JP7058940B2 - 凍結乾燥第ｉｘ因子製剤 - Google Patents
凍結乾燥第ｉｘ因子製剤 Download PDFInfo
- Publication number
- JP7058940B2 JP7058940B2 JP2016558751A JP2016558751A JP7058940B2 JP 7058940 B2 JP7058940 B2 JP 7058940B2 JP 2016558751 A JP2016558751 A JP 2016558751A JP 2016558751 A JP2016558751 A JP 2016558751A JP 7058940 B2 JP7058940 B2 JP 7058940B2
- Authority
- JP
- Japan
- Prior art keywords
- lyophilized
- vial
- concentration
- fix
- item
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102100022641 Coagulation factor IX Human genes 0.000 title claims description 272
- 108010076282 Factor IX Proteins 0.000 title claims description 252
- 229960004222 factor ix Drugs 0.000 title claims description 247
- 238000002360 preparation method Methods 0.000 title claims description 85
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 173
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 166
- 229920001184 polypeptide Polymers 0.000 claims description 160
- 238000004108 freeze drying Methods 0.000 claims description 118
- 239000000203 mixture Substances 0.000 claims description 93
- 239000012931 lyophilized formulation Substances 0.000 claims description 84
- 238000009472 formulation Methods 0.000 claims description 82
- 239000000872 buffer Substances 0.000 claims description 64
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 52
- 238000011049 filling Methods 0.000 claims description 36
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 34
- 208000009429 hemophilia B Diseases 0.000 claims description 22
- 230000009467 reduction Effects 0.000 claims description 21
- 229960002885 histidine Drugs 0.000 claims description 20
- 229930006000 Sucrose Natural products 0.000 claims description 19
- 239000005720 sucrose Substances 0.000 claims description 19
- 229940127557 pharmaceutical product Drugs 0.000 claims description 17
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 15
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 15
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 15
- 229940068977 polysorbate 20 Drugs 0.000 claims description 15
- 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 14
- 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 13
- 208000032843 Hemorrhage Diseases 0.000 claims description 13
- 208000034158 bleeding Diseases 0.000 claims description 13
- 230000000740 bleeding effect Effects 0.000 claims description 13
- 229930195725 Mannitol Natural products 0.000 claims description 12
- 239000000594 mannitol Substances 0.000 claims description 12
- 235000010355 mannitol Nutrition 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 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 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 4
- 239000004472 Lysine Substances 0.000 claims description 3
- 210000004899 c-terminal region Anatomy 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 229950008882 polysorbate Drugs 0.000 claims description 2
- 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 claims 2
- 238000000034 method Methods 0.000 description 140
- 239000008176 lyophilized powder Substances 0.000 description 99
- 238000001035 drying Methods 0.000 description 91
- 239000000047 product Substances 0.000 description 57
- 230000000694 effects Effects 0.000 description 54
- 238000007710 freezing Methods 0.000 description 47
- 230000008014 freezing Effects 0.000 description 47
- 239000004094 surface-active agent Substances 0.000 description 43
- 239000000945 filler Substances 0.000 description 41
- 239000003381 stabilizer Substances 0.000 description 41
- 238000000137 annealing Methods 0.000 description 36
- 229940126534 drug product Drugs 0.000 description 36
- 150000001413 amino acids Chemical group 0.000 description 33
- 108700007283 factor IX Fc fusion Proteins 0.000 description 33
- 230000008569 process Effects 0.000 description 29
- 229940024606 amino acid Drugs 0.000 description 28
- 235000001014 amino acid Nutrition 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 25
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 25
- 108010088751 Albumins Proteins 0.000 description 23
- 102000009027 Albumins Human genes 0.000 description 23
- 238000012792 lyophilization process Methods 0.000 description 22
- 238000004458 analytical method Methods 0.000 description 19
- 238000013400 design of experiment Methods 0.000 description 19
- 239000002202 Polyethylene glycol Substances 0.000 description 18
- 229920001223 polyethylene glycol Polymers 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 239000000843 powder Substances 0.000 description 17
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 230000035772 mutation Effects 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 229940050526 hydroxyethylstarch Drugs 0.000 description 12
- 238000001542 size-exclusion chromatography Methods 0.000 description 11
- 230000015271 coagulation Effects 0.000 description 10
- 238000005345 coagulation Methods 0.000 description 10
- 239000000902 placebo Substances 0.000 description 10
- 229940068196 placebo Drugs 0.000 description 10
- 101800001415 Bri23 peptide Proteins 0.000 description 9
- 101800000655 C-terminal peptide Proteins 0.000 description 9
- 102400000107 C-terminal peptide Human genes 0.000 description 9
- 235000004279 alanine Nutrition 0.000 description 9
- 208000031169 hemorrhagic disease Diseases 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 8
- 239000000427 antigen Substances 0.000 description 8
- 102000036639 antigens Human genes 0.000 description 8
- 108091007433 antigens Proteins 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 238000000859 sublimation Methods 0.000 description 8
- 230000008022 sublimation Effects 0.000 description 8
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 229940088679 drug related substance Drugs 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- 108091033319 polynucleotide Proteins 0.000 description 7
- 102000040430 polynucleotide Human genes 0.000 description 7
- 239000002157 polynucleotide Substances 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 102000004338 Transferrin Human genes 0.000 description 6
- 108090000901 Transferrin Proteins 0.000 description 6
- 239000008186 active pharmaceutical agent Substances 0.000 description 6
- 239000003125 aqueous solvent Substances 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000012581 transferrin Substances 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- 125000002066 L-histidyl group Chemical group [H]N1C([H])=NC(C([H])([H])[C@](C(=O)[*])([H])N([H])[H])=C1[H] 0.000 description 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 238000007726 management method Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 125000000185 sucrose group Chemical group 0.000 description 5
- 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 4
- 208000031220 Hemophilia Diseases 0.000 description 4
- 208000009292 Hemophilia A Diseases 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 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 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000013595 glycosylation Effects 0.000 description 4
- 238000006206 glycosylation reaction Methods 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 230000000087 stabilizing effect Effects 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 3
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 3
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000023555 blood coagulation Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 3
- -1 hydroxyethyl group Chemical group 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 229940068968 polysorbate 80 Drugs 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 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 2
- 108010074864 Factor XI Proteins 0.000 description 2
- 101000823435 Homo sapiens Coagulation factor IX Proteins 0.000 description 2
- 108010073807 IgG Receptors Proteins 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
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 108010094028 Prothrombin Proteins 0.000 description 2
- 108010000499 Thromboplastin Proteins 0.000 description 2
- 102000002262 Thromboplastin Human genes 0.000 description 2
- 102000007238 Transferrin Receptors Human genes 0.000 description 2
- 108010033576 Transferrin Receptors Proteins 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000008228 bacteriostatic water for injection Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 238000005251 capillar electrophoresis Methods 0.000 description 2
- 238000005277 cation exchange chromatography Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- SYELZBGXAIXKHU-UHFFFAOYSA-N dodecyldimethylamine N-oxide Chemical compound CCCCCCCCCCCC[N+](C)(C)[O-] SYELZBGXAIXKHU-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 229940052349 human coagulation factor ix Drugs 0.000 description 2
- 210000001503 joint Anatomy 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000000569 multi-angle light scattering Methods 0.000 description 2
- 108010068617 neonatal Fc receptor Proteins 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 230000006320 pegylation Effects 0.000 description 2
- 238000013439 planning Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000013169 thromboelastometry Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 238000012384 transportation and delivery Methods 0.000 description 2
- 229940075601 voluven Drugs 0.000 description 2
- 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 description 1
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 description 1
- 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 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- 229920000945 Amylopectin Polymers 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000014914 Carrier Proteins Human genes 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
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010016077 Factor IX deficiency Diseases 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 108010080865 Factor XII Proteins 0.000 description 1
- 102000000429 Factor XII Human genes 0.000 description 1
- 108010071289 Factor XIII Proteins 0.000 description 1
- 108010021468 Fc gamma receptor IIA Proteins 0.000 description 1
- 108010021472 Fc gamma receptor IIB Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000024659 Hemostatic disease Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 206010021137 Hypovolaemia Diseases 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 206010060820 Joint injury Diseases 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 102100035792 Kininogen-1 Human genes 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
- 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
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
- 102100029205 Low affinity immunoglobulin gamma Fc region receptor II-b Human genes 0.000 description 1
- 101710099301 Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 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 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010027514 Metrorrhagia Diseases 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091006006 PEGylated Proteins Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 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 description 1
- 101000913100 Rattus norvegicus IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010038460 Renal haemorrhage Diseases 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 108700011201 Streptococcus IgG Fc-binding Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- 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 description 1
- 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 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000009056 active transport Effects 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
- 125000000217 alkyl group Chemical group 0.000 description 1
- 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 description 1
- 102000004139 alpha-Amylases Human genes 0.000 description 1
- 108090000637 alpha-Amylases Proteins 0.000 description 1
- 229940024171 alpha-amylase Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229940031422 benefix Drugs 0.000 description 1
- 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 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940019700 blood coagulation factors Drugs 0.000 description 1
- 238000009529 body temperature measurement Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000007820 coagulation assay Methods 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 229940012444 factor xiii Drugs 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000004545 gene duplication Effects 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 208000002085 hemarthrosis Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([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])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 150000003147 proline derivatives Chemical group 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 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 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 238000012419 revalidation Methods 0.000 description 1
- 238000000518 rheometry Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000005092 sublimation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21022—Coagulation factor IXa (3.4.21.22)
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F26—DRYING
- F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
- F26B5/00—Drying solid materials or objects by processes not involving the application of heat
- F26B5/04—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
- F26B5/06—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mechanical Engineering (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Mobile Radio Communication Systems (AREA)
- Monitoring And Testing Of Transmission In General (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022007013A JP7503583B2 (ja) | 2014-03-24 | 2022-01-20 | 凍結乾燥第ｉｘ因子製剤 |
| JP2024033771A JP7759978B2 (ja) | 2014-03-24 | 2024-03-06 | 凍結乾燥第ｉｘ因子製剤 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461969801P | 2014-03-24 | 2014-03-24 | |
| US61/969,801 | 2014-03-24 | ||
| PCT/US2015/022141 WO2015148444A1 (en) | 2014-03-24 | 2015-03-24 | Lyophilized factor ix formulations |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020016131A Division JP2020063313A (ja) | 2014-03-24 | 2020-02-03 | 凍結乾燥第ｉｘ因子製剤 |
| JP2022007013A Division JP7503583B2 (ja) | 2014-03-24 | 2022-01-20 | 凍結乾燥第ｉｘ因子製剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017510585A JP2017510585A (ja) | 2017-04-13 |
| JP2017510585A5 JP2017510585A5 (enExample) | 2018-05-10 |
| JP7058940B2 true JP7058940B2 (ja) | 2022-04-25 |
Family
ID=54196282
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016558751A Active JP7058940B2 (ja) | 2014-03-24 | 2015-03-24 | 凍結乾燥第ｉｘ因子製剤 |
| JP2020016131A Pending JP2020063313A (ja) | 2014-03-24 | 2020-02-03 | 凍結乾燥第ｉｘ因子製剤 |
| JP2022007013A Active JP7503583B2 (ja) | 2014-03-24 | 2022-01-20 | 凍結乾燥第ｉｘ因子製剤 |
| JP2024033771A Active JP7759978B2 (ja) | 2014-03-24 | 2024-03-06 | 凍結乾燥第ｉｘ因子製剤 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020016131A Pending JP2020063313A (ja) | 2014-03-24 | 2020-02-03 | 凍結乾燥第ｉｘ因子製剤 |
| JP2022007013A Active JP7503583B2 (ja) | 2014-03-24 | 2022-01-20 | 凍結乾燥第ｉｘ因子製剤 |
| JP2024033771A Active JP7759978B2 (ja) | 2014-03-24 | 2024-03-06 | 凍結乾燥第ｉｘ因子製剤 |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US10772942B2 (enExample) |
| EP (1) | EP3123090A4 (enExample) |
| JP (4) | JP7058940B2 (enExample) |
| KR (1) | KR102385372B1 (enExample) |
| AR (1) | AR099838A1 (enExample) |
| AU (2) | AU2015236340B2 (enExample) |
| CA (1) | CA2943034C (enExample) |
| CL (1) | CL2016002386A1 (enExample) |
| EA (2) | EA202092926A3 (enExample) |
| IL (3) | IL247869B (enExample) |
| MA (1) | MA39779A (enExample) |
| MX (2) | MX387269B (enExample) |
| PH (1) | PH12016501877A1 (enExample) |
| SG (3) | SG10201913735SA (enExample) |
| TW (1) | TWI700101B (enExample) |
| WO (1) | WO2015148444A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2024053015A (ja) * | 2014-03-24 | 2024-04-12 | バイオベラティブ セラピューティクス インコーポレイテッド | 凍結乾燥第ｉｘ因子製剤 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI788044B (zh) * | 2013-03-15 | 2022-12-21 | 美商百歐維拉提夫治療公司 | 因子ｉｘ多肽調配物 |
| BR112019011115A2 (pt) * | 2016-12-02 | 2019-10-01 | Bioverativ Therapeutics Inc. | métodos para tratar artropatia hemofílica usando fatores de coagulação quiméricos |
| MX2020000480A (es) * | 2017-07-11 | 2020-09-10 | Universal Stabilization Tech Inc | Método para la conservación de material biológico. |
| CN112175088B (zh) * | 2019-07-02 | 2023-03-28 | 江苏晟斯生物制药有限公司 | 改进的fix融合蛋白、缀合物及其应用 |
| MX2022009558A (es) | 2020-02-04 | 2022-09-09 | Regeneron Pharma | Contenido de humedad residual objetivo para farmaco liofilizado. |
| JP2023526024A (ja) * | 2020-05-11 | 2023-06-20 | アルカームス ファーマ アイルランド リミテッド | Ｉｌ－２融合ポリペプチド組成物ならびにその作製及び使用方法 |
| CN118557531B (zh) * | 2024-08-02 | 2024-10-18 | 成都蓉生药业有限责任公司 | 一种重组人凝血因子VIII-Fc融合蛋白冻干制剂的制备方法 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002513390A (ja) | 1996-10-16 | 2002-05-08 | アルザ コーポレイション | 低い反応性を有する非水性、無水の非プロトン性疎水性非極性ビヒクルを用いる安定なたんぱく質および核酸配合物 |
| JP2006257099A (ja) | 1996-01-25 | 2006-09-28 | Genetics Inst Llc | 高度に濃縮された、凍結乾燥された、および液体の、因子ｉｘ処方 |
| JP2009513705A (ja) | 2005-11-01 | 2009-04-02 | ワイス | 薬剤復元または希釈のための塩化ナトリウム溶液 |
| US20120116054A1 (en) | 2005-07-22 | 2012-05-10 | Sampathkumar Krishnan | Concentrated protein lyophilates, methods, and uses |
| JP2013534426A (ja) | 2010-07-09 | 2013-09-05 | バイオジェン アイデック ヘモフィリア インコーポレイテッド | 第ｉｘ因子ポリペプチドおよびその使用方法 |
| WO2013185113A1 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Procoagulant compounds |
| JP2014051503A (ja) | 2006-04-04 | 2014-03-20 | Zymenex As | ポリペプチドの濃縮方法 |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0154316B1 (en) | 1984-03-06 | 1989-09-13 | Takeda Chemical Industries, Ltd. | Chemically modified lymphokine and production thereof |
| WO1990006952A1 (fr) | 1988-12-22 | 1990-06-28 | Kirin-Amgen, Inc. | Facteur de stimulation de colonies de granulocytes modifies chimiquement |
| WO1990009800A1 (en) | 1989-02-21 | 1990-09-07 | Washington University | Modified forms of reproductive hormones |
| US6552170B1 (en) | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
| DK0575545T3 (da) | 1991-03-15 | 2003-09-15 | Amgen Inc | Pegylering af polypeptider |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| WO1994007510A1 (en) | 1992-10-02 | 1994-04-14 | Kabi Pharmacia Ab | Composition comprising coagulation factor viii formulation, process for its preparation and use of a surfactant as stabilizer |
| DE4405426A1 (de) | 1994-02-21 | 1995-08-24 | Boehringer Mannheim Gmbh | Pharmazeutisches Präparat enthaltend Plasminogenaktivator (t-PA) oder dessen Derivate |
| US6372716B1 (en) | 1994-04-26 | 2002-04-16 | Genetics Institute, Inc. | Formulations for factor IX |
| US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
| US20010031721A1 (en) | 1999-05-05 | 2001-10-18 | Chandra Webb | Highly concentrated, lyophilized, and liquid factor IX formulations |
| JP2001151694A (ja) | 1999-09-17 | 2001-06-05 | Takeda Chem Ind Ltd | タンパク質粉体の製造法 |
| KR20020063853A (ko) * | 1999-09-17 | 2002-08-05 | 다케다 야쿠힌 고교 가부시키가이샤 | 단백질 분체의 제조 방법 |
| AU4314801A (en) | 2000-02-11 | 2001-08-20 | Lexigen Pharm Corp | Enhancing the circulating half-life of antibody-based fusion proteins |
| WO2002040544A2 (en) | 2000-11-14 | 2002-05-23 | Board Of Regents, University Of Texas Systems | Mutant human factor ix with an increased resistance to inhibition by heparin |
| EP1427820A2 (en) | 2001-09-04 | 2004-06-16 | MERCK PATENT GmbH | Modified factor ix |
| WO2003060071A2 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| EP3552627A1 (en) | 2003-05-06 | 2019-10-16 | Bioverativ Therapeutics Inc. | Clotting factor-fc chimeric proteins to treat hemophilia |
| US7348004B2 (en) | 2003-05-06 | 2008-03-25 | Syntonix Pharmaceuticals, Inc. | Immunoglobulin chimeric monomer-dimer hybrids |
| TWI353991B (en) * | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| JP2005060378A (ja) | 2003-07-28 | 2005-03-10 | Yamanouchi Pharmaceut Co Ltd | 生理活性蛋白質含有凍結乾燥製剤 |
| US20050152979A1 (en) | 2003-09-05 | 2005-07-14 | Cell Therapeutics, Inc. | Hydrophobic drug compositions containing reconstitution enhancer |
| EP2311437A1 (en) | 2003-12-19 | 2011-04-20 | Novo Nordisk Health Care AG | Stabilised compositions of factor VII polypeptides |
| CA2554018A1 (en) | 2004-03-04 | 2005-09-29 | Wyeth | Lyophilization method to improve excipient crystallization |
| WO2006029467A1 (en) | 2004-09-16 | 2006-03-23 | Btf Pty Ltd | Rapid freeze drying process |
| US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
| LT2371856T (lt) | 2004-11-12 | 2022-08-25 | Bayer Healthcare Llc | Fviii modifikacija, nukreipta į tam tikrą vietą |
| KR101283736B1 (ko) | 2004-12-15 | 2013-07-08 | 스위디쉬 오르펀 바이오비트럼 에이비(피유비엘) | 케라티노사이트 성장 인자의 치료학적 제형 |
| EP1951757B1 (en) * | 2005-10-06 | 2014-05-14 | Xencor, Inc. | Optimized anti-cd30 antibodies |
| US8048848B2 (en) | 2006-02-03 | 2011-11-01 | Prolor Biotech Ltd. | Long-acting interferons and derivatives thereof and methods thereof |
| EP2004683B1 (en) | 2006-03-24 | 2016-05-11 | Biogen Hemophilia Inc. | Pc5 as a factor ix propeptide processing enzyme |
| TW200804416A (en) | 2006-06-19 | 2008-01-16 | Nautilus Technology Llc | Modified coagulation factor IX polypeptides and use thereof for treatment |
| US8015841B2 (en) | 2006-09-08 | 2011-09-13 | Praxair Technology, Inc. | Cryogenic refrigeration system for lyophilization |
| US7700734B2 (en) | 2007-01-09 | 2010-04-20 | Shu-Wha Lin | Recombinant human factor IX and use thereof |
| KR101631323B1 (ko) | 2007-06-21 | 2016-06-17 | 엑스엘-프로테인 게엠베하 | 증가된 생체내 및/또는 시험관내 안정성을 갖는 생물학적 활성 단백질 |
| CN102026653B (zh) | 2007-10-15 | 2014-06-18 | 北卡罗来纳-查佩尔山大学 | 半衰期延长的人因子ⅸ变体 |
| CN101903030A (zh) | 2007-12-21 | 2010-12-01 | 灵感生物制药学有限公司 | 含海藻糖的稳定化因子ix制剂 |
| NZ585835A (en) | 2007-12-27 | 2012-07-27 | Baxter Int | Chemically modified factor IX comprising a hydrophilic polymer attached via a releasable linker |
| JP2011517950A (ja) | 2008-04-16 | 2011-06-23 | バイエル・ヘルスケア・エルエルシー | 第ｉｘ因子の部位特異的修飾 |
| WO2009137254A2 (en) | 2008-04-16 | 2009-11-12 | Bayer Healthcare Llc | Modified factor ix polypeptides and uses thereof |
| WO2009130198A2 (en) | 2008-04-21 | 2009-10-29 | Novo Nordisk A/S | Hyperglycosylated human coagulation factor ix |
| AU2009239641B2 (en) | 2008-04-24 | 2013-11-07 | Cantab Biopharmaceuticals Patents Limited | Factor IX conjugates with extended half-lives |
| ES2755029T3 (es) | 2008-08-05 | 2020-04-21 | Wyeth Llc | Liofilización por encima de la temperatura de colapso |
| CN102164943A (zh) | 2008-09-24 | 2011-08-24 | 稳定技术有限公司 | 使用糖和聚乙烯亚胺保存多肽的方法 |
| US20120114646A1 (en) | 2009-06-18 | 2012-05-10 | Wyeth Llc | Lyophilized formulations for small modular immunopharmaceuticals |
| EP2458990B1 (en) * | 2009-07-28 | 2016-03-30 | Merck Sharp & Dohme Corp. | Methods for producing high concentration lyophilized pharmaceutical formulations |
| US20130217708A1 (en) | 2010-09-30 | 2013-08-22 | Toyama Chemical Co., Ltd. | Meglumine salt of 6-fluoro-3-hydroxy-2-pyrazine carboxamide |
| US10286037B2 (en) | 2011-02-09 | 2019-05-14 | Glaxosmithkline Llc | Methods of producing lyophilized polypeptide composition formulations comprising volatile additives |
| WO2014052490A1 (en) * | 2012-09-25 | 2014-04-03 | Biogen Idec Ma Inc. | Methods of using fix polypeptides |
| TWI788044B (zh) | 2013-03-15 | 2022-12-21 | 美商百歐維拉提夫治療公司 | 因子ｉｘ多肽調配物 |
| SG10201913735SA (en) * | 2014-03-24 | 2020-03-30 | Bioverativ Therapeutics Inc | Lyophilized factor ix formulations |
-
2015
- 2015-03-24 SG SG10201913735SA patent/SG10201913735SA/en unknown
- 2015-03-24 MA MA039779A patent/MA39779A/fr unknown
- 2015-03-24 CA CA2943034A patent/CA2943034C/en active Active
- 2015-03-24 WO PCT/US2015/022141 patent/WO2015148444A1/en not_active Ceased
- 2015-03-24 KR KR1020167028692A patent/KR102385372B1/ko active Active
- 2015-03-24 AU AU2015236340A patent/AU2015236340B2/en not_active Withdrawn - After Issue
- 2015-03-24 EA EA202092926A patent/EA202092926A3/ru unknown
- 2015-03-24 SG SG10201808249VA patent/SG10201808249VA/en unknown
- 2015-03-24 SG SG11201607642RA patent/SG11201607642RA/en unknown
- 2015-03-24 TW TW104109389A patent/TWI700101B/zh active
- 2015-03-24 JP JP2016558751A patent/JP7058940B2/ja active Active
- 2015-03-24 US US15/128,951 patent/US10772942B2/en active Active
- 2015-03-24 EP EP15769411.8A patent/EP3123090A4/en active Pending
- 2015-03-24 EA EA201691807A patent/EA038573B1/ru unknown
- 2015-03-24 MX MX2016012447A patent/MX387269B/es unknown
- 2015-03-25 AR ARP150100880A patent/AR099838A1/es unknown
-
2016
- 2016-09-18 IL IL247869A patent/IL247869B/en active IP Right Grant
- 2016-09-22 CL CL2016002386A patent/CL2016002386A1/es unknown
- 2016-09-23 MX MX2021012939A patent/MX2021012939A/es unknown
- 2016-09-23 PH PH12016501877A patent/PH12016501877A1/en unknown
-
2020
- 2020-01-26 IL IL272257A patent/IL272257B/en active IP Right Grant
- 2020-02-03 JP JP2020016131A patent/JP2020063313A/ja active Pending
- 2020-04-30 AU AU2020202863A patent/AU2020202863B2/en active Active
- 2020-08-17 US US16/995,173 patent/US12128092B2/en active Active
-
2021
- 2021-03-02 IL IL281197A patent/IL281197B/en unknown
-
2022
- 2022-01-20 JP JP2022007013A patent/JP7503583B2/ja active Active
-
2024
- 2024-03-06 JP JP2024033771A patent/JP7759978B2/ja active Active
- 2024-09-24 US US18/894,851 patent/US20250121042A1/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006257099A (ja) | 1996-01-25 | 2006-09-28 | Genetics Inst Llc | 高度に濃縮された、凍結乾燥された、および液体の、因子ｉｘ処方 |
| JP2002513390A (ja) | 1996-10-16 | 2002-05-08 | アルザ コーポレイション | 低い反応性を有する非水性、無水の非プロトン性疎水性非極性ビヒクルを用いる安定なたんぱく質および核酸配合物 |
| US20120116054A1 (en) | 2005-07-22 | 2012-05-10 | Sampathkumar Krishnan | Concentrated protein lyophilates, methods, and uses |
| JP2009513705A (ja) | 2005-11-01 | 2009-04-02 | ワイス | 薬剤復元または希釈のための塩化ナトリウム溶液 |
| JP2014051503A (ja) | 2006-04-04 | 2014-03-20 | Zymenex As | ポリペプチドの濃縮方法 |
| JP2013534426A (ja) | 2010-07-09 | 2013-09-05 | バイオジェン アイデック ヘモフィリア インコーポレイテッド | 第ｉｘ因子ポリペプチドおよびその使用方法 |
| WO2013185113A1 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Procoagulant compounds |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2024053015A (ja) * | 2014-03-24 | 2024-04-12 | バイオベラティブ セラピューティクス インコーポレイテッド | 凍結乾燥第ｉｘ因子製剤 |
| JP7759978B2 (ja) | 2014-03-24 | 2025-10-24 | バイオベラティブ セラピューティクス インコーポレイテッド | 凍結乾燥第ｉｘ因子製剤 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7759978B2 (ja) | 凍結乾燥第ｉｘ因子製剤 | |
| JP7636481B2 (ja) | 第ｖｉｉｉ因子キメラおよびハイブリッドポリペプチドならびにその使用法 | |
| US10898554B1 (en) | Factor IX polypeptides and methods of use thereof | |
| TWI629993B (zh) | 因子ｖｉｉｉ多肽調配物 | |
| HK40015680A (en) | Factor ix polypeptides and methods of use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20171114 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180323 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180323 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20181108 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181113 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190212 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190415 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190802 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20191101 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20191219 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200203 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20200427 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200826 |
|
| C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20200826 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20200918 |
|
| C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20200923 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20201023 |
|
| C211 | Notice of termination of reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C211 Effective date: 20201027 |
|
| C22 | Notice of designation (change) of administrative judge |
Free format text: JAPANESE INTERMEDIATE CODE: C22 Effective date: 20210713 |
|
| C13 | Notice of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: C13 Effective date: 20210921 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211213 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220120 |
|
| C23 | Notice of termination of proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C23 Effective date: 20220221 |
|
| C03 | Trial/appeal decision taken |
Free format text: JAPANESE INTERMEDIATE CODE: C03 Effective date: 20220317 |
|
| C30A | Notification sent |
Free format text: JAPANESE INTERMEDIATE CODE: C3012 Effective date: 20220317 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220413 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7058940 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |