CS114290A3 - Specifically glycosylated insulin derivatives - Google Patents

Specifically glycosylated insulin derivatives Download PDF

Info

Publication number: CS114290A3
Authority: CS; Czechoslovakia
Prior art keywords: insulin; glycosylated insulin; residues; specifically; human
Prior art date: 1989-03-08

Application number

CS901142A

Other languages

Czech (cs)

English (en)

Inventor

John Broberg Halstrom

Original Assignee

Novo Nordisk As

Priority date (The priority date 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 date listed.)

1989-03-08

Filing date

1990-03-08

Publication date

1992-02-19

1990-03-08 Application filed by Novo Nordisk As filed Critical Novo Nordisk As

1992-02-19 Publication of CS114290A3 publication Critical patent/CS114290A3/cs

Links

NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class 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 title claims description 126
102000004877 Insulin Human genes 0.000 claims description 47
108090001061 Insulin Proteins 0.000 claims description 47
229940125396 insulin Drugs 0.000 claims description 45
108700004813 glycosylated insulin Proteins 0.000 claims description 16
PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 16
101000976075 Homo sapiens Insulin Proteins 0.000 claims description 14
150000002482 oligosaccharides Polymers 0.000 claims description 11
239000000203 mixture Substances 0.000 claims description 9
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239000011541 reaction mixture Substances 0.000 claims description 6
238000000034 method Methods 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
150000003839 salts Chemical class 0.000 claims description 4
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KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 23
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 16
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 16
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 15
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 14
239000008103 glucose Substances 0.000 description 14
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
150000001413 amino acids Chemical class 0.000 description 8
238000006206 glycosylation reaction Methods 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
206010012601 diabetes mellitus Diseases 0.000 description 6
230000013595 glycosylation Effects 0.000 description 6
239000000047 product Substances 0.000 description 5
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
150000001875 compounds Chemical class 0.000 description 4
239000004026 insulin derivative Substances 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
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DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
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239000012736 aqueous medium Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 3
-1 galactosyl insulin derivatives Chemical class 0.000 description 3
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OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
125000000729 N-terminal amino-acid group Chemical group 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
230000008901 benefit Effects 0.000 description 2
150000001720 carbohydrates Chemical group 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
229950004152 insulin human Drugs 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
230000009467 reduction Effects 0.000 description 2
239000000243 solution Substances 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
DBTMGCOVALSLOR-UHFFFAOYSA-N 32-alpha-galactosyl-3-alpha-galactosyl-galactose Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(OC2C(C(CO)OC(O)C2O)O)OC(CO)C1O DBTMGCOVALSLOR-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
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RXVWSYJTUUKTEA-UHFFFAOYSA-N D-maltotriose Natural products OC1C(O)C(OC(C(O)CO)C(O)C(O)C=O)OC(CO)C1OC1C(O)C(O)C(O)C(CO)O1 RXVWSYJTUUKTEA-UHFFFAOYSA-N 0.000 description 1
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239000004472 Lysine Substances 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
101000993800 Sus scrofa Insulin Proteins 0.000 description 1
PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
229960000583 acetic acid Drugs 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
239000000427 antigen Substances 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
DLRVVLDZNNYCBX-ZZFZYMBESA-N beta-melibiose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)O1 DLRVVLDZNNYCBX-ZZFZYMBESA-N 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 1
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150000001991 dicarboxylic acids Chemical class 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
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230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
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239000012467 final product Substances 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
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230000003914 insulin secretion Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
125000000311 mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
FYGDTMLNYKFZSV-UHFFFAOYSA-N mannotriose Natural products OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(OC2C(OC(O)C(O)C2O)CO)C(O)C1O FYGDTMLNYKFZSV-UHFFFAOYSA-N 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
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230000007935 neutral effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000002245 particle Substances 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
239000000590 phytopharmaceutical Substances 0.000 description 1
238000000918 plasma mass spectrometry Methods 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000004445 quantitative analysis Methods 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
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239000011780 sodium chloride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
FYGDTMLNYKFZSV-BYLHFPJWSA-N β-1,4-galactotrioside 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]2[C@@H](O[C@@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-BYLHFPJWSA-N 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
- C07K14/62—Insulins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Biochemistry (AREA)
Genetics & Genomics (AREA)
Gastroenterology & Hepatology (AREA)
Toxicology (AREA)
Endocrinology (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Zoology (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Diabetes (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Medicinal Preparation (AREA)

CS901142A 1989-03-08 1990-03-08 Specifically glycosylated insulin derivatives CS114290A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DK111489A DK111489D0 (da)	1989-03-08	1989-03-08	Peptider

Publications (1)

Publication Number	Publication Date
CS114290A3 true CS114290A3 (en)	1992-02-19

Family

ID=8101165

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS901142A CS114290A3 (en)	1989-03-08	1990-03-08	Specifically glycosylated insulin derivatives

Country Status (19)

Country	Link
EP (1)	EP0462192A1 (de)
JP (1)	JPH04504117A (de)
KR (1)	KR920701249A (de)
CN (1)	CN1045586A (de)
AU (1)	AU638701B2 (de)
CA (1)	CA2049937A1 (de)
CS (1)	CS114290A3 (de)
DD (1)	DD296933A5 (de)
DK (1)	DK111489D0 (de)
FI (1)	FI914226A7 (de)
GR (1)	GR1000604B (de)
HU (1)	HUT59942A (de)
IL (1)	IL93674A0 (de)
NO (1)	NO913517L (de)
NZ (1)	NZ232808A (de)
PT (1)	PT93366A (de)
WO (1)	WO1990010645A1 (de)
YU (1)	YU45490A (de)
ZA (1)	ZA901737B (de)

Families Citing this family (23)

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ES2642214T3 (es)	2004-01-21	2017-11-15	Novo Nordisk Health Care Ag	Conjugación de péptidos mediante transglutaminasa
US7597884B2 (en)	2004-08-09	2009-10-06	Alios Biopharma, Inc.	Hyperglycosylated polypeptide variants and methods of use
WO2010088268A1 (en)	2009-01-28	2010-08-05	Smartcells, Inc.	Exogenously triggered controlled release materials and uses thereof
WO2010088300A1 (en)	2009-01-28	2010-08-05	Smartcells, Inc.	Crystalline insulin-conjugates
BRPI1007457A2 (pt)	2009-01-28	2015-08-25	Smartcells Inc	Conjungado, formulação de liberação prolongada, e, sistema de distribuição de bomba.
WO2010107520A1 (en)	2009-03-20	2010-09-23	Smartcells, Inc.	Soluble non-depot insulin conjugates and uses thereof
US8623345B2 (en)	2009-03-20	2014-01-07	Smartcells	Terminally-functionalized conjugates and uses thereof
EP2598522A4 (de)	2010-07-28	2014-11-12	Smartcells Inc	Rekombinante lektine, bindungsstellenmodifizierte lektine und anwendungen davon
AU2011282977A1 (en)	2010-07-28	2013-02-21	Smartcells, Inc.	Drug-ligand conjugates, synthesis thereof, and intermediates thereto
JP2013535467A (ja)	2010-07-28	2013-09-12	スマートセルズ・インコーポレイテツド	組換えにより発現されたインスリンポリペプチドおよびその使用
US9624287B2 (en)	2012-07-17	2017-04-18	Case Western Reserve University	O-linked carbohydrate-modified insulin analogues
EP2877200B1 (de) *	2012-07-17	2019-05-08	Case Western Reserve University	O-verknüpfte kohlenhydratmodifizierte insulinanaloga
CN104902922B (zh)	2012-11-13	2017-12-12	阿道恰公司	包含经取代阴离子化合物的速效胰岛素制剂
US9707276B2 (en)	2012-12-03	2017-07-18	Merck Sharp & Dohme Corp.	O-glycosylated carboxy terminal portion (CTP) peptide-based insulin and insulin analogues
WO2014160185A2 (en)	2013-03-14	2014-10-02	The Board Of Trustees Of The Leland Stanford Junior University	Mitochondrial aldehyde dehydrogenase-2 modulators and methods of use thereof
KR20160065930A (ko)	2013-10-04	2016-06-09	머크 샤프 앤드 돔 코포레이션	글루코스-반응성 인슐린 접합체
FR3020947B1 (fr)	2014-05-14	2018-08-31	Adocia	Composition aqueuse comprenant au moins une proteine et un agent solubilisant, sa preparation et ses utilisations
US9795678B2 (en)	2014-05-14	2017-10-24	Adocia	Fast-acting insulin composition comprising a substituted anionic compound and a polyanionic compound
FR3043557B1 (fr)	2015-11-16	2019-05-31	Adocia	Composition a action rapide d'insuline comprenant un citrate substitue
CN105597080A (zh) *	2016-01-29	2016-05-25	程潜	一种用于治疗尿毒症和尿蛋白的药物
CN105535927A (zh) *	2016-01-29	2016-05-04	山东中海制药有限公司	一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物
CN105709207A (zh) *	2016-01-29	2016-06-29	徐宝贞	一种用于治疗痛风的药物
CA3025988A1 (en)	2016-06-02	2017-12-07	Sanofi	Conjugates of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3847890A (en) *	1971-11-01	1974-11-12	A Green	Acidic monosaccharide-substituted proteins
US4444683A (en) *	1982-11-17	1984-04-24	University Of Utah	Glycosylated insulin derivatives
EP0119650A3 (de) *	1983-03-21	1987-09-30	THE PROCTER & GAMBLE COMPANY	Galactosyl-Insulin-Konjugate für die Behandlung von Zuckerkranken
NL194729C (nl) *	1986-10-13	2003-01-07	Novartis Ag	Werkwijze voor de bereiding van peptidealcoholen via vaste fase.

1989
- 1989-03-08 DK DK111489A patent/DK111489D0/da not_active Application Discontinuation
1990
- 1990-03-06 WO PCT/DK1990/000062 patent/WO1990010645A1/en not_active Ceased
- 1990-03-06 KR KR1019910701014A patent/KR920701249A/ko not_active Withdrawn
- 1990-03-06 JP JP2504720A patent/JPH04504117A/ja active Pending
- 1990-03-06 CA CA002049937A patent/CA2049937A1/en not_active Abandoned
- 1990-03-06 EP EP19900904777 patent/EP0462192A1/de not_active Ceased
- 1990-03-06 HU HU8727A patent/HUT59942A/hu unknown
- 1990-03-06 FI FI914226A patent/FI914226A7/fi not_active Application Discontinuation
- 1990-03-06 NZ NZ232808A patent/NZ232808A/en unknown
- 1990-03-06 AU AU52807/90A patent/AU638701B2/en not_active Expired - Fee Related
- 1990-03-07 PT PT93366A patent/PT93366A/pt not_active Application Discontinuation
- 1990-03-07 IL IL93674A patent/IL93674A0/xx unknown
- 1990-03-07 ZA ZA901737A patent/ZA901737B/xx unknown
- 1990-03-07 DD DD90338488A patent/DD296933A5/de not_active IP Right Cessation
- 1990-03-07 GR GR900100159A patent/GR1000604B/el unknown
- 1990-03-07 YU YU00454/90A patent/YU45490A/xx unknown
- 1990-03-07 CN CN90101282A patent/CN1045586A/zh active Pending
- 1990-03-08 CS CS901142A patent/CS114290A3/cs unknown
1991
- 1991-09-06 NO NO91913517A patent/NO913517L/no unknown

Also Published As

Publication number	Publication date
JPH04504117A (ja)	1992-07-23
HU902787D0 (en)	1991-11-28
HUT59942A (en)	1992-07-28
NZ232808A (en)	1992-04-28
PT93366A (pt)	1990-11-07
NO913517D0 (no)	1991-09-06
DD296933A5 (de)	1991-12-19
GR900100159A (en)	1990-07-31
GR1000604B (el)	1992-08-26
WO1990010645A1 (en)	1990-09-20
NO913517L (no)	1991-11-06
EP0462192A1 (de)	1991-12-27
AU638701B2 (en)	1993-07-08
FI914226A0 (fi)	1991-09-06
CA2049937A1 (en)	1990-09-09
KR920701249A (ko)	1992-08-11
CN1045586A (zh)	1990-09-26
AU5280790A (en)	1990-10-09
ZA901737B (en)	1990-11-28
DK111489D0 (da)	1989-03-08
YU45490A (en)	1991-10-31
FI914226A7 (fi)	1991-09-06
IL93674A0 (en)	1990-12-23

Publication	Publication Date	Title
CS114290A3 (en)	1992-02-19	Specifically glycosylated insulin derivatives
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Volpin et al.	1973	Cyanogen bromide peptides from insoluble skin and dentin bovine collagens
JP5586669B2 (ja)	2014-09-10	Ｎ末端ポリシアリル化
JP4416184B2 (ja)	2010-02-17	長期作用型薬物およびこれらを含む薬剤組成物
US9452224B2 (en)	2016-09-27	Sialic acid derivatives for protein derivatisation and conjugation
EP1680073B1 (de)	2013-01-02	Verbindungen und verfahren zur behandlung von krebs
US20020160938A1 (en)	2002-10-31	Covalently bridged insulin dimers
EP0119650A2 (de)	1984-09-26	Galactosyl-Insulin-Konjugate für die Behandlung von Zuckerkranken
ZA200406332B (en)	2005-09-28	ACC inhibitors.
MX2011000847A (es)	2011-02-25	Proteinas conjugadas con eficacia prolongada in vivo.
IE910579A1 (en)	1991-08-28	Novel protein compositions
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Goussault et al.	1970	Chemical characterization of two urinary sialic acid-rich glycopeptides