ES2218569T3 - Reduccion de la gelacion de proteinas aciladas con acidos grasos usando un tampon citrato. - Google Patents

Reduccion de la gelacion de proteinas aciladas con acidos grasos usando un tampon citrato.

Info

Publication number: ES2218569T3
Authority: ES; Spain
Prior art keywords: acylated; insulin; fatty acids; protein; citrate
Prior art date: 1995-06-07
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

ES96303973T

Other languages

English (en)

Spanish (es)

Inventor

Jeffrey Clayton Baker

Jose M. Hanquier

Warren E. Shrader

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

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.)

1995-06-07

Filing date

1996-05-31

Publication date

2004-11-16

1996-05-31 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

2004-11-16 Application granted granted Critical

2004-11-16 Publication of ES2218569T3 publication Critical patent/ES2218569T3/es

2016-05-31 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

102000004169 proteins and genes Human genes 0.000 title claims abstract description 33
108090000623 proteins and genes Proteins 0.000 title claims abstract description 33
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 title claims abstract description 28
238000001879 gelation Methods 0.000 title claims abstract description 20
235000014113 dietary fatty acids Nutrition 0.000 title claims description 74
229930195729 fatty acid Natural products 0.000 title claims description 74
239000000194 fatty acid Substances 0.000 title claims description 74
150000004665 fatty acids Chemical class 0.000 title claims description 70
238000000034 method Methods 0.000 claims abstract description 37
239000006172 buffering agent Substances 0.000 claims abstract description 15
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 126
102000004877 Insulin Human genes 0.000 claims description 61
108090001061 Insulin Proteins 0.000 claims description 61
229940125396 insulin Drugs 0.000 claims description 48
239000007864 aqueous solution Substances 0.000 claims description 27
239000000243 solution Substances 0.000 claims description 26
108091005647 acylated proteins Proteins 0.000 claims description 16
108010076181 Proinsulin Proteins 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 11
125000000539 amino acid group Chemical group 0.000 claims description 8
239000012460 protein solution Substances 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 6
239000012528 membrane Substances 0.000 claims description 6
-1 acids fatty acids Chemical class 0.000 claims description 5
238000010828 elution Methods 0.000 claims description 4
230000003139 buffering effect Effects 0.000 claims description 3
TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 claims description 2
235000021360 Myristic acid Nutrition 0.000 claims description 2
TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 claims description 2
238000009295 crossflow filtration Methods 0.000 claims description 2
238000001914 filtration Methods 0.000 claims description 2
230000002378 acidificating effect Effects 0.000 claims 1
238000013375 chromatographic separation Methods 0.000 claims 1
238000012545 processing Methods 0.000 abstract description 21
101000976075 Homo sapiens Insulin Proteins 0.000 abstract description 7
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 abstract description 7
239000000872 buffer Substances 0.000 abstract description 6
239000007979 citrate buffer Substances 0.000 abstract description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 26
235000018102 proteins Nutrition 0.000 description 23
239000004026 insulin derivative Substances 0.000 description 21
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
238000000108 ultra-filtration Methods 0.000 description 14
238000000746 purification Methods 0.000 description 12
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 11
239000000499 gel Substances 0.000 description 10
238000005917 acylation reaction Methods 0.000 description 7
239000012071 phase Substances 0.000 description 7
239000000843 powder Substances 0.000 description 7
239000002904 solvent Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
239000004471 Glycine Substances 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
230000001851 biosynthetic effect Effects 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
239000008194 pharmaceutical composition Substances 0.000 description 6
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
230000010933 acylation Effects 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
230000000052 comparative effect Effects 0.000 description 4
235000018417 cysteine Nutrition 0.000 description 4
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
239000002798 polar solvent Substances 0.000 description 4
239000011347 resin Substances 0.000 description 4
229920005989 resin Polymers 0.000 description 4
238000002560 therapeutic procedure Methods 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
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 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
239000003480 eluent Substances 0.000 description 3
239000008103 glucose Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000000203 mixture Substances 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
238000001742 protein purification Methods 0.000 description 3
238000011282 treatment Methods 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
239000004472 Lysine Substances 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
235000021314 Palmitic acid Nutrition 0.000 description 2
108020004511 Recombinant DNA Proteins 0.000 description 2
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
239000004327 boric acid Substances 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
150000001860 citric acid derivatives Chemical class 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
230000007717 exclusion Effects 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
230000002209 hydrophobic effect Effects 0.000 description 2
229950004152 insulin human Drugs 0.000 description 2
238000011068 loading method Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
239000000047 product Substances 0.000 description 2
230000020978 protein processing Effects 0.000 description 2
230000000717 retained effect Effects 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
108010075254 C-Peptide Proteins 0.000 description 1
241000207199 Citrus Species 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
101500025354 Homo sapiens Insulin B chain Proteins 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical class [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
229940053200 antiepileptics fatty acid derivative Drugs 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
239000008366 buffered solution Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
235000020971 citrus fruits Nutrition 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
238000007865 diluting Methods 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
235000019262 disodium citrate Nutrition 0.000 description 1
239000002526 disodium citrate Substances 0.000 description 1
CEYULKASIQJZGP-UHFFFAOYSA-L disodium;2-(carboxymethyl)-2-hydroxybutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O CEYULKASIQJZGP-UHFFFAOYSA-L 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical group CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
201000001421 hyperglycemia Diseases 0.000 description 1
230000003914 insulin secretion Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
229940100630 metacresol Drugs 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 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
239000000312 peanut oil Substances 0.000 description 1
125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
239000003495 polar organic solvent Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000009145 protein modification Effects 0.000 description 1
238000011403 purification operation Methods 0.000 description 1
230000001698 pyrogenic effect Effects 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000004064 recycling Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
238000012552 review Methods 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000010129 solution processing Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 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

Landscapes

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

ES96303973T 1995-06-07 1996-05-31 Reduccion de la gelacion de proteinas aciladas con acidos grasos usando un tampon citrato. Expired - Lifetime ES2218569T3 (es)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US484545		1995-06-07
US08/484,545 US5631347A (en)	1995-06-07	1995-06-07	Reducing gelation of a fatty acid-acylated protein

Publications (1)

Publication Number	Publication Date
ES2218569T3 true ES2218569T3 (es)	2004-11-16

Family

ID=23924602

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES96303973T Expired - Lifetime ES2218569T3 (es)	1995-06-07	1996-05-31	Reduccion de la gelacion de proteinas aciladas con acidos grasos usando un tampon citrato.

Country Status (10)

Country	Link
US (1)	US5631347A (2)
EP (1)	EP0747390B1 (2)
JP (1)	JP3962430B2 (2)
AT (1)	ATE264867T1 (2)
AU (1)	AU5951596A (2)
CA (1)	CA2223531A1 (2)
DE (1)	DE69632224T2 (2)
DK (1)	DK0747390T3 (2)
ES (1)	ES2218569T3 (2)
WO (1)	WO1996040188A1 (2)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9316895D0 (en)	1993-08-13	1993-09-29	Guy S And St Thomas Hospitals	Hepatoselective insulin analogues
US6451970B1 (en) *	1996-02-21	2002-09-17	Novo Nordisk A/S	Peptide derivatives
US5948751A (en) *	1996-06-20	1999-09-07	Novo Nordisk A/S	X14-mannitol
US7658938B2 (en) *	1999-02-22	2010-02-09	Merrion Reasearch III Limited	Solid oral dosage form containing an enhancer
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- 1996-05-31 DE DE69632224T patent/DE69632224T2/de not_active Expired - Fee Related
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Also Published As

Publication number	Publication date
EP0747390A3 (en)	1997-06-04
EP0747390A2 (en)	1996-12-11
JPH11506739A (ja)	1999-06-15
ATE264867T1 (de)	2004-05-15
WO1996040188A1 (en)	1996-12-19
DE69632224D1 (de)	2004-05-27
AU5951596A (en)	1996-12-30
DK0747390T3 (da)	2004-07-26
JP3962430B2 (ja)	2007-08-22
EP0747390B1 (en)	2004-04-21
CA2223531A1 (en)	1996-12-19
DE69632224T2 (de)	2005-04-14
US5631347A (en)	1997-05-20

Publication	Publication Date	Title
EP0747390B1 (en)	2004-04-21	Reducing gelation of a fatty acid acylated protein using a citrate buffer
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ES2691534T3 (es)	2018-11-27	Derivados de exendina-4 como agonistas selectivos del receptor de glucagón
ES2526924T3 (es)	2015-01-16	Insulinas con una fracción acilo que comprende unidades repetitivas de aminoácidos que contienen alquilenglicol
ES2611040T3 (es)	2017-05-04	Derivados de insulina
ES2218622T3 (es)	2004-11-16	Derivados de insulina con actividad de union al zinc incrementada.
AU2009226910A1 (en)	2009-09-24	Protease stabilized, acylated insulin analogues
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AU2013205270B2 (en)	2015-01-15	Protease stabilized, acylated insulin analogues
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HK1014009A (en)	1999-09-17	Acylated insulin analogs
MXPA97003506A (en)	1997-12-01	Selective acilacion of epsilon-am groups