69 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 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 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.

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.

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.

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.

The invention relates to a bispecific antibody targeting B7H7 and CD3 and application of the bispecific antibody. Wherein the bispecific antibody comprises: a first antigen binding region, the first antigen binding region having CD3 binding activity; and a second antigen binding region, the second antigen binding region having B7H7 binding activity; wherein the first antigen binding region comprises an anti-CD3 antibody, the anti-CD3 antibody comprises a heavy chain complementarity determining region HCDR, and the HCDR comprises an amino acid sequence selected from at least one of SEQ ID NO: 4-6 and 66; the second antigen binding region comprises an anti-B7H7 antibody, the anti-B7H7 antibody comprises a heavy chain complementarity determining region HCDR, and the HCDR of the anti-B7H7 antibody comprises an amino acid sequence selected from at least one of SEQ ID NO: 26-28. The bispecific antibody with the sequence can be combined with human and monkey B7H7 with high specificity and high affinity, can be combined with human and monkey CD3 with low affinity and high specificity, can promote PBMC to kill tumor cells, and has good anti-cancer activity and higher treatment safety; the occurrence risk of cytokine storm caused by the CD3 bispecific antibody is effectively reduced.

The invention belongs to the technical field of biochemical detection, and discloses a rapid new pollutant screening method based on PPAR or ER protein affinity binding, PPAR or ER protein with a His tag is selectively adsorbed to a Ni-magnetic bead carrier, and then a new pollutant is screened according to the principle of affinity binding of a nuclear receptor and ligand small molecules. Effect substances with binding activity are specifically captured from a complex environmental medium by using nuclear receptor protein, and the core is to convert environmental endocrine disruption effect activity into measurable signal output (fluorescence), so that rapid screening of new pollutants is realized. According to the method, the efficiency of screening new pollutants is improved, and the method can be applied to rapid screening of effector activity new pollutants combined with PPAR or ER protein in the environment.

The application provides two kinds of anti-rabies virus full human monoclonal antibodies or a combination thereof, a heavy chain variable region of the antibodies comprises three CDR regions, sequences of the three CDR regions are respectively shown as SEQ ID NO:1-3 and SEQ ID NO:9-11, and a light chain variable region of the antibodies comprises three CDR regions, sequences of the three CDR regions are respectively shown as SEQ ID NO:4-6 and SEQ ID NO:12-14. The application also provides application of the antibodies to anti-rabies virus. The antibodies are high in affinity to different antigen epitopes of a rabies virus G protein, and are high in potency in neutralizing rabies virus strains derived from different genetic subtypes, and the combination of the antibodies does not affect antigen binding and virus neutralization activities of the antibodies.

The present invention provides rapid, sensitive high-throughput methods and systems for characterizing peptides or proteins using affinity-based chromatography-coupled native mass spectrometry to improve manufacturing process of biopharmaceutical products, such as identifying impurities during antibody purification, monitoring post-translational modification variants during production, or characterizing drug-to-antibody ratio of antibody-drug conjugates. The separation profiles of the peptides or proteins are generated and compared to identify or qualify the peptides or proteins, wherein the separation profile is based on differential affinity binding.

Aptamer detection techniques with chemistry attachment with proximity hybridization and extension are described in an aptamer-based assay. In an embodiment, capture oligonucleotides can be used such that the capture oligonucleotides attach to spatially-fixed analytes in a fixed tissue sample. Aptamers that hybridize to the capture oligonucleotides are tagged with an extension sequence that can then be used for subsequent capture and spatial tagging steps.

The invention relates to the technical field of biological pharmacy, and provides a double-target inhibition polypeptide or pharmaceutically acceptable salt and application thereof, the polypeptide comprises an amino acid sequence: TASPILYQMCCDYKR, and an amino acid fragment: X1WGIX2HSHFTHTX3WKX4 (I) with a structure as shown in a formula (I) is connected to the C tail end of the sequence. The polypeptide or the pharmaceutically acceptable salt thereof can generate high-affinity binding with PD-1 and CTLA-4 at the same time, has excellent biological blocking activity, can significantly improve the proportion of effector T cell subsets in tumor tissues, and effectively enhances the anti-tumor immune response of a body. Therefore, the polypeptide or the pharmaceutically acceptable salt thereof can be used for related detection of PD-1 and CTLA-4, can also be used as a novel anti-tumor candidate drug, and provides a brand new treatment scheme for cancer patients.

The invention relates to a method for purifying a protein of interest, comprising the preparation of a fusion protein in which this protein of interest is fused to a protein tag comprising the Mmi1 protein of a microorganism of the genus Schizosaccharomyces or a fragment thereof, bringing this fusion protein into contact with a ribonucleic acid molecule containing at least one UNAAAC nucleotide sequence motif, so as to allow the affinity binding of the protein tag with this ribonucleic acid molecule, and recovering the protein of interest.

The invention discloses a GPC3 derived antigen peptide vaccine, an mRNA vaccine, a saRNA vaccine and a preparation method and application thereof. The amino acid sequence of the antigen peptide vaccine is one or any combination of more of amino acid sequences shown as SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5 and SEQ ID NO: 6. According to the invention, an efficient pGPC3 model antigen peptide is screened based on GPC protein, and pGPC3 mRNA and pGPC3 saRNA are designed according to a pGPC3 sequence example. The pGPC3 saRNA (at) Lipi vaccine is prepared through a liposome technology, and due to the fact that limiting conditions such as nonapeptide and high-affinity binding with H-2 I type molecules (H-2Kb) are adopted during pGPC3 polypeptide antigen screening, APC cells are facilitated to present antigens through an MHCI restrictive pathway and activate CD8 + T cells, and GPC3 specific CTL is triggered to efficiently kill liver cancer cells. Finally, the pGPC3 saRNA (at) Lipi vaccine can completely inhibit the growth of the liver cancer, the inhibition rate reaches 99.8%, and the liver cancer of 4 / 8 mice completely fades down. In addition, the method can be used for vaccine adjuvant and carrier research on a liver cancer subcutaneous transplantation tumor model.