WO2023155132A1 - Anticorps monoclonal de protéine rac1, son procédé de préparation et son utilisation - Google Patents

Anticorps monoclonal de protéine rac1, son procédé de préparation et son utilisation Download PDF

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Publication number
WO2023155132A1
WO2023155132A1 PCT/CN2022/076830 CN2022076830W WO2023155132A1 WO 2023155132 A1 WO2023155132 A1 WO 2023155132A1 CN 2022076830 W CN2022076830 W CN 2022076830W WO 2023155132 A1 WO2023155132 A1 WO 2023155132A1
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monoclonal antibody
rac1 protein
rac1
cells
preparation
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PCT/CN2022/076830
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English (en)
Chinese (zh)
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张浩洋
石坚
徐爱华
朱国方
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绍兴守仁医疗健康科技有限公司
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Priority to PCT/CN2022/076830 priority Critical patent/WO2023155132A1/fr
Publication of WO2023155132A1 publication Critical patent/WO2023155132A1/fr

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10Cells modified by introduction of foreign genetic material
    • C12N5/12Fused cells, e.g. hybridomas
    • C12N5/16Animal cells
    • C12N5/163Animal cells one of the fusion partners being a B or a T lymphocyte
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/573Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/577Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens

Definitions

  • the present application relates to the technical field of biological immunology, in particular to a RAC1 protein monoclonal antibody and its preparation method and application.
  • Rho family acts as a "molecular switch" in some basic functions of cells, and is involved in cell movement, actin reorganization, malignant transformation of tumors, invasion and metastasis, regulation of transcription factors, cell apoptosis, and tumor blood vessels generation process.
  • the protein encoded by the Rac1 gene is GTPase, which belongs to the RAS superfamily of small GTP-binding proteins; it plays an important role in cell motility and adhesion, cell proliferation, differentiation and apoptosis, tumor invasion and metastasis, and immune regulation.
  • immunological detection methods are used to detect RAC1 protein, wherein the immunological detection methods include ELISA, fluorescent immunosorbent, chemiluminescence and immunochromatography.
  • the difficulty of immunological detection lies in finding antibodies with high accuracy and good stability.
  • the antibodies used for RAC1 protein are all polyclonal antibodies. Polyclonal antibodies refer to the same antigenic determinant. Antibodies can also be produced by several clones in the body, forming a mixture of several monoclonal antibodies, resulting in In addition, the specificity of the detection of RAC1 protein is poor, and false positives are prone to occur, which is not conducive to accurate judgment.
  • One of the purposes of the embodiments of the present application is to provide a RAC1 protein monoclonal antibody and its preparation method and application, aiming to solve the poor specificity of the RAC1 protein polyclonal antibody in the prior art, which is not conducive to accurate and rapid detection of RAC1 protein The problem.
  • a RAC1 protein monoclonal antibody comprises: the amino acid sequence of the heavy chain variable region of the RAC1 protein monoclonal antibody sequence is SEQ ID NO.1, the amino acid sequence of the light chain variable region of the RAC1 protein monoclonal antibody sequence is SEQ ID NO.2.
  • the monoclonal antibody to RAC1 protein belongs to IgG subclass.
  • the relative molecular mass of the RAC1 protein monoclonal antibody is 150-160 kDa.
  • the antibody titer of the RAC1 protein monoclonal antibody is 10E4-10E5.
  • a method for preparing a monoclonal antibody to RAC1 protein includes the following steps:
  • Spleen cells and myeloma cells of immunized mice were cultured separately, and subjected to cell fusion treatment, and screened by indirect ELISA and indirect competition ELISA to obtain hybridoma cell lines;
  • the strong positive monoclonal cells were inoculated into mice, and the monoclonal antibody to RAC1 protein was prepared by inducing ascites in vivo.
  • the protein concentration of the RAC1 protein solution is 50-55 mg/mL, and the pH of the RAC1 protein solution is 7.4-7.5.
  • the step of using the RAC1 protein solution for immunizing the mice includes performing primary immunization and booster immunization on the mice with the RAC1 protein solution, wherein the number of booster immunizations is 3-4 times.
  • the step of initial immunization includes: configuring the RAC1 protein solution to a concentration of 0.1 ⁇ g/ ⁇ L-10 ⁇ g/ ⁇ L antigen solution, mixing with an equal volume of complete Freund’s adjuvant to obtain the first antigen stock solution, using the first antigen stock solution to immunize mice for the first time.
  • the step of boosting immunization includes: configuring the RAC1 protein solution to a concentration of 0.1 ⁇ g/ ⁇ L-10 ⁇ g/ ⁇ L antigen solution, mixing with an equal volume of Freund’s incomplete adjuvant to obtain the second Antigen stock solution, the mice were boosted with the second antigen stock solution.
  • the steps of culturing the spleen cells and myeloma cells of the immunized mice respectively, and performing cell fusion treatment include: providing the immunized mice, collecting the spleens of the immunized mice and grinding them to obtain the spleen cells and provide myeloma cells for culture, keep the myeloma cells in the logarithmic growth stage, and make myeloma cell suspension; combine the spleen cell suspension and myeloma cell suspension and centrifuge to collect the precipitate, and use polyethylene Diol is used for cell fusion treatment to obtain fused cells.
  • the cell fusion treatment includes the following steps: absorbing the cell suspensions containing 6-6.5 ⁇ 107 splenocytes and 1.2-1.3 ⁇ 107 hybridoma cells respectively, and putting them together into centrifuge tubes , centrifuge at 1000-1200 rpm for 5-6 min, discard the supernatant, and collect the cell pellet;
  • the number of the spleen cells and the hybridoma cells is (4.8-5):1.
  • the step of adding 25 to 26 mL of DMEM medium to the cell suspension within 5 to 6 minutes includes: adding 1 mL of DMEM medium within 1 minute, adding 4 mL of DMEM medium within 2 minutes, and adding the remaining 20 mL of DMEM medium within 3 minutes Added.
  • a monoclonal antibody to RAC1 protein or the use of the monoclonal antibody to RAC1 protein prepared by the method for preparing the monoclonal antibody to RAC1 protein is provided in the preparation of a detection reagent for RAC1 protein.
  • kits for detecting RAC1 protein includes a monoclonal antibody to RAC1 protein or a monoclonal antibody to RAC1 protein prepared by a method for preparing a monoclonal antibody to RAC1 protein.
  • the beneficial effect of the RAC1 protein monoclonal antibody provided in the embodiment of the present application is that the sequence of the monoclonal antibody includes: the amino acid sequence of the heavy chain variable region of the RAC1 protein monoclonal antibody sequence is SEQ ID NO.1, and the RAC1 protein monoclonal The amino acid sequence of the light chain variable region of the antibody sequence is SEQ ID NO.2; the RAC1 protein monoclonal antibody provided has strong specificity, can accurately and quickly detect RAC1 protein, specifically binds to RAC1 protein, and is guaranteed to bind to RHO There is no cross-reaction with other proteins in the protein family, which is conducive to wide application in immunological detection.
  • the beneficial effect of the preparation method of the RAC1 protein monoclonal antibody is that the preparation method uses the RAC1 protein as a raw material to prepare the RAC1 protein monoclonal antibody. Tumor cells are fused, screened by indirect ELISA and indirect competitive ELISA to obtain strong positive monoclonal cells; and then the ascites induced in vivo method is used to prepare the RAC1 protein monoclonal antibody.
  • the preparation method is clear, easy to operate, and the synthesis method is simple.
  • the synthesis efficiency is high, and the prepared RAC1 protein monoclonal antibody can specifically bind to the RAC1 protein, and the antibody titer ensures no cross-reaction with other proteins of the RHO protein family, which is conducive to wide application in immunological detection.
  • the beneficial effect of the application of the RAC1 protein monoclonal antibody provided in the examples of the present application or the RAC1 protein monoclonal antibody prepared by the preparation method of the RAC1 protein monoclonal antibody in the preparation of RAC1 protein detection reagents is: due to the RAC1 protein monoclonal antibody It has high specificity, can accurately bind to RAC1 protein during application, and ensures no cross-reaction with other proteins of the RHO protein family, which is conducive to wide application.
  • the beneficial effect of the kit for detecting the RAC1 protein provided in the embodiment of the present application is that the kit includes the RAC1 protein monoclonal antibody or the RAC1 protein monoclonal antibody prepared by the method for preparing the RAC1 protein monoclonal antibody, because the RAC1 protein monoclonal antibody
  • the cloned antibody has high specificity, can accurately bind to the RAC1 protein during application, and ensures no cross-reaction with other proteins of the RHO protein family, which is conducive to widespread use.
  • the first aspect of the embodiment of the present application provides a RAC1 protein monoclonal antibody.
  • the sequence of the RAC1 protein monoclonal antibody includes: the amino acid sequence of the heavy chain variable region of the RAC1 protein monoclonal antibody sequence is SEQ ID NO.1, and the RAC1 protein monoclonal antibody sequence is SEQ ID NO.1.
  • the amino acid sequence of the light chain variable region of the cloned antibody sequence is SEQ ID NO.2.
  • the sequence of the monoclonal antibody includes: the amino acid sequence of the heavy chain variable region of the monoclonal antibody sequence to the RAC1 protein is SEQ ID NO.1, and the monoclonal antibody to the RAC1 protein The amino acid sequence of the light chain variable region of the sequence is SEQ ID NO.2; the RAC1 protein monoclonal antibody provided has strong specificity, can accurately and quickly detect RAC1 protein, specifically binds to RAC1 protein, and is guaranteed to bind to RHO protein There is no cross-reaction with other proteins in the family, which is conducive to wide application in immunological detection.
  • sequence of the RAC1 protein monoclonal antibody includes: the amino acid sequence of the heavy chain variable region of the RAC1 protein monoclonal antibody sequence is SEQ ID NO.1, and the amino acid sequence of the light chain variable region of the RAC1 protein monoclonal antibody sequence is SEQ ID NO.2.
  • SEQ ID NO.1 is EVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWRGGSTDYNTAFMSRLRITKDNSKSQVFFKMNSLQADDTAIYYCAKNSYGSRNFDVWGAGTTVTVSS;
  • SEQ ID NO.2 is DIVMTQSPATLSVTPGDSVSLSCRASQSISNNLHWY QQKSHESPRLLIKYVSQSISGIPSRFSGSGSGTDFTLSINSVETEDFGMYFCQQSNSWPVTFGAGTKLELK.
  • the RAC1 protein monoclonal antibody is of the IgG subclass.
  • the IgG subclass refers to the formation of immune complexes between IgG1-IgG3 and antigens, activating complement through the classical pathway, and exerting the functions of bacteriolysis and cell lysis.
  • the provided monoclonal antibody to RAC1 protein activates complement through the classical pathway, and exerts the functions of bacteriolysis and cell lysis.
  • the relative molecular mass of the RAC1 protein monoclonal antibody is 150-160 kDa.
  • the relative molecular mass of the provided RAC1 protein monoclonal antibody is small, which is conducive to rapid preparation.
  • the antibody titer of the RAC1 protein monoclonal antibody is 10E4-10E5, and the antibody titer of the provided RAC1 protein monoclonal antibody is higher, which is conducive to specific binding to the RAC1 protein, thereby improving the interaction with the RAC1 protein Effect.
  • the second aspect of the embodiment of the present application provides a method for preparing a monoclonal antibody to the RAC1 protein.
  • the method for preparing the monoclonal antibody to the RAC1 protein includes the following steps:
  • the strong positive monoclonal cells were inoculated into mice, and the monoclonal antibody to RAC1 protein was prepared by in vivo induction of ascites.
  • the preparation method of the RAC1 protein monoclonal antibody uses the RAC1 protein as a raw material to prepare the RAC1 protein monoclonal antibody.
  • the immune spleen cells and the mouse myeloma Cell fusion using indirect ELISA and indirect competitive ELISA to screen, to obtain strong positive monoclonal cells; then use in vivo induced ascitic fluid method to prepare monoclonal antibody to RAC1 protein, the preparation method is clear, easy to operate, simple synthesis method, synthetic
  • the efficiency is high, and the prepared RAC1 protein monoclonal antibody can specifically bind to the RAC1 protein, and the antibody titer is guaranteed to have no cross-reaction with other proteins of the RHO protein family, which is conducive to wide application in immunological detection.
  • step S01 the RAC1 protein is dissolved in a buffer to obtain a RAC1 protein solution, and the RAC1 protein solution is used to immunize mice to obtain immunized mice and immune serum.
  • the provided buffer is PBS buffer, which is used to dissolve the RAC1 protein to obtain the RAC1 protein solution.
  • the protein concentration of the RAC1 protein solution is 50-55 mg/mL, and the pH of the RAC1 protein solution is 7.4-7.5.
  • the obtained RAC1 protein solution has a protein concentration of 50 mg/mL and a pH of 7.4.
  • the step of using the RAC1 protein solution for immunizing mice includes using the RAC1 protein solution to perform initial immunization and booster immunization on the mice, wherein the number of booster immunizations is 3-4 times.
  • the step of initial immunization includes: configuring the RAC1 protein solution to a concentration of 0.1 ⁇ g/ ⁇ L-10 ⁇ g/ ⁇ L antigen solution, mixing with an equal volume of Freund’s complete adjuvant to obtain the first antigen stock solution, using the first The first antigen stock solution was used to immunize the mice for the first time;
  • the steps of boosting immunization include: configuring the RAC1 protein solution to an antigen solution with a concentration of 0.1 ⁇ g/ ⁇ L to 10 ⁇ g/ ⁇ L, mixing it with an equal volume of Freund’s incomplete adjuvant to obtain a second antigen stock solution, and using the second antigen stock solution for small Rats were boosted.
  • immunized mice are obtained, and immune serum of the immunized mice is obtained.
  • the immune serum is screened by indirect ELISA and indirect competitive ELISA, and the screening step includes: using RAC1 protein as the coating source, after the serum is serially diluted, the titer of the antiserum is determined by the method of indirect ELISA; if the serum The titer is higher than 10E4, and the serum titer is determined by indirect competition ELISA with RAC1 protein standard substance, and the mouse with the highest affinity between serum and RAC1 protein is selected for the preparation of monoclonal antibody.
  • the serial dilution of the serum includes: 2-3 times of serial dilution using a PBS solution containing 5% skim milk by mass fraction.
  • step S02 the splenocytes and myeloma cells of the immunized mice were respectively cultured, and subjected to cell fusion treatment and screening to obtain hybridoma cell lines.
  • an immunized mouse is provided, the spleen of the immunized mouse is collected and ground to obtain a spleen cell suspension, and myeloma cells are provided for culture, and the myeloma cells are kept in the logarithmic growth phase to form a myeloma Cell suspension: the spleen cell suspension and the myeloma cell suspension are combined and centrifuged to collect the precipitate, and polyethylene glycol is used for cell fusion treatment to obtain fused cells.
  • the cell fusion treatment includes the following steps:
  • the number of spleen cells and hybridoma cells is (4.8-5):1.
  • the step of adding 25 to 26 mL of DMEM medium to the cell suspension within 5 to 6 minutes includes: adding 1 mL of DMEM medium within 1 minute, adding 4 mL of DMEM medium within 2 minutes, and adding the remaining 20 mL of DMEM medium within 3 minutes Added.
  • the fused cells are screened to obtain hybridoma cell lines.
  • the step of screening the fused cells includes: detecting the culture supernatants of all clonal growth wells of the fused cells by indirect competition ELISA, and selecting cells with high OD value, high inhibition rate and small number of clones The wells were cloned and expanded for culture; the hybridoma cells were screened by indirect ELISA and indirect competition ELISA, and the hybridoma cell lines with high supernatant titer, good competitive inhibition effect and vigorous growth were selected for the next test.
  • step S03 the hybridoma cell line is subjected to cell cloning to obtain strongly positive monoclonal cells.
  • the obtained hybridoma cell line is cloned by limiting dilution method to obtain strongly positive monoclonal cells.
  • step S04 the strongly positive monoclonal cells were inoculated into mice, and the monoclonal antibody to RAC1 protein was prepared by in vivo induction of ascites.
  • the method of inducing ascites in vivo is used to prepare monoclonal antibodies, inoculating strong positive monoclonal cells into the mice, and after 10 to 14 days, the ascites is collected and centrifuged to collect the supernatant to obtain monoclonal antibodies to RAC1 protein, which are aliquoted. Store frozen for later use.
  • the third aspect of the embodiment of the present application provides the application of the RAC1 protein monoclonal antibody or the RAC1 protein monoclonal antibody prepared by the preparation method of the RAC1 protein monoclonal antibody in the preparation of the RAC1 protein detection reagent.
  • a RAC1 protein monoclonal antibody provided by the third aspect of the embodiment of the present application or the RAC1 protein monoclonal antibody prepared by the preparation method of the RAC1 protein monoclonal antibody in the preparation of RAC1 protein detection reagents, because the RAC1 protein monoclonal
  • the antibody has high specificity, can accurately bind to the RAC1 protein during application, and ensures no cross-reaction with other proteins of the RHO protein family, which is conducive to widespread use.
  • the fourth aspect of the embodiment of the present application provides a kit for detecting RAC1 protein.
  • the kit includes a monoclonal antibody to RAC1 protein or a monoclonal antibody to RAC1 protein prepared by a method for preparing a monoclonal antibody to RAC1 protein.
  • kits for detecting RAC1 protein provided in the fourth aspect of the embodiment of the present application, includes RAC1 protein monoclonal antibody or RAC1 protein monoclonal antibody prepared by the method for preparing RAC1 protein monoclonal antibody, because RAC1 protein
  • the monoclonal antibody has high specificity, can accurately bind to the RAC1 protein during application, and guarantees no cross-reaction with other proteins of the RHO protein family, which is conducive to widespread use.
  • sequence of the RAC1 protein monoclonal antibody includes: the amino acid sequence SEQ ID NO.1 of the heavy chain variable region of the RAC1 protein monoclonal antibody sequence and the amino acid sequence SEQ ID NO.1 of the light chain variable region of the RAC1 protein monoclonal antibody sequence .2.
  • the preparation method of RAC1 protein monoclonal antibody is as follows:
  • Antigen preparation Weigh 100 mg RAC1 protein and dissolve it in 1.8 mL PBS, adjust the pH to 7.4, and dilute to 2 ml to prepare a 50 mg/ml RAC1 protein solution.
  • mice Take several healthy BALB/c mice aged 6-8 weeks and number them separately, take 50mg/ml antigen solution, mix with an equal volume of complete Freund's adjuvant, fully emulsify, and immunize mice at 100 ⁇ g/mouse for initial immunization, Afterwards, boost immunization once every 2 to 4 weeks.
  • RAC1 protein was mixed with physiological saline to make 0.1 ⁇ g/ ⁇ L-10 ⁇ g/ ⁇ L antigen solution, mixed with an equal volume of incomplete Freund’s adjuvant, fully emulsified, and 100 ⁇ g/ ⁇ L Multiple subcutaneous injections on the back of each mouse.
  • mice with the highest affinity between serum and RAC1 protein were taken, and 3 days after booster immunization, the eyeballs were picked for blood collection, and the serum was collected for later use.
  • the mice were killed, and the spleen was aseptically removed, and the spleen was ground to obtain a spleen cell suspension. Wash 2-3 times with DMEM medium, add a certain amount of DMEM medium to resuspend the cells, stain and count.
  • the revived SP2/0 myeloma cells were cultured in complete medium containing 10% (v/v) fetal calf serum. One day before confluence, cells were exchanged and cells were kept in logarithmic growth phase.
  • the steps of cell fusion include:
  • the culture supernatant of all clone growth wells can be detected by indirect competitive ELISA method, and the clones with high OD value, high inhibition rate and small number of clones can be selected. Small cell wells were cloned and expanded for culture.
  • the hybridoma cells were screened by indirect ELISA and indirect competition ELISA as follows:
  • Indirect ELISA primary screening Add 1 ⁇ g/mL RAC1 protein solution diluted with coating buffer, 100 ⁇ L/well to coat the ELISA plate overnight; after washing the plate, block with PBS solution containing 5% skimmed milk, 150 ⁇ L/well, incubate at 37°C 2h; add cell culture supernatant 30 ⁇ L/well after washing the plate, add PBST70 ⁇ L/well, incubate at 37°C for 1h, wash the plate 5 times; add enzyme-labeled goat anti-mouse secondary antibody, 100 ⁇ L/well, incubate at 37°C for 1h, wash the plate 5 times; add tetramethylbenzidine TMB chromogenic solution, 100 ⁇ L per well, 37°C, 10-15 min; add 50 ⁇ L stop solution (2M H2SO4), measure the absorbance value at 450 nm with an enzyme-linked immunosorbent assay instrument; measure the cell supernatant Whether it is positive (when the OD450nm value of the positive control
  • the obtained hybridoma cell line is cell cloned by the limiting dilution method to obtain strongly positive monoclonal cells.
  • mice The strong positive monoclonal cells were inoculated into mice, and the monoclonal antibody to RAC1 protein was prepared by inducing ascites in vivo.
  • the monoclonal antibody was prepared by inducing ascites in vivo, and the strong positive monoclonal cells were inoculated into the mice. After 10 to 14 days, the ascites was collected and centrifuged to collect the supernatant to obtain the monoclonal antibody of RAC1 protein, which was subpackaged and frozen for future use.
  • the preparation method of RAC1 protein polyclonal antibody comprises the following steps:
  • the titer of the RAC1 protein monoclonal antibody prepared in Example 1 reached 10E4 ⁇ 10E5, and the titer of the RAC1 protein polyclonal antibody prepared in Comparative Example 1 was XXX. It can be seen that the RAC1 protein monoclonal antibody prepared in Example 1 It has strong binding ability to RAC1 antigen; it can accurately and quickly detect RAC1 protein, specifically binds to RAC1 protein, and ensures no cross-reaction with other proteins of the RHO protein family, which is conducive to wide application in immunological detection.

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Abstract

L'invention concerne un anticorps monoclonal de protéine RAC1 et son procédé de préparation. La séquence d'acides aminés de la région variable de chaîne lourde de l'anticorps monoclonal est SEQ ID NO 1, et la séquence d'acides aminés de la région variable de chaîne légère est SEQ ID NO 2. L'anticorps monoclonal peut se lier spécifiquement à la protéine RAC1 et détecter la protéine RAC1, et ne réagit pas avec d'autres protéines de la famille des protéines RHO, etc. L'anticorps monoclonal s'applique à des dosages immunologiques.
PCT/CN2022/076830 2022-02-18 2022-02-18 Anticorps monoclonal de protéine rac1, son procédé de préparation et son utilisation WO2023155132A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030018003A1 (en) * 2001-06-16 2003-01-23 Sebti Said M. Rhob as a suppressor of cancer cell growth and cell transformation
US20090324708A1 (en) * 2006-11-06 2009-12-31 Universidad Nacional De Quilmes Compound having inhibitory activity on a rho-gtpase cell protein, a process for obtaining the same, pharmaceutical compositions comprising thereof and a method for the treatment of rho-gtpase cell protein-mediated condition
CN101986784A (zh) * 2008-02-07 2011-03-16 先灵公司 基因工程tslpr抗体
CN104293791A (zh) * 2014-10-22 2015-01-21 首都医科大学附属北京友谊医院 miR-200b在制备Rac-1蛋白表达抑制剂中的新用途
CN110167592A (zh) * 2016-12-23 2019-08-23 莫纳什大学 抗il-37抗体

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030018003A1 (en) * 2001-06-16 2003-01-23 Sebti Said M. Rhob as a suppressor of cancer cell growth and cell transformation
US20090324708A1 (en) * 2006-11-06 2009-12-31 Universidad Nacional De Quilmes Compound having inhibitory activity on a rho-gtpase cell protein, a process for obtaining the same, pharmaceutical compositions comprising thereof and a method for the treatment of rho-gtpase cell protein-mediated condition
CN101986784A (zh) * 2008-02-07 2011-03-16 先灵公司 基因工程tslpr抗体
CN104293791A (zh) * 2014-10-22 2015-01-21 首都医科大学附属北京友谊医院 miR-200b在制备Rac-1蛋白表达抑制剂中的新用途
CN110167592A (zh) * 2016-12-23 2019-08-23 莫纳什大学 抗il-37抗体

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