DK170741B1 - Bifunktionelle proteiner, deres fremstilling, et lægemiddel deraf og anvendelse deraf til fremstilling af et lægemiddel - Google Patents
Bifunktionelle proteiner, deres fremstilling, et lægemiddel deraf og anvendelse deraf til fremstilling af et lægemiddel Download PDFInfo
- Publication number
- DK170741B1 DK170741B1 DK209188A DK209188A DK170741B1 DK 170741 B1 DK170741 B1 DK 170741B1 DK 209188 A DK209188 A DK 209188A DK 209188 A DK209188 A DK 209188A DK 170741 B1 DK170741 B1 DK 170741B1
- Authority
- DK
- Denmark
- Prior art keywords
- asp
- thr
- protein
- drug
- protein according
- Prior art date
Links
- 108090000623 proteins and genes Proteins 0.000 title claims description 46
- 102000004169 proteins and genes Human genes 0.000 title claims description 40
- 230000001588 bifunctional effect Effects 0.000 title claims description 17
- 239000003814 drug Substances 0.000 title claims description 8
- 229940079593 drug Drugs 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title description 4
- 108010002350 Interleukin-2 Proteins 0.000 claims description 24
- 150000001413 amino acids Chemical class 0.000 claims description 14
- 210000004027 cell Anatomy 0.000 claims description 8
- 210000003714 granulocyte Anatomy 0.000 claims description 5
- 210000002540 macrophage Anatomy 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 102100020873 Interleukin-2 Human genes 0.000 claims 4
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 28
- 102000000588 Interleukin-2 Human genes 0.000 description 20
- 239000013612 plasmid Substances 0.000 description 17
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- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
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- 238000012986 modification Methods 0.000 description 3
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 2
- PFPUFNLHBXKPHY-HTFCKZLJSA-N Ile-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)O)N PFPUFNLHBXKPHY-HTFCKZLJSA-N 0.000 description 2
- RRRRCRYTLZVCEN-HJGDQZAQSA-N Thr-Leu-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O RRRRCRYTLZVCEN-HJGDQZAQSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 108010093581 aspartyl-proline Proteins 0.000 description 2
- 230000002281 colonystimulating effect Effects 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
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- 102000037865 fusion proteins Human genes 0.000 description 2
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108010039224 Amidophosphoribosyltransferase Proteins 0.000 description 1
- 101100148606 Caenorhabditis elegans pst-1 gene Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- NURNJECQNNCRBK-FLBSBUHZSA-N Ile-Thr-Thr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NURNJECQNNCRBK-FLBSBUHZSA-N 0.000 description 1
- 108010054278 Lac Repressors Proteins 0.000 description 1
- WIDZHJTYKYBLSR-DCAQKATOSA-N Leu-Glu-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WIDZHJTYKYBLSR-DCAQKATOSA-N 0.000 description 1
- LJBVRCDPWOJOEK-PPCPHDFISA-N Leu-Thr-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LJBVRCDPWOJOEK-PPCPHDFISA-N 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
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- 108091081024 Start codon Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- GRIUMVXCJDKVPI-IZPVPAKOSA-N Thr-Thr-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O GRIUMVXCJDKVPI-IZPVPAKOSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY 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)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=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 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
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- 239000004202 carbamide Substances 0.000 description 1
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- 230000003196 chaotropic effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
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- 102000013165 exonuclease Human genes 0.000 description 1
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- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
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- 238000002703 mutagenesis Methods 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
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- 235000015097 nutrients Nutrition 0.000 description 1
- 238000000424 optical density measurement Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
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- 230000028327 secretion Effects 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
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- 230000001225 therapeutic effect Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
Classifications
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/55—IL-2
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
- C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (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)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3712985 | 1987-04-16 | ||
DE19873712985 DE3712985A1 (de) | 1987-04-16 | 1987-04-16 | Bifunktionelle proteine |
Publications (3)
Publication Number | Publication Date |
---|---|
DK209188D0 DK209188D0 (da) | 1988-04-15 |
DK209188A DK209188A (da) | 1988-10-17 |
DK170741B1 true DK170741B1 (da) | 1996-01-08 |
Family
ID=6325799
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK209188A DK170741B1 (da) | 1987-04-16 | 1988-04-15 | Bifunktionelle proteiner, deres fremstilling, et lægemiddel deraf og anvendelse deraf til fremstilling af et lægemiddel |
Country Status (20)
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5662896A (en) * | 1988-03-21 | 1997-09-02 | Chiron Viagene, Inc. | Compositions and methods for cancer immunotherapy |
US5116964A (en) * | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
US6406697B1 (en) | 1989-02-23 | 2002-06-18 | Genentech, Inc. | Hybrid immunoglobulins |
US5225538A (en) * | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
AU5355790A (en) * | 1989-04-19 | 1990-11-16 | Cetus Corporation | Multifunctional m-csf proteins and genes encoding therefor |
EP0489116B1 (en) * | 1989-08-22 | 1994-04-06 | Immunex Corporation | Fusion proteins comprising gm-csf and il-3 |
US5073627A (en) * | 1989-08-22 | 1991-12-17 | Immunex Corporation | Fusion proteins comprising GM-CSF and IL-3 |
US5108910A (en) * | 1989-08-22 | 1992-04-28 | Immunex Corporation | DNA sequences encoding fusion proteins comprising GM-CSF and IL-3 |
US5376367A (en) * | 1991-11-22 | 1994-12-27 | Immunex Corporation | Fusion proteins comprising MGF and IL-3 |
US5723125A (en) * | 1995-12-28 | 1998-03-03 | Tanox Biosystems, Inc. | Hybrid with interferon-alpha and an immunoglobulin Fc linked through a non-immunogenic peptide |
DK1037927T3 (da) | 1997-12-08 | 2004-09-06 | Emd Lexigen Res Ct Corp | Heterodimere fusionsproteiner, der er nyttige til målrettet immunterapi og generel immunstimulering |
SK782002A3 (en) | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
US7067110B1 (en) | 1999-07-21 | 2006-06-27 | Emd Lexigen Research Center Corp. | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
DK1200479T3 (da) | 1999-08-09 | 2006-05-15 | Emd Lexigen Res Ct Corp | Multiple cytokin-antistof-komplekser |
WO2001036489A2 (en) | 1999-11-12 | 2001-05-25 | Merck Patent Gmbh | Erythropoietin forms with improved properties |
JP4553290B2 (ja) * | 1999-11-30 | 2010-09-29 | 塩野義製薬株式会社 | ケモカインslc−il2融合タンパク質とその遺伝子 |
WO2001058957A2 (en) | 2000-02-11 | 2001-08-16 | Lexigen Pharmaceuticals Corp. | Enhancing the circulating half-life of antibody-based fusion proteins |
DK1294401T3 (da) | 2000-06-29 | 2007-10-08 | Merck Patent Gmbh | Forbedring af antistof/cytokin-fusionsproteinmedierede immunresponser ved kombineret behandling med immuncytokin-optagelsesforberende midler |
HUP0303428A2 (hu) | 2001-03-07 | 2004-01-28 | Merck Patent Gmbh. | Expressziós eljárás hibrid izotípusú antitestcsoportot tartalmazó fehérjékhez |
US6992174B2 (en) | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
BR0209177A (pt) | 2001-05-03 | 2004-10-05 | Merck Patent Gmbh | Anticorpo especìfico a tumor recombinante e uso do mesmo |
WO2003031464A2 (en) | 2001-10-10 | 2003-04-17 | Neose Technologies, Inc. | Remodeling and glycoconjugation of peptides |
BR0214650A (pt) | 2001-12-04 | 2005-05-03 | Merck Patent Gmbh | Imunocitoquinas com seletividade modulada |
CN100432105C (zh) | 2002-12-17 | 2008-11-12 | 默克专利有限公司 | 与gd2结合的小鼠14.18抗体的人源化抗体(h14.18)以及其与il-2的融合 |
CA2678736A1 (en) * | 2003-07-21 | 2005-02-17 | Transgene S.A. | Novel multifunctional il-2 - il-18 fusion proteins |
DE602004031341D1 (de) | 2003-07-21 | 2011-03-24 | Transgene Sa | Multifunktionelle cytokine |
WO2010001414A1 (en) * | 2008-07-03 | 2010-01-07 | Lupin Limited | Expression of heterologous proteins in bacterial system using a gm-csf fusion tag |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1985000817A1 (en) * | 1983-08-10 | 1985-02-28 | Amgen | Microbial expression of interleukin ii |
GB8327880D0 (en) * | 1983-10-18 | 1983-11-16 | Ajinomoto Kk | Saccharomyces cerevisiae |
EP0158198A1 (en) * | 1984-03-29 | 1985-10-16 | Takeda Chemical Industries, Ltd. | DNA and use thereof |
WO1985004673A1 (en) * | 1984-04-10 | 1985-10-24 | Takeda Chemical Industries, Ltd. | Novel dna and its use |
DE3419995A1 (de) * | 1984-05-29 | 1985-12-05 | Hoechst Ag, 6230 Frankfurt | Gentechnologisches verfahren zur herstellung von human-interleukin-2 und mittel zur durchfuehrung dieses verfahrens |
AU588819B2 (en) * | 1984-10-29 | 1989-09-28 | Immunex Corporation | Cloning of human granulocyte-macrophage colony stimulating factor gene |
JPS61128889A (ja) * | 1984-11-27 | 1986-06-16 | Green Cross Corp:The | 組換えdna及び該dnaによる形質転換体 |
JPH0646957B2 (ja) * | 1985-03-11 | 1994-06-22 | 武田薬品工業株式会社 | インタ−ロイキン−2の製造方法 |
AU606585B2 (en) * | 1985-10-03 | 1991-02-14 | Biogen, Inc. | Human granulocyte-macrophage colony stimulating factor-like polypeptides and processes for producing them in high yields in microbial cells |
DE3541856A1 (de) * | 1985-11-27 | 1987-06-04 | Hoechst Ag | Eukaryotische fusionsproteine, ihre herstellung und verwendung sowie mittel zur durchfuehrung des verfahrens |
DE3545568A1 (de) * | 1985-12-21 | 1987-07-16 | Hoechst Ag | Gm-csf-protein, seine derivate, herstellung solcher proteine und ihre verwendung |
-
1987
- 1987-04-16 DE DE19873712985 patent/DE3712985A1/de not_active Withdrawn
-
1988
- 1988-04-09 DE DE8888105693T patent/DE3873397D1/de not_active Expired - Fee Related
- 1988-04-09 ES ES198888105693T patent/ES2033981T3/es not_active Expired - Lifetime
- 1988-04-09 EP EP88105693A patent/EP0288809B1/de not_active Expired - Lifetime
- 1988-04-09 AT AT88105693T patent/ATE79135T1/de not_active IP Right Cessation
- 1988-04-14 FI FI881743A patent/FI98830C/fi not_active IP Right Cessation
- 1988-04-14 PT PT87237A patent/PT87237B/pt active IP Right Grant
- 1988-04-14 NZ NZ224247A patent/NZ224247A/en unknown
- 1988-04-15 IL IL8608688A patent/IL86086A/en not_active IP Right Cessation
- 1988-04-15 ZA ZA882659A patent/ZA882659B/xx unknown
- 1988-04-15 AR AR88310585A patent/AR242991A1/es active
- 1988-04-15 NO NO881658A patent/NO176922C/no not_active IP Right Cessation
- 1988-04-15 CA CA000564322A patent/CA1322157C/en not_active Expired - Fee Related
- 1988-04-15 IE IE114688A patent/IE61574B1/en not_active IP Right Cessation
- 1988-04-15 DK DK209188A patent/DK170741B1/da not_active IP Right Cessation
- 1988-04-15 AU AU14661/88A patent/AU613022B2/en not_active Ceased
- 1988-04-15 JP JP63093321A patent/JP2667193B2/ja not_active Expired - Fee Related
- 1988-04-15 HU HU881966A patent/HU204303B/hu not_active IP Right Cessation
- 1988-04-16 KR KR1019880004345A patent/KR970000187B1/ko not_active Expired - Fee Related
-
1989
- 1989-04-14 PH PH36799A patent/PH25327A/en unknown
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1992
- 1992-11-04 GR GR920402185T patent/GR3006141T3/el unknown
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