JP2019150037A - 無血清細胞培養培地 - Google Patents
無血清細胞培養培地 Download PDFInfo
- Publication number
- JP2019150037A JP2019150037A JP2019083625A JP2019083625A JP2019150037A JP 2019150037 A JP2019150037 A JP 2019150037A JP 2019083625 A JP2019083625 A JP 2019083625A JP 2019083625 A JP2019083625 A JP 2019083625A JP 2019150037 A JP2019150037 A JP 2019150037A
- Authority
- JP
- Japan
- Prior art keywords
- cell culture
- protein
- cells
- cell
- culture medium
- 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.)
- Granted
Links
- 239000006143 cell culture medium Substances 0.000 title claims abstract description 91
- 210000004027 cell Anatomy 0.000 claims abstract description 227
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 claims abstract description 206
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims abstract description 156
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims abstract description 149
- 229960003104 ornithine Drugs 0.000 claims abstract description 149
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims abstract description 147
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 121
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 120
- 239000005700 Putrescine Substances 0.000 claims abstract description 103
- 238000004519 manufacturing process Methods 0.000 claims abstract description 22
- 239000001963 growth medium Substances 0.000 claims abstract description 5
- 239000002609 medium Substances 0.000 claims description 165
- 235000018102 proteins Nutrition 0.000 claims description 116
- 238000000034 method Methods 0.000 claims description 96
- 229940024606 amino acid Drugs 0.000 claims description 67
- 235000001014 amino acid Nutrition 0.000 claims description 67
- 150000001413 amino acids Chemical class 0.000 claims description 66
- 238000004113 cell culture Methods 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 34
- 239000000654 additive Substances 0.000 claims description 27
- 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 claims description 26
- 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 claims description 22
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 22
- 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 claims description 22
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 22
- 210000004962 mammalian cell Anatomy 0.000 claims description 22
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 21
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims description 20
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 17
- 235000004554 glutamine Nutrition 0.000 claims description 17
- 230000000996 additive effect Effects 0.000 claims description 16
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 16
- 239000000194 fatty acid Substances 0.000 claims description 15
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 14
- 229930195729 fatty acid Natural products 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 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 claims description 13
- 102000004877 Insulin Human genes 0.000 claims description 13
- 108090001061 Insulin Proteins 0.000 claims description 13
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 13
- 238000012258 culturing Methods 0.000 claims description 13
- 150000004665 fatty acids Chemical class 0.000 claims description 13
- 239000008103 glucose Substances 0.000 claims description 13
- 229940125396 insulin Drugs 0.000 claims description 13
- 239000002777 nucleoside Substances 0.000 claims description 13
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 12
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims description 11
- 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 claims description 11
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 11
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims description 11
- 108091006020 Fc-tagged proteins Proteins 0.000 claims description 11
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 11
- 229960005305 adenosine Drugs 0.000 claims description 11
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims description 11
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 11
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims description 11
- 239000012634 fragment Substances 0.000 claims description 11
- 125000003835 nucleoside group Chemical group 0.000 claims description 11
- 229940104230 thymidine Drugs 0.000 claims description 11
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 11
- 229940045145 uridine Drugs 0.000 claims description 11
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims description 10
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims description 10
- 229940029575 guanosine Drugs 0.000 claims description 10
- 102000037865 fusion proteins Human genes 0.000 claims description 9
- 108020001507 fusion proteins Proteins 0.000 claims description 9
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 8
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 8
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 8
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 8
- 239000011575 calcium Substances 0.000 claims description 8
- 229910052791 calcium Inorganic materials 0.000 claims description 8
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 claims description 8
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 8
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 claims description 8
- 229940033355 lauric acid Drugs 0.000 claims description 8
- 239000011777 magnesium Substances 0.000 claims description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 7
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 7
- 108010002352 Interleukin-1 Proteins 0.000 claims description 7
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 7
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 7
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 7
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 7
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 7
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 7
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 7
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 7
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 7
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 7
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 7
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 7
- 229960003767 alanine Drugs 0.000 claims description 7
- 102000025171 antigen binding proteins Human genes 0.000 claims description 7
- 108091000831 antigen binding proteins Proteins 0.000 claims description 7
- 229960001230 asparagine Drugs 0.000 claims description 7
- 229960005261 aspartic acid Drugs 0.000 claims description 7
- 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 claims description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 7
- 229960002989 glutamic acid Drugs 0.000 claims description 7
- 229960003646 lysine Drugs 0.000 claims description 7
- 229960005190 phenylalanine Drugs 0.000 claims description 7
- 229960004441 tyrosine Drugs 0.000 claims description 7
- 235000002374 tyrosine Nutrition 0.000 claims description 7
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 7
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims description 6
- 239000004475 Arginine Substances 0.000 claims description 6
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 6
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 6
- 239000004471 Glycine Substances 0.000 claims description 6
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 6
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 6
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 6
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 6
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 6
- 239000004472 Lysine Substances 0.000 claims description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
- 241000080590 Niso Species 0.000 claims description 6
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 6
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 6
- 239000004473 Threonine Substances 0.000 claims description 6
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 6
- 235000004279 alanine Nutrition 0.000 claims description 6
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 6
- -1 antibody Proteins 0.000 claims description 6
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 claims description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 6
- 229960003121 arginine Drugs 0.000 claims description 6
- 235000009697 arginine Nutrition 0.000 claims description 6
- 235000009582 asparagine Nutrition 0.000 claims description 6
- 235000003704 aspartic acid Nutrition 0.000 claims description 6
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 229960002433 cysteine Drugs 0.000 claims description 6
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 6
- 235000018417 cysteine Nutrition 0.000 claims description 6
- 235000013922 glutamic acid Nutrition 0.000 claims description 6
- 239000004220 glutamic acid Substances 0.000 claims description 6
- 229960002449 glycine Drugs 0.000 claims description 6
- 229960002885 histidine Drugs 0.000 claims description 6
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 6
- 229960000310 isoleucine Drugs 0.000 claims description 6
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 6
- 229960003136 leucine Drugs 0.000 claims description 6
- 235000019136 lipoic acid Nutrition 0.000 claims description 6
- 229910052749 magnesium Inorganic materials 0.000 claims description 6
- 229930182817 methionine Natural products 0.000 claims description 6
- 229960004452 methionine Drugs 0.000 claims description 6
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 6
- 229960001153 serine Drugs 0.000 claims description 6
- 235000004400 serine Nutrition 0.000 claims description 6
- 229960002663 thioctic acid Drugs 0.000 claims description 6
- 229960002898 threonine Drugs 0.000 claims description 6
- 235000008521 threonine Nutrition 0.000 claims description 6
- 229960004799 tryptophan Drugs 0.000 claims description 6
- 229960004295 valine Drugs 0.000 claims description 6
- 239000004474 valine Substances 0.000 claims description 6
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 5
- 229960002429 proline Drugs 0.000 claims description 5
- 235000013930 proline Nutrition 0.000 claims description 5
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 claims description 4
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 4
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 claims description 4
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 claims description 4
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 4
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 4
- 241000271566 Aves Species 0.000 claims description 4
- 235000021357 Behenic acid Nutrition 0.000 claims description 4
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 4
- 241000238631 Hexapoda Species 0.000 claims description 4
- 239000005639 Lauric acid Substances 0.000 claims description 4
- 235000021360 Myristic acid Nutrition 0.000 claims description 4
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 claims description 4
- 239000005642 Oleic acid Substances 0.000 claims description 4
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 4
- 235000021314 Palmitic acid Nutrition 0.000 claims description 4
- 235000021355 Stearic acid Nutrition 0.000 claims description 4
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 claims description 4
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 claims description 4
- 235000020661 alpha-linolenic acid Nutrition 0.000 claims description 4
- 239000005557 antagonist Substances 0.000 claims description 4
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 229940116226 behenic acid Drugs 0.000 claims description 4
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 4
- 229940003092 decanoic acid Drugs 0.000 claims description 4
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 4
- 229960004488 linolenic acid Drugs 0.000 claims description 4
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 claims description 4
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 4
- 108020004707 nucleic acids Proteins 0.000 claims description 4
- 102000039446 nucleic acids Human genes 0.000 claims description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 4
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 4
- 235000021313 oleic acid Nutrition 0.000 claims description 4
- 239000008117 stearic acid Substances 0.000 claims description 4
- 210000005253 yeast cell Anatomy 0.000 claims description 4
- 235000021353 Lignoceric acid Nutrition 0.000 claims description 3
- CQXMAMUUWHYSIY-UHFFFAOYSA-N Lignoceric acid Natural products CCCCCCCCCCCCCCCCCCCCCCCC(=O)OCCC1=CC=C(O)C=C1 CQXMAMUUWHYSIY-UHFFFAOYSA-N 0.000 claims description 3
- 229940114079 arachidonic acid Drugs 0.000 claims description 3
- 235000021342 arachidonic acid Nutrition 0.000 claims description 3
- FARYTWBWLZAXNK-WAYWQWQTSA-N ethyl (z)-3-(methylamino)but-2-enoate Chemical compound CCOC(=O)\C=C(\C)NC FARYTWBWLZAXNK-WAYWQWQTSA-N 0.000 claims description 3
- 230000003833 cell viability Effects 0.000 abstract description 8
- 210000004102 animal cell Anatomy 0.000 abstract description 5
- 239000006887 os medium Substances 0.000 description 26
- 108090000765 processed proteins & peptides Proteins 0.000 description 25
- 102000004196 processed proteins & peptides Human genes 0.000 description 23
- 230000014616 translation Effects 0.000 description 23
- 235000002639 sodium chloride Nutrition 0.000 description 17
- 239000000306 component Substances 0.000 description 16
- 229920001184 polypeptide Polymers 0.000 description 15
- 210000002966 serum Anatomy 0.000 description 15
- 108060003951 Immunoglobulin Proteins 0.000 description 11
- 230000010261 cell growth Effects 0.000 description 11
- 102000018358 immunoglobulin Human genes 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 235000010469 Glycine max Nutrition 0.000 description 9
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 9
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 9
- 239000003102 growth factor Substances 0.000 description 9
- 239000012679 serum free medium Substances 0.000 description 9
- 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 8
- 230000002378 acidificating effect Effects 0.000 description 8
- 229960000074 biopharmaceutical Drugs 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 230000027455 binding Effects 0.000 description 7
- 239000002738 chelating agent Substances 0.000 description 7
- 210000004602 germ cell Anatomy 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 6
- 102000000589 Interleukin-1 Human genes 0.000 description 6
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 6
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000001186 cumulative effect Effects 0.000 description 6
- GHOKWGTUZJEAQD-UHFFFAOYSA-N pantothenic acid Chemical compound OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 6
- 108091033319 polynucleotide Proteins 0.000 description 6
- 102000040430 polynucleotide Human genes 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- 229930003799 tocopherol Natural products 0.000 description 6
- 239000011732 tocopherol Substances 0.000 description 6
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 229940088679 drug related substance Drugs 0.000 description 5
- 239000012526 feed medium Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000003531 protein hydrolysate Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 229940088594 vitamin Drugs 0.000 description 5
- 229930003231 vitamin Natural products 0.000 description 5
- 235000013343 vitamin Nutrition 0.000 description 5
- 239000011782 vitamin Substances 0.000 description 5
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 108010009736 Protein Hydrolysates Proteins 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- 230000001133 acceleration Effects 0.000 description 4
- 210000000628 antibody-producing cell Anatomy 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 235000010384 tocopherol Nutrition 0.000 description 4
- 229960001295 tocopherol Drugs 0.000 description 4
- 238000012549 training Methods 0.000 description 4
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 3
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 3
- 235000019743 Choline chloride Nutrition 0.000 description 3
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 3
- 235000000638 D-biotin Nutrition 0.000 description 3
- 239000011665 D-biotin Substances 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 3
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 3
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 3
- 229930003779 Vitamin B12 Natural products 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 230000003698 anagen phase Effects 0.000 description 3
- 229940053200 antiepileptics fatty acid derivative Drugs 0.000 description 3
- 238000010923 batch production Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229960003178 choline chloride Drugs 0.000 description 3
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 3
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 3
- 210000004748 cultured cell Anatomy 0.000 description 3
- 230000001351 cycling effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000411 inducer Substances 0.000 description 3
- 229960000367 inositol Drugs 0.000 description 3
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 229960003966 nicotinamide Drugs 0.000 description 3
- 235000005152 nicotinamide Nutrition 0.000 description 3
- 239000011570 nicotinamide Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 150000003212 purines Chemical class 0.000 description 3
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 3
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 3
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 229960002477 riboflavin Drugs 0.000 description 3
- 235000019192 riboflavin Nutrition 0.000 description 3
- 239000002151 riboflavin Substances 0.000 description 3
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 3
- 230000009469 supplementation Effects 0.000 description 3
- 229960003495 thiamine Drugs 0.000 description 3
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 3
- 235000019163 vitamin B12 Nutrition 0.000 description 3
- 239000011715 vitamin B12 Substances 0.000 description 3
- 229940011671 vitamin b6 Drugs 0.000 description 3
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 2
- 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 2
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102000003951 Erythropoietin Human genes 0.000 description 2
- 108090000394 Erythropoietin Proteins 0.000 description 2
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 2
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 2
- 244000068988 Glycine max Species 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
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 102000004858 Growth differentiation factor-9 Human genes 0.000 description 2
- 108090001086 Growth differentiation factor-9 Proteins 0.000 description 2
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 2
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102000044594 Interleukin-1 Receptor Accessory Human genes 0.000 description 2
- 101710180389 Interleukin-1 receptor accessory protein Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 108010056852 Myostatin Proteins 0.000 description 2
- BNQSTAOJRULKNX-UHFFFAOYSA-N N-(6-acetamidohexyl)acetamide Chemical compound CC(=O)NCCCCCCNC(C)=O BNQSTAOJRULKNX-UHFFFAOYSA-N 0.000 description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- 102100035194 Placenta growth factor Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000013275 Somatomedins Human genes 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- 102000036693 Thrombopoietin Human genes 0.000 description 2
- 108010041111 Thrombopoietin Proteins 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 2
- 108010081667 aflibercept Proteins 0.000 description 2
- 229960002833 aflibercept Drugs 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 229940112869 bone morphogenetic protein Drugs 0.000 description 2
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229910000365 copper sulfate Inorganic materials 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 238000011143 downstream manufacturing Methods 0.000 description 2
- 229940105423 erythropoietin Drugs 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- LGQLOGILCSXPEA-UHFFFAOYSA-L nickel sulfate Chemical compound [Ni+2].[O-]S([O-])(=O)=O LGQLOGILCSXPEA-UHFFFAOYSA-L 0.000 description 2
- 229910000363 nickel(II) sulfate Inorganic materials 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 229920000768 polyamine Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 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 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 108010046141 rilonacept Proteins 0.000 description 2
- 229960001886 rilonacept Drugs 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000005460 tetrahydrofolate Substances 0.000 description 2
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 2
- 125000002640 tocopherol group Chemical class 0.000 description 2
- 235000019149 tocopherols Nutrition 0.000 description 2
- 239000011573 trace mineral Substances 0.000 description 2
- 235000013619 trace mineral Nutrition 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 239000012137 tryptone Substances 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 210000003501 vero cell Anatomy 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 description 2
- 229960001763 zinc sulfate Drugs 0.000 description 2
- GGTYBZJRPHEQDG-WCCKRBBISA-N (2s)-2,5-diaminopentanoic acid hydrochloride Chemical compound Cl.NCCC[C@H](N)C(O)=O GGTYBZJRPHEQDG-WCCKRBBISA-N 0.000 description 1
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- PMUNIMVZCACZBB-UHFFFAOYSA-N 2-hydroxyethylazanium;chloride Chemical compound Cl.NCCO PMUNIMVZCACZBB-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- LIVAPJSLWQXLJZ-RIOAMYLKSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoic acid;(2s)-2-[[4-[(2-amino-4-oxo-1h-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21.C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 LIVAPJSLWQXLJZ-RIOAMYLKSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102000009840 Angiopoietins Human genes 0.000 description 1
- 108010009906 Angiopoietins Proteins 0.000 description 1
- KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- FFEARJCKVFRZRR-SCSAIBSYSA-N D-methionine Chemical compound CSCC[C@@H](N)C(O)=O FFEARJCKVFRZRR-SCSAIBSYSA-N 0.000 description 1
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 1
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 101150048336 Flt1 gene Proteins 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 102100031000 Hepatoma-derived growth factor Human genes 0.000 description 1
- 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 102000005237 Isophane Insulin Human genes 0.000 description 1
- 108010081368 Isophane Insulin Proteins 0.000 description 1
- 101150088608 Kdr gene Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- IFQSXNOEEPCSLW-DKWTVANSSA-N L-cysteine hydrochloride Chemical compound Cl.SC[C@H](N)C(O)=O IFQSXNOEEPCSLW-DKWTVANSSA-N 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- 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 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 244000000188 Vaccinium ovalifolium Species 0.000 description 1
- 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000004156 Wnt signaling pathway Effects 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 235000021120 animal protein Nutrition 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect 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
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 238000012777 commercial manufacturing Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 230000006251 gamma-carboxylation Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 108010052188 hepatoma-derived growth factor Proteins 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000012007 large scale cell culture Methods 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 229960004232 linoleic acid Drugs 0.000 description 1
- 230000004576 lipid-binding Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000012533 medium component Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000001814 protein method Methods 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0018—Culture media for cell or tissue culture
- C12N5/0031—Serum-free culture media
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0018—Culture media for cell or tissue culture
- C12N5/0037—Serum-free medium, which may still contain naturally-sourced components
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0018—Culture media for cell or tissue culture
- C12N5/0043—Medium free of human- or animal-derived components
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0018—Culture media for cell or tissue culture
- C12N5/005—Protein-free medium
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0681—Cells of the genital tract; Non-germinal cells from gonads
- C12N5/0682—Cells of the female genital tract, e.g. endometrium; Non-germinal cells from ovaries, e.g. ovarian follicle 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/12—Light metals, i.e. alkali, alkaline earth, Be, Al, Mg
- C12N2500/14—Calcium; Ca chelators; Calcitonin
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/12—Light metals, i.e. alkali, alkaline earth, Be, Al, Mg
- C12N2500/16—Magnesium; Mg chelators
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/20—Transition metals
- C12N2500/22—Zinc; Zn chelators
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/20—Transition metals
- C12N2500/24—Iron; Fe chelators; Transferrin
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/32—Amino acids
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/34—Sugars
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/36—Lipids
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/40—Nucleotides, nucleosides, bases
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/46—Amines, e.g. putrescine
-
- 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
- C12N2511/00—Cells for large scale 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
- C12N2523/00—Culture process characterised by temperature
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Reproductive Health (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
[本発明1001]
≧0.09mM±0.014mMのオルニチンを含む、無血清である細胞培養培地。
[本発明1002]
≧0.20±0.03mMのプトレシンを含む、本発明1001の細胞培養培地。
[本発明1003]
0.09±0.014mM〜0.9±0.14mMのオルニチンを含む、本発明1001および1002のいずれかの細胞培養培地。
[本発明1004]
0.09±0.014mM、0.3±0.05mM、0.6±0.09mMまたは0.9±0.14mMでオルニチンを含む、本発明1001から1003のいずれかの細胞培養培地。
[本発明1005]
0.20±0.03mM〜0.714±0.11mMのプトレシンを含む、本発明1001から1004のいずれかの細胞培養培地。
[本発明1006]
0.20±0.03mM、0.35±0.06または0.714±0.11mMでプトレシンを含む、本発明1001から1004のいずれかの細胞培養培地。
[本発明1007]
加水分解物を含まない、本発明1001から1006のいずれかの細胞培養培地。
[本発明1008]
化学的に規定されている、本発明1001から1006のいずれかの細胞培養培地。
[本発明1009]
≧40±6mMのアミノ酸またはその塩の混合物を含む、本発明1001から1008のいずれかの細胞培養培地。
[本発明1010]
アミノ酸の前記混合物が、アラニン、アルギニン、アスパラギン、アスパラギン酸、システイン、グルタミン酸、グリシン、ヒスチジン、イソロイシン、ロイシン、リシン、メチオニン、フェニルアラニン、プロリン、セリン、スレオニン、トリプトファン、チロシンおよびバリンからなる、本発明1009の細胞培養培地。
[本発明1011]
1種または複数の脂肪酸を含む、本発明1001から1010のいずれかの細胞培養培地。
[本発明1012]
前記1種または複数の脂肪酸が、リノール酸、リノレン酸、チオクト酸、オレイン酸、パルミチン酸、ステアリン酸、アラキジン酸、アラキドン酸、ラウリン酸、ベヘン酸、デカン酸、ドデカン酸、ヘキサン酸、リグノセリン酸、ミリスチン酸およびオクタン酸からなる群より選択される、本発明1011の細胞培養培地。
[本発明1013]
ヌクレオシドの混合物を含む、本発明1001から1012のいずれかの細胞培養培地。
[本発明1014]
ヌクレオシドの前記混合物が、アデノシン、グアノシン、シチジン、ウリジン、チミジンおよびヒポキサンチンのうちの1種または複数を含む、本発明1013の細胞培養培地。
[本発明1015]
アデノシン、グアノシン、シチジン、ウリジン、チミジンおよびヒポキサンチンを含む、本発明1001から1014のいずれかの細胞培養培地。
[本発明1016]
1種または複数の二価カチオンを含む、本発明1001から1015のいずれかの細胞培養培地。
[本発明1017]
前記二価カチオンが、マグネシウム、カルシウムまたはそれらの両方である、本発明1016の細胞培養培地。
[本発明1018]
Ca2+およびMg2+を含む、本発明1001から1017のいずれかの細胞培養培地。
[本発明1019]
細胞を培養するための方法であって、(a)本発明1001から1018のいずれかの細胞培養培地を提供するステップ、および(b)前記細胞培養培地中で細胞を成長させるかまたは維持して、細胞培養物を形成するステップを含む、方法。
[本発明1020]
前記細胞が、哺乳動物細胞、鳥類細胞、昆虫細胞、細菌細胞および酵母細胞からなる群より選択される、本発明1019の方法。
[本発明1021]
前記細胞がCHO細胞である、本発明1019または本発明1020の方法。
[本発明1022]
前記細胞が目的のタンパク質を発現する、本発明1019から1021のいずれかの方法。
[本発明1023]
前記目的のタンパク質が抗原結合性タンパク質である、本発明1022の方法。
[本発明1024]
前記目的のタンパク質がFcドメインを含む、本発明1022または1023の方法。
[本発明1025]
前記目的のタンパク質が受容体−Fc−融合タンパク質である、本発明1022から1024のいずれかの方法。
[本発明1026]
前記受容体−Fc−融合タンパク質がtrapタンパク質である、本発明1025の方法。
[本発明1027]
前記trapタンパク質が、IL−1アンタゴニストまたはVEGFアンタゴニストである、本発明1026の方法。
[本発明1028]
前記目的のタンパク質が、抗体または抗体断片である、本発明1022または1023の方法。
[本発明1029]
前記抗体または前記抗体断片が、組換えヒト抗体またはその断片である、本発明1028の方法。
[本発明1030]
前記細胞が、≦30時間の平均倍加時間を有する、本発明1019から1029のいずれかの方法。
[本発明1031]
前記細胞が、≦24時間の平均倍加時間を有する、本発明1019から1030のいずれかの方法。
[本発明1032]
前記細胞が、<0.3±0.045mMのオルニチンおよび<0.2±0.03mMのプトレシンを含む細胞培養培地において増殖した細胞の平均倍加時間の少なくとも3分の1である平均倍加時間を有する、本発明1019から1031のいずれかの方法。
[本発明1033]
前記細胞培養物が、<0.09±0.014mMのオルニチンおよび<0.2±0.03mMのプトレシンを含む培地中の類似の細胞培養物よりも少なくとも15%大きい生存細胞計数密度に達することが可能である、本発明1019から1032のいずれかの方法。
[本発明1034]
前記細胞培養物が、<0.09±0.014mMのオルニチンおよび<0.2±0.03mMのプトレシンを含む類似の細胞培養培地中の類似の細胞培養物よりも少なくとも3倍大きい生存細胞計数密度に達することが可能である、本発明1019から1033のいずれかの方法。
[本発明1035]
1種または複数のユースポイント添加物を、前記細胞培養培地に添加するステップを含む、本発明1019から1034のいずれかの方法。
[本発明1036]
前記ユースポイント添加物が、NaHCO3、グルタミン、インスリン、グルコース、CuSO4、ZnSO4、FeCl3、NiSO4、Na4 EDTAおよびクエン酸Na3のうちの1種または複数を含む、本発明1035の方法。
[本発明1037]
NaHCO3、グルタミン、インスリン、グルコース、CuSO4、ZnSO4、FeCl3、NiSO4、Na4 EDTAおよびクエン酸Na3の各々が、ユースポイント添加物として前記培地に添加される、本発明1035または1036の方法。
[本発明1038]
タンパク質を生成するための方法であって、前記方法は、(a)目的のタンパク質をコードする配列を含む核酸を細胞中に導入するステップ;(b)前記核酸を保有する細胞を選択するステップ;(c)本発明1001から1018のいずれかの細胞培養培地において、または本発明1019から1037のいずれかの方法に従って、選択された前記細胞を培養するステップ;および(d)前記細胞において前記目的のタンパク質を発現させるステップを含み、前記目的のタンパク質が前記培地中に分泌される、方法。
[本発明1039]
前記細胞が、CHO細胞、293細胞またはBHK細胞である、本発明1038の方法。
[本発明1040]
前記目的のタンパク質が抗原結合性タンパク質である、本発明1038または1039の方法。
[本発明1041]
前記目的のタンパク質がFcドメインを含む、本発明1038から1040のいずれかの方法。
[本発明1042]
前記目的のタンパク質が、受容体−Fc−融合タンパク質(TRAP)、可溶性TCR−Fc融合タンパク質、抗体、Fc−融合タンパク質およびScFvタンパク質からなる群より選択される、本発明1038から1041のいずれかの方法。
[本発明1043]
前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも7%大きい平均7日目力価で生成される、本発明1038から1042のいずれかの方法。
[本発明1044]
前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも14%大きい平均7日目力価で生成される、本発明1038から1043のいずれかの方法。
[本発明1045]
前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも80%大きい平均7日目力価で生成される、本発明1038から1044のいずれかの方法。
[本発明1046]
前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも2倍大きい平均7日目力価で生成される、本発明1038から1045のいずれかの方法。
[本発明1047]
前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも3倍大きい平均7日目力価で生成される、本発明1038から1046のいずれかの方法。
[本発明1048]
前記目的のタンパク質が組換えヒト抗体である、本発明1038から1047のいずれかの方法。
本明細書で使用する場合、「ペプチド」、「ポリペプチド」および「タンパク質」は、至る所で相互交換可能に使用され、ペプチド結合によって互いに接続された2つまたはそれ超のアミノ酸残基を含む分子を指す。ペプチド、ポリペプチドおよびタンパク質は、改変、例えばグリコシル化、脂質結合、硫酸化、グルタミン酸残基のガンマ−カルボキシル化、アルキル化、ヒドロキシル化およびADP−リボシル化もまた含み得る。ペプチド、ポリペプチドおよびタンパク質は、タンパク質ベースの薬物を含む、科学的または商業的に興味を持たれるものであり得る。ペプチド、ポリペプチドおよびタンパク質には、とりわけ、抗体およびキメラまたは融合タンパク質が含まれる。ペプチド、ポリペプチドおよびタンパク質は、細胞培養方法を使用して組換え動物細胞株によって生成される。
本発明は、細胞を培養する際およびバイオ医薬品薬物物質を生成する際に有用な無血清培地を提供する。「無血清」は、動物血清、例えば胎仔ウシ血清を含まない細胞培養培地に適用される。この無血清培地は、≦7.5g/Lの加水分解物、例えばダイズ加水分解物を含み得る。本発明はまた、無血清なだけでなく、加水分解物もまた含まない、化学的に規定された培地を提供する。「加水分解物を含まない」は、外因性タンパク質加水分解物、例えば動物または植物のタンパク質加水分解物、例えば、ペプトン、トリプトンなどを含まない細胞培養培地に適用される。
本発明は、上記OS培地中に目的のタンパク質を発現する細胞株を含む細胞培養物を提供する。一実施形態では、この細胞培養物は、ユースポイント成分として培地に添加され得るまたは培地処方中に含まれ得る、インスリンを含む。一実施形態では、この細胞株は、生物治療剤タンパク質を生成することが可能な細胞を含む。タンパク質生物治療剤を生成するために慣用的に使用される細胞株の例には、とりわけ、初代細胞、BSC細胞、HeLa細胞、HepG2細胞、LLC−MK細胞、CV−1細胞、COS細胞、VERO細胞、MDBK細胞、MDCK細胞、CRFK細胞、RAF細胞、RK細胞、TCMK−1細胞、LLCPK細胞、PK15細胞、LLC−RK細胞、MDOK細胞、BHK細胞、BHK−21細胞、CHO細胞、CHO−K1細胞、NS−1細胞、MRC−5細胞、WI−38細胞、BHK細胞、3T3細胞、293細胞、RK細胞、Per.C6細胞およびニワトリ胚細胞が含まれる。一実施形態では、この細胞株は、CHO細胞株、または大規模タンパク質生成のために最適化されたいくつかの特定のCHO細胞バリアントのうちの1つもしくは複数、例えば、CHO−K1である。
化学的に規定されたOS培地およびOS培地中で細胞を培養する方法に加えて、本発明は、OS培地中で培養された細胞において、タンパク質、例えば、治療的に有効な抗体または他のバイオ医薬品薬物物質を生成する方法を提供する。
改善された生存細胞培養物密度
250mL振盪フラスコに、CHO K1から誘導した組換え抗体生成細胞株の種培養物を接種した。接種した細胞を、36.5℃で7日間増殖させ、3日目および5日目にグルコースを供給した。細胞を、2つの別々の化学的に規定された(加水分解物を含まない無血清の)培地の各々において増殖させた。第1の培地は、約75mMのアミノ酸を含み(培地1)、第2の培地は、約40mMのアミノ酸を含み(培地2)、両方の処方が、2.5μM(0.4mg/L)以下のプトレシンを含んだ。別の群の培地条件を、7.5g/Lの濃度のダイズ加水分解物を培地2に添加することによって生成した。3つの対照培地の各々に、約593μMのオルニチン(100mg/LのL−オルニチン・HClとして)、または約593μMのオルニチン(100mg/LのL−オルニチン・HClとして)および約714μMのプトレシン(115mg/Lのプトレシン・2HClとして)の組合せを添加した。3mL培養物のアリコートを、3日目、5日目および7日目に取り出し、生存細胞計数を、BioProfile FLEX(商標)機器(Nova Biomedical)でトリパンブルー排除を使用して実施した。0日目に、全ての培養物が、1mL当たり0.8×106の生存細胞を含んだ。所与の培地(培地1、培地2または培地2+ダイズ)について、7日の期間にわたる生存細胞計数により、オルニチン(ornitihine)またはオルニチン+プトレシンを補充した培地中で増殖したCHO細胞が、増加した生存細胞密度を有したことが明らかになった。この効果は、7日の期間の間、加水分解物を含まない培地において特に顕著であった(即ち、生存細胞密度における2倍〜4倍またはそれ超の増加)。加水分解物を含まないOS培地2は、ダイズ含有非OS培地2と同等に機能し、ダイズ加水分解物の細胞増殖利益がオルニチン置き換えによって複製できることを示す。オルニチンまたはオルニチンおよびプトレシンを培地2+ダイズに添加することによって増加した細胞密度もまた観察された。結果を表1に示す。
改善された細胞培養物の倍加時間
対数増殖期にある、CHO K1細胞から誘導した組換え抗体生成細胞株の倍加時間を、種々の細胞培養培地条件下で決定した。種訓練培養物を、3つの別々の培地:培地1、培地2、およびダイズ加水分解物を含む培地2(培地2+ダイズ)の各々において、14日間の期間にわたって250mLシェーカーフラスコ中で36.5℃で継代した。1mLのアリコートを、0日目および種訓練継代の時点(2日毎または3日毎)で各条件から取り出し、生存細胞計数を、CDV(商標)機器(Nova Biomedical)でトリパンブルー排除を使用して実施した。培地1を、未補充で、または100mg/Lのオルニチン・HClもしくは115mg/Lのプトレシン・2HClおよび100mg/Lのオルニチン・HClの両方を補充して試験した。低プトレシン・2HCl(0.4mg/L)を含む培地2を、未補充で、または100mg/Lのオルニチン・HClもしくは115mg/Lのプトレシン・2HClおよび100mg/Lのオルニチン・HClの両方を補充して試験した。結果を表3および4に示す。プトレシンありまたはなしのいずれかでの培地1へのオルニチン補充が、顕著な増殖を達成するために必要であった。オルニチンまたはオルニチン+プトレシンを、加水分解物を含まない培地2に補充することで、細胞倍加時間は約25%〜30%減少した。倍加時間はまた、加水分解物含有培地2へのオルニチンまたはオルニチン+プトレシンの添加の際に、より小さい程度まで低減された。
改善された抗体力価
オルニチンまたはオルニチン+プトレシンを含めることが培養物中の細胞増殖(proliferation)および生存細胞密度を改善することを確立してから、本発明者らは、組換えタンパク質生成力価に対するこれらの条件の影響をさらに調査した。本発明者らは、CHO−K1由来細胞株による組換えIgGの発現および分泌を試験した。この実験では、平均抗体力価を、種々の培地形式下の培養物中で7日目に決定した。上記のように、低いプトレシン(0.4mg/Lのプトレシン・2HCl)、オルニチン(100mg/Lのオルニチン・HCl)、ならびにオルニチンおよびプトレシンの両方(100mg/Lのオルニチン・HCl/115mg/Lのプトレシン・2HCl)を含む培地1を試験した。低いプトレシン(0.4mg/Lのプトレシン・2HCl)、オルニチン(100mg/Lのオルニチン・HCl)、ならびにオルニチンおよびプトレシンの両方(100mg/Lのオルニチン・HCl/115mg/Lのプトレシン・2HCl)を含む培地2および培地2+ダイズもまた試験した。全ての場合において、オルニチンまたはオルニチンおよび0.4mg/L超のレベルのプトレシンを含めることは、顕著により高いタンパク質力価、即ち、少なくとも約2倍高い力価を生じた。結果を表5に示す。
Claims (48)
- ≧0.09mM±0.014mMのオルニチンを含む、無血清である細胞培養培地。
- ≧0.20±0.03mMのプトレシンを含む、請求項1に記載の細胞培養培地。
- 0.09±0.014mM〜0.9±0.14mMのオルニチンを含む、請求項1および2のいずれか一項に記載の細胞培養培地。
- 0.09±0.014mM、0.3±0.05mM、0.6±0.09mMまたは0.9±0.14mMでオルニチンを含む、請求項1から3のいずれか一項に記載の細胞培養培地。
- 0.20±0.03mM〜0.714±0.11mMのプトレシンを含む、請求項1から4のいずれか一項に記載の細胞培養培地。
- 0.20±0.03mM、0.35±0.06または0.714±0.11mMでプトレシンを含む、請求項1から4のいずれか一項に記載の細胞培養培地。
- 加水分解物を含まない、請求項1から6のいずれか一項に記載の細胞培養培地。
- 化学的に規定されている、請求項1から6のいずれか一項に記載の細胞培養培地。
- ≧40±6mMのアミノ酸またはその塩の混合物を含む、請求項1から8のいずれか一項に記載の細胞培養培地。
- アミノ酸の前記混合物が、アラニン、アルギニン、アスパラギン、アスパラギン酸、システイン、グルタミン酸、グリシン、ヒスチジン、イソロイシン、ロイシン、リシン、メチオニン、フェニルアラニン、プロリン、セリン、スレオニン、トリプトファン、チロシンおよびバリンからなる、請求項9に記載の細胞培養培地。
- 1種または複数の脂肪酸を含む、請求項1から10のいずれか一項に記載の細胞培養培地。
- 前記1種または複数の脂肪酸が、リノール酸、リノレン酸、チオクト酸、オレイン酸、パルミチン酸、ステアリン酸、アラキジン酸、アラキドン酸、ラウリン酸、ベヘン酸、デカン酸、ドデカン酸、ヘキサン酸、リグノセリン酸、ミリスチン酸およびオクタン酸からなる群より選択される、請求項11に記載の細胞培養培地。
- ヌクレオシドの混合物を含む、請求項1から12のいずれか一項に記載の細胞培養培地。
- ヌクレオシドの前記混合物が、アデノシン、グアノシン、シチジン、ウリジン、チミジンおよびヒポキサンチンのうちの1種または複数を含む、請求項13に記載の細胞培養培地。
- アデノシン、グアノシン、シチジン、ウリジン、チミジンおよびヒポキサンチンを含む、請求項1から14のいずれか一項に記載の細胞培養培地。
- 1種または複数の二価カチオンを含む、請求項1から15のいずれか一項に記載の細胞培養培地。
- 前記二価カチオンが、マグネシウム、カルシウムまたはそれらの両方である、請求項16に記載の細胞培養培地。
- Ca2+およびMg2+を含む、請求項1から17のいずれか一項に記載の細胞培養培地。
- 細胞を培養するための方法であって、(a)請求項1から18のいずれか一項に記載の細胞培養培地を提供するステップ、および(b)前記細胞培養培地中で細胞を成長させるかまたは維持して、細胞培養物を形成するステップを含む、方法。
- 前記細胞が、哺乳動物細胞、鳥類細胞、昆虫細胞、細菌細胞および酵母細胞からなる群より選択される、請求項19に記載の方法。
- 前記細胞がCHO細胞である、請求項19または請求項20に記載の方法。
- 前記細胞が目的のタンパク質を発現する、請求項19から21のいずれか一項に記載の方法。
- 前記目的のタンパク質が抗原結合性タンパク質である、請求項22に記載の方法。
- 前記目的のタンパク質がFcドメインを含む、請求項22または23に記載の方法。
- 前記目的のタンパク質が受容体−Fc−融合タンパク質である、請求項22から24のいずれか一項に記載の方法。
- 前記受容体−Fc−融合タンパク質がtrapタンパク質である、請求項25に記載の方法。
- 前記trapタンパク質が、IL−1アンタゴニストまたはVEGFアンタゴニストである、請求項26に記載の方法。
- 前記目的のタンパク質が、抗体または抗体断片である、請求項22または23に記載の方法。
- 前記抗体または前記抗体断片が、組換えヒト抗体またはその断片である、請求項28に記載の方法。
- 前記細胞が、≦30時間の平均倍加時間を有する、請求項19から29のいずれか一項に記載の方法。
- 前記細胞が、≦24時間の平均倍加時間を有する、請求項19から30のいずれか一項に記載の方法。
- 前記細胞が、<0.3±0.045mMのオルニチンおよび<0.2±0.03mMのプトレシンを含む細胞培養培地において増殖した細胞の平均倍加時間の少なくとも3分の1である平均倍加時間を有する、請求項19から31のいずれか一項に記載の方法。
- 前記細胞培養物が、<0.09±0.014mMのオルニチンおよび<0.2±0.03mMのプトレシンを含む培地中の類似の細胞培養物よりも少なくとも15%大きい生存細胞計数密度に達することが可能である、請求項19から32のいずれか一項に記載の方法。
- 前記細胞培養物が、<0.09±0.014mMのオルニチンおよび<0.2±0.03mMのプトレシンを含む類似の細胞培養培地中の類似の細胞培養物よりも少なくとも3倍大きい生存細胞計数密度に達することが可能である、請求項19から33のいずれか一項に記載の方法。
- 1種または複数のユースポイント添加物を、前記細胞培養培地に添加するステップを含む、請求項19から34のいずれか一項に記載の方法。
- 前記ユースポイント添加物が、NaHCO3、グルタミン、インスリン、グルコース、CuSO4、ZnSO4、FeCl3、NiSO4、Na4 EDTAおよびクエン酸Na3のうちの1種または複数を含む、請求項35に記載の方法。
- NaHCO3、グルタミン、インスリン、グルコース、CuSO4、ZnSO4、FeCl3、NiSO4、Na4 EDTAおよびクエン酸Na3の各々が、ユースポイント添加物として前記培地に添加される、請求項35または36に記載の方法。
- タンパク質を生成するための方法であって、前記方法は、(a)目的のタンパク質をコードする配列を含む核酸を細胞中に導入するステップ;(b)前記核酸を保有する細胞を選択するステップ;(c)請求項1から18のいずれか一項に記載の細胞培養培地において、または請求項19から37のいずれか一項に記載の方法に従って、選択された前記細胞を培養するステップ;および(d)前記細胞において前記目的のタンパク質を発現させるステップを含み、前記目的のタンパク質が前記培地中に分泌される、方法。
- 前記細胞が、CHO細胞、293細胞またはBHK細胞である、請求項38に記載の方法。
- 前記目的のタンパク質が抗原結合性タンパク質である、請求項38または39に記載の方法。
- 前記目的のタンパク質がFcドメインを含む、請求項38から40のいずれか一項に記載の方法。
- 前記目的のタンパク質が、受容体−Fc−融合タンパク質(TRAP)、可溶性TCR−Fc融合タンパク質、抗体、Fc−融合タンパク質およびScFvタンパク質からなる群より選択される、請求項38から41のいずれか一項に記載の方法。
- 前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも7%大きい平均7日目力価で生成される、請求項38から42のいずれか一項に記載の方法。
- 前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも14%大きい平均7日目力価で生成される、請求項38から43のいずれか一項に記載の方法。
- 前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも80%大きい平均7日目力価で生成される、請求項38から44のいずれか一項に記載の方法。
- 前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも2倍大きい平均7日目力価で生成される、請求項38から45のいずれか一項に記載の方法。
- 前記目的のタンパク質が、0.09±0.014mM未満のオルニチンおよび0.2±0.03mM未満のプトレシンを含む細胞培養培地中の類似の細胞によって生成される平均7日目力価よりも少なくとも3倍大きい平均7日目力価で生成される、請求項38から46のいずれか一項に記載の方法。
- 前記目的のタンパク質が組換えヒト抗体である、請求項38から47のいずれか一項に記載の方法。
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2021132239A JP2021180682A (ja) | 2013-03-15 | 2021-08-16 | 無血清細胞培養培地 |
JP2022145754A JP7429743B2 (ja) | 2013-03-15 | 2022-09-14 | 無血清細胞培養培地 |
JP2023189068A JP2024001357A (ja) | 2013-03-15 | 2023-11-06 | 無血清細胞培養培地 |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361790136P | 2013-03-15 | 2013-03-15 | |
US61/790,136 | 2013-03-15 | ||
US14/211,245 | 2014-03-14 | ||
US14/211,245 US20140273095A1 (en) | 2013-03-15 | 2014-03-14 | Serum-Free Cell Culture Medium |
JP2016502807A JP6781039B2 (ja) | 2013-03-15 | 2014-03-14 | 無血清細胞培養培地 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016502807A Division JP6781039B2 (ja) | 2013-03-15 | 2014-03-14 | 無血清細胞培養培地 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021132239A Division JP2021180682A (ja) | 2013-03-15 | 2021-08-16 | 無血清細胞培養培地 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2019150037A true JP2019150037A (ja) | 2019-09-12 |
JP6944969B2 JP6944969B2 (ja) | 2021-10-06 |
Family
ID=51528781
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016502807A Active JP6781039B2 (ja) | 2013-03-15 | 2014-03-14 | 無血清細胞培養培地 |
JP2019083625A Active JP6944969B2 (ja) | 2013-03-15 | 2019-04-25 | 無血清細胞培養培地 |
JP2021132239A Withdrawn JP2021180682A (ja) | 2013-03-15 | 2021-08-16 | 無血清細胞培養培地 |
JP2022145754A Active JP7429743B2 (ja) | 2013-03-15 | 2022-09-14 | 無血清細胞培養培地 |
JP2023189068A Pending JP2024001357A (ja) | 2013-03-15 | 2023-11-06 | 無血清細胞培養培地 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016502807A Active JP6781039B2 (ja) | 2013-03-15 | 2014-03-14 | 無血清細胞培養培地 |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021132239A Withdrawn JP2021180682A (ja) | 2013-03-15 | 2021-08-16 | 無血清細胞培養培地 |
JP2022145754A Active JP7429743B2 (ja) | 2013-03-15 | 2022-09-14 | 無血清細胞培養培地 |
JP2023189068A Pending JP2024001357A (ja) | 2013-03-15 | 2023-11-06 | 無血清細胞培養培地 |
Country Status (22)
Country | Link |
---|---|
US (5) | US20140273095A1 (ja) |
EP (4) | EP3378932A1 (ja) |
JP (5) | JP6781039B2 (ja) |
KR (6) | KR102278316B1 (ja) |
CN (2) | CN113481148A (ja) |
AR (1) | AR095196A1 (ja) |
AU (4) | AU2014227804B2 (ja) |
BR (2) | BR112015022682B1 (ja) |
CA (5) | CA3188491A1 (ja) |
DK (1) | DK2970876T3 (ja) |
EA (3) | EA037568B1 (ja) |
ES (1) | ES2682929T3 (ja) |
HK (1) | HK1213289A1 (ja) |
HU (1) | HUE040233T2 (ja) |
IL (5) | IL281515B2 (ja) |
MX (3) | MX357977B (ja) |
MY (1) | MY175957A (ja) |
PL (1) | PL2970876T3 (ja) |
PT (1) | PT2970876T (ja) |
SG (3) | SG10201707153UA (ja) |
TW (4) | TWI782295B (ja) |
WO (1) | WO2014144198A1 (ja) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR095196A1 (es) * | 2013-03-15 | 2015-09-30 | Regeneron Pharma | Medio de cultivo celular libre de suero |
DK3122869T3 (da) * | 2014-03-24 | 2019-09-09 | Biogen Ma Inc | Fremgangsmåder til afhjælpning af glutamindeprivation under pattedyrecellekultur |
TW202340452A (zh) | 2015-08-04 | 2023-10-16 | 美商再生元醫藥公司 | 補充牛磺酸之細胞培養基及用法 |
KR101936049B1 (ko) * | 2015-10-15 | 2019-01-08 | (주)알테오젠 | IgG Fc 도메인을 가지는 융합 단백질의 생산방법 |
US20180355304A1 (en) * | 2015-12-03 | 2018-12-13 | Merck Patent Gmbh | Chemically defined media for the growth or detection of microorganisms |
KR20180047404A (ko) * | 2016-10-31 | 2018-05-10 | 삼성바이오에피스 주식회사 | 세포 배양 배지에서 원치 않는 배양 부산물을 감소시키는 공정 |
CN108220228A (zh) * | 2016-12-09 | 2018-06-29 | 上海迈泰君奥生物技术有限公司 | 无血清细胞培养基及高效表达重组蛋白质的方法 |
CN106635953B (zh) * | 2016-12-13 | 2021-02-19 | 昆明润什生物科技有限公司 | 无血清无蛋白细胞培养基 |
US11248054B2 (en) | 2017-06-12 | 2022-02-15 | Bluefin Biomedicine, Inc. | Anti-IL1RAP antibodies and antibody drug conjugates |
CN110914293A (zh) * | 2017-07-06 | 2020-03-24 | 里珍纳龙药品有限公司 | 用于制备糖蛋白的细胞培养工艺 |
CN108103003B (zh) * | 2017-12-12 | 2021-03-05 | 四川百诺吉科技有限公司 | 一种适应pk-15全悬浮生长的无血清培养基及其制备方法和应用于pk-15细胞的全悬浮驯化方法 |
WO2019135238A1 (en) * | 2018-01-03 | 2019-07-11 | Technion Research & Development Foundation Limited | Naive pluripotent stem cell media |
US10961500B1 (en) * | 2019-04-23 | 2021-03-30 | Regeneron Pharmaceuticals, Inc. | Cell culture medium for eukaryotic cells |
EP3969564A1 (en) * | 2019-05-16 | 2022-03-23 | Formycon AG | Method for reducing methionine oxidation in recombinant proteins |
CN110438066B (zh) * | 2019-08-19 | 2021-01-12 | 杭州百凌生物科技有限公司 | 一种可稳定传代的可悬浮培养的哺乳动物细胞系293 c18p及其制备方法和应用 |
IL302538A (en) | 2019-12-06 | 2023-07-01 | Regeneron Pharma | Anti-VEGF protein preparations and methods for their production |
CN115398236B (zh) | 2020-01-21 | 2024-06-11 | 瑞泽恩制药公司 | 用于糖基化的蛋白质的电泳的去糖基化方法 |
WO2022047108A1 (en) | 2020-08-31 | 2022-03-03 | Regeneron Pharmaceuticals, Inc. | Asparagine feed strategies to improve cell culture performance and mitigate asparagine sequence variants |
KR20230134117A (ko) | 2021-01-20 | 2023-09-20 | 리제너론 파마슈티칼스 인코포레이티드 | 세포 배양물에서 단백질 역가를 개선시키는 방법 |
KR20220127465A (ko) | 2021-03-11 | 2022-09-20 | 주식회사 만도 | 조향 제어 장치 및 방법 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1321515A1 (en) * | 2001-12-21 | 2003-06-25 | Ingenium Pharmaceuticals AG | Method of culturing cells |
JP2009521941A (ja) * | 2006-01-04 | 2009-06-11 | バクスター・インターナショナル・インコーポレイテッド | 無オリゴペプチド細胞培地 |
JP2011509089A (ja) * | 2008-01-09 | 2011-03-24 | セルカ ゲーエムベーハー | 改善された培養培地添加物及びそれを用いる方法 |
JP2016514452A (ja) * | 2013-03-15 | 2016-05-23 | 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Regeneron Pharmaceuticals, Inc. | 無血清細胞培養培地 |
Family Cites Families (120)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4072565A (en) | 1974-11-04 | 1978-02-07 | The Dow Chemical Company | Production of viruses in tissue culture without use of serum |
USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
DE3271210D1 (en) | 1981-12-24 | 1986-06-19 | Asahi Chemical Ind | Method for the cultivation of normal diploid cells and cultivation medium used therefor |
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 |
FR2543158B1 (fr) | 1983-03-24 | 1985-11-15 | Inst Nat Sante Rech Med | Milieu de culture de cellules animales sans serum, sans hormones et sans facteurs de croissance et procedes de culture primaire et d'obtention de lignees cellulaires utilisant ce milieu |
DE3801236A1 (de) | 1988-01-18 | 1989-07-27 | Boehringer Mannheim Gmbh | Pentosansulfat-medium |
US6048728A (en) | 1988-09-23 | 2000-04-11 | Chiron Corporation | Cell culture medium for enhanced cell growth, culture longevity, and product expression |
WO1990007007A1 (en) | 1988-12-14 | 1990-06-28 | The United States Of America, Represented By The Secretary, United States Department Of Commerce | Cell culture medium for human liver epithelial cell line |
US5529920A (en) | 1988-12-14 | 1996-06-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Human liver epithelial cell line and culture media therefor |
EP1132471A3 (de) | 1989-09-12 | 2001-11-28 | F. Hoffmann-La Roche Ag | TNF-bindende Proteine |
US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
US5426699A (en) | 1993-10-25 | 1995-06-20 | Antec Corporation | Method and apparatus for digitizing a scrambled analog video signal |
EP0666312A1 (en) | 1994-02-08 | 1995-08-09 | Wolfgang A. Renner | Process for the improvement of mammalian cell growth |
US5856179A (en) | 1994-03-10 | 1999-01-05 | Genentech, Inc. | Polypeptide production in animal cell culture |
US5705364A (en) | 1995-06-06 | 1998-01-06 | Genentech, Inc. | Mammalian cell culture process |
US6656466B1 (en) | 1995-06-06 | 2003-12-02 | Genetech, Inc. | Human tumor necrosis factor—immunoglobulin(TNFR1-IgG1) chimera composition |
AU6698496A (en) | 1995-07-17 | 1997-02-18 | Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. | Metal-containing ribonucleotide polypeptides |
JP4306813B2 (ja) | 1995-09-19 | 2009-08-05 | アスビオファーマ株式会社 | 動物細胞の新規培養方法 |
US6043092A (en) | 1996-03-18 | 2000-03-28 | University Of Pittsburgh | Cell culture media for mammalian cells |
US6146847A (en) | 1996-11-01 | 2000-11-14 | Genespan Corporation | Stabilized transient gene expression |
AU2455199A (en) | 1998-01-12 | 1999-07-26 | Betagene, Inc. | Compositions and methods for regulated secretion from neuroendocrine cell lines |
US6528286B1 (en) | 1998-05-29 | 2003-03-04 | Genentech, Inc. | Mammalian cell culture process for producing glycoproteins |
US6589759B1 (en) | 1999-03-30 | 2003-07-08 | Trustees Of Boston University | Compositions and methods for producing platelets and/or proplatelets from megakaryocytes |
AT409379B (de) | 1999-06-02 | 2002-07-25 | Baxter Ag | Medium zur protein- und serumfreien kultivierung von zellen |
US7087411B2 (en) | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
US7070959B1 (en) | 1999-06-08 | 2006-07-04 | Regeneron Pharmaceuticals, Inc. | Modified chimeric polypeptides with improved pharmacokinetic properties |
ES2319305T3 (es) * | 1999-06-08 | 2009-05-06 | Regeneron Pharmaceuticals, Inc. | Quimeras del receptor del vegf para el tratamiento de trastornos oculares caracterizados por la permeabilidad vascular. |
CN1114619C (zh) * | 1999-06-25 | 2003-07-16 | 中国科学院上海细胞生物学研究所 | 小鼠杂交瘤株Hepama-1分泌的肝癌鼠源单克隆抗体的制备方法 |
US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
IL156910A0 (en) | 2001-01-16 | 2004-02-08 | Regeneron Pharma | Isolating cells expressing secreted proteins |
US20090137416A1 (en) | 2001-01-16 | 2009-05-28 | Regeneron Pharmaceuticals, Inc. | Isolating Cells Expressing Secreted Proteins |
DE60130494D1 (de) | 2001-03-05 | 2007-10-25 | Council Scient Ind Res | Verfahren zur herstellung von proteinhydrolysate aus sojamehl |
CN1180080C (zh) * | 2002-01-18 | 2004-12-15 | 中国科学院上海细胞生物学研究所 | 一种改进的肝癌鼠源单克隆抗体的制备方法 |
US6927004B2 (en) | 2002-03-08 | 2005-08-09 | Asml Netherlands B.V. | Mask for use in lithography, method of making a mask, lithographic apparatus, and device manufacturing method |
WO2003101189A1 (en) | 2002-05-29 | 2003-12-11 | Regeneron Pharmaceuticals, Inc. | Inducible eukaryotic expression system |
US8673589B2 (en) | 2002-05-29 | 2014-03-18 | Regeneron Pharmaceuticals, Inc. | Inducible eukaryotic expression system |
US6924124B1 (en) | 2002-08-23 | 2005-08-02 | Immunex Corporation | Feeding strategies for cell culture |
PT1623019E (pt) | 2003-05-15 | 2010-07-20 | Wyeth Llc | ALIMENTAÃO COM GLUCOSE DE MODO LIMITADO PARA CULTURA DE CéLULAS ANIMAIS |
WO2005010160A2 (en) | 2003-07-17 | 2005-02-03 | Wisconsin Alumni Research Foundation | Liquid crystals with reduced toxicity and applications thereof |
JP4532493B2 (ja) | 2003-09-18 | 2010-08-25 | レイベン バイオテクノロジーズ,インコーポレイティド | 細胞培養培地 |
JP4680997B2 (ja) | 2004-06-08 | 2011-05-11 | ツェンドゥー カンホン バイオテクノロジーズ カンパニー リミテッド | 血管新生を阻害するキメラタンパク質およびその利用 |
US7294484B2 (en) | 2004-08-27 | 2007-11-13 | Wyeth Research Ireland Limited | Production of polypeptides |
WO2006050050A2 (en) | 2004-10-29 | 2006-05-11 | Centocor, Inc. | Chemically defined media compositions |
US20060094104A1 (en) | 2004-10-29 | 2006-05-04 | Leopold Grillberger | Animal protein-free media for cultivation of cells |
US8273553B2 (en) | 2004-11-02 | 2012-09-25 | Ares Trading S.A. | Production of growth hormone in serum-free cell culture medium for mammalian cells |
AR058568A1 (es) | 2005-12-20 | 2008-02-13 | Bristol Myers Squibb Co | Metodos para producir una composicion con moleculas ctla4-ig a partir de un medio de cultivo |
EP1818392B1 (en) * | 2006-02-14 | 2010-08-25 | Genetix Limited | Cell culture medium |
US8216575B2 (en) | 2006-03-31 | 2012-07-10 | Chengdu Kanghong Biotechnologies Co., Ltd. | Inhibition of neovascularization with a soluble chimeric protein comprising VEGF FLT-1 and KDR domains |
DK2374818T3 (da) | 2006-06-02 | 2013-01-21 | Regeneron Pharma | Højaffinitetsantistoffer mod human IL-6-receptor |
US7608693B2 (en) | 2006-10-02 | 2009-10-27 | Regeneron Pharmaceuticals, Inc. | High affinity human antibodies to human IL-4 receptor |
TW200827445A (en) * | 2006-11-08 | 2008-07-01 | Wyeth Corp | Rationally designed media for cell culture |
US7771997B2 (en) | 2007-06-04 | 2010-08-10 | Regeneron Pharmaceuticals, Inc. | Enhanced expression and stability regions |
WO2008154014A2 (en) | 2007-06-11 | 2008-12-18 | Amgen Inc. | A method for culturing mammalian cells to improve recombinant protein production |
CA2695199C (en) | 2007-07-31 | 2016-07-19 | Regeneron Pharmaceuticals, Inc. | Human antibodies to human cd20 and method of using thereof |
US8309088B2 (en) | 2007-08-10 | 2012-11-13 | Regeneron Pharmaceuticals, Inc. | Method of treating osteoarthritis with an antibody to NGF |
CN100482786C (zh) * | 2007-12-28 | 2009-04-29 | 天津百若克医药生物技术有限责任公司 | 一种人胚肾293细胞扩增无蛋白培养基 |
EP2342318A1 (en) * | 2008-09-26 | 2011-07-13 | Schering Corporation | High titer antibody production |
EP2977461A1 (en) | 2008-11-12 | 2016-01-27 | Baxalta Incorporated | Method of producing serum-free insulin-free factor vii |
JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
TWI513818B (zh) | 2009-06-02 | 2015-12-21 | Regeneron Pharma | 岩藻糖基化(fucosylation)-缺乏之細胞 |
CN101603026B (zh) | 2009-06-19 | 2011-01-19 | 华东理工大学 | 适于动物细胞产品生产的无动物来源低蛋白培养基 |
KR20120027055A (ko) | 2009-06-26 | 2012-03-20 | 리제네론 파라마큐티칼스 인코포레이티드 | 천연 면역글로불린 포맷을 가지는 용이하게 분리된 이중특이성 항체 |
JP5451884B2 (ja) | 2009-07-31 | 2014-03-26 | バクスター・インターナショナル・インコーポレイテッド | Adamtsタンパク質発現のための細胞培養培地 |
EP2516624B1 (en) * | 2009-12-23 | 2020-02-05 | Merck Sharp & Dohme Corp. | Cell line 3m |
JO3417B1 (ar) | 2010-01-08 | 2019-10-20 | Regeneron Pharma | الصيغ المستقرة التي تحتوي على الأجسام المضادة لمضاد مستقبل( interleukin-6 (il-6r |
SI2538968T1 (en) | 2010-02-24 | 2018-04-30 | Chiesi Farmaceutici S.P.A. | A process for the production and purification of recombinant lysosomal alpha-manosidase |
RU2577972C2 (ru) | 2010-04-26 | 2016-03-20 | Новартис Аг | Способ получения рекомбинантного полипептида |
JO3340B1 (ar) | 2010-05-26 | 2019-03-13 | Regeneron Pharma | مضادات حيوية لـعامل تمايز النمو 8 البشري |
MX343604B (es) | 2010-05-28 | 2016-11-11 | Genentech Inc | Disminuir nivel de lactato e incrementar producción de polipéptidos por regulación a la baja de la expresión de lactato dehidrogenasa y piruvato dehidrogenasa quinasa. |
CN103097522A (zh) * | 2010-07-08 | 2013-05-08 | 巴克斯特国际公司 | 在细胞培养物中生产重组adamts13的方法 |
JOP20190250A1 (ar) | 2010-07-14 | 2017-06-16 | Regeneron Pharma | صيغ مستقرة تحتوي على الأجسام المضادة لمضاد عامل نمو الأعصاب |
SG187885A1 (en) | 2010-08-31 | 2013-03-28 | Friesland Brands Bv | Culture medium for eukaryotic cells |
AR083044A1 (es) | 2010-09-27 | 2013-01-30 | Regeneron Pharma | Anticuerpos anti-cd48 y usos de los mismos |
EP3733711A1 (en) | 2010-10-06 | 2020-11-04 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-interleukin-4 receptor (il-4r) antibodies |
JO3756B1 (ar) | 2010-11-23 | 2021-01-31 | Regeneron Pharma | اجسام مضادة بشرية لمستقبلات الجلوكاجون |
SG191371A1 (en) | 2010-12-28 | 2013-08-30 | Chugai Pharmaceutical Co Ltd | Animal cell culturing method |
JO3412B1 (ar) | 2011-06-17 | 2019-10-20 | Regeneron Pharma | أجسام مضادة ل angptl3 واستخداماتها |
AU2012339722B2 (en) | 2011-11-14 | 2017-09-14 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for increasing muscle mass and muscle strength by specifically antagonizing GDF8 and/or Activin A |
WO2013112438A1 (en) | 2012-01-23 | 2013-08-01 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-ang2 antibodies |
WO2013120497A1 (en) | 2012-02-15 | 2013-08-22 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded therapeutic protein |
JP6090735B2 (ja) | 2012-03-02 | 2017-03-08 | 国立大学法人山口大学 | 消化器系がん幹細胞を培養するための無血清培地、及びそれを用いた消化器系がん幹細胞の増殖方法 |
WO2013158279A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Protein purification methods to reduce acidic species |
WO2013158273A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Methods to modulate c-terminal lysine variant distribution |
EP2843042B1 (en) | 2012-04-25 | 2018-11-07 | Riken | Cell preparation containing myocardium-committed cell |
JO3820B1 (ar) | 2012-05-03 | 2021-01-31 | Regeneron Pharma | أجسام مضادة بشرية لـ fel d1وطرق لاستخدامها |
CN104640969A (zh) | 2012-06-21 | 2015-05-20 | 巴克斯特国际公司 | 细胞培养基的病毒过滤 |
CA2888281A1 (en) | 2012-08-02 | 2014-02-06 | Sanofi | Article of manufacture comprising aflibercept or ziv-aflibercept |
US9540449B2 (en) | 2012-08-13 | 2017-01-10 | Regeneron Pharmaceuticals, Inc. | Anti-PCSK9 antibodies with pH-dependent binding characteristics |
JOP20200236A1 (ar) | 2012-09-21 | 2017-06-16 | Regeneron Pharma | الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها |
MX363702B (es) | 2012-10-23 | 2019-03-29 | Genzyme Corp | Metodos de cultivo de perfusion y aplicaciones de los mismos. |
JO3405B1 (ar) | 2013-01-09 | 2019-10-20 | Regeneron Pharma | الأجسام المضادة لمضاد مستقبل عامل النمو المشتق من الصفائح الدموية - بيتا واستخداماتها |
CA2901950A1 (en) | 2013-02-22 | 2014-08-28 | Genzyme Corporation | Microcarrier perfusion culturing methods and uses thereof |
CA2904125C (en) | 2013-03-12 | 2022-06-07 | Cmc Icos Biologics, Inc. | Improved recombinant protein expression using a hybrid chef1 promoter |
JO3532B1 (ar) | 2013-03-13 | 2020-07-05 | Regeneron Pharma | الأجسام المضادة لمضاد انترلوكين-33 واستعمالاتها |
US9217168B2 (en) * | 2013-03-14 | 2015-12-22 | Momenta Pharmaceuticals, Inc. | Methods of cell culture |
WO2014159633A1 (en) | 2013-03-14 | 2014-10-02 | Medimmune, Llc | Recombinant polypeptide production |
TWI659968B (zh) | 2013-03-14 | 2019-05-21 | 再生元醫藥公司 | 針對呼吸道融合病毒f蛋白質的人類抗體及其使用方法 |
US9637535B2 (en) | 2013-03-15 | 2017-05-02 | Regeneron Pharmaceuticals, Inc. | IL-33 antagonists and uses thereof |
US20160237400A1 (en) | 2013-03-15 | 2016-08-18 | The Jackson Laboratory | Isolation of non-embryonic stem cells and uses thereof |
JP6594860B2 (ja) | 2013-05-29 | 2019-10-23 | エフ.ホフマン−ラ ロシュ アーゲー | シアル酸付加の定量的調節 |
TWI641620B (zh) | 2013-08-21 | 2018-11-21 | 再生元醫藥公司 | 抗-prlr抗體及其用途 |
US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
JP6732660B2 (ja) | 2014-01-13 | 2020-07-29 | アムジエン・インコーポレーテツド | 組換えタンパク質の高マンノースグリコフォーム含有量を操作するためのオルニチン代謝の調節 |
TWI680138B (zh) | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗pd-l1之人類抗體 |
TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
JP6632984B2 (ja) | 2014-03-11 | 2020-01-22 | 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Regeneron Pharmaceuticals, Inc. | 抗EGFRvIII抗体およびその使用 |
TWI701042B (zh) | 2014-03-19 | 2020-08-11 | 美商再生元醫藥公司 | 用於腫瘤治療之方法及抗體組成物 |
EP3636073B1 (en) | 2014-05-05 | 2023-11-15 | Regeneron Pharmaceuticals, Inc. | Humanized c5 and c3 animals |
JO3701B1 (ar) | 2014-05-23 | 2021-01-31 | Regeneron Pharma | مضادات حيوية بشرية لمتلازمة الشرق الأوسط التنفسية - بروتين كورونا فيروس الشوكي |
JP7093612B2 (ja) | 2014-05-27 | 2022-06-30 | アカデミア シニカ | Bacteroides由来のフコシダーゼおよびそれを使用する方法 |
MA40021A (fr) | 2014-06-03 | 2015-12-10 | Lupin Ltd | Processus de culture cellulaire destiné à produire une protéine |
EP3194441A1 (en) | 2014-09-16 | 2017-07-26 | Regeneron Pharmaceuticals, Inc. | Anti-glucagon antibodies and uses thereof |
TWI710573B (zh) | 2015-01-26 | 2020-11-21 | 美商再生元醫藥公司 | 抗伊波拉病毒醣蛋白之人類抗體 |
CN114807010A (zh) | 2015-04-01 | 2022-07-29 | 勃林格殷格翰国际公司 | 细胞培养基 |
TW202340452A (zh) | 2015-08-04 | 2023-10-16 | 美商再生元醫藥公司 | 補充牛磺酸之細胞培養基及用法 |
KR101936049B1 (ko) | 2015-10-15 | 2019-01-08 | (주)알테오젠 | IgG Fc 도메인을 가지는 융합 단백질의 생산방법 |
TW202140776A (zh) | 2016-04-26 | 2021-11-01 | 美商美國泰福生技股份有限公司 | 細胞培養基 |
CN110914293A (zh) | 2017-07-06 | 2020-03-24 | 里珍纳龙药品有限公司 | 用于制备糖蛋白的细胞培养工艺 |
-
2014
- 2014-03-10 AR ARP140100803A patent/AR095196A1/es not_active Application Discontinuation
- 2014-03-13 TW TW109124000A patent/TWI782295B/zh active
- 2014-03-13 TW TW103108931A patent/TWI629359B/zh active
- 2014-03-13 TW TW111136096A patent/TW202325723A/zh unknown
- 2014-03-13 TW TW107120469A patent/TWI701333B/zh active
- 2014-03-14 CN CN202110770669.9A patent/CN113481148A/zh active Pending
- 2014-03-14 CA CA3188491A patent/CA3188491A1/en active Pending
- 2014-03-14 KR KR1020217007530A patent/KR102278316B1/ko active IP Right Grant
- 2014-03-14 KR KR1020157027270A patent/KR102166166B1/ko active IP Right Grant
- 2014-03-14 CN CN201480023485.4A patent/CN105143444A/zh active Pending
- 2014-03-14 CA CA3135232A patent/CA3135232C/en active Active
- 2014-03-14 EA EA201591817A patent/EA037568B1/ru unknown
- 2014-03-14 DK DK14723561.8T patent/DK2970876T3/en active
- 2014-03-14 CA CA3238123A patent/CA3238123A1/en active Pending
- 2014-03-14 AU AU2014227804A patent/AU2014227804B2/en active Active
- 2014-03-14 PT PT14723561T patent/PT2970876T/pt unknown
- 2014-03-14 MY MYPI2015702985A patent/MY175957A/en unknown
- 2014-03-14 ES ES14723561.8T patent/ES2682929T3/es active Active
- 2014-03-14 HU HUE14723561A patent/HUE040233T2/hu unknown
- 2014-03-14 PL PL14723561T patent/PL2970876T3/pl unknown
- 2014-03-14 KR KR1020217021749A patent/KR20210090732A/ko not_active IP Right Cessation
- 2014-03-14 EP EP18172141.6A patent/EP3378932A1/en active Pending
- 2014-03-14 BR BR112015022682-5A patent/BR112015022682B1/pt active IP Right Grant
- 2014-03-14 BR BR122020021864-9A patent/BR122020021864B1/pt active IP Right Grant
- 2014-03-14 EP EP14723561.8A patent/EP2970876B1/en active Active
- 2014-03-14 EA EA202191602A patent/EA202191602A3/ru unknown
- 2014-03-14 EP EP21184357.8A patent/EP3919611A1/en active Pending
- 2014-03-14 IL IL281515A patent/IL281515B2/en unknown
- 2014-03-14 US US14/211,245 patent/US20140273095A1/en not_active Abandoned
- 2014-03-14 CA CA2906768A patent/CA2906768C/en active Active
- 2014-03-14 SG SG10201707153UA patent/SG10201707153UA/en unknown
- 2014-03-14 IL IL300911A patent/IL300911A/en unknown
- 2014-03-14 MX MX2015013176A patent/MX357977B/es active IP Right Grant
- 2014-03-14 KR KR1020227027409A patent/KR20220116571A/ko not_active Application Discontinuation
- 2014-03-14 EA EA202190326A patent/EA202190326A3/ru unknown
- 2014-03-14 SG SG11201507072TA patent/SG11201507072TA/en unknown
- 2014-03-14 KR KR1020247014487A patent/KR20240065185A/ko active Search and Examination
- 2014-03-14 EP EP22209628.1A patent/EP4159841A1/en active Pending
- 2014-03-14 WO PCT/US2014/028501 patent/WO2014144198A1/en active Application Filing
- 2014-03-14 CA CA3238121A patent/CA3238121A1/en active Pending
- 2014-03-14 KR KR1020207028935A patent/KR102229380B1/ko active IP Right Grant
- 2014-03-14 SG SG10202107444XA patent/SG10202107444XA/en unknown
- 2014-03-14 JP JP2016502807A patent/JP6781039B2/ja active Active
-
2015
- 2015-09-06 IL IL241195A patent/IL241195B/en active IP Right Grant
- 2015-09-15 MX MX2021001859A patent/MX2021001859A/es unknown
- 2015-09-15 MX MX2021008627A patent/MX2021008627A/es unknown
-
2016
- 2016-01-29 HK HK16101075.8A patent/HK1213289A1/zh unknown
-
2019
- 2019-01-28 IL IL264499A patent/IL264499A/en unknown
- 2019-04-25 JP JP2019083625A patent/JP6944969B2/ja active Active
-
2020
- 2020-01-03 AU AU2020200052A patent/AU2020200052B2/en active Active
- 2020-01-14 US US16/742,695 patent/US11332771B2/en active Active
-
2021
- 2021-07-08 US US17/370,389 patent/US11970724B2/en active Active
- 2021-07-15 AU AU2021205088A patent/AU2021205088B2/en active Active
- 2021-08-16 JP JP2021132239A patent/JP2021180682A/ja not_active Withdrawn
-
2022
- 2022-01-10 IL IL289724A patent/IL289724B2/en unknown
- 2022-04-04 US US17/712,697 patent/US20220228187A1/en active Pending
- 2022-08-04 AU AU2022211862A patent/AU2022211862A1/en active Pending
- 2022-08-05 US US17/882,224 patent/US20220372436A1/en active Pending
- 2022-09-14 JP JP2022145754A patent/JP7429743B2/ja active Active
-
2023
- 2023-11-06 JP JP2023189068A patent/JP2024001357A/ja active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1321515A1 (en) * | 2001-12-21 | 2003-06-25 | Ingenium Pharmaceuticals AG | Method of culturing cells |
JP2009521941A (ja) * | 2006-01-04 | 2009-06-11 | バクスター・インターナショナル・インコーポレイテッド | 無オリゴペプチド細胞培地 |
JP2011509089A (ja) * | 2008-01-09 | 2011-03-24 | セルカ ゲーエムベーハー | 改善された培養培地添加物及びそれを用いる方法 |
JP2016514452A (ja) * | 2013-03-15 | 2016-05-23 | 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Regeneron Pharmaceuticals, Inc. | 無血清細胞培養培地 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7429743B2 (ja) | 無血清細胞培養培地 | |
NZ711935B2 (en) | Serum-free cell culture medium | |
EA044302B1 (ru) | Не содержащая сыворотки среда для культивирования клеток | |
EA047026B1 (ru) | Не содержащая сыворотки среда для культивирования клеток | |
EA045169B1 (ru) | Не содержащая сыворотки среда для культивирования клеток |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190524 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190524 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190531 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200511 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200806 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20201006 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201106 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20210129 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210322 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210617 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210816 |
|
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: 20210830 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210913 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6944969 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |