JP2016531581A - 予測可能で、一貫性のある、且つ再現可能な糖型特性を示すFc含有分子 - Google Patents
予測可能で、一貫性のある、且つ再現可能な糖型特性を示すFc含有分子 Download PDFInfo
- Publication number
- JP2016531581A JP2016531581A JP2016540433A JP2016540433A JP2016531581A JP 2016531581 A JP2016531581 A JP 2016531581A JP 2016540433 A JP2016540433 A JP 2016540433A JP 2016540433 A JP2016540433 A JP 2016540433A JP 2016531581 A JP2016531581 A JP 2016531581A
- Authority
- JP
- Japan
- Prior art keywords
- containing molecule
- substitution
- composition
- antibody
- linked glycosylation
- 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
- 238000006467 substitution reaction Methods 0.000 claims abstract description 100
- 239000000203 mixture Substances 0.000 claims abstract description 85
- 238000000034 method Methods 0.000 claims abstract description 66
- 108091006020 Fc-tagged proteins Proteins 0.000 claims abstract description 41
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims abstract description 26
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 20
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 88
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 80
- 229920001184 polypeptide Polymers 0.000 claims description 79
- 150000007523 nucleic acids Chemical class 0.000 claims description 42
- 108020004707 nucleic acids Proteins 0.000 claims description 41
- 102000039446 nucleic acids Human genes 0.000 claims description 41
- 230000004988 N-glycosylation Effects 0.000 claims description 38
- 230000014509 gene expression Effects 0.000 claims description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- 239000013604 expression vector Substances 0.000 claims description 12
- 241000699802 Cricetulus griseus Species 0.000 claims description 8
- 210000001672 ovary Anatomy 0.000 claims description 6
- 238000012258 culturing Methods 0.000 claims description 5
- 230000013595 glycosylation Effects 0.000 abstract description 32
- 238000006206 glycosylation reaction Methods 0.000 abstract description 32
- 238000012545 processing Methods 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 15
- 230000035800 maturation Effects 0.000 abstract description 8
- 230000001225 therapeutic effect Effects 0.000 abstract description 7
- 230000004927 fusion Effects 0.000 abstract description 5
- 238000012136 culture method Methods 0.000 abstract 1
- 230000002349 favourable effect Effects 0.000 abstract 1
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 101
- 108090000623 proteins and genes Proteins 0.000 description 93
- 235000018102 proteins Nutrition 0.000 description 66
- 102000004169 proteins and genes Human genes 0.000 description 66
- 238000009472 formulation Methods 0.000 description 37
- 150000004676 glycans Chemical class 0.000 description 32
- 239000013598 vector Substances 0.000 description 26
- 108020004414 DNA Proteins 0.000 description 23
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 22
- 235000001014 amino acid Nutrition 0.000 description 21
- 238000004519 manufacturing process Methods 0.000 description 20
- 230000006870 function Effects 0.000 description 19
- 230000035772 mutation Effects 0.000 description 19
- 239000011324 bead Substances 0.000 description 18
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 17
- 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 17
- 241000894007 species Species 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 15
- 239000003755 preservative agent Substances 0.000 description 15
- 150000001413 amino acids Chemical class 0.000 description 14
- 150000002482 oligosaccharides Chemical class 0.000 description 14
- 239000000872 buffer Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 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 12
- 108010076504 Protein Sorting Signals Proteins 0.000 description 12
- 230000003321 amplification Effects 0.000 description 12
- 239000012636 effector Substances 0.000 description 12
- 238000003199 nucleic acid amplification method Methods 0.000 description 12
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 11
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 11
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 238000009396 hybridization Methods 0.000 description 11
- 229920001542 oligosaccharide Polymers 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 238000012384 transportation and delivery Methods 0.000 description 11
- 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 10
- 238000003556 assay Methods 0.000 description 10
- 229930182830 galactose Natural products 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 108060003951 Immunoglobulin Proteins 0.000 description 9
- 239000000427 antigen Substances 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 239000003623 enhancer Substances 0.000 description 9
- 102000018358 immunoglobulin Human genes 0.000 description 9
- 230000003993 interaction Effects 0.000 description 9
- 210000004962 mammalian cell Anatomy 0.000 description 9
- 239000002773 nucleotide Substances 0.000 description 9
- 125000003729 nucleotide group Chemical group 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 235000002639 sodium chloride Nutrition 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 239000003963 antioxidant agent Substances 0.000 description 8
- 235000006708 antioxidants Nutrition 0.000 description 8
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 8
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 8
- 239000008103 glucose Substances 0.000 description 8
- 238000013507 mapping Methods 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000002335 preservative effect Effects 0.000 description 8
- 235000000346 sugar Nutrition 0.000 description 8
- 108010021468 Fc gamma receptor IIA Proteins 0.000 description 7
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 7
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- -1 mannose glycan Chemical class 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000004094 surface-active agent Substances 0.000 description 7
- 108091026890 Coding region Proteins 0.000 description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 6
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000002265 Human Growth Hormone Human genes 0.000 description 6
- 108010000521 Human Growth Hormone Proteins 0.000 description 6
- 239000000854 Human Growth Hormone Substances 0.000 description 6
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 6
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 6
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 6
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 6
- 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 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 229920005862 polyol Polymers 0.000 description 6
- 150000003077 polyols Chemical class 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 238000001542 size-exclusion chromatography Methods 0.000 description 6
- 239000000600 sorbitol Substances 0.000 description 6
- 235000010356 sorbitol Nutrition 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 229930195725 Mannitol Natural products 0.000 description 5
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical class CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 238000010923 batch production Methods 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 239000000594 mannitol Substances 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 238000003752 polymerase chain reaction Methods 0.000 description 5
- 229920000136 polysorbate Polymers 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 238000002741 site-directed mutagenesis Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 230000033581 fucosylation Effects 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 210000003292 kidney cell Anatomy 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 125000000311 mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 238000001757 thermogravimetry curve Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102100034608 Angiopoietin-2 Human genes 0.000 description 3
- 108010048036 Angiopoietin-2 Proteins 0.000 description 3
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- SQVRNKJHWKZAKO-PFQGKNLYSA-N N-acetyl-beta-neuraminic acid Chemical group CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-PFQGKNLYSA-N 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- 241000256251 Spodoptera frugiperda Species 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 108010022394 Threonine synthase Proteins 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- WYUKJASPBYYQRJ-VSJOFRJTSA-N beta-D-GlcpNAc-(1->2)-alpha-D-Manp-(1->3)-[beta-D-GlcpNAc-(1->2)-alpha-D-Manp-(1->6)]-beta-D-Manp-(1->4)-beta-GlcpNAc-(1->4)-beta-D-GlcpNAc Chemical compound O[C@@H]1[C@@H](NC(=O)C)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)NC(C)=O)[C@H](O)[C@@H](CO[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)NC(C)=O)O2)O)[C@@H](CO)O1 WYUKJASPBYYQRJ-VSJOFRJTSA-N 0.000 description 3
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 239000013522 chelant Substances 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000000113 differential scanning calorimetry Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 102000004419 dihydrofolate reductase Human genes 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000011067 equilibration Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 108010068617 neonatal Fc receptor Proteins 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229940068965 polysorbates Drugs 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 3
- 230000009450 sialylation Effects 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000005030 transcription termination Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 238000012815 AlphaLISA Methods 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- 108700012439 CA9 Proteins 0.000 description 2
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 2
- 102000015225 Connective Tissue Growth Factor Human genes 0.000 description 2
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 101001019455 Homo sapiens ICOS ligand Proteins 0.000 description 2
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 2
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102100034980 ICOS ligand Human genes 0.000 description 2
- 108010058683 Immobilized Proteins Proteins 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102000010787 Interleukin-4 Receptors Human genes 0.000 description 2
- 108010038486 Interleukin-4 Receptors Proteins 0.000 description 2
- 102100021592 Interleukin-7 Human genes 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108010021466 Mutant Proteins Proteins 0.000 description 2
- 102000008300 Mutant Proteins Human genes 0.000 description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 108010067372 Pancreatic elastase Proteins 0.000 description 2
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 2
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 102100038567 Properdin Human genes 0.000 description 2
- 108010005642 Properdin Proteins 0.000 description 2
- 102000014128 RANK Ligand Human genes 0.000 description 2
- 108010025832 RANK Ligand Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 2
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 102000004060 Transforming Growth Factor-beta Type II Receptor Human genes 0.000 description 2
- 108010082684 Transforming Growth Factor-beta Type II Receptor Proteins 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 241000711975 Vesicular stomatitis virus Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 108010023082 activin A Proteins 0.000 description 2
- 238000001261 affinity purification Methods 0.000 description 2
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 2
- 238000003016 alphascreen Methods 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 102000025171 antigen binding proteins Human genes 0.000 description 2
- 108091000831 antigen binding proteins Proteins 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- GRHWEVYJIHXESA-HBHDJDHDSA-N beta-D-Galp-(1->4)-beta-D-GlcpNAc-(1->2)-alpha-D-Manp-(1->3)-[beta-D-Galp-(1->4)-beta-D-GlcpNAc-(1->2)-alpha-D-Manp-(1->6)]-beta-D-Manp-(1->4)-beta-D-GlcpNAc-(1->4)-beta-D-GlcpNAc Chemical compound O[C@@H]1[C@@H](NC(=O)C)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@H]4[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O4)O)[C@@H](CO)O3)NC(C)=O)[C@H](O)[C@@H](CO[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@H]4[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O4)O)[C@@H](CO)O3)NC(C)=O)O2)O)[C@@H](CO)O1 GRHWEVYJIHXESA-HBHDJDHDSA-N 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 239000004067 bulking agent Substances 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
- 239000011575 calcium Substances 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000003196 chaotropic effect Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000000368 destabilizing effect Effects 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 238000002013 hydrophilic interaction chromatography Methods 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 229940100994 interleukin-7 Drugs 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229960000318 kanamycin Drugs 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229930182823 kanamycin A Natural products 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- 238000001668 nucleic acid synthesis Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000010525 oxidative degradation reaction Methods 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229950008882 polysorbate Drugs 0.000 description 2
- 229940068977 polysorbate 20 Drugs 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000013587 production medium Substances 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000013197 protein A assay Methods 0.000 description 2
- 230000004845 protein aggregation Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000004451 qualitative analysis Methods 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000005185 salting out Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229910052715 tantalum Inorganic materials 0.000 description 2
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- RYXGNICFFBWCJA-LRRROBGASA-N (2S,4S,5R,6R)-5-acetamido-4-hydroxy-2-[(2R,3S,4S,5R)-2,4,5,6-tetrahydroxy-1-oxohexan-3-yl]oxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O[C@H]([C@@H](O)C=O)[C@@H](O)[C@H](O)CO)(O[C@H]1[C@H](O)[C@H](O)CO)C(O)=O RYXGNICFFBWCJA-LRRROBGASA-N 0.000 description 1
- XSYUPRQVAHJETO-WPMUBMLPSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidaz Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 XSYUPRQVAHJETO-WPMUBMLPSA-N 0.000 description 1
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
- XJOTXKZIRSHZQV-RXHOOSIZSA-N (3S)-3-amino-4-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S,3S)-1-[[(1R,6R,12R,17R,20S,23S,26R,31R,34R,39R,42S,45S,48S,51S,59S)-51-(4-aminobutyl)-31-[[(2S)-6-amino-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxohexan-2-yl]carbamoyl]-20-benzyl-23-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-48-(hydroxymethyl)-42-(1H-imidazol-4-ylmethyl)-59-(2-methylsulfanylethyl)-7,10,19,22,25,33,40,43,46,49,52,54,57,60,63,64-hexadecaoxo-3,4,14,15,28,29,36,37-octathia-8,11,18,21,24,32,41,44,47,50,53,55,58,61,62,65-hexadecazatetracyclo[32.19.8.26,17.212,39]pentahexacontan-26-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)[C@@H](C)O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@@H]4CSSC[C@H](NC(=O)[C@H](Cc5ccccc5)NC(=O)[C@@H](NC1=O)[C@@H](C)CC)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1cnc[nH]1)NC3=O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N2)C(=O)NCC(=O)N4)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XJOTXKZIRSHZQV-RXHOOSIZSA-N 0.000 description 1
- WHBMMWSBFZVSSR-GSVOUGTGSA-N (R)-3-hydroxybutyric acid Chemical compound C[C@@H](O)CC(O)=O WHBMMWSBFZVSSR-GSVOUGTGSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 108091007505 ADAM17 Proteins 0.000 description 1
- 108091010839 ATAXIN1-like Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108010059616 Activins Proteins 0.000 description 1
- ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 239000012114 Alexa Fluor 647 Substances 0.000 description 1
- 102100021266 Alpha-(1,6)-fucosyltransferase Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 1
- 102000009088 Angiopoietin-1 Human genes 0.000 description 1
- 108010048154 Angiopoietin-1 Proteins 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102100035021 Ataxin-1-like Human genes 0.000 description 1
- 241000713842 Avian sarcoma virus Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102100020683 Beta-klotho Human genes 0.000 description 1
- 101710104526 Beta-klotho Proteins 0.000 description 1
- 102100032487 Beta-mannosidase Human genes 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 101100166100 Candida parapsilosis SAPP2 gene Proteins 0.000 description 1
- 102100029391 Cardiotrophin-like cytokine factor 1 Human genes 0.000 description 1
- 101710107109 Cardiotrophin-like cytokine factor 1 Proteins 0.000 description 1
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000000018 Chemokine CCL2 Human genes 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010043942 Ephrin-A2 Proteins 0.000 description 1
- 102100033919 Ephrin-A2 Human genes 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 108010075944 Erythropoietin Receptors Proteins 0.000 description 1
- 102100036509 Erythropoietin receptor Human genes 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 241000700662 Fowlpox virus Species 0.000 description 1
- 229940123457 Free radical scavenger Drugs 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
- 101100067254 Fusarium sp. (strain FN080326) fsa1 gene Proteins 0.000 description 1
- 101100067255 Fusarium sp. (strain FN080326) fsa2 gene Proteins 0.000 description 1
- 102400001370 Galanin Human genes 0.000 description 1
- 101800002068 Galanin Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108010063919 Glucagon Receptors Proteins 0.000 description 1
- 102100040890 Glucagon receptor Human genes 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 101000819490 Homo sapiens Alpha-(1,6)-fucosyltransferase Proteins 0.000 description 1
- 101000623903 Homo sapiens Cell surface glycoprotein MUC18 Proteins 0.000 description 1
- 101000864646 Homo sapiens Dickkopf-related protein 1 Proteins 0.000 description 1
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 1
- 101000611892 Homo sapiens Platelet-derived growth factor D Proteins 0.000 description 1
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 description 1
- 101000845170 Homo sapiens Thymic stromal lymphopoietin Proteins 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 102000038455 IGF Type 1 Receptor Human genes 0.000 description 1
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 238000012369 In process control Methods 0.000 description 1
- 102100026818 Inhibin beta E chain Human genes 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 102000014429 Insulin-like growth factor Human genes 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 102100035018 Interleukin-17 receptor A Human genes 0.000 description 1
- 101710186083 Interleukin-17 receptor A Proteins 0.000 description 1
- 102000004557 Interleukin-18 Receptors Human genes 0.000 description 1
- 108010017537 Interleukin-18 Receptors Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 102100039897 Interleukin-5 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 108091092195 Intron 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
- 101710172072 Kexin Proteins 0.000 description 1
- 241000235649 Kluyveromyces Species 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 101710170181 Metalloproteinase inhibitor Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 108010056852 Myostatin Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 102000008108 Osteoprotegerin Human genes 0.000 description 1
- 108010035042 Osteoprotegerin Proteins 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 229940123973 Oxygen scavenger Drugs 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- 102100040682 Platelet-derived growth factor D Human genes 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100034136 Serine/threonine-protein kinase receptor R3 Human genes 0.000 description 1
- 101710082813 Serine/threonine-protein kinase receptor R3 Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- 108010016283 TCF Transcription Factors Proteins 0.000 description 1
- 102000000479 TCF Transcription Factors Human genes 0.000 description 1
- 108010000449 TNF-Related Apoptosis-Inducing Ligand Receptors Proteins 0.000 description 1
- 102000002259 TNF-Related Apoptosis-Inducing Ligand Receptors Human genes 0.000 description 1
- 102100031294 Thymic stromal lymphopoietin Human genes 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000488 activin Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910001508 alkali metal halide Inorganic materials 0.000 description 1
- 150000008045 alkali metal halides Chemical class 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 108010055059 beta-Mannosidase Proteins 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 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
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 201000010276 collecting duct carcinoma Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 210000001840 diploid cell Anatomy 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000001516 effect on protein Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 108700014844 flt3 ligand Proteins 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 101150023212 fut8 gene Proteins 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940063135 genotropin Drugs 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 230000010005 growth-factor like effect Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 102000018511 hepcidin Human genes 0.000 description 1
- 108060003558 hepcidin Proteins 0.000 description 1
- 229940066919 hepcidin Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229960002163 hydrogen peroxide Drugs 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000010965 in-process control Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229940041682 inhalant solution Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940100602 interleukin-5 Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 229950003188 isovaleryl diethylamide Drugs 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 239000012092 media component Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229940126170 metalloproteinase inhibitor Drugs 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- SLZIZIJTGAYEKK-CIJSCKBQSA-N molport-023-220-247 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CNC=N1 SLZIZIJTGAYEKK-CIJSCKBQSA-N 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940063137 norditropin Drugs 0.000 description 1
- 229940063149 nutropin Drugs 0.000 description 1
- XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000027086 plasmid maintenance Effects 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000029983 protein stabilization Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 210000002325 somatostatin-secreting cell Anatomy 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 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
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
- C07K2317/41—Glycosylation, sialylation, or fucosylation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/71—Decreased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/72—Increased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Abstract
Description
本出願は、参照によって本明細書に組み入れられる2013年9月5日に出願されたUS61/874,222号の利益を主張する。
本出願は、ASCII形式で電子的に提出されており、その全体が参照によって本明細書に組み入れられる配列表を含有する。2014年9月5日に作成された前記ASCIIコピーはA−1859−WO−PCT_SL.txtと名付けられ、98,304バイトのサイズである。
定義
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(配列番号1)である。
CH3ドメインに相当するVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(配列番号4)。
YTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(配列番号5)である。
Fc含有ポリペプチド
S239DとV264D
任意のさらなる修飾
S239D/I332E
S239D/A330S/I332E
S239D/A330L/I332E
S298A/D333A/K334A
P247I/A339D
P247I/A339Q
D280H/K290S
D280H/K290S/S298D
D280H/K290S/S298V
F243L/R292P/Y300L
F243L/R292P/Y300L/P396L
F243L/R292P/Y300L/V305I/P396L
G236A/S239D/I332E
K326A/E333A
K326W/E333S
K290E/S298G/T299A
K290N/S298G/T299A
K290E/S298G/T299A/K326E
K290N/S298G/T299A/K326E
K334V
L235S+S239D+K334V
Q311M+K334V
S239D+K334V
F243V+K334V
E294L+K334V
S298T+K334V
E233L+Q311M+K334V
L234I+Q311M+K334V
S298T+K334V
A330M+K334V
A330F+K334V
Q311M+A330M+K334V
Q311M+A330F+K334V
S298T+A330M+K334V
S298T+A330F+K334V
S239D+A330M+K334V
S239D+S298T+K334V
L234Y+K290Y+Y296W
L234Y+F243V+Y296W
L234Y+E294L+Y296W
L234Y+Y296W
K290Y+Y296W
N297A(IgG1)
L234A/L235A(IgG1)
V234A/G237A(IgG2)
L235A/G237A/E318A(IgG4)
H268Q/V309L/A330S/A331S(IgG2)
C220S/C226S/C229S/P238S(IgG1)
C226S/C229S/E233P/L234V/L235A(IgG1)
L234F/L235E/P331S(IgG1)
S267E/L328F(IgG1)。
操作された抗体及びFc融合タンパク質をコードするポリヌクレオチド
医薬組成物
キット
実施例1
結果
[Fc変異体mAbは予想された折り畳みを示す]
実施例2
[N−グリコシル化操作のための位置の選択]。
[DNA構築物、細胞培養、形質移入、増幅及び産生]。
[MAbの精製及び定量]。
[MAb生成物の質的解析]。
[親水性相互作用クロマトグラフィ(HILIC−MS)−グリカンマッピング法]。
[示差走査熱量測定(DSC)]。
[Fc変異体のFcγRIIAへの相対的な結合の測定]
[FcRnのAlphaScreenに基づく結合アッセイ]。
[マウスにおける薬物動態(PK)試験]
結果
[mAbのグリカンのプロセッシングに影響を与える残基の選択]
Claims (54)
- Fc内で1以上のアミノ酸置換を含むFc含有分子であって、前記Fcが239位、241位、262位、264位、265位、296位、または301位で置換を含む、前記Fc含有分子。
- 239位での置換がS239D、S239EまたはS239Kである請求項1に記載のFc含有分子。
- 前記FcがS239Dの置換を含む請求項2に記載のFc含有分子。
- 241位での置換がF241Aである請求項1に記載のFc含有分子。
- 262位での置換がV262Aである請求項1に記載のFc含有分子。
- 264位での置換がV264D、V264L、V264AまたはV264Sである請求項1に記載のFc含有分子。
- 前記FcがV264Dの置換を含む請求項6に記載のFc含有分子。
- 前記FcがV264Lの置換を含む請求項6に記載のFc含有分子。
- 265位での置換がD265A、D265VまたはD265Sである請求項1に記載のFc含有分子。
- 前記FcがD265Aの置換を含む請求項9に記載のFc含有分子。
- 前記FcがD265Vの置換を含む請求項9に記載のFc含有分子。
- 前記FcがF296Aの置換を含む請求項1に記載のFc含有分子。
- 前記FcがF301Aの置換を含む請求項1に記載のFc含有分子。
- 前記Fcが239位での置換と264位での置換とを含む請求項1に記載のFc含有分子。
- 前記FcがS239Dの置換を含む請求項14に記載のFc含有分子。
- 前記FcがV264Dの置換を含む請求項15に記載のFc含有分子。
- 前記FcがV264Lの置換を含む請求項15に記載のFc含有分子。
- 前記Fcが239位での置換と265位での置換とを含む請求項1に記載のFc含有分子。
- 前記FcがS239Dの置換を含む請求項18に記載のFc含有分子。
- 前記FcがD265Aの置換を含む請求項19に記載のFc含有分子。
- 前記Fcが264位での置換と296位での置換とを含む請求項1に記載のFc含有分子。
- 前記FcがV264Dの置換を含む請求項21に記載のFc含有分子。
- 前記FcがF296Aの置換を含む請求項22に記載のFc含有分子。
- 前記Fcが264位での置換と265位での置換とを含む請求項1に記載のFc含有分子。
- 前記FcがV264Lの置換を含む請求項24に記載のFc含有分子。
- 前記FcがD265Aの置換を含む請求項25に記載のFc含有分子。
- 前記Fcが、配列番号1または配列番号5で示されるアミノ酸配列に対して少なくとも90%同一であるアミノ酸配列を含む請求項1〜26のいずれか一項に記載のFc含有分子。
- 前記Fcが、配列番号1または配列番号5で示されるアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む請求項27に記載のFc含有分子。
- 前記Fc含有分子が抗体である請求項1〜28のいずれか一項に記載のFc含有分子。
- 前記Fc含有分子がFc融合タンパク質である請求項1〜28のいずれか一項に記載のFc含有分子。
- 前記Fc含有分子がN結合型グリコシル化を含む請求項1〜30のいずれか一項に記載のFc含有分子。
- 前記Fc含有分子が哺乳類宿主細胞における発現によってグリコシル化される請求項31に記載のFc含有分子。
- 前記哺乳類宿主細胞がチャイニーズハムスター卵巣(CHO)細胞株である請求項32に記載のFc含有分子。
- 請求項31〜33のいずれか一項に記載のFc含有分子を含む組成物であって、Fc含有分子の40%を超えるものが成熟N結合型グリコシル化を含む、前記組成物。
- Fc含有分子の50%を超えるものが成熟N結合型グリコシル化を含む請求項34に記載の組成物。
- Fc含有分子の70%を超えるものが成熟N結合型グリコシル化を含む請求項35に記載の組成物。
- Fc含有分子の90%未満が成熟N結合型グリコシル化を含む請求項34〜36のいずれか一項に記載の組成物。
- 請求項31〜37のいずれか一項に記載のFc含有分子を含む組成物であって、Fc含有分子の50%未満が未成熟のN結合型グリコシル化を含む、前記組成物。
- Fc含有分子の30%未満が未成熟のN結合型グリコシル化を含む請求項38に記載の組成物。
- Fc含有分子の10%未満が未成熟のN結合型グリコシル化を含む請求項39に記載の組成物。
- Fc含有分子の5%未満がマンノース5(M5)N結合型グリコシル化を含む請求項31〜39のいずれか一項に記載の組成物。
- Fc含有分子の2%未満がマンノース5(M5)N結合型グリコシル化を含む請求項41に記載の組成物。
- Fc含有分子の1%未満がマンノース5(M5)N結合型グリコシル化を含む請求項42に記載の組成物。
- 前記組成物が医薬組成物である請求項34〜43のいずれか一項に記載の組成物。
- 請求項44に記載の医薬組成物を含むバイアル。
- 請求項44に記載の医薬組成物を含む注射器。
- Fc領域を含むポリペプチドであって、前記Fc領域が239位、241位、262位、264位、265位、296位、または301位でアミノ酸置換を含む、前記ポリペプチド。
- 請求項47に記載のポリペプチドをコードする核酸。
- プロモータに作動可能に連結されている請求項48に記載の核酸を含む発現ベクター。
- 請求項48に記載の1以上の核酸を含む宿主細胞。
- 前記核酸がプロモータに作動可能に連結される請求項50に記載の宿主細胞。
- 前記宿主細胞がチャイニーズハムスター卵巣(CHO)細胞株である請求項50に記載の宿主細胞。
- Fc含有分子の産生方法であって、前記方法が
(a)Fc含有ポリペプチドの発現を生じる条件下で請求項50〜52のいずれか一項に記載の宿主細胞を培養することと、
(b)前記培養物から前記Fc含有分子を単離することとを含む、前記方法。 - Fc含有分子の組成物の製造方法であって、前記方法が
(a)Fc含有ポリペプチドの発現を生じる条件下で請求項50〜52のいずれか一項に記載の宿主細胞を培養することと、
(b)前記培養物から前記Fc含有分子を単離してFc含有分子の組成物を得ることとを含む、前記方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361874222P | 2013-09-05 | 2013-09-05 | |
US61/874,222 | 2013-09-05 | ||
PCT/US2014/054359 WO2015035215A1 (en) | 2013-09-05 | 2014-09-05 | Fc-containing molecules exhibiting predictable, consistent, and reproducible glycoform profiles |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2016531581A true JP2016531581A (ja) | 2016-10-13 |
JP2016531581A5 JP2016531581A5 (ja) | 2017-10-12 |
JP6668241B2 JP6668241B2 (ja) | 2020-03-18 |
Family
ID=52628971
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016540433A Active JP6668241B2 (ja) | 2013-09-05 | 2014-09-05 | 予測可能で、一貫性のある、且つ再現可能な糖型特性を示すFc含有分子 |
Country Status (7)
Country | Link |
---|---|
US (2) | US11427627B2 (ja) |
EP (2) | EP3712166A1 (ja) |
JP (1) | JP6668241B2 (ja) |
AU (1) | AU2014318017B2 (ja) |
CA (1) | CA2923145A1 (ja) |
MX (1) | MX2016002870A (ja) |
WO (1) | WO2015035215A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2021521854A (ja) * | 2018-05-01 | 2021-08-30 | アムジエン・インコーポレーテツド | 調節されたグリカンプロファイルを有する抗体 |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR112012030179A8 (pt) * | 2010-05-27 | 2023-03-14 | Merck Sharp & Dohme | Polipeptídeo contendo fc |
LT2672994T (lt) | 2011-02-11 | 2018-07-25 | Merck Patent Gmbh | Anti-alfa-v integrino antikūnas, skirtas prostatos vėžio gydymui |
KR20200006526A (ko) * | 2017-03-28 | 2020-01-20 | 리브젠 바이오파마 홀딩스 리미티드 | 종양 미세 환경에서 면역 반응을 향상시키기 위한 치료제 및 방법 |
US20220098307A1 (en) * | 2019-02-22 | 2022-03-31 | Wuhan Yzy Biopharma Co., Ltd. | Modified fc fragment, antibody comprising same, and application thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006512407A (ja) * | 2002-09-27 | 2006-04-13 | ゼンコー・インコーポレイテッド | 最適化Fc変異体およびそれらの生成方法 |
US20070111281A1 (en) * | 2005-05-09 | 2007-05-17 | Glycart Biotechnology Ag | Antigen binding molecules having modified Fc regions and altered binding to Fc receptors |
Family Cites Families (132)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US4263428A (en) | 1978-03-24 | 1981-04-21 | The Regents Of The University Of California | Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same |
IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
EP0088046B1 (de) | 1982-02-17 | 1987-12-09 | Ciba-Geigy Ag | Lipide in wässriger Phase |
HUT35524A (en) | 1983-08-02 | 1985-07-29 | Hoechst Ag | Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance |
EP0143949B1 (en) | 1983-11-01 | 1988-10-12 | TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION | Pharmaceutical composition containing urokinase |
US4965195A (en) | 1987-10-26 | 1990-10-23 | Immunex Corp. | Interleukin-7 |
US4968607A (en) | 1987-11-25 | 1990-11-06 | Immunex Corporation | Interleukin-1 receptors |
AU643427B2 (en) | 1988-10-31 | 1993-11-18 | Immunex Corporation | Interleukin-4 receptors |
US5714465A (en) | 1989-05-19 | 1998-02-03 | Amgen Inc. | Method of inhibiting tumor cell dissemination with a metalloproteinase inhibitor |
US7144731B2 (en) | 1989-10-16 | 2006-12-05 | Amgen Inc. | SCF antibody compositions and methods of using the same |
WO1991018982A1 (en) | 1990-06-05 | 1991-12-12 | Immunex Corporation | Type ii interleukin-1 receptors |
GB9014932D0 (en) | 1990-07-05 | 1990-08-22 | Celltech Ltd | Recombinant dna product and method |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
JPH05244982A (ja) | 1991-12-06 | 1993-09-24 | Sumitomo Chem Co Ltd | 擬人化b−b10 |
US6239328B1 (en) | 1992-10-05 | 2001-05-29 | North Carolina State University | Method for reducing expression variability of transgenes in plant cells |
US5574138A (en) | 1993-03-08 | 1996-11-12 | Immunex Corporation | Epithelium-derived T-cell factor |
US7211259B1 (en) | 1993-05-07 | 2007-05-01 | Immunex Corporation | 4-1BB polypeptides and DNA encoding 4-1BB polypeptides |
US7138500B1 (en) | 1993-05-07 | 2006-11-21 | Immunex Corporation | Antibodies to human 4-1BB |
US6630143B1 (en) | 1993-05-24 | 2003-10-07 | Immunex Corporation | Antibodies against flt3 ligand |
US7045128B2 (en) | 1993-05-24 | 2006-05-16 | Immunex Corporation | Antibodies against flt3-ligand |
US6303769B1 (en) | 1994-07-08 | 2001-10-16 | Immunex Corporation | Lerk-5 dna |
US5885574A (en) | 1994-07-26 | 1999-03-23 | Amgen Inc. | Antibodies which activate an erythropoietin receptor |
US5919905A (en) | 1994-10-05 | 1999-07-06 | Immunex Corporation | Cytokine designated LERK-6 |
US6406901B1 (en) | 1995-06-08 | 2002-06-18 | Immunex Corporation | TNF-a converting enzyme |
AU720232B2 (en) | 1996-07-19 | 2000-05-25 | Amgen, Inc. | Analogs of cationic proteins |
US6037525A (en) | 1996-08-01 | 2000-03-14 | North Carolina State University | Method for reducing expression variability of transgenes in plant cells |
EP2371962A3 (en) | 1996-12-23 | 2011-12-21 | Immunex Corporation | Receptor activator of NF-KAPPA B, receptor is member of TNF receptor superfamily |
US5741772A (en) | 1997-02-03 | 1998-04-21 | Amgen Inc. | Neurotrophic factor NNT-1 |
US6316408B1 (en) | 1997-04-16 | 2001-11-13 | Amgen Inc. | Methods of use for osetoprotegerin binding protein receptors |
RO128635A2 (ro) | 1997-04-16 | 2013-07-30 | Amgen Inc. | Anticorp sau fragment al acestuia care se leagă la opgbp şi utilizarea acestuia, utilizarea unei forme solubile de odar, şi metodă de identificare a unui compus care descreşte activitatea opgbp |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
US20020173629A1 (en) | 1997-05-05 | 2002-11-21 | Aya Jakobovits | Human monoclonal antibodies to epidermal growth factor receptor |
US6245974B1 (en) | 1997-08-06 | 2001-06-12 | North Carolina State University | Matrix attachment regions |
EP1037991B1 (en) | 1997-12-17 | 2005-09-28 | Immunex Corporation | Cell surface glycoproteins associated with human b cell lymphomas - ulbp, dna and polypeptides |
AU755391B2 (en) | 1997-12-23 | 2002-12-12 | Immunex Corporation | SIGIRR DNA and polypeptides |
US6562618B1 (en) | 1997-12-25 | 2003-05-13 | Japan Tobacco, Inc. | Monoclonal antibody against connective tissue growth factor and medicinal uses thereof |
JP4409763B2 (ja) | 1998-01-23 | 2010-02-03 | イミュネックス・コーポレーション | Acpldnaおよびポリペプチド |
US6177612B1 (en) | 1998-07-31 | 2001-01-23 | Her Majesty The Queen In Right Of Canada, As Represented By The Department Of Agriculture And Agri-Food Canada | Matrix attachment regions |
WO2000008057A2 (en) | 1998-08-07 | 2000-02-17 | Immunex Corporation | Molecules designated b7l-1 |
DE69942861D1 (de) | 1998-08-07 | 2010-11-25 | Immunex Corp | Ldcam genannte moleküle |
US6210924B1 (en) | 1998-08-11 | 2001-04-03 | Amgen Inc. | Overexpressing cyclin D 1 in a eukaryotic cell line |
WO2000018938A1 (en) | 1998-09-29 | 2000-04-06 | Pioneer Hi-Bred International, Inc. | Mar/sar elements flanking rsyn7-driven construct |
IL143034A0 (en) | 1998-11-13 | 2002-04-21 | Immunex Corp | Human tslp dna and polypeptides |
US6682736B1 (en) | 1998-12-23 | 2004-01-27 | Abgenix, Inc. | Human monoclonal antibodies to CTLA-4 |
US7109003B2 (en) | 1998-12-23 | 2006-09-19 | Abgenix, Inc. | Methods for expressing and recovering human monoclonal antibodies to CTLA-4 |
US6737056B1 (en) * | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
US7435796B1 (en) | 1999-02-03 | 2008-10-14 | Amgen Inc. | Antibodies which bind B7RP1 |
US7459540B1 (en) | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
JP2001206899A (ja) | 1999-11-18 | 2001-07-31 | Japan Tobacco Inc | TGF−βII型受容体に対するヒトモノクローナル抗体及びその医薬用途 |
US20030103978A1 (en) | 2000-02-23 | 2003-06-05 | Amgen Inc. | Selective binding agents of osteoprotegerin binding protein |
DK2990420T3 (en) | 2000-05-26 | 2017-04-03 | Immunex Corp | USE OF INTERLEUKIN-4 RECEPTOR ANTIBODIES AND COMPOSITIONS THEREOF |
KR100408844B1 (ko) | 2000-07-29 | 2003-12-06 | 한국산업기술평가원 | 동물세포 발현벡터 |
WO2002020762A2 (en) | 2000-09-05 | 2002-03-14 | Amgen Inc. | Tnf receptor-like molecules and uses thereof |
AU2002216443A1 (en) | 2000-12-15 | 2002-06-24 | Pangen Biotech Inc. | Expression vector for animal cell containing nuclear matrix attachment region fointerferon beta |
OA12589A (en) | 2001-01-05 | 2006-06-08 | Abgenix Inc | Antibodies to insulin-like growth factor i receptor. |
DK1395669T3 (da) | 2001-01-26 | 2009-11-16 | Selexis Sa | Matriks bindingsregioner og fremgangsmåder til anvendelse af disse |
US6887687B2 (en) | 2001-07-30 | 2005-05-03 | Immunex Corporation | Nucleic acids encoding human ataxin-1-like polypeptide IMX97018 |
US7084257B2 (en) | 2001-10-05 | 2006-08-01 | Amgen Inc. | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity |
US7658924B2 (en) | 2001-10-11 | 2010-02-09 | Amgen Inc. | Angiopoietin-2 specific binding agents |
US7521053B2 (en) | 2001-10-11 | 2009-04-21 | Amgen Inc. | Angiopoietin-2 specific binding agents |
JP5355839B2 (ja) | 2001-10-23 | 2013-11-27 | ピーエスエムエー デベロプメント カンパニー, エル.エル.シー. | Psma抗体およびタンパク質マルチマー |
AR039067A1 (es) | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
EP1461081A4 (en) | 2001-12-03 | 2006-05-17 | Abgenix Inc | ANTI-CD45RB ANTIBODY FOR USE IN THE TREATMENT OF AUTOIMMUNE DISEASES AND TRANSPLANT ABLUSION |
US7378091B2 (en) | 2001-12-03 | 2008-05-27 | Amgen Fremont Inc. | Antibodies against carbonic anhydrase IX (CA IX) tumor antigen |
JP2005514409A (ja) | 2001-12-28 | 2005-05-19 | アブジェニックス・インコーポレーテッド | Muc18抗原に対する抗体の使用 |
JP2005516965A (ja) | 2001-12-28 | 2005-06-09 | アブジェニックス・インコーポレーテッド | 抗muc18抗体を使用する方法 |
WO2003057838A2 (en) | 2001-12-28 | 2003-07-17 | Abgenix, Inc. | Antibodies against the muc18 antigen |
US7135174B2 (en) | 2002-01-07 | 2006-11-14 | Amgen Fremont, Inc. | Antibodies directed to PDGFD and uses thereof |
US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
US8188231B2 (en) * | 2002-09-27 | 2012-05-29 | Xencor, Inc. | Optimized FC variants |
MXPA04009418A (es) | 2002-03-29 | 2005-06-08 | Schering Corp | Anticuerpos monoclonales humanos par interleucina-5, y metodos y composiciones que comprenden los mismos. |
JP4761710B2 (ja) | 2002-04-05 | 2011-08-31 | アムジェン インコーポレイテッド | 選択的opgl経路インヒビターとしてのヒト抗opgl中和抗体 |
WO2004016769A2 (en) | 2002-08-19 | 2004-02-26 | Abgenix, Inc. | Antibodies directed to monocyte chemo-attractant protein-1 (mcp-1) and uses thereof |
EA033750B1 (ru) | 2002-09-06 | 2019-11-21 | Amgen Inc | Изолированная молекула нуклеиновой кислоты, кодирующая антитело человека к рецептору интерлейкина-1, и ее применение |
WO2004034988A2 (en) | 2002-10-16 | 2004-04-29 | Amgen Inc. | Human anti-ifn-ϝ neutralizing antibodies as selective ifn-ϝ pathway inhibitors |
WO2004050683A2 (en) | 2002-12-02 | 2004-06-17 | Abgenix, Inc. | Antibodies directed to tumor necrosis factor and uses thereof |
US20090010920A1 (en) * | 2003-03-03 | 2009-01-08 | Xencor, Inc. | Fc Variants Having Decreased Affinity for FcyRIIb |
BRPI0411803A (pt) | 2003-06-27 | 2006-05-23 | Abgenix Inc | anticorpos dirigidos aos mutantes de deleção de receptor de fator de crescimento epidérmico e seus usos |
MEP31508A (en) | 2003-07-15 | 2010-10-10 | Amgen Inc | Human anti-ngf neutralizing antibodies as selective ngf pathway inhibitors |
JP2007500132A (ja) | 2003-07-25 | 2007-01-11 | アムジェン インコーポレイテッド | Ldcamのアンタゴニストおよびアゴニスト、並びにその使用法 |
HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
US7318925B2 (en) | 2003-08-08 | 2008-01-15 | Amgen Fremont, Inc. | Methods of use for antibodies against parathyroid hormone |
MXPA06001353A (es) | 2003-08-08 | 2006-05-04 | Abgenix Inc | Anticuerpos dirigidos a hormona paratiroides(pth) y usos de los mismos. |
AR045563A1 (es) | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
JP4931597B2 (ja) | 2003-11-07 | 2012-05-16 | イミュネックス・コーポレーション | インターロイキン−4受容体を結合する抗体 |
ATE514783T1 (de) | 2003-11-12 | 2011-07-15 | Schering Corp | Plasmidsystem zur expression mehrerer gene |
US7371381B2 (en) | 2003-12-12 | 2008-05-13 | Amgen Inc. | Anti-galanin antibodies and uses thereof |
AP2006003689A0 (en) | 2004-01-09 | 2006-08-31 | Pfizer | Antibodies to MAdCAM |
CA2561861A1 (en) | 2004-04-23 | 2005-12-15 | Amgen Inc. | Antibodies to angiogenesis inhibiting domains of cd148 |
AU2005249381A1 (en) | 2004-04-23 | 2005-12-15 | Amgen Inc. | Antibodies of angiogenesis inhibiting domains of CD148 |
CN101987870B (zh) | 2004-07-15 | 2013-07-03 | 赞科股份有限公司 | 优化的Fc变体 |
EP2336177A1 (en) | 2004-08-04 | 2011-06-22 | Amgen, Inc | Antibodies to DKK-1 |
US7423128B2 (en) | 2004-11-03 | 2008-09-09 | Amgen Fremont Inc. | Anti-properdin antibodies, and methods for making and using same |
EP1824886B1 (en) | 2004-11-17 | 2010-12-22 | Amgen Inc. | Fully human monoclonal antibodies to il-13 |
MY146381A (en) | 2004-12-22 | 2012-08-15 | Amgen Inc | Compositions and methods relating relating to anti-igf-1 receptor antibodies |
CA2589860A1 (en) | 2005-01-24 | 2006-08-03 | Amgen Inc. | Humanized anti-amyloid antibody |
CA2590164A1 (en) | 2005-01-26 | 2006-08-03 | Amgen Fremont Inc. | Antibodies against interleukin-1 beta |
EP1868647A4 (en) | 2005-03-24 | 2009-04-01 | Millennium Pharm Inc | OV064 BINDING ANTIBODIES AND METHOD FOR THEIR USE |
CA2605723A1 (en) | 2005-04-25 | 2006-11-02 | Pfizer Inc. | Antibodies to myostatin |
US7592429B2 (en) | 2005-05-03 | 2009-09-22 | Ucb Sa | Sclerostin-binding antibody |
SG162788A1 (en) | 2005-06-14 | 2010-07-29 | Amgen Inc | Self-buffering protein formulations |
EP2397498A3 (en) | 2005-07-18 | 2013-11-27 | Amgen, Inc | Human anti-B7RP1 neutralizing antibodies |
PE20071101A1 (es) | 2005-08-31 | 2007-12-21 | Amgen Inc | Polipeptidos y anticuerpos |
UA94060C2 (ru) | 2005-09-07 | 2011-04-11 | Эмджен Фримонт Инк. | Моноклональное антитело, которое специфически связывает alk-1 |
EP1979001B1 (en) | 2005-12-13 | 2012-04-11 | Medimmune Limited | Binding proteins specific for insulin-like growth factors and uses thereof |
AR056857A1 (es) | 2005-12-30 | 2007-10-24 | U3 Pharma Ag | Anticuerpos dirigidos hacia her-3 (receptor del factor de crecimiento epidérmico humano-3) y sus usos |
US7888482B2 (en) | 2006-02-10 | 2011-02-15 | Amgen Inc. | Antibodies that bind PAR-2 |
TWI395754B (zh) | 2006-04-24 | 2013-05-11 | Amgen Inc | 人類化之c-kit抗體 |
EP2035454A2 (en) | 2006-05-19 | 2009-03-18 | Amgen, Inc. | Antibodies to sars coronavirus |
CL2007002567A1 (es) | 2006-09-08 | 2008-02-01 | Amgen Inc | Proteinas aisladas de enlace a activina a humana. |
CL2007002668A1 (es) | 2006-09-20 | 2008-05-09 | Amgen Inc | Proteina de union a antigeno que se une al receptor de glucagon humano; acido nucleico que la codifica; metodo de produccion; composicion farmaceutica que la comprende; y su uso para tratar o prevenir la diabetes tipo 2. |
US7767206B2 (en) | 2006-10-02 | 2010-08-03 | Amgen Inc. | Neutralizing determinants of IL-17 Receptor A and antibodies that bind thereto |
MX2009010765A (es) | 2007-04-02 | 2009-10-26 | Amgen Fremont Inc | Anticuerpos anti-ige. |
EP2148929A4 (en) * | 2007-04-30 | 2011-03-23 | Centocor Ortho Biotech Inc | TISSUE ANTI-FACTOR ANTIBODIES AND COMPOSITIONS WITH INCREASED EFFECTOR FUNCTION |
CL2008001887A1 (es) | 2007-06-29 | 2008-10-03 | Amgen Inc | Proteinas de union a antigeno que se unen al receptor activado por proteasas 2 (par-2); acido nucleico que las codifica; vector y celula huesped; metodo de produccion; y composicion que las comprende. |
JP5341889B2 (ja) * | 2007-07-17 | 2013-11-13 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 操作された抗αVインテグリンハイブリッド抗体 |
CL2008002153A1 (es) | 2007-07-24 | 2009-06-05 | Amgen Inc | Anticuerpo aislado o fragmanto de unión de antigeno del mismo que se une al receptor de il-18 (il-18r); molecula de ácido nucleico codificante; celula huesped que la comprende; composición farmaceutica; uso médico para tratar o prevenir una condición asociada con il-18r; método in vitro para inhibir la unión de il-18 al il-18r. |
WO2009026303A1 (en) | 2007-08-21 | 2009-02-26 | Amgen Inc. | Human c-fms antigen binding proteins |
JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
US7982016B2 (en) | 2007-09-10 | 2011-07-19 | Amgen Inc. | Antigen binding proteins capable of binding thymic stromal lymphopoietin |
US8414893B2 (en) | 2007-12-21 | 2013-04-09 | Amgen Inc. | Anti-amyloid antibodies and uses thereof |
JO2913B1 (en) | 2008-02-20 | 2015-09-15 | امجين إنك, | Antibodies directed towards angiopoietin-1 and angiopoietin-2 proteins and their uses |
AU2009246946B2 (en) | 2008-05-01 | 2013-09-26 | Amgen Inc. | Anti-hepcidin antibodies and methods of use |
ES2751946T3 (es) | 2009-03-20 | 2020-04-02 | Amgen Inc | Anticuerpo antagonista específico del heterodímero alfa-4-beta-7 |
EP2233500A1 (en) | 2009-03-20 | 2010-09-29 | LFB Biotechnologies | Optimized Fc variants |
UA109888C2 (uk) | 2009-12-07 | 2015-10-26 | ІЗОЛЬОВАНЕ АНТИТІЛО АБО ЙОГО ФРАГМЕНТ, ЩО ЗВ'ЯЗУЄТЬСЯ З β-КЛОТО, РЕЦЕПТОРАМИ FGF І ЇХНІМИ КОМПЛЕКСАМИ | |
WO2011120134A1 (en) | 2010-03-29 | 2011-10-06 | Zymeworks, Inc. | Antibodies with enhanced or suppressed effector function |
US8722044B2 (en) * | 2011-03-15 | 2014-05-13 | Janssen Biotech, Inc. | Human tissue factor antibody and uses thereof |
TW201817745A (zh) | 2011-09-30 | 2018-05-16 | 日商中外製藥股份有限公司 | 具有促進抗原清除之FcRn結合域的治療性抗原結合分子 |
WO2013180295A1 (ja) | 2012-06-01 | 2013-12-05 | 日本電信電話株式会社 | パケット転送処理方法およびパケット転送処理装置 |
US9300829B2 (en) | 2014-04-04 | 2016-03-29 | Canon Kabushiki Kaisha | Image reading apparatus and correction method thereof |
-
2014
- 2014-09-05 US US14/916,993 patent/US11427627B2/en active Active
- 2014-09-05 EP EP20169362.9A patent/EP3712166A1/en active Pending
- 2014-09-05 MX MX2016002870A patent/MX2016002870A/es unknown
- 2014-09-05 AU AU2014318017A patent/AU2014318017B2/en active Active
- 2014-09-05 JP JP2016540433A patent/JP6668241B2/ja active Active
- 2014-09-05 CA CA2923145A patent/CA2923145A1/en active Pending
- 2014-09-05 EP EP14842255.3A patent/EP3041863A4/en not_active Withdrawn
- 2014-09-05 WO PCT/US2014/054359 patent/WO2015035215A1/en active Application Filing
-
2022
- 2022-07-14 US US17/865,364 patent/US20230235024A1/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006512407A (ja) * | 2002-09-27 | 2006-04-13 | ゼンコー・インコーポレイテッド | 最適化Fc変異体およびそれらの生成方法 |
US20070111281A1 (en) * | 2005-05-09 | 2007-05-17 | Glycart Biotechnology Ag | Antigen binding molecules having modified Fc regions and altered binding to Fc receptors |
Non-Patent Citations (1)
Title |
---|
IIDA S. ET AL., BMC CANCER, vol. Vol.9(2009), JPN6018029447, pages 58, ISSN: 0004075913 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2021521854A (ja) * | 2018-05-01 | 2021-08-30 | アムジエン・インコーポレーテツド | 調節されたグリカンプロファイルを有する抗体 |
Also Published As
Publication number | Publication date |
---|---|
US11427627B2 (en) | 2022-08-30 |
EP3712166A1 (en) | 2020-09-23 |
US20160207980A1 (en) | 2016-07-21 |
AU2014318017A1 (en) | 2016-03-24 |
JP6668241B2 (ja) | 2020-03-18 |
MX2016002870A (es) | 2017-02-23 |
EP3041863A1 (en) | 2016-07-13 |
WO2015035215A1 (en) | 2015-03-12 |
CA2923145A1 (en) | 2015-03-12 |
AU2014318017B2 (en) | 2020-02-06 |
EP3041863A4 (en) | 2017-08-16 |
US20230235024A1 (en) | 2023-07-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7344858B2 (ja) | Fc含有ポリペプチドの安定化 | |
JP6480409B2 (ja) | アグリコシル化Fc含有ポリペプチド | |
US20230235024A1 (en) | Fc-Containing Molecules Exhibiting Predictable, Consistent, and Reproducible Glycoform Profiles | |
CA2853809A1 (en) | Method for preparing antibodies having improved properties | |
NZ712066B2 (en) | Interleukin-2 muteins for the expansion of t-regulatory cells |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170904 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170904 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180723 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180807 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20181101 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190206 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190716 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20191015 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191021 |
|
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: 20200128 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200226 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6668241 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |