CN105924531B - 一种抗il-4r单链抗体与蜂毒肽融合蛋白及其应用 - Google Patents
一种抗il-4r单链抗体与蜂毒肽融合蛋白及其应用 Download PDFInfo
- Publication number
- CN105924531B CN105924531B CN201610367676.3A CN201610367676A CN105924531B CN 105924531 B CN105924531 B CN 105924531B CN 201610367676 A CN201610367676 A CN 201610367676A CN 105924531 B CN105924531 B CN 105924531B
- Authority
- CN
- China
- Prior art keywords
- scfv
- gene
- mlt
- melittin
- chain antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 108010036176 Melitten Proteins 0.000 title claims abstract description 90
- VDXZNPDIRNWWCW-JFTDCZMZSA-N melittin Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-JFTDCZMZSA-N 0.000 title claims abstract description 73
- 102000037865 fusion proteins Human genes 0.000 title claims abstract description 69
- 108020001507 fusion proteins Proteins 0.000 title claims abstract description 69
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 129
- 238000000034 method Methods 0.000 claims abstract description 27
- 239000013612 plasmid Substances 0.000 claims abstract description 27
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 23
- 201000005202 lung cancer Diseases 0.000 claims abstract description 23
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 23
- 230000014509 gene expression Effects 0.000 claims abstract description 20
- 238000007857 nested PCR Methods 0.000 claims abstract description 11
- 238000005516 engineering process Methods 0.000 claims abstract description 10
- 230000009465 prokaryotic expression Effects 0.000 claims abstract description 10
- 241000894006 Bacteria Species 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 238000000746 purification Methods 0.000 claims abstract description 8
- 238000004153 renaturation Methods 0.000 claims abstract description 8
- 239000012634 fragment Substances 0.000 claims description 50
- 102000004190 Enzymes Human genes 0.000 claims description 25
- 108090000790 Enzymes Proteins 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 238000001976 enzyme digestion Methods 0.000 claims description 18
- 239000013598 vector Substances 0.000 claims description 15
- 239000000499 gel Substances 0.000 claims description 12
- 239000003659 bee venom Substances 0.000 claims description 8
- 230000029087 digestion Effects 0.000 claims description 8
- 238000011084 recovery Methods 0.000 claims description 8
- 238000001962 electrophoresis Methods 0.000 claims description 7
- 230000001939 inductive effect Effects 0.000 claims description 7
- 238000013461 design Methods 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 239000011543 agarose gel Substances 0.000 claims description 5
- 238000012258 culturing Methods 0.000 claims description 5
- 108010075254 C-Peptide Proteins 0.000 claims description 4
- 102000012410 DNA Ligases Human genes 0.000 claims description 4
- 108010061982 DNA Ligases Proteins 0.000 claims description 4
- 238000000246 agarose gel electrophoresis Methods 0.000 claims description 4
- 238000000137 annealing Methods 0.000 claims description 4
- 238000010276 construction Methods 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 238000004925 denaturation Methods 0.000 claims description 4
- 230000036425 denaturation Effects 0.000 claims description 4
- 230000000415 inactivating effect Effects 0.000 claims description 4
- 238000012257 pre-denaturation Methods 0.000 claims description 4
- 101000761020 Dinoponera quadriceps Poneritoxin Proteins 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 2
- 101150084750 1 gene Proteins 0.000 claims 1
- 102000004533 Endonucleases Human genes 0.000 claims 1
- 108010042407 Endonucleases Proteins 0.000 claims 1
- 230000003321 amplification Effects 0.000 claims 1
- 239000007853 buffer solution Substances 0.000 claims 1
- 239000012154 double-distilled water Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 31
- 230000004927 fusion Effects 0.000 abstract description 15
- 238000003752 polymerase chain reaction Methods 0.000 abstract description 14
- 238000000338 in vitro Methods 0.000 abstract description 11
- 239000013604 expression vector Substances 0.000 abstract description 3
- 231100000957 no side effect Toxicity 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 46
- 206010028980 Neoplasm Diseases 0.000 description 37
- 241000699670 Mus sp. Species 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 19
- 230000002637 immunotoxin Effects 0.000 description 15
- 229940051026 immunotoxin Drugs 0.000 description 15
- 239000002596 immunotoxin Substances 0.000 description 15
- 231100000608 immunotoxin Toxicity 0.000 description 15
- 229940079593 drug Drugs 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 210000004881 tumor cell Anatomy 0.000 description 12
- 230000002147 killing effect Effects 0.000 description 10
- 102000010787 Interleukin-4 Receptors Human genes 0.000 description 9
- 108010038486 Interleukin-4 Receptors Proteins 0.000 description 9
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 9
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 9
- 230000000259 anti-tumor effect Effects 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 238000011160 research Methods 0.000 description 9
- 231100000765 toxin Toxicity 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 8
- 238000002626 targeted therapy Methods 0.000 description 8
- 108700012359 toxins Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000003053 toxin Substances 0.000 description 7
- 241000256844 Apis mellifera Species 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 230000006907 apoptotic process Effects 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 210000003000 inclusion body Anatomy 0.000 description 6
- 201000007270 liver cancer Diseases 0.000 description 6
- 208000014018 liver neoplasm Diseases 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 229960004397 cyclophosphamide Drugs 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000001742 protein purification Methods 0.000 description 4
- 229940051173 recombinant immunotoxin Drugs 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 3
- 229960003669 carbenicillin Drugs 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 239000012149 elution buffer Substances 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 230000035777 life prolongation Effects 0.000 description 3
- 201000005249 lung adenocarcinoma Diseases 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 230000005760 tumorsuppression Effects 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- SCULJPGYOQQXTK-OLRINKBESA-N Cinobufagin Chemical compound C=1([C@@H]2[C@@]3(C)CC[C@@H]4[C@@]5(C)CC[C@H](O)C[C@H]5CC[C@H]4[C@@]43O[C@@H]4[C@@H]2OC(=O)C)C=CC(=O)OC=1 SCULJPGYOQQXTK-OLRINKBESA-N 0.000 description 2
- SCULJPGYOQQXTK-UHFFFAOYSA-N Cinobufagin Natural products CC(=O)OC1C2OC22C3CCC4CC(O)CCC4(C)C3CCC2(C)C1C=1C=CC(=O)OC=1 SCULJPGYOQQXTK-UHFFFAOYSA-N 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000424 Matrix Metalloproteinase 2 Human genes 0.000 description 2
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 2
- 229930192392 Mitomycin Natural products 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 2
- HCQPHKMLKXOJSR-IRCPFGJUSA-N cecropin-a Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(N)=O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)CCCCN)C1=CC=CC=C1 HCQPHKMLKXOJSR-IRCPFGJUSA-N 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 210000004967 non-hematopoietic stem cell Anatomy 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000012474 protein marker Substances 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 229940126585 therapeutic drug Drugs 0.000 description 2
- 230000005909 tumor killing Effects 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- JDLKFOPOAOFWQN-VIFPVBQESA-N Allicin Natural products C=CCS[S@](=O)CC=C JDLKFOPOAOFWQN-VIFPVBQESA-N 0.000 description 1
- 101100298249 Arabidopsis thaliana TOPP2 gene Proteins 0.000 description 1
- 206010003402 Arthropod sting Diseases 0.000 description 1
- 101800003223 Cecropin-A Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 238000011537 Coomassie blue staining Methods 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 102000007317 Farnesyltranstransferase Human genes 0.000 description 1
- 108010007508 Farnesyltranstransferase Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 241001655218 Heterogenys Species 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001416180 Moschidae Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
- 108091036333 Rapid DNA Proteins 0.000 description 1
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 241001052560 Thallis Species 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- JDLKFOPOAOFWQN-UHFFFAOYSA-N allicin Chemical compound C=CCSS(=O)CC=C JDLKFOPOAOFWQN-UHFFFAOYSA-N 0.000 description 1
- 235000010081 allicin Nutrition 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002946 anti-pancreatic effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 239000003131 biological toxin Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000011393 cytotoxic chemotherapy Methods 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 238000012917 library technology Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000011242 molecular targeted therapy Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- -1 radioactive isotopes Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000037425 regulation of transcription Effects 0.000 description 1
- JAABVEXCGCXWRR-FBXFSONDSA-N rel-norcantharidin Chemical compound C1C[C@H]2[C@@H]3C(=O)OC(=O)[C@@H]3[C@@H]1O2 JAABVEXCGCXWRR-FBXFSONDSA-N 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012772 sequence design Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000008791 toxic response Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229940126673 western medicines Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43563—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects
- C07K14/43568—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects from wasps
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/10—Plasmid DNA
- C12N2800/101—Plasmid DNA for bacteria
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Insects & Arthropods (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Plant Pathology (AREA)
- Toxicology (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
组别 | 剂量(mg/kg) | OD值(均值±标准差) | 抑制率(%) |
本底对照组 | -- | 0.06±0.01 | -- |
对照组 | -- | 0.39±0.01 | -- |
环磷酰胺 | 2.0 | 0.19±0.01<sup>##</sup> | 59.77 |
融合蛋白低剂量组 | 1 | 0.31±0.02<sup>##</sup> | 25.61 |
融合蛋白中剂量组 | 2 | 0.22±0.01<sup>##</sup> | 51.83 |
融合蛋白高剂量组 | 4 | 0.19±0.01<sup>##</sup> | 62.20 |
组别 | 剂量(mg/kg) | OD值(均值±标准差) | 抑制率(%) |
对照组 | — | 1.06±0.09 | — |
环磷酰胺 | 40 | 0.59±0.01<sup>##</sup> | 43.94 |
融合蛋白低剂量组 | 20 | 0.80±0.02<sup>##</sup> | 24.62 |
融合蛋白中剂量组 | 50 | 0.66±0.03<sup>##</sup> | 37.12 |
融合蛋白高剂量组 | 100 | 0.62±0.05<sup>##</sup> | 41.48 |
组别 | 剂量(mg/kg) | OD值(均值±标准差) | 抑制率(%) |
对照组 | — | 14.6±1.85 | — |
环磷酰胺 | 20 | 27.8±1.72<sup>##</sup> | 90.41 |
融合蛋白低剂量组 | 50 | 21.2±1.72<sup>##</sup> | 45.21 |
融合蛋白中剂量组 | 100 | 24.4±1.02<sup>##</sup> | 67.12 |
融合蛋白高剂量组 | 150 | 25.8±3.06<sup>##</sup> | 76.71 |
Claims (2)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610367676.3A CN105924531B (zh) | 2016-05-30 | 2016-05-30 | 一种抗il-4r单链抗体与蜂毒肽融合蛋白及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610367676.3A CN105924531B (zh) | 2016-05-30 | 2016-05-30 | 一种抗il-4r单链抗体与蜂毒肽融合蛋白及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105924531A CN105924531A (zh) | 2016-09-07 |
CN105924531B true CN105924531B (zh) | 2020-04-21 |
Family
ID=56842433
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610367676.3A Expired - Fee Related CN105924531B (zh) | 2016-05-30 | 2016-05-30 | 一种抗il-4r单链抗体与蜂毒肽融合蛋白及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105924531B (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111407880A (zh) * | 2019-01-08 | 2020-07-14 | 上海中医药大学附属龙华医院 | 蜂毒素作为Wnt/β-Catenin信号通路抑制剂防治骨肉瘤的用途 |
CN111825766B (zh) * | 2019-10-31 | 2021-05-11 | 上海洛启生物医药技术有限公司 | 抗il-4r单域抗体及其应用 |
CN113214409B (zh) * | 2021-06-03 | 2022-05-20 | 中基高科(北京)生物技术有限公司 | 一种蜂毒素-死亡素杂合肽突变体mtm及其应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102206281A (zh) * | 2011-03-28 | 2011-10-05 | 中国人民解放军第三军医大学第一附属医院 | 融合蛋白tetph、表达载体及其构建方法 |
-
2016
- 2016-05-30 CN CN201610367676.3A patent/CN105924531B/zh not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102206281A (zh) * | 2011-03-28 | 2011-10-05 | 中国人民解放军第三军医大学第一附属医院 | 融合蛋白tetph、表达载体及其构建方法 |
Non-Patent Citations (5)
Title |
---|
Antigen binding and cytotoxic properties of a recombinant immunotoxin incorporating the lytic peptide,melittin;Rosanne D. Dunna,et al;《Immunotechnology》;19961231;229-240页 * |
Rosanne D. Dunna,et al.Antigen binding and cytotoxic properties of a recombinant immunotoxin incorporating the lytic peptide,melittin.《Immunotechnology》.1996,229-240页. * |
抗IL-4R单链抗体与蜂毒肽融合蛋白的构建、表达与纯化;杨光勇等;《华中科技大学学报(医学版)》;20180430;第47卷(第2期);193-197页 * |
抗白介素-4受体单抗与眼镜蛇毒细胞毒素构建的免疫毒素靶向治疗胰腺癌的实验研究;王鸿程;《中国博士学位论文全文数据库 医药卫生科技辑》;20090315(第3期);E059-37 * |
王鸿程.抗白介素-4受体单抗与眼镜蛇毒细胞毒素构建的免疫毒素靶向治疗胰腺癌的实验研究.《中国博士学位论文全文数据库 医药卫生科技辑》.2009,(第3期),E059-37. * |
Also Published As
Publication number | Publication date |
---|---|
CN105924531A (zh) | 2016-09-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11807661B2 (en) | Antibody fusion protein and related compositions for targeting cancer | |
TW201934579A (zh) | 一種結合bcma的嵌合抗原受體(car)及其應用 | |
CN110835371A (zh) | 抗ccr8单克隆抗体及其应用 | |
CN105924531B (zh) | 一种抗il-4r单链抗体与蜂毒肽融合蛋白及其应用 | |
ES2718399T3 (es) | Moléculas que se acoplan a anticuerpos EGFRVIII biespecíficas humanas | |
US11472860B2 (en) | Chimeric antigen receptors | |
TWI633118B (zh) | 用於癌症標靶治療之包含基於重組血紅素蛋白或次單元之治療劑的醫藥組成物 | |
CA2947525C (en) | Heterologous polypeptide expression cassette | |
AU2016264363A1 (en) | Cancer vaccine comprising mRNA encoding a M-like-protein | |
CN110144011B (zh) | 针对t淋巴细胞免疫球蛋白黏蛋白3的单域抗体 | |
US10682401B2 (en) | Multi-indication mRNA cancer immunotherapy | |
AU2013271428A1 (en) | Human bispecific EGFRvIII antibody engaging molecules | |
JP2022513586A (ja) | 抗liv1免疫細胞癌療法 | |
CN106810610A (zh) | 抗EpCAM和CD3特异性双靶向抗体及其制备方法和应用、含该双靶向抗体表达盒的微环DNA及应用 | |
US20170066817A1 (en) | Monoclonal antibody against human prpc and use thereof | |
CN106632686B (zh) | 一种抗il-4r单链抗体与蛇毒l-氨基酸氧化酶融合蛋白及应用 | |
CN112390875B (zh) | 一种识别afp的高亲和力t细胞受体 | |
KR20210108941A (ko) | Afp 항원 인식을 위한 고친화력 t 세포 수용체 | |
Namvar et al. | Cloning and soluble expression of mature ${\alpha} $-luffin from Luffa cylindrica in E. coli using SUMO fusion protein | |
EP3618856A1 (en) | Multi-indication mrna cancer immunotherapy | |
WO2015166641A1 (ja) | 抗体遺伝子の発現・分泌システム | |
JP7054143B2 (ja) | キメラ抗原受容体、及びその利用 | |
KR20220120910A (ko) | Egfr-gst-울리서티닙 복합체, 및 이를 포함하는 암 예방 또는 치료용 약학적 조성물 | |
RU2619050C1 (ru) | Рекомбинантная плазмидная ДНК pET-15b_T1_RL, обеспечивающая синтез рекомбинантного слитого белка, состоящего из опухоль-специфического пептида и противоопухолевого пептида RL2, и рекомбинантный слитый белок, обладающий цитотоксической активностью по отношению к раковым клеткам и таргетными свойствами к опухолевой ткани | |
CN109879964B (zh) | 抗egfr单链抗体、抗pd1单链抗体及融合蛋白 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CP03 | Change of name, title or address |
Address after: 550000, No. 50 East City Road, Nanming District, Guizhou, Guiyang Patentee after: Guizhou University of Traditional Chinese Medicine Address before: Department of Microbiology, Guiyang University of traditional Chinese Medicine Patentee before: GUIYANG College OF TRADITIONAL CHINESE MEDICINE |
|
CP03 | Change of name, title or address | ||
CP02 | Change in the address of a patent holder | ||
CP02 | Change in the address of a patent holder |
Address after: 550025 No.4, Dongqing Road, Huaxi University Town, Huaxi District, Guiyang City, Guizhou Province Patentee after: Guizhou University of Traditional Chinese Medicine Address before: 550000 No. 50 Shidong Road, Nanming District, Guiyang City, Guizhou Province Patentee before: Guizhou University of Traditional Chinese Medicine |
|
EE01 | Entry into force of recordation of patent licensing contract | ||
EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20160907 Assignee: First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Assignor: Guizhou University of Traditional Chinese Medicine Contract record no.: X2021520000001 Denomination of invention: A fusion protein of anti-il-4r scFv and melittin and its application Granted publication date: 20200421 License type: Common License Record date: 20210305 |
|
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200421 |