HRP20201071T1 - Protuotrovi za inhibitore faktora xa i postupci njihove uporabe - Google Patents
Protuotrovi za inhibitore faktora xa i postupci njihove uporabe Download PDFInfo
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- HRP20201071T1 HRP20201071T1 HRP20201071TT HRP20201071T HRP20201071T1 HR P20201071 T1 HRP20201071 T1 HR P20201071T1 HR P20201071T T HRP20201071T T HR P20201071TT HR P20201071 T HRP20201071 T HR P20201071T HR P20201071 T1 HRP20201071 T1 HR P20201071T1
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- Prior art keywords
- polypeptide
- factor
- amino acid
- seq
- inhibitor
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- 229940123583 Factor Xa inhibitor Drugs 0.000 title claims 13
- 238000000034 method Methods 0.000 title claims 3
- 239000000729 antidote Substances 0.000 title 1
- 229940075522 antidotes Drugs 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 claims 30
- 102000004196 processed proteins & peptides Human genes 0.000 claims 30
- 108090000765 processed proteins & peptides Proteins 0.000 claims 30
- 125000003275 alpha amino acid group Chemical group 0.000 claims 14
- 230000003197 catalytic effect Effects 0.000 claims 8
- 239000000825 pharmaceutical preparation Substances 0.000 claims 6
- 238000002560 therapeutic procedure Methods 0.000 claims 6
- 239000012634 fragment Substances 0.000 claims 4
- 108010014806 prothrombinase complex Proteins 0.000 claims 4
- 238000007911 parenteral administration Methods 0.000 claims 3
- QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 claims 2
- 108010074860 Factor Xa Proteins 0.000 claims 2
- 108010022999 Serine Proteases Proteins 0.000 claims 2
- 102000012479 Serine Proteases Human genes 0.000 claims 2
- 125000000539 amino acid group Chemical group 0.000 claims 2
- 230000010100 anticoagulation Effects 0.000 claims 2
- 229960003886 apixaban Drugs 0.000 claims 2
- 229950011103 betrixaban Drugs 0.000 claims 2
- XHOLNRLADUSQLD-UHFFFAOYSA-N betrixaban Chemical compound C=1C=C(Cl)C=NC=1NC(=O)C1=CC(OC)=CC=C1NC(=O)C1=CC=C(C(=N)N(C)C)C=C1 XHOLNRLADUSQLD-UHFFFAOYSA-N 0.000 claims 2
- MVPQUSQUURLQKF-MCPDASDXSA-E nonasodium;(2s,3s,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3s,4s,5r,6r)-2-carboxylato-4,5-dimethoxy-6-[(2r,3r,4s,5r,6s)-6-methoxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-di Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]S(=O)(=O)O[C@@H]1[C@@H](OS([O-])(=O)=O)[C@@H](OC)O[C@H](COS([O-])(=O)=O)[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@@H]2[C@@H]([C@@H](OS([O-])(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](OC)[C@H](O[C@@H]4[C@@H]([C@@H](OC)[C@H](OC)[C@@H](COS([O-])(=O)=O)O4)OC)[C@H](O3)C([O-])=O)OC)[C@@H](COS([O-])(=O)=O)O2)OS([O-])(=O)=O)[C@H](C([O-])=O)O1 MVPQUSQUURLQKF-MCPDASDXSA-E 0.000 claims 2
- -1 rNAPc2 Proteins 0.000 claims 2
- 229960001148 rivaroxaban Drugs 0.000 claims 2
- KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 claims 2
- OFJRNBWSFXEHSA-UHFFFAOYSA-N 2-(3-amino-1,2-benzoxazol-5-yl)-n-[4-[2-[(dimethylamino)methyl]imidazol-1-yl]-2-fluorophenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide Chemical compound CN(C)CC1=NC=CN1C(C=C1F)=CC=C1NC(=O)C1=CC(C(F)(F)F)=NN1C1=CC=C(ON=C2N)C2=C1 OFJRNBWSFXEHSA-UHFFFAOYSA-N 0.000 claims 1
- NPBKHEMDWREFJJ-UHFFFAOYSA-N 2-[(7-carbamimidoylnaphthalen-2-yl)methyl-[4-(1-ethanimidoylpiperidin-4-yl)oxyphenyl]sulfamoyl]acetic acid Chemical compound C1CN(C(=N)C)CCC1OC1=CC=C(N(CC=2C=C3C=C(C=CC3=CC=2)C(N)=N)S(=O)(=O)CC(O)=O)C=C1 NPBKHEMDWREFJJ-UHFFFAOYSA-N 0.000 claims 1
- 229940123688 Direct Factor Xa inhibitor Drugs 0.000 claims 1
- HGVDHZBSSITLCT-JLJPHGGASA-N Edoxaban Chemical compound N([C@H]1CC[C@@H](C[C@H]1NC(=O)C=1SC=2CN(C)CCC=2N=1)C(=O)N(C)C)C(=O)C(=O)NC1=CC=C(Cl)C=N1 HGVDHZBSSITLCT-JLJPHGGASA-N 0.000 claims 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims 1
- 101001024703 Homo sapiens Nck-associated protein 5 Proteins 0.000 claims 1
- 229940122093 Indirect Factor Xa inhibitor Drugs 0.000 claims 1
- 102100036946 Nck-associated protein 5 Human genes 0.000 claims 1
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 claims 1
- 230000000740 bleeding effect Effects 0.000 claims 1
- IJNIQYINMSGIPS-UHFFFAOYSA-N darexaban Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=CC(O)=C1NC(=O)C1=CC=C(N2CCN(C)CCC2)C=C1 IJNIQYINMSGIPS-UHFFFAOYSA-N 0.000 claims 1
- 229960000622 edoxaban Drugs 0.000 claims 1
- 229960000610 enoxaparin Drugs 0.000 claims 1
- QQBKAVAGLMGMHI-WIYYLYMNSA-N eribaxaban Chemical compound N1([C@H](C[C@H](C1)OC)C(=O)NC=1C(=CC(=CC=1)N1C(C=CC=C1)=O)F)C(=O)NC1=CC=C(Cl)C=C1 QQBKAVAGLMGMHI-WIYYLYMNSA-N 0.000 claims 1
- KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 claims 1
- 229960001318 fondaparinux Drugs 0.000 claims 1
- 229940087051 fragmin Drugs 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 claims 1
- 239000003055 low molecular weight heparin Substances 0.000 claims 1
- 229940127215 low-molecular weight heparin Drugs 0.000 claims 1
- VYNKVNDKAOGAAQ-RUZDIDTESA-N n-[(1r)-2-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-2-oxo-1-phenylethyl]-1h-indole-6-carboxamide Chemical compound C1CN(C)CCC1N1CCN(C(=O)[C@H](NC(=O)C=2C=C3NC=CC3=CC=2)C=2C=CC=CC=2)CC1 VYNKVNDKAOGAAQ-RUZDIDTESA-N 0.000 claims 1
- PFGVNLZDWRZPJW-OPAMFIHVSA-N otamixaban Chemical compound C([C@@H](C(=O)OC)[C@@H](C)NC(=O)C=1C=CC(=CC=1)C=1C=C[N+]([O-])=CC=1)C1=CC=CC(C(N)=N)=C1 PFGVNLZDWRZPJW-OPAMFIHVSA-N 0.000 claims 1
- 229950009478 otamixaban Drugs 0.000 claims 1
- 229950010535 razaxaban Drugs 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4826—Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4833—Thrombin (3.4.21.5)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4853—Kallikrein (3.4.21.34 or 3.4.21.35)
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- 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
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- 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
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- 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)
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- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
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Claims (18)
1. Farmaceutski pripravak koji sadrži nosač i polipeptid za uporabu u terapiji naznačen time što polipeptid sadrži aminokiselinsku sekvencu koja ima najmanje 80% homologije sa SEQ ID NO. 12,
pri čemu polipeptid:
(i) ima smanjenu katalitičku aktivnost;
(ii) sposoban je za vezanje na inhibitor faktora Xa; i
(iii) ne može se sastaviti u kompleks protrombinaze.
2. Farmaceutski pripravak koji sadrži nosač i dvolančani polipeptid za uporabu u terapiji naznačen time što dvolančani polipeptid sadrži aminokiselinsku sekvencu koja ima najmanje 80% homologije sa SEQ ID NO.13,
pri čemu polipeptid:
(i) ima smanjenu katalitičku aktivnost;
(ii) sposoban je za vezanje na inhibitor faktora Xa; i
(iii) ne može se sastaviti u kompleks protrombinaze.
3. Farmaceutski pripravak za uporabu prema patentnom zahtjevu 2, naznačen time što dvolančani polipeptid sadrži aminokiselinsku sekvencu koja ima najmanje 90% homologije sa SEQ ID NO: 13.
4. Farmaceutski pripravak za uporabu prema patentnom zahtjevu 2, naznačen time što dvolančani polipeptid sadrži aminokiselinsku sekvencu koja ima najmanje 95% homologije sa SEQ ID NO: 13.
5. Farmaceutski pripravak koji sadrži nosač i polipeptid za uporabu u terapiji naznačen time što polipeptid sadrži aminokiselinsku sekvencu koja ima najmanje 80% homologije sa SEQ ID NO. 15, te koji ne uključuje laki lanac faktora Xa ali sadrži katalitičku domenu serinske proteaze prisutnu u teškom lancu,
pri čemu polipeptid (i) ima smanjenu katalitičku aktivnost; i (ii) sposoban je za vezanje na inhibitor faktora Xa.
6. Farmaceutski pripravak koji sadrži nosač i polipeptid za uporabu u terapiji naznačen time što polipeptid sadrži ulomak fXa lakog lanca koji ima aminokiselinsku sekvencu SEQ ID NO.14 i ulomak fXa teškog lanca koji ima aminokiselinsku sekvencu SEQ ID NO. 15.
7. Polipeptid pogodan za uporabu u parenteralnoj primjeni naznačen time što sadrži aminokiselinsku sekvencu koja ima najmanje 80% homologije sa SEQ ID NO. 12,
pri čemu polipeptid:
(i) ima smanjenu katalitičku aktivnost;
(ii) sposoban je za vezanje na inhibitor faktora Xa;
(iii) ne može se sastaviti u kompleks protrombinaze; i
(iv) sadrži modificiranu Gla domenu kojoj nedostaju aminokiselinski ostatci 6-39 iz SEQ ID NO.3.
8. Dvolančani polipeptid pogodan za uporabu u parenteralnoj primjeni naznačen time što sadrži aminokiselinsku sekvencu koja ima najmanje 80% homologije sa SEQ ID NO.13,
pri čemu polipeptid:
(i) ima smanjenu katalitičku aktivnost;
(ii) sposoban je za vezanje na inhibitor faktora Xa;
(iii) ne može se sastaviti u kompleks protrombinaze; i
(iv) sadrži modificiranu Gla domenu kojoj nedostaju aminokiselinski ostatci 6-39 iz SEQ ID NO.3.
9. Polipeptid prema patentnom zahtjevu 8, naznačen time što dvolančani polipeptid sadrži aminokiselinsku sekvencu koja ima najmanje 90% homologije sa SEQ ID NO:13.
10. Polipeptid prema patentnom zahtjevu 8, naznačen time što dvolančani polipeptid sadrži aminokiselinsku sekvencu koja ima najmanje 95% homologije sa SEQ ID NO:13.
11. Polipeptid pogodan za uporabu u parenteralnoj primjeni koji sadrži aminokiselinsku sekvencu koja ima najmanje 80% homologije sa SEQ ID NO. 15, i koji ne uključuje laki lanac faktora Xa ali sadrži katalitičku domenu serinske proteaze prisutnu u teškom lancu, pri čemu polipeptid (i) ima smanjenu katalitičku aktivnost; i (ii) sposoban je za vezanje na inhibitor faktora Xa.
12. Dvolančani polipeptid koji sadrži ulomak fXa lakog lanca ha koji ima aminokiselinsku sekvencu SEQ ID NO.14 i ulomak fXa teškog lanca koji ima aminokiselinsku sekvencu SEQ ID NO. 15.
13. Pripravak za uporabu prema bilo kojem od patentnih zahtjeva 1 do 6, ili polipeptid prema bilo kojem od patentnih zahtjeva 7-12, naznačen time što se upotrebljava u postupku prevencije ili smanjenja krvarenja kod subjekta koji je podvrgnut antikoagulacijskoj terapiji s inhibitorom faktora Xa.
14. Pripravak za uporabu prema bilo kojem od patentnih zahtjeva 1 do 6, ili polipeptid prema bilo kojem od patentnih zahtjeva 7-12 naznačen time što se upotrebljava u postupku selektivnog vezanja i inhibiranja egzogeno primijenjenog inhibitora faktora Xa kod subjekta koji je podvrgnut antikoagulacijskoj terapiji.
15. Pripravak za upotrebu ili polipeptid prema patentnom zahtjevu 13 ili 14, naznačen time što je inhibitor faktora Xa neizravni inhibitor faktora Xa.
16. Pripravak za upotrebu ili polipeptid prema patentnom zahtjevu 13 ili 14, naznačen time što je inhibitor faktora Xa izravni inhibitor faktora Xa.
17. Pripravak za upotrebu ili polipeptid prema patentnom zahtjevu 15 ili 16, naznačen time što je inhibitor faktora Xa odabran iz skupine koja sadrži fondaparinuks, idraparinuks, biotinilirani idraparinuks, enoksaparin, fragmin, NAP-5, rNAPc2, inhibitor puta tkivnog faktora, DX-9065a, YM-60828, YM-150, apiksaban, rivaroksaban, PD-348292, otamiksaban, DU-176b, LY517717, GSK913893, razaksaban, heparin niske molekularne težine, betriksaban ili njihovu farmaceutski prihvatljivu sol, i njihove kombinacije.
18. Pripravak za upotrebu ili polipeptid prema patentnom zahtjevu 17, naznačen time što je inhibitor faktora Xa apiksaban, rivaroksaban ili betriksaban.
Applications Claiming Priority (3)
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| US97634307P | 2007-09-28 | 2007-09-28 | |
| US9057408P | 2008-08-20 | 2008-08-20 | |
| EP16167534.3A EP3078743B1 (en) | 2007-09-28 | 2008-09-26 | Antidotes for factor xa inhibitors and methods of using the same |
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| HRP20201071TT HRP20201071T1 (hr) | 2007-09-28 | 2020-07-08 | Protuotrovi za inhibitore faktora xa i postupci njihove uporabe |
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| HRP20161255TT HRP20161255T1 (hr) | 2007-09-28 | 2016-10-03 | Antidoti za inhibitore faktora xa i postupci za njihovu uporabu |
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| EP (4) | EP2915564B1 (hr) |
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