Application of anti-IL-5 antibody

Abstract

The invention belongs to the field of biological medicine, and discloses application of an anti-IL-5 antibody. The complementarity determining regions HCDR1, HCDR2 and HCDR3 of the heavy chain variable region of the anti-IL-5 antibody are respectively SGYWV, SISYSGTTYYNPSLKS and GIPMDS; and the complementary determining regions LCDR1, LCDR2 and LCDR3 of the variable region of the light chain are respectively RASESVDSYGNSFMH, RASNLES and QQSNEDPYT. The IL-5 antibody of some examples is subjected to humanized transformation, the affinity and proliferation blocking effect of the IL-5 antibody are kept, the IL-5 antibody has the remarkable capability of blocking combination of IL-5 and IL-5R alpha, the affinity of the IL-5 antibody is larger than 10 <-11 > M, and immune side reactions are effectively reduced.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to the application of anti-IL-5 antibodies. Background Technology

[0002] Severe eosinophilic asthma (SEA) is a refractory respiratory disease with poor clinical control. Eosinophils play a crucial role in the pathogenesis of SEA, leading to airway epithelial damage and bronchial remodeling. Eosinophil counts are associated with a higher frequency of exacerbations, thus reducing lung function. Current treatment for asthma involves inhaled corticosteroids, but long-term use can lead to osteoporosis and hypertension. Biologics have shown promising results in treating severe asthma. 50% to 70% of asthma patients experience type 2 inflammation, with increased production of Th2 cell-mediated inflammatory factors IL-5, IL-4, and IL-13, along with elevated levels of eosinophils (EOS), IgE, and exhaled nitric oxide (FeNO). Therefore, reducing eosinophil counts by inhibiting pro-inflammatory factors is a highly effective treatment option for SEA.

[0003] IL-5 is a homodimeric cytokine linked by interchain disulfide bonds, crucial for regulating the proliferation, activation, and maturation of eosinophils. It promotes the release of eosinophils from the bone marrow into the bloodstream. While Th2 lymphocytes are the primary source of IL-5 production, mast cells, type II innate lymphocytes (ILC2s), natural killer T cells, and even eosinophils also express and produce IL-5. IL-5Rα is an IL-5-binding receptor expressed on the surface of mature eosinophils and basophils. The intermediate complex formed after IL-5 binds to IL-5Rα recruits the β-common (βc) receptor (CD131) to form a ternary complex, which then activates the JAK / STAT signaling cascade, thereby promoting eosinophil proliferation. Currently marketed antibodies against IL-5 include mepolizumab and reslizumab, which neutralize IL-5 levels in the body, thereby reducing eosinophil levels, inhibiting eosinophil differentiation and activation, and thus slowing the rate of asthma exacerbation. In clinical trials, antibodies targeting the IL-5 / IL-5Rα complex have reduced the rate of severe asthma exacerbations, improved forced expiratory volume in one second (FEV1), reduced the use of oral corticosteroids, and so on. Furthermore, since eosinophils are associated with mucus formation, reducing the number of airway eosinophils can consequently reduce airway obstruction, thereby improving lung function. Anti-IL-5 antibodies have been shown to be a potential treatment for steroid-resistant acute severe eosinophilic asthma. In addition, the approved IL-5-targeting mepolizmab antibody has been approved for the treatment of granulomatous polyangiitis, eosinophilic granuloma, chronic sinusitis with nasal polyps, and Churg-Strauss syndrome.

[0004] Currently available monoclonal antibody drugs targeting IL-5 are all imported, expensive, and have low accessibility. Therefore, developing a novel anti-IL5 monoclonal antibody for injection administration has promising clinical application prospects. Summary of the Invention

[0005] The purpose of this invention is to overcome at least one deficiency of the prior art and to provide an anti-IL-5 antibody and its application.

[0006] The technical solution adopted in this invention is: The first aspect of the present invention provides: An anti-IL-5 antibody comprises a heavy chain and a light chain. The variable region of the heavy chain includes three complementarity-determining regions (CDR1, HCDR2, and HCDR3), and the variable region of the light chain includes three CDR1, LCDR2, and LCDR3. The amino acid sequences of these CDRs are as follows: H_CDR1: SGYWV (SEQ ID NO. 1), H_CDR2: SISYSGTTYYNPSLKS (SEQ ID NO. 2) and H_CDR3: GIPMDS (SEQ ID NO. 3); L_CDR1: RASESVDSYGNSFMH (SEQ ID NO. 4), L_CDR2: RASNLES (SEQ ID NO. 5), and L_CDR3: QQSNEDPYT (SEQ ID NO. 6).

[0007] In some examples of anti-IL-5 antibodies, the framework region of the heavy chain variable region is a humanized framework region.

[0008] In some examples of anti-IL-5 antibodies, the amino acid sequence of the heavy chain variable region is selected from one of the following: MIL-A97-H, whose amino acid sequence is shown in SEQ ID NO. 7; VH1, whose amino acid sequence is shown in SEQ ID NO. 9; VH2, whose amino acid sequence is shown in SEQ ID NO. 10; VH3, whose amino acid sequence is shown in SEQ ID NO. 11; VH4, whose amino acid sequence is shown in SEQ ID NO. 12; VH5, whose amino acid sequence is shown in SEQ ID NO. 13; VH6, whose amino acid sequence is shown in SEQ ID NO. 14; The amino acid sequence of the light chain variable region is selected from one of the following, and its amino acid sequence is shown in SEQ ID NO. 8, 15-18; MIL-A97-L, the amino acid sequence of which is shown in SEQ ID NO. 8; VL1, whose amino acid sequence is shown in SEQ ID NO. 15; VL2, whose amino acid sequence is shown in SEQ ID NO. 16; VL3, whose amino acid sequence is shown in SEQ ID NO. 17; VL4, whose amino acid sequence is shown in SEQ ID NO. 18.

[0009] In some examples of anti-IL-5 antibodies, the amino acid sequence combinations of their heavy chain variable region and light chain variable region are: MIL-A97-H+MIL-A97-L, VH1+VL1, VH1+VL2, VH1+VL3, VH1+VL4, VH2+VL2, VH2+VL3, VH2+VL4, VH3+VL2, VH3+VL3, VH3+VL4, VH4+VL2, VH4+VL3, VH4+VL4, VH5+VL3, VH5+VL4, VH6+VL3, VH6+VL4.

[0010] In some examples of anti-IL-5 antibodies, the antibody is a monoclonal antibody, a Fab antibody, a single-domain antibody, or a multivalent antibody. Specific antibodies can be designed using existing technologies.

[0011] A second aspect of the present invention provides: The use of the anti-IL-5 antibody described in the first aspect of the present invention in the preparation of a drug for treating IL-5-related respiratory diseases.

[0012] In some applications, the drug is an injection or an inhaler.

[0013] In some application examples, the IL-5-related respiratory diseases are selected from severe eosinophilic asthma, granuloma with polyangiitis, eosinophilic granuloma, chronic sinusitis with nasal polyps, Churg-Strauss syndrome, and pulmonary eosinophilia.

[0014] A third aspect of the present invention provides: The application of the anti-IL-5 antibody described in the first aspect of the present invention in the preparation of an IL-5 detection kit.

[0015] A fourth aspect of the present invention provides: The gene encoding the anti-IL-5 antibody described in the first aspect of the present invention.

[0016] Specific gene sequences can be designed and synthesized using existing methods.

[0017] The beneficial effects of this invention are: In some examples of this invention, the IL-5 antibody has been humanized, maintaining its affinity and proliferation-blocking effect, and exhibiting a significant ability to block the binding of IL-5 to IL-5Rα, with an affinity greater than 10. -11 M, and effectively reduced immune side effects. Attached Figure Description

[0018] Figure 1 This is the result of the antibody recombinant supernatant binding to human IL-5.

[0019] Figure 2 This is the result of ELISA blocking detection of recombinant supernatant.

[0020] Figure 3 This is the result of the monoclonal antibody FACS blocking test.

[0021] Figure 4 This is the result of the monoclonal antibody TF-1 cell proliferation inhibition test.

[0022] Figure 5 These are the epitope analysis results for hu39D10 (P33964) and MIL-A97 (P41791).

[0023] Figure 6 These are the results of epitope analysis for Mepolizumab (P33965) and MIL-A97 (P41791).

[0024] Figure 7 This is the result of the affinity test.

[0025] Figure 8 and Figure 9 This is the result of FACS blocking detection using the MIL-A97 humanized antibody.

[0026] Figures 10-14 These are the results of TF-1 proliferation inhibition detection for different MIL-A97 humanized antibodies. Detailed Implementation

[0027] The technical solution of the present invention will be further illustrated below with examples.

[0028] Example 1: Mouse immunization BalB / C mice were immunized with proteins A (hIL-5-hFc), B (hIL-5-his), C (cyIL-5-His), and D (hIL-5-hFc+cyIL-5-His). After four rounds of routine immunization, serum was collected for titer testing. Then, ELISA plates were coated with IL-5-hFc, hIL-5-his, and cyIL-5-His antigens, respectively, and the results were analyzed. All mice were then given booster immunizations.

[0029] Example 2: Mouse Immune Bank Construction RNA was extracted from the spleen tissue of each mouse in Example 1 using the Trizol method. RNA reverse transcription was performed according to the method provided by the TaKaRa reverse transcription kit. PCR amplification was performed using cDNA as a template and heavy and light chain primers. A Fab phage display library was constructed based on existing methods.

[0030] Example 3: Antibody Screening The experiment used magnetic bead and immunotube methods for the preliminary selection of mouse immune banks. The mouse immune phage bank bacteria from Example 2 were inoculated into 2YT (C) glucose-containing medium at a specific inoculation rate. + -T + In the culture medium, shake and incubate until OD 600 ≈0.5, add Helper Phage for 1 h to 1.5 h of incubation, then centrifuge, discard the supernatant, and pour in 2YT (C + -K + Incubate overnight in culture medium. On the second day, centrifuge and collect the supernatant, add PEG6000, mix well, and place on ice to precipitate. After 1 hour, centrifuge and discard the supernatant, add pre-cooled PBS, and dissolve by pipetting to prepare a phage suspension.

[0031] 3.1 Screening using magnetic beads Magnetic bead screening is based on biotin labeling of antigen proteins (human IL-5 or monkey IL-5), followed by binding to magnetic beads conjugated with streptavidin. The screening process involves incubating, washing, and eluting the antigen-bound magnetic beads and antibody gene phage display libraries.

[0032] Mouse immune library bacterial suspensions were diluted with 2.5% BSA and blocked for negative screening (positive screening antigens carry an Fc tag, requiring the addition of negative screening protein during incubation, with the amount of negative screening protein being 10 times that of positive screening protein). Phages incubated after negative screening were collected. Binding and washing were performed according to the Kingfisher magnetic bead screening system, and finally, the phages were eluted with Trypsin. Subsequently, the eluted phages were used to infect SS320 bacteria in the logarithmic growth phase, and the resulting phages were used for the next round of panning. Through 3-4 rounds of panning, a phage pool specifically targeting IL-5 was finally enriched.

[0033] 3.2 Screening using immunotubes Immunotube screening involves coating the surface of an immunotube (human IL-5 or monkey IL-5) with an antigen protein (human IL-5 or monkey IL-5) that has a high adsorption capacity. The screening process involves adding a phage display antibody library into the immunotube and incubating, washing, and eluting the antigen protein adsorbed on the surface of the immunotube.

[0034] 3.3 Single-clone selection Clones with good enrichment effects were selected for monoclonal plating, and Fab expression in the monoclonal supernatant was induced. Using ELISA with IL-5 as the antigen, the binding signal between the monoclonal supernatant and IL-5 was detected, resulting in 555 positive clones. The positive clones were selected for sequencing analysis, yielding 50 sequence-unique positive antibodies. Through sequence similarity analysis and modification analysis, 46 antibodies were finally selected for recombinant expression.

[0035] Example 4: Detection of the binding activity of recombinant monoclonal antibody expression with IL-5 protein The heavy chain of 46 Fab sequences was constructed into a pcDNA3.4 vector containing an Fc tag to obtain a recombinant plasmid expressing the complete heavy chain; the light chain was constructed into a pcDNA3.4 vector to obtain a recombinant plasmid expressing the complete light chain. The recombinant plasmids were expressed in expi CHO-S cells, and the supernatant was used for ELISA detection.

[0036] Human IL-5-His was diluted to 2 μg / mL with PBS and added to each well of an ELISA plate (30 μL). After overnight coating, the plate was washed 5 times with PBST and then blocked with 5% milk at 37 °C for 1 h. Serially diluted recombinant antibody was added and incubated at 37 °C for 1 h. After washing 5 times with PBST, secondary antibody Anti-human-IgG-Fc-HRP (diluted 1:10000 with PBS) was added and incubated at 37 °C for 1 h. The plate was then washed 5 times with PBST. 30 μL of TMB chromogenic solution was added to each well and the plate was incubated at room temperature in the dark for 5 min. The reaction was then terminated by adding 2 M sulfuric acid. The absorbance was measured at 450 nm using an ELISA reader.

[0037] Figure 1 The binding of a portion of the antibody supernatant to human IL-5 is shown, with IPI and milk as negative controls.

[0038] Example 5: Detection of blocking activity of recombinant supernatant ELISA Dilute hIL-5-hFc to 2 μg / mL with PBS, add 30 µL to an ELISA plate, and incubate overnight at 4 °C. Wash the plate three times with PBST, and block with 5% milk at room temperature for 2 h. Wash the plate three times with PBST, dilute the recombinant antibody to be tested with 1% milk, add 30 µL to each well of the ELISA plate, and incubate at room temperature for 1 h. Without washing, add hIL-5Rα-cHis (4 μg / mL) and incubate at room temperature for 1 h. Wash the plate three times with PBST, add 1:4000 diluted 6×his-HRP (proteintech; HRP-66005) antibody, and incubate at room temperature for 1 h. After washing, add 30 μL of TMB chromogenic solution to each well, react at room temperature in the dark for 5 min, and then add 50 μL of 2M sulfuric acid to stop the reaction. Measure the absorbance at 450 nm using an ELISA reader.

[0039] Figure 2 This study demonstrates how partial antibody supernatants blocked the binding of IL-5 and IL-5R at the ELISA level. The negative controls were IPI and milk. IPI did not fit the data successfully, and milk data is a single point.

[0040] Example 6: Antibody purification and blocking activity detection The cell supernatant exhibiting blocking effect in Example 5 was purified using a protein A purification column, and its purity was analyzed by SDS-PAGE. Following the method described in Example 5, the purified monoclonal antibody was subjected to an ELISA retest for blocking effect.

[0041] A stable CHO-S cell line co-expressing IL-5Rα and CD131 proteins was constructed. CHO-S-IL-5Rα-CD131 cells were collected by centrifugation, washed with FACS staining buffer, and resuspended to prepare a cell suspension. The cell density was adjusted to 1×10⁻⁶ cells / mL. 6 cells / mL, centrifuged and supernatant discarded. FACS blocking detection was performed according to the method in patent CN116606375A. Results are as follows... Figure 3 As shown, the MIL-A97 antibody can block the binding of IL-5 to IL-5Rα on the cell surface at the FACS level. Figure 3 This study demonstrates the blocking effect of some antibodies on the binding of IL-5 to IL-5R at the FACS level, with hIL-5-mFc and cell only data being single-point data.

[0042] Example 7: Detection of Proliferation Inhibition by Recombinant Antibody TF-1 The recombinant antibody MIL-A97 was used to detect TF-1 proliferation inhibition. The specific detection method followed the method disclosed in CN116606375A. Results are as follows... Figure 4As shown, MIL-A97 significantly inhibited the proliferation of the TF-1-IL-5Rα-A17 cell line, and the blocking effect of MIL-A97 was comparable to that of the positive control hu39D10. The amino acid sequences of the heavy chain variable region and light chain variable region of the MIL-A97 antibody are as follows: MIL-A97 Heavy Chain Variable Region: QVQLKESGPSLVKPSQTLSLTCSVTGDSVT- SGYWV -WIRKFPGNKLEYMG- SISYSGTTYYNPSLKS -RISITRDTSMNQYYLQLNSVTTEDTATYYCAG- GIPMDS -WGQGTSVTVSS (SEQ ID NO. 7) MIL-A97 Light Chain Variable Region: DIVLTQSPASLAVSLGQRATISC- RASESVDSYGNSFMH -WYQQKPGQPPKLLIY- RASNLES -GIPARFSGSGSRTDFTLTINPVEADDVATYYC- QQSNEDPYT -FGGGTKLEIK (SEQ ID NO. 8).

[0043] In the above amino acid sequences, the italicized regions are the CDR regions determined according to the kabat database.

[0044] Example 8: Antibody Epitope Analysis 8.1 Competition analysis with hu39D10 epitope hu39D10 is Reslizumab.

[0045] Human IL-5-His was diluted to 1 μg / mL with PBS and added to each well of an ELISA plate (30 μL). The plate was incubated overnight at 4 °C. After washing three times, the plate was blocked with 5% skim milk at room temperature for 2 h. The antibody to be analyzed was diluted with 1% milk and added to the ELISA plate, then incubated at room temperature for 1 h. 0.5 μg / mL hu39D10-Biotin was added to each well (30 µL), and the plate was incubated at room temperature for 1 h. The plate was washed three times with PBST, and NeutrAvidin-HRP (Thermo Fisher; 31001) diluted 1:2000 was added, and the plate was incubated at room temperature for 1 h. After washing, 30 μL of TMB chromogenic solution was added to each well, and the plate was incubated at room temperature in the dark for 5 min. The reaction was then terminated by adding 50 μL of 2M sulfuric acid, and the absorbance was measured at 450 nm using an ELISA reader.

[0046] The results are as follows Figure 5 As shown, hu39D10 (P33964) and MIL-A97 (P41791) have an epitope competition relationship.

[0047] 8.2 Epitope Competition Analysis between Candidate Antibodies and Mepolizumab Human IL-5-His was diluted to 4 μg / mL with PBS and added to each well of an ELISA plate (30 μL). The plate was incubated overnight at 4 °C. After washing three times, the plate was blocked with 5% skim milk at room temperature for 2 h. The antibody to be analyzed was diluted with 1% milk and added to the ELISA plate, then incubated at room temperature for 1 h. 0.5 μg / mL Mepolizumab-Biotin-Biotin was added to each well (30 μL), and the plate was incubated at room temperature for 1 h. The plate was washed three times with PBST, and NeutrAvidin-HRP (Thermo Fisher; 31001) diluted 1:2000 was added, and the plate was incubated at room temperature for 1 h. After washing, 30 μL of TMB chromogenic solution was added to each well, and the plate was incubated at room temperature in the dark for 5 min. The reaction was then terminated by adding 50 μL of 2M sulfuric acid, and the absorbance was measured at 450 nm using an ELISA reader.

[0048] The results are as follows Figure 6 As shown, MIL-A97 (P41791) and Mepolizumab (P33965) are not the same epitope.

[0049] Example 9: ELISA-based detection of the binding activity of candidate antibodies to monkey IL-5 and mouse IL-5 proteins Monkey IL-5-His, rat IL-5-His, and mouse IL-5-His proteins were coated on ELISA plates, and MIL-A97 (P41791) was added to detect their binding activity. The specific method is described in Example 4. The results are shown in Table 1.

[0050] Table 1: Results of MIL-A97 binding activity with IL-5 in different animals (ECG) 50 )

[0051] The results show that MIL-A97 exhibits cross-activity between humans, mice, and monkeys.

[0052] Example 10: Antibody Affinity Assay Antibody affinity was determined using a Biacore T200 (Cytiva) microarray. The antibody was captured using a protein A chip, and different concentrations of the antigen IL-5-His were added for affinity testing. The results are as follows: Figure 7 As shown in Table 2.

[0053] Table 2: Antibody Affinity Assay

[0054] The results show that the affinity of MIL-A97 is comparable to that of the positive control hu39D10.

[0055] Example 11: ELISA Detection of MIL-A97 Humanized Antibody Binding and Blocking Based on the results of affinity blocking activity detection, the MIL-A97 antibody (named A97-mVH-A97-mVL) was selected for humanization. The germline with the highest similarity to MIL-A97 was selected by IgBlast, and the CDR region of MIL-A97 was transplanted. Reversion mutations were performed at different sites, and the sequence was synthesized and constructed in an expression vector. The sequence is shown in Table 3. It was expressed in expiCHO-S cells and purified using a protein A protein purification column. ELISA binding and ELISA blocking activity were detected according to the methods in Examples 4-5. The results are shown in Table 4.

[0056] Table 3: Amino acid sequences of the heavy and light chain variable regions of humanized MIL-A97 antibody

[0057] Note that in the table, VH refers to heavy chain and VL refers to light chain.

[0058] Table 4: ELISA activity assay results of different humanized monoclonal antibodies against different IL-5 / EC 50 (μg / mL)

[0059] Note: In the table, VH1 to VH6 refer to the heavy chains with the same number in Table 3, and VL1 to VL4 refer to the light chains with the same number in Table 3.

[0060] Example 12: FACS blocking detection using MIL-A97 humanized antibody The FACS blocking assay of the humanized antibody was performed according to the method in Example 6, and the results are as follows: Figure 8 and Figure 9 As shown (where hIL-5-mFc is single-point data), A97-huVH1-A97-huVL1, A97-huVH1-A97-huVL2, A97-huVH1-A97-huVL3, A97-huVH2-A97-huVL2, A97-huVH3-A97-huVL2, A97-huVH3-A97-huVL3, huVH4-A97-huVL2, and A97-huVH4-A97-huVL3 have good blocking effects.

[0061] Example 13: Detection of affinity for MIL-A97 humanized antibody Humanized antibodies with good ELISA binding, blocking, and FACS blocking abilities were selected for affinity testing. The affinity of the humanized antibodies was tested according to the method in Example 10, and the results, shown in Table 5, indicate that the candidate humanized antibodies had comparable affinity to the parent antibody.

[0062] Table 5. Humanized Antibody Affinity Detection

[0063] Example 14: Detection of MIL-A97 humanized antibody TF-1 proliferation inhibition Humanized antibodies were used to detect TF-1 proliferation inhibition. The specific detection method is described in patent CN116606375A. Results are as follows: Figure 10-14 As shown (where IgG1 and Cell+IL-5-hFc are single-point data), all candidate humanized antibodies have the effect of inhibiting TF-1 cell proliferation.

[0064] The above is a further detailed description of the present invention and should not be considered as a limitation on the specific implementation of the present invention. For those skilled in the art, simple deductions or substitutions without departing from the concept of the present invention are all within the protection scope of the present invention.

Claims

1. The use of an anti-IL-5 antibody in the preparation of a drug for treating IL-5-related respiratory diseases, wherein the anti-IL-5 antibody comprises a heavy chain and a light chain, wherein the variable region of the heavy chain includes three complementarity-determining regions H_CDR1, H_CDR2, and H_CDR3, and the variable region of the light chain includes three complementarity-determining regions L_CDR1, L_CDR2, and L_CDR3, characterized in that, The amino acid sequence of the complementarity-determining region is as follows: H_CDR1:SGYWV H_CDR2: SISYSGTTYYNPSLKS H_CDR3: GIPMDS L_CDR1:RASESVDSYGNSFMH L_CDR2:RASNLES L_CDR3:QQSNEDPYT.

2. The application according to claim 1, characterized in that, The frame region of the heavy chain variable region is the frame region after humanization modification.

3. The application according to claim 1, characterized in that, The amino acid sequence of the heavy chain variable region is selected from one of the following: MIL-A97-H: QVQLKESGPSLVKPSQTLSLTCSVTGDSVTSGYWVWIRKFPGNKLEYMGSISYSGTTYYNPSLKSRISITRDTSMNQYYLQLNSVTTEDTATYYCAGGIPMDSWGQGTSVTVSS VH1: QVQLKESGPGLVKPSQTLSLTCSVTGDSVTSGYWVWIRKHPGKGLEYMGSISYSGTTYYNPSLKSRITISRDTSMNQYYLKLSSVTAADTAVYYCAGGIPMDSWGQGTTVTVSS VH2: QVQLQESGPGLVKPSQTLSLTCSVTGDSVTSGYWVWIRQHPGKGLEYMGSISYSGTTYYNPSLKSRITISRDTSMNQYSLKLSSVTAADTAVYYCAGGIPMDSWGQGTTVTVSS VH3: QVQLQESGPGLVKPSQTLSLTCSVTGDSVTSGYWVWIRQHPGKGLEYMGSISYSGTTYYNPSLKSRVTISRDTSKNQYSLKLSSVTAADTAVYYCAGGIPMDSWGQGTTVTVSS VH4: QVQLQESGPGLVKPSQTLSLTCTVSGDSVTSGYWVWIRQHPGKGLEYMGSISYSGTTYYNPSLKSRVTISRDTSKNQYSLKLSSVTAADTAVYYCAGGIPMDSWGQGTTVTVSS VH5: QVQLQESGPGLVKPSQTLSLTCTVSGDSVTSGYWVWIRQHPGKGLEYIGSISYSGTTYYNPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCAGGIPMDSWGQGTTVTVSS VH6: QVQLQESGPGLVKPSQTLSLTCTVSGDSISSGYWVWIRQHPGKGLEYIGSISYSGTTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAGGIPMDSWGQGTTVTVSS; The amino acid sequence of the light chain variable region is selected from one of the following: MIL-A97-L: DIVLTQSPASLAVSLGQRATISCRASESVDSYGNSFMHWYQQKPGQPPKLLIYRASNLESGIPARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPYTFGGGTKLEIK VL1: DIQLTQSPSSLSVSVGDRATISCRASESVDSYGNSFMHWYQQKPGQPPKLLIYRASNLESGIPARFSGSGSRTDFTLTISSVQAEDFATYYCQQSNEDPYTFGGGTKLEIK VL2: DIQLTQSPSSLSVSVGDRATITCRASESVDSYGNSFMHWYQQKPGKAPKLLIYRASNLESGIPARFSGSGSRTDFTLTISSLQPEDFATYYCQQSNEDPYTFGGGTKLEIK VL3: DIQLTQSPSSSLSASVGDRVTITCRASESVDSYGNSFMHWYQQKPGKAPKLLIYRASNLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSNEDPYTFGGGTKLEIK VL4: DIQMTQSPSSSLSASVGDRVTITCRASESVDSYGNSFMHWYQQKPGKAPKLLIYRASNLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSNEDPYTFGGGTKLEIK.

4. The application according to claim 3, characterized in that, The amino acid sequence combinations of its heavy chain variable region and light chain variable region are: MIL-A97-H+MIL-A97-L, VH1+VL1, VH1+VL2, VH1+VL3, VH1+VL4, VH2+VL2, VH2+VL3, VH2+VL4, VH3+VL2, VH3+VL3, VH3+VL4, VH4+VL2, VH4+VL3, VH4+VL4, VH5+VL3, VH5+VL4, VH6+VL3, VH6+VL4.

5. The application according to claim 1, characterized in that, The antibody is a monoclonal antibody, a Fab antibody, or a multivalent antibody.

6. The application according to claim 1, characterized in that, The drug is an injectable or inhaled formulation.

7. The application according to claim 1, characterized in that, The IL-5-related respiratory diseases mentioned are selected from severe eosinophilic asthma, granuloma with polyangiitis, eosinophilic granuloma, chronic sinusitis with nasal polyps, Churg-Strauss syndrome, and pulmonary eosinophilia.

8. A medicament for treating IL-5-related respiratory diseases, comprising an active ingredient and excipients, characterized in that, The active ingredient includes the anti-IL-5 antibody as described in any one of claims 1 to 5.

9. A method for detecting IL-5 protein content, characterized in that, This includes using the anti-IL-5 antibody according to any one of claims 1 to 5 to determine the IL-5 protein content by ELISA.

10. The use of the anti-IL-5 antibody according to any one of claims 1 to 5 in the preparation of an inhibitor that blocks the binding of IL-5 to IL-5R or IL-5Rα.

Images