CA2070781A1 - Method of producing peptides or proteins - Google Patents
Method of producing peptides or proteinsInfo
- Publication number
- CA2070781A1 CA2070781A1 CA002070781A CA2070781A CA2070781A1 CA 2070781 A1 CA2070781 A1 CA 2070781A1 CA 002070781 A CA002070781 A CA 002070781A CA 2070781 A CA2070781 A CA 2070781A CA 2070781 A1 CA2070781 A1 CA 2070781A1
- Authority
- CA
- Canada
- Prior art keywords
- arg
- proteins
- protein
- protease
- lys
- 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
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 190
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 115
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 97
- 238000000034 method Methods 0.000 title claims description 64
- 102000004196 processed proteins & peptides Human genes 0.000 title claims description 57
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 101
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 101
- 239000004365 Protease Substances 0.000 claims abstract description 81
- 108091005804 Peptidases Proteins 0.000 claims abstract description 79
- 108010016626 Dipeptides Proteins 0.000 claims abstract description 53
- 210000004899 c-terminal region Anatomy 0.000 claims abstract description 42
- 150000001413 amino acids Chemical class 0.000 claims abstract description 35
- 244000005700 microbiome Species 0.000 claims abstract description 25
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 23
- NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 claims abstract description 22
- 108010006303 Carboxypeptidases Proteins 0.000 claims abstract description 18
- 102000005367 Carboxypeptidases Human genes 0.000 claims abstract description 18
- 108090000915 Aminopeptidases Proteins 0.000 claims abstract description 16
- 102000004400 Aminopeptidases Human genes 0.000 claims abstract description 16
- 102000035195 Peptidases Human genes 0.000 claims description 77
- 235000019419 proteases Nutrition 0.000 claims description 69
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 claims description 29
- 102400000015 Vasoactive intestinal peptide Human genes 0.000 claims description 29
- 125000000539 amino acid group Chemical group 0.000 claims description 20
- 244000063299 Bacillus subtilis Species 0.000 claims description 16
- 235000014469 Bacillus subtilis Nutrition 0.000 claims description 16
- OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 claims description 12
- 108010068380 arginylarginine Proteins 0.000 claims description 12
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 10
- 239000002243 precursor Substances 0.000 claims description 9
- 230000003248 secreting effect Effects 0.000 claims description 8
- 102000002260 Alkaline Phosphatase Human genes 0.000 claims description 5
- 108020004774 Alkaline Phosphatase Proteins 0.000 claims description 5
- 101800001288 Atrial natriuretic factor Proteins 0.000 claims description 5
- 102400001282 Atrial natriuretic peptide Human genes 0.000 claims description 5
- 101800001890 Atrial natriuretic peptide Proteins 0.000 claims description 5
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 5
- 108090000087 Carboxypeptidase B Proteins 0.000 claims description 5
- 102000003670 Carboxypeptidase B Human genes 0.000 claims description 5
- 102100032378 Carboxypeptidase E Human genes 0.000 claims description 5
- 108010058255 Carboxypeptidase H Proteins 0.000 claims description 5
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 claims description 5
- 241000235648 Pichia Species 0.000 claims description 4
- 241000235070 Saccharomyces Species 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 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 4
- 108090000145 Bacillolysin Proteins 0.000 claims description 3
- 108091005658 Basic proteases Proteins 0.000 claims description 3
- 108010085169 Lysine carboxypeptidase Proteins 0.000 claims description 3
- 108091005507 Neutral proteases Proteins 0.000 claims description 3
- 241000191940 Staphylococcus Species 0.000 claims description 3
- 241000191967 Staphylococcus aureus Species 0.000 claims description 3
- 239000003102 growth factor Substances 0.000 claims description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 3
- 102100032126 Aminopeptidase B Human genes 0.000 claims description 2
- 239000004382 Amylase Substances 0.000 claims description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims description 2
- 108060001064 Calcitonin Proteins 0.000 claims description 2
- 108010059892 Cellulase Proteins 0.000 claims description 2
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- 108050009340 Endothelin Proteins 0.000 claims description 2
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- 241000588722 Escherichia Species 0.000 claims description 2
- 241000233866 Fungi Species 0.000 claims description 2
- 102400001370 Galanin Human genes 0.000 claims description 2
- 101800002068 Galanin Proteins 0.000 claims description 2
- 102400000921 Gastrin Human genes 0.000 claims description 2
- 108010052343 Gastrins Proteins 0.000 claims description 2
- 108010007267 Hirudins Proteins 0.000 claims description 2
- 102000007625 Hirudins Human genes 0.000 claims description 2
- 102000002265 Human Growth Hormone Human genes 0.000 claims description 2
- 108010000521 Human Growth Hormone Proteins 0.000 claims description 2
- 239000000854 Human Growth Hormone Substances 0.000 claims description 2
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 2
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 2
- 108010026459 IRCM-serine protease 1 Proteins 0.000 claims description 2
- 108090001061 Insulin Proteins 0.000 claims description 2
- 102000004877 Insulin Human genes 0.000 claims description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 2
- 241000235649 Kluyveromyces Species 0.000 claims description 2
- 102000008072 Lymphokines Human genes 0.000 claims description 2
- 108010074338 Lymphokines Proteins 0.000 claims description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 2
- 102000001490 Opioid Peptides Human genes 0.000 claims description 2
- 108010093625 Opioid Peptides Proteins 0.000 claims description 2
- 108010087702 Penicillinase Proteins 0.000 claims description 2
- 108010044159 Proprotein Convertases Proteins 0.000 claims description 2
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- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 2
- 101100408135 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) phnA gene Proteins 0.000 claims description 2
- 102000001218 Rec A Recombinases Human genes 0.000 claims description 2
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- 108010022394 Threonine synthase Proteins 0.000 claims description 2
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 claims description 2
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- 108090000449 aminopeptidase B Proteins 0.000 claims description 2
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 claims description 2
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- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 2
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- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 claims description 2
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- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 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
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/305—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F)
- C07K14/31—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
-
- 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
- C07K14/57563—Vasoactive intestinal peptide [VIP]; Related peptides
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/705—Fusion polypeptide containing domain for protein-protein interaction containing a protein-A fusion
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP271880/1990 | 1990-10-09 | ||
| JP2271880A JPH07108232B2 (ja) | 1990-10-09 | 1990-10-09 | ペプチド又は蛋白質の製造方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2070781A1 true CA2070781A1 (en) | 1992-04-10 |
Family
ID=17506194
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002070781A Abandoned CA2070781A1 (en) | 1990-10-09 | 1991-02-25 | Method of producing peptides or proteins |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US5506120A (cg-RX-API-DMAC7.html) |
| EP (1) | EP0591524A1 (cg-RX-API-DMAC7.html) |
| JP (1) | JPH07108232B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2070781A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO1992006211A1 (cg-RX-API-DMAC7.html) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994019469A1 (fr) * | 1993-02-22 | 1994-09-01 | Centre National De La Recherche Scientifique (Cnrs) | Proteine de fusion multi-vip et procede de preparation de vip recombinant |
| US7410779B2 (en) | 1992-01-31 | 2008-08-12 | Novozymes Biopharma Uk Limited | Fusion polypeptides of human serum albumin and a therapeutically active polypeptide |
| US7482013B2 (en) | 2000-04-12 | 2009-01-27 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7507413B2 (en) | 2001-04-12 | 2009-03-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7521424B2 (en) | 2003-01-22 | 2009-04-21 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7550432B2 (en) | 1995-12-30 | 2009-06-23 | Novozymes Biopharma Uk Limited | Recombinant fusion proteins to growth hormone and serum albumin |
| US7569384B2 (en) | 2004-02-09 | 2009-08-04 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7592010B2 (en) | 2001-12-21 | 2009-09-22 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7977306B2 (en) | 2001-12-21 | 2011-07-12 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8287859B2 (en) | 2001-12-21 | 2012-10-16 | Human Genome Sciences, Inc. | Methods of reducing toxicity and effects of cocaine by administering a butyrylcholinesterase (BChE)-albumin fusion protein |
| US8334365B2 (en) | 2006-06-07 | 2012-12-18 | Human Genome Sciences, Inc. | Albumin fusion proteins |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2090969C (en) * | 1990-09-04 | 2001-08-21 | Russell Arthur Brierley | Production of insulin-like growth factor-1 in methylotrophic yeast cells |
| US5612198A (en) * | 1990-09-04 | 1997-03-18 | The Salk Institute | Production of insulin-like growth factor-1 in methylotrophic yeast cells |
| AU661844B2 (en) * | 1991-04-01 | 1995-08-10 | Merck Sharp & Dohme Corp. | Genes which influence (pichia) proteolytic activity, and uses therefor |
| US6316004B1 (en) * | 1993-06-22 | 2001-11-13 | T. Tikhonenko | Chimeric somatostatin containing protein and encoding DNA, plasmids of expression, method for preparing chimeric protein, strain-producers, immunogenic composition, method for increasing the productivity of farm animals |
| US5888775A (en) * | 1994-04-29 | 1999-03-30 | Dade International Inc | Peptide synthesis and purification by fusion to penI protein or precipitation effective portion thereof |
| US6037145A (en) * | 1994-09-07 | 2000-03-14 | Suntory Limited | Process for production of protein |
| WO1996032468A2 (en) * | 1995-04-11 | 1996-10-17 | Merck & Co., Inc. | Bioprocess for production of dipeptide based compounds |
| US6037321A (en) * | 1995-05-03 | 2000-03-14 | Biostar Inc. | Fusion proteins comprising vasoactive intestinal peptide or PACAP |
| WO1996034958A1 (en) * | 1995-05-03 | 1996-11-07 | Biostar Inc. | Vasoactive intestinal peptide |
| WO1997001627A1 (en) * | 1995-06-27 | 1997-01-16 | Igen International, Inc. | High-level expression and efficient recovery of ubiquitin fusion proteins from escherichia coli |
| GB9513967D0 (en) * | 1995-07-08 | 1995-09-06 | Univ Leicester | Insulin |
| US20080286228A1 (en) * | 1995-10-20 | 2008-11-20 | Tarantolo Stefano R | Compositions and methods for enhancing immune responses mediated by antigen-presenting cells |
| ATE399022T1 (de) * | 1995-10-20 | 2008-07-15 | Univ Nebraska | Zusammensetzung und verfahren zur verstärkung der immunantwort antigen-präsentierender zellen |
| US5935824A (en) * | 1996-01-31 | 1999-08-10 | Technologene, Inc. | Protein expression system |
| CA2198966C (en) * | 1996-03-04 | 2011-06-21 | Yuji Suzuki | Method for cleaving chimeric protein using processing enzyme |
| US6265204B1 (en) | 1997-01-17 | 2001-07-24 | Genencor International, Inc. | DNA sequences, vectors, and fusion polypeptides for secretion of polypeptides in filamentous fungi |
| GB9716790D0 (en) | 1997-08-07 | 1997-10-15 | Creative Peptides Sweden Ab | Recombinant DNA molecules comprising multimeric copies of a gene sequence and expression thereof |
| KR100368073B1 (ko) * | 1999-03-09 | 2003-01-24 | 한국생명공학연구원 | 융합파트너를 이용한 재조합 단백질의 제조방법 |
| JP4472998B2 (ja) * | 2002-04-22 | 2010-06-02 | ダウ グローバル テクノロジーズ インコーポレイティド | 低コストのペプチド製造 |
| DE60334109D1 (de) * | 2002-06-29 | 2010-10-21 | Leadbio Inc | Yapsin-mangelmutantenstamm von hansenula polymorpha sowie verfahren zur herstellung rekombinanter proteine damit |
| SI1583562T1 (sl) * | 2003-01-06 | 2011-10-28 | Angiochem Inc | AngioPep-1, sorodne spojine in njihove uporabe |
| ES2398463T3 (es) * | 2003-09-30 | 2013-03-19 | Daiichi Sankyo Company, Limited | Método de escisión de polipéptidos usando un mutante de la proteasa OmpT |
| RU2369404C2 (ru) * | 2004-02-09 | 2009-10-10 | Хьюман Дженом Сайенсиз, Инк. | Слитые белки альбумина |
| US20130172274A1 (en) | 2005-12-20 | 2013-07-04 | Duke University | Methods and compositions for delivering active agents with enhanced pharmacological properties |
| US9365634B2 (en) * | 2007-05-29 | 2016-06-14 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
| CN105727261A (zh) | 2008-06-27 | 2016-07-06 | 杜克大学 | 包含弹性蛋白样肽的治疗剂 |
| CA2740316A1 (en) | 2008-10-15 | 2010-04-22 | Angiochem Inc. | Conjugates of glp-1 agonists and uses thereof |
| KR101943420B1 (ko) | 2009-08-14 | 2019-04-17 | 파세비오 파마수티컬스 인코포레이티드 | 변형된 혈관활성 장 펩티드 |
| EP2717902B1 (en) | 2011-06-06 | 2018-01-24 | Phasebio Pharmaceuticals, Inc. | Use of modified vasoactive intestinal peptides in the treatment of hypertension |
| CA2947982C (en) | 2014-05-08 | 2022-11-29 | Phasebio Pharmaceuticals, Inc. | Methods and compositions for treating cystic fibrosis |
| CN107427556B (zh) | 2015-02-09 | 2022-02-25 | 费斯生物制药公司 | 用于治疗肌肉疾病和病症的方法和组合物 |
| CA2989400A1 (en) | 2015-06-15 | 2016-12-22 | Angiochem Inc. | Ang1005 for the treatment of leptomeningeal carcinomatosis |
| JP2020513834A (ja) | 2017-03-20 | 2020-05-21 | ルピン・リミテッド | ペプチドの発現および大規模生産 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE7811458L (sv) * | 1977-11-08 | 1979-05-09 | Genentech Inc | Forfarande och medel for polypeptidbildning via mikrober |
| CA1200773A (en) * | 1980-02-29 | 1986-02-18 | William J. Rutter | Expression linkers |
| SE8300693L (sv) * | 1983-02-09 | 1984-08-10 | Sven Lofdahl | Sett att framstella och isolera proteiner och polypeptider samt en hybridvektor for detta |
| US4703004A (en) * | 1984-01-24 | 1987-10-27 | Immunex Corporation | Synthesis of protein with an identification peptide |
| CA1213537A (en) * | 1984-05-01 | 1986-11-04 | Canadian Patents And Development Limited - Societe Canadienne Des Brevets Et D'exploitation Limitee | Polypeptide expression method |
| US4828994A (en) * | 1984-09-21 | 1989-05-09 | Genex Corporation | Bacillus strains with reduced extracellular protease levels |
| EP0196056B1 (en) * | 1985-03-28 | 1991-05-22 | Chiron Corporation | Improved expression using fused genes providing for protein product |
| JP2862870B2 (ja) * | 1986-09-12 | 1999-03-03 | 協和醗酵工業株式会社 | 新規ペプチド |
| EP0312346B1 (en) * | 1987-10-16 | 1994-08-17 | Genencor International, Inc. | E. coli sequence specific acid protease |
| EP0336056B1 (en) * | 1988-01-27 | 1995-04-05 | M & D RESEARCH CO., LTD. | Protease |
| JPH01191683A (ja) * | 1988-01-27 | 1989-08-01 | M D Res Kk | 新規なプロテアーゼ |
| JPH0249585A (ja) * | 1988-08-12 | 1990-02-19 | M D Res Kk | 新規なプロテアーゼ |
| JP2643968B2 (ja) * | 1988-02-03 | 1997-08-25 | サントリー株式会社 | Ｋｅｘ２エンドプロテアーゼ及びその製造方法 |
| JPH02271880A (ja) * | 1989-04-13 | 1990-11-06 | Suzuki Gakki Seisakusho:Kk | 呼吸器官鍛練器 |
-
1990
- 1990-10-09 JP JP2271880A patent/JPH07108232B2/ja not_active Expired - Lifetime
-
1991
- 1991-02-25 WO PCT/JP1991/000239 patent/WO1992006211A1/ja not_active Ceased
- 1991-02-25 CA CA002070781A patent/CA2070781A1/en not_active Abandoned
- 1991-02-25 EP EP91904654A patent/EP0591524A1/en not_active Ceased
-
1994
- 1994-05-16 US US08/243,082 patent/US5506120A/en not_active Expired - Fee Related
Cited By (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7410779B2 (en) | 1992-01-31 | 2008-08-12 | Novozymes Biopharma Uk Limited | Fusion polypeptides of human serum albumin and a therapeutically active polypeptide |
| US7435410B2 (en) | 1992-01-31 | 2008-10-14 | Novozymes Biopharma Uk Limited | Methods of treatment with interferson and albumin fusion protein |
| FR2701953A1 (fr) * | 1993-02-22 | 1994-09-02 | Centre Nat Rech Scient | Protéine de fusion multi-VIP et procédé de préparation de VIP recombinant. |
| WO1994019469A1 (fr) * | 1993-02-22 | 1994-09-01 | Centre National De La Recherche Scientifique (Cnrs) | Proteine de fusion multi-vip et procede de preparation de vip recombinant |
| US7550432B2 (en) | 1995-12-30 | 2009-06-23 | Novozymes Biopharma Uk Limited | Recombinant fusion proteins to growth hormone and serum albumin |
| US8642542B2 (en) | 1995-12-30 | 2014-02-04 | Novozymes Biopharma Dk A/S | Recombinant fusion proteins to growth hormone and serum albumin |
| US7785599B2 (en) | 2000-04-12 | 2010-08-31 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7482013B2 (en) | 2000-04-12 | 2009-01-27 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7507414B2 (en) | 2000-04-12 | 2009-03-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8946156B2 (en) | 2000-04-12 | 2015-02-03 | Human Genome Sciences, Inc. | Albumin Fusion Proteins |
| US7507413B2 (en) | 2001-04-12 | 2009-03-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7799759B2 (en) | 2001-12-21 | 2010-09-21 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8993517B2 (en) | 2001-12-21 | 2015-03-31 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7977306B2 (en) | 2001-12-21 | 2011-07-12 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8071539B2 (en) | 2001-12-21 | 2011-12-06 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7592010B2 (en) | 2001-12-21 | 2009-09-22 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8211439B2 (en) | 2001-12-21 | 2012-07-03 | Human Genome Sciences, Inc. | Albumin fusion proteins comprising insulin polypeptides |
| US8252739B2 (en) | 2001-12-21 | 2012-08-28 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8287859B2 (en) | 2001-12-21 | 2012-10-16 | Human Genome Sciences, Inc. | Methods of reducing toxicity and effects of cocaine by administering a butyrylcholinesterase (BChE)-albumin fusion protein |
| US9296809B2 (en) | 2001-12-21 | 2016-03-29 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8513189B2 (en) | 2001-12-21 | 2013-08-20 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US9221896B2 (en) | 2001-12-21 | 2015-12-29 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7521424B2 (en) | 2003-01-22 | 2009-04-21 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8143026B2 (en) | 2004-02-09 | 2012-03-27 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7569384B2 (en) | 2004-02-09 | 2009-08-04 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8969538B2 (en) | 2006-06-07 | 2015-03-03 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US8334365B2 (en) | 2006-06-07 | 2012-12-18 | Human Genome Sciences, Inc. | Albumin fusion proteins |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0591524A4 (cg-RX-API-DMAC7.html) | 1994-08-03 |
| US5506120A (en) | 1996-04-09 |
| EP0591524A1 (en) | 1994-04-13 |
| WO1992006211A1 (en) | 1992-04-16 |
| JPH04148694A (ja) | 1992-05-21 |
| JPH07108232B2 (ja) | 1995-11-22 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |