TW202330017A

TW202330017A - 凍乾的enpp1多肽調配物及其用途

凍乾的enpp1多肽調配物及其用途 Download PDF

Info

Publication number: TW202330017A
Authority: TW; Taiwan
Prior art keywords: formulation; enpp1; seq; polypeptide; enpp1 polypeptide
Prior art date: 2021-09-24

Application number

TW111136212A

Other languages

English (en)

Chinese (zh)

Inventor

史蒂芬詹格斯

Original Assignee

美商伊諾臻醫藥公司

Priority date

2021-09-24

Filing date

2022-09-23

Publication date

2023-08-01

2022-09-23 Application filed by 美商伊諾臻醫藥公司 filed Critical 美商伊諾臻醫藥公司

2023-08-01 Publication of TW202330017A publication Critical patent/TW202330017A/zh

Links

239000000203 mixture Substances 0.000 title claims abstract description 613
238000009472 formulation Methods 0.000 title claims abstract description 585
108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 490
102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 477
229920001184 polypeptide Polymers 0.000 title claims abstract description 476
101000812677 Homo sapiens Nucleotide pyrophosphatase Proteins 0.000 claims abstract description 612
102100039306 Nucleotide pyrophosphatase Human genes 0.000 claims abstract description 611
238000000034 method Methods 0.000 claims abstract description 155
230000007812 deficiency Effects 0.000 claims abstract description 49
230000002308 calcification Effects 0.000 claims abstract description 47
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 43
201000010099 disease Diseases 0.000 claims abstract description 35
230000001575 pathological effect Effects 0.000 claims abstract description 32
208000034970 Heterotopic Ossification Diseases 0.000 claims abstract description 16
239000000872 buffer Substances 0.000 claims description 132
239000004094 surface-active agent Substances 0.000 claims description 116
108090000623 proteins and genes Proteins 0.000 claims description 111
102000004169 proteins and genes Human genes 0.000 claims description 110
235000018102 proteins Nutrition 0.000 claims description 109
150000001413 amino acids Chemical class 0.000 claims description 91
239000003381 stabilizer Substances 0.000 claims description 90
235000001014 amino acid Nutrition 0.000 claims description 75
239000000654 additive Substances 0.000 claims description 64
229930006000 Sucrose Natural products 0.000 claims description 62
239000005720 sucrose Substances 0.000 claims description 62
229920001213 Polysorbate 20 Polymers 0.000 claims description 60
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 60
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 60
229940068977 polysorbate 20 Drugs 0.000 claims description 59
239000000243 solution Substances 0.000 claims description 58
-1 octyl glycoside Chemical class 0.000 claims description 54
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 claims description 53
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 claims description 52
235000002639 sodium chloride Nutrition 0.000 claims description 47
208000004434 Calcinosis Diseases 0.000 claims description 46
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 45
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 42
229920000136 polysorbate Polymers 0.000 claims description 41
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 39
229950008882 polysorbate Drugs 0.000 claims description 38
150000003839 salts Chemical class 0.000 claims description 37
102100028187 ATP-binding cassette sub-family C member 6 Human genes 0.000 claims description 36
229930195725 Mannitol Natural products 0.000 claims description 35
239000001110 calcium chloride Substances 0.000 claims description 35
229910001628 calcium chloride Inorganic materials 0.000 claims description 35
235000011148 calcium chloride Nutrition 0.000 claims description 35
239000000594 mannitol Substances 0.000 claims description 35
235000010355 mannitol Nutrition 0.000 claims description 35
229960002713 calcium chloride Drugs 0.000 claims description 34
230000000694 effects Effects 0.000 claims description 34
230000015572 biosynthetic process Effects 0.000 claims description 33
108020001507 fusion proteins Proteins 0.000 claims description 33
102000037865 fusion proteins Human genes 0.000 claims description 33
239000013628 high molecular weight specie Substances 0.000 claims description 23
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 22
208000005475 Vascular calcification Diseases 0.000 claims description 22
KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 22
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 21
229920000053 polysorbate 80 Polymers 0.000 claims description 21
101000986621 Homo sapiens ATP-binding cassette sub-family C member 6 Proteins 0.000 claims description 20
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 20
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 19
229940068968 polysorbate 80 Drugs 0.000 claims description 19
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 claims description 17
201000004613 Pseudoxanthoma elasticum Diseases 0.000 claims description 17
208000023558 pseudoxanthoma elasticum (inherited or acquired) Diseases 0.000 claims description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
239000012931 lyophilized formulation Substances 0.000 claims description 16
229910019142 PO4 Inorganic materials 0.000 claims description 15
230000011164 ossification Effects 0.000 claims description 15
210000001519 tissue Anatomy 0.000 claims description 15
UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 claims description 14
208000020832 chronic kidney disease Diseases 0.000 claims description 14
235000011180 diphosphates Nutrition 0.000 claims description 14
235000000346 sugar Nutrition 0.000 claims description 14
UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 claims description 13
FSYKKLYZXJSNPZ-UHFFFAOYSA-N N-methylaminoacetic acid Natural products C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims description 13
LNQVTSROQXJCDD-UHFFFAOYSA-N adenosine monophosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)C(OP(O)(O)=O)C1O LNQVTSROQXJCDD-UHFFFAOYSA-N 0.000 claims description 13
229960003237 betaine Drugs 0.000 claims description 13
239000007979 citrate buffer Substances 0.000 claims description 13
239000003937 drug carrier Substances 0.000 claims description 13
208000024891 symptom Diseases 0.000 claims description 13
239000004475 Arginine Substances 0.000 claims description 12
108010077895 Sarcosine Proteins 0.000 claims description 12
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 12
235000009697 arginine Nutrition 0.000 claims description 12
239000010452 phosphate Substances 0.000 claims description 12
229940043230 sarcosine Drugs 0.000 claims description 12
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical group O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 12
150000003890 succinate salts Chemical group 0.000 claims description 12
239000004471 Glycine Substances 0.000 claims description 11
230000000996 additive effect Effects 0.000 claims description 11
229920001223 polyethylene glycol Polymers 0.000 claims description 11
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 10
239000011780 sodium chloride Substances 0.000 claims description 10
229960004793 sucrose Drugs 0.000 claims description 10
KKMIHKCGXQMFEU-UHFFFAOYSA-N 2-[dimethyl(tetradecyl)azaniumyl]acetate Chemical compound CCCCCCCCCCCCCC[N+](C)(C)CC([O-])=O KKMIHKCGXQMFEU-UHFFFAOYSA-N 0.000 claims description 9
108010009413 Pyrophosphatases Proteins 0.000 claims description 9
102000009609 Pyrophosphatases Human genes 0.000 claims description 9
LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 claims description 9
229940052299 calcium chloride dihydrate Drugs 0.000 claims description 9
239000008223 sterile water Substances 0.000 claims description 9
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 9
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 8
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 8
239000011575 calcium Substances 0.000 claims description 8
229910052791 calcium Inorganic materials 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
HSEMFIZWXHQJAE-UHFFFAOYSA-N hexadecanamide Chemical compound CCCCCCCCCCCCCCCC(N)=O HSEMFIZWXHQJAE-UHFFFAOYSA-N 0.000 claims description 8
235000014304 histidine Nutrition 0.000 claims description 8
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 8
229940102223 injectable solution Drugs 0.000 claims description 8
210000004446 longitudinal ligament Anatomy 0.000 claims description 8
239000002245 particle Substances 0.000 claims description 8
125000000185 sucrose group Chemical group 0.000 claims description 8
238000011282 treatment Methods 0.000 claims description 8
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 claims description 7
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 7
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 7
241000124008 Mammalia Species 0.000 claims description 7
239000002202 Polyethylene glycol Substances 0.000 claims description 7
235000004279 alanine Nutrition 0.000 claims description 7
229940079593 drug Drugs 0.000 claims description 7
238000002347 injection Methods 0.000 claims description 7
239000007924 injection Substances 0.000 claims description 7
229910021645 metal ion Inorganic materials 0.000 claims description 7
HLERILKGMXJNBU-UHFFFAOYSA-N norvaline betaine Chemical compound CCCC(C([O-])=O)[N+](C)(C)C HLERILKGMXJNBU-UHFFFAOYSA-N 0.000 claims description 7
235000019333 sodium laurylsulphate Nutrition 0.000 claims description 7
239000000600 sorbitol Substances 0.000 claims description 7
239000000126 substance Substances 0.000 claims description 7
239000008215 water for injection Substances 0.000 claims description 7
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 6
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 6
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 6
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 6
229960005069 calcium Drugs 0.000 claims description 6
201000000523 end stage renal failure Diseases 0.000 claims description 6
150000004676 glycans Chemical class 0.000 claims description 6
TVZISJTYELEYPI-UHFFFAOYSA-N hypodiphosphoric acid Chemical compound OP(O)(=O)P(O)(O)=O TVZISJTYELEYPI-UHFFFAOYSA-N 0.000 claims description 6
239000002504 physiological saline solution Substances 0.000 claims description 6
229920001282 polysaccharide Polymers 0.000 claims description 6
239000005017 polysaccharide Substances 0.000 claims description 6
235000013930 proline Nutrition 0.000 claims description 6
208000007442 rickets Diseases 0.000 claims description 6
235000004400 serine Nutrition 0.000 claims description 6
239000008227 sterile water for injection Substances 0.000 claims description 6
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 6
229910052725 zinc Inorganic materials 0.000 claims description 6
239000011701 zinc Substances 0.000 claims description 6
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 5
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 claims description 5
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 claims description 5
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 5
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 5
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 claims description 5
RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 5
HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 5
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 5
125000002252 acyl group Chemical group 0.000 claims description 5
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 5
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
239000008101 lactose Substances 0.000 claims description 5
IZWSFJTYBVKZNK-UHFFFAOYSA-N lauryl sulfobetaine Chemical compound CCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O IZWSFJTYBVKZNK-UHFFFAOYSA-N 0.000 claims description 5
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 5
229960000502 poloxamer Drugs 0.000 claims description 5
229920001983 poloxamer Polymers 0.000 claims description 5
ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 5
230000009467 reduction Effects 0.000 claims description 5
239000011592 zinc chloride Substances 0.000 claims description 5
235000005074 zinc chloride Nutrition 0.000 claims description 5
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 4
XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 claims description 4
DIHXSRXTECMMJY-MURFETPASA-N 2-[dimethyl-[(9z,12z)-octadeca-9,12-dienyl]azaniumyl]acetate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC[N+](C)(C)CC([O-])=O DIHXSRXTECMMJY-MURFETPASA-N 0.000 claims description 4
TYIOVYZMKITKRO-UHFFFAOYSA-N 2-[hexadecyl(dimethyl)azaniumyl]acetate Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)CC([O-])=O TYIOVYZMKITKRO-UHFFFAOYSA-N 0.000 claims description 4
MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims description 4
DIROHOMJLWMERM-UHFFFAOYSA-N 3-[dimethyl(octadecyl)azaniumyl]propane-1-sulfonate Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O DIROHOMJLWMERM-UHFFFAOYSA-N 0.000 claims description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 4
241000675108 Citrus tangerina Species 0.000 claims description 4
GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose 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)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 claims description 4
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 description 4
239000005715 Fructose Substances 0.000 claims description 4
229930091371 Fructose Natural products 0.000 claims description 4
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 4
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
206010020751 Hypersensitivity Diseases 0.000 claims description 4
AYRXSINWFIIFAE-SCLMCMATSA-N Isomaltose Natural products OC[C@H]1O[C@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)[C@@H](O)[C@@H](O)[C@@H]1O AYRXSINWFIIFAE-SCLMCMATSA-N 0.000 claims description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical group [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 4
AYRXSINWFIIFAE-UHFFFAOYSA-N O6-alpha-D-Galactopyranosyl-D-galactose Natural products OCC1OC(OCC(O)C(O)C(O)C(O)C=O)C(O)C(O)C1O AYRXSINWFIIFAE-UHFFFAOYSA-N 0.000 claims description 4
229920002562 Polyethylene Glycol 3350 Polymers 0.000 claims description 4
229920001219 Polysorbate 40 Polymers 0.000 claims description 4
229920001214 Polysorbate 60 Polymers 0.000 claims description 4
229920002642 Polysorbate 65 Polymers 0.000 claims description 4
229920002651 Polysorbate 85 Polymers 0.000 claims description 4
MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 claims description 4
239000007983 Tris buffer Substances 0.000 claims description 4
MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 claims description 4
BHATUINFZWUDIX-UHFFFAOYSA-N Zwittergent 3-14 Chemical compound CCCCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O BHATUINFZWUDIX-UHFFFAOYSA-N 0.000 claims description 4
208000026935 allergic disease Diseases 0.000 claims description 4
PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 claims description 4
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims description 4
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 4
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 4
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 4
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 4
DLRVVLDZNNYCBX-CQUJWQHSSA-N gentiobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-CQUJWQHSSA-N 0.000 claims description 4
229960002442 glucosamine Drugs 0.000 claims description 4
239000008103 glucose Substances 0.000 claims description 4
229930182470 glycoside Natural products 0.000 claims description 4
YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 claims description 4
238000003384 imaging method Methods 0.000 claims description 4
238000010255 intramuscular injection Methods 0.000 claims description 4
239000007927 intramuscular injection Substances 0.000 claims description 4
238000010253 intravenous injection Methods 0.000 claims description 4
DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 claims description 4
230000007774 longterm Effects 0.000 claims description 4
229960001855 mannitol Drugs 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
ZUHZZVMEUAUWHY-UHFFFAOYSA-N n,n-dimethylpropan-1-amine Chemical compound CCCN(C)C ZUHZZVMEUAUWHY-UHFFFAOYSA-N 0.000 claims description 4
235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 claims description 4
239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 claims description 4
235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 4
239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 4
235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 claims description 4
239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 claims description 4
229920001451 polypropylene glycol Polymers 0.000 claims description 4
229940101027 polysorbate 40 Drugs 0.000 claims description 4
229940113124 polysorbate 60 Drugs 0.000 claims description 4
229940099511 polysorbate 65 Drugs 0.000 claims description 4
229940113171 polysorbate 85 Drugs 0.000 claims description 4
MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 claims description 4
239000011734 sodium Substances 0.000 claims description 4
229910052708 sodium Inorganic materials 0.000 claims description 4
229940048109 sodium methyl cocoyl taurate Drugs 0.000 claims description 4
230000002037 soft tissue calcification Effects 0.000 claims description 4
238000010254 subcutaneous injection Methods 0.000 claims description 4
239000007929 subcutaneous injection Substances 0.000 claims description 4
229940117986 sulfobetaine Drugs 0.000 claims description 4
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 4
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 claims description 4
BMYCCWYAFNPAQC-UHFFFAOYSA-N 2-[dodecyl(methyl)azaniumyl]acetate Chemical compound CCCCCCCCCCCCN(C)CC(O)=O BMYCCWYAFNPAQC-UHFFFAOYSA-N 0.000 claims description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 3
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 3
SFIHQZFZMWZOJV-UHFFFAOYSA-N Linolsaeure-amid Natural products CCCCCC=CCC=CCCCCCCCC(N)=O SFIHQZFZMWZOJV-UHFFFAOYSA-N 0.000 claims description 3
BZAFXHFMLNPZTA-UHFFFAOYSA-N N,N-dimethylpropan-1-amine octadecan-1-amine Chemical compound C(CC)N(C)C.C(CCCCCCCCCCCCCCCCC)N BZAFXHFMLNPZTA-UHFFFAOYSA-N 0.000 claims description 3
230000007815 allergy Effects 0.000 claims description 3
235000019270 ammonium chloride Nutrition 0.000 claims description 3
238000004458 analytical method Methods 0.000 claims description 3
150000001720 carbohydrates Chemical class 0.000 claims description 3
235000014633 carbohydrates Nutrition 0.000 claims description 3
208000028208 end stage renal disease Diseases 0.000 claims description 3
235000013922 glutamic acid Nutrition 0.000 claims description 3
239000004220 glutamic acid Substances 0.000 claims description 3
SFIHQZFZMWZOJV-HZJYTTRNSA-N linoleamide Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(N)=O SFIHQZFZMWZOJV-HZJYTTRNSA-N 0.000 claims description 3
229940071088 methyl cocoyl taurate Drugs 0.000 claims description 3
239000003186 pharmaceutical solution Substances 0.000 claims description 3
235000015424 sodium Nutrition 0.000 claims description 3
108010008488 Glycylglycine Proteins 0.000 claims description 2
239000007864 aqueous solution Substances 0.000 claims description 2
229940043257 glycylglycine Drugs 0.000 claims description 2
229960001714 calcium phosphate Drugs 0.000 claims 2
125000003473 lipid group Chemical group 0.000 claims 2
239000000310 rehydration solution Substances 0.000 claims 2
229940104261 taurate Drugs 0.000 claims 2
XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims 2
229940077935 zinc phosphate Drugs 0.000 claims 2
LPJKDVHMUUZHRY-KVVVOXFISA-N (z)-octadec-9-en-1-amine;hydrochloride Chemical compound Cl.CCCCCCCC\C=C/CCCCCCCCN LPJKDVHMUUZHRY-KVVVOXFISA-N 0.000 claims 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 1
108010068370 Glutens Proteins 0.000 claims 1
QMXOFBXZEKTJIK-UHFFFAOYSA-N Glycinol Natural products C1=C(O)C=C2OCC3(O)C4=CC=C(O)C=C4OC3C2=C1 QMXOFBXZEKTJIK-UHFFFAOYSA-N 0.000 claims 1
150000001412 amines Chemical class 0.000 claims 1
208000030220 autosomal recessive inherited pseudoxanthoma elasticum Diseases 0.000 claims 1
235000021312 gluten Nutrition 0.000 claims 1
125000003275 alpha amino acid group Chemical group 0.000 description 56
229940024606 amino acid Drugs 0.000 description 53
239000000945 filler Substances 0.000 description 53
230000004927 fusion Effects 0.000 description 33
108010076504 Protein Sorting Signals Proteins 0.000 description 28
239000000546 pharmaceutical excipient Substances 0.000 description 19
108060003951 Immunoglobulin Proteins 0.000 description 17
210000004027 cell Anatomy 0.000 description 17
102000018358 immunoglobulin Human genes 0.000 description 17
150000001875 compounds Chemical class 0.000 description 16
239000002243 precursor Substances 0.000 description 15
108020004414 DNA Proteins 0.000 description 14
238000010790 dilution Methods 0.000 description 14
239000012895 dilution Substances 0.000 description 14
239000002773 nucleotide Substances 0.000 description 14
230000001225 therapeutic effect Effects 0.000 description 14
125000006850 spacer group Chemical group 0.000 description 11
239000004480 active ingredient Substances 0.000 description 10
238000004108 freeze drying Methods 0.000 description 10
240000004808 Saccharomyces cerevisiae Species 0.000 description 9
235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 9
239000006172 buffering agent Substances 0.000 description 9
230000002354 daily effect Effects 0.000 description 9
239000012634 fragment Substances 0.000 description 9
235000021317 phosphate Nutrition 0.000 description 9
101150011046 NPP1 gene Proteins 0.000 description 8
101100080092 Phytophthora capsici NLP1 gene Proteins 0.000 description 8
230000002776 aggregation Effects 0.000 description 8
238000004220 aggregation Methods 0.000 description 8
239000003755 preservative agent Substances 0.000 description 8
239000013598 vector Substances 0.000 description 8
239000003963 antioxidant agent Substances 0.000 description 7
208000035475 disorder Diseases 0.000 description 7
108010067341 ectonucleotide pyrophosphatase phosphodiesterase 1 Proteins 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
210000004872 soft tissue Anatomy 0.000 description 7
235000011178 triphosphate Nutrition 0.000 description 7
239000001226 triphosphate Substances 0.000 description 7
102000004190 Enzymes Human genes 0.000 description 6
108090000790 Enzymes Proteins 0.000 description 6
239000003599 detergent Substances 0.000 description 6
229940088598 enzyme Drugs 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 6
125000003729 nucleotide group Chemical group 0.000 description 6
RWOAVOYBVRQNIZ-BFHYXJOUSA-N p-nitrophenyl thymidine 5'-monophosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OC=2C=CC(=CC=2)[N+]([O-])=O)[C@@H](O)C1 RWOAVOYBVRQNIZ-BFHYXJOUSA-N 0.000 description 6
239000000047 product Substances 0.000 description 6
238000000746 purification Methods 0.000 description 6
230000000087 stabilizing effect Effects 0.000 description 6
239000000758 substrate Substances 0.000 description 6
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
230000003143 atherosclerotic effect Effects 0.000 description 5
238000001035 drying Methods 0.000 description 5
150000002632 lipids Chemical class 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
238000007911 parenteral administration Methods 0.000 description 5
239000013612 plasmid Substances 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
208000016216 Choristoma Diseases 0.000 description 4
102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 description 4
102100036093 Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 Human genes 0.000 description 4
101000897035 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 4
101000876377 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 Proteins 0.000 description 4
UGTHTQWIQKEDEH-BQBZGAKWSA-N L-alanyl-L-prolylglycine zwitterion Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UGTHTQWIQKEDEH-BQBZGAKWSA-N 0.000 description 4
208000002193 Pain Diseases 0.000 description 4
108091005804 Peptidases Proteins 0.000 description 4
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 4
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 4
239000004365 Protease Substances 0.000 description 4
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 4
108010069020 alanyl-prolyl-glycine Proteins 0.000 description 4
229940009098 aspartate Drugs 0.000 description 4
201000003674 autosomal dominant hypophosphatemic rickets Diseases 0.000 description 4
230000004071 biological effect Effects 0.000 description 4
230000033558 biomineral tissue development Effects 0.000 description 4
230000003139 buffering effect Effects 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
230000005713 exacerbation Effects 0.000 description 4
230000006870 function Effects 0.000 description 4
230000012010 growth Effects 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
208000011111 hypophosphatemic rickets Diseases 0.000 description 4
238000007918 intramuscular administration Methods 0.000 description 4
230000007246 mechanism Effects 0.000 description 4
201000008482 osteoarthritis Diseases 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
238000012545 processing Methods 0.000 description 4
238000007920 subcutaneous administration Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
238000005303 weighing Methods 0.000 description 4
JARGNLJYKBUKSJ-KGZKBUQUSA-N (2r)-2-amino-5-[[(2r)-1-(carboxymethylamino)-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid;hydrobromide Chemical compound Br.OC(=O)[C@H](N)CCC(=O)N[C@H](CO)C(=O)NCC(O)=O JARGNLJYKBUKSJ-KGZKBUQUSA-N 0.000 description 3
206010003210 Arteriosclerosis Diseases 0.000 description 3
102100021962 Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 Human genes 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
208000033173 Generalized arterial calcification of infancy Diseases 0.000 description 3
108010070675 Glutathione transferase Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 3
101000897063 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 Proteins 0.000 description 3
208000025500 Hutchinson-Gilford progeria syndrome Diseases 0.000 description 3
208000007932 Progeria Diseases 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000251539 Vertebrata <Metazoa> Species 0.000 description 3
108010047495 alanylglycine Proteins 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
208000004900 arterial calcification of infancy Diseases 0.000 description 3
208000011775 arteriosclerosis disease Diseases 0.000 description 3
210000001367 artery Anatomy 0.000 description 3
238000003556 assay Methods 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
230000037396 body weight Effects 0.000 description 3
238000002144 chemical decomposition reaction Methods 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
150000001860 citric acid derivatives Chemical class 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
230000000295 complement effect Effects 0.000 description 3
238000006731 degradation reaction Methods 0.000 description 3
238000001514 detection method Methods 0.000 description 3
238000006471 dimerization reaction Methods 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
238000007710 freezing Methods 0.000 description 3
230000008014 freezing Effects 0.000 description 3
108010044804 gamma-glutamyl-seryl-glycine Proteins 0.000 description 3
230000002209 hydrophobic effect Effects 0.000 description 3
229910052588 hydroxylapatite Inorganic materials 0.000 description 3
208000000740 hypophosphatemic bone disease Diseases 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000001802 infusion Methods 0.000 description 3
230000007794 irritation Effects 0.000 description 3
108010051673 leucyl-glycyl-phenylalanine Proteins 0.000 description 3
238000012792 lyophilization process Methods 0.000 description 3
239000002736 nonionic surfactant Substances 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
229910052760 oxygen Inorganic materials 0.000 description 3
XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
229920005862 polyol Polymers 0.000 description 3
150000003077 polyols Chemical class 0.000 description 3
229940068965 polysorbates Drugs 0.000 description 3
230000002265 prevention Effects 0.000 description 3
230000007017 scission Effects 0.000 description 3
238000003860 storage Methods 0.000 description 3
150000008163 sugars Chemical class 0.000 description 3
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
XRILCFTWUCUKJR-INFSMZHSSA-N 2'-3'-cGAMP Chemical compound C([C@H]([C@H]1O)O2)OP(O)(=O)O[C@H]3[C@@H](O)[C@H](N4C5=NC=NC(N)=C5N=C4)O[C@@H]3COP(O)(=O)O[C@H]1[C@@H]2N1C=NC2=C1NC(N)=NC2=O XRILCFTWUCUKJR-INFSMZHSSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
101150095012 ABCC6 gene Proteins 0.000 description 2
YLTKNGYYPIWKHZ-ACZMJKKPSA-N Ala-Ala-Glu Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O YLTKNGYYPIWKHZ-ACZMJKKPSA-N 0.000 description 2
YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 2
VGPWRRFOPXVGOH-BYPYZUCNSA-N Ala-Gly-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)NCC(O)=O VGPWRRFOPXVGOH-BYPYZUCNSA-N 0.000 description 2
VHAQSYHSDKERBS-XPUUQOCRSA-N Ala-Val-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O VHAQSYHSDKERBS-XPUUQOCRSA-N 0.000 description 2
206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
SGYSTDWPNPKJPP-GUBZILKMSA-N Arg-Ala-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SGYSTDWPNPKJPP-GUBZILKMSA-N 0.000 description 2
XVLLUZMFSAYKJV-GUBZILKMSA-N Arg-Asp-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XVLLUZMFSAYKJV-GUBZILKMSA-N 0.000 description 2
LFAUVOXPCGJKTB-DCAQKATOSA-N Arg-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N LFAUVOXPCGJKTB-DCAQKATOSA-N 0.000 description 2
BIVYLQMZPHDUIH-WHFBIAKZSA-N Asp-Gly-Cys Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N)C(=O)O BIVYLQMZPHDUIH-WHFBIAKZSA-N 0.000 description 2
BWJZSLQJNBSUPM-FXQIFTODSA-N Asp-Pro-Asn Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O BWJZSLQJNBSUPM-FXQIFTODSA-N 0.000 description 2
HJZLUGQGJWXJCJ-CIUDSAMLSA-N Asp-Pro-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O HJZLUGQGJWXJCJ-CIUDSAMLSA-N 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 2
229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
108091026890 Coding region Proteins 0.000 description 2
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
IZUNQDRIAOLWCN-YUMQZZPRSA-N Cys-Leu-Gly Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N IZUNQDRIAOLWCN-YUMQZZPRSA-N 0.000 description 2
229920002307 Dextran Polymers 0.000 description 2
241000701533 Escherichia virus T4 Species 0.000 description 2
JXYMPBCYRKWJEE-BQBZGAKWSA-N Gly-Arg-Ala Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O JXYMPBCYRKWJEE-BQBZGAKWSA-N 0.000 description 2
GGEJHJIXRBTJPD-BYPYZUCNSA-N Gly-Asn-Gly Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O GGEJHJIXRBTJPD-BYPYZUCNSA-N 0.000 description 2
SOEATRRYCIPEHA-BQBZGAKWSA-N Gly-Glu-Glu Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SOEATRRYCIPEHA-BQBZGAKWSA-N 0.000 description 2
GDOZQTNZPCUARW-YFKPBYRVSA-N Gly-Gly-Glu Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O GDOZQTNZPCUARW-YFKPBYRVSA-N 0.000 description 2
GGLIDLCEPDHEJO-BQBZGAKWSA-N Gly-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)CN GGLIDLCEPDHEJO-BQBZGAKWSA-N 0.000 description 2
YOBGUCWZPXJHTN-BQBZGAKWSA-N Gly-Ser-Arg Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YOBGUCWZPXJHTN-BQBZGAKWSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
102000008100 Human Serum Albumin Human genes 0.000 description 2
108091006905 Human Serum Albumin Proteins 0.000 description 2
PFPUFNLHBXKPHY-HTFCKZLJSA-N Ile-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)O)N PFPUFNLHBXKPHY-HTFCKZLJSA-N 0.000 description 2
102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 2
108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 2
241000235058 Komagataella pastoris Species 0.000 description 2
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-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
WSGXUIQTEZDVHJ-GARJFASQSA-N Leu-Ala-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(O)=O WSGXUIQTEZDVHJ-GARJFASQSA-N 0.000 description 2
XBBKIIGCUMBKCO-JXUBOQSCSA-N Leu-Ala-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XBBKIIGCUMBKCO-JXUBOQSCSA-N 0.000 description 2
IEWBEPKLKUXQBU-VOAKCMCISA-N Leu-Leu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IEWBEPKLKUXQBU-VOAKCMCISA-N 0.000 description 2
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
FZIJIFCXUCZHOL-CIUDSAMLSA-N Lys-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN FZIJIFCXUCZHOL-CIUDSAMLSA-N 0.000 description 2
101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
DSWOTZCVCBEPOU-IUCAKERBSA-N Met-Arg-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CCCNC(N)=N DSWOTZCVCBEPOU-IUCAKERBSA-N 0.000 description 2
FVKRQMQQFGBXHV-QXEWZRGKSA-N Met-Asp-Val Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O FVKRQMQQFGBXHV-QXEWZRGKSA-N 0.000 description 2
KQBJYJXPZBNEIK-DCAQKATOSA-N Met-Glu-Arg Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQBJYJXPZBNEIK-DCAQKATOSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
108010047562 NGR peptide Proteins 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 2
GMWNQSGWWGKTSF-LFSVMHDDSA-N Phe-Thr-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O GMWNQSGWWGKTSF-LFSVMHDDSA-N 0.000 description 2
BPIMVBKDLSBKIJ-FCLVOEFKSA-N Phe-Thr-Phe Chemical compound C([C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 BPIMVBKDLSBKIJ-FCLVOEFKSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
OOLOTUZJUBOMAX-GUBZILKMSA-N Pro-Ala-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O OOLOTUZJUBOMAX-GUBZILKMSA-N 0.000 description 2
IHCXPSYCHXFXKT-DCAQKATOSA-N Pro-Arg-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O IHCXPSYCHXFXKT-DCAQKATOSA-N 0.000 description 2
HFNPOYOKIPGAEI-SRVKXCTJSA-N Pro-Leu-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 HFNPOYOKIPGAEI-SRVKXCTJSA-N 0.000 description 2
229920002684 Sepharose Polymers 0.000 description 2
208000002847 Surgical Wound Diseases 0.000 description 2
ZUXQFMVPAYGPFJ-JXUBOQSCSA-N Thr-Ala-Lys Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN ZUXQFMVPAYGPFJ-JXUBOQSCSA-N 0.000 description 2
CJEHCEOXPLASCK-MEYUZBJRSA-N Thr-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@H](O)C)CC1=CC=C(O)C=C1 CJEHCEOXPLASCK-MEYUZBJRSA-N 0.000 description 2
LIQJSDDOULTANC-QSFUFRPTSA-N Val-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)N LIQJSDDOULTANC-QSFUFRPTSA-N 0.000 description 2
230000005856 abnormality Effects 0.000 description 2
150000001242 acetic acid derivatives Chemical class 0.000 description 2
238000001042 affinity chromatography Methods 0.000 description 2
108010076324 alanyl-glycyl-glycine Proteins 0.000 description 2
108010087924 alanylproline Proteins 0.000 description 2
125000000539 amino acid group Chemical group 0.000 description 2
239000003945 anionic surfactant Substances 0.000 description 2
108010091092 arginyl-glycyl-proline Proteins 0.000 description 2
201000003672 autosomal recessive hypophosphatemic rickets Diseases 0.000 description 2
230000008901 benefit Effects 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000008112 carboxymethyl-cellulose Substances 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000003093 cationic surfactant Substances 0.000 description 2
210000000170 cell membrane Anatomy 0.000 description 2
210000002230 centromere Anatomy 0.000 description 2
239000002738 chelating agent Substances 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
239000013078 crystal Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
230000002950 deficient Effects 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
230000002526 effect on cardiovascular system Effects 0.000 description 2
239000003792 electrolyte Substances 0.000 description 2
238000004520 electroporation Methods 0.000 description 2
230000009881 electrostatic interaction Effects 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 2
XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 2
108010037850 glycylvaline Proteins 0.000 description 2
230000036541 health Effects 0.000 description 2
229920001519 homopolymer Polymers 0.000 description 2
230000005847 immunogenicity Effects 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
238000001155 isoelectric focusing Methods 0.000 description 2
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
229960000310 isoleucine Drugs 0.000 description 2
108010027338 isoleucylcysteine Proteins 0.000 description 2
229960003136 leucine Drugs 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
108010003700 lysyl aspartic acid Proteins 0.000 description 2
108010025153 lysyl-alanyl-alanine Proteins 0.000 description 2
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
229930182817 methionine Natural products 0.000 description 2
238000002156 mixing Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
239000000178 monomer Substances 0.000 description 2
230000035772 mutation Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
210000000963 osteoblast Anatomy 0.000 description 2
239000006174 pH buffer Substances 0.000 description 2
230000001717 pathogenic effect Effects 0.000 description 2
239000000816 peptidomimetic Substances 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
108010024607 phenylalanylalanine Proteins 0.000 description 2
230000001323 posttranslational effect Effects 0.000 description 2
239000000843 powder Substances 0.000 description 2
230000002028 premature Effects 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
239000002516 radical scavenger Substances 0.000 description 2
239000000523 sample Substances 0.000 description 2
238000012216 screening Methods 0.000 description 2
208000007056 sickle cell anemia Diseases 0.000 description 2
238000012360 testing method Methods 0.000 description 2
230000004797 therapeutic response Effects 0.000 description 2
230000014616 translation Effects 0.000 description 2
108020005087 unfolded proteins Proteins 0.000 description 2
230000002792 vascular Effects 0.000 description 2
230000003442 weekly effect Effects 0.000 description 2
239000002888 zwitterionic surfactant Substances 0.000 description 2
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
JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
IDOQDZANRZQBTP-UHFFFAOYSA-N 2-[2-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=CC=C1OCCO IDOQDZANRZQBTP-UHFFFAOYSA-N 0.000 description 1
AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
GUQQBLRVXOUDTN-XOHPMCGNSA-N 3-[dimethyl-[3-[[(4r)-4-[(3r,5s,7r,8r,9s,10s,12s,13r,14s,17r)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]propyl]azaniumyl]-2-hydroxypropane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CC(O)CS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 GUQQBLRVXOUDTN-XOHPMCGNSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
ZVFVBBGVOILKPO-WHFBIAKZSA-N Ala-Gly-Ala Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O ZVFVBBGVOILKPO-WHFBIAKZSA-N 0.000 description 1
SOBIAADAMRHGKH-CIUDSAMLSA-N Ala-Leu-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O SOBIAADAMRHGKH-CIUDSAMLSA-N 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
101100133992 Amycolatopsis sp Aaar gene Proteins 0.000 description 1
208000035404 Autolysis Diseases 0.000 description 1
102100030009 Azurocidin Human genes 0.000 description 1
101710154607 Azurocidin Proteins 0.000 description 1
244000063299 Bacillus subtilis Species 0.000 description 1
235000014469 Bacillus subtilis Nutrition 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
206010057248 Cell death Diseases 0.000 description 1
LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
108090000317 Chymotrypsin Proteins 0.000 description 1
244000060011 Cocos nucifera Species 0.000 description 1
235000013162 Cocos nucifera Nutrition 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
102000053602 DNA Human genes 0.000 description 1
102000012410 DNA Ligases Human genes 0.000 description 1
108010061982 DNA Ligases Proteins 0.000 description 1
102000004594 DNA Polymerase I Human genes 0.000 description 1
108010017826 DNA Polymerase I Proteins 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 description 1
GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
102100031780 Endonuclease Human genes 0.000 description 1
108010042407 Endonucleases Proteins 0.000 description 1
108010074860 Factor Xa Proteins 0.000 description 1
208000005050 Familial Hypophosphatemic Rickets Diseases 0.000 description 1
108091006020 Fc-tagged proteins Proteins 0.000 description 1
102000004042 Fibroblast Growth Factor-23 Human genes 0.000 description 1
108090000569 Fibroblast Growth Factor-23 Proteins 0.000 description 1
108010067306 Fibronectins Proteins 0.000 description 1
102000016359 Fibronectins Human genes 0.000 description 1
241000233866 Fungi Species 0.000 description 1
102100035233 Furin Human genes 0.000 description 1
108090001126 Furin Proteins 0.000 description 1
241001123946 Gaga Species 0.000 description 1
KOSRFJWDECSPRO-WDSKDSINSA-N Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O KOSRFJWDECSPRO-WDSKDSINSA-N 0.000 description 1
108010037370 Glu-Glu-Glu-Glu-Glu-Glu-Glu-Pro-Arg-Gly-Asp-Thr Proteins 0.000 description 1
WNZOCXUOGVYYBJ-CDMKHQONSA-N Gly-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CN)O WNZOCXUOGVYYBJ-CDMKHQONSA-N 0.000 description 1
YDIDLLVFCYSXNY-RCOVLWMOSA-N Gly-Val-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN YDIDLLVFCYSXNY-RCOVLWMOSA-N 0.000 description 1
101150105462 HIS6 gene Proteins 0.000 description 1
101710154606 Hemagglutinin Proteins 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
101001128634 Homo sapiens NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial Proteins 0.000 description 1
101000897042 Homo sapiens Nucleotide pyrophosphatase Proteins 0.000 description 1
229920001612 Hydroxyethyl starch Polymers 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
PPSQSIDMOVPKPI-BJDJZHNGSA-N Ile-Cys-Leu Chemical compound N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)O PPSQSIDMOVPKPI-BJDJZHNGSA-N 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
102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
208000012659 Joint disease Diseases 0.000 description 1
241001138401 Kluyveromyces lactis Species 0.000 description 1
LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-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
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
OTXBNHIUIHNGAO-UWVGGRQHSA-N Leu-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN OTXBNHIUIHNGAO-UWVGGRQHSA-N 0.000 description 1
YWKNKRAKOCLOLH-OEAJRASXSA-N Leu-Phe-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(O)=O)CC1=CC=CC=C1 YWKNKRAKOCLOLH-OEAJRASXSA-N 0.000 description 1
PPGBXYKMUMHFBF-KATARQTJSA-N Leu-Ser-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PPGBXYKMUMHFBF-KATARQTJSA-N 0.000 description 1
VKVDRTGWLVZJOM-DCAQKATOSA-N Leu-Val-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O VKVDRTGWLVZJOM-DCAQKATOSA-N 0.000 description 1
102000003960 Ligases Human genes 0.000 description 1
108090000364 Ligases Proteins 0.000 description 1
OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
LNMKRJJLEFASGA-BZSNNMDCSA-N Lys-Phe-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O LNMKRJJLEFASGA-BZSNNMDCSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
101710141452 Major surface glycoprotein G Proteins 0.000 description 1
GWADARYJIJDYRC-XGEHTFHBSA-N Met-Thr-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O GWADARYJIJDYRC-XGEHTFHBSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
WRXBPBQIVVVJQD-UHFFFAOYSA-N N-methyl-N-propylpentadecan-1-amine Chemical compound C(CCCCCCCCCCCCC)CN(CCC)C WRXBPBQIVVVJQD-UHFFFAOYSA-N 0.000 description 1
102100032194 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial Human genes 0.000 description 1
101100395023 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) his-7 gene Proteins 0.000 description 1
108091028043 Nucleic acid sequence Proteins 0.000 description 1
102100021969 Nucleotide pyrophosphatase Human genes 0.000 description 1
101710199133 Nucleotide pyrophosphatase/phosphodiesterase Proteins 0.000 description 1
206010031240 Osteodystrophy Diseases 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
108090000284 Pepsin A Proteins 0.000 description 1
102000057297 Pepsin A Human genes 0.000 description 1
SEPNOAFMZLLCEW-UBHSHLNASA-N Phe-Ala-Val Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O SEPNOAFMZLLCEW-UBHSHLNASA-N 0.000 description 1
DVOCGBNHAUHKHJ-DKIMLUQUSA-N Phe-Ile-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O DVOCGBNHAUHKHJ-DKIMLUQUSA-N 0.000 description 1
229920001363 Polidocanol Polymers 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
229920000388 Polyphosphate Polymers 0.000 description 1
101710176177 Protein A56 Proteins 0.000 description 1
108020004511 Recombinant DNA Proteins 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
102000004523 Sulfate Adenylyltransferase Human genes 0.000 description 1
108010022348 Sulfate adenylyltransferase Proteins 0.000 description 1
108090001109 Thermolysin Proteins 0.000 description 1
102100036407 Thioredoxin Human genes 0.000 description 1
ABWNZPOIUJMNKT-IXOXFDKPSA-N Thr-Phe-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O ABWNZPOIUJMNKT-IXOXFDKPSA-N 0.000 description 1
108090000190 Thrombin Proteins 0.000 description 1
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
101710120037 Toxin CcdB Proteins 0.000 description 1
101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
108030003004 Triphosphatases Proteins 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
229920004929 Triton X-114 Polymers 0.000 description 1
108090000631 Trypsin Proteins 0.000 description 1
102000004142 Trypsin Human genes 0.000 description 1
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
201000006035 X-linked dominant hypophosphatemic rickets Diseases 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
230000001594 aberrant effect Effects 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
230000001464 adherent effect Effects 0.000 description 1
238000001261 affinity purification Methods 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
239000002280 amphoteric surfactant Substances 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
238000000137 annealing Methods 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
210000002565 arteriole Anatomy 0.000 description 1
210000001188 articular cartilage Anatomy 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
239000000022 bacteriostatic agent Substances 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
230000033228 biological regulation Effects 0.000 description 1
229960000074 biopharmaceutical Drugs 0.000 description 1
230000000157 blood function Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
238000005251 capillar electrophoresis Methods 0.000 description 1
230000021523 carboxylation Effects 0.000 description 1
238000006473 carboxylation reaction Methods 0.000 description 1
210000000845 cartilage Anatomy 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
238000005277 cation exchange chromatography Methods 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
238000000423 cell based assay Methods 0.000 description 1
230000007248 cellular mechanism Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
NFCRBQADEGXVDL-UHFFFAOYSA-M cetylpyridinium chloride monohydrate Chemical compound O.[Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NFCRBQADEGXVDL-UHFFFAOYSA-M 0.000 description 1
230000008859 change Effects 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
229960001091 chenodeoxycholic acid Drugs 0.000 description 1
210000001612 chondrocyte Anatomy 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
239000003593 chromogenic compound Substances 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
229960002376 chymotrypsin Drugs 0.000 description 1
238000010367 cloning Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229910017052 cobalt Inorganic materials 0.000 description 1
239000010941 cobalt Substances 0.000 description 1
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
210000002808 connective tissue Anatomy 0.000 description 1
238000011109 contamination Methods 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
150000004696 coordination complex Chemical class 0.000 description 1
239000002577 cryoprotective agent Substances 0.000 description 1
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
229960003067 cystine Drugs 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000006240 deamidation Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
229960003964 deoxycholic acid Drugs 0.000 description 1
230000008021 deposition Effects 0.000 description 1
230000001687 destabilization Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
238000000502 dialysis Methods 0.000 description 1
230000029087 digestion Effects 0.000 description 1
UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 1
UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 1
238000007865 diluting Methods 0.000 description 1
239000000539 dimer Substances 0.000 description 1
235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
YHAIUSTWZPMYGG-UHFFFAOYSA-L disodium;2,2-dioctyl-3-sulfobutanedioate Chemical compound [Na+].[Na+].CCCCCCCCC(C([O-])=O)(C(C([O-])=O)S(O)(=O)=O)CCCCCCCC YHAIUSTWZPMYGG-UHFFFAOYSA-L 0.000 description 1
229940126534 drug product Drugs 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
230000029142 excretion Effects 0.000 description 1
239000013604 expression vector Substances 0.000 description 1
210000003722 extracellular fluid Anatomy 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
102000034287 fluorescent proteins Human genes 0.000 description 1
108091006047 fluorescent proteins Proteins 0.000 description 1
239000011888 foil Substances 0.000 description 1
210000003108 foot joint Anatomy 0.000 description 1
239000012537 formulation buffer Substances 0.000 description 1
108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
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 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
229940100242 glycol stearate Drugs 0.000 description 1
102000035122 glycosylated proteins Human genes 0.000 description 1
108091005608 glycosylated proteins Proteins 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
238000006206 glycosylation reaction Methods 0.000 description 1
210000002478 hand joint Anatomy 0.000 description 1
239000000185 hemagglutinin Substances 0.000 description 1
208000014092 hereditary hypophosphatemic rickets Diseases 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000003054 hormonal effect Effects 0.000 description 1
229920002674 hyaluronan Polymers 0.000 description 1
229960003160 hyaluronic acid Drugs 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
SKHIBNDAFWIOPB-UHFFFAOYSA-N hydron;2-phenylethanamine;chloride Chemical compound Cl.NCCC1=CC=CC=C1 SKHIBNDAFWIOPB-UHFFFAOYSA-N 0.000 description 1
125000001165 hydrophobic group Chemical group 0.000 description 1
230000005661 hydrophobic surface Effects 0.000 description 1
229940050526 hydroxyethylstarch Drugs 0.000 description 1
230000009610 hypersensitivity Effects 0.000 description 1
230000003553 hypophosphatemic effect Effects 0.000 description 1
238000012405 in silico analysis Methods 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
239000002563 ionic surfactant Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
238000005304 joining Methods 0.000 description 1
229950006462 lauromacrogol 400 Drugs 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
108010034529 leucyl-lysine Proteins 0.000 description 1
235000020778 linoleic acid Nutrition 0.000 description 1
OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
230000029226 lipidation Effects 0.000 description 1
YFVGRULMIQXYNE-UHFFFAOYSA-M lithium;dodecyl sulfate Chemical compound [Li+].CCCCCCCCCCCCOS([O-])(=O)=O YFVGRULMIQXYNE-UHFFFAOYSA-M 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910001425 magnesium ion Inorganic materials 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
244000005700 microbiome Species 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000012900 molecular simulation Methods 0.000 description 1
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
150000004712 monophosphates Chemical class 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
238000002887 multiple sequence alignment Methods 0.000 description 1
230000003387 muscular Effects 0.000 description 1
UTBABEVADWVTHM-UHFFFAOYSA-N n,n-dimethylpropan-1-amine;octadecanamide Chemical compound CCCN(C)C.CCCCCCCCCCCCCCCCCC(N)=O UTBABEVADWVTHM-UHFFFAOYSA-N 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
150000007523 nucleic acids Chemical group 0.000 description 1
239000002777 nucleoside Substances 0.000 description 1
150000003833 nucleoside derivatives Chemical class 0.000 description 1
FATBGEAMYMYZAF-KTKRTIGZSA-N oleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(N)=O FATBGEAMYMYZAF-KTKRTIGZSA-N 0.000 description 1
FATBGEAMYMYZAF-UHFFFAOYSA-N oleicacidamide-heptaglycolether Natural products CCCCCCCCC=CCCCCCCCC(N)=O FATBGEAMYMYZAF-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
150000002895 organic esters Chemical class 0.000 description 1
210000002997 osteoclast Anatomy 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
230000004792 oxidative damage Effects 0.000 description 1
238000010525 oxidative degradation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
239000006179 pH buffering agent Substances 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
229940111202 pepsin Drugs 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
239000008046 pharmaceutical antioxidant Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
150000003904 phospholipids Chemical class 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
239000013600 plasmid vector Substances 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
210000002706 plastid Anatomy 0.000 description 1
108010094020 polyglycine Proteins 0.000 description 1
229920000232 polyglycine polymer Polymers 0.000 description 1
229920002704 polyhistidine Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
230000037048 polymerization activity Effects 0.000 description 1
239000001205 polyphosphate Substances 0.000 description 1
235000011176 polyphosphates Nutrition 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910001414 potassium ion Inorganic materials 0.000 description 1
239000008057 potassium phosphate buffer Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
229940071643 prefilled syringe Drugs 0.000 description 1
238000004321 preservation Methods 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
230000008569 process Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
230000004845 protein aggregation Effects 0.000 description 1
230000012846 protein folding Effects 0.000 description 1
238000001742 protein purification Methods 0.000 description 1
230000029983 protein stabilization Effects 0.000 description 1
230000012743 protein tagging Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
230000001696 purinergic effect Effects 0.000 description 1
239000002994 raw material Substances 0.000 description 1
239000003642 reactive oxygen metabolite Substances 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011347 resin Substances 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
230000028043 self proteolysis Effects 0.000 description 1
230000035807 sensation Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000011664 signaling Effects 0.000 description 1
238000001542 size-exclusion chromatography Methods 0.000 description 1
101150027996 smb1 gene Proteins 0.000 description 1
NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical group [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
VMSNAUAEKXEYGP-YEUHZSMFSA-M sodium glycodeoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 VMSNAUAEKXEYGP-YEUHZSMFSA-M 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
ADWNFGORSPBALY-UHFFFAOYSA-M sodium;2-[dodecyl(methyl)amino]acetate Chemical class [Na+].CCCCCCCCCCCCN(C)CC([O-])=O ADWNFGORSPBALY-UHFFFAOYSA-M 0.000 description 1
HRQDCDQDOPSGBR-UHFFFAOYSA-M sodium;octane-1-sulfonate Chemical compound [Na+].CCCCCCCCS([O-])(=O)=O HRQDCDQDOPSGBR-UHFFFAOYSA-M 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
230000000392 somatic effect Effects 0.000 description 1
239000008347 soybean phospholipid Substances 0.000 description 1
241000894007 species Species 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000013112 stability test Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000011146 sterile filtration Methods 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000002344 surface layer Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
230000008685 targeting Effects 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
108060008226 thioredoxin Proteins 0.000 description 1
229940094937 thioredoxin Drugs 0.000 description 1
108010072986 threonyl-seryl-lysine Proteins 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
229910001428 transition metal ion Inorganic materials 0.000 description 1
108091007466 transmembrane glycoproteins Proteins 0.000 description 1
UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
241000701447 unidentified baculovirus Species 0.000 description 1
241000712461 unidentified influenza virus Species 0.000 description 1
210000003708 urethra Anatomy 0.000 description 1
210000001215 vagina Anatomy 0.000 description 1
239000004474 valine Substances 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
238000011100 viral filtration Methods 0.000 description 1
239000012905 visible particle Substances 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1