48 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 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 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.

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 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 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.

This invention belongs to the fields of molecular virology and immunology, and provides an alpaca-derived nanobody that specifically binds to Chikungunya virus (CHIKV), its preparation method, and its applications. The nanobody has a heavy chain variable region (VHH), which comprises the following CDRs: CDR1 (amino acid sequence as shown in SEQ ID NO:1), CDR2 (amino acid sequence as shown in SEQ ID NO:2), and CDR3 (amino acid sequence as shown in SEQ ID NO:3). The VHH includes four frame regions FR1-FR4; FR1, FR2, FR3, and FR4 are arranged alternately with CDR1, CDR2, and CDR3 in sequence. The nanobody of this invention can efficiently neutralize CHIKV virus and inhibit its infection, and has the potential to prepare drugs or kits for the prevention, treatment, and / or detection of CHIKV infection. The nanobody of this invention can bind with high affinity to the E protein of CHIKV, effectively inhibiting CHIKV pseudovirus infection.

The invention relates to application of Chinese yam protein, in particular to application of Chinese yam active protein in preparation of medicine for regulating blood testis barrier to treat testis dysfunction. L-YP has unique fluorescence characteristics and remarkable antioxidant activity, and can effectively improve testis immune microenvironment disorder by repairing blood testis barriers and inhibiting NLRP3 and TLR4 / MyD88 / NF-kappa B inflammatory pathways. In combination with a molecular docking technology, a molecular mechanism that key components such as YP2 (mitochondrial ornithine aminotransferase) and the like realize immunoregulation through high-affinity binding is clarified for the first time. According to the application disclosed by the invention, a molecular docking technology is creatively combined with system experimental analysis, and a molecular mechanism of improving testis injury by the Chinese yam protein is illuminated from the perspective of a'structure-function-target 'synergistic effect, so that a novel dietary intervention strategy is provided for preventing reproductive toxicity caused by chemotherapy; the application potential of medicinal and edible components in the field of male reproductive health is highlighted.

Two or more peptides or polypeptides and an adjuvant for use in a method of inducing a tumor specific immune response, wherein the peptides or polypeptides have been identified by a method comprising: identifying a plurality of neoantigenic peptides for preparing a subject-specific immunogenic composition, each neoantigenic peptide comprising a tumor-specific neoepitope comprising a tumor-specific mutation, the method comprising: a. identifying a plurality of subject-specific tumor mutations in expressed genes of a subject having cancer by whole genome or whole exome nucleic acid sequencing of tumor and normal tissue samples from the subject, wherein the mutations are present in the genome of cancer cells of the subject but not in normal tissue from the subject; b. wherein when a mutation identified in step (a) is a point mutation: i. identifying a mutant peptide having the mutation identified in step (a), wherein said mutant peptide comprises a tumor-specific neoepitope which binds to a class I HLA protein with a greater affinity than a wild -type peptide; and has an IC50 less than 500 nm; c. wherein when a mutation identified in step (a) is a splice-site, frameshift, read-through or gene-fusion mutation: i. identifying a mutant polypeptide encoded by the mutation identified in step (a), wherein said mutant polypeptide comprises a tumor-specific neoepitope which binds to a class I HLA protein.

The invention relates to the technical field of biological pharmacy, and provides a polypeptide capable of inhibiting PD-1 and CTLA-4 at the same time or a pharmaceutically acceptable salt of the polypeptide and application of the polypeptide, and the polypeptide has a structure as shown in a formula (I): TASPILYQMX1CDYKRCVX2VX3NGX4 (I). 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 application discloses a kind of multilocular hydatid Em Preparation method of 6B protein and application thereof in preparation of anti-host inflammatory response preparation. By protein structure modeling, molecular docking technology, it is confirmed that Em 6B can be combined with host 26S proteasome key subunit with high affinity, affect the assembly of host proteasome in vivo, and then intervene the activity of NF-κB signal pathway, so as to regulate host inflammatory response. Through animal experiment, it is shown that recombinant Em 6B intervention can significantly alleviate the colon injury of inflammatory bowel disease mice, regulate the expression level of pro-inflammatory and anti-inflammatory factors, and improve the survival rate of sepsis mice, and no obvious toxic side effects are observed. The application opens up a new path for developing anti-inflammatory preparations using parasite-host immune interaction natural molecules, and provides a kind of anti-host inflammatory response biological preparation technical scheme with novel mechanism of action and good biological safety, which has good application potential in the prevention and treatment of human and livestock inflammatory diseases.

This invention discloses a multilocular echinococcosis larva. In Preparation method of -6B protein and its application in the preparation of anti-host inflammatory agents. Through protein structure modeling and molecular docking technology, the preparation method was confirmed. In -6B can bind with high affinity to a key subunit of the host 26S proteasome, affecting the assembly of the proteasome in the host and thus interfering with the activity of the NF-κB signaling pathway, thereby regulating the host inflammatory response. Animal experiments have shown that recombinant... In -6B intervention significantly alleviated colonic damage in mice with inflammatory bowel disease, regulated the expression levels of pro-inflammatory and anti-inflammatory factors, and improved the survival rate of septic mice, with no obvious toxic side effects observed. This invention opens up a new pathway for developing anti-inflammatory agents using natural molecules that interact with the parasite's immune system, and provides a novel mechanism of action and biosafety for anti-host inflammatory biological agents, showing great potential for application in the prevention and treatment of inflammatory diseases in humans and livestock.

A protein-based probe for detecting the presence of one of two distinct states of a target membrane-associated molecule by means of polarization microscopy is disclosed. The probe contains an anchoring moiety consisting of at least one lipidated peptide and / or at least one transmembrane α-helical peptide, a peptide linker moiety having the length of at least 5 amino acids, wherein at least 50% of the amino acids forming the linker are selected from glycine, serine, and threonine, a fluorescent moiety, and an affinity binding moiety capable of binding the target membrane-associated molecule. The moieties are arranged in the order a-b-c-d or d-c-b-a in the direction from the N-terminus to the C-terminus. Methods of detecting presence or absence of the target molecule, detecting activated or inactive forms of the target molecule, and detecting the activation of the target molecule are also described.

The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules, such as vitamin C or malaria histidine-rich protein II (HRP2).

Peptide sequences that are ACE2 homologues are provided. Compared to the wild-type ACE2 in the host, the peptide sequences bind with higher affinity to the receptor-binding domain (RBD), thus inhibiting this interaction by competitively inhibiting the binding of the virus RBD region of SARS-COV-2 with the human ACE2. The peptide sequences can be included in a pharmaceutical composition.

The present invention relates to a monoclonal antibody mutant for T4 detection and a coding nucleic acid molecule thereof, the monoclonal antibody mutant comprises complementary determining regions CDR-VL1, CDR-VL2 and CDR-VL3, the CDR-VL1 is represented by QNIYSN, the CDR-VL2 is represented by RAS, and the fifth amino acid Y, represented by QSYYYASGSTYANA, of the CDR-VL3 is deleted or substituted by a non-Y amino acid residue. According to the monoclonal antibody mutant, the cross reactivity with a free anti-T4 antibody is remarkably reduced while high-affinity binding of the monoclonal antibody mutant to a T4-T4 antibody compound is maintained. When the kit is used for T4 detection, a target immune complex and a free antibody component can be clearly and accurately distinguished in a complex clinical sample, and the kit has important clinical application value.