JP5697983B2 - 修飾成長ホルモンポリペプチド - Google Patents
修飾成長ホルモンポリペプチド Download PDFInfo
- Publication number
- JP5697983B2 JP5697983B2 JP2010528468A JP2010528468A JP5697983B2 JP 5697983 B2 JP5697983 B2 JP 5697983B2 JP 2010528468 A JP2010528468 A JP 2010528468A JP 2010528468 A JP2010528468 A JP 2010528468A JP 5697983 B2 JP5697983 B2 JP 5697983B2
- Authority
- JP
- Japan
- Prior art keywords
- seq
- nucleic acid
- acid sequence
- amino acid
- polypeptide
- 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.)
- Expired - Fee Related
Links
- 108010051696 Growth Hormone Proteins 0.000 title claims description 65
- 102000018997 Growth Hormone Human genes 0.000 title claims description 65
- 150000007523 nucleic acids Chemical class 0.000 claims description 69
- 239000000122 growth hormone Substances 0.000 claims description 64
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 53
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 52
- 229920001184 polypeptide Polymers 0.000 claims description 51
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 36
- 108020004707 nucleic acids Proteins 0.000 claims description 33
- 102000039446 nucleic acids Human genes 0.000 claims description 33
- 239000000710 homodimer Substances 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 102100020948 Growth hormone receptor Human genes 0.000 claims description 19
- 239000005557 antagonist Substances 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 10
- 108010068542 Somatotropin Receptors Proteins 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 206010000599 Acromegaly Diseases 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000003442 weekly effect Effects 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 229940124013 Growth hormone receptor antagonist Drugs 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 description 46
- 210000004027 cell Anatomy 0.000 description 18
- 238000000034 method Methods 0.000 description 15
- 101001075287 Homo sapiens Growth hormone receptor Proteins 0.000 description 13
- 201000011510 cancer Diseases 0.000 description 10
- 238000009396 hybridization Methods 0.000 description 10
- 201000009030 Carcinoma Diseases 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108091008146 restriction endonucleases Proteins 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 239000013598 vector Substances 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 230000035772 mutation Effects 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 239000013613 expression plasmid Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 238000007792 addition Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 3
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 102000005157 Somatostatin Human genes 0.000 description 3
- 108010056088 Somatostatin Proteins 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000001817 pituitary effect Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 229960000553 somatostatin Drugs 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 101710099093 Growth hormone receptor Proteins 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108700005078 Synthetic Genes Proteins 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000004198 anterior pituitary gland Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000002429 large intestine Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
- PUDHBTGHUJUUFI-SCTWWAJVSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2r)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-p Chemical compound C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 PUDHBTGHUJUUFI-SCTWWAJVSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 201000000274 Carcinosarcoma Diseases 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
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101001075374 Homo sapiens Gamma-glutamyl hydrolase Proteins 0.000 description 1
- 101000664737 Homo sapiens Somatotropin Proteins 0.000 description 1
- 229940123502 Hormone receptor antagonist Drugs 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-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
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 108010016076 Octreotide Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 101150052859 Slc9a1 gene Proteins 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 208000018554 digestive system carcinoma Diseases 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- -1 elixirs Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000004553 finger phalanx Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 210000004007 growth hormone secreting cell Anatomy 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 239000003689 hormone receptor blocking agent Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 210000001847 jaw Anatomy 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 108010021336 lanreotide Proteins 0.000 description 1
- 229960002437 lanreotide Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000001426 native polyacrylamide gel electrophoresis Methods 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000004412 neuroendocrine cell Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 229960002700 octreotide Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 108700037519 pegvisomant Proteins 0.000 description 1
- 229960002995 pegvisomant Drugs 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 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
- 208000010916 pituitary tumor Diseases 0.000 description 1
- 210000004258 portal system Anatomy 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000012747 synergistic agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000003853 toe phalanges Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/61—Growth hormone [GH], i.e. somatotropin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A61P5/08—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Endocrinology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97901007P | 2007-10-10 | 2007-10-10 | |
| US60/979,010 | 2007-10-10 | ||
| GBGB0719818.7A GB0719818D0 (en) | 2007-10-11 | 2007-10-11 | Growth hormone fusion polypeptides |
| GB0719818.7 | 2007-10-11 | ||
| PCT/GB2008/003056 WO2009047474A2 (en) | 2007-10-10 | 2008-09-10 | Modified growth hormone polypeptides |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011507487A JP2011507487A (ja) | 2011-03-10 |
| JP2011507487A5 JP2011507487A5 (enExample) | 2011-10-27 |
| JP5697983B2 true JP5697983B2 (ja) | 2015-04-08 |
Family
ID=38787949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010528468A Expired - Fee Related JP5697983B2 (ja) | 2007-10-10 | 2008-09-10 | 修飾成長ホルモンポリペプチド |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US8273552B2 (enExample) |
| EP (2) | EP2886553A1 (enExample) |
| JP (1) | JP5697983B2 (enExample) |
| KR (1) | KR20100067686A (enExample) |
| CN (1) | CN101932600B (enExample) |
| AR (1) | AR068038A1 (enExample) |
| AU (1) | AU2008309386A1 (enExample) |
| BR (1) | BRPI0818639A2 (enExample) |
| CA (1) | CA2701369A1 (enExample) |
| DK (1) | DK2209798T3 (enExample) |
| ES (1) | ES2532600T3 (enExample) |
| GB (1) | GB0719818D0 (enExample) |
| IL (1) | IL203073A0 (enExample) |
| MX (1) | MX2010003892A (enExample) |
| RU (1) | RU2471808C2 (enExample) |
| TW (1) | TW200918098A (enExample) |
| WO (1) | WO2009047474A2 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0606946D0 (en) * | 2006-04-06 | 2006-05-17 | Asterion Ltd | Polypeptide antagonist |
| GB201104285D0 (en) * | 2011-03-15 | 2011-04-27 | Asterion Ltd | Modified receptor fusion proteins |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH20A (fr) * | 1888-12-05 | Joseph Magnat | Une pompe à bière automatique fonctionnant par la pression de l'eau | |
| DE851925T1 (de) * | 1995-09-21 | 2003-08-14 | Genentech Inc., San Francisco | Varianten des menschlichen wachstumshormons |
| GB0018891D0 (en) * | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
| EP1290170A2 (en) * | 2000-06-16 | 2003-03-12 | Asterion Limited | Binding agents: chimeric ligand/receptor proteins |
| EP1456398B1 (en) * | 2001-11-21 | 2011-05-11 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Recovery of recombinant human parainfluenza virus type 1 (hpivi) from cdna |
| GB2389115B (en) * | 2001-12-14 | 2005-03-16 | Asterion Ltd | Polypeptide having a plurality of modified growth hormone receptor binding domains of growth hormone |
| US7625998B2 (en) * | 2003-04-09 | 2009-12-01 | Asterion Limited | Cytokine polypeptides and antibodies containing a signal sequence for the attachment of glycosylphosphatidylinositol |
| US20090221477A1 (en) * | 2004-07-26 | 2009-09-03 | Asterion Limited | Linkers |
| GB0717985D0 (en) * | 2007-07-20 | 2007-10-24 | Asterion Ltd | Growth hormone fusion proteins |
| JP2011512134A (ja) * | 2008-02-19 | 2011-04-21 | アステリオン・リミテッド | 修飾リンカー |
-
2007
- 2007-10-11 GB GBGB0719818.7A patent/GB0719818D0/en not_active Ceased
-
2008
- 2008-08-20 TW TW097131758A patent/TW200918098A/zh unknown
- 2008-08-26 AR ARP080103700A patent/AR068038A1/es not_active Application Discontinuation
- 2008-09-10 EP EP14197613.4A patent/EP2886553A1/en not_active Withdrawn
- 2008-09-10 WO PCT/GB2008/003056 patent/WO2009047474A2/en not_active Ceased
- 2008-09-10 CN CN200880106595.1A patent/CN101932600B/zh not_active Expired - Fee Related
- 2008-09-10 BR BRPI0818639 patent/BRPI0818639A2/pt not_active Application Discontinuation
- 2008-09-10 KR KR1020107010215A patent/KR20100067686A/ko not_active Ceased
- 2008-09-10 ES ES08788565.3T patent/ES2532600T3/es active Active
- 2008-09-10 MX MX2010003892A patent/MX2010003892A/es not_active Application Discontinuation
- 2008-09-10 EP EP08788565.3A patent/EP2209798B1/en not_active Not-in-force
- 2008-09-10 DK DK08788565T patent/DK2209798T3/en active
- 2008-09-10 AU AU2008309386A patent/AU2008309386A1/en not_active Abandoned
- 2008-09-10 JP JP2010528468A patent/JP5697983B2/ja not_active Expired - Fee Related
- 2008-09-10 CA CA2701369A patent/CA2701369A1/en not_active Abandoned
- 2008-09-10 US US12/678,282 patent/US8273552B2/en not_active Expired - Fee Related
- 2008-09-10 RU RU2010103159/10A patent/RU2471808C2/ru not_active IP Right Cessation
-
2009
- 2009-12-31 IL IL203073A patent/IL203073A0/en unknown
-
2012
- 2012-08-22 US US13/592,252 patent/US20120322735A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| RU2471808C2 (ru) | 2013-01-10 |
| AR068038A1 (es) | 2009-10-28 |
| RU2010103159A (ru) | 2011-11-20 |
| EP2886553A1 (en) | 2015-06-24 |
| US20120322735A1 (en) | 2012-12-20 |
| KR20100067686A (ko) | 2010-06-21 |
| TW200918098A (en) | 2009-05-01 |
| WO2009047474A2 (en) | 2009-04-16 |
| MX2010003892A (es) | 2010-05-17 |
| GB0719818D0 (en) | 2007-11-21 |
| DK2209798T3 (en) | 2015-03-23 |
| EP2209798B1 (en) | 2014-12-31 |
| ES2532600T3 (es) | 2015-03-30 |
| CN101932600B (zh) | 2014-05-28 |
| IL203073A0 (en) | 2010-11-30 |
| EP2209798A2 (en) | 2010-07-28 |
| BRPI0818639A2 (pt) | 2015-04-07 |
| WO2009047474A3 (en) | 2010-09-02 |
| CA2701369A1 (en) | 2009-04-16 |
| CN101932600A (zh) | 2010-12-29 |
| AU2008309386A1 (en) | 2009-04-16 |
| JP2011507487A (ja) | 2011-03-10 |
| US8273552B2 (en) | 2012-09-25 |
| US20100197589A1 (en) | 2010-08-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI760333B (zh) | Ｇｄｆ１５融合蛋白及其用途 | |
| CN101679988B (zh) | 结合生长因子的融合蛋白 | |
| AU778939B2 (en) | Expression and export of anti-obesity proteins as Fc fusion proteins | |
| FI117055B (fi) | Menetelmä asyloidun insuliinin valmistamiseksi | |
| EP0954588B1 (en) | Ob fusion protein compositions and methods | |
| US20110077199A1 (en) | Growth hormone polypeptides and methods of making and using same | |
| AU2008278907B2 (en) | Growth hormone fusion proteins | |
| JP2010043100A (ja) | 修飾ポリペプチド | |
| WO2010017198A2 (en) | Fgfr extracellular domain acidic region muteins | |
| CN110678550B (zh) | 长效肾上腺髓质素衍生物 | |
| JP5697983B2 (ja) | 修飾成長ホルモンポリペプチド | |
| EP3711772A1 (en) | Recombinant proteins and fusion proteins | |
| JPH02207099A (ja) | ＰＴＨｒＰ関連ペプチド、その製造法及び用途 | |
| JP6029601B2 (ja) | 改変受容体融合タンパク質 | |
| CA3190959A1 (en) | Exendin-4 peptide analogues | |
| HK1021388B (en) | Ob fusion protein compositions and methods |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110830 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110830 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130222 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130516 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130523 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130614 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130621 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130718 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130725 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130821 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140418 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140710 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140717 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141017 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150130 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150212 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5697983 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |