DK1891091T3 - Koaguleringsfaktor-X-polypeptider med modificerede aktiveringsegenskaber - Google Patents
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- DK1891091T3 DK1891091T3 DK06753967.6T DK06753967T DK1891091T3 DK 1891091 T3 DK1891091 T3 DK 1891091T3 DK 06753967 T DK06753967 T DK 06753967T DK 1891091 T3 DK1891091 T3 DK 1891091T3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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)
- C12N9/6432—Coagulation factor Xa (3.4.21.6)
-
- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- 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
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- 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
-
- 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)
- C12Y304/21006—Coagulation factor Xa (3.4.21.6)
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- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
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- Plant Pathology (AREA)
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (23)
1. Modificeret biologisk aktiv rekombinant faktor-X-variant, hvori en modifikation består i indføring af et yderligere spaltningssted for en protease, og hvori det yderligere spaltningssted er indført mellem 11e235 og Val236, eller mellem Val236 og Gly237 eller mellem Gly237 og Gly238 i den tunge kæde af faktor X, og hvor sletninger i aktiveringspeptidsekvensen af faktor X - sådan at proteaser, som naturligt aktiverer faktor X, ikke længere er i stand til at spalte og aktivere denne faktor-X-variant - er udelukket.
2. Modificeret biologisk aktiv rekombinant faktor-X-variant ifølge krav 1, som aktiveres ved spaltning af det yderligere spaltningssted med proteasen.
3. Modificeret biologisk aktiv rekombinant faktor-X-variant ifølge krav 1 eller 2, hvori proteasen ikke naturligt aktiverer faktor X.
4. Modificeret biologisk aktiv rekombinant faktor-X-variant ifølge ethvert af de foregående krav, hvori det indførte proteasespaltningssted tillader aktiveringen af den modificerede faktor-X-variant med en serinprotease.
5. Modificeret biologisk aktiv rekombinant faktor-X-variant ifølge ethvert af de foregående krav, hvori det indførte proteasespaltningssted tillader aktiveringen af den modificerede faktor-X-variant med faktor IXa, faktor Xa, faktor Xla, faktor XI la, aktiveret protein C, elastase eller kallikrein.
6. Modificeret biologisk aktiv rekombinant faktor-X-variant ifølge ethvert af de foregående krav, hvori det indførte spaltningssted omfatter mindst 3 aminosyrer.
7. Modificeret biologisk aktiv rekombinant faktor-X-variant ifølge ethvert af de foregående krav, hvori faktor-X-varianten har forstærket hæmostatisk bypass-aktivitet sammenlignet med faktor-X-varianter med en modifikation inden i sekvensen af det naturligt forekommende faktor-X-aktiveringsspaltningspeptid, hvilken modifikation repræsentere et processted for en protease, som ikke naturligt spalter i dette område af faktor-X-sekvensen, og som ved spaltning af det yderligere spaltningssted aktiverer denne faktor-X-variant.
8. Polynukleotid, der koder en biologisk aktiv rekombinant faktor-X-variant ifølge Λ+ h\//M*+ ni 1/ i" n \ / H + i I “7
9. Plasmid eller vektor omfattende en nukleinsyre ifølge krav 8.
10. Plasmid eller vektor ifølge krav 9, som er en ekspressionsvektor.
11. Plasmid eller vektor ifølge krav 9, som er en transfervektor til brug ved human genterapi.
12. Værtscelle omfattende et polynukleotid ifølge krav 9 eller et plasmid eller vektor ifølge ethvert af krav 9 til 11.
13. Fremgangsmåde til fremstilling af en biologisk aktiv rekombinant faktor-X-variant ifølge ethvert af krav 1 til 7, omfattende: - dyrkning af værtsceller ifølge krav 12 under betingelser, sådan at den modificerede rekombinante faktor-X-variant udtrykkes, og - valgfri genvinding af den modificerede rekombinante faktor-X-variant fra værtscellerne eller fra dyrkningsmediet.
14. Farmaceutisk sammensætning omfattende en biologisk aktiv rekombinant faktor-X-variant ifølge ethvert af krav 1 til 7, et polynukleotid ifølge krav 8 eller et plasmid eller en vektor ifølge ethvert af krav 9 til 11.
15. Anvendelse af en biologisk aktiv rekombinant faktor-X-variant ifølge ethvert af krav 1 til 7, af et polynukleotid ifølge krav 8, af et plasmid eller vektor ifølge ethvert af krav 9 til 11 eller af en værtscelle ifølge krav 12 til fremstilling af et medikament til behandling eller forebyggelse af en blodkoaguleringslidelse.
16. Anvendelse ifølge krav 15, hvori blodkoaguleringslidelsen er hæmofili A.
17. Anvendelse ifølge krav 16, hvori hæmofili A forårsages eller forværres af autoantistoffer mod FVIII.
18. Anvendelse ifølge krav 15, hvori blodkoaguleringslidelsen er hæmofili B.
19. Anvendelse ifølge krav 18, hvori hæmofili A forårsages eller forværres af autoantistoffer mod FIX.
20. Anvendelse ifølge krav 15, hvori blodkoaguleringslidelsen er FVII- og/el ler FVI la-mangel.
21. Anvendelse ifølge krav 20, hvori FVII- og/eller FVI la-manglen er forårsaget eller forværret af autoantistoffer mod FVII og/eller FVI la.
22. Anvendelse ifølge ethvert af krav 15 til 21, hvori behandlingen omfatter human genterapi.
23. Anvendelse af en biologisk aktiv rekombinant faktor-X-variant ifølge ethvert af krav 1 til 7, af et polynukleotid ifølge krav 8, af et plasmid eller en vektor ifølge ethvert af krav 9 til 11 eller af en værtscelle ifølge krav 12 til fremstilling af et medikament med koaguleringsfremmende egenskaber.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05011773A EP1728798A1 (en) | 2005-06-01 | 2005-06-01 | Coagulation factor X polypeptides with modified activation properties |
| US68870405P | 2005-06-09 | 2005-06-09 | |
| PCT/EP2006/005131 WO2006128668A2 (en) | 2005-06-01 | 2006-05-30 | Coagulation factor x polypeptides with modified activation properties |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK1891091T3 true DK1891091T3 (da) | 2014-02-17 |
Family
ID=34937115
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK06753967.6T DK1891091T3 (da) | 2005-06-01 | 2006-05-30 | Koaguleringsfaktor-X-polypeptider med modificerede aktiveringsegenskaber |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9249404B2 (da) |
| EP (2) | EP1728798A1 (da) |
| JP (1) | JP5049271B2 (da) |
| KR (1) | KR101273229B1 (da) |
| AU (1) | AU2006254311B2 (da) |
| CA (1) | CA2609226C (da) |
| DK (1) | DK1891091T3 (da) |
| ES (1) | ES2445394T3 (da) |
| WO (1) | WO2006128668A2 (da) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1728798A1 (en) | 2005-06-01 | 2006-12-06 | ZLB Behring GmbH | Coagulation factor X polypeptides with modified activation properties |
| MX336958B (es) | 2005-11-15 | 2016-02-05 | Philadelphia Children Hospital | Metodos y composiciones para modular la hemostasia. |
| US8450269B2 (en) | 2006-02-03 | 2013-05-28 | Prolor Biotech Ltd. | Long-acting growth hormone and methods of producing same |
| US8946155B2 (en) | 2006-02-03 | 2015-02-03 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US8759292B2 (en) | 2006-02-03 | 2014-06-24 | Prolor Biotech, Llc | Long-acting coagulation factors and methods of producing same |
| US10351615B2 (en) | 2006-02-03 | 2019-07-16 | Opko Biologics Ltd. | Methods of treatment with long-acting growth hormone |
| US20150038413A1 (en) | 2006-02-03 | 2015-02-05 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US20140113860A1 (en) | 2006-02-03 | 2014-04-24 | Prolor Biotech Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US8476234B2 (en) * | 2006-02-03 | 2013-07-02 | Prolor Biotech Inc. | Long-acting coagulation factors and methods of producing same |
| US7553941B2 (en) | 2006-02-03 | 2009-06-30 | Modigene Inc | Long-acting polypeptides and methods of producing same |
| US9458444B2 (en) | 2006-02-03 | 2016-10-04 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| US10221228B2 (en) | 2006-02-03 | 2019-03-05 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
| US9249407B2 (en) | 2006-02-03 | 2016-02-02 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| US8048848B2 (en) | 2006-02-03 | 2011-11-01 | Prolor Biotech Ltd. | Long-acting interferons and derivatives thereof and methods thereof |
| US8048849B2 (en) | 2006-02-03 | 2011-11-01 | Modigene, Inc. | Long-acting polypeptides and methods of producing same |
| EP1820508A1 (en) | 2006-02-21 | 2007-08-22 | CSL Behring GmbH | Coagulation factor X polypeptides with modified activation properties |
| WO2009048067A1 (ja) * | 2007-10-09 | 2009-04-16 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | 糖鎖を持たない遺伝子組換え血液凝固第x因子およびその製法 |
| US9663778B2 (en) | 2009-07-09 | 2017-05-30 | OPKO Biologies Ltd. | Long-acting coagulation factors and methods of producing same |
| US12203113B2 (en) | 2009-07-09 | 2025-01-21 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
| WO2013049804A1 (en) | 2011-09-30 | 2013-04-04 | The Children's Hospital Of Philadelphia | Compositions and methods for modulating hemostasis |
| HK1205188A1 (en) * | 2012-02-14 | 2015-12-11 | Portola Pharmaceuticals, Inc. | Process for making recombinant antidote to factor xa inhibitor |
| EP2838552A4 (en) | 2012-04-19 | 2016-05-18 | Opko Biolog Ltd | OXYNTOMODULIN VARIANTS WITH EXTENDED ACTION AND PROCESSES FOR PRODUCING SAME |
| BR112015001628A2 (pt) | 2012-07-25 | 2017-11-07 | Catalyst Biosciences Inc | polipeptídeos de fator x modificados e uso dos mesmos |
| CN114317505A (zh) | 2012-11-20 | 2022-04-12 | 奥普科生物制品有限公司 | 通过连接至促性腺激素羧基端肽来增加多肽的流体动力学体积的方法 |
| US20150343034A1 (en) | 2013-01-31 | 2015-12-03 | Pfizer Inc. | Compositions and methods for counteracting factor xa inhibition |
| FR3001729B1 (fr) * | 2013-02-04 | 2015-03-06 | Lab Francais Du Fractionnement | Mutants du facteur x |
| RU2648144C2 (ru) | 2013-09-24 | 2018-03-22 | Пфайзер Инк. | КОМПОЗИЦИИ, СОДЕРЖАЩИЕ ГЕТЕРОГЕННЫЕ ПОПУЛЯЦИИ РЕКОМБИНАНТНЫХ БЕЛКОВ ЧЕЛОВЕЧЕСКОГО ФАКТОРА СВЕРТЫВАНИЯ КРОВИ Ха |
| US20150158926A1 (en) | 2013-10-21 | 2015-06-11 | Opko Biologics, Ltd. | Long-acting polypeptides and methods of producing and administering same |
| EA037991B1 (ru) | 2014-05-26 | 2021-06-21 | Академиш Зикенхёйс Лейден | Прогемостатические белки для лечения кровотечений |
| US10676731B2 (en) | 2014-08-19 | 2020-06-09 | The Children's Hospital Of Philadelphia | Compositions and methods for modulating factor IX function |
| US10676730B2 (en) | 2015-01-07 | 2020-06-09 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Mutated factor X polypeptides and uses thereof for the treatment of haemophilia |
| CN108289851B (zh) | 2015-06-19 | 2021-06-01 | Opko生物科学有限公司 | 长效凝固因子及其产生方法 |
| CA3030533A1 (en) | 2016-07-11 | 2018-01-18 | Oren HERSHKOVITZ | Long-acting coagulation factor vii and methods of producing same |
| JP7668783B2 (ja) * | 2019-08-08 | 2025-04-25 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 第ｘａ因子及び誘導体を調製するための組成物及び方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4501731A (en) | 1983-06-27 | 1985-02-26 | Tishkoff Garson H | Treatment of disparate bleeding disorders with factor X zymogen |
| GR860984B (en) | 1985-04-17 | 1986-08-18 | Zymogenetics Inc | Expression of factor vii and ix activities in mammalian cells |
| AT405516B (de) | 1997-02-27 | 1999-09-27 | Immuno Ag | Faktor x-analoge mit modifizierter proteasespaltstelle |
| AT405517B (de) * | 1997-02-27 | 1999-09-27 | Immuno Ag | Faktor x-deletionsmutanten und analoge davon |
| AU6673898A (en) * | 1997-03-07 | 1998-09-22 | Washington University | Factor x variant |
| US5955594A (en) * | 1997-04-30 | 1999-09-21 | Mishra; Lopa | Nucleic acids encoding proteins for early liver development |
| AT410216B (de) | 1999-08-10 | 2003-03-25 | Baxter Ag | Faktor x-analogon mit verbesserter aktivierbarkeit |
| EP1407780B1 (en) | 2001-07-10 | 2013-05-01 | The Chemo-Sero-Therapeutic Research Institute | Pharmaceutically stable hemostatic compositions |
| FR2831170B1 (fr) | 2001-10-19 | 2004-03-19 | Inst Nat Sante Rech Med | Proteines c modifiees activables directement par la thrombine |
| FR2841904B1 (fr) | 2002-07-03 | 2004-08-20 | Inst Nat Sante Rech Med | Analogues de facteurs x clivables par la thrombine |
| EP1728798A1 (en) | 2005-06-01 | 2006-12-06 | ZLB Behring GmbH | Coagulation factor X polypeptides with modified activation properties |
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2005
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- 2006-05-30 JP JP2008514002A patent/JP5049271B2/ja not_active Expired - Fee Related
- 2006-05-30 KR KR1020077028129A patent/KR101273229B1/ko active Active
- 2006-05-30 DK DK06753967.6T patent/DK1891091T3/da active
- 2006-05-30 US US11/921,399 patent/US9249404B2/en not_active Expired - Fee Related
- 2006-05-30 EP EP06753967.6A patent/EP1891091B1/en not_active Not-in-force
- 2006-05-30 CA CA2609226A patent/CA2609226C/en not_active Expired - Fee Related
- 2006-05-30 WO PCT/EP2006/005131 patent/WO2006128668A2/en active Application Filing
- 2006-05-30 ES ES06753967.6T patent/ES2445394T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| KR20080022086A (ko) | 2008-03-10 |
| AU2006254311A1 (en) | 2006-12-07 |
| AU2006254311B2 (en) | 2011-04-07 |
| JP2008541742A (ja) | 2008-11-27 |
| US20090053185A1 (en) | 2009-02-26 |
| WO2006128668A3 (en) | 2007-02-22 |
| ES2445394T3 (es) | 2014-03-03 |
| US9249404B2 (en) | 2016-02-02 |
| JP5049271B2 (ja) | 2012-10-17 |
| CA2609226A1 (en) | 2006-12-07 |
| KR101273229B1 (ko) | 2013-06-11 |
| EP1891091A2 (en) | 2008-02-27 |
| CA2609226C (en) | 2015-03-31 |
| EP1728798A1 (en) | 2006-12-06 |
| WO2006128668A2 (en) | 2006-12-07 |
| EP1891091B1 (en) | 2013-11-20 |
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