JP2010536341A5 - - Google Patents

Info

Publication number

JP2010536341A5

JP2010536341A5 JP2010521048A JP2010521048A JP2010536341A5 JP 2010536341 A5 JP2010536341 A5 JP 2010536341A5 JP 2010521048 A JP2010521048 A JP 2010521048A JP 2010521048 A JP2010521048 A JP 2010521048A JP 2010536341 A5 JP2010536341 A5 JP 2010536341A5

Authority

JP

Japan

Prior art keywords

polypeptide

item

accessory

amino acids

composition

Prior art date

2008-08-15

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.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 102000004196 processed proteins & peptides Human genes 0.000 claims description 302
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 302
• 229920001184 polypeptide Polymers 0.000 claims description 301
• 150000001413 amino acids Chemical class 0.000 claims description 115
• 229940024606 amino acid Drugs 0.000 claims description 104
• 235000001014 amino acid Nutrition 0.000 claims description 104
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 100
• 239000000203 mixture Substances 0.000 claims description 88
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 49
• 239000004471 Glycine Substances 0.000 claims description 47
• 238000000034 method Methods 0.000 claims description 45
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 39
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 30
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 30
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 30
• 239000004473 Threonine Substances 0.000 claims description 30
• 235000013922 glutamic acid Nutrition 0.000 claims description 30
• 239000004220 glutamic acid Substances 0.000 claims description 30
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 27
• 235000004279 alanine Nutrition 0.000 claims description 27
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 25
• 235000003704 aspartic acid Nutrition 0.000 claims description 21
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 21
• 210000004027 cell Anatomy 0.000 claims description 21
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 17
• 239000004475 Arginine Substances 0.000 claims description 16
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 16
• 239000004472 Lysine Substances 0.000 claims description 16
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 16
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 12
• 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 12
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 12
• 102000002265 Human Growth Hormone Human genes 0.000 claims description 12
• 108010000521 Human Growth Hormone Proteins 0.000 claims description 12
• 239000000854 Human Growth Hormone Substances 0.000 claims description 12
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 12
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 12
• 235000009582 asparagine Nutrition 0.000 claims description 12
• 229960001230 asparagine Drugs 0.000 claims description 12
• 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 claims description 12
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 12
• 229940009098 aspartate Drugs 0.000 claims description 9
• 229930195712 glutamate Natural products 0.000 claims description 9
• 230000003252 repetitive effect Effects 0.000 claims description 9
• 108091005804 Peptidases Proteins 0.000 claims description 8
• 239000004365 Protease Substances 0.000 claims description 8
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 8
• 125000000539 amino acid group Chemical group 0.000 claims description 7
• 210000002966 serum Anatomy 0.000 claims description 7
• 102000003951 Erythropoietin Human genes 0.000 claims description 6
• 108090000394 Erythropoietin Proteins 0.000 claims description 6
• 108010011459 Exenatide Proteins 0.000 claims description 6
• HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=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](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 claims description 6
• 102000004877 Insulin Human genes 0.000 claims description 6
• 108090001061 Insulin Proteins 0.000 claims description 6
• 102000006992 Interferon-alpha Human genes 0.000 claims description 6
• 108010047761 Interferon-alpha Proteins 0.000 claims description 6
• 102000003996 Interferon-beta Human genes 0.000 claims description 6
• 108090000467 Interferon-beta Proteins 0.000 claims description 6
• 102000008070 Interferon-gamma Human genes 0.000 claims description 6
• 108010074328 Interferon-gamma Proteins 0.000 claims description 6
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 6
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 6
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 6
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 6
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 6
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 6
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 6
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 6
• 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 6
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 6
• 108010092464 Urate Oxidase Proteins 0.000 claims description 6
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 6
• 235000018417 cysteine Nutrition 0.000 claims description 6
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 6
• 229940105423 erythropoietin Drugs 0.000 claims description 6
• 229960001519 exenatide Drugs 0.000 claims description 6
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 6
• 238000000338 in vitro Methods 0.000 claims description 6
• 229940125396 insulin Drugs 0.000 claims description 6
• 229960003130 interferon gamma Drugs 0.000 claims description 6
• 229960001388 interferon-beta Drugs 0.000 claims description 6
• 229960000310 isoleucine Drugs 0.000 claims description 6
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 6
• 229930182817 methionine Natural products 0.000 claims description 6
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 6
• 108091033319 polynucleotide Proteins 0.000 claims description 6
• 102000040430 polynucleotide Human genes 0.000 claims description 6
• 239000002157 polynucleotide Substances 0.000 claims description 6
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 6
• GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound 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(=O)NCC(O)=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 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 claims description 6
• 239000004474 valine Substances 0.000 claims description 6
• -1 IL-1RA Chemical compound 0.000 claims description 5
• 238000003776 cleavage reaction Methods 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 108090000623 proteins and genes Proteins 0.000 claims description 5
• 230000007017 scission Effects 0.000 claims description 5
• 235000018102 proteins Nutrition 0.000 claims description 4
• 102000004169 proteins and genes Human genes 0.000 claims description 4
• 230000001086 cytosolic effect Effects 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• 238000002955 isolation Methods 0.000 claims 2
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 1
• 230000004071 biological effect Effects 0.000 claims 1
• 238000001727 in vivo Methods 0.000 claims 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• 239000002994 raw material Substances 0.000 claims 1
• 239000003795 chemical substances by application Substances 0.000 description 9
• 239000011159 matrix material Substances 0.000 description 8
• 229920000642 polymer Polymers 0.000 description 8
• 239000008194 pharmaceutical composition Substances 0.000 description 5
• 108091028043 Nucleic acid sequence Proteins 0.000 description 4
• 230000002068 genetic effect Effects 0.000 description 4
• 150000007523 nucleic acids Chemical group 0.000 description 4
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
• 229920001661 Chitosan Polymers 0.000 description 2
• 229920002307 Dextran Polymers 0.000 description 2
• 241000588724 Escherichia coli Species 0.000 description 2
• 229920006022 Poly(L-lactide-co-glycolide)-b-poly(​ethylene glycol) Polymers 0.000 description 2
• 229940072056 alginate Drugs 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 2
• 238000001542 size-exclusion chromatography Methods 0.000 description 2
• 102100029727 Enteropeptidase Human genes 0.000 description 1
• 108010013369 Enteropeptidase Proteins 0.000 description 1
• 108010074860 Factor Xa Proteins 0.000 description 1
• 102000001398 Granzyme Human genes 0.000 description 1
• 108060005986 Granzyme Proteins 0.000 description 1
• 108010076818 TEV protease Proteins 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 210000001236 prokaryotic cell Anatomy 0.000 description 1
• 108090000250 sortase A Proteins 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 210000005253 yeast cell Anatomy 0.000 description 1