CA2193399A1 - Facteur de croissance de type proche de l'insuline i authentique, o-glycosyle, variantes tronquees de celui-ci, procede de preparation et compositions pharmaceutiques - Google Patents
Facteur de croissance de type proche de l'insuline i authentique, o-glycosyle, variantes tronquees de celui-ci, procede de preparation et compositions pharmaceutiquesInfo
- Publication number
- CA2193399A1 CA2193399A1 CA002193399A CA2193399A CA2193399A1 CA 2193399 A1 CA2193399 A1 CA 2193399A1 CA 002193399 A CA002193399 A CA 002193399A CA 2193399 A CA2193399 A CA 2193399A CA 2193399 A1 CA2193399 A1 CA 2193399A1
- Authority
- CA
- Canada
- Prior art keywords
- igf
- glycosylated
- amino acid
- polypeptide chain
- mannose residues
- Prior art date
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract 4
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims abstract description 108
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims abstract description 106
- 150000001413 amino acids Chemical class 0.000 claims abstract description 29
- 125000000311 mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims abstract description 26
- 229920001184 polypeptide Polymers 0.000 claims abstract description 26
- 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 abstract description 18
- 102000003746 Insulin Receptor Human genes 0.000 claims abstract description 15
- 108010001127 Insulin Receptor Proteins 0.000 claims abstract description 15
- 230000012010 growth Effects 0.000 claims abstract description 12
- 102000004877 Insulin Human genes 0.000 claims abstract description 9
- 108090001061 Insulin Proteins 0.000 claims abstract description 9
- 229940125396 insulin Drugs 0.000 claims abstract description 9
- 239000003085 diluting agent Substances 0.000 claims abstract description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 6
- 230000007812 deficiency Effects 0.000 claims abstract description 5
- 239000003937 drug carrier Substances 0.000 claims abstract description 4
- 210000005253 yeast cell Anatomy 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims abstract 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 38
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 32
- 102000028416 insulin-like growth factor binding Human genes 0.000 claims description 8
- 108091022911 insulin-like growth factor binding Proteins 0.000 claims description 8
- 208000001362 Fetal Growth Retardation Diseases 0.000 claims description 5
- 206010070531 Foetal growth restriction Diseases 0.000 claims description 5
- 208000030941 fetal growth restriction Diseases 0.000 claims description 5
- 101001081567 Homo sapiens Insulin-like growth factor-binding protein 1 Proteins 0.000 claims description 3
- 102100027636 Insulin-like growth factor-binding protein 1 Human genes 0.000 claims description 3
- 230000016784 immunoglobulin production Effects 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 230000006870 function Effects 0.000 claims description 2
- 230000009395 genetic defect Effects 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- 102100036202 Serum amyloid P-component Human genes 0.000 description 45
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 27
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 22
- 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 description 22
- 235000001014 amino acid Nutrition 0.000 description 20
- 239000012634 fragment Substances 0.000 description 15
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 10
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 10
- 102000004375 Insulin-like growth factor-binding protein 1 Human genes 0.000 description 10
- 108090000957 Insulin-like growth factor-binding protein 1 Proteins 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 9
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 9
- 230000002608 insulinlike Effects 0.000 description 9
- 210000004899 c-terminal region Anatomy 0.000 description 7
- 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 6
- 108010062580 Concanavalin A Proteins 0.000 description 5
- 230000013595 glycosylation Effects 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 230000004989 O-glycosylation Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000006206 glycosylation reaction Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 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
- 239000002253 acid Substances 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 210000001789 adipocyte Anatomy 0.000 description 3
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 102000044162 human IGF1 Human genes 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 210000000689 upper leg Anatomy 0.000 description 3
- 101100106497 Bacillus subtilis (strain 168) ylaL gene Proteins 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 101001044927 Homo sapiens Insulin-like growth factor-binding protein 3 Proteins 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- 102100022708 Insulin-like growth factor-binding protein 3 Human genes 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000008468 bone growth Effects 0.000 description 2
- 210000003837 chick embryo Anatomy 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 108700001680 des-(1-3)- insulin-like growth factor 1 Proteins 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 208000037824 growth disorder Diseases 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000004132 lipogenesis Effects 0.000 description 2
- 230000003520 lipogenic effect Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- SBKVPJHMSUXZTA-MEJXFZFPSA-N (2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound 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)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=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 SBKVPJHMSUXZTA-MEJXFZFPSA-N 0.000 description 1
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 description 1
- 241000736839 Chara Species 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
- 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102000004374 Insulin-like growth factor binding protein 3 Human genes 0.000 description 1
- 108090000965 Insulin-like growth factor binding protein 3 Proteins 0.000 description 1
- 108010038049 Mating Factor Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 101150046509 SAP9 gene Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000012511 carbohydrate analysis Methods 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 230000004578 fetal growth Effects 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 231100000001 growth retardation Toxicity 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000007775 late Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000036435 stunted growth Effects 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 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
- C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- 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)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
La présente invention concerne des facteurs de croissance de type proche de l'insuline I (IGF-I) authentique O-glycosylés, portant au moins 3 restes de mannose sur l'acide aminé Ser¿69? de la chaîne polypeptidique du facteur IGF, ou tronqués et portant 2 restes de mannose sur l'acide aminé Thr¿29? de la chaîne polypeptidique tronquée du facteur IGF. Les facteurs IGF-I O-glycosylés selon la présente invention ne présentent sensiblement aucune affinité pour le récepteur de l'insuline, ce qui les rend précieux dans un traitement thérapeutique. L'invention concerne également un procédé d'obtention desdits facteurs IGF-I qui consiste à exprimer les facteurs IGF-I dans des cellules de levure, et à isoler de leur milieu les facteurs IGF-I O-glycosylés de la présente invention. L'invention concerne en outre une composition pharmaceutique contenant ces facteurs IGF-I ainsi qu'un vecteur, un diluant ou un excipient pharmaceutiquement acceptables. L'invention concerne enfin l'utilisation des facteurs IGF-I O-glycosylés pour la préparation d'un médicament destiné notamment au traitement des états liés au déficit de croissance et des états insulino-résistants.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9402332-2 | 1994-07-01 | ||
| SE9402332A SE9402332D0 (sv) | 1994-07-01 | 1994-07-01 | Igf-1 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2193399A1 true CA2193399A1 (fr) | 1996-01-18 |
Family
ID=20394599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002193399A Abandoned CA2193399A1 (fr) | 1994-07-01 | 1995-06-22 | Facteur de croissance de type proche de l'insuline i authentique, o-glycosyle, variantes tronquees de celui-ci, procede de preparation et compositions pharmaceutiques |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0769022A1 (fr) |
| JP (1) | JPH10502623A (fr) |
| AU (1) | AU2940695A (fr) |
| CA (1) | CA2193399A1 (fr) |
| IL (1) | IL114270A0 (fr) |
| SE (1) | SE9402332D0 (fr) |
| WO (1) | WO1996001275A1 (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9501472D0 (sv) * | 1995-04-21 | 1995-04-21 | Pharmacia Ab | Truncated IGF-I |
| SE9802938D0 (sv) | 1998-09-01 | 1998-09-01 | Astra Ab | Improved stability for injection solutions |
| DK2241575T3 (en) | 2005-01-07 | 2015-08-24 | Regeneron Pharma | IGF-1 fusion polypeptides and therapeutic uses thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8819826D0 (en) * | 1988-08-20 | 1988-09-21 | Kabivitrum Ab | Glycosylated igf-1 |
| DE69218948T2 (de) * | 1991-08-01 | 1997-07-31 | Auckland Uniservices Ltd | IGF-I zur Verbesserung der neuronale Lage |
-
1994
- 1994-07-01 SE SE9402332A patent/SE9402332D0/xx unknown
-
1995
- 1995-06-22 JP JP8503823A patent/JPH10502623A/ja active Pending
- 1995-06-22 WO PCT/SE1995/000774 patent/WO1996001275A1/fr not_active Ceased
- 1995-06-22 EP EP95925201A patent/EP0769022A1/fr not_active Withdrawn
- 1995-06-22 AU AU29406/95A patent/AU2940695A/en not_active Abandoned
- 1995-06-22 CA CA002193399A patent/CA2193399A1/fr not_active Abandoned
- 1995-06-22 IL IL11427095A patent/IL114270A0/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE9402332D0 (sv) | 1994-07-01 |
| JPH10502623A (ja) | 1998-03-10 |
| AU2940695A (en) | 1996-01-25 |
| EP0769022A1 (fr) | 1997-04-23 |
| IL114270A0 (en) | 1995-10-31 |
| WO1996001275A1 (fr) | 1996-01-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |