CN105218682B - 经il-12/cd62l融合蛋白改造的肿瘤治疗剂及其制法和用途 - Google Patents
经il-12/cd62l融合蛋白改造的肿瘤治疗剂及其制法和用途 Download PDFInfo
- Publication number
- CN105218682B CN105218682B CN201510702467.5A CN201510702467A CN105218682B CN 105218682 B CN105218682 B CN 105218682B CN 201510702467 A CN201510702467 A CN 201510702467A CN 105218682 B CN105218682 B CN 105218682B
- Authority
- CN
- China
- Prior art keywords
- protein
- fusion protein
- cd62l
- cell
- tumor
- 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.)
- Active
Links
- 108010065805 Interleukin-12 Proteins 0.000 title claims abstract description 131
- 102000013462 Interleukin-12 Human genes 0.000 title claims abstract description 129
- 101001018097 Homo sapiens L-selectin Proteins 0.000 title claims abstract description 109
- 102100033467 L-selectin Human genes 0.000 title claims abstract description 102
- 108020001507 fusion proteins Proteins 0.000 title claims abstract description 100
- 102000037865 fusion proteins Human genes 0.000 title claims abstract description 100
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 82
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000003814 drug Substances 0.000 title claims abstract description 10
- 229940124597 therapeutic agent Drugs 0.000 title abstract description 5
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 106
- 210000000170 cell membrane Anatomy 0.000 claims abstract description 9
- 230000004927 fusion Effects 0.000 claims abstract description 9
- 210000004027 cell Anatomy 0.000 claims description 89
- 108090000623 proteins and genes Proteins 0.000 claims description 69
- 239000013598 vector Substances 0.000 claims description 44
- 102000004169 proteins and genes Human genes 0.000 claims description 43
- 210000002865 immune cell Anatomy 0.000 claims description 36
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 30
- 230000014509 gene expression Effects 0.000 claims description 25
- 108091033319 polynucleotide Proteins 0.000 claims description 19
- 102000040430 polynucleotide Human genes 0.000 claims description 19
- 239000002157 polynucleotide Substances 0.000 claims description 19
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 18
- 238000003776 cleavage reaction Methods 0.000 claims description 17
- 230000007017 scission Effects 0.000 claims description 17
- 241000713666 Lentivirus Species 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 13
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 claims description 12
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 claims description 12
- 229920001184 polypeptide Polymers 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 11
- 239000013612 plasmid Substances 0.000 claims description 8
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 7
- 238000012258 culturing Methods 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 5
- 102000043279 ADAM17 Human genes 0.000 claims description 4
- 108010075254 C-Peptide Proteins 0.000 claims description 4
- 239000000178 monomer Substances 0.000 claims description 4
- 239000013603 viral vector Substances 0.000 claims description 4
- 108091007505 ADAM17 Proteins 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- 201000010989 colorectal carcinoma Diseases 0.000 claims description 3
- 239000000539 dimer Substances 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 241000710772 Yellow fever virus Species 0.000 claims description 2
- 238000012546 transfer Methods 0.000 claims description 2
- 241000701161 unidentified adenovirus Species 0.000 claims description 2
- 229940051021 yellow-fever virus Drugs 0.000 claims description 2
- 210000004899 c-terminal region Anatomy 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 39
- 239000000427 antigen Substances 0.000 abstract description 27
- 108091007433 antigens Proteins 0.000 abstract description 27
- 102000036639 antigens Human genes 0.000 abstract description 27
- 230000000694 effects Effects 0.000 abstract description 24
- 231100000331 toxic Toxicity 0.000 abstract description 14
- 230000002588 toxic effect Effects 0.000 abstract description 14
- 241000700605 Viruses Species 0.000 abstract description 8
- 230000004913 activation Effects 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 abstract description 7
- 230000001900 immune effect Effects 0.000 abstract description 2
- 230000000118 anti-neoplastic effect Effects 0.000 abstract 1
- 231100000053 low toxicity Toxicity 0.000 abstract 1
- 239000012528 membrane Substances 0.000 description 21
- 210000004881 tumor cell Anatomy 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 239000012634 fragment Substances 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 13
- 108091008874 T cell receptors Proteins 0.000 description 13
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 13
- 238000000338 in vitro Methods 0.000 description 13
- 239000006228 supernatant Substances 0.000 description 13
- 239000002609 medium Substances 0.000 description 12
- 239000013604 expression vector Substances 0.000 description 11
- 238000000684 flow cytometry Methods 0.000 description 9
- 230000028327 secretion Effects 0.000 description 9
- 230000000295 complement effect Effects 0.000 description 8
- 101001023379 Homo sapiens Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 7
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 7
- 230000003321 amplification Effects 0.000 description 7
- 238000010276 construction Methods 0.000 description 7
- 238000007796 conventional method Methods 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 238000003199 nucleic acid amplification method Methods 0.000 description 7
- 230000009257 reactivity Effects 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 238000008157 ELISA kit Methods 0.000 description 6
- 238000010361 transduction Methods 0.000 description 6
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 5
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 5
- 108010004469 allophycocyanin Proteins 0.000 description 5
- 238000003501 co-culture Methods 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 230000026683 transduction Effects 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 108010092694 L-Selectin Proteins 0.000 description 4
- 102000016551 L-selectin Human genes 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 108010033276 Peptide Fragments Proteins 0.000 description 4
- 102000007079 Peptide Fragments Human genes 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000036046 immunoreaction Effects 0.000 description 4
- 238000011081 inoculation Methods 0.000 description 4
- 238000010188 recombinant method Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- NEHKZPHIKKEMAZ-ZFVKSOIMSA-N (2s)-2-[[(2s,3r)-2-[[(2s)-2-[[(2s,3s)-2-[[2-[[(2s,3s)-2-[[2-[[(2s)-2-[[(2s)-2-azaniumylpropanoyl]amino]propanoyl]amino]acetyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylb Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O NEHKZPHIKKEMAZ-ZFVKSOIMSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
- 108010010995 MART-1 Antigen Proteins 0.000 description 3
- 102000016200 MART-1 Antigen Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000012408 PCR amplification Methods 0.000 description 3
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 3
- 230000001588 bifunctional effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 239000005090 green fluorescent protein Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000007910 systemic administration Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000002463 transducing effect Effects 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- HBOMLICNUCNMMY-KJFJCRTCSA-N 1-[(4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1C1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-KJFJCRTCSA-N 0.000 description 2
- 108091033380 Coding strand Proteins 0.000 description 2
- 108010062580 Concanavalin A Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 108010019160 Pancreatin Proteins 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000012215 gene cloning Methods 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 102000051200 human SELL Human genes 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000003071 memory t lymphocyte Anatomy 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229940055695 pancreatin Drugs 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- -1 polypropylene Polymers 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 101150056050 ADAM17 gene Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700023863 Gene Components Proteins 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 description 1
- 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000924345 Homo sapiens Ankyrin repeat domain-containing protein 36B Proteins 0.000 description 1
- 101000930801 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 2 chain Proteins 0.000 description 1
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 101710118186 Neomycin resistance protein Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 102000004503 Perforin Human genes 0.000 description 1
- 108010056995 Perforin Proteins 0.000 description 1
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 102100021696 Syncytin-1 Human genes 0.000 description 1
- 230000033540 T cell apoptotic process Effects 0.000 description 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000008106 antitumoral immune reaction Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229940124644 immune regulator Drugs 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000003632 microfilament Anatomy 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 230000003278 mimic effect Effects 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
- 230000009456 molecular mechanism Effects 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000004153 renaturation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- 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
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- 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
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/861—Adenoviral vectors
-
- 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
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/867—Retroviral vectors
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cell Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
Claims (27)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510702467.5A CN105218682B (zh) | 2015-10-26 | 2015-10-26 | 经il-12/cd62l融合蛋白改造的肿瘤治疗剂及其制法和用途 |
PCT/CN2016/080420 WO2017071173A1 (zh) | 2015-10-26 | 2016-04-27 | 经il-12/cd62l融合蛋白改造的肿瘤治疗剂及其制法和用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510702467.5A CN105218682B (zh) | 2015-10-26 | 2015-10-26 | 经il-12/cd62l融合蛋白改造的肿瘤治疗剂及其制法和用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105218682A CN105218682A (zh) | 2016-01-06 |
CN105218682B true CN105218682B (zh) | 2019-05-07 |
Family
ID=54988006
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510702467.5A Active CN105218682B (zh) | 2015-10-26 | 2015-10-26 | 经il-12/cd62l融合蛋白改造的肿瘤治疗剂及其制法和用途 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN105218682B (zh) |
WO (1) | WO2017071173A1 (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105218682B (zh) * | 2015-10-26 | 2019-05-07 | 杨晶 | 经il-12/cd62l融合蛋白改造的肿瘤治疗剂及其制法和用途 |
CN105585637B (zh) * | 2015-12-23 | 2020-04-03 | 杨晶 | 基于il-12稳定膜表达的肿瘤治疗剂及其制法和用途 |
CN109306340B (zh) * | 2017-07-27 | 2023-06-06 | 上海细胞治疗研究院 | 一种高效扩增全t细胞的人工抗原递呈细胞及其用途 |
CN109337872B (zh) * | 2017-07-27 | 2023-06-23 | 上海细胞治疗研究院 | 高效扩增car-t细胞的人工抗原递呈细胞及其用途 |
CN110396133B (zh) * | 2018-04-25 | 2021-07-23 | 免疫靶向有限公司 | 一种以白介素12为活性成分的融合蛋白型药物前体 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1318644A (zh) * | 2000-04-18 | 2001-10-24 | 西安医科大学 | 一种重组人单链白细胞介素-12的构建方法 |
CN1432064A (zh) * | 2000-03-23 | 2003-07-23 | 格林维尔医院系统公司 | 双功能癌症治疗剂 |
WO2003092737A1 (en) * | 2002-04-30 | 2003-11-13 | Molmed Spa | Fusions of cytokines and tumor targeting proteins |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105218682B (zh) * | 2015-10-26 | 2019-05-07 | 杨晶 | 经il-12/cd62l融合蛋白改造的肿瘤治疗剂及其制法和用途 |
-
2015
- 2015-10-26 CN CN201510702467.5A patent/CN105218682B/zh active Active
-
2016
- 2016-04-27 WO PCT/CN2016/080420 patent/WO2017071173A1/zh active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1432064A (zh) * | 2000-03-23 | 2003-07-23 | 格林维尔医院系统公司 | 双功能癌症治疗剂 |
CN1318644A (zh) * | 2000-04-18 | 2001-10-24 | 西安医科大学 | 一种重组人单链白细胞介素-12的构建方法 |
WO2003092737A1 (en) * | 2002-04-30 | 2003-11-13 | Molmed Spa | Fusions of cytokines and tumor targeting proteins |
Also Published As
Publication number | Publication date |
---|---|
WO2017071173A1 (zh) | 2017-05-04 |
CN105218682A (zh) | 2016-01-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7262403B2 (ja) | 新規の細胞タグの発現 | |
US20210177902A1 (en) | Ror-1 specific chimeric antigen receptors and uses thereof | |
CN105218682B (zh) | 经il-12/cd62l融合蛋白改造的肿瘤治疗剂及其制法和用途 | |
CN111286493B (zh) | 一种溶瘤病毒疫苗及其与免疫细胞联合治疗肿瘤的药物 | |
CN109306016B (zh) | 共表达细胞因子il-7的nkg2d-car-t细胞及其用途 | |
CN113913379B (zh) | T淋巴细胞及其应用 | |
WO2017184553A1 (en) | Cancer gene therapy targeting cd47 | |
KR20220029584A (ko) | 바이러스 벡터 및 입양 세포 요법에서 그 사용 | |
WO2014011993A2 (en) | Epitope spreading associated with car t-cells | |
MX2014003176A (es) | Celulas t diseñadas mediante arn para el tratamiento de cancer. | |
CN113896801B (zh) | 靶向人Claudin18.2和NKG2DL的嵌合抗原受体细胞及其制备方法和应用 | |
TWI811278B (zh) | 表現特異性辨識人類間皮素之細胞表面分子、il-7、及ccl19之免疫活性細胞 | |
CN113416260B (zh) | 靶向Claudin18.2的特异性嵌合抗原受体细胞及其制备方法和应用 | |
WO2024113649A1 (zh) | 提高nk细胞存活和抗肿瘤活性的方法及其应用 | |
WO2009139413A1 (ja) | サイトカイン誘導キラー細胞含有細胞集団の製造方法 | |
WO2020163634A1 (en) | Chimeric cytokine receptors | |
CN117024598A (zh) | 长效的Meso-B7H3双靶点嵌合抗原受体及其应用 | |
CN111499766B (zh) | 针对慢性淋巴细胞白血病的免疫效应细胞、其制备方法和应用 | |
WO2017117890A1 (zh) | Il-12/cd107a融合蛋白及其制法和用途 | |
WO2012096376A1 (ja) | 制御性t細胞の製造方法 | |
CN105585637B (zh) | 基于il-12稳定膜表达的肿瘤治疗剂及其制法和用途 | |
CN115975056A (zh) | 利用天然蛋白tsh作为抗原结合位点构建靶向tshr的car-t细胞 | |
JPWO2007058235A1 (ja) | 融合蛋白質およびその薬学的用途 | |
WO2023015822A1 (zh) | 缺氧触发的人工转录因子、转录控制系统及其应用 | |
CN110139875B (zh) | Col14a1衍生的肿瘤抗原多肽及其应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20160803 Address after: 518048, Guangdong, Shenzhen, Futian District Fu Rong Road, Blue Sea Mangrove Park 4 7C Applicant after: Yang Jing Address before: 518061 room A012, building, mango net building, 5 Shenzhen Road, Nanshan District, Guangdong, China Applicant before: SHENZHEN GENTARGET MEDICAL TECHNOLOGY CO., LTD. |
|
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CP02 | Change in the address of a patent holder |
Address after: 518048, Shenzhen, Guangdong, Futian District, Fu Rong Road, Blue Sea Mangrove Park 4 7C Patentee after: Yang Jing Address before: 518048, Guangdong, Shenzhen, Futian District Fu Rong Road, Blue Sea Mangrove Park 4 7C Patentee before: Yang Jing |
|
CP02 | Change in the address of a patent holder |