LT3328B - Process for the preparation of insulin - Google Patents
Process for the preparation of insulin Download PDFInfo
- Publication number
- LT3328B LT3328B LTIP712A LTIP712A LT3328B LT 3328 B LT3328 B LT 3328B LT IP712 A LTIP712 A LT IP712A LT IP712 A LTIP712 A LT IP712A LT 3328 B LT3328 B LT 3328B
- Authority
- LT
- Lithuania
- Prior art keywords
- amino acid
- arginine
- clostripan
- insulin
- process according
- Prior art date
Links
- 102000004877 Insulin Human genes 0.000 title claims abstract description 20
- 108090001061 Insulin Proteins 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title claims abstract description 19
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- 229940125396 insulin Drugs 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 title claims description 5
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- 108090000087 Carboxypeptidase B Proteins 0.000 claims abstract description 16
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 13
- 239000004026 insulin derivative Substances 0.000 claims abstract description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 5
- 230000007062 hydrolysis Effects 0.000 claims abstract description 4
- 235000001014 amino acid Nutrition 0.000 claims description 38
- 150000001413 amino acids Chemical class 0.000 claims description 37
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- 238000006243 chemical reaction Methods 0.000 claims description 12
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 claims description 11
- 125000000539 amino acid group Chemical group 0.000 claims description 11
- 229930064664 L-arginine Natural products 0.000 claims description 10
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- 238000003776 cleavage reaction Methods 0.000 claims description 9
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- 230000000694 effects Effects 0.000 claims description 7
- 230000007017 scission Effects 0.000 claims description 7
- 108010076181 Proinsulin Proteins 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 6
- 101500021084 Locusta migratoria 5 kDa peptide Proteins 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 108090001092 clostripain Proteins 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract 2
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- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
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- 239000000654 additive Substances 0.000 description 1
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- 239000003513 alkali Substances 0.000 description 1
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- 108010068380 arginylarginine Proteins 0.000 description 1
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- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical class CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- VHJLVAABSRFDPM-ZXZARUISSA-N dithioerythritol Chemical compound SC[C@H](O)[C@H](O)CS VHJLVAABSRFDPM-ZXZARUISSA-N 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 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 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 108010025306 histidylleucine Proteins 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 108010012058 leucyltyrosine Proteins 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 229940066779 peptones Drugs 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4028118 | 1990-09-05 |
Publications (2)
Publication Number | Publication Date |
---|---|
LTIP712A LTIP712A (en) | 1995-01-31 |
LT3328B true LT3328B (en) | 1995-07-25 |
Family
ID=6413629
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LTIP712A LT3328B (en) | 1990-09-05 | 1993-06-25 | Process for the preparation of insulin |
Country Status (26)
Country | Link |
---|---|
US (1) | US5728543A (cs) |
EP (1) | EP0474212B1 (cs) |
JP (1) | JP3005335B2 (cs) |
KR (1) | KR100188800B1 (cs) |
AT (1) | ATE145922T1 (cs) |
AU (1) | AU637254B2 (cs) |
CA (1) | CA2050606C (cs) |
CZ (1) | CZ283234B6 (cs) |
DE (1) | DE59108392D1 (cs) |
DK (1) | DK0474212T3 (cs) |
ES (1) | ES2095891T3 (cs) |
FI (1) | FI103805B1 (cs) |
GR (1) | GR3021909T3 (cs) |
HR (1) | HRP940766A2 (cs) |
HU (1) | HU214676B (cs) |
IE (1) | IE75723B1 (cs) |
IL (1) | IL99383A (cs) |
LT (1) | LT3328B (cs) |
LV (1) | LV10508B (cs) |
NO (1) | NO300980B1 (cs) |
NZ (1) | NZ239652A (cs) |
PL (1) | PL167810B1 (cs) |
RU (1) | RU2062301C1 (cs) |
SK (1) | SK279686B6 (cs) |
YU (1) | YU147491A (cs) |
ZA (1) | ZA917008B (cs) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2122549C1 (ru) * | 1997-12-29 | 1998-11-27 | Закрытое акционерное общество "Фосфосорб" | Способ хроматографического выделения и очистки белков, пептидов и их комплексов |
RU2238951C2 (ru) * | 1998-03-31 | 2004-10-27 | Тонгхуа Гэнтеч Биотекнолоджи Лтд. | Химерный белок, обеспечивающий образование биоактивной конформации, способ получения белка с инсулиновой активностью, способ идентификации пептидильного фрагмента |
US6461834B1 (en) * | 1998-11-06 | 2002-10-08 | Bionebraska, Inc. | Clostripain catalyzed amidation of peptides |
DE19915938A1 (de) * | 1999-04-09 | 2000-10-19 | Aventis Pharma Gmbh | Herstellung von pankreatischer Procarboxypeptidase B, Isoformen und Muteinen davon und ihre Verwendung |
EP1513945A4 (en) * | 2002-05-24 | 2008-12-24 | Restoragen Inc | PROCESS FOR UNIVERSAL ENZYMATIC PRODUCTION OF BIOACTIVE PEPTIDES |
EP1572720A4 (en) * | 2002-05-24 | 2008-12-24 | Nps Allelix Corp | PROCESS FOR THE ENZYMATIC PRODUCTION OF GLP-2 (1-34) AND GLP-2 (1-33) PEPTIDES |
WO2003099847A2 (en) * | 2002-05-24 | 2003-12-04 | Restoragen, Inc. | Method for enzymatic production of glp-1 (7-36) amide peptides |
HRP20120315T1 (hr) * | 2003-11-21 | 2012-05-31 | Nps Pharmaceuticals | Proizvodnja peptida 2 nalik glukagonu i analoga |
WO2013015697A1 (en) * | 2011-07-28 | 2013-01-31 | Mabion S.A. | A recombinant protein, a polynucleotide encoding it as well as a method of obtaining insulin or its an analogue |
KR102646845B1 (ko) * | 2018-08-08 | 2024-03-14 | 주식회사 대웅제약 | 클로스트리파인을 이용한 지속형 인슐린 아날로그 복합체의 활성형 제조방법 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0024250A1 (de) | 1979-08-14 | 1981-02-25 | Arbed S.A. | Verfahren und Einrichtung zur Wiederverwertung kohlenstoffreicher Abfälle |
EP0095691A1 (de) | 1982-05-27 | 1983-12-07 | Neiman S.A. | Zylinderschloss, insbesondere Lenkschloss für ein Kraftfahrzeug |
DE3440988A1 (de) | 1984-11-09 | 1986-07-10 | Hoechst Ag, 6230 Frankfurt | Verfahren zur spaltung von peptiden und proteinen an der methionyl-bindung |
EP0264250A2 (en) | 1986-10-14 | 1988-04-20 | Eli Lilly And Company | Process for transforming a human insulin precursor to human insulin |
EP0347781A2 (de) | 1988-06-23 | 1989-12-27 | Hoechst Aktiengesellschaft | Mini-Proinsulin, seine Herstellung und Verwendung |
EP0367163A2 (de) | 1988-11-03 | 1990-05-09 | Hoechst Aktiengesellschaft | Verfahren zur Herstellung eines Insulin-Vorprodukts in Streptomyceten |
EP0890007A1 (en) | 1996-02-29 | 1999-01-13 | Sweepy International S.A. | Fluted swimming pool cleaner discs |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3209184A1 (de) * | 1982-03-13 | 1983-09-15 | Hoechst Ag, 6230 Frankfurt | Verfahren zur umwandlung von praeproinsulinanaloga zu insulinen |
JPS60217894A (ja) * | 1984-04-14 | 1985-10-31 | Suntory Ltd | 新規プロテア−ゼ及びその製造方法 |
DK129385A (da) * | 1985-03-22 | 1986-09-23 | Novo Industri As | Peptider og fremstilling deraf |
DE4012818A1 (de) * | 1990-04-21 | 1991-10-24 | Hoechst Ag | Verfahren zur herstellung von fremdproteinen in streptomyceten |
DE3919852A1 (de) * | 1988-06-23 | 1989-12-28 | Hoechst Ag | Mini-proinsulin, seine herstellung und verwendung |
-
1991
- 1991-09-03 CZ CS912711A patent/CZ283234B6/cs not_active IP Right Cessation
- 1991-09-03 FI FI914151A patent/FI103805B1/fi not_active IP Right Cessation
- 1991-09-03 KR KR1019910015314A patent/KR100188800B1/ko not_active Expired - Lifetime
- 1991-09-03 SK SK2711-91A patent/SK279686B6/sk not_active IP Right Cessation
- 1991-09-03 IL IL9938391A patent/IL99383A/en not_active IP Right Cessation
- 1991-09-03 NZ NZ239652A patent/NZ239652A/xx not_active IP Right Cessation
- 1991-09-04 JP JP3223243A patent/JP3005335B2/ja not_active Expired - Lifetime
- 1991-09-04 ZA ZA917008A patent/ZA917008B/xx unknown
- 1991-09-04 DE DE59108392T patent/DE59108392D1/de not_active Expired - Lifetime
- 1991-09-04 YU YU147491A patent/YU147491A/sh unknown
- 1991-09-04 CA CA002050606A patent/CA2050606C/en not_active Expired - Lifetime
- 1991-09-04 AT AT91114934T patent/ATE145922T1/de not_active IP Right Cessation
- 1991-09-04 DK DK91114934.2T patent/DK0474212T3/da active
- 1991-09-04 IE IE311791A patent/IE75723B1/en not_active IP Right Cessation
- 1991-09-04 EP EP91114934A patent/EP0474212B1/de not_active Expired - Lifetime
- 1991-09-04 RU SU915001486A patent/RU2062301C1/ru active
- 1991-09-04 AU AU83567/91A patent/AU637254B2/en not_active Expired
- 1991-09-04 ES ES91114934T patent/ES2095891T3/es not_active Expired - Lifetime
- 1991-09-04 NO NO913474A patent/NO300980B1/no not_active IP Right Cessation
- 1991-09-04 PL PL91291617A patent/PL167810B1/pl unknown
- 1991-09-05 HU HU912875A patent/HU214676B/hu unknown
-
1993
- 1993-05-05 LV LVP-93-288A patent/LV10508B/xx unknown
- 1993-06-25 LT LTIP712A patent/LT3328B/lt not_active IP Right Cessation
-
1994
- 1994-08-08 US US08/291,060 patent/US5728543A/en not_active Expired - Lifetime
- 1994-10-25 HR HRP-1474/91A patent/HRP940766A2/hr not_active Application Discontinuation
-
1996
- 1996-12-05 GR GR960403067T patent/GR3021909T3/el unknown
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0024250A1 (de) | 1979-08-14 | 1981-02-25 | Arbed S.A. | Verfahren und Einrichtung zur Wiederverwertung kohlenstoffreicher Abfälle |
EP0095691A1 (de) | 1982-05-27 | 1983-12-07 | Neiman S.A. | Zylinderschloss, insbesondere Lenkschloss für ein Kraftfahrzeug |
DE3440988A1 (de) | 1984-11-09 | 1986-07-10 | Hoechst Ag, 6230 Frankfurt | Verfahren zur spaltung von peptiden und proteinen an der methionyl-bindung |
EP0264250A2 (en) | 1986-10-14 | 1988-04-20 | Eli Lilly And Company | Process for transforming a human insulin precursor to human insulin |
EP0347781A2 (de) | 1988-06-23 | 1989-12-27 | Hoechst Aktiengesellschaft | Mini-Proinsulin, seine Herstellung und Verwendung |
EP0367163A2 (de) | 1988-11-03 | 1990-05-09 | Hoechst Aktiengesellschaft | Verfahren zur Herstellung eines Insulin-Vorprodukts in Streptomyceten |
EP0890007A1 (en) | 1996-02-29 | 1999-01-13 | Sweepy International S.A. | Fluted swimming pool cleaner discs |
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