JP7097433B2 - 宿主細胞ガレクチンおよび他の夾雑物からグリコシル化タンパク質を精製する方法 - Google Patents
宿主細胞ガレクチンおよび他の夾雑物からグリコシル化タンパク質を精製する方法 Download PDFInfo
- Publication number
- JP7097433B2 JP7097433B2 JP2020505786A JP2020505786A JP7097433B2 JP 7097433 B2 JP7097433 B2 JP 7097433B2 JP 2020505786 A JP2020505786 A JP 2020505786A JP 2020505786 A JP2020505786 A JP 2020505786A JP 7097433 B2 JP7097433 B2 JP 7097433B2
- Authority
- JP
- Japan
- Prior art keywords
- protein
- galectin
- matrix
- poi
- buffer
- 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
- 239000000356 contaminant Substances 0.000 title claims description 37
- 102000007563 Galectins Human genes 0.000 title claims description 36
- 108010046569 Galectins Proteins 0.000 title claims description 36
- 102000035122 glycosylated proteins Human genes 0.000 title 1
- 108091005608 glycosylated proteins Proteins 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 claims description 330
- 102000004169 proteins and genes Human genes 0.000 claims description 298
- 108010001517 Galectin 3 Proteins 0.000 claims description 157
- 102000000802 Galectin 3 Human genes 0.000 claims description 157
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 124
- 239000011159 matrix material Substances 0.000 claims description 101
- 238000000034 method Methods 0.000 claims description 101
- 239000000872 buffer Substances 0.000 claims description 81
- 238000005341 cation exchange Methods 0.000 claims description 74
- 229910052742 iron Inorganic materials 0.000 claims description 66
- 230000027455 binding Effects 0.000 claims description 51
- -1 β-galactosyl residues Chemical group 0.000 claims description 51
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 48
- 108010081667 aflibercept Proteins 0.000 claims description 43
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims description 42
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims description 42
- 238000004191 hydrophobic interaction chromatography Methods 0.000 claims description 38
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 32
- 229960002833 aflibercept Drugs 0.000 claims description 31
- 229910052751 metal Inorganic materials 0.000 claims description 30
- 239000002184 metal Substances 0.000 claims description 30
- 239000003480 eluent Substances 0.000 claims description 27
- 150000001768 cations Chemical class 0.000 claims description 22
- 238000011068 loading method Methods 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 20
- 239000005909 Kieselgur Substances 0.000 claims description 18
- 241000700605 Viruses Species 0.000 claims description 18
- 230000001965 increasing effect Effects 0.000 claims description 17
- 108060003951 Immunoglobulin Proteins 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 16
- 229910052802 copper Inorganic materials 0.000 claims description 15
- 239000010949 copper Substances 0.000 claims description 15
- 102000018358 immunoglobulin Human genes 0.000 claims description 15
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 14
- 239000012535 impurity Substances 0.000 claims description 14
- 230000002779 inactivation Effects 0.000 claims description 14
- 238000005406 washing Methods 0.000 claims description 14
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 12
- 239000001110 calcium chloride Substances 0.000 claims description 12
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 12
- 238000004113 cell culture Methods 0.000 claims description 12
- 229910052725 zinc Inorganic materials 0.000 claims description 12
- 239000011701 zinc Substances 0.000 claims description 12
- 239000000706 filtrate Substances 0.000 claims description 11
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 9
- 229960002459 alefacept Drugs 0.000 claims description 8
- 239000012228 culture supernatant Substances 0.000 claims description 8
- 108700019309 factor VIII-Fc fusion Proteins 0.000 claims description 8
- 239000003792 electrolyte Substances 0.000 claims description 7
- 229960003697 abatacept Drugs 0.000 claims description 6
- 239000007853 buffer solution Substances 0.000 claims description 6
- 108010008165 Etanercept Proteins 0.000 claims description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 5
- 229960000403 etanercept Drugs 0.000 claims description 5
- 108010046141 rilonacept Proteins 0.000 claims description 5
- 229960001886 rilonacept Drugs 0.000 claims description 5
- 229910052782 aluminium Inorganic materials 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- 229910052791 calcium Inorganic materials 0.000 claims description 3
- 239000011575 calcium Substances 0.000 claims description 3
- 229910017052 cobalt Inorganic materials 0.000 claims description 3
- 239000010941 cobalt Substances 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 229910052753 mercury Inorganic materials 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 229910052712 strontium Inorganic materials 0.000 claims description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052788 barium Inorganic materials 0.000 claims description 2
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 2
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 2
- 239000006228 supernatant Substances 0.000 claims description 2
- 235000018102 proteins Nutrition 0.000 description 278
- 210000004027 cell Anatomy 0.000 description 121
- 235000002639 sodium chloride Nutrition 0.000 description 99
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 74
- 150000003839 salts Chemical class 0.000 description 74
- 239000000047 product Substances 0.000 description 72
- 108090000765 processed proteins & peptides Proteins 0.000 description 67
- 238000010828 elution Methods 0.000 description 65
- 102000004196 processed proteins & peptides Human genes 0.000 description 57
- 239000011347 resin Substances 0.000 description 50
- 229920005989 resin Polymers 0.000 description 50
- 229920001184 polypeptide Polymers 0.000 description 49
- 150000007523 nucleic acids Chemical class 0.000 description 39
- 239000011780 sodium chloride Substances 0.000 description 37
- 102000039446 nucleic acids Human genes 0.000 description 36
- 108020004707 nucleic acids Proteins 0.000 description 36
- 108020004414 DNA Proteins 0.000 description 34
- 239000012541 Fractogel® Substances 0.000 description 30
- 238000012216 screening Methods 0.000 description 27
- 239000010432 diamond Substances 0.000 description 26
- 230000014509 gene expression Effects 0.000 description 26
- 239000000126 substance Substances 0.000 description 26
- 235000001014 amino acid Nutrition 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- 238000002965 ELISA Methods 0.000 description 21
- 229940024606 amino acid Drugs 0.000 description 20
- 150000001413 amino acids Chemical class 0.000 description 20
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 20
- 125000003729 nucleotide group Chemical group 0.000 description 20
- 108091033319 polynucleotide Proteins 0.000 description 20
- 102000040430 polynucleotide Human genes 0.000 description 20
- 239000002157 polynucleotide Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000007983 Tris buffer Substances 0.000 description 19
- 238000002474 experimental method Methods 0.000 description 19
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 18
- 108091026890 Coding region Proteins 0.000 description 17
- 238000001542 size-exclusion chromatography Methods 0.000 description 17
- 239000013540 Fractogel® SO3- Substances 0.000 description 16
- 239000003446 ligand Substances 0.000 description 16
- 239000002773 nucleotide Substances 0.000 description 15
- 229920002684 Sepharose Polymers 0.000 description 14
- 239000001509 sodium citrate Substances 0.000 description 14
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 14
- 125000003275 alpha amino acid group Chemical group 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 13
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 12
- 230000004071 biological effect Effects 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- 239000007979 citrate buffer Substances 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 239000013604 expression vector Substances 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 239000002609 medium Substances 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 11
- 238000011021 bench scale process Methods 0.000 description 11
- 102000037865 fusion proteins Human genes 0.000 description 11
- 108020001507 fusion proteins Proteins 0.000 description 11
- 238000005342 ion exchange Methods 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 239000001632 sodium acetate Substances 0.000 description 11
- 235000017281 sodium acetate Nutrition 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 238000013518 transcription Methods 0.000 description 11
- 230000035897 transcription Effects 0.000 description 11
- 102000014914 Carrier Proteins Human genes 0.000 description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 description 10
- 108091034117 Oligonucleotide Proteins 0.000 description 10
- 108091008324 binding proteins Proteins 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 238000013537 high throughput screening Methods 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 238000004458 analytical method Methods 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
- 239000006167 equilibration buffer Substances 0.000 description 9
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- 239000007790 solid phase Substances 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- 239000004475 Arginine Substances 0.000 description 8
- 239000007987 MES buffer Substances 0.000 description 8
- 239000012515 MabSelect SuRe Substances 0.000 description 8
- 238000005349 anion exchange Methods 0.000 description 8
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 8
- 238000010586 diagram Methods 0.000 description 8
- 239000012149 elution buffer Substances 0.000 description 8
- 230000004927 fusion Effects 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- SADPCIINLASURY-UHFFFAOYSA-N 2-morpholin-4-ylethanesulfonic acid;sodium Chemical compound [Na].OS(=O)(=O)CCN1CCOCC1 SADPCIINLASURY-UHFFFAOYSA-N 0.000 description 7
- 108020004511 Recombinant DNA Proteins 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000005277 cation exchange chromatography Methods 0.000 description 7
- 239000006143 cell culture medium Substances 0.000 description 7
- 238000011109 contamination Methods 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 238000001742 protein purification Methods 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 108020004705 Codon Proteins 0.000 description 6
- 102000004856 Lectins Human genes 0.000 description 6
- 108090001090 Lectins Proteins 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 238000004422 calculation algorithm Methods 0.000 description 6
- 238000012374 filter flush Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 230000004962 physiological condition Effects 0.000 description 6
- 238000003259 recombinant expression Methods 0.000 description 6
- 239000001488 sodium phosphate Substances 0.000 description 6
- 229910000162 sodium phosphate Inorganic materials 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 230000014616 translation Effects 0.000 description 6
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 6
- 239000011534 wash buffer Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- 102000044445 Galectin-8 Human genes 0.000 description 5
- 101000608769 Homo sapiens Galectin-8 Proteins 0.000 description 5
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 5
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 5
- 201000005667 central retinal vein occlusion Diseases 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 210000001723 extracellular space Anatomy 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 239000002523 lectin Substances 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 208000004644 retinal vein occlusion Diseases 0.000 description 5
- 230000003248 secreting effect Effects 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 229940006486 zinc cation Drugs 0.000 description 5
- QJYNZEYHSMRWBK-NIKIMHBISA-N 1,2,3,4,6-pentakis-O-galloyl-beta-D-glucose Chemical compound OC1=C(O)C(O)=CC(C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(O)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(O)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(O)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(O)C(O)=C(O)C=2)=C1 QJYNZEYHSMRWBK-NIKIMHBISA-N 0.000 description 4
- 229920000936 Agarose Polymers 0.000 description 4
- 241000699800 Cricetinae Species 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 108010001515 Galectin 4 Proteins 0.000 description 4
- 102000000805 Galectin 4 Human genes 0.000 description 4
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 241000191967 Staphylococcus aureus Species 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000001042 affinity chromatography Methods 0.000 description 4
- 206010064930 age-related macular degeneration Diseases 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 239000012062 aqueous buffer Substances 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 238000004590 computer program Methods 0.000 description 4
- 239000005547 deoxyribonucleotide Substances 0.000 description 4
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 210000003292 kidney cell Anatomy 0.000 description 4
- 208000002780 macular degeneration Diseases 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000003908 quality control method Methods 0.000 description 4
- 238000005215 recombination Methods 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 238000000108 ultra-filtration Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 108010001498 Galectin 1 Proteins 0.000 description 3
- 102100021736 Galectin-1 Human genes 0.000 description 3
- 102000044464 Galectin-12 Human genes 0.000 description 3
- 102100031351 Galectin-9 Human genes 0.000 description 3
- 101710121810 Galectin-9 Proteins 0.000 description 3
- 238000012855 HCP-ELISA Methods 0.000 description 3
- 101001051083 Homo sapiens Galectin-12 Proteins 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 239000013522 chelant Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 230000009827 complement-dependent cellular cytotoxicity Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 201000011190 diabetic macular edema Diseases 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000011067 equilibration Methods 0.000 description 3
- 238000011010 flushing procedure Methods 0.000 description 3
- 229930182830 galactose Natural products 0.000 description 3
- 229940074391 gallic acid Drugs 0.000 description 3
- 235000004515 gallic acid Nutrition 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000002736 nonionic surfactant Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 230000008488 polyadenylation Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 229960000160 recombinant therapeutic protein Drugs 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000007974 sodium acetate buffer Substances 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000005030 transcription termination Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
- 102100022641 Coagulation factor IX Human genes 0.000 description 2
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 2
- 102000036364 Cullin Ring E3 Ligases Human genes 0.000 description 2
- 108091007045 Cullin Ring E3 Ligases Proteins 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 108091029865 Exogenous DNA Proteins 0.000 description 2
- 108010076282 Factor IX Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 2
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102100035194 Placenta growth factor Human genes 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- 239000008351 acetate buffer Substances 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000010364 biochemical engineering Methods 0.000 description 2
- 238000005842 biochemical reaction Methods 0.000 description 2
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 230000003196 chaotropic effect Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000031902 chemoattractant activity Effects 0.000 description 2
- 239000012504 chromatography matrix Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000412 dendrimer Substances 0.000 description 2
- 229920000736 dendritic polymer Polymers 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000011026 diafiltration Methods 0.000 description 2
- 239000000032 diagnostic agent Substances 0.000 description 2
- 229940039227 diagnostic agent Drugs 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 229940051306 eylea Drugs 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 2
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000006320 pegylation Effects 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 239000012562 protein A resin Substances 0.000 description 2
- 238000012797 qualification Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical class 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000011573 trace mineral Substances 0.000 description 2
- 235000013619 trace mineral Nutrition 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 1
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 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
- AGFIRQJZCNVMCW-UAKXSSHOSA-N 5-bromouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 AGFIRQJZCNVMCW-UAKXSSHOSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 235000004035 Cryptotaenia japonica Nutrition 0.000 description 1
- 101150097493 D gene Proteins 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 101150096839 Fcmr gene Proteins 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 description 1
- 102000044466 Galectin-10 Human genes 0.000 description 1
- 102000044513 Galectin-13 Human genes 0.000 description 1
- 102100040510 Galectin-3-binding protein Human genes 0.000 description 1
- 101710197901 Galectin-3-binding protein Proteins 0.000 description 1
- 101710121821 Galectin-6 Proteins 0.000 description 1
- 102000044465 Galectin-7 Human genes 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 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
- 239000004471 Glycine Substances 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001057612 Homo sapiens Dual specificity protein phosphatase 5 Proteins 0.000 description 1
- 101000620927 Homo sapiens Galactoside-binding soluble lectin 13 Proteins 0.000 description 1
- 101001051087 Homo sapiens Galectin-10 Proteins 0.000 description 1
- 101000608772 Homo sapiens Galectin-7 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108010055795 Integrin alpha1beta1 Proteins 0.000 description 1
- 108010030465 Integrin alpha6beta1 Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- 206010025415 Macular oedema Diseases 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 230000026279 RNA modification Effects 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 235000001537 Ribes X gardonianum Nutrition 0.000 description 1
- 235000001535 Ribes X utile Nutrition 0.000 description 1
- 235000016919 Ribes petraeum Nutrition 0.000 description 1
- 244000281247 Ribes rubrum Species 0.000 description 1
- 235000002355 Ribes spicatum Nutrition 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 241000235088 Saccharomyces sp. Species 0.000 description 1
- 108091058545 Secretory proteins Proteins 0.000 description 1
- 102000040739 Secretory proteins Human genes 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 108010088160 Staphylococcal Protein A Proteins 0.000 description 1
- 101100096298 Staphylococcus aureus spa gene Proteins 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 102000007000 Tenascin Human genes 0.000 description 1
- 108010008125 Tenascin Proteins 0.000 description 1
- 102100028644 Tenascin-R Human genes 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 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 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 102000007641 Trefoil Factors Human genes 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 235000015724 Trifolium pratense Nutrition 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000003732 agents acting on the eye Substances 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 229940118888 barium cation Drugs 0.000 description 1
- XDFCIPNJCBUZJN-UHFFFAOYSA-N barium(2+) Chemical compound [Ba+2] XDFCIPNJCBUZJN-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229950004221 besilate Drugs 0.000 description 1
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical group OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 238000013368 capillary electrophoresis sodium dodecyl sulfate analysis Methods 0.000 description 1
- TWFZGCMQGLPBSX-UHFFFAOYSA-N carbendazim Chemical compound C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- BHYOQNUELFTYRT-DPAQBDIFSA-N cholesterol sulfate Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 BHYOQNUELFTYRT-DPAQBDIFSA-N 0.000 description 1
- 229940080277 cholesteryl sulfate Drugs 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000005289 controlled pore glass Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000004395 cytoplasmic granule Anatomy 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000006240 deamidation Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000011143 downstream manufacturing Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 108010090623 galactose binding protein Proteins 0.000 description 1
- 102000021529 galactose binding proteins Human genes 0.000 description 1
- 150000008195 galaktosides Chemical group 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 102000058223 human VEGFA Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 229940121354 immunomodulator Drugs 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
- 238000009655 industrial fermentation Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 108010043603 integrin alpha4beta7 Proteins 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000000050 ionisation spectroscopy Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 238000000670 ligand binding assay Methods 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 239000012516 mab select resin Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 201000010230 macular retinal edema Diseases 0.000 description 1
- 229940096405 magnesium cation Drugs 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 238000013178 mathematical model Methods 0.000 description 1
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 235000018343 nutrient deficiency Nutrition 0.000 description 1
- 229920002114 octoxynol-9 Polymers 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229940125702 ophthalmic agent Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 108010071401 peptidase N Proteins 0.000 description 1
- 238000012510 peptide mapping method Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 210000001957 retinal vein Anatomy 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000004739 secretory vesicle Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 125000005629 sialic acid group Chemical group 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 101150065015 spa gene Proteins 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 108010020387 tenascin R Proteins 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 208000020854 vein disease Diseases 0.000 description 1
- 238000011100 viral filtration Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000012905 visible particle Substances 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 229940036061 zaltrap Drugs 0.000 description 1
- 229960002760 ziv-aflibercept Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/165—Extraction; Separation; Purification by chromatography mixed-mode chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/22—Affinity chromatography or related techniques based upon selective absorption processes
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Cell Biology (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
(a)プロテインAマトリックスに、ほぼ中性のpHで、関心対象のグリコシル化組換えタンパク質(POI)およびガレクチン宿主細胞タンパク質夾雑物を含む宿主細胞培養上清またはろ液を負荷する工程であって、ここで、POIは、免疫グロブリンFcドメインのCH2およびCH3ドメインならびにガレクチン宿主細胞タンパク質夾雑物が可逆的に結合している1つ以上の末端β-ガラクトシル残基を含む、工程;
(b)POIが結合したプロテインAマトリックスを、1~3Mの塩化カルシウムを含む約pH6.0~6.5の緩衝液で洗浄する;
(c)約pH4未満のクエン酸またはクエン酸塩を含む緩衝液でPOIをプロテインAマトリックスから溶出液プールに溶出する工程であって、
(i)溶出液プールがpH3.3~3.7のpH範囲よりも塩基性である場合、溶出液プールをクエン酸でpH3.3~3.7に滴定し、および
(ii)任意で、ウイルス不活性化に十分な期間(典型的には30~90分、ただしウイルス不活性化のウイルスパネル検証によって必要に応じて経験的に)溶出液プールをpH3.3~3.7に保持する工程;
(d)(c)からの溶出液プール中のPOIを、pH5.0~5.5で、約2~15ミリシーメンス(mS)の低伝導率緩衝液中の陽イオン交換マトリックスに結合する工程;
(e)陽イオン交換マトリックスから、最大約40~100mSまで次第に高くなる伝導率の電解質濃度勾配でPOIをCEX溶出液プールに溶出する工程;ならびに
(f)CEX溶出液プールを、pH5.0~6.0の高伝導率緩衝液中の疎水性相互作用クロマトグラフィ(HIC)マトリックスに負荷し、HICマトリックスを洗浄する工程。本発明の方法は、β-ガラクトシル結合ガレクチン宿主細胞タンパク質夾雑物(1または複数)および金属カチオン夾雑物などの他の望ましくない夾雑物からPOIを分離する。
(a)プロテインAマトリックスに、ほぼ中性のpHで、関心対象のグリコシル化組換えタンパク質(POI)およびガレクチン宿主細胞タンパク質(HCP)夾雑物を含む宿主細胞培養上清またはろ液を負荷する工程であって、ここで、POIは、免疫グロブリンFcドメインのCH2およびCH3ドメインならびにガレクチン-3夾雑物が可逆的に結合した1つ以上の末端β-ガラクトシル残基を含む、工程;
(b)POIが結合したプロテインAマトリックスを、1~3Mの塩化カルシウムを含む約pH6.0~6.5の緩衝液で洗浄する工程;
(c)約pH4未満のクエン酸またはクエン酸塩を含む緩衝液でPOIをプロテインAマトリックスから溶出液プールに溶出する工程であって、
(i)溶出液プールがpH3.3~3.7のpH範囲よりも塩基性である場合、溶出液プールをクエン酸でpH3.3~3.7に滴定し、および
(ii)任意で、ウイルス不活性化に十分な期間、溶出液プールをpH3.3~3.7に保持する工程;
(d)(c)からの溶出液プール中のPOIを、pH5.0~5.5で、約2~15mSの低伝導率緩衝液中の陽イオン交換マトリックスに結合する工程;
(e)陽イオン交換マトリックスから、最大約40~100mSまで次第に高くなる伝導率の電解質濃度勾配で、POIをCEX溶出液プールに溶出する工程;ならびに
(f)CEX溶出液プールを、pH5.0~6.0の高伝導率緩衝液中の疎水性相互作用クロマトグラフィ(HIC)マトリックスに負荷し、HICマトリックスを洗浄し、それによってPOIをガレクチンHCP夾雑物から分離する工程
を含む方法。
25mMトリス、480mMラクトース pH7.3;
25mM MES、2M CaCl2 pH6.0;
25mM MES、2M CaCl2 pH6.5;
25mMトリス、2M CaCl2 pH7.0;
25mM MES、750mMアルギニン pH6.0;
25mM MES、750mMアルギニン pH6.5;または
25mMトリス、750mMアルギニン pH7.0。
50mMクエン酸ナトリウム pH6.0;
50mMクエン酸ナトリウム pH7.0;
200mMクエン酸ナトリウム pH6.0;
200mMクエン酸ナトリウム pH7.0;
125mMトリス、500mM NaCl、pH7.4;
25mMトリス、100mM NaCl、pH7.4;
25mMトリス、100mM NaCl、5mM EDTA、pH7.0;または
25Mトリス、100mM NaCl、5mM EDTA、pH8.0。
Wash 2の後に、さらなる3CVの平衡化緩衝液で洗浄した。上記のように、Wash 2および溶出画分をタンパク質濃度について分析した。これらの画分は、従来の誘導結合プラズマ質量分析(ICP-MS)アッセイを使用して、鉄レベルについBrooks Analytical Laboratory(Bothell,WA,USA)によっても分析された。
Claims (9)
- 夾雑物から関心対象のグリコシル化組換えタンパク質を精製する方法であって、以下の工程:
(a)プロテインAマトリックスに、中性のpHで、関心対象の前記グリコシル化組換えタンパク質(POI)およびガレクチン宿主細胞タンパク質(HCP)夾雑物、これはガレクチン-3を含む、を含む宿主細胞培養上清またはろ液を負荷する工程であって、前記POIが、免疫グロブリンFcドメインのCH2およびCH3ドメインならびにガレクチン-3が可逆的に結合した1つ以上の末端β-ガラクトシル残基を含む、工程;
(b)前記POIが結合した前記プロテインAマトリックスを、1~3Mの塩化カルシウムを含むpH6.0~6.5の緩衝液で洗浄する工程;
(c)pH4未満のクエン酸またはクエン酸塩を含む緩衝液で前記POIを前記プロテインAマトリックスから溶出液プールに溶出する工程であって、
(i)前記溶出液プールがpH3.3~3.7のpH範囲よりも塩基性である場合、前記溶出液プールをクエン酸でpH3.3~3.7に滴定し、および
(ii)任意で、ウイルス不活性化に十分な期間、前記溶出液プールをpH3.3~3.7に保持する工程;
(d)(c)からの前記溶出液プール中の前記POIを、pH5.0~5.5で、2~15mSの低伝導率緩衝液中の陽イオン交換マトリックス(CEX)に結合する工程;
(e)前記陽イオン交換マトリックスから、40~100mSまで次第に高くなる伝導率の電解質濃度勾配で、前記POIをCEX溶出液プールに溶出する工程;ならびに
(f)前記CEX溶出液プールを、pH5.0~6.0の、40~100mSの伝導率、又はそれ以上の高伝導率緩衝液中の疎水性相互作用クロマトグラフィ(HIC)マトリックスに負荷し、前記HICマトリックスを洗浄し、それによって前記POIを前記ガレクチン-3から分離する工程
を含む方法。 - (b)において、前記POIが結合している前記プロテインAマトリックスを洗浄する工程が、2~2.7Mの塩化カルシウムを含む緩衝液を使用する、請求項1に記載の方法。
- 前記POIが、アフリベルセプト、アレファセプト、エタネルセプト、アバタセプト、ベラタセプト、rFVIIIFc、rFIXFc、およびリロナセプトから選択される、請求項1に記載の方法。
- 前記POIがアフリベルセプトである、請求項3に記載の方法。
- 前記宿主細胞培養上清またはろ液が金属カチオン夾雑物をさらに含み、および前記POIが前記金属カチオン夾雑物からも分離される、請求項1に記載の方法。
- 前記金属カチオン夾雑物が、アルミニウム、バリウム、カルシウム、コバルト、銅、亜鉛、鉄、マグネシウム、マンガン、水銀、ニッケル、およびストロンチウムカチオンから選択される、請求項5に記載の方法。
- 前記金属カチオン夾雑物が鉄カチオンである、請求項6に記載の方法。
- (c)からの前記溶出液プール中の前記POIを陽イオン交換マトリックスに結合する前に、前記溶出液プールを、珪藻土によるろ過を含む深層ろ過に供する工程をさらに含む、請求項1に記載の方法。
- 前記珪藻土がクエン酸緩衝液で前処理された、請求項8に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762546558P | 2017-08-17 | 2017-08-17 | |
US62/546,558 | 2017-08-17 | ||
PCT/US2018/046919 WO2019036626A1 (en) | 2017-08-17 | 2018-08-17 | PROCESS FOR PURIFYING GLYCOSYLATED PROTEIN FROM GALECTINES AND OTHER HOST CELL CONTAMINANTS |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2020531411A JP2020531411A (ja) | 2020-11-05 |
JPWO2019036626A5 JPWO2019036626A5 (ja) | 2022-05-09 |
JP7097433B2 true JP7097433B2 (ja) | 2022-07-07 |
Family
ID=63684424
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020505786A Active JP7097433B2 (ja) | 2017-08-17 | 2018-08-17 | 宿主細胞ガレクチンおよび他の夾雑物からグリコシル化タンパク質を精製する方法 |
Country Status (9)
Country | Link |
---|---|
US (1) | US11358983B2 (ja) |
EP (1) | EP3668985B1 (ja) |
JP (1) | JP7097433B2 (ja) |
KR (1) | KR102578087B1 (ja) |
CN (1) | CN111344410B (ja) |
CA (1) | CA3067735A1 (ja) |
DK (1) | DK3668985T3 (ja) |
ES (1) | ES2887046T3 (ja) |
WO (1) | WO2019036626A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102578087B1 (ko) | 2017-08-17 | 2023-09-18 | 저스트-에보텍 바이오로직스, 아이엔씨. | 숙주세포 갈렉틴(galectins) 및 다른 오염물(contaminant)로부터 글리코실화 단백질을 정제하는 방법 |
JP2022552052A (ja) * | 2019-12-06 | 2022-12-15 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | 抗vegfタンパク質組成物及びその製造方法 |
WO2023192926A2 (en) * | 2022-03-30 | 2023-10-05 | Ionis Pharmaceuticals, Inc. | Methods for separating certain oligonucleotide compounds |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008543868A (ja) | 2005-06-17 | 2008-12-04 | ワイス | Fc領域含有タンパク質を精製する方法 |
JP2010516651A (ja) | 2007-01-17 | 2010-05-20 | メルク セローノ ソシエテ アノニム | Fc含有タンパク質の精製のための方法 |
JP2011530606A (ja) | 2008-08-14 | 2011-12-22 | メルク・シャープ・エンド・ドーム・コーポレイション | プロテインaアフィニティークロマトグラフィーを用いる抗体の精製方法 |
Family Cites Families (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
DE68925893T2 (de) | 1988-07-23 | 1996-08-08 | Delta Biotechnology Ltd | Sekretorische leader-sequenzen |
ATE135397T1 (de) | 1988-09-23 | 1996-03-15 | Cetus Oncology Corp | Zellenzuchtmedium für erhöhtes zellenwachstum, zur erhöhung der langlebigkeit und expression der produkte |
US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
US5429746A (en) | 1994-02-22 | 1995-07-04 | Smith Kline Beecham Corporation | Antibody purification |
AT403989B (de) | 1996-09-16 | 1998-07-27 | Immuno Ag | Verfahren zur herstellung eines plasmaprotein-hältigen arzneimittels |
SI0950067T1 (sl) | 1996-11-27 | 2007-12-31 | Genentech Inc | Afinitetno čiščenje polipeptida na proteinskemA matriksu |
US6022952A (en) | 1998-04-01 | 2000-02-08 | University Of Alberta | Compositions and methods for protein secretion |
US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
CA2350226C (en) | 1998-11-20 | 2012-04-24 | Fuso Pharmaceutical Industries, Ltd. | Protein expression vector and utilization thereof |
CA2368068A1 (en) | 1999-03-18 | 2000-09-21 | Steven M. Ruben | 27 human secreted proteins |
ATE417928T1 (de) | 1999-06-08 | 2009-01-15 | Regeneron Pharma | Vegf-rezeptorchimären zur behandlung von augenkrankheiten, welche durch vaskuläre permeabilität charakterisiert sind. |
US7306799B2 (en) | 1999-06-08 | 2007-12-11 | Regeneron Pharmaceuticals, Inc. | Use of VEGF inhibitors for treatment of eye disorders |
US7303746B2 (en) | 1999-06-08 | 2007-12-04 | Regeneron Pharmaceuticals, Inc. | Methods of treating eye disorders with modified chimeric polypeptides |
US7070959B1 (en) | 1999-06-08 | 2006-07-04 | Regeneron Pharmaceuticals, Inc. | Modified chimeric polypeptides with improved pharmacokinetic properties |
JP4460302B2 (ja) | 2002-02-05 | 2010-05-12 | ジェネンテック インコーポレイテッド | タンパク質精製法 |
AU2004285928B2 (en) | 2003-10-24 | 2012-02-02 | Amgen, Inc. | Process for purifying proteins in a hydrophobic interaction chromatography flow-through fraction |
FR2894146B1 (fr) | 2005-12-07 | 2008-06-06 | Ifremer | Utilisation d'un polysaccharide excrete par l'espece vibrio diabolicus a des fins d'ingenierie des tissus conjonctifs non mineralises |
US8263750B2 (en) | 2006-03-16 | 2012-09-11 | Amgen Inc. | Method for purifying a protein using protein-A affinity chromatography using an intermediate wash step |
US7998927B2 (en) | 2006-06-23 | 2011-08-16 | Aegis Therapeutics, Llc | Stabilizing alkylglycoside compositions and methods thereof |
AR067536A1 (es) | 2007-07-17 | 2009-10-14 | Hoffmann La Roche | Metodo para obtener una eritropoyetina mono-pegilada en una forma sustancialmente homogenea |
CN105111309A (zh) | 2008-10-20 | 2015-12-02 | Abbvie公司 | 使用a蛋白亲和层析分离和纯化抗体 |
MX2011004558A (es) | 2008-10-29 | 2011-06-01 | Wyeth Llc | Procedimientos para la purificacion de moleculas de union a antigeno de un unico dominio. |
WO2011038894A1 (en) | 2009-10-01 | 2011-04-07 | F. Hoffmann-La Roche Ag | Protein a chromatography |
HUE053489T2 (hu) * | 2009-10-20 | 2021-06-28 | Abbvie Inc | Az anti-il-13 antitestek izolálása és tisztítása a protein A affinitás kromatográviával |
PT2513134T (pt) | 2009-12-18 | 2017-12-14 | Novartis Ag | Solução de lavagem e método para cromatografia de afinidade |
EP2649087A1 (en) | 2010-12-08 | 2013-10-16 | Amgen Inc. | Ion exchange chromatography in the presence of an amino acid |
TW201823460A (zh) | 2012-05-29 | 2018-07-01 | 美商再生元醫藥公司 | 生產細胞株增強子 |
CA2951766A1 (en) * | 2014-06-13 | 2015-12-17 | Lupin Limited | Process for the purification of tnfr:fc fusion protein |
EP3236772A4 (en) * | 2014-12-22 | 2018-10-17 | Alexion Pharmaceuticals, Inc. | Methods of purifying recombinant proteins |
TW201702380A (zh) * | 2015-02-27 | 2017-01-16 | 再生元醫藥公司 | 宿主細胞蛋白質修飾 |
WO2016183222A1 (en) | 2015-05-12 | 2016-11-17 | Regeneron Pharmaceuticals, Inc. | Multimeric protein purity determination |
CN106749660B (zh) * | 2016-12-27 | 2020-02-14 | 嘉和生物药业有限公司 | 单克隆抗体下游纯化过程中有效去除宿主蛋白的方法 |
KR102578087B1 (ko) | 2017-08-17 | 2023-09-18 | 저스트-에보텍 바이오로직스, 아이엔씨. | 숙주세포 갈렉틴(galectins) 및 다른 오염물(contaminant)로부터 글리코실화 단백질을 정제하는 방법 |
US20220119757A1 (en) * | 2019-02-15 | 2022-04-21 | Just-Evotec Biologics, Inc. | Automated biomanufacturing systems, facilities, and processes |
-
2018
- 2018-08-17 KR KR1020207007328A patent/KR102578087B1/ko active IP Right Grant
- 2018-08-17 EP EP18778588.6A patent/EP3668985B1/en active Active
- 2018-08-17 JP JP2020505786A patent/JP7097433B2/ja active Active
- 2018-08-17 DK DK18778588.6T patent/DK3668985T3/da active
- 2018-08-17 WO PCT/US2018/046919 patent/WO2019036626A1/en unknown
- 2018-08-17 ES ES18778588T patent/ES2887046T3/es active Active
- 2018-08-17 CA CA3067735A patent/CA3067735A1/en active Pending
- 2018-08-17 CN CN201880052805.7A patent/CN111344410B/zh active Active
- 2018-08-18 US US16/630,458 patent/US11358983B2/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008543868A (ja) | 2005-06-17 | 2008-12-04 | ワイス | Fc領域含有タンパク質を精製する方法 |
JP2010516651A (ja) | 2007-01-17 | 2010-05-20 | メルク セローノ ソシエテ アノニム | Fc含有タンパク質の精製のための方法 |
JP2011530606A (ja) | 2008-08-14 | 2011-12-22 | メルク・シャープ・エンド・ドーム・コーポレイション | プロテインaアフィニティークロマトグラフィーを用いる抗体の精製方法 |
Non-Patent Citations (5)
Title |
---|
Atsuhiro Kanda et al.,Scientific Reports,2015年12月09日,5:17946,p. 1-11 |
G. Joucla et al.,Journal of Chrmatography B,2013年,Vol. 942-943,p. 126-133 |
Kerstin A. Heyl et al.,Biochemical and Biophysical Research Communications,2016年,Vol. 479,p. 86-90 |
Nabila Aboulaich et al.,Biotehnol. Prog.,2014年07月26日,Vol. 30, No. 5,p. 1114-1124 |
Santosh Kumar Patnaik et al.,Glycobiology,2005年11月29日,Vol.16, No. 4,pp. 305-317 |
Also Published As
Publication number | Publication date |
---|---|
US20210163528A1 (en) | 2021-06-03 |
KR20200037396A (ko) | 2020-04-08 |
CN111344410B (zh) | 2023-09-15 |
CN111344410A (zh) | 2020-06-26 |
EP3668985A1 (en) | 2020-06-24 |
KR102578087B1 (ko) | 2023-09-18 |
JP2020531411A (ja) | 2020-11-05 |
ES2887046T3 (es) | 2021-12-21 |
EP3668985B1 (en) | 2021-06-16 |
US11358983B2 (en) | 2022-06-14 |
WO2019036626A1 (en) | 2019-02-21 |
CA3067735A1 (en) | 2019-02-21 |
DK3668985T3 (da) | 2021-09-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6979442B2 (ja) | オーバーロード/溶出クロマトグラフィー | |
JP7489953B2 (ja) | 精製された組み換えポリペプチドを含む方法及び組成物 | |
CN109937034B (zh) | 阿柏西普制剂及其用途 | |
KR101370253B1 (ko) | 재조합 항체의 재접힘 방법 | |
US20180327446A1 (en) | Purification of fkpa and uses thereof for producing recombinant polypeptides | |
AU2016223095B2 (en) | Antibodies to tau and uses thereof | |
US11760802B2 (en) | ILT3-binding agents and methods of use thereof | |
JP7097433B2 (ja) | 宿主細胞ガレクチンおよび他の夾雑物からグリコシル化タンパク質を精製する方法 | |
JPWO2019088143A1 (ja) | 生物活性が低下した抗体バリアントおよびアイソフォーム | |
CN110678482A (zh) | 包含pd-1结合蛋白的制剂及其制备方法 | |
US20230073034A1 (en) | Multispecific antibodies, compositions comprising the same, and vectors and uses thereof | |
US20230279136A1 (en) | Stable formulations comprising a bispecific bcma/cd3 antibody | |
JP7183268B2 (ja) | 等張化剤としてリジン塩を含有するアフリベルセプト製剤及びその使用 | |
TW202112799A (zh) | 過載層析管柱之再生方法 | |
RU2793783C1 (ru) | Способы и композиции, включающие очищенные рекомбинантные полипептиды | |
WO2023108115A1 (en) | Ph-selective antibody fc domains | |
TW202340249A (zh) | 生物活性降低之抗體變體 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210324 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20220124 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220128 |
|
A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20220422 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20220425 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20220621 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220627 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7097433 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |