92 results about "Human immunoglobulin" patented technology

The invention belongs to the field of biological medicine, and particularly relates to a respiratory syncytial virus F protein mutant and application thereof. The respiratory syncytial virus F protein mutant is characterized in that at least one pair of amino acid residues in an F1 subunit and / or an F2 subunit of F protein polypeptide are substituted by cysteine, and / or an F protein signal peptide part is substituted by a human immunoglobulin light chain signal peptide, and / or alanine A at the 107 site of a multi-base sequence is mutated into arginine R, lysine K at the 134 site is mutated into arginine R, and the amino acid residues in the F1 subunit and / or the F2 subunit of the F protein polypeptide are mutated into arginine. According to the invention, more neutralizing antibody epitopes can be exposed, the stable pre-fusion conformation is maintained, effective neutralizing antibody reaction and antibody binding reaction to the RSV subtypes A and B can be ensured, and the vaccine is suitable for various vaccine forms taking the RSV F protein as the antigen.

The invention belongs to the technical field of immunodetection, and discloses a specific monoclonal antibody mAb48 of rabbit anti-human immunoglobulin G2 subtype (IgG2), the specific monoclonal antibody mAb48 comprises a light chain variable region and a heavy chain variable region, the light chain variable region comprises LCDR1-3, the LCDR1 comprises an amino acid sequence EDIGYG, the LCDR2 comprises an amino acid sequence GAS, and the LCDR3 comprises an amino acid sequence QQGFS; the heavy chain variable region comprises HCDR1-3, the HCDR1 comprises an amino acid sequence GFSLSNYE, the HCDR2 comprises an amino acid sequence ISSSGST, and the HCDR3 comprises an amino acid sequence ARNNNN. The monoclonal antibody disclosed by the invention can be combined with human immune globulin G2 subtype (IgG2) in a high-specificity manner, can be applied to immunodetection, and provides a basis for the preparation of engineering antibodies in the next step.

Disclosed herein are kits and methods for treating pulmonary arterial hypertension (PAH), the method comprising administering to a subject in need thereof: * a therapeutically effective amount of a tyrosine kinase inhibitor or a pharmaceutically acceptable salt thereof; and * a therapeutically effective amount of a dimeric fusion protein comprising: * an extracellular domain of activin type 2A (ACTR IIA) or activin type 2B receptor (ACTR IIB); and an Fc domain of human immunoglobulin G1 (IgG1). In some embodiments, the tyrosine kinase inhibitor is cellatinib or a pharmaceutically acceptable salt thereof, and the fusion protein is sotasercept.

The invention relates to a preparation method and application of a human immune globulin preparation stock solution, the preparation method comprises the steps of pretreatment of an initial raw material, ultrafiltration concentration and dialysis, and virus inactivation and filtration, the ultrafiltration concentration and dialysis process is completed under the participation of a dialysis buffer solution composed of a main functional component L-proline, and the human immune globulin preparation stock solution is obtained. The L-proline is used for effectively protecting human immune globulin in the preparation process of the human immune globulin preparation stock solution and the preparation, so that the influence of various unstable factors possibly causing polymerization of the human immune globulin product in the preparation process of the human immune globulin product in the prior art is effectively overcome; therefore, the stability and the quality of the human immune globulin preparation stock solution and the prepared product are effectively improved, and compared with the prior art, the technical scheme provided by the invention is simple, convenient and practical, and can achieve an extremely good technical effect, so that the human immune globulin preparation has outstanding beneficial effects and remarkable progress, and has extremely high popularization and application values.

The invention discloses a method for detecting the biological activity of human immunoglobulin ADCP, which is characterized in that CHO-K1 / SPIKESARS2 is taken as a target cell, THP-1 cells (human leukemia monocytes which naturally express CD32a (Fc gamma RIIa) and CD64a (Fc gamma RIIa) and stably transfect NF-kB-Luc luciferase reporter genes) modified by genetic engineering are taken as effector cells, and a fluorescence reporter gene method is adopted for detection. Based on specific target cells and effector cells, the ADCP biological activity of two different human immune globulin preparations, namely intravenous injection human immune globulin and subcutaneous injection human immune globulin, can be accurately and reliably reflected by a drawn dose-effect curve through a detection system matched with specific human immune globulin solution concentration, and the method is simple and easy to implement. Cost is low, and practical application and popularization value is achieved.

The present invention relates to stable formulations of antibodies or antigen-binding fragments thereof that bind to human immunoglobulin-like transcript 4 (ILT4). The formulations provided herein may also include buffers, non-ionic surfactants, non-reducing sugars, antioxidants, and other compositions and adjuvants. Also provided are methods of treating various cancers using the formulations disclosed herein. The formulations can be prepared as a medicament and administered to a patient in need thereof.

The present invention relates to the field of medicine, and specifically discloses an influenza virus vaccine fusion protein, which is a fusion protein formed by connecting an HA antigen fragment encoded by an influenza HA antigen gene and an M2 extracellular region fragment (M2e; Membrane Protein (M2) Extracellular Region (M2e) in series with an Fc fragment encoded by a human immunoglobulin gene in series. The fusion protein of the present invention has higher antigenicity than a single HA antigen or a single M2 extracellular region fragment antigen, and the Fc fragment can improve protein purification efficiency and prolong the half-life of the antigen in vivo. Therefore, the influenza vaccine provided by the present invention has great advantages and great application value.

The invention relates to a pair of anti-TSH receptor (TSHR) autoantibody-binding fusion proteins consisting of a capture fusion protein and a detection fusion protein, and a method for detecting autoantibodies to the thyroid stimulating hormone receptor (TSHR) in a biological fluid sample, which employs said fusion proteins pair. More specifically, the capture and detection fusion proteins of the pair of the invention comprise an extracellular domain of a human TSHR and a monomeric non-human immunoglobulin Fc domain, or fragment thereof, or a bacterial maltose binding protein (MBP). Also disclosed is a kit for carrying out the method of the invention. In a preferred embodiment, the method of the invention is a sandwich immunoassay.

To provide a humanized rodent that expresses a heavy chain containing a VL domain. [Solution] A non-human animal, tissue, cell, and genetic material is provided which includes a modification of an endogenous non-human heavy chain immunoglobulin sequence and contains functional ADAM6 activity in a rodent (e.g., mouse), wherein the non-human animal rearranges the human immunoglobulin light chain gene segment in relation to the heavy chain constant domain and expresses an immunoglobulin-like molecule which contains a human immunoglobulin light chain variable domain fused to the heavy chain constant domain and is a cognitive of a human immunoglobulin light chain variable domain fused to the light chain constant domain.

The invention relates to an anti-ovarian antibody chemiluminiscence kit and a preparation method thereof. The kit comprises amino magnetic beads coated with anti-ovarian antibody recombinant protein, anti-human immune globulin labeled by alkaline phosphatase, an anti-ovarian antibody calibrator and a chemiluminiscence substrate. The method has the beneficial effects that the 7-day acceleration stability of the AOAb coated amino magnetic bead is improved to 95% or above, the signal-to-noise ratio is high, the correlation coefficient is greater than 0.999, the test repeatability CV is less than 3.5%, the reagent correlation and the magnetic bead stability can be better improved, and the test result is ensured to be accurate. By optimizing the amino magnetic bead cross-linking agent, 60 clinical samples are tested and compared with the result of a comparison manufacturer, the total coincidence rate is as high as 98%, and false positive can be effectively reduced. Meanwhile, a detection system is formed by matching with a Guilin superior chemiluminescence immunoassay analyzer IA-260, the testing amount per hour reaches 130 tests, and compared with a traditional colloidal gold immunochromatography method and a traditional enzyme-linked immunosorbent assay method, the detection speed is greatly increased, and the result optimization accuracy is greatly improved.

The application discloses a nanobody 3A2 for human adenovirus and a preparation method and application thereof, and belongs to the technical field of biotechnology, and particularly relates to a nanobody 3A2 for human adenovirus and a preparation method and application thereof. The nanobody or antigen-binding fragment containing the nanobody for targeting human adenovirus has three complementarity determining regions CDR1, CDR2 and CDR3; the amino acid sequence of CDR1 is SEQ ID No. 1, the amino acid sequence of CDR2 is SEQ ID No. 2, and the amino acid sequence of CDR3 is SEQ ID No. 3. The nanobody 3A2 is fused with an Fc segment (hFc) of human immunoglobulin to obtain a fusion protein, and the obtained h3A2-hFc can effectively inhibit infection of human adenovirus type 55, and the IC 50 is 0.62 nM.

Provided are human anti-thymocyte globulin (ATG) products, and methods of making and using the same. In particular, the disclosure provides an ungulate-derived polyclonal immunoglobulin, comprising a population of fully human or substantially human immunoglobulins. The population of fully human or substantially human immunoglobulins specifically binds human thymocytes, T cells, B cells, and / or monocytes. Such compositions may be made by immunization of transgenic animals having a human Ig locus with human thymocytes. This method generates polyclonal immunoglobulin with yield, purity, and antigen specificity that enable the use of this product in medical applications.

A combination drug contains hypoxanthine and human immunoglobulin (HIg). HIg has a therapeutic effect on radiation injuries, and the combination of hypoxanthine and HIg can further enhance this therapeutic effect. The combination drug can be administered to patients undergoing radiotherapy and to those who accidentally have excessive irradiation.

The application discloses a fusion protein ABD / Fc / IL-2, a coding gene thereof, a preparation method and application, and belongs to the field of biopharmaceuticals. The fusion protein ABD / Fc / IL-2 provided comprises a human serum albumin binding domain ABD, a full-length human immunoglobulin Fc segment and IL-2 or a mutant thereof. The fusion protein can effectively stimulate the proliferation of immune cells in the body, enhance the immunity of the body, and has high biological activity and a long plasma circulation half-life, or has high biological activity, a long plasma circulation half-life and low toxic side effects. The fusion protein can be used for preparing medicines for treating various diseases such as malignant tumors, infectious diseases and low immunity of the body, and can play an important role in the fields of medicine and biopharmaceuticals.

The plasma mixing device for tetanus human immune globulin comprises a bottom plate, a sliding table is slidably connected to the top of the bottom plate, a driving assembly is arranged in the sliding table, a supporting rod is arranged at the top of the driving assembly and rotatably connected with the sliding table, a guiding assembly is arranged at the top of the supporting rod, and the guiding assembly is rotatably connected with the sliding table. A transmission rod is arranged at the top of the guide assembly, a supporting table is rotationally connected to the outer side of the transmission rod, the bottom of the supporting table is fixedly connected with the top of the sliding table, a cylinder is fixedly connected to the top of the transmission rod, a screw cap is in threaded connection with the top of the cylinder, and a disc is arranged on the rear side of the driving assembly. A cylindrical rod is arranged on the rear side of the disc, a limiting frame is connected to the rear side of the cylindrical rod in a sliding mode, and the problems that a simple stirring or shaking mode is mostly adopted in an existing uniform mixing device and method, the efficiency of the mode is low, uneven distribution of components in plasma is easily caused, and the quality and the effect of a final product are affected are effectively solved.

The present invention provides a preparation process of a human immunoglobulin preparation for intravenous injection, which belongs to the field of protein production technology. The preparation process provided by the present invention comprises: dissolving the component II+III precipitate with a precipitation dissolving solution containing 0.8%-1.2% sodium dihydrogen phosphate and 0.66%-1.0% sodium citrate, adding low-temperature ethanol, adding a filter-aid mixed powder for filter pressing, wherein the weight ratio of diatomaceous earth, cellulose and silicon dioxide in the filter-aid mixed powder is 4-5:2-3:1-1.5. The human immunoglobulin preparation for intravenous injection prepared by the present invention has an anti-complement activity of only 5%-7%, has good thermal stability, and a purity of up to 99.3%-100%.

The invention relates to the technical field of immune globulin preparation systems, in particular to a human immune globulin preparation system for subcutaneous injection, which comprises the following modules: a visualization module, an intelligent monitoring module, a power supply module, a central control management module and an execution module, the central control management module is in communication connection with the visualization module, the intelligent monitoring module and the execution module, and the intelligent monitoring module is in communication connection with the visualization module. According to the full-automatic intelligent production system, a large number of production tasks can be completed in a short time through the automation and intelligentization technology, compared with traditional production, the production efficiency can be improved by several times or even dozens of times, the labor cost is greatly reduced, and in the low-temperature production environment with the high cleanliness requirement, the production efficiency is greatly improved. The full-automatic intelligent production line can reduce manual operation and reduce operation and pollution risks.

The invention relates to the technical field of preparation and application of bioindustry peptides and immune globulins, in particular to a preparation method of human immune globulins stored at normal temperature. The preparation method comprises the following steps: treating an FI + II + III / FII + III precipitation dissolving solution by using fumed silica Aerosil380, and adsorbing and removing unstable substances such as lipoprotein and lipoid in the precipitation dissolving solution so as to reduce protein polymerization caused by the unstable substances in a long-term normal-temperature storage process, so that the long-term stability of the human immune globulin is improved; l-proline is added into the final formula of the product to reduce the polymerization and oxidation effects of protein in the storage process, trace Tween 80 is added into the final formula of the product to reduce the viscosity of the protein, and the operation conditions of adding the L-proline through ultrafiltration and concentration are further optimized to further prevent or reduce the polymerization of the protein so as to realize normal-temperature storage of the human immune globulin.

The present application relates to the technical field of biological medicine, and more particularly to a multifunctional antibody K1932 binding human CD19, CD3 and Fc gamma R, wherein the multifunctional antibody is composed of a bivalent Fab fragment specifically recognizing CD19 on the surface of B lymphocyte, a bivalent single-chain antibody recognizing CD3 molecule on the surface of T lymphocyte, and a human immunoglobulin Fc domain binding with Fc receptor, wherein the single-chain antibody recognizing CD3 molecule is connected with the C-terminal of Fab light chain through a connecting peptide Linker1, and the heavy chain and the light chain of the CD3 single-chain antibody are connected by a flexible Linker2; the biological macromolecule with the three functional domains is a highly directional immunotherapy drug, which is suitable for injection administration, can guide T cells to attack CD19-positive B lymphocytes, and the Fc domain is combined with Fc gamma R, so that the in-vivo half-life of the biological macromolecule is adjusted and the unnecessary influence on normal cells is reduced.

The invention provides a method for preparing human immunoglobulin for intravenous injection by a sodium caprylate precipitation process. Comprising the following steps: raw material plasma preparation, FI reaction, FI + II + III separation, FI + II + III filter pressing, FI + II + III precipitation and dissolution, sodium caprylate precipitation reaction, filter pressing filtration, ultrafiltration concentration, DEAE chromatography, TMAE chromatography, ultrafiltration dialysis, nanofiltration, low-pH incubation, ultrafiltration concentration (stock solution), semi-finished product solution preparation, degerming and split charging to obtain the human immunoglobulin finished product for intravenous injection. According to the process, plasma is adopted as an initial raw material, FI + II + III is prepared through an ethanol reaction, and albumin, IgA, IgM and other impure proteins are removed more thoroughly through a method of sodium caprylate precipitation primary purification and multi-step chromatography refining purification, so that the risk of hemolysis and adverse reaction after infusion is reduced. Meanwhile, saccharides are not added into the preparation as a stabilizer, and safer glycine is used as the stabilizer, so that the kidney load of a patient is reduced.

This invention relates to the field of irregular antibody detection technology, specifically to an automated washing microfluidic chip for irregular antibody detection. The chip includes a chip body, a membrane, and a detection component comprising a sample application chamber and a detection chamber arranged sequentially away from the center of rotation. The sample application chamber and the detection chamber are connected by a washing channel. The detection component is pre-filled with a washing solution that can fill the detection chamber and the washing channel under centrifugation. The washing solution contains anti-human immunoglobulin that reacts with erythrocyte antigen-antibody complexes. The specific gravity of the washing solution is configured to be greater than the specific gravity of the sample to be tested but less than the specific gravity of the erythrocyte antigen. This configuration solves the problems of cumbersome procedures, excessive time consumption, high operator dependence, and difficulty in standardization caused by multiple manual washing steps required in traditional test tube methods for detecting irregular antibodies. It effectively ensures detection sensitivity and accuracy and reduces the false negative rate.

The purpose of the present invention is to provide, as a platform technique that may serve as preparation for pandemics, a rapid antibody production technique in which a non-human animal having a human antibody gene is used. More specifically, the purpose of the present invention is to provide an immunization method with which it is possible to induce, in a short period of time, a high antigen-binding ability of an antibody or a high antibody titer of an antiserum, and a method for producing a human antibody / antiserum with which it is possible to rapidly produce a wide range of neutralizing antibodies.　(1) An immunization method for rapidly inducing a human monoclonal antibody having a high ability to bind to a desired antigen or a human polyclonal antibody having a high antibody titer, the method comprising a step for immunizing a non-human animal a plurality of times with a desired antigen or a nucleic acid encoding the antigen within 30 days from the first immunization, the non-human animal having a human antibody gene or locus, and the non-human animal being such that an endogenous gene or locus of the non-human animal corresponding to the human antibody gene or locus is disrupted or deleted, or mutated so as to result in a loss of expression or low expression. (2) A method for producing a human antibody against a desired antigen using a non-human animal, the method comprising: an immunization step for immunizing the non-human animal with the antigen or a nucleic acid encoding the antigen; a human immunoglobulin-positive B cell isolation step for isolating B cells that are human immunoglobulin-positive from a tissue of the immunized non-human animal; an antibody base sequence acquisition step for acquiring the base sequences of antibody light-chain mRNA-derived cDNA and antibody heavy-chain mRNA-derived cDNA prepared from the isolated B cells; and an antibody production step for producing an antibody on the basis of the acquired antibody base sequence, the non-h

The invention relates to the technical field of biological pharmacy, and discloses a tetanus human immune globulin preparation method, which comprises: S1, plasma pretreatment: taking anticoagulant plasma with a tetanus antibody titer of more than or equal to 10 IU / mL, and carrying out filtration treatment on the anticoagulant plasma; an improved self-adaptive algorithm is adopted to determine various parameters in the extraction process, S3, composite chromatographic purification, S4, collaborative virus inactivation, and S5, preparation preparation. According to the method, through linkage of an improved adaptive particle swarm-response surface coupling algorithm, first, 40 groups of initial sample sets are constructed by Latin hypercube sampling, a double-response surface model (R2gt; 0.95) is fitted by using a quadratic polynomial, and then a particle swarm depends on the model to predict fitness and dynamically adjust inertia weight balance optimization. By means of the linkage, the TT-IgG extraction rate is increased by 13-15%, the impurity protein removal rate is increased by 14-16%, RSD of three parallel experiments is smaller than or equal to 3%, and it is guaranteed that parameters are accurate and repeated.

The purpose of the present invention is to provide a novel HVEM-binding protein. The present invention provides a human HVEM-binding protein comprising at least one immunoglobulin single variable region, wherein: the immunoglobulin single variable region includes complementarity determining regions 1-3 which have the amino acid sequence of SEQ ID NO: 1, the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of SEQ ID NO: 3, respectively; and the immunoglobulin single variable region is a humanized VHH. The protein according to the present invention may further comprise a human immunoglobulin Fc region or a human serum albumin-binding protein, and the immunoglobulin Fc region may be an Fc region of human IgG4.

The application discloses a nanobody 2C10 for human adenovirus and a preparation method and application thereof, and belongs to the technical field of biotechnology, and particularly relates to a nanobody 2C10 for human adenovirus and a preparation method and application thereof. The nanobody or antigen-binding fragment containing the nanobody for targeting human adenovirus has three complementarity determining regions CDR1, CDR2 and CDR3; the amino acid sequence of CDR1 is SEQ ID No. 1, the amino acid sequence of CDR2 is SEQ ID No. 2, and the amino acid sequence of CDR3 is SEQ ID No. 3. The nanobody 2C10 is fused with an Fc segment (hFc) of human immunoglobulin to obtain a fusion protein, and the obtained h2C10-hFc can effectively inhibit infection of human adenovirus type 55, and the IC 50 is 5.33 nM.

The invention provides a method for detecting ADCP activity of human immune globulin products in the field of infectious diseases, and belongs to the technical field of immunological detection. The invention provides an accurate and visual immunoglobulin product antibody-dependent cell-mediated phagocytosis biological activity detection method through the steps of target cell screening, efficiency-target ratio optimization, test sample concentration gradient optimization and the like. The accurate detection on the biological activity of the antibody-dependent cell-mediated phagocytosis of the human immunoglobulin product is realized. The detection method disclosed by the invention is intuitive and high in precision and accuracy, fills the blank of detection of the antibody-dependent cell-mediated phagocytosis of the human immunoglobulin products at present, and has important significance in improving the quality control and clinical application of the human immunoglobulin products.

The invention discloses a technology for removing viruses from tetanus human immune globulin through a nano film. The process comprises the following steps: pretreating a feed liquid, so that the protein concentration of the feed liquid is 50-60g / L, the pH is 3.8-4.4, and the feed liquid contains 90-110g / L maltose and 50-150mmol / L sodium chloride; then, the feed liquid is subjected to two-stage filtration through a 0.1-micron nylon pre-filtration membrane bag with negative charges and a 20-nm regenerated cellulose (RC) virus removal membrane bag in sequence. According to the process, through optimizing the physical and chemical state of the feed liquid and the synergistic effect of the feed liquid and the functionalized filter membrane, the protein aggregation is effectively inhibited, the membrane pollution is reduced, the virus removal effect is ensured not to be lower than 4log10, the protein load of the RC membrane is remarkably improved to be more than 200L / m, and the product purity is more than or equal to 98%. The invention solves the technical problems of low flux and easy blockage of high-concentration immune globulin in small-aperture virus removal filtration, and is suitable for efficient, safe and large-scale production of blood products.

The invention belongs to the field of immunological detection, and provides an anti-human immunoglobulin lambda type light chain antibody 6B6 and application thereof. The monoclonal antibody 6B6 with good specificity and stability is obtained after fusion screening is conducted on natural human IgG and immune mice, the monoclonal antibody 6B6 can specifically recognize human immune globulin lambda type light chains, the antibody is verified through an immunoblotting method, and the antibody 6B6 shows good specificity and sensitivity. In addition, the human IgG-Fc is purified by using the antibody, and related reagents and kits for purifying the human IgG-Fc can be developed subsequently. The monoclonal antibody can also be used as a detection raw material for medical diagnosis, and has a good application prospect in detection of human immune globulin (especially a human immune globulin lambda type light chain).

The invention belongs to the technical field of medical biology, and particularly relates to an EBV (Epstein-Barr Virus) neutralizing antibody-specifically-immune plasma high-throughput screening method and application thereof. EB virus envelope glycoprotein gp350 is selected as a screening target antigen, EBV specific plasma containing a high-titer EBV neutralizing antibody is rapidly screened in a high-throughput mode and used for preparing EBV specific human immune globulin, the titer of the EBV neutralizing antibody is obviously higher than that of listed intravenous gamma-C products, and the content of the EBV neutralizing antibody is about 4-8 times that of the EBV neutralizing antibody with the same concentration. The method provided by the invention can realize large-scale collection of EBV specific plasma through rapid high-throughput screening, reduces the workload of plasma screening, is suitable for large-scale production of EBV specific human immune globulin, and has a good application prospect.

The invention provides a human immunoglobulin preparation for subcutaneous injection and a preparation method thereof. The preparation method comprises the following steps: S1) performing FI reaction, FI + II + III separation and purification on plasma to obtain a stock solution before concentration; s2) performing ultrafiltration concentration on the stock solution before concentration by utilizing unidirectional tangential flow ultrafiltration to obtain an ultrafiltration concentrated solution; and S3) mixing the ultrafiltration concentrated solution, the protective agent and the diluent to obtain the human immune globulin preparation for subcutaneous injection. The problem that a high-concentration human immunoglobulin preparation for subcutaneous injection prepared in the prior art is low in activity can be solved, and the method is suitable for the technical fields of biological pharmacy and blood products.