CA2271697C - Variantes d'activateur plasminogene de type tissulaire (t-pa): compositions et techniques d'utilisation - Google Patents
Variantes d'activateur plasminogene de type tissulaire (t-pa): compositions et techniques d'utilisation Download PDFInfo
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- CA2271697C CA2271697C CA002271697A CA2271697A CA2271697C CA 2271697 C CA2271697 C CA 2271697C CA 002271697 A CA002271697 A CA 002271697A CA 2271697 A CA2271697 A CA 2271697A CA 2271697 C CA2271697 C CA 2271697C
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- protein variant
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- MHHAWNPHDLCPLF-ULQDDVLXSA-N Val-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=CC=C1 MHHAWNPHDLCPLF-ULQDDVLXSA-N 0.000 description 1
- RTJPAGFXOWEBAI-SRVKXCTJSA-N Val-Val-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RTJPAGFXOWEBAI-SRVKXCTJSA-N 0.000 description 1
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- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
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- 239000012153 distilled water Substances 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- 108010078144 glutaminyl-glycine Proteins 0.000 description 1
- 230000010005 growth-factor like effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 108010018006 histidylserine Proteins 0.000 description 1
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- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
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- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000009290 primary effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
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- 238000012552 review Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 108010073863 saruplase Proteins 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 108010071207 serylmethionine Proteins 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000000213 tara gum Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003462 zymogenic effect Effects 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
- 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)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6456—Plasminogen activators
- C12N9/6459—Plasminogen activators t-plasminogen activator (3.4.21.68), i.e. tPA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21069—Protein C activated (3.4.21.69)
-
- 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)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
La présente invention concerne des variantes du facteur plasminogène tissulaire qui font preuve d'une amélioration notable de la stimulation de la fibrine, d'une discrimination considérablement accrue entre cofacteurs de la fibrine, d'une résistance marquée à l'inhibition par PAI-1, et d'une zymogénicité sensiblement accrue, une combinaison de propriétés qui renforcent l'utilité thérapeutique de l'enzyme.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3065596P | 1996-11-12 | 1996-11-12 | |
| US60/030,655 | 1996-11-12 | ||
| PCT/US1997/020226 WO1998021320A2 (fr) | 1996-11-12 | 1997-11-12 | VARIANTES D'ACTIVATEUR PLASMINOGENE DE TYPE TISSULAIRE (t-PA): COMPOSITIONS ET TECHNIQUES D'UTILISATION |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2271697A1 CA2271697A1 (fr) | 1998-05-22 |
| CA2271697C true CA2271697C (fr) | 2007-10-23 |
Family
ID=21855292
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002271697A Expired - Fee Related CA2271697C (fr) | 1996-11-12 | 1997-11-12 | Variantes d'activateur plasminogene de type tissulaire (t-pa): compositions et techniques d'utilisation |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0950095A2 (fr) |
| JP (1) | JP2001505765A (fr) |
| CN (1) | CN1244894A (fr) |
| AU (1) | AU735519B2 (fr) |
| CA (1) | CA2271697C (fr) |
| WO (1) | WO1998021320A2 (fr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU8864398A (en) * | 1997-08-13 | 1999-03-08 | Boehringer Mannheim Gmbh | Plasminogen activator with enhanced zymogenic power and reduced fibrin linking |
| WO2002072786A2 (fr) | 2001-03-13 | 2002-09-19 | Corvas International, Inc. | Molecules d'acides nucleiques codant pour une serine protease transmembranaire 7, polypeptides codes et procedes associes |
| AU2002254357A1 (en) | 2001-03-22 | 2002-10-08 | Dendreon Corporation | Nucleic acid molecules encoding serine protease cvsp14, the encoded polypeptides and methods based thereon |
| CA2442089A1 (fr) | 2001-03-27 | 2002-10-03 | Dendreon San Diego Llc | Molecules d'acide nucleique codant une serine protease transmembranaire 9, polypeptides codes et procedes fondes sur ces derniers |
| US7112430B2 (en) | 2001-05-14 | 2006-09-26 | Dendreon Corporation | Nucleic acid molecules encoding a transmembrane serine protease 10, the encoded polypeptides and methods based thereon |
| US10160813B2 (en) * | 2013-01-22 | 2018-12-25 | University Of Tennessee Research Foundation | Tissue plasminogen activator antibodies and methods of use |
| CN114736948B (zh) * | 2022-06-10 | 2022-11-08 | 深圳市帝迈生物技术有限公司 | 一种α2-抗纤溶酶活性测定试剂盒 |
| CN117327682A (zh) * | 2023-10-07 | 2024-01-02 | 福州大学 | 一种兼顾高效性与安全性的新型溶栓剂的设计及其应用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GR861037B (en) * | 1985-04-22 | 1986-07-16 | Genentech Inc | Novel human tissue plasminogen activator mutants |
| US5108901A (en) * | 1988-09-02 | 1992-04-28 | Genentech, Inc. | Tissue plasminogen activator having zymogenic or fibrin specific properties |
-
1997
- 1997-11-12 AU AU55850/98A patent/AU735519B2/en not_active Ceased
- 1997-11-12 JP JP52266198A patent/JP2001505765A/ja not_active Ceased
- 1997-11-12 EP EP97952176A patent/EP0950095A2/fr not_active Withdrawn
- 1997-11-12 CN CN97181346A patent/CN1244894A/zh active Pending
- 1997-11-12 CA CA002271697A patent/CA2271697C/fr not_active Expired - Fee Related
- 1997-11-12 WO PCT/US1997/020226 patent/WO1998021320A2/fr not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998021320A2 (fr) | 1998-05-22 |
| AU735519B2 (en) | 2001-07-12 |
| CN1244894A (zh) | 2000-02-16 |
| CA2271697A1 (fr) | 1998-05-22 |
| EP0950095A2 (fr) | 1999-10-20 |
| WO1998021320A3 (fr) | 1998-07-09 |
| AU5585098A (en) | 1998-06-03 |
| JP2001505765A (ja) | 2001-05-08 |
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