CN110156890A - Semaphorin7A monoclonal antibody and its application in terms of preparation is for treating inflammation disease drug - Google Patents
Semaphorin7A monoclonal antibody and its application in terms of preparation is for treating inflammation disease drug Download PDFInfo
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Abstract
The invention discloses Semaphorin7A monoclonal antibody and its applications in terms of preparation is for treating inflammation disease drug, belong to immunology and cardiovascular disease medicine preparation field, it is disclosed by the invention using Semaphorin7A monoclonal antibody as the drug of main active, in the septicopyemia blood inflammation and enterovirus EV 71 acute infection model that vital myocarditis disease, staphylococcus aureus induce, the treatment for giving morbidity mouse Semaphorin7A monoclonal antibody can be effectively relieved above-mentioned inflammation and improve mouse survival rate；In research and development and production of the preparation for treating the above-mentioned drug for vital myocarditis disease, the septicopyemia blood inflammation that staphylococcus aureus induces and enterovirus EV 71 acute infection, which invents with important application prospects and promotional value.
Description
Technical field
The invention belongs to immunology and cardiovascular disease medicine preparation field more particularly to Semaphorin7A monoclonal are anti-
Body and its application in terms of preparation is for treating inflammation disease drug.
Background technique
Avidin Semaphorins is axon guidance molecule protein family, is a kind of secretion or transmembrane protein family.
The classification of Semaphorin protein family is classified with protein structure domain, and Semaphorins structure includes that a N-terminal is thin
Extracellular matrix architecture domain (Sema structural domain), this structural domain contain about 500 amino acid, wherein abundant containing the residual of cysteine
Base.Central domain is plexin-Semaphorin (PSI) integrin structural domain, and C-terminal is a variable protein structural domain.The end C
The variation of end group sequence is the key factor of Semaphorin family classification.Semaphorins protein family one shares 8 subclass.1
Class and 2 classes are there are in invertebrate, and 3 classes to 7 classes are to be present in vertebrate, and the 8th class molecule is compiled by virus
Code.Wherein Isosorbide-5-Nitrae~7 classes are mainly transmembrane protein, and 2,3,8 be mainly secreted protein.Semaphorins is initially to make
It is found for axon guidance molecule, can be with the interaction or chemotaxis between mediated cell and cell, but it is made now
With being far above during neural axon growth, Semaphorins is found to participate in many pathological processes, for example,
Organ growth is mature, the regulation of immunocyte and the formation of blood vessel.
Semaphorin7A (Sema7A, amino acid sequence is as shown in SEQ ID NO.1) gene is located at No. 15 chromosomes of people
On, it is to be found in red blood cell, and be named as CDw108 for the first time earliest.Yamada et al. clones people's for the first time
CDw108 cDNA sequence, he encodes 666 amino acid altogether.The correspondence albumen of source of mouse is made of 664 amino acid and and people
Sema7A have 90% homology.Until 1998, CDw108 was just proved to belong to Semaphorin family, and is named as
SemaK-1.1999, which was renamed as Sema7A, because the specificity of its GPI anchoring, is located in one for him
It is that a kind of unique glycosyl-phosphatidyl inositol anchor determines albumen in new Semaphorin family subclass.The Sema7A of source and source of mouse is
Containing a 7 paddle β spiral Semaphorin N-terminal structural domains, a PSI structural domain, one be immunized spherical spline structure domain and
The C-terminal of one GPI anchoring.Sema7A is usually to pass through Sema structural domain to connect to form dimerization with spherical spline structure centre is immunized
Body.Sema7A can be combined with encoding viral Semaphorin protein receptor (VESPR), i.e. plexinC1.It can also be with integration
Plain 1 β 1 of α is combined.
Inducing neural axon growth and regulation inflammatory and immune response etc. are concentrated mainly on for the research of Sema7A at present
Aspect.Have been reported that the maintenance for showing that Sema7A takes part in Intestinal Mucosal Immunity system, Kang etc. is steady in research Intestinal Mucosal Immunity
It is found when state, the Sema7A that intestinal epithelial cell generates can induce macrophage and generate IL-10, so that it is anti-to mitigate intestinal inflammatory
It answers, and this effect can be blocked by the neutralizing antibody of IL-10.In addition, Sema7A is in scytitis, virus infection and a variety of
Also play key player in autoimmune disease.Kamata etc. is in research scytitis, Eponychium cell and monokaryon
Cell finds that Sema7A and the interaction of 1 β of α, 1 integrin and activated mononuclear cell, induced monocyte are generated when interacting
The inflammatory factors such as IL-8 aggravate scytitis.Sultana etc. can be led in research west nile virus (WNV) Shi Faxian, WNV infection
Sema7A expression in blood and tissue is caused to increase, the inflammatory reaction after Sema7A deficient mice infection WNV is substantially reduced, and
Sema7A defect is injected intraperitoneally in the mouse of Sema7A antibody, and the lethality of WNV infection is significantly reduced.Sema7A can promote
The progress of the autoimmune diseases such as multiple sclerosis, its receptor alpha 1 β 1 on Sema7A and macrophage on activating T cell
Integrin combines, and plays pro-inflammatory effect.In addition also there is research to confirm, on the Sema7A and macrophage on enterocyte its by
1 integrin of body α v β combines, and secretion IL-10 adjusts intestinal inflammation.
Currently, the either monoclonal antibody of Sema7A or Sema7A antibody grinding in genetic engineering neutrality antibody
Hair, is in the laboratory research stage, without a kind of Sema7A monoclonal antibody neutralizing antibody as clinical medicine list marketing.
Summary of the invention
In order to treat macrophage related inflammatory diseases, the embodiment of the invention provides a kind of Semaphorin7A monoclonals
Antibody and its application in terms of preparation is for treating inflammation disease drug, the Semaphorin7A monoclonal antibody are used in preparation
Application in terms for the treatment of inflammation disease drug is of great significance.
On the one hand, the embodiment of the invention discloses a kind of Semaphorin7A monoclonal antibody, the Semaphorin7A
Monoclonal antibody includes heavy chain amino variable region and light chain amino acid variable region, in which: the Semaphorin7A monoclonal
6 cdr amino acid sequences of antibody are as follows:
The amino acid sequence of VH CDR1 is SEQ ID NO.2,
The amino acid sequence of VH CDR2 is SEQ ID NO.3,
The amino acid sequence of VH CDR3 is SEQ ID NO.4,
The amino acid sequence of VL CDR1 is SEQ ID NO.6,
The amino acid sequence of VL CDR2 is SEQ ID NO.7,
The amino acid sequence of VL CDR3 is SEQ ID NO.8；Or
The amino acid sequence of VH CDR1 is SEQ ID NO.10,
The amino acid sequence of VH CDR2 is SEQ ID NO.11,
The amino acid sequence of VH CDR3 is SEQ ID NO.12,
The amino acid sequence of VL CDR1 is SEQ ID NO.14,
The amino acid sequence of VL CDR2 is SEQ ID NO.15,
The amino acid sequence of VL CDR3 is SEQ ID NO.16；
In some embodiments, the homology of 6 cdr amino acids is at least in the Semaphorin7A monoclonal antibody
90%.
In some embodiments, the amino acid sequence of the Semaphorin7A monoclonal antibody includes:
The heavy chain and the amino acid sequence structure as shown in SEQ ID NO.9 that the amino acid sequence shown in SEQ ID NO.5 is constituted
At light chain；Or；
The heavy chain and the amino acid sequence as shown in SEQ ID NO.17 that the amino acid sequence shown in SEQ ID NO.13 is constituted
The light chain of composition.
On the other hand, the embodiment of the invention also discloses a kind of Semaphorin7A monoclonal antibodies is used in preparation
The application in terms of inflammation disease drug is treated, the inflammation disease includes at least vital myocarditis disease, staphylococcus aureus
(S.aureus) the septicopyemia blood inflammation and enterovirus EV 71 acute infection induced.
In some embodiments, verify the drug treat it is in the vital myocarditis disease in application, selection
Tissue includes at least serum, heart tissue.
In some embodiments, the drug is verified in the purulence for treating staphylococcus aureus (S.aureus) induction
It is in malicious blood inflammation in application, the tissue of selection include at least serum, lung tissue, renal tissue.
In some embodiments, verify the drug treat it is in the enterovirus EV 71 acute infection in application,
The tissue of selection includes at least: skeletal muscle tissue, small intestine, brain stem tissue.
In some embodiments, described for treat the drug of inflammation disease to further include excipient substance and medicinal substrate.
In some embodiments, the drug for treating inflammation disease is liquid preparation or lyophilized preparation.
Technical solution provided in an embodiment of the present invention has the benefit that
1, the present invention is using truncating expression and the technologies such as section of synthesized peptide, to Semaphorin7A monoclonal antibody 2567-1,
The epitope that 2567-3 is identified carries out elutriation and obtains its consistent epitope sequences, and sequence alignment result shows this
The polypeptide sequence that Semaphorin7A monoclonal antibody is identified falls in Semaphorin7A β coil region.Further, applicant utilizes anti-
Light chain, the heavy chain that body gene sequencing technology analyzes 2567-1,2567-3 monoclonal antibody and Sema7A is specifically bound
Sequence.
2, the present embodiment gives the septicopyemia of vital myocarditis disease, staphylococcus aureus (S.aureus) induction respectively
Above-mentioned inflammation can be effectively relieved with the treatment of Semaphorin7A monoclonal antibody in blood inflammation and enterovirus EV 71 acute infection
Disease infection and raising mouse survival rate, have apparent curative effect in the treatment of above-mentioned inflammation infection；
3, present embodiment discloses Semaphorin7A monoclonal antibodies to prepare for treating vital myocarditis disease, gold
The drug of the inflammation diseases such as the septicopyemia blood inflammation of staphylococcus aureus (S.aureus) induction and enterovirus EV 71 acute infection
The application of aspect；It is stated in the research and development and production of the drug of inflammation disease in the treatment, the use of Semaphorin7A monoclonal antibody
Way invention is of great significance；
4, the embodiment of the present invention establishes healthy Balb/c male mice model, as a kind of inflammation for accepting extensively and applying
Disease animal model, which is suitble to clinical application research, for vital myocarditis disease, staphylococcus aureus
(S.aureus) medicament research and development of the inflammation diseases such as the septicopyemia blood inflammation induced and enterovirus EV 71 acute infection has important
Application and popularization value.
Detailed description of the invention
To describe the technical solutions in the embodiments of the present invention more clearly, make required in being described below to embodiment
Attached drawing is briefly described, it should be apparent that, drawings in the following description are only some embodiments of the invention, for
For those of ordinary skill in the art, without creative efforts, it can also be obtained according to these attached drawings other
Attached drawing.
Fig. 1 is Sema7A_truncated albumen Bacillus coli expression figure；
Fig. 2 is Sema7A monoclonal antibody WB proof diagram；
Fig. 3, which is that Sema7A antibody ELISA is verified and GST-1, GST-2, GST-3 are affine, to try hard to；
Fig. 4 is the verifying of Sema7A antibody ELISA and peptide fragment P1, P2, P3, and P4, P5 are affine to try hard to；
Fig. 5 is the verifying of Sema7A antibody ELISA and peptide fragment 2, and 3,4,5 affine try hard to；
Fig. 6 is that CVB3 infecting mouse gives serum blood flesh calcium variation diagram after Sema7A Antybody therapy；
Fig. 7 is that CVB3 infecting mouse passes through heart tissue sections immunohistochemical staining figure after Sema7A Antybody therapy；
Fig. 8 is mouse heart tissue inflammatory factor detection figure after Sema7A Antybody therapy；
Fig. 9 is the survival rate figure of CVB3 virus infection myocarditis mouse after Sema7A Antybody therapy；
Figure 10 is Sema7A Antybody therapy infection of staphylococcus aureus mice serum inflammatory factor detection figure；
Figure 11 is Sema7A Antybody therapy infection of staphylococcus aureus mouse lung damage check figure；
Figure 12 is Sema7A Antybody therapy infection of staphylococcus aureus mouse kidney slice immunohistochemical staining figure；
Figure 13 is the survival rate figure of Sema7A Antybody therapy infection of staphylococcus aureus mouse；
Figure 14 is Sema7A Antybody therapy EV71 infecting mouse skeletal muscle slice immunohistochemical staining figure；
Figure 15 is Sema7A Antybody therapy EV71 infecting mouse small intestine sections immunohistochemical staining figure；
Figure 16 is Sema7A Antybody therapy EV71 infecting mouse brainstem slice immunohistochemical staining figure；
Figure 17 is Sema7A Antybody therapy EV71 infecting mouse inflammatory factor detection figure；
Figure 18 is the survival rate figure of Sema7A Antybody therapy EV71 infecting mouse；
Figure 19 is the survival rate figure of Sema7A antibody and antiviral drugs acyclovir treatment EV71 infecting mouse.
Specific embodiment
To make the object, technical solutions and advantages of the present invention clearer, below in conjunction with attached in the embodiment of the present invention
Figure, technical scheme in the embodiment of the invention is clearly and completely described, it is clear that described embodiment is only this
Invention a part of the embodiment, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art exist
Every other embodiment obtained under the premise of creative work is not made, shall fall within the protection scope of the present invention.
Embodiment 1
The present embodiment provides two kinds of Semaphorin7A monoclonal antibodies: 2567-1,2567-3, both
Semaphorin7A monoclonal antibody includes heavy chain variable region and light chain variable region.
Wherein, the heavy chain variable region of Semaphorin7A monoclonal antibody 2567-1 includes following 3 cdr amino acid sequences
An and nucleotide sequence: amino acid sequence is the VH CDR1 of SEQ ID NO.2, and amino acid sequence is the VH of SEQ ID NO.3
CDR2, amino acid sequence are the VH CDR3 of SEQ ID NO.4, and nucleotides sequence is classified as the nucleotide of SEQ ID NO.5.
The light chain variable region of Semaphorin7A monoclonal antibody 2567-1 includes following 3 cdr amino acid sequences and a nucleotide
Sequence: amino acid sequence is the VL CDR1 of SEQ ID NO.6, and amino acid sequence is the VL CDR2 of SEQ ID NO.7, amino acid
Sequence is the VL CDR3 of SEQ ID NO.8, and nucleotides sequence is classified as the nucleotide of SEQ ID NO.9.
Likewise, the heavy chain variable region of Semaphorin7A monoclonal antibody 2567-3 includes following 3 cdr amino acid sequences
Column and a nucleotide sequence: amino acid sequence is the VH CDR1 of SEQ ID NO.10, and amino acid sequence is SEQ ID NO.11
VH CDR2, amino acid sequence is the VHCDR3 of SEQ ID NO.12, and nucleotides sequence is classified as the nucleotide of SEQ ID NO.13.
The light chain variable region of Semaphorin7A monoclonal antibody 2567-3 includes following 3 cdr amino acid sequences and a nucleotide
Sequence: amino acid sequence is the VL CDR1 of SEQ ID NO.14, and amino acid sequence is the VL CDR2 of SEQ ID NO.15, amino
Acid sequence is the VL CDR3 of SEQ ID NO.16, and nucleotides sequence is classified as the nucleotide of SEQ ID NO.17.
The present embodiment additionally provides a kind of preparation method of Semaphorin7A monoclonal antibody, which specifically wraps
Include following steps:
(1) firstly, by protean program in Lasergene software package, to the antigenicity of mouse Sema7A gene order
It is analyzed, obtains antigenic preferable protein sequence Sema7A_truncated (SEQ ID NO.18).
(2) as shown in Figure 1, Sema7A_truncated sequence is cloned into pET28a prokaryotic expression carrier, in large intestine bar
By IPTG inducing expression in bacterium, the antigen protein of Sema7A_truncated is expressed.
(3) antigen protein of Sema7A_truncated is by subcutaneous inoculation mouse, take immune Mouse spleen cells with
Sp20 cell fusion obtains 3 plants of Sema7A specific mouse monoclonal antibodies.As shown in the Elisa potency table of table 1, in order to test
The neutralization titer for demonstrate,proving the antibody of preparation carries out various concentration dilution, hair to the antibody of preparation with the antigen coat plank of 1 microgram
Show this 3 plants antibody under 1: 80000 dilution ratio, or well can be in conjunction with antigen Sema7A_truncated.
The Elisa potency table of table 1 Semaphorin7A monoclonal antibody 2567-1,2567-2,2567-3
* judgment criteria: S/N > 2.1 (S: antibody test OD value, N: blank control detects OD value)
Conclusion: gained antibody titer complies with standard, and Elisa testing result is qualified.
(4) as shown in Fig. 2, we demonstrate the specificity of 3 strain antibodies of acquisition also by western blot mode,
Mouse lung tissue is taken to run PAGE gel, our antibody 1: 1000 or 1: 5000 can detect Sema7A albumen
Expression, positive control is the antibody of commercialization, shows that be successfully prepared 3 plants of mouse Sema7A special by testing us above
Anisotropic monoclonal antibody.
Further, the present embodiment additionally provides identification and the antibody sequence of Semaphorin7A monoclonal antibody antigen epitope
Analysis, specifically comprise the following steps:
(1) in order to which the epitope to Semaphorin7A monoclonal antibody is analyzed, Sema7A_truncated
Albumen is further divided into 3 sections: (amino acid sequence is respectively such as SEQ ID NO.19-SEQ ID by GST-1, GST-2, GST-3
Shown in NO.21).By doing amalgamation and expression with prokaryotic expression carrier GST, the GST-1 of expression and purification, GST-2, GST-3 albumen
It is coated with plank, then does Enzyme-linked Immunosorbent Assay reaction with antibody, the results showed that with the albumen of Sema7A_truncated
(Sema7A-His) it can be good at and 2567-1,2567-3 antibody combine.As shown in figs.3 a and 3b, further analysis
It is found that GST-3 protein sequence can be combined with 2567-1,2567-3 respectively in the albumen of Sema7A_truncated.
(2) on the basis of GST-3 amino acid sequence, 5 peptide fragments: P1, P2, P3, P4 and P5 are further divided into,
5 peptide fragments of synthesis as shown in NO.22~26 SEQ ID, are coated with plank respectively by the amino acid sequence of middle P1 to P5, same to use
Antibody does Enzyme-linked Immunosorbent Assay reaction, detects the compatibility of 2567-1 and 2567-3 antibody and its.Result hair as shown in Figure 4
Existing: P2 peptide section sequence has very high compatibility as GST-3 positive control, with 2567-1 and 2567-3 antibody.
(3) as shown in figure 5, analyzing the sequence that P2 peptide fragment and monoclonal antibody combine in order to be more accurate, further
P2 successively decreases from N-terminal or C-terminal, is divided into 4 peptide fragments 2~5, amino acid sequence is respectively such as SEQ ID NO.27-SEQ ID
Shown in NO.30.After carrying out biochemical synthesis, the peptide fragment of synthesis is coated with plank, equally Enzyme-linked Immunosorbent Assay reaction is done with antibody, examines
The compatibility of 2567-1 and 2567-3 antibody and its is surveyed, as a result, it has been found that combination of the N-terminal amino acid sequence of P2 peptide fragment for antibody,
Serve critically important.As shown in Figure 5A, if C-terminal has been done the missing of 4 amino acid, No. 2 peptide fragments and P2 peptide fragment
2567-1 and 2567-3 affinity of antibody is changed less, and it is as shown in Figure 5 B, if P2 peptide fragment is done 4 amino from N-terminal
Acid missing, then the affinity with 2567-1 and 2567-3 antibody weakens significantly.Therefore, above-mentioned test proves, No. 2 peptide fragments:
FSPDENSLVLFEGDEV is that the antigen for the 2567-1 and 2567-3Sema7A monoclonal antibody that we prepare determines epitope.
(4) in order to analyze the sequence of 2567-1 and 2567-3 monoclonal antibody and antigen binding, for the present embodiment provides
The variable region of 2567-1 and 2567-3 monoclonal antibody carried out gene cloning and sequencing.
Further, the amino acid sequence of Semaphorin7A monoclonal antibody includes:
The heavy chain and the amino acid sequence as shown in SEQ ID NO.32 that the amino acid sequence shown in SEQ ID NO.31 is constituted
The light chain (2567-1) of composition；Or；
The heavy chain and the amino acid sequence as shown in SEQ ID NO.34 that the amino acid sequence shown in SEQ ID NO.33 is constituted
The light chain (2567-3) of composition.
The present embodiment using truncating expression and the technologies such as section of synthesized peptide, to Semaphorin7A monoclonal antibody 2567-1,
The epitope that 2567-3 is identified carries out elutriation and obtains its consistent epitope sequences.Sequence alignment result shows this
The polypeptide sequence that Semaphorin7A monoclonal antibody is identified falls in Semaphorin7A β coil region.Further, applicant utilizes anti-
Light chain, the heavy chain that body gene sequencing technology analyzes 2567-1,2567-3 monoclonal antibody and Sema7A is specifically bound
Sequence.
Embodiment 2
A kind of Semaphorin7A monoclonal antibody (2567-1,2567-3) is present embodiments provided in treatment CVB3 induction
Vital myocarditis disease in application.
The viral myocarditis model of building CVB3 induction first；The construction step of the model specifically includes:
(1) the male Balb/c mouse of 6-8 week old is taken, divides 4 groups, every group 6, every mouse is given in a manner of intraperitoneal injection
103The CVB3 virus of TCID50 dosage, inducing mouse vital myocarditis disease model.
(2) at first day of virus infection, third day and mouse is given in a manner of intraperitoneal injection respectively on the 5th day
Only, CVB3 group is virus infection non-treatment control group to Sema7A2567-1 2567-3 antibody 50ug/, and control is health
Mouse group.
As shown in fig. 6, observation mouse core myositis index was compared with control group at the 7th day of infection, mouse Sema7A is given
After antibody 2567-1 treatment, serum blood flesh calcium index cTnI content is 2.77ng/ml, gives mouse Sema7A antibody 2567-3
After treatment, serum blood flesh calcium index cTnI content is 4.24ng/ml, and the cTnI content of CVB3 control group is 10.83ng/
Ml, control group cTnI content is 0.54ng/ml in healthy mice serum.
It takes infecting mouse heart tissue within the 7th day after infection, is dyed with haematoxylin (Hematoxylin)-Yihong (Eosin)
The inflammatory cell of infiltration.As shown in fig. 7, mouse heart pathological section again shows that, Sema7A 2567-1,2567-3 antibody is controlled
Treatment group mouse heart was shown in a little inflammation at the 7th day, and control group CVB3 mouse heart increased inflammation, had big amount lymphocyte to soak
Profit, heart is in diffusivity necrosis, and as indicated by the arrows in the figure, myocardium markers slice dyeing is consistent with serum cTnI result.
Further, the 7th day heart tissue of infecting mouse is ground, is secreted in detection heart tissue related to inflammation
Cell factor, testing result is as shown in Figure 8, the results showed that: inflammatory cytokine IL-6, IL-1 β and TNF-a in 2567-1,
2567-3 Antybody therapy group mouse decreases drastically compared with CVB3 group, and MCP-1 inflammatory factor is in 2567-1,2567-
3 Antybody therapy group mouse and CVB3 group compare, and do not change significantly.
Further referring to figure 9, the daily Survival of observation each group mouse, Sema7A2567-1 antibody group can effectively improve
The survival rate of mouse reaches 83.3% (5, n=6), and the survival rate that Sema7A2567-3 antibody group can effectively improve mouse reaches
67.7% (4, n=6), and the survival rate of control group mice only has 50% (3, n=6).
Technical solution provided in this embodiment has the benefit that
1, the present embodiment gives the vital myocarditis disease of CVB3 induction with the treatment of Semaphorin7A monoclonal antibody,
Cardiac muscle cell's inflammation can be effectively relieved and improve mouse survival rate, there is apparent curative effect in treatment myocarditis disease；
2, present embodiment discloses Semaphorin7A monoclonal antibodies to prepare for treating the viral of CVB3 induction
Application in terms of myocardial inflammation drug；In the research and development and production for the treatment of myocardial inflammation drug, Semaphorin7A monoclonal is anti-
The purposes invention of body is of great significance；
3, the embodiment of the present invention establishes healthy Balb/c male mice model, as a kind of heart for accepting extensively and applying
Myositis animal model, the model are suitble to clinical application research, have important application valence for the medicament research and development of myocarditis
Value.
Embodiment 3
It present embodiments provides a kind of Semaphorin7A monoclonal antibody (2567-1,2567-3) and is treating golden yellow Portugal
Application in the septicopyemia blood inflammation of grape coccus (S.aureus) induction.
The septicopyemia blood inflammatory model of same building staphylococcus aureus (S.aureus) induction；The building of the model walks
Suddenly it specifically includes:
(1) the male C57bl/6 mouse of 6-8 week old is taken, it is points 4 groups, every group 6, old to every in a manner of intraperitoneal injection
Mouse 107The staphylococcus aureus of CFU0 dosage induces septicopyemia blood mouse inflammatory model.
(2) at first day of bacterium infection, third day and mouse is given in a manner of intraperitoneal injection respectively on the 5th day
Only, S.aureus group is bacterium infection non-treatment control group to Sema7A 2567-1 or 2567-3 antibody 50ug/, and control is
Healthy mice group.
The 6th day serum inflammatory cell factor of infecting mouse is detected, testing result is as shown in Figure 10.As a result table
Bright: inflammatory cytokine IL-6, MCP-1 and TNF-ot are in 2567-1,2567-3 Antybody therapy group mouse and S.aureus group ratio
Compared with decreasing drastically, and IL-10 inflammatory factor, in 2567-1,2567-3 Antybody therapy group mouse and CVB3 group compare, and do not have
It changes significantly.
As shown in figure 11, we detect mouse lung organ.Wet/dry weight ratio of lung tissue is lung injury
An index, we infection have detected within the 6th day each group mouse lung tissue wet/dry weight ratio, testing result such as Figure 11 A institute
Show, 2567-1,2567-3 Antybody therapy group mouse is compared with S.aureus group, under wet/dry weight ratio of lung tissue has significantly
Drop, likewise, as shown in Figure 11 B, the carrying capacity of Bacteria in Blood is by 2567-1, and after 2567-3 Antybody therapy, there has also been bright
Aobvious decline.Likewise, as shown in Figure 11 C, while protein content in pulmonary lavage liquid is detected, pass through 2567-1,2567-3 antibody
After treatment, there has also been be decreased obviously.The above result shows that Sema7A antibody 2567-1,2567-3 treatment can improve golden yellow
The pulmonary lesion of staphy lococcus infection.
Meanwhile we also detect mouse kidney organ.Pass through HE Kidney sections, testing result such as Figure 12 institute
Show: S.aureus group Kidney sections mesonephric glomerulus structure has destruction, is rendered as irregular shape or flat, some kidneys are small
Spherical structure intermediate bladder cavity gap becomes smaller or disappears (as indicated by the arrows in the figure).
Referring to Fig.1 shown in 3, the daily Survival of observation each group mouse, Sema7A2567-1 antibody group can be effectively improved
The survival rate of mouse reaches 83.3% (5, n=6), and the survival rate that Sema7A2567-3 antibody group can effectively improve mouse reaches
67.7% (4, n=6), and the survival rate of control group mice only has 33.3% (2, n=6).
Technical solution provided in this embodiment has the benefit that
1, the present embodiment give staphylococcus aureus (S.aureus) induction septicopyemia blood inflammation with
The treatment of Semaphorin7A monoclonal antibody can be effectively relieved septicopyemia blood inflammation and improve mouse survival rate, in golden yellow
There is apparent curative effect in the septicopyemia blood inflammation treatment of staphylococcus (S.aureus) induction；
2, present embodiment discloses Semaphorin7A monoclonal antibodies to prepare for treating staphylococcus aureus
(S.aureus) application in terms of the septicopyemia blood anti-inflammatory drugs induced；In the septicopyemia of staphylococcus aureus (S.aureus) induction
In the research and development and production of blood anti-inflammatory drugs, the purposes invention of Semaphorin7A monoclonal antibody is of great significance；
3, the embodiment of the present invention establishes healthy Balb/c male mice model, as a kind of gold for accepting extensively and applying
The septicopyemia blood inflammatory animal model of staphylococcus aureus (S.aureus) induction, which is suitble to clinical application research, for gold
The medicament research and development of the septicopyemia blood inflammation of staphylococcus aureus (S.aureus) induction has important application and popularization value.
Embodiment 4
A kind of Semaphorin7A monoclonal antibody (2567-1,2567-3) is present embodiments provided in treatment enterovirus
Application in EV71 acute infection.EV7 virus Central nervous system has high infectivity, clinically the symptom packet of appearance
Include encephalitis (encephalitis), aseptic meningitis (aseptic meningitis), acute powerless limb paralysis (acute
Flaccid paralysis), brothers' mouthful disease (hand-foot-mouth disease), bubble rash angina
(herpangina), acute hemorrhagic conjunctivitis (acute hemorrhagic conjuctivitis) etc., especially to infant
It endangers huge.
It is same to construct enterovirus EV 71 acute infection model in the present embodiment；The construction step of the model specifically wraps
It includes:
(1) animal model for having initially set up EV71 infection suckling mouse, takes 3-5 days male Balb/c mouse, divides 4 groups, often
Group 6, directly to mouse peritoneal injection 107PFU EV71 virus.
(2) at first day of virus infection, third day and mouse is given in a manner of intraperitoneal injection respectively on the 5th day
Only, CVB3 group is virus infection non-treatment control group to Sema7A 2567-1 or 2567-3 antibody 50ug/, and control is health
Mouse group.
At first day of virus infection, third day and mouse Sema7A is given in a manner of intraperitoneal injection respectively on the 5th day
Only, CVB3 group is virus infection non-treatment control group to 2567-1 2567-3 antibody 50ug/, and control is healthy mice group.
It takes infecting mouse skeletal muscle tissue within the 5th day after infection, is contaminated with haematoxylin (Hematoxylin)-Yihong (Eosin)
The inflammatory cell of color infiltration.As shown in figure 14, mice skeletal pathological section shows that Sema7A 2567-1,2567-3 antibody are controlled
The infiltration for the treatment of group mice skeletal inflammatory cell will infect non-treatment group considerably less than EV71.We are to infecting mouse small intestine simultaneously
Tissue carries out HE slice dyeing, and as shown in figure 15, compared with non-treatment group, Sema7A 2567-1,2567-3 Antybody therapy group is small
Mouse intestinal microvillus structure, which is destroyed, to be improved.Especially in nerve fiber, as shown in figure 16, we also observe identical existing
As the infiltration in the brain stem area of infecting mouse, the inflammatory cell of Sema7A 2567-1,2567-3 Antybody therapy group mouse is bright
It is aobvious to be less than non-treatment group EV71.
As shown in figure 17, to the inflammatory cytokine in infecting mouse the 5th day skeletal muscle, small intestine and brain stem, we are used quantitatively
The mode of PCR is detected；Testing result shows: inflammatory cytokine IL-6, MCP-1 and TNF-α are in 2567-1,2567-3
Antybody therapy group mouse compared with EV71 non-treatment group, decreases drastically in skeletal muscle, small intestine and brain stem.
With further reference to the daily Survival of each group mouse shown in Figure 18, is observed, although Antybody therapy cannot finally mention
The survival rate of high mouse, but it is all dead at infection the 7th day compared to non-treatment group, and Sema7A antibody 2567-1 and 2567-3 are controlled
Relatively 1 times of mouse survival time and control group can be extended significantly by treating.
In addition, we establish EV7 virus infection and are controlled by Sema7A antibody and antiviral drugs acyclovir
The mouse model for the treatment of.3-5 days male Balb/c mouse are taken, divides 4 groups, every group 6, injects 107PFU directly to mouse peritoneal
EV71 virus.At first day of virus infection, third day and mouse Sema7A is given in a manner of intraperitoneal injection respectively on the 5th day
2567-150ug/ or acyclovir (25mg/kg) drug, or both give, and EV71 group is virus infection non-treatment
Control group, control are healthy mice group.
Observe the daily Survival of each group mouse, Semaphorin7A antibody shown in Figure 19 and antiviral drugs
The survival rate figure of acyclovir treatment EV71 infecting mouse, the results showed that if being given only acyclovir drug therapy, that
The survival rate of the one mouse is 33.4% (n=6), but if with Sema7A antibody drug combination therapy, that the one mouse
Survival rate can greatly improve 1 times to 66.7%, therefore, can further illustrate the Semaphorin7A monoclonal that we prepare
Antibody has huge application value in the clinical treatment of EV71.
Technical solution provided in this embodiment has the benefit that
1, the present embodiment gives enterovirus EV 71 acute infection with the treatment of Semaphorin7A monoclonal antibody, energy
EV71 acute infection is enough effectively relieved and improves mouse survival rate, has in enterovirus EV 71 acute infection treatment apparent
Curative effect；
2, it is acute for treating enterovirus EV 71 in preparation that present embodiment discloses Semaphorin7A monoclonal antibodies
Application in terms of the drug of infection；In the research and development and production of the drug of enterovirus EV 71 acute infection, Semaphorin7A
The purposes invention of monoclonal antibody is of great significance；
3, the embodiment of the present invention establishes healthy Balb/c male mice model, as a kind of intestines for accepting extensively and applying
The animal model of road virus EV71 acute infection, which is suitble to clinical application research, for enterovirus EV 71 acute infection
Medicament research and development have important application and popularization value.
Embodiment 5
The present embodiment further provide it is a kind of for treating the drug of inflammation disease, in the present embodiment pharmaceutical dosage form be liquid
Body preparation, active constituent include Semaphorin7A monoclonal antibody above-mentioned.Wherein, Semaphorin7A monoclonal antibody
Content is 75-120mg.The drug of the treatment inflammation disease further includes excipient substance and medicinal substrate.
Specifically, excipient substance includes immunologic adjuvant, stabilizer, preservative.Wherein the 1% white egg of people can be selected in stabilizer
It is white；In specific implementation, the carbohydrates biological agent stabilizers such as maltose, glucose, sorbierite are also often selected.Immunologic adjuvant is selected
Vegetable oil adjuvant is specifically chosen as glycerol；Preservative is the chloroform that concentration is 0.5%.
In addition, pharmaceutical preparation can also contain other common adjuvant materials or additive, such as antioxidant such as gluathione
The substances such as peptide or ascorbic acid.
Specifically, include Semaphorin7A monoclonal antibody as active component in the embodiment of the present invention and prepare drug
Matrix is preferably the antibody-solutions of the buffering containing sodium chloride, such as injection.The antibody-solutions and the sugared, amino containing additive
The aqueous solution of acid and surfactant mixes, while adjusting pH to 5-8 with acid or alkali.Appropriate phosphoric acid or phosphate and chlorination is added
Sodium, so that solution reaches previously determined concentration.
Technical solution provided in an embodiment of the present invention has the benefit that
1, the embodiment of the present invention gives controlling for morbidity mouse Semaphorin7A monoclonal antibody (2567-1,2567-3)
It treats, the septicopyemia blood inflammation and enteron aisle of vital myocarditis disease, staphylococcus aureus (S.aureus) induction can be effectively relieved
Inflammation caused by viral EV71 acute infection and raising mouse survival rate have apparent curative effect in treatment part inflammation disease；
2, the embodiment of the invention discloses Semaphorin7A monoclonal antibodies (2567-1,2567-3) to prepare for controlling
Treat the application in the drug of inflammation disease；In the research and development and production of the drug for the treatment of inflammation, Semaphorin7A monoclonal is anti-
The new application invention of body (2567-1,2567-3) is of great significance.
Embodiment 6
Solution first such as the preparation process preparation of embodiment 5 as ejection preparation, then, filtration sterilization, freeze-drying
The solution, is made lyophilized preparation.
The embodiment of the present invention also added in medicinal substrate to be passed through containing the unstable aqueous solution to freezing sensitive antibody
The mode of freeze-drying is transformed into stable preparation, and the stabilization formulations also never degenerate at high temperature and keep stable.Having
During body is implemented, the carbohydrates biological agent stabilizers such as maltose, glucose, sorbierite are also often selected.
According to the present invention, the freeze-drying object additional advantage is that in addition to freezing during avoid antibody damage other than,
Even if the antibody content of the long term storage at 50 DEG C, the freeze-drying object is not reduced, and is formed or do not occurred without aggregation
Flocculation.Therefore, the content and purity of antibody, is stable.After regenerating freeze-drying object with water for injection, low turbidity value is shown
The formation of particulate matter is avoided by.
The foregoing is merely presently preferred embodiments of the present invention, is not intended to limit the invention, it is all in spirit of the invention and
Within principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Sequence table
<110>University Of Suzhou
<120>Semaphorin7A monoclonal antibody and its application in terms of preparation is for treating inflammation disease drug
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Met Thr Pro Pro Pro Pro Gly Arg Ala Ala Pro Ser Ala Pro Arg Ala
1 5 10 15
Arg Val Leu Ser Leu Pro Ala Arg Phe Gly Leu Pro Leu Arg Leu Arg
20 25 30
Leu Leu Leu Val Phe Trp Val Ala Ala Ala Ser Ala Gln Gly His Ser
35 40 45
Arg Ser Gly Pro Arg Ile Ser Ala Val Trp Lys Gly Gln Asp His Val
50 55 60
Asp Phe Ser Gln Pro Glu Pro His Thr Val Leu Phe His Glu Pro Gly
65 70 75 80
Ser Phe Ser Val Trp Val Gly Gly Arg Gly Lys Val Tyr His Phe Asn
85 90 95
Phe Pro Glu Gly Lys Asn Ala Ser Val Arg Thr Val Asn Ile Gly Ser
100 105 110
Thr Lys Gly Ser Cys Gln Asp Lys Gln Asp Cys Gly Asn Tyr Ile Thr
115 120 125
Leu Leu Glu Arg Arg Gly Asn Gly Leu Leu Val Cys Gly Thr Asn Ala
130 135 140
Arg Lys Pro Ser Cys Trp Asn Leu Val Asn Asp Ser Val Val Met Ser
145 150 155 160
Leu Gly Glu Met Lys Gly Tyr Ala Pro Phe Ser Pro Asp Glu Asn Ser
165 170 175
Leu Val Leu Phe Glu Gly Asp Glu Val Tyr Ser Thr Ile Arg Lys Gln
180 185 190
Glu Tyr Asn Gly Lys Ile Pro Arg Phe Arg Arg Ile Arg Gly Glu Ser
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210 215 220
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225 230 235 240
Phe Phe Arg Glu Asp Asn Pro Asp Lys Asn Pro Glu Ala Pro Leu Asn
245 250 255
Val Ser Arg Val Ala Gln Leu Cys Arg Gly Asp Gln Gly Gly Glu Ser
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Ser Leu Ser Val Ser Lys Trp Asn Thr Phe Leu Lys Ala Met Leu Val
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Cys Ser Asp Ala Ala Thr Asn Arg Asn Phe Asn Arg Leu Gln Asp Val
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Phe Leu Leu Pro Asp Pro Ser Gly Gln Trp Arg Asp Thr Arg Val Tyr
305 310 315 320
Gly Val Phe Ser Asn Pro Trp Asn Tyr Ser Ala Val Cys Val Tyr Ser
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Leu Gly Asp Ile Asp Arg Val Phe Arg Thr Ser Ser Leu Lys Gly Tyr
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His Met Gly Leu Pro Asn Pro Arg Pro Gly Met Cys Leu Pro Lys Lys
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Gln Pro Ile Pro Thr Glu Thr Phe Gln Val Ala Asp Ser His Pro Glu
370 375 380
Val Ala Gln Arg Val Glu Pro Met Gly Pro Leu Lys Thr Pro Leu Phe
385 390 395 400
His Ser Lys Tyr His Tyr Gln Lys Val Val Val His Arg Met Gln Ala
405 410 415
Ser Asn Gly Glu Thr Phe His Val Leu Tyr Leu Thr Thr Asp Arg Gly
420 425 430
Thr Ile His Lys Val Val Glu Ser Gly Asp Gln Asp His Ser Phe Val
435 440 445
Phe Asn Ile Met Glu Ile Gln Pro Phe His Arg Ala Ala Ala Ile Gln
450 455 460
Ala Ile Ser Leu Asp Ala Asp Arg Arg Lys Leu Tyr Val Thr Ser Gln
465 470 475 480
Trp Glu Val Ser Gln Val Pro Leu Asp Met Cys Glu Val Tyr Ser Gly
485 490 495
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500 505 510
Gln Asp Arg Cys Val Ser Ile Tyr Ser Ser Gln Arg Ser Val Leu Gln
515 520 525
Ser Ile Asn Pro Ala Glu Pro His Arg Glu Cys Pro Asn Pro Lys Pro
530 535 540
Asp Glu Ala Pro Leu Gln Lys Val Ser Leu Ala Arg Asn Ser Arg Tyr
545 550 555 560
Tyr Leu Thr Cys Pro Met Glu Ser Arg His Ala Thr Tyr Leu Trp Arg
565 570 575
His Glu Glu Asn Val Glu Gln Ser Cys Glu Pro Gly His Gln Ser Pro
580 585 590
Ser Cys Ile Leu Phe Ile Glu Asn Leu Thr Ala Arg Gln Tyr Gly His
595 600 605
Tyr Arg Cys Glu Ala Gln Glu Gly Ser Tyr Leu Arg Glu Ala Gln His
610 615 620
Trp Glu Leu Leu Pro Glu Asp Arg Ala Leu Ala Glu Gln Leu Met Gly
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Leu Ile Leu Gly Leu Leu Val His
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Gly Tyr Thr Phe Thr Ser Tyr Tyr
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Thr Thr Pro Ala Arg Ala Thr Phe Ala Tyr
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caggtccaac tgcagcagtc tggggctgaa ctggtgaagc ctggggcttc agtgaagttg 60
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cctggacaag gccttgagtg gattggagag attaatccta gcaatggtga tactaacttc 180
aatgagaagt tcaagagcaa ggccacactg actgtagaca aatcctccag cacagcttac 240
atgcaactca gcagcctgac atctgaggac tctgcggtct attactgtac aacaccagct 300
cgggctacgt ttgcttactg gggccaaggg actctggtca ctgtctctgc ag 352
<210> 6
<211> 11
<212> PRT
<213>artificial sequence (Artificial Sequence)
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Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr
1 5 10
<210> 7
<211> 3
<212> PRT
<213>artificial sequence (Artificial Sequence)
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Lys Val Ser
1
<210> 8
<211> 9
<212> PRT
<213>artificial sequence (Artificial Sequence)
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Ser Gln Ser Thr His Val Pro Tyr Thr
1 5
<210> 9
<211> 337
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 9
gatgttgtga tgacccaaac tccactctcc ctgcctgtca gtcttggaga tcaagcctcc 60
atctcttgca gatctagtca gagccttgta cacagtaatg gaaacaccta tttacattgg 120
tacctgcaga agccaggcca gtctccaaag ctcctgatct acaaagtttc caaccgattt 180
tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc 240
agcagagtgg aggctgagga tctgggagtt tatttctgct ctcaaagtac acatgttccg 300
tacacgttcg gaggggggac caagctggaa ataaaac 337
<210> 10
<211> 8
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 10
Gly Tyr Thr Phe Thr Ser Tyr Trp
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<210> 11
<211> 8
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 11
Ile Asp Pro Ser Asp Ser Tyr Thr
1 5
<210> 12
<211> 6
<212> PRT
<213>artificial sequence (Artificial Sequence)
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Ala Arg Asp Gly Gly Tyr
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<210> 13
<211> 340
<212> DNA
<213>artificial sequence (Artificial Sequence)
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caggtccaac tgcagcagcc tggggctgag cttgtgaagt ctggggcttc agtgaagctg 60
tcctgcaagg cttctggcta caccttcacc agctactgga tgcactgggt gaagcagagg 120
cctggacaag gccttgagtg gatcggagag attgatcctt ctgatagtta tactaactac 180
aatcaaaagt ttaagggcaa ggccacattg actgttgaca aatcctccag cacagcctac 240
atgcagctca gcagcctgac atctgaggag tctgcggtct attactgtgc aagagatggc 300
ggctactggg gccaaggcac cactctcaca gtctcctcag 340
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<211> 6
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<213>artificial sequence (Artificial Sequence)
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Gln Asp Val Ser Thr Ala
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<210> 15
<211> 3
<212> PRT
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Ser Ala Ser
1
<210> 16
<211> 9
<212> PRT
<213>artificial sequence (Artificial Sequence)
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Gln Gln His Tyr Ser Thr Pro Trp Thr
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<210> 17
<211> 322
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 17
gacattgtga tgacccagtc tcacaaattc atgtccacat cagtaggaga cagggtcatc 60
atcacctgca aggccagtca ggatgtgagt actgctgtag cctggtatca acagaaacca 120
ggacaatctc ctaaattact aatttactcg gcatcctacc gatacactgg agtccctgat 180
cgcttcactg gcagtggatc tgggacggat ttcactttca ccatcagcag tgtgcaggct 240
gaagacctgg cagtttatta ctgtcagcaa cattatagta ctccgtggac gttcggtgga 300
ggcaccaagc tggaaatcag ac 322
<210> 18
<211> 161
<212> PRT
<213>artificial sequence (Artificial Sequence)
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Lys Gly Gln Asp His Val Asp Phe Ser Gln Pro Glu Pro His Thr Val
1 5 10 15
Leu Phe His Glu Pro Gly Ser Phe Ser Val Trp Val Gly Gly Arg Gly
20 25 30
Lys Val Tyr His Phe Asn Phe Pro Glu Gly Lys Asn Ala Ser Val Arg
35 40 45
Thr Val Asn Ile Gly Ser Thr Lys Gly Ser Cys Gln Asp Lys Gln Asp
50 55 60
Cys Gly Asn Tyr Ile Thr Leu Leu Glu Arg Arg Gly Asn Gly Leu Leu
65 70 75 80
Val Cys Gly Thr Asn Ala Arg Lys Pro Ser Cys Trp Asn Leu Val Asn
85 90 95
Asp Ser Val Val Met Ser Leu Gly Glu Met Lys Gly Tyr Ala Pro Phe
100 105 110
Ser Pro Asp Glu Asn Ser Leu Val Leu Phe Glu Gly Asp Glu Val Tyr
115 120 125
Ser Thr Ile Arg Lys Gln Glu Tyr Asn Gly Lys Ile Pro Arg Phe Arg
130 135 140
Arg Ile Arg Gly Glu Ser Glu Leu Tyr Thr Ser Asp Thr Val Met Gln
145 150 155 160
Asn
<210> 19
<211> 50
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 19
Lys Gly Gln Asp His Val Asp Phe Ser Gln Pro Glu Pro His Thr Val
1 5 10 15
Leu Phe His Glu Pro Gly Ser Phe Ser Val Trp Val Gly Gly Arg Gly
20 25 30
Lys Val Tyr His Phe Asn Phe Pro Glu Gly Lys Asn Ala Ser Val Arg
35 40 45
Thr Val
50
<210> 20
<211> 51
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 20
Asn Ile Gly Ser Thr Lys Gly Ser Cys Gln Asp Lys Gln Asp Cys Gly
1 5 10 15
Asn Tyr Ile Thr Leu Leu Glu Arg Arg Gly Asn Gly Leu Leu Val Cys
20 25 30
Gly Thr Asn Ala Arg Lys Pro Ser Cys Trp Asn Leu Val Asn Asp Ser
35 40 45
Val Val Met
50
<210> 21
<211> 60
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 21
Ser Leu Gly Glu Met Lys Gly Tyr Ala Pro Phe Ser Pro Asp Glu Asn
1 5 10 15
Ser Leu Val Leu Phe Glu Gly Asp Glu Val Tyr Ser Thr Ile Arg Lys
20 25 30
Gln Glu Tyr Asn Gly Lys Ile Pro Arg Phe Arg Arg Ile Arg Gly Glu
35 40 45
Ser Glu Leu Tyr Thr Ser Asp Thr Val Met Gln Asn
50 55 60
<210> 22
<211> 20
<212> PRT
<213>artificial sequence (Artificial Sequence)
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Ser Leu Gly Glu Met Lys Gly Tyr Ala Pro Phe Ser Pro Asp Glu Asn
1 5 10 15
Ser Leu Val Leu
20
<210> 23
<211> 20
<212> PRT
<213>artificial sequence (Artificial Sequence)
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Phe Ser Pro Asp Glu Asn Ser Leu Val Leu Phe Glu Gly Asp Glu Val
1 5 10 15
Tyr Ser Thr Ile
20
<210> 24
<211> 20
<212> PRT
<213>artificial sequence (Artificial Sequence)
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Phe Glu Gly Asp Glu Val Tyr Ser Thr Ile Arg Lys Gln Glu Tyr Asn
1 5 10 15
Gly Lys Ile Pro
20
<210> 25
<211> 20
<212> PRT
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Arg Lys Gln Glu Tyr Asn Gly Lys Ile Pro Arg Phe Arg Arg Ile Arg
1 5 10 15
Gly Glu Ser Glu
20
<210> 26
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<212> PRT
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Arg Phe Arg Arg Ile Arg Gly Glu Ser Glu Leu Tyr Thr Ser Asp Thr
1 5 10 15
Val Met Gln Asn
20
<210> 27
<211> 16
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 27
Phe Ser Pro Asp Glu Asn Ser Leu Val Leu Phe Glu Gly Asp Glu Val
1 5 10 15
<210> 28
<211> 12
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 28
Phe Ser Pro Asp Glu Asn Ser Leu Val Leu Phe Glu
1 5 10
<210> 29
<211> 16
<212> PRT
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<400> 29
Glu Asn Ser Leu Val Leu Phe Glu Gly Asp Glu Val Tyr Ser Thr Ile
1 5 10 15
<210> 30
<211> 12
<212> PRT
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Val Leu Phe Glu Gly Asp Glu Val Tyr Ser Thr Ile
1 5 10
<210> 31
<211> 117
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 31
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Tyr Met Tyr Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Ser Asn Gly Asp Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Ser Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Thr Pro Ala Arg Ala Thr Phe Ala Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ala
115
<210> 32
<211> 112
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 32
Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly
1 5 10 15
Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser
85 90 95
Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 33
<211> 113
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 33
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Ser Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asp Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Glu Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Gly Gly Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser
100 105 110
Ser
<210> 34
<211> 107
<212> PRT
<213>artificial sequence (Artificial Sequence)
<400> 34
Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val Gly
1 5 10 15
Asp Arg Val Ile Ile Thr Cys Lys Ala Ser Gln Asp Val Ser Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Ala Ser Tyr Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Ala
65 70 75 80
Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Arg
100 105
Claims (9)
1. a kind of Semaphorin7A monoclonal antibody, it is characterised in that: the Semaphorin7A monoclonal antibody includes weight
Chain amino acid variable region and light chain amino acid variable region, in which: 6 CDR amino of the Semaphorin7A monoclonal antibody
Acid sequence is as follows:
The amino acid sequence of VH CDR1 is SEQ ID NO.2,
The amino acid sequence of VH CDR2 is SEQ ID NO.3,
The amino acid sequence of VH CDR3 is SEQ ID NO.4,
The amino acid sequence of VL CDR1 is SEQ ID NO.6,
The amino acid sequence of VL CDR2 is SEQ ID NO.7,
The amino acid sequence of VL CDR3 is SEQ ID NO.8；Or
The amino acid sequence of VH CDR1 is SEQ ID NO.10,
The amino acid sequence of VH CDR2 is SEQ ID NO.11,
The amino acid sequence of VH CDR3 is SEQ ID NO.12,
The amino acid sequence of VL CDR1 is SEQ ID NO.14,
The amino acid sequence of VL CDR2 is SEQ ID NO.15,
The amino acid sequence of VL CDR3 is SEQ ID NO.16.
2. a kind of Semaphorin7A monoclonal antibody according to claim 1, it is characterised in that: described
The homology of 6 cdr amino acids is at least 90% in Semaphorin7A monoclonal antibody.
3. a kind of Semaphorin7A monoclonal antibody according to claim 1, it is characterised in that: described
The amino acid sequence of Semaphorin7A monoclonal antibody includes:
What the heavy chain and the amino acid sequence shown in SEQ ID NO.9 that the amino acid sequence shown in SEQ ID NO.5 is constituted were constituted
Light chain；Or；
The heavy chain and the amino acid sequence shown in SEQ ID NO.17 that the amino acid sequence shown in SEQ ID NO.13 is constituted are constituted
Light chain.
4. one kind Semaphorin7A monoclonal antibody as described in any one of claims 1 to 3 is being prepared for treating inflammation disease
Application in terms of medicine, it is characterised in that: the inflammation disease includes at least vital myocarditis disease, staphylococcus aureus
The septicopyemia blood inflammation and enterovirus EV 71 acute infection of induction.
5. Semaphorin7A monoclonal antibody according to claim 4 is preparing answering in the drug for treating inflammation
With, it is characterised in that: verify the drug treat in the vital myocarditis disease in application, the tissue of selection at least wraps
Include serum, heart tissue.
6. Semaphorin7A monoclonal antibody according to claim 4 is preparing answering in the drug for treating inflammation
With, it is characterised in that: verify the drug in the septicopyemia blood inflammation for treating staphylococcus aureus induction in application,
The tissue of selection includes at least serum, lung tissue, renal tissue.
7. Semaphorin7A monoclonal antibody according to claim 4 is preparing answering in the drug for treating inflammation
With, it is characterised in that: verify the drug treat in the enterovirus EV 71 acute infection in application, the tissue of selection
It includes at least: skeletal muscle tissue, small intestine, brain stem tissue.
8. Semaphorin7A monoclonal antibody according to claim 4 is preparing answering in the drug for treating inflammation
With, it is characterised in that: it is described for treat the drug of inflammation disease to further include excipient substance and medicinal substrate.
9. according to the drug of the described in any item treatment inflammation diseases of claim 4~8, which is characterized in that described for treating inflammation
The drug of disease is liquid preparation or lyophilized preparation.
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| CN201910278507.6A CN110156890B (en) | 2019-04-09 | 2019-04-09 | Semaphorin7A monoclonal antibody and application thereof in preparation of drugs for treating inflammatory diseases |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2023190465A1 (en) * | 2022-03-29 | 2023-10-05 | 株式会社カイオム・バイオサイエンス | Human anti-sema7a antibody |
| WO2023235765A1 (en) * | 2022-06-01 | 2023-12-07 | The Regents Of The University Of Colorado, A Body Corporate | Methods, compositions and uses for sema7a monoclonal antibodies |
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| CN112390884B (en) | 2022-07-08 |
| CN110156890B (en) | 2021-02-02 |
| CN112390884A (en) | 2021-02-23 |
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