NO323043B1 - peptid, farmasoytisk preparat som omfatter et slikt, og anvendelse av et slikt peptid til fremstilling av et farmasoytisk preparat for appetittundertrykkelse eller metthetsinduksjon. - Google Patents
peptid, farmasoytisk preparat som omfatter et slikt, og anvendelse av et slikt peptid til fremstilling av et farmasoytisk preparat for appetittundertrykkelse eller metthetsinduksjon. Download PDFInfo
- Publication number
- NO323043B1 NO323043B1 NO19984005A NO984005A NO323043B1 NO 323043 B1 NO323043 B1 NO 323043B1 NO 19984005 A NO19984005 A NO 19984005A NO 984005 A NO984005 A NO 984005A NO 323043 B1 NO323043 B1 NO 323043B1
- Authority
- NO
- Norway
- Prior art keywords
- peptide
- arg
- glp
- lys
- ile
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 69
- 206010061428 decreased appetite Diseases 0.000 title claims abstract description 27
- 230000003880 negative regulation of appetite Effects 0.000 title claims abstract description 17
- 230000036186 satiety Effects 0.000 title claims abstract description 13
- 235000019627 satiety Nutrition 0.000 title claims abstract description 13
- 230000006698 induction Effects 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 title 2
- 239000012634 fragment Substances 0.000 claims abstract description 9
- 238000011282 treatment Methods 0.000 claims abstract description 9
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 230000001939 inductive effect Effects 0.000 claims abstract description 5
- 238000011321 prophylaxis Methods 0.000 claims abstract description 4
- 208000008589 Obesity Diseases 0.000 claims abstract description 3
- 235000020824 obesity Nutrition 0.000 claims abstract description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 16
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical group C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 13
- 102100040918 Pro-glucagon Human genes 0.000 claims description 13
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 235000021229 appetite regulation Nutrition 0.000 claims description 2
- OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 claims 3
- JQFZHHSQMKZLRU-IUCAKERBSA-N Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N JQFZHHSQMKZLRU-IUCAKERBSA-N 0.000 claims 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims 3
- NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 claims 3
- 108010068380 arginylarginine Proteins 0.000 claims 3
- 108010062796 arginyllysine Proteins 0.000 claims 3
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 13
- 150000001413 amino acids Chemical class 0.000 abstract description 7
- 108010088406 Glucagon-Like Peptides Proteins 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 61
- 101800000221 Glucagon-like peptide 2 Proteins 0.000 description 54
- 108010076504 Protein Sorting Signals Proteins 0.000 description 28
- 102400000326 Glucagon-like peptide 2 Human genes 0.000 description 25
- TWSALRJGPBVBQU-PKQQPRCHSA-N glucagon-like peptide 2 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=CC=C1 TWSALRJGPBVBQU-PKQQPRCHSA-N 0.000 description 25
- 108091028043 Nucleic acid sequence Proteins 0.000 description 23
- 108090000623 proteins and genes Proteins 0.000 description 23
- 239000013598 vector Substances 0.000 description 20
- 238000000034 method Methods 0.000 description 17
- 108020004414 DNA Proteins 0.000 description 15
- 108060003199 Glucagon Proteins 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 15
- 206010028980 Neoplasm Diseases 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 102000051325 Glucagon Human genes 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 14
- 229960004666 glucagon Drugs 0.000 description 14
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 11
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 229930006000 Sucrose Natural products 0.000 description 10
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 10
- 239000002299 complementary DNA Substances 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000005720 sucrose Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 230000003248 secreting effect Effects 0.000 description 9
- 108010065511 Amylases Proteins 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 241000228245 Aspergillus niger Species 0.000 description 7
- 101500028771 Homo sapiens Glucagon-like peptide 2 Proteins 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000004382 Amylase Substances 0.000 description 6
- 102000013142 Amylases Human genes 0.000 description 6
- 206010018404 Glucagonoma Diseases 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 235000019418 amylase Nutrition 0.000 description 6
- 238000002523 gelfiltration Methods 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 210000005253 yeast cell Anatomy 0.000 description 6
- 240000006439 Aspergillus oryzae Species 0.000 description 5
- 102000035554 Proglucagon Human genes 0.000 description 5
- 108010058003 Proglucagon Proteins 0.000 description 5
- 230000001539 anorectic effect Effects 0.000 description 5
- 230000035622 drinking Effects 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 241000233866 Fungi Species 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 208000022531 anorexia Diseases 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 210000000349 chromosome Anatomy 0.000 description 4
- 230000002538 fungal effect Effects 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 210000001322 periplasm Anatomy 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000228212 Aspergillus Species 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 3
- 102100022624 Glucoamylase Human genes 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- 241000276498 Pollachius virens Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 108090000637 alpha-Amylases Proteins 0.000 description 3
- 102000004139 alpha-Amylases Human genes 0.000 description 3
- 229940024171 alpha-amylase Drugs 0.000 description 3
- 239000002830 appetite depressant Substances 0.000 description 3
- -1 aromatic amino acids Chemical class 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 235000012631 food intake Nutrition 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- 102100034042 Alcohol dehydrogenase 1C Human genes 0.000 description 2
- 241000351920 Aspergillus nidulans Species 0.000 description 2
- 241000193744 Bacillus amyloliquefaciens Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- 108091005658 Basic proteases Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- 101000796894 Coturnix japonica Alcohol dehydrogenase 1 Proteins 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 241000193385 Geobacillus stearothermophilus Species 0.000 description 2
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 2
- 108010024044 Glucagon-Like Peptide-2 Receptor Proteins 0.000 description 2
- 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 description 2
- 102100032879 Glucagon-like peptide 2 receptor Human genes 0.000 description 2
- 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 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 101000780463 Homo sapiens Alcohol dehydrogenase 1C Proteins 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 2
- 241000235648 Pichia Species 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 101500026175 Rattus norvegicus Glucagon-like peptide 2 Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 101000968489 Rhizomucor miehei Lipase Proteins 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical group C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000003277 amino acid sequence analysis Methods 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 210000003158 enteroendocrine cell Anatomy 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000004634 feeding behavior Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 101150021650 gluA gene Proteins 0.000 description 2
- 210000001511 glucagon-secreting cell Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000000185 intracerebroventricular administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 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
- 239000003550 marker Substances 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000002751 oligonucleotide probe Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- OCUSNPIJIZCRSZ-ZTZWCFDHSA-N (2s)-2-amino-3-methylbutanoic acid;(2s)-2-amino-4-methylpentanoic acid;(2s,3s)-2-amino-3-methylpentanoic acid Chemical compound CC(C)[C@H](N)C(O)=O.CC[C@H](C)[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O OCUSNPIJIZCRSZ-ZTZWCFDHSA-N 0.000 description 1
- DDYAPMZTJAYBOF-ZMYDTDHYSA-N (3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-4-amino-1-[[(2S,3S)-1-[[(1S)-1-carboxyethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoic acid Chemical class [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)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](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O DDYAPMZTJAYBOF-ZMYDTDHYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 1
- 101800002326 Adipokinetic hormone Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010021809 Alcohol dehydrogenase Proteins 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
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
- 102000035101 Aspartic proteases Human genes 0.000 description 1
- 108091005502 Aspartic proteases Proteins 0.000 description 1
- 241001513093 Aspergillus awamori Species 0.000 description 1
- 241001367049 Autographa Species 0.000 description 1
- 101150071434 BAR1 gene Proteins 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000193752 Bacillus circulans Species 0.000 description 1
- 241000193749 Bacillus coagulans Species 0.000 description 1
- 241000193422 Bacillus lentus Species 0.000 description 1
- 108010029675 Bacillus licheniformis alpha-amylase Proteins 0.000 description 1
- 241000194107 Bacillus megaterium Species 0.000 description 1
- 241000194103 Bacillus pumilus Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 241000193388 Bacillus thuringiensis Species 0.000 description 1
- 241000149420 Bothrometopus brevis Species 0.000 description 1
- 101100280051 Brucella abortus biovar 1 (strain 9-941) eryH gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000005367 Carboxypeptidases Human genes 0.000 description 1
- 108010006303 Carboxypeptidases Proteins 0.000 description 1
- 241000699662 Cricetomys gambianus Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000223218 Fusarium Species 0.000 description 1
- 241000223221 Fusarium oxysporum Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 108010063919 Glucagon Receptors Proteins 0.000 description 1
- 102100040890 Glucagon receptor Human genes 0.000 description 1
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101100295959 Halobacterium salinarum (strain ATCC 700922 / JCM 11081 / NRC-1) arcB gene Proteins 0.000 description 1
- 241000125500 Hedypnois rhagadioloides Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000886868 Homo sapiens Gastric inhibitory polypeptide Proteins 0.000 description 1
- 101000741885 Homo sapiens Protection of telomeres protein 1 Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 241001135569 Human adenovirus 5 Species 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 108700001097 Insect Genes Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 241000235649 Kluyveromyces Species 0.000 description 1
- 241001138401 Kluyveromyces lactis Species 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 241000235087 Lachancea kluyveri Species 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
- 241000255777 Lepidoptera Species 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000255908 Manduca sexta Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100235161 Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) lerI gene Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 101100378536 Ovis aries ADRB1 gene Proteins 0.000 description 1
- 241000194109 Paenibacillus lautus Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 101710182846 Polyhedrin Proteins 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100038745 Protection of telomeres protein 1 Human genes 0.000 description 1
- 101500026178 Rattus norvegicus Glucagon-like peptide 1 Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000235403 Rhizomucor miehei Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 241000235346 Schizosaccharomyces Species 0.000 description 1
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241000187398 Streptomyces lividans Species 0.000 description 1
- 241001468239 Streptomyces murinus Species 0.000 description 1
- 101500014015 Sus scrofa Glucagon-like peptide 2 Proteins 0.000 description 1
- 101150033985 TPI gene Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 241000223258 Thermomyces lanuginosus Species 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- 241000255993 Trichoplusia ni Species 0.000 description 1
- 102000005924 Triose-Phosphate Isomerase Human genes 0.000 description 1
- 108700015934 Triose-phosphate isomerases Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108091034131 VA RNA Proteins 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 108010048241 acetamidase Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 101150069003 amdS gene Proteins 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000578 anorexic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 101150008194 argB gene Proteins 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 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 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003398 denaturant Substances 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000008508 epithelial proliferation Effects 0.000 description 1
- 238000002481 ethanol extraction Methods 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000001400 expression cloning Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013350 formula milk Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 101150039489 lysZ gene Proteins 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 101150095344 niaD gene Proteins 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 101150054232 pyrG gene Proteins 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 210000004739 secretory vesicle Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 101150080369 tpiA gene Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000004580 weight loss Effects 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
- C07K14/605—Glucagons
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Endocrinology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK23196 | 1996-03-01 | ||
| DK23096 | 1996-03-01 | ||
| PCT/DK1997/000086 WO1997031943A1 (en) | 1996-03-01 | 1997-02-27 | Use of a pharmaceutical composition comprising an appetite-suppressing peptide |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO984005L NO984005L (no) | 1998-08-31 |
| NO984005D0 NO984005D0 (no) | 1998-08-31 |
| NO323043B1 true NO323043B1 (no) | 2006-12-27 |
Family
ID=26063575
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19984005A NO323043B1 (no) | 1996-03-01 | 1998-08-31 | peptid, farmasoytisk preparat som omfatter et slikt, og anvendelse av et slikt peptid til fremstilling av et farmasoytisk preparat for appetittundertrykkelse eller metthetsinduksjon. |
| NO2013006C NO2013006I1 (no) | 1996-03-01 | 2013-03-12 | Teduglutide i alle dens former slik som de er beskyttet av de grunnleggende patentene |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2013006C NO2013006I1 (no) | 1996-03-01 | 2013-03-12 | Teduglutide i alle dens former slik som de er beskyttet av de grunnleggende patentene |
Country Status (22)
| Country | Link |
|---|---|
| EP (4) | EP2295453A3 (pt) |
| JP (1) | JP4064460B2 (pt) |
| KR (1) | KR100611130B1 (pt) |
| CN (1) | CN1112367C (pt) |
| AT (3) | ATE395359T1 (pt) |
| AU (1) | AU710818B2 (pt) |
| BR (1) | BR9707807A (pt) |
| CA (1) | CA2246733C (pt) |
| CY (2) | CY2619B2 (pt) |
| CZ (1) | CZ297338B6 (pt) |
| DE (3) | DE69738695D1 (pt) |
| DK (2) | DK1975177T3 (pt) |
| ES (3) | ES2306685T3 (pt) |
| FR (1) | FR13C0009I2 (pt) |
| HU (1) | HU229234B1 (pt) |
| IL (1) | IL125805A0 (pt) |
| NO (2) | NO323043B1 (pt) |
| PL (1) | PL187095B1 (pt) |
| PT (1) | PT1975177E (pt) |
| RU (1) | RU2197261C2 (pt) |
| UA (1) | UA70283C2 (pt) |
| WO (1) | WO1997031943A1 (pt) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6184201B1 (en) | 1995-04-14 | 2001-02-06 | Nps Allelix Corp. | Intestinotrophic glucagon-like peptide-2 analogs |
| US5990077A (en) | 1995-04-14 | 1999-11-23 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
| US5834428A (en) | 1995-04-14 | 1998-11-10 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
| US6852690B1 (en) | 1995-08-22 | 2005-02-08 | Amylin Pharmaceuticals, Inc. | Method and composition for enhanced parenteral nutrition |
| CA2246733C (en) * | 1996-03-01 | 2010-07-20 | Novo Nordisk A/S | Use of a pharmaceutical composition comprising an appetite-suppressing peptide |
| EP1231219B1 (en) | 1996-04-12 | 2010-08-25 | 1149336 Ontario Inc. | GLucagon-like peptide-2 analogs |
| US7235627B2 (en) | 1996-08-30 | 2007-06-26 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| US6458924B2 (en) | 1996-08-30 | 2002-10-01 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| UA65549C2 (uk) | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
| ES2290799T3 (es) * | 1996-11-12 | 2008-02-16 | Novo Nordisk A/S | Uso de peptidos glp-1. |
| US6051557A (en) * | 1997-05-16 | 2000-04-18 | 1149336 Ontario Inc. | Methods of enhancing functioning of the upper gastrointestinal tract |
| ATE273996T1 (de) * | 1997-09-12 | 2004-09-15 | Pharis Biotec Gmbh | Zusammensetzung zur therapie von diabetes mellitus und fettsucht |
| EP1049486A4 (en) | 1997-12-05 | 2006-01-04 | Lilly Co Eli | GLP-1 FORMULATIONS |
| JP2002508162A (ja) * | 1998-02-27 | 2002-03-19 | ノボ ノルディスク アクティーゼルスカブ | Ｎ末端を短縮したｇｌｐ−１誘導体 |
| AU2610899A (en) * | 1998-02-27 | 1999-09-15 | Novo Nordisk A/S | N-terminally modified glp-1 derivatives |
| JP2002504527A (ja) * | 1998-02-27 | 2002-02-12 | ノボ ノルディスク アクティーゼルスカブ | 部分的に組織化したミセル様凝集物を形成する２５％を越えるヘリックス成分を有するｇｌｐ−２誘導体 |
| WO1999047161A1 (en) * | 1998-03-19 | 1999-09-23 | Bionebraska, Inc. | Human appetite control by glucagon-like peptide receptor binding compounds |
| US6998387B1 (en) | 1998-03-19 | 2006-02-14 | Amylin Pharmaceuticals, Inc. | Human appetite control by glucagon-like peptide receptor binding compounds |
| GB2396815B (en) | 1999-10-27 | 2004-09-08 | Phytopharm Plc | A composition comprising a pregnenone derivative and an NSAID |
| GB2363985B (en) | 2000-06-30 | 2004-09-29 | Phytopharm Plc | Extracts,compounds & pharmaceutical compositions having anti-diabetic activity and their use |
| ES2310192T3 (es) * | 2000-09-18 | 2009-01-01 | Sanos Bioscience A/S | Uso de peptidos glp-2. |
| US7371721B2 (en) | 2000-09-18 | 2008-05-13 | Sanos Bioscience A/S | Use of GLP-2 and related compounds for the treatment, prevention, diagnosis, and prognosis of bone-related disorders and calcium homeostasis related syndromes |
| US7186683B2 (en) | 2000-09-18 | 2007-03-06 | Sanos Bioscience A/S | Use of GLP for the treatment, prevention, diagnosis, and prognosis of bone-related and nutrition-related disorders |
| WO2002043709A1 (fr) | 2000-12-01 | 2002-06-06 | Takeda Chemical Industries, Ltd. | Procede de production d'une preparation contenant une substance bioactive |
| GB0121709D0 (en) * | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
| WO2003059934A2 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| ES2545090T3 (es) | 2001-12-21 | 2015-09-08 | Human Genome Sciences, Inc. | Proteínas de fusión de albúmina y GCSF |
| US7411039B2 (en) | 2002-10-14 | 2008-08-12 | Novo Nordisk A/S | GLP-2 compounds, formulations, and uses thereof |
| EP1592471B1 (en) | 2003-02-04 | 2011-03-23 | Novo Nordisk A/S | Injection device with rotatable dose setting mechanism |
| JP4865565B2 (ja) | 2003-12-09 | 2012-02-01 | ノヴォ ノルディスク アー／エス | Ｇｌｐ−１アゴニストを用いた食物選択の制御 |
| ES2397241T3 (es) | 2004-01-21 | 2013-03-05 | Novo Nordisk Health Care Ag | Conjugación de péptidos mediante transglutaminasa |
| SI1729795T1 (sl) | 2004-02-09 | 2016-04-29 | Human Genome Sciences, Inc. | Albuminski fuzijski proteini |
| US7456254B2 (en) | 2004-04-15 | 2008-11-25 | Alkermes, Inc. | Polymer-based sustained release device |
| KR101040415B1 (ko) * | 2004-04-15 | 2011-06-09 | 알케르메스,인코포레이티드 | 중합체 기재 지속적 방출 방법 |
| EP1758575A1 (en) | 2004-06-11 | 2007-03-07 | Novo Nordisk A/S | Counteracting drug-induced obesity using glp-1 agonists |
| US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
| ATE498631T1 (de) † | 2005-05-04 | 2011-03-15 | Zealand Pharma As | Glucagon-like-peptide-2- (glp-2-) analoga |
| ES2336575T3 (es) | 2005-09-22 | 2010-04-14 | Biocompatibles Uk Limited | Polipeptidos de fusion glp-1 (peptido-1 similar al glucagon) con resistencia aumentada a la peptidasa. |
| ATE444741T1 (de) | 2006-05-10 | 2009-10-15 | Biocompatibles Uk Ltd | Glp-1 peptide enthaltende kugelförmige mikrokapseln, deren produktion und deren verwendung |
| EP2363112B8 (en) | 2006-08-09 | 2018-11-21 | Intarcia Therapeutics, Inc. | Osmotic delivery systems and piston assemblies |
| CN101573376B (zh) | 2006-11-08 | 2013-11-06 | 西兰制药公司 | 选择性胰高血糖素样肽-2（glp-2）类似物 |
| EP2157967B1 (en) | 2007-04-23 | 2013-01-16 | Intarcia Therapeutics, Inc | Suspension formulations of insulinotropic peptides and uses thereof |
| CA2694863A1 (en) * | 2007-08-16 | 2009-02-19 | Garvan Institute Of Medical Research | Agents and methods for modulating macrophage inhibitory cytokine (mic-1) activity |
| US8343140B2 (en) | 2008-02-13 | 2013-01-01 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
| ES2360782B1 (es) * | 2009-07-28 | 2012-03-12 | Grifols, S.A. | Medios para cultivo de células de mamíferos que comprenden sobrenadante de etapas del fraccionamiento de Cohn y uso de los mismos. |
| AU2010298733B2 (en) | 2009-09-28 | 2014-10-09 | Intarcia Therapeutics, Inc. | Rapid establishment and/or termination of substantial steady-state drug delivery |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| CN104540850B (zh) | 2012-05-03 | 2018-05-18 | 西兰制药公司 | 胰高血糖素样肽2(glp-2)类似物 |
| WO2014010586A1 (ja) | 2012-07-10 | 2014-01-16 | 武田薬品工業株式会社 | 注射用製剤 |
| US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
| KR101576126B1 (ko) | 2014-12-29 | 2015-12-11 | 부경대학교 산학협력단 | αＡＬ１４ 펩타이드를 유효성분으로 함유하는 신규 비만 예방 및 치료용 약학적 조성물 |
| KR101669140B1 (ko) * | 2015-04-28 | 2016-10-26 | (주)케어젠 | 항비만 및 항당뇨 효능을 갖는 펩타이드 및 이의 용도 |
| EP3302354B1 (en) | 2015-06-03 | 2023-10-04 | i2o Therapeutics, Inc. | Implant placement systems |
| US10188135B2 (en) * | 2015-11-04 | 2019-01-29 | Stokley-Van Camp, Inc. | Method for inducing satiety |
| KR101887576B1 (ko) * | 2016-04-15 | 2018-08-13 | (주)케어젠 | 항비만 및 항당뇨 효능을 갖는 펩타이드 및 이의 용도 |
| RU2760007C2 (ru) | 2016-05-16 | 2021-11-22 | Интарсия Терапьютикс, Инк. | Полипептиды, селективные к рецепторам глюкагона, и способы их применения |
| USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
| USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
| RU2753193C2 (ru) | 2016-12-09 | 2021-08-12 | Зилэнд Фарма А/С | Ацилированные двойные агонисты glp-1/glp-2 |
| IL307966A (en) | 2017-01-03 | 2023-12-01 | Intarcia Therapeutics Inc | Methods involving continuous administration of a GLP-1 receptor agonist and co-administration of a drug |
| AU2020268087A1 (en) * | 2019-05-06 | 2021-11-25 | The University Of Sydney | Methods for the fractionation of proteins |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4203570A (en) | 1978-08-23 | 1980-05-20 | The Western States Machine Company | Power-operated loading gate for centrifugal machines incorporating an auxiliary drive device |
| US4546082A (en) | 1982-06-17 | 1985-10-08 | Regents Of The Univ. Of California | E. coli/Saccharomyces cerevisiae plasmid cloning vector containing the alpha-factor gene for secretion and processing of hybrid proteins |
| US4599311A (en) | 1982-08-13 | 1986-07-08 | Kawasaki Glenn H | Glycolytic promotersfor regulated protein expression: protease inhibitor |
| EP0116201B1 (en) | 1983-01-12 | 1992-04-22 | Chiron Corporation | Secretory expression in eukaryotes |
| WO1984004330A1 (en) | 1983-04-22 | 1984-11-08 | Amgen | Secretion of exogenous polypeptides from yeast |
| NZ207926A (en) | 1983-04-25 | 1988-04-29 | Genentech Inc | Use of yeast #a#-factor to assist in expression of proteins heterologus to yeast |
| US4745051A (en) | 1983-05-27 | 1988-05-17 | The Texas A&M University System | Method for producing a recombinant baculovirus expression vector |
| US4870008A (en) | 1983-08-12 | 1989-09-26 | Chiron Corporation | Secretory expression in eukaryotes |
| US4879236A (en) | 1984-05-16 | 1989-11-07 | The Texas A&M University System | Method for producing a recombinant baculovirus expression vector |
| US4931373A (en) | 1984-05-25 | 1990-06-05 | Zymogenetics, Inc. | Stable DNA constructs for expression of α-1 antitrypsin |
| DK58285D0 (da) | 1984-05-30 | 1985-02-08 | Novo Industri As | Peptider samt fremstilling og anvendelse deraf |
| US4766073A (en) | 1985-02-25 | 1988-08-23 | Zymogenetics Inc. | Expression of biologically active PDGF analogs in eucaryotic cells |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4882279A (en) | 1985-10-25 | 1989-11-21 | Phillips Petroleum Company | Site selective genomic modification of yeast of the genus pichia |
| JP2523562B2 (ja) | 1985-10-25 | 1996-08-14 | ザイモジェネティックス インコーポレーテッド | 外来タンパク質を分泌することを目的としたｂａｒ１の使用法 |
| AU607690B2 (en) | 1985-12-24 | 1991-03-14 | Marion Laboratories, Inc. | Use of synthetic sulfated saccharides to enhance wound healing |
| US4935349A (en) | 1986-01-17 | 1990-06-19 | Zymogenetics, Inc. | Expression of higher eucaryotic genes in aspergillus |
| US5024947A (en) | 1987-07-24 | 1991-06-18 | Cetus Corporation | Serum free media for the growth on insect cells and expression of products thereby |
| ATE170557T1 (de) | 1987-07-24 | 1998-09-15 | Chiron Corp | Züchtung von insektenzellen mit airlift-reaktoren |
| DK463887D0 (da) | 1987-09-07 | 1987-09-07 | Novo Industri As | Gaerleader |
| US5037743A (en) | 1988-08-05 | 1991-08-06 | Zymogenetics, Inc. | BAR1 secretion signal |
| WO1990005783A1 (en) | 1988-11-18 | 1990-05-31 | Cetus Corporation | Insect signal peptide mediated secretion of recombinant proteins |
| GB8910962D0 (en) | 1989-05-12 | 1989-06-28 | Natural Environment Res | Novel baculovirus expression vectors and use thereof in the expression of foreign proteins in insects or insect cells |
| US5162222A (en) | 1989-07-07 | 1992-11-10 | Guarino Linda A | Use of baculovirus early promoters for expression of foreign genes in stably transformed insect cells or recombinant baculoviruses |
| US5077214A (en) | 1989-07-07 | 1991-12-31 | The Texas A&M University System | Use of baculovirus early promoters for expression of foreign genes in stably transformed insect cells |
| US5155037A (en) | 1989-08-04 | 1992-10-13 | The Texas A&M University System | Insect signal sequences useful to improve the efficiency of processing and secretion of foreign genes in insect systems |
| US5023328A (en) | 1989-08-04 | 1991-06-11 | The Texas A&M University System | Lepidopteran AKH signal sequence |
| DK300090D0 (da) | 1990-12-19 | 1990-12-19 | Novo Nordisk As | Fremgangsmaade til fremstilling af leadersekvenser |
| DK36392D0 (da) * | 1992-03-19 | 1992-03-19 | Novo Nordisk As | Anvendelse af kemisk forbindelse |
| US5990077A (en) | 1995-04-14 | 1999-11-23 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
| CA2246733C (en) * | 1996-03-01 | 2010-07-20 | Novo Nordisk A/S | Use of a pharmaceutical composition comprising an appetite-suppressing peptide |
-
1997
- 1997-02-27 CA CA2246733A patent/CA2246733C/en not_active Expired - Lifetime
- 1997-02-27 CZ CZ0273698A patent/CZ297338B6/cs not_active IP Right Cessation
- 1997-02-27 AT AT01122701T patent/ATE395359T1/de not_active IP Right Cessation
- 1997-02-27 DE DE69738695T patent/DE69738695D1/de not_active Revoked
- 1997-02-27 EP EP10180925A patent/EP2295453A3/en not_active Withdrawn
- 1997-02-27 AT AT97905000T patent/ATE227737T1/de active
- 1997-02-27 ES ES01122701T patent/ES2306685T3/es not_active Expired - Lifetime
- 1997-02-27 ES ES08103786T patent/ES2364705T3/es not_active Expired - Lifetime
- 1997-02-27 EP EP08103786A patent/EP1975177B1/en not_active Expired - Lifetime
- 1997-02-27 EP EP01122701A patent/EP1231218B1/en not_active Revoked
- 1997-02-27 IL IL12580597A patent/IL125805A0/xx not_active IP Right Cessation
- 1997-02-27 WO PCT/DK1997/000086 patent/WO1997031943A1/en active IP Right Grant
- 1997-02-27 DE DE69740176T patent/DE69740176D1/de not_active Expired - Lifetime
- 1997-02-27 UA UA98084651A patent/UA70283C2/uk unknown
- 1997-02-27 AT AT08103786T patent/ATE505485T1/de active
- 1997-02-27 CN CN97193525A patent/CN1112367C/zh not_active Expired - Lifetime
- 1997-02-27 AU AU18715/97A patent/AU710818B2/en not_active Expired
- 1997-02-27 DK DK08103786.3T patent/DK1975177T3/da active
- 1997-02-27 JP JP53052497A patent/JP4064460B2/ja not_active Expired - Lifetime
- 1997-02-27 PT PT08103786T patent/PT1975177E/pt unknown
- 1997-02-27 DK DK97905000T patent/DK0891378T3/da active
- 1997-02-27 EP EP97905000A patent/EP0891378B1/en not_active Expired - Lifetime
- 1997-02-27 PL PL97328732A patent/PL187095B1/pl unknown
- 1997-02-27 BR BR9707807A patent/BR9707807A/pt not_active Application Discontinuation
- 1997-02-27 RU RU98117915/14A patent/RU2197261C2/ru active
- 1997-02-27 DE DE69717092T patent/DE69717092T2/de not_active Expired - Lifetime
- 1997-02-27 HU HU9902670A patent/HU229234B1/hu unknown
- 1997-02-27 ES ES97905000T patent/ES2187756T3/es not_active Expired - Lifetime
- 1997-02-27 KR KR1019980706861A patent/KR100611130B1/ko not_active IP Right Cessation
-
1998
- 1998-08-31 NO NO19984005A patent/NO323043B1/no not_active IP Right Cessation
-
2012
- 2012-10-12 CY CY201200011A patent/CY2619B2/el unknown
-
2013
- 2013-02-12 FR FR13C0009C patent/FR13C0009I2/fr active Active
- 2013-02-27 CY CY2013008C patent/CY2013008I1/el unknown
- 2013-03-12 NO NO2013006C patent/NO2013006I1/no unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0891378B1 (en) | Use of a pharmaceutical composition comprising an appetite-suppressing peptide | |
| US5912229A (en) | Use of a pharmaceutical composition comprising an appetite-suppressing peptide | |
| US12071456B2 (en) | Extended recombinant polypeptides and compositions comprising same | |
| US10000543B2 (en) | Glucose-regulating polypeptides and methods of making and using same | |
| US8703717B2 (en) | Growth hormone polypeptides and methods of making and using same | |
| KR101729986B1 (ko) | 프로테아제 내성 인슐린 유사체 | |
| JP2007161720A (ja) | 三つ葉状のペプチド２量体 | |
| US9849188B2 (en) | Growth hormone polypeptides and methods of making and using same | |
| CN113396157A (zh) | 具有降低的胰岛素受体结合亲和力的胰岛素类似物 | |
| KR20160007295A (ko) | 인슐린 아날로그 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| SPCF | Filing of supplementary protection certificate |
Free format text: PRODUCT NAME: TEDUGLUTIDE; REG. NO/DATE: EU/1/12/787/001 20120926 Spc suppl protection certif: 2013006 Filing date: 20130312 |
|
| SPCG | Granted supplementary protection certificate |
Free format text: PRODUCT NAME: TEDUGLUTIDE I ALLE DENS FORMER SLIK SOM DE ER BESKYTTET AV DE GRUNNLEGGENDE PATENTENE; REG. NO/DATE: EU/1/12/787/001 20120926 Spc suppl protection certif: 2013006 Filing date: 20130312 |
|
| MK1K | Patent expired | ||
| SPCX | Expiry of an spc |
Spc suppl protection certif: 2013006 |