JP2017523140A5 - - Google Patents

Info

Publication number

JP2017523140A5

JP2017523140A5 JP2016572453A JP2016572453A JP2017523140A5 JP 2017523140 A5 JP2017523140 A5 JP 2017523140A5 JP 2016572453 A JP2016572453 A JP 2016572453A JP 2016572453 A JP2016572453 A JP 2016572453A JP 2017523140 A5 JP2017523140 A5 JP 2017523140A5

Authority

JP

Japan

Prior art keywords

amino acid

polypeptide

seq

item

acid sequence

Prior art date

2015-06-12

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 229920001184 polypeptide Polymers 0.000 claims description 252
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 252
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 252
• 150000001413 amino acids Chemical group 0.000 claims description 148
• 108020001507 fusion proteins Proteins 0.000 claims description 26
• 102000037865 fusion proteins Human genes 0.000 claims description 26
• 230000002378 acidificating effect Effects 0.000 claims description 20
• 108060003951 Immunoglobulin Proteins 0.000 claims description 14
• 208000007502 anemia Diseases 0.000 claims description 14
• 102000018358 immunoglobulin Human genes 0.000 claims description 14
• 208000011580 syndromic disease Diseases 0.000 claims description 14
• 208000005980 beta thalassemia Diseases 0.000 claims description 12
• 102100040898 Growth/differentiation factor 11 Human genes 0.000 claims description 11
• 102100039939 Growth/differentiation factor 8 Human genes 0.000 claims description 11
• 101000893545 Homo sapiens Growth/differentiation factor 11 Proteins 0.000 claims description 11
• 101000886562 Homo sapiens Growth/differentiation factor 8 Proteins 0.000 claims description 11
• 208000002903 Thalassemia Diseases 0.000 claims description 8
• 206010040943 Skin Ulcer Diseases 0.000 claims description 7
• 231100000019 skin ulcer Toxicity 0.000 claims description 7
• 125000003473 lipid group Chemical group 0.000 claims description 4
• 230000004048 modification Effects 0.000 claims description 4
• 238000012986 modification Methods 0.000 claims description 4
• 235000001014 amino acid Nutrition 0.000 claims 29
• 238000000423 cell based assay Methods 0.000 claims 2
• 230000011664 signaling Effects 0.000 claims 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims 1
• 201000006288 alpha thalassemia Diseases 0.000 claims 1
• 235000003704 aspartic acid Nutrition 0.000 claims 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 claims 1
• 235000013922 glutamic acid Nutrition 0.000 claims 1
• 239000004220 glutamic acid Substances 0.000 claims 1
• 125000003275 alpha amino acid group Chemical group 0.000 description 159
• 239000005557 antagonist Substances 0.000 description 77
• 238000000034 method Methods 0.000 description 60
• 101100437153 Rattus norvegicus Acvr2b gene Proteins 0.000 description 15
• 238000009120 supportive therapy Methods 0.000 description 15
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 12
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
• 108010059616 Activins Proteins 0.000 description 9
• 108010092408 Eosinophil Peroxidase Proteins 0.000 description 9
• 102100026818 Inhibin beta E chain Human genes 0.000 description 9
• 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 9
• 239000000488 activin Substances 0.000 description 9
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 9
• 208000007056 sickle cell anemia Diseases 0.000 description 7
• 108010023082 activin A Proteins 0.000 description 6
• 239000002738 chelating agent Substances 0.000 description 6
• 230000013595 glycosylation Effects 0.000 description 6
• 238000006206 glycosylation reaction Methods 0.000 description 6
• 229910052742 iron Inorganic materials 0.000 description 6
• 102000004169 proteins and genes Human genes 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• 108091006084 receptor activators Proteins 0.000 description 6
• 230000002159 abnormal effect Effects 0.000 description 4
• 208000007475 hemolytic anemia Diseases 0.000 description 4
• XJOTXKZIRSHZQV-RXHOOSIZSA-N (3S)-3-amino-4-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S,3S)-1-[[(1R,6R,12R,17R,20S,23S,26R,31R,34R,39R,42S,45S,48S,51S,59S)-51-(4-aminobutyl)-31-[[(2S)-6-amino-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxohexan-2-yl]carbamoyl]-20-benzyl-23-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-48-(hydroxymethyl)-42-(1H-imidazol-4-ylmethyl)-59-(2-methylsulfanylethyl)-7,10,19,22,25,33,40,43,46,49,52,54,57,60,63,64-hexadecaoxo-3,4,14,15,28,29,36,37-octathia-8,11,18,21,24,32,41,44,47,50,53,55,58,61,62,65-hexadecazatetracyclo[32.19.8.26,17.212,39]pentahexacontan-26-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)[C@@H](C)O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@@H]4CSSC[C@H](NC(=O)[C@H](Cc5ccccc5)NC(=O)[C@@H](NC1=O)[C@@H](C)CC)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1cnc[nH]1)NC3=O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N2)C(=O)NCC(=O)N4)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XJOTXKZIRSHZQV-RXHOOSIZSA-N 0.000 description 3
• 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 3
• 108010074604 Epoetin Alfa Proteins 0.000 description 3
• TZXKOCQBRNJULO-UHFFFAOYSA-N Ferriprox Chemical compound CC1=C(O)C(=O)C=CN1C TZXKOCQBRNJULO-UHFFFAOYSA-N 0.000 description 3
• 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 description 3
• VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 3
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 3
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 3
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 3
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 3
• UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 3
• 102000007562 Serum Albumin Human genes 0.000 description 3
• 108010071390 Serum Albumin Proteins 0.000 description 3
• 208000025865 Ulcer Diseases 0.000 description 3
• 108010023079 activin B Proteins 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
• 230000009918 complex formation Effects 0.000 description 3
• 108010084052 continuous erythropoietin receptor activator Proteins 0.000 description 3
• 229960001489 deferasirox Drugs 0.000 description 3
• FMSOAWSKCWYLBB-VBGLAJCLSA-N deferasirox Chemical compound C1=CC(C(=O)O)=CC=C1N(N\C(N\1)=C\2C(C=CC=C/2)=O)C/1=C\1C(=O)C=CC=C/1 FMSOAWSKCWYLBB-VBGLAJCLSA-N 0.000 description 3
• 229960003266 deferiprone Drugs 0.000 description 3
• 229960000958 deferoxamine Drugs 0.000 description 3
• 229960003388 epoetin alfa Drugs 0.000 description 3
• 108010002601 epoetin beta Proteins 0.000 description 3
• 229960004579 epoetin beta Drugs 0.000 description 3
• 108010067416 epoetin delta Proteins 0.000 description 3
• 229950002109 epoetin delta Drugs 0.000 description 3
• 108010090921 epoetin omega Proteins 0.000 description 3
• 229950008767 epoetin omega Drugs 0.000 description 3
• 210000003743 erythrocyte Anatomy 0.000 description 3
• 230000000913 erythropoietic effect Effects 0.000 description 3
• 239000012634 fragment Substances 0.000 description 3
• 102000018511 hepcidin Human genes 0.000 description 3
• 108060003558 hepcidin Proteins 0.000 description 3
• 229940066919 hepcidin Drugs 0.000 description 3
• 229960001330 hydroxycarbamide Drugs 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 230000004807 localization Effects 0.000 description 3
• 229960001046 methoxy polyethylene glycol-epoetin beta Drugs 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 231100000397 ulcer Toxicity 0.000 description 3
• 108010019673 Darbepoetin alfa Proteins 0.000 description 2
• 229960005029 darbepoetin alfa Drugs 0.000 description 2
• 239000003814 drug Substances 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• -1 darbepoetin alpha Proteins 0.000 description 1
• 230000003319 supportive effect Effects 0.000 description 1