PT1533380E - Produção de proteínas recombinantes numa célula humana compreendendo pelo menos uma proteína e1 de adenovírus - Google Patents
Produção de proteínas recombinantes numa célula humana compreendendo pelo menos uma proteína e1 de adenovírus Download PDFInfo
- Publication number
- PT1533380E PT1533380E PT05100732T PT05100732T PT1533380E PT 1533380 E PT1533380 E PT 1533380E PT 05100732 T PT05100732 T PT 05100732T PT 05100732 T PT05100732 T PT 05100732T PT 1533380 E PT1533380 E PT 1533380E
- Authority
- PT
- Portugal
- Prior art keywords
- cells
- per
- human
- cell
- quot
- Prior art date
Links
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 title claims abstract description 49
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 title claims abstract description 49
- 108090000623 proteins and genes Proteins 0.000 title abstract description 105
- 102000004169 proteins and genes Human genes 0.000 title abstract description 71
- 210000005260 human cell Anatomy 0.000 title abstract description 35
- 241000701161 unidentified adenovirus Species 0.000 title description 17
- 230000014616 translation Effects 0.000 title description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 78
- 238000000034 method Methods 0.000 claims abstract description 52
- 102000003951 Erythropoietin Human genes 0.000 claims description 117
- 108090000394 Erythropoietin Proteins 0.000 claims description 117
- 229940105423 erythropoietin Drugs 0.000 claims description 114
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 113
- 239000012634 fragment Substances 0.000 claims description 36
- 150000007523 nucleic acids Chemical class 0.000 claims description 30
- 210000002966 serum Anatomy 0.000 claims description 26
- 239000002299 complementary DNA Substances 0.000 claims description 22
- 108020004707 nucleic acids Proteins 0.000 claims description 21
- 102000039446 nucleic acids Human genes 0.000 claims description 21
- 102000003839 Human Proteins Human genes 0.000 claims description 9
- 108090000144 Human Proteins Proteins 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 7
- 238000012258 culturing Methods 0.000 claims description 7
- 108010046068 N-Acetyllactosamine Synthase Proteins 0.000 claims description 3
- 238000003306 harvesting Methods 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 abstract description 382
- 230000013595 glycosylation Effects 0.000 abstract description 28
- 238000006206 glycosylation reaction Methods 0.000 abstract description 28
- 241000699802 Cricetulus griseus Species 0.000 abstract description 6
- 239000000203 mixture Substances 0.000 abstract description 6
- 210000001672 ovary Anatomy 0.000 abstract description 5
- 230000010473 stable expression Effects 0.000 abstract description 4
- 239000013612 plasmid Substances 0.000 description 77
- 235000018102 proteins Nutrition 0.000 description 68
- 102100038313 Transcription factor E2-alpha Human genes 0.000 description 63
- 239000002609 medium Substances 0.000 description 56
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 51
- 229960000485 methotrexate Drugs 0.000 description 51
- 239000013615 primer Substances 0.000 description 50
- 108060003951 Immunoglobulin Proteins 0.000 description 47
- 102000018358 immunoglobulin Human genes 0.000 description 47
- 108020004414 DNA Proteins 0.000 description 45
- 238000003752 polymerase chain reaction Methods 0.000 description 39
- 238000001890 transfection Methods 0.000 description 39
- 229940072221 immunoglobulins Drugs 0.000 description 36
- 239000000047 product Substances 0.000 description 33
- 230000014509 gene expression Effects 0.000 description 32
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 28
- 239000013598 vector Substances 0.000 description 28
- 108091008146 restriction endonucleases Proteins 0.000 description 27
- 239000000499 gel Substances 0.000 description 25
- 238000002965 ELISA Methods 0.000 description 22
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 22
- 108010067390 Viral Proteins Proteins 0.000 description 22
- 101150074155 DHFR gene Proteins 0.000 description 21
- 239000006228 supernatant Substances 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- 102000005348 Neuraminidase Human genes 0.000 description 19
- 108010006232 Neuraminidase Proteins 0.000 description 19
- 108020001096 dihydrofolate reductase Proteins 0.000 description 19
- 125000005629 sialic acid group Chemical group 0.000 description 18
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 17
- 239000011543 agarose gel Substances 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 16
- 230000003321 amplification Effects 0.000 description 16
- 102000044890 human EPO Human genes 0.000 description 16
- 238000003199 nucleic acid amplification method Methods 0.000 description 16
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 15
- 108090000790 Enzymes Proteins 0.000 description 15
- 239000013604 expression vector Substances 0.000 description 15
- 230000012010 growth Effects 0.000 description 15
- 239000002773 nucleotide Substances 0.000 description 15
- 125000003729 nucleotide group Chemical group 0.000 description 15
- 239000000126 substance Substances 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 13
- 230000010354 integration Effects 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 241000701022 Cytomegalovirus Species 0.000 description 11
- 241001529936 Murinae Species 0.000 description 11
- 241000933095 Neotragus moschatus Species 0.000 description 11
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 11
- 229960005486 vaccine Drugs 0.000 description 11
- 230000001464 adherent effect Effects 0.000 description 10
- 210000003719 b-lymphocyte Anatomy 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 238000011144 upstream manufacturing Methods 0.000 description 10
- 230000035899 viability Effects 0.000 description 10
- 108010074604 Epoetin Alfa Proteins 0.000 description 9
- 241000282412 Homo Species 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 239000000427 antigen Substances 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 239000012737 fresh medium Substances 0.000 description 9
- 230000004481 post-translational protein modification Effects 0.000 description 9
- 108091026890 Coding region Proteins 0.000 description 8
- 108090001090 Lectins Proteins 0.000 description 8
- 102000004856 Lectins Human genes 0.000 description 8
- 108010076504 Protein Sorting Signals Proteins 0.000 description 8
- 238000010367 cloning Methods 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 239000002523 lectin Substances 0.000 description 8
- 210000004962 mammalian cell Anatomy 0.000 description 8
- 239000003550 marker Substances 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 229920000136 polysorbate Polymers 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 241000711404 Avian avulavirus 1 Species 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- OOIBFPKQHULHSQ-UHFFFAOYSA-N (3-hydroxy-1-adamantyl) 2-methylprop-2-enoate Chemical compound C1C(C2)CC3CC2(O)CC1(OC(=O)C(=C)C)C3 OOIBFPKQHULHSQ-UHFFFAOYSA-N 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- SXTAYKAGBXMACB-UHFFFAOYSA-N methionine sulfoximine Chemical compound CS(=N)(=O)CCC(N)C(O)=O SXTAYKAGBXMACB-UHFFFAOYSA-N 0.000 description 6
- 108020004635 Complementary DNA Proteins 0.000 description 5
- 102000003886 Glycoproteins Human genes 0.000 description 5
- 108090000288 Glycoproteins Proteins 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 238000004873 anchoring Methods 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 238000004520 electroporation Methods 0.000 description 5
- 230000008030 elimination Effects 0.000 description 5
- 238000003379 elimination reaction Methods 0.000 description 5
- 102000005396 glutamine synthetase Human genes 0.000 description 5
- 108020002326 glutamine synthetase Proteins 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 210000004408 hybridoma Anatomy 0.000 description 5
- 238000000099 in vitro assay Methods 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 238000011081 inoculation Methods 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 201000000050 myeloid neoplasm Diseases 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 229920001542 oligosaccharide Polymers 0.000 description 5
- 150000002482 oligosaccharides Chemical class 0.000 description 5
- 230000001323 posttranslational effect Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 230000010474 transient expression Effects 0.000 description 5
- 238000003146 transient transfection Methods 0.000 description 5
- 101710186708 Agglutinin Proteins 0.000 description 4
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 4
- 101150074355 GS gene Proteins 0.000 description 4
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 4
- 101710146024 Horcolin Proteins 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- 101710189395 Lectin Proteins 0.000 description 4
- 101710179758 Mannose-specific lectin Proteins 0.000 description 4
- 101710150763 Mannose-specific lectin 1 Proteins 0.000 description 4
- 101710150745 Mannose-specific lectin 2 Proteins 0.000 description 4
- 229930193140 Neomycin Natural products 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 238000002105 Southern blotting Methods 0.000 description 4
- 108700019146 Transgenes Proteins 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000910 agglutinin Substances 0.000 description 4
- 125000003275 alpha amino acid group Chemical group 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 108010064886 beta-D-galactoside alpha 2-6-sialyltransferase Proteins 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 108010030074 endodeoxyribonuclease MluI Proteins 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 238000011031 large-scale manufacturing process Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229960004927 neomycin Drugs 0.000 description 4
- 230000010412 perfusion Effects 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 229960004641 rituximab Drugs 0.000 description 4
- 238000004114 suspension culture Methods 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 239000003154 D dimer Substances 0.000 description 3
- 238000008157 ELISA kit Methods 0.000 description 3
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 3
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 3
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 description 3
- 108091092195 Intron Proteins 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 241000276498 Pollachius virens Species 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 101710172711 Structural protein Proteins 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 238000012761 co-transfection Methods 0.000 description 3
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000011143 downstream manufacturing Methods 0.000 description 3
- -1 encoding tTa) Chemical class 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000013613 expression plasmid Substances 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 238000009331 sowing Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 3
- 241000712461 unidentified influenza virus Species 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 229930024421 Adenine Natural products 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000709661 Enterovirus Species 0.000 description 2
- 241000991587 Enterovirus C Species 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108700023372 Glycosyltransferases Proteins 0.000 description 2
- 102000051366 Glycosyltransferases Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101100332578 Homo sapiens DHFR gene Proteins 0.000 description 2
- 101000908713 Homo sapiens Dihydrofolate reductase Proteins 0.000 description 2
- 241001135569 Human adenovirus 5 Species 0.000 description 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 101100384798 Lupinus albus Cgamma gene Proteins 0.000 description 2
- 241001521394 Maackia amurensis Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- PKVZBNCYEICAQP-UHFFFAOYSA-N Mecamylamine hydrochloride Chemical compound Cl.C1CC2C(C)(C)C(NC)(C)C1C2 PKVZBNCYEICAQP-UHFFFAOYSA-N 0.000 description 2
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 108091034057 RNA (poly(A)) Proteins 0.000 description 2
- 240000006028 Sambucus nigra Species 0.000 description 2
- 235000003142 Sambucus nigra Nutrition 0.000 description 2
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 235000021120 animal protein Nutrition 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 229940042406 direct acting antivirals neuraminidase inhibitors Drugs 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 230000007783 downstream signaling Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 235000008995 european elder Nutrition 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 102000035122 glycosylated proteins Human genes 0.000 description 2
- 108091005608 glycosylated proteins Proteins 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229940022353 herceptin Drugs 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 229960003971 influenza vaccine Drugs 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000012269 metabolic engineering Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108010067988 prolactin-binding protein Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- 239000002911 sialidase inhibitor Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 229940113082 thymine Drugs 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 231100000588 tumorigenic Toxicity 0.000 description 2
- 230000000381 tumorigenic effect Effects 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- VIGKUFXFTPWYER-BIIVOSGPSA-N Ala-Cys-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N VIGKUFXFTPWYER-BIIVOSGPSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 241000143060 Americamysis bahia Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 101100268670 Caenorhabditis elegans acc-3 gene Proteins 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 241000710777 Classical swine fever virus Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 241000710945 Eastern equine encephalitis virus Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 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 1
- JPVGHHQGKPQYIL-KBPBESRZSA-N Gly-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 JPVGHHQGKPQYIL-KBPBESRZSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 101000980814 Homo sapiens CAMPATH-1 antigen Proteins 0.000 description 1
- 101100495232 Homo sapiens MS4A1 gene Proteins 0.000 description 1
- 101001138480 Homo sapiens Olfactory receptor 5AC2 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- RKQAYOWLSFLJEE-SVSWQMSJSA-N Ile-Thr-Cys Chemical group CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)O)N RKQAYOWLSFLJEE-SVSWQMSJSA-N 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- LAGPXKYZCCTSGQ-JYJNAYRXSA-N Leu-Glu-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LAGPXKYZCCTSGQ-JYJNAYRXSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 102100020806 Olfactory receptor 5AC2 Human genes 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 241000710778 Pestivirus Species 0.000 description 1
- 101100395821 Pichia angusta HSA2 gene Proteins 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 241000725681 Swine influenza virus Species 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 241000710771 Tick-borne encephalitis virus Species 0.000 description 1
- 101710132316 Transactivation protein Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 241000711484 Transmissible gastroenteritis virus Species 0.000 description 1
- NMCBVGFGWSIGSB-NUTKFTJISA-N Trp-Ala-Leu Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N NMCBVGFGWSIGSB-NUTKFTJISA-N 0.000 description 1
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000710951 Western equine encephalitis virus Species 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 125000000613 asparagine group Chemical class N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 108700000707 bcl-2-Associated X Proteins 0.000 description 1
- 102000055102 bcl-2-Associated X Human genes 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229940112129 campath Drugs 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- FHIVAFMUCKRCQO-UHFFFAOYSA-N diazinon Chemical compound CCOP(=S)(OCC)OC1=CC(C)=NC(C(C)C)=N1 FHIVAFMUCKRCQO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 108010052295 fibrin fragment D Proteins 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 108010001671 galactoside 3-fucosyltransferase Proteins 0.000 description 1
- 150000002256 galaktoses Chemical class 0.000 description 1
- 230000006251 gamma-carboxylation Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical group 0.000 description 1
- 108700014210 glycosyltransferase activity proteins Proteins 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 229940106780 human fibrinogen Drugs 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 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
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 108010051242 phenylalanylserine Proteins 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 239000000376 reactant Substances 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
- 238000011160 research Methods 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940031626 subunit vaccine Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 108091006107 transcriptional repressors Proteins 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 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 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
- 229960004854 viral vaccine Drugs 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Classifications
-
- 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
- C07K14/475—Growth factors; Growth regulators
- C07K14/505—Erythropoietin [EPO]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
- C12N2510/00—Genetically modified cells
- C12N2510/02—Cells for production
-
- 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
- C12N2510/00—Genetically modified cells
- C12N2510/04—Immortalised cells
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10341—Use of virus, viral particle or viral elements as a vector
- C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2800/108—Plasmid DNA episomal 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
- C12N2830/00—Vector systems having a special element relevant for transcription
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/15—Vector systems having a special element relevant for transcription chimeric enhancer/promoter combination
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/60—Vector systems having a special element relevant for transcription from viruses
-
- 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
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Plant Pathology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99201176 | 1999-04-15 | ||
| EP99204434 | 1999-12-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT1533380E true PT1533380E (pt) | 2010-02-09 |
Family
ID=26153302
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT05100732T PT1533380E (pt) | 1999-04-15 | 2000-04-17 | Produção de proteínas recombinantes numa célula humana compreendendo pelo menos uma proteína e1 de adenovírus |
| PT00921175T PT1161548E (pt) | 1999-04-15 | 2000-04-17 | Producao de proteinas recombinantes numa celula humana utilizando sequencias codificando a proteina e1 de adenovirus |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT00921175T PT1161548E (pt) | 1999-04-15 | 2000-04-17 | Producao de proteinas recombinantes numa celula humana utilizando sequencias codificando a proteina e1 de adenovirus |
Country Status (18)
| Country | Link |
|---|---|
| EP (3) | EP1161548B2 (enExample) |
| JP (1) | JP4210036B2 (enExample) |
| CN (1) | CN100457914C (enExample) |
| AT (3) | ATE289354T1 (enExample) |
| AU (1) | AU772352B2 (enExample) |
| CA (1) | CA2370477C (enExample) |
| CY (1) | CY1109759T1 (enExample) |
| DE (2) | DE60018171T3 (enExample) |
| DK (3) | DK1533380T3 (enExample) |
| ES (3) | ES2237420T5 (enExample) |
| HK (1) | HK1048138B (enExample) |
| IL (2) | IL145849A0 (enExample) |
| MX (1) | MXPA01010360A (enExample) |
| NO (1) | NO328951B1 (enExample) |
| NZ (1) | NZ514951A (enExample) |
| PT (2) | PT1533380E (enExample) |
| SI (2) | SI1533380T1 (enExample) |
| WO (1) | WO2000063403A2 (enExample) |
Families Citing this family (117)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003089468A1 (en) * | 2002-04-19 | 2003-10-30 | Crucell Holland B.V. | Methods and means for producing proteins with predetermined post-translational modifications |
| WO2003050286A1 (en) * | 2001-10-29 | 2003-06-19 | Crucell Holland B.V. | Methods and means for producing proteins with predetermined post-translational modifications |
| US8236561B2 (en) | 1999-04-15 | 2012-08-07 | Crucell Holland B.V. | Efficient production of IgA in recombinant mammalian cells |
| WO2003048197A1 (en) * | 2001-12-07 | 2003-06-12 | Crucell Holland B.V. | Production and of viruses, viral isolates and vaccines |
| US7297680B2 (en) * | 1999-04-15 | 2007-11-20 | Crucell Holland B.V. | Compositions of erythropoietin isoforms comprising Lewis-X structures and high sialic acid content |
| US6855544B1 (en) | 1999-04-15 | 2005-02-15 | Crucell Holland B.V. | Recombinant protein production in a human cell |
| US7604960B2 (en) | 1999-04-15 | 2009-10-20 | Crucell Holland B.V. | Transient protein expression methods |
| US7527961B2 (en) | 1999-11-26 | 2009-05-05 | Crucell Holland B.V. | Production of vaccines |
| US7425437B2 (en) * | 1999-11-26 | 2008-09-16 | Crucell Holland B.V. | Vaccines against West Nile Virus |
| US7521220B2 (en) * | 1999-11-26 | 2009-04-21 | Crucell Holland B.V. | Production of vaccines |
| US7192759B1 (en) | 1999-11-26 | 2007-03-20 | Crucell Holland B.V. | Production of vaccines |
| EP1256803A1 (en) | 2001-05-07 | 2002-11-13 | Crucell Holland B.V. | Methods for the identification of antiviral compounds |
| CN100347306C (zh) * | 2001-10-29 | 2007-11-07 | 克鲁塞尔荷兰公司 | 生产具有预定的翻译后修饰的蛋白质的方法和手段 |
| CN100547069C (zh) * | 2001-12-07 | 2009-10-07 | 克鲁塞尔荷兰公司 | 病毒、病毒分离物和疫苗的生产 |
| US20050048038A1 (en) * | 2001-12-17 | 2005-03-03 | Jones David Halford Ashton | Efficient production of f(ab')2 fragments in mammalian cells |
| KR100454016B1 (ko) * | 2002-01-05 | 2004-10-26 | 한국과학기술원 | 항예정사 유전자로 형질전환되고 dhfr 유전자가결핍된 신규한 cho 세포주, 그의 제조 방법 및 상기형질전환된 cho 숙주 세포를 이용한 목적단백질의 생산방법 |
| ATE359087T1 (de) * | 2002-01-09 | 2007-05-15 | Crucell Holland Bv | Verwendung von erythropoietin zur behandlung oder vorbeugung von herzversagen |
| CN100522999C (zh) | 2002-02-14 | 2009-08-05 | 免疫医疗公司 | 抗cd20抗体及其融合蛋白和使用方法 |
| US8287864B2 (en) | 2002-02-14 | 2012-10-16 | Immunomedics, Inc. | Structural variants of antibodies for improved therapeutic characteristics |
| EP1483294B2 (en) | 2002-03-01 | 2019-10-30 | Immunomedics, Inc. | Internalizing anti-cd74 antibodies and methods of use |
| MXPA04012656A (es) | 2002-06-14 | 2005-08-15 | Immunomedics Inc | Anticuerpo hpam4 monoclonal humanizado. |
| SI1523496T1 (sl) | 2002-07-18 | 2011-11-30 | Merus B V | Rekombinantno proizvajanje zmesi protiteles |
| USRE47770E1 (en) | 2002-07-18 | 2019-12-17 | Merus N.V. | Recombinant production of mixtures of antibodies |
| EP1546203B1 (en) | 2002-08-01 | 2012-06-20 | Immunomedics, Inc. | Alpha-fetoprotein immu31 antibodies and fusion proteins and methods of use thereof |
| US7541440B2 (en) | 2002-09-30 | 2009-06-02 | Immunomedics, Inc. | Chimeric, human and humanized anti-granulocyte antibodies and methods of use |
| US8524477B2 (en) | 2002-10-29 | 2013-09-03 | Crucell Holland B.V. | Methods to obtain recombinant proteins with increased sialylation from cells that express adenovirus E1A protein, and proteins obtained thereby |
| US7534427B2 (en) | 2002-12-31 | 2009-05-19 | Immunomedics, Inc. | Immunotherapy of B cell malignancies and autoimmune diseases using unconjugated antibodies and conjugated antibodies and antibody combinations and fusion proteins |
| CA2520891C (en) | 2003-05-09 | 2014-07-08 | Crucell Holland B.V. | Cultures of e1-immortalized cells and processes for culturing the same to increase product yields therefrom |
| AU2004240782B2 (en) * | 2003-05-23 | 2011-04-21 | Crucell Holland B.V. | Production of recombinant IGM in per.C6 cells |
| EP2395017A3 (en) | 2003-05-30 | 2012-12-19 | Merus B.V. | Design and use of paired variable regions of specific binding molecules |
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| NZ543635A (en) | 2003-06-25 | 2008-05-30 | Crucell Holland Bv | Human C-type lectin: a suitable target molecule for binding molecules, particularly immunoconjugates, in the diagnosis, prevention and/or treatment of myeloid neoplastic diseases such as AML and CML |
| US7109304B2 (en) | 2003-07-31 | 2006-09-19 | Immunomedics, Inc. | Humanized anti-CD19 antibodies |
| EP1508576A1 (en) * | 2003-08-20 | 2005-02-23 | Crucell Holland B.V. | Efficient production of IgA in recombinant mammalian cells |
| CN1863918B (zh) | 2003-10-02 | 2011-03-30 | 克鲁塞尔荷兰公司 | 用于重组腺病毒的包装细胞 |
| WO2005059149A2 (en) * | 2003-12-12 | 2005-06-30 | Chromagenics B.V. | Improved protein production |
| DK1737971T3 (da) | 2004-01-20 | 2017-11-13 | Merus Nv | Blandinger af bindingsproteiner |
| PL1720972T3 (pl) * | 2004-03-05 | 2014-06-30 | Dpx Holdings Bv | Proces hodowli komórek poprzez ciągłą perfuzję i zmienny przepływ styczny |
| CN102139106B (zh) | 2004-05-27 | 2014-10-08 | 克鲁塞尔荷兰公司 | 能中和狂犬病病毒的结合分子及其应用 |
| JP4852046B2 (ja) | 2004-10-12 | 2012-01-11 | クルセル ホランド ベー ヴェー | 癌の治療及び検出に用いる結合分子 |
| AU2005300503B2 (en) | 2004-11-08 | 2010-12-16 | Chromagenics B.V. | Selection of host cells expressing protein at high levels |
| ATE550037T1 (de) | 2004-11-11 | 2012-04-15 | Crucell Holland Bv | Zusammensetzungen gegen das sars-coronavirus und ihre verwendungen |
| CA2591665C (en) | 2004-12-20 | 2015-05-05 | Crucell Holland B.V. | Binding molecules capable of neutralizing west nile virus and uses thereof |
| US8349332B2 (en) | 2005-04-06 | 2013-01-08 | Ibc Pharmaceuticals, Inc. | Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseases |
| US8475794B2 (en) | 2005-04-06 | 2013-07-02 | Ibc Pharmaceuticals, Inc. | Combination therapy with anti-CD74 antibodies provides enhanced toxicity to malignancies, Autoimmune disease and other diseases |
| WO2006120230A2 (en) | 2005-05-12 | 2006-11-16 | Crucell Holland B.V. | Host cell specific binding molecules capable of neutralizing viruses and uses thereof |
| EP1739179A1 (en) | 2005-06-30 | 2007-01-03 | Octapharma AG | Serum-free stable transfection and production of recombinant human proteins in human cell lines |
| US20080286819A1 (en) * | 2005-11-07 | 2008-11-20 | Ravetch Jeffrey V | Reagents, Methods and Systems for Selecting a Cytotoxic Antibody or Variant Thereof |
| US20080206246A1 (en) * | 2006-04-05 | 2008-08-28 | Ravetch Jeffrey V | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
| US8470318B2 (en) | 2005-11-07 | 2013-06-25 | The Rockefeller University | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
| AR053416A1 (es) | 2005-11-10 | 2007-05-09 | Protech Pharma S A | Combinacion de glicoisoformas para el tratamiento o prevencion de la septicemia, linea celular transgenica productora de glicoformas de eritropoyetina, composicion farmaceutica que comprende a dicha combinacion, procedimientos para obtener la linea celular, procedimiento para producir dicha combinac |
| DE102005054628A1 (de) | 2005-11-16 | 2007-05-24 | Cevec Pharmaceuticals Gmbh | Verfahren zur Herstellung von permanenten humanen Zelllinien |
| US7642078B2 (en) | 2005-12-28 | 2010-01-05 | Crucell Holland B.V. | Methods to obtain recombinant proteins with increased sialylation from cells that express adenovirus E1A protein, and proteins obtained thereby |
| WO2007107578A1 (en) | 2006-03-20 | 2007-09-27 | Chromagenics B.V. | Expression augmenting dna fragments, use thereof, and methods for finding thereof |
| MX2008012843A (es) * | 2006-04-05 | 2009-01-19 | Univ Rockefeller | Polipeptidos con propiedades antiinflamatorias aumentadas y citotoxicas reducidas y metodos relacionados. |
| EP3018142A1 (en) | 2006-06-06 | 2016-05-11 | Crucell Holland B.V. | Human binding molecules having killing activity against staphylococci and uses thereof |
| JP5586952B2 (ja) | 2006-06-06 | 2014-09-10 | クルセル ホランド ベー ヴェー | 腸球菌に対する殺活性を有するヒトの結合分子及びその使用方法 |
| AU2007272054C1 (en) | 2006-07-14 | 2014-08-28 | Dpx Holdings B.V. | Improved process for the culturing of cells |
| MY170607A (en) | 2006-09-07 | 2019-08-20 | Crucell Holland Bv | Human binding molecules capable of neutralizing influenza virus h5n1 and uses thereof |
| PT2059532E (pt) | 2006-09-07 | 2013-03-07 | Crucell Holland Bv | Moléculas de ligação humanas capazes de neutralizar o vírus da gripe h5n1 e seus usos |
| AU2007317755A1 (en) * | 2006-10-27 | 2008-05-15 | The Rockefeller University | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
| JP2010512306A (ja) * | 2006-10-27 | 2010-04-22 | ザ ロックフェラー ユニバーシティー | 抗炎症特性が増強され、細胞毒性特性が減少したポリペプチドおよび関連する方法 |
| US8071332B2 (en) | 2007-08-10 | 2011-12-06 | Toto Ltd. | Recombinant mammal cells, method of producing thereof, and method of producing proteins of interest |
| WO2009074318A2 (en) * | 2007-12-13 | 2009-06-18 | Roche Diagnostics Gmbh | Novel rubella e1 envelope protein variants and their use in the detection of anti-rubella antibodies |
| US20120039939A1 (en) * | 2008-04-11 | 2012-02-16 | The Johns Hopkins University | Compositions and methods for vaccine and virus production |
| EP2279410B1 (en) | 2008-04-22 | 2015-11-11 | The Rockefeller University | Methods of identifying anti-inflammatory compounds |
| DK2307538T3 (da) * | 2008-07-15 | 2016-01-18 | Crucell Holland Bv | Skalérbar fremgangsmåde til dyrkning af per.c6-celler og fremstilling af produkter derfra |
| MX2011000891A (es) | 2008-07-21 | 2011-06-01 | Immunomedics Inc | Variantes estructurales de anticuerpos para caracteristicas terapeuticas mejoradas. |
| WO2010127939A1 (en) | 2009-04-23 | 2010-11-11 | Crucell Holland B.V. | Recombinant human alpha1-antitrypsin |
| US8470327B2 (en) | 2009-05-11 | 2013-06-25 | Crucell Holland B.V. | Human binding molecules capable of neutralizing influenza virus H3N2 and uses thereof |
| US20120270264A1 (en) | 2009-10-01 | 2012-10-25 | Toto Ltd. | Dna construct, and process for production of recombinant cho cell using same |
| DK2505654T4 (da) | 2010-02-08 | 2020-07-27 | Regeneron Pharma | Mus med fælles letkæde |
| US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| US8961978B2 (en) | 2011-07-14 | 2015-02-24 | Crucell Holland B.V. | Human binding molecules capable of neutralizing influenza A viruses of phylogenetic group 1 and phylogenetic group 2 and influenza B viruses |
| MY172718A (en) | 2011-08-05 | 2019-12-11 | Regeneron Pharma | Humanized universal light chain mice |
| WO2013093760A2 (en) | 2011-12-19 | 2013-06-27 | Grifols, S.A. | Compositions, methods, and kits for preparing sialylated recombinant proteins |
| CN102827273A (zh) * | 2012-02-16 | 2012-12-19 | 张小莺 | 抗痘苗病毒IgY抗体的制备 |
| ES2664625T3 (es) | 2012-03-08 | 2018-04-20 | Janssen Vaccines & Prevention B.V. | Moléculas de unión humanas que pueden unirse a los virus de la influenza b y neutralizarlos, y sus usos |
| CA2870821C (en) | 2012-04-20 | 2022-06-14 | Merus B.V. | Methods and means for the production of ig-like molecules |
| US9657290B2 (en) | 2012-07-03 | 2017-05-23 | The Board Of Trustees Of The Leland Stanford Junior University | Scalable bio-element analysis |
| WO2014006217A1 (en) | 2012-07-06 | 2014-01-09 | Genmab B.V. | Dimeric protein with triple mutations |
| WO2014048910A1 (en) | 2012-09-27 | 2014-04-03 | Crucell Holland B.V. | Human binding molecules capable of binding to and neutralizing hepatitis b viruses and uses thereof |
| LT2900694T (lt) | 2012-09-27 | 2018-11-12 | Merus N.V. | Bispecifiniai igg antikūnai kaip t ląstelių aktyvatoriai |
| EA035846B1 (ru) | 2013-04-15 | 2020-08-20 | Янссен Вэксинс Энд Превеншн Б.В. | Антитела человека, связывающиеся с g-белком rsv |
| CN105189547B (zh) | 2013-04-15 | 2020-01-17 | 扬森疫苗与预防公司 | 结合到rsv g蛋白的人类抗体 |
| DE112014003136A5 (de) | 2013-07-01 | 2016-04-21 | Charité - Universitätsmedizin Berlin | Immortalisierte humane Chorionzelllinie sowie Verfahren zur Immortalisierung humaner Chorionzellen |
| CN104693308B (zh) * | 2013-12-05 | 2020-08-04 | 同济大学 | 感受胞内pH变化的Smad5蛋白及其应用 |
| EP2883883A1 (en) | 2013-12-16 | 2015-06-17 | Cardio3 Biosciences S.A. | Therapeutic targets and agents useful in treating ischemia reperfusion injury |
| WO2015130172A1 (en) | 2014-02-28 | 2015-09-03 | Merus B.V. | Antibodies that bind egfr and erbb3 |
| JP6967853B2 (ja) | 2014-02-28 | 2021-11-17 | メルス ナムローゼ フェンノートシャップ | ErbB−2およびErbB−3に結合する抗体 |
| BR112016021572A2 (pt) | 2014-03-21 | 2017-10-03 | Regeneron Pharma | Métodos para preparar um animal não humano geneticamente modificado e para produzir proteínas de ligação, hibridoma, ácido nucleico, célula, e, proteína de ligação |
| TWI743024B (zh) | 2014-06-06 | 2021-10-21 | 美商健臻公司 | 灌注培養方法及其用途 |
| CA2975655C (en) | 2015-02-05 | 2023-09-19 | Janssen Vaccines & Prevention B.V. | Binding molecules directed against influenza hemagglutinin and uses thereof |
| WO2016124682A1 (en) | 2015-02-05 | 2016-08-11 | Janssen Vaccines & Prevention B.V. | Human neutralizing antibodies binding to influenza neuraminidase |
| US10370653B2 (en) | 2015-02-22 | 2019-08-06 | The Board Of Trustees Of The Leland Stanford Junior University | Micro-screening apparatus, process, and products |
| CA2979702A1 (en) | 2015-03-19 | 2016-09-22 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| PL3115376T3 (pl) | 2015-07-10 | 2019-01-31 | Merus N.V. | Ludzkie przeciwciało wiążące cd3 |
| SG11201803359VA (en) | 2015-10-23 | 2018-05-30 | Merus Nv | Binding molecules that inhibit cancer growth |
| WO2017148889A1 (en) | 2016-03-01 | 2017-09-08 | Janssen Vaccines & Prevention B.V. | Human neutralizing antibodies binding to influenza b neuraminidase |
| CN115254210A (zh) | 2016-11-14 | 2022-11-01 | 浩康生物系统公司 | 用于分选目标颗粒的方法和装置 |
| SG11201907927SA (en) | 2017-03-28 | 2019-10-30 | Janssen Vaccines & Prevention Bv | Binding molecules that specifically bind to tau |
| US11780925B2 (en) | 2017-03-31 | 2023-10-10 | Merus N.V. | ErbB-2 and ErbB3 binding bispecific antibodies for use in the treatment of cells that have an NRG1 fusion gene |
| WO2018192974A1 (en) | 2017-04-18 | 2018-10-25 | Université Libre de Bruxelles | Biomarkers and targets for proliferative diseases |
| BR112019024230A2 (pt) | 2017-05-17 | 2020-06-09 | Merus N.V. | combinação de um anticorpo bispecífico erbb-2 / erbb-3 com terapia endócrina para câncer de mama |
| SG11202001050PA (en) | 2017-08-09 | 2020-03-30 | Merus Nv | Antibodies that bind egfr and cmet |
| TW201930351A (zh) | 2017-10-06 | 2019-08-01 | 日商小野藥品工業股份有限公司 | 雙特異性抗體 |
| EA202091350A1 (ru) | 2017-12-04 | 2020-09-02 | Янссен Вэксинс Энд Превеншн Б.В. | Связывающие молекулы, специфично связывающиеся с тау-белком |
| WO2019149798A1 (en) | 2018-02-01 | 2019-08-08 | Janssen Vaccines & Prevention B.V. | Binding molecules that specifically bind to tau |
| TWI849895B (zh) | 2018-02-09 | 2024-07-21 | 日商小野藥品工業股份有限公司 | 雙特異性抗體 |
| EP3768701B1 (en) | 2018-03-23 | 2023-08-02 | Université Libre de Bruxelles | Wnt signaling agonist molecules |
| TW202509079A (zh) | 2019-04-04 | 2025-03-01 | 日商小野藥品工業股份有限公司 | 雙特異性抗體 |
| TWI809286B (zh) | 2019-07-05 | 2023-07-21 | 日商小野藥品工業股份有限公司 | 以pd-1/cd3雙特異性蛋白質所進行之血液性癌症治療 |
| TW202118790A (zh) | 2019-07-30 | 2021-05-16 | 日商小野藥品工業股份有限公司 | 雙特異性抗體 |
| US20220332825A1 (en) | 2019-08-08 | 2022-10-20 | Ono Pharmaceutical Co., Ltd. | Bispecific protein |
| AU2022288080A1 (en) * | 2021-06-11 | 2023-12-07 | Monsanto Technology Llc | Methods and compositions for altering protein accumulation |
| EP4578876A1 (en) | 2022-08-23 | 2025-07-02 | ONO Pharmaceutical Co., Ltd. | Bispecific antibody |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2573436B1 (fr) * | 1984-11-20 | 1989-02-17 | Pasteur Institut | Adn recombinant comportant une sequence nucleotidique codant pour un polypeptide determine sous le controle d'un promoteur d'adenovirus, vecteurs contenant cet adn recombinant, cellules eucaryotes transformees par cet adn recombinant, produits d'excretion de ces cellules transformees et leurs applications, notamment a la constitution de vaccins |
| US4892737A (en) * | 1988-09-22 | 1990-01-09 | University Of Florida | Composition and method for enhancing permeability of topical drugs |
| GB8900483D0 (en) * | 1989-01-10 | 1989-03-08 | Celltech Ltd | Recombinant dna method |
| ATE150486T1 (de) * | 1991-08-01 | 1997-04-15 | Fond Nat Transfusion Sanguine | Expression in nicht-tumorbildenden menschlichen lymphoblasten zellinien mit einem integrierenden vektor |
| FI951138L (fi) * | 1993-07-13 | 1995-04-13 | Rhone Poulenc Rorer Sa | Puuttellisia adenovirusvektoreita ja niiden käyttö geeniterapiassa |
| US5610043A (en) * | 1994-04-28 | 1997-03-11 | The United States Of America As Represented By The Department Of Health And Human Services | Human prostatic cell lines immortalized by adenovirus 12-simian virus 40 (AD12/SV40) hybrid virus |
| DE69638058D1 (de) * | 1995-06-15 | 2009-11-26 | Crucell Holland Bv | Verpackungssysteme für humane rekombinante Adenoviren zur Gentherapie |
-
2000
- 2000-04-17 WO PCT/NL2000/000247 patent/WO2000063403A2/en not_active Ceased
- 2000-04-17 EP EP00921175A patent/EP1161548B2/en not_active Expired - Lifetime
- 2000-04-17 EP EP09174441A patent/EP2163640B1/en not_active Expired - Lifetime
- 2000-04-17 ES ES00921175T patent/ES2237420T5/es not_active Expired - Lifetime
- 2000-04-17 SI SI200031051T patent/SI1533380T1/sl unknown
- 2000-04-17 ES ES05100732T patent/ES2335775T3/es not_active Expired - Lifetime
- 2000-04-17 DE DE60018171T patent/DE60018171T3/de not_active Expired - Lifetime
- 2000-04-17 CA CA2370477A patent/CA2370477C/en not_active Expired - Lifetime
- 2000-04-17 CN CNB008089388A patent/CN100457914C/zh not_active Expired - Lifetime
- 2000-04-17 AU AU41520/00A patent/AU772352B2/en not_active Expired
- 2000-04-17 IL IL14584900A patent/IL145849A0/xx unknown
- 2000-04-17 EP EP05100732A patent/EP1533380B1/en not_active Expired - Lifetime
- 2000-04-17 DK DK05100732.6T patent/DK1533380T3/da active
- 2000-04-17 HK HK03100323.5A patent/HK1048138B/zh unknown
- 2000-04-17 DK DK09174441.7T patent/DK2163640T3/da active
- 2000-04-17 NZ NZ514951A patent/NZ514951A/xx not_active IP Right Cessation
- 2000-04-17 SI SI200030662T patent/SI1161548T2/sl unknown
- 2000-04-17 ES ES09174441T patent/ES2378272T3/es not_active Expired - Lifetime
- 2000-04-17 AT AT00921175T patent/ATE289354T1/de active
- 2000-04-17 MX MXPA01010360A patent/MXPA01010360A/es active IP Right Grant
- 2000-04-17 JP JP2000612481A patent/JP4210036B2/ja not_active Expired - Lifetime
- 2000-04-17 DK DK00921175.6T patent/DK1161548T4/da active
- 2000-04-17 PT PT05100732T patent/PT1533380E/pt unknown
- 2000-04-17 AT AT09174441T patent/ATE536417T1/de active
- 2000-04-17 DE DE60043273T patent/DE60043273D1/de not_active Expired - Lifetime
- 2000-04-17 AT AT05100732T patent/ATE447617T1/de active
- 2000-04-17 PT PT00921175T patent/PT1161548E/pt unknown
-
2001
- 2001-10-10 IL IL145849A patent/IL145849A/en not_active IP Right Cessation
- 2001-10-12 NO NO20014977A patent/NO328951B1/no not_active IP Right Cessation
-
2010
- 2010-01-27 CY CY20101100084T patent/CY1109759T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2237420T3 (es) | Produccion de proteina recombinante en una celula humana. | |
| US6855544B1 (en) | Recombinant protein production in a human cell | |
| US7833753B2 (en) | Methods of producing erythropoietin isoforms comprising Lewis-X structures and high sialic acid content and compositions of the same | |
| US20070231860A1 (en) | Over-expression of enzymes involved in post-translational protein modifications in human cells | |
| JP6721797B2 (ja) | 異種遺伝子発現のための強力で短いプロモーター | |
| US7604960B2 (en) | Transient protein expression methods | |
| US20060099685A1 (en) | Recombinant expression of factor VIII in human cells | |
| US20140308704A1 (en) | Adenovirus producing novel cell line and the use thereof | |
| US20050170463A1 (en) | Recombinant protein production in permanent amniocytic cells that comprise nucleic acid encoding adenovirus E1A and E1B proteins | |
| EA045609B1 (ru) | Высокоактивный и короткий промотор, предназначенный для экспрессии гетерологичных генов | |
| CN109154000A (zh) | 有效和平衡的双向启动子 |