H -CDR3 sublibrary and (3)V L It includes or is derived from sublibraries, each of which includes multiple members. Preferably, each member of the sublibrary includes at least one random cassette having multiple degenerate base positions.

The invention provides an application of a CRISPR (clustered regularly interspaced short palindromic repeats) / Cas12a (CRISPR / Cas12a)-nano enzyme bimodal aptamer sensing method in the detection of KIM-1. An aptamer used in the method is an oligonucleotide aptamer combined with KIM-1 with high specificity and high affinity, and is used as a target recognition element and an activation switch of a CRISPR system; a CRISPR / Cas12a system is adopted as a signal amplifier, and the activity of the CRISPR / Cas12a system is controlled by a binding event of the aptamer and a target; a FeNi MOF (at) AgNPs-MBs report substrate is used as a cut unit and a bimodal signal source, and a cut product of the report substrate is used for generating measurable fluorescence and colorimetric signals. The method provided by the invention is high in detection sensitivity and good in accuracy, the detection time is shortened to be within 2 hours from 4 hours required by ELISA, and the analysis efficiency is remarkably improved.

The application relates to the technical field of biopharmaceuticals, and discloses a PD-1 and CTLA-4 double-target inhibiting polypeptide or a pharmaceutically acceptable salt thereof and an application thereof, wherein the polypeptide has a structure as shown in formula (I): X1SPILYQMCDYKRX2 (I). The polypeptide or the pharmaceutically acceptable salt thereof can simultaneously produce high-affinity binding to PD-1 and CTLA-4, has excellent biological blocking activity, can significantly improve the proportion of effector T cell subgroups in tumor tissues, and effectively enhances the anti-tumor immune response of the body. Therefore, the polypeptide or the pharmaceutically acceptable salt thereof can be used for related detection of PD-1 and CTLA-4, and can be used as a new anti-tumor candidate drug, thereby providing a brand-new treatment scheme for cancer patients.

The invention relates to a monoclonal antibody capable of specifically recognizing a tumor-associated antigen PZR as well as a preparation method and application of the monoclonal antibody. The anti-PZR monoclonal antibody can specifically recognize natural PZR protein expressed by triple negative breast cancer cells, and can realize high-affinity binding with recombinant PZR extracellular domain protein. The compound also has the capability of remarkably inhibiting migration and metastasis of PZR positive triple negative breast cancer cells, and has the characteristic of repression function. The anti-PZR monoclonal antibody provided by the invention can be used for preventing and treating PZR positive triple negative breast cancer metastasis, and is suitable for developing antibody drugs for targeted therapy of PZR positive tumors.

Provided are multivalent D-peptide compounds that specifically bind to a protein of interest. The multivalent D-peptide compounds may include two or more different variant D-peptide domains linked via a linking component. The D-peptide compounds may include a plurality of different domains that specifically bind to different binding sites on a protein of interest to provide high affinity binding to and potent activity against the protein of interest. Also provided are D-peptide variant GA domain polypeptides and D-peptide variant Z domain polypeptides having a Specific Determining Motif (SDM) for specific binding to a protein of interest, such as VEGF-A or PD-1. In some embodiments in which the protein of interest is a homodimeric protein of interest (e.g., VEGF-A, PD-1), the D-peptide compounds may be similarly dimeric and include dimers of multivalent (e.g., divalent) D-peptide compounds. Methods of using the compounds are provided, including methods of treating a disease or condition associated with a protein of interest in a subject.

The invention relates to a method for amplifying an acridine system of a chemiluminescence platform, and particularly provides a method for enhancing the luminous intensity in chemiluminescence immunoassay, which comprises the step of enhancing the luminous intensity by using a composition, and the composition comprises biotin labeled by an anti-acridine analogue antibody and streptavidin labeled by an acridine analogue. According to the method, the sensitivity and the luminescence value are amplified by utilizing the specific binding of the biotin and the avidin and then utilizing the superposition of the specific affinity binding mode of the acridine analogue and the acridine analogue antibody, the sensitivity can be improved by 5-10 times on the existing acridine analogue platform, and the application prospect is excellent.

The present invention relates to the detection of modifications in polynucleotides by binding an affinity binding element to a nucleotide sequence. The affinity binding element may include a compound that binds to a modified nucleotide base and a nucleotide sequence complementary to a target nucleotide sequence, an oligonucleotide primer complementary to the target nucleotide sequence, or a nucleotide sequence complementary to an oligonucleotide linker. The present invention provides methods for detecting one or more modifications in a nucleotide sequence. The invention also provides affinity binding elements, and optionally, oligonucleotide primers and / or oligonucleotide probes, and methods of using the affinity binding elements in assays to detect modified bases. The methods of the invention enable the detection of modified nucleotides associated with cancer, psychiatric disorders or metabolic diseases.

The present invention relates to antigen-binding proteins, such as antibodies, that bind to leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1) and LILRB2 without binding or with significantly lower affinity to leukocyte immunoglobulin-like receptor subfamily A (LILRA), which can also inhibit the interaction between LILRB1 and / or LILRB2 and a native ligand of the LILRB receptor (interacting protein, such as HLA-G) on an immune cell, such as LILRB1 and LILRB2. And the inhibition of the interaction can reduce the inhibition of immune cells, thereby supporting the anti-infection and anti-tumor immune response of subjects suffering from the disease. In particular, the present invention provides products, compositions and methods for treating disease using antigen binding proteins of LILRB1 and / or LILRB2, particularly antigen binding proteins that preferably specifically bind to LILRB1 and LILRB2, such as antigen binding proteins that further do not bind or bind with lower affinity to one or more LILRA receptor proteins (e.g., LILRA1 and / or LILRA3). Also provided are methods of using LILRB1 and / or LILRB2 antigen binding proteins, such as antibodies that bind to LILRB1 and / or LILRB2, to reduce immunosuppression of cells involved in a cell-mediated immune response and / or to treat infectious and / or proliferative diseases, as well as certain related aspects, including methods of detection, diagnosis, and screening.

Provided herein are methods for interrogating interactions between a binding molecule and a polypeptide of interest using hydrogen-deuterium exchange mass spectrometry, optionally in combination with in silico modelling of the binding interaction between the binding molecule and the polypeptide. The polypeptides of interest that are interrogated in a disordered domain include, without limitation, androgen receptor polypeptides, alpha-synuclein polypeptides, p27 polypeptides, c-myc polypeptides, and Tau polypeptides. Further described herein are enrichment of molecules that bind to a polypeptide described herein with high affinity, as well as methods of treating diseases or conditions by administering a binding molecule described herein to a subject in need thereof.

The invention relates to an anti-ROR1 antibody and application thereof, and belongs to the field of biological medicine. Specifically, the invention discloses a specific binding ROR1 antibody or an antigen binding fragment thereof, a nucleic acid molecule for coding the antibody or an antigen binding part thereof, a vector for expressing the nucleic acid molecule, a method for preparing and purifying the antibody, a recombinant cell, a composition, and an application of the antibody or the antigen binding fragment in preparation of medicines for treating and / or preventing tumors. Meanwhile, the provided antibody has strong specificity, high affinity, high binding capacity and a mediating cell endocytosis effect.

The invention provides a nucleic acid molecule capable of being combined with oxytetracycline in a high-affinity mode. The nucleic acid molecule can detect the oxytetracycline with high sensitivity after being labeled with a fluorescent dye. Nucleic acid molecules (SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5) capable of specifically recognizing oxytetracycline are used as affinity ligands, and sensitive detection of oxytetracycline is realized by using nucleic acid molecules marked with fluorescent dye. According to the detection method disclosed by the invention, the detection limit of oxytetracycline reaches nM level, and the sensitivity is high.

The application discloses an endogenous polypeptide, a preparation method and application thereof. A structural formula of the polypeptide is shown in formula (I): R1-(AA1)m-AA2-AA3-(AA4)n-R2, formula (I); wherein m is independently 2 or 3; n is independently 1, 2 or 3; AA1 is independently K, R or H; AA2 is independently I or W; AA3 is independently I or W; AA4 is independently K, R or H; R1 is any one of -H, Y, LY, PLY or LLY; and R2 is any one of -OH, L, LL, E, EL, EW, W, EH or EHL. The polypeptide has removed a high-affinity heparin binding domain while retaining the targeted antioxidant and anti-inflammatory functions, thereby avoiding signal interference and potential biological safety risks possibly caused by full-length PF4, and meeting the safety requirements of cosmetic ingredients.

The present application relates to an anti-ROR1 antibody and its application, and belongs to the field of biological medicine. Specifically, the application discloses an antibody or an antigen-binding fragment thereof specifically binding to ROR1, a nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof, a vector expressing the nucleic acid molecule, a method for preparing and purifying the antibody, a recombinant cell, a composition, and a use thereof, in particular, in the preparation of a drug for treating and / or preventing a tumor. Meanwhile, the provided antibody has high specificity, high affinity, high binding capacity, and can mediate intracellular endocytosis.

Aspects of the present disclosure include compositions and methods for treating tumors expressing CD70 with engineered γδ T cells. In some embodiments, the γδ-T cells comprise a chimeric antigen receptor (CAR) construct. The CAR construct can include the full-length CD27 receptor domain, a co-stimulatory domain, an intracellular signaling domain, combinations thereof, or all of them. The CAR construct can contain a domain encoding an additional polypeptide that confers advantageous functions to the γδ T cells.

The present invention provides a method for preparing NK cells and their application in treating cancer. First, a monoclonal antibody targeting PD-L1 is screened and obtained, which can bind to the target antigen with high affinity. Second, the activation mode of NK cells is optimized, and cytokines such as IL-15, IL-12 and IL-18 are used to progressively activate NK cells, thereby improving the activation level of NK cells. Third, the combination of NK cells and antibodies targeting PD-L1 can effectively prevent tumor immune escape and enhance anti-tumor activity.