JP2012533552A5 - - Google Patents
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- JP2012533552A5 JP2012533552A5 JP2012520756A JP2012520756A JP2012533552A5 JP 2012533552 A5 JP2012533552 A5 JP 2012533552A5 JP 2012520756 A JP2012520756 A JP 2012520756A JP 2012520756 A JP2012520756 A JP 2012520756A JP 2012533552 A5 JP2012533552 A5 JP 2012533552A5
- Authority
- JP
- Japan
- Prior art keywords
- unit dose
- dose formulation
- formulation
- inhibitor
- polypeptide
- 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.)
- Granted
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- 239000000203 mixture Substances 0.000 claims description 83
- 238000009472 formulation Methods 0.000 claims description 81
- 229920001184 polypeptide Polymers 0.000 claims description 30
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 30
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 30
- 229940123583 Factor Xa inhibitor Drugs 0.000 claims description 20
- 235000013305 food Nutrition 0.000 claims description 14
- 239000003112 inhibitor Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 9
- 229950011103 betrixaban Drugs 0.000 claims description 8
- 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 description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- 230000010100 anticoagulation Effects 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 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 description 6
- 229960003886 apixaban Drugs 0.000 claims description 6
- 239000003055 low molecular weight heparin Substances 0.000 claims description 6
- 229940127215 low-molecular weight heparin Drugs 0.000 claims description 6
- 239000003550 marker Substances 0.000 claims description 6
- 229960001148 rivaroxaban Drugs 0.000 claims description 6
- 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 description 6
- 230000003285 pharmacodynamic effect Effects 0.000 claims description 5
- -1 rNAPc2 Proteins 0.000 claims description 5
- 230000000740 bleeding effect Effects 0.000 claims description 4
- 238000001802 infusion Methods 0.000 claims description 4
- 230000003472 neutralizing effect Effects 0.000 claims description 4
- 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 description 4
- LJCBAPRMNYSDOP-LVCYMWGESA-N (2s)-3-(7-carbamimidoylnaphthalen-2-yl)-2-[4-[(3s)-1-ethanimidoylpyrrolidin-3-yl]oxyphenyl]propanoic acid;hydron;chloride;pentahydrate Chemical compound O.O.O.O.O.Cl.C1N(C(=N)C)CC[C@@H]1OC1=CC=C([C@H](CC=2C=C3C=C(C=CC3=CC=2)C(N)=N)C(O)=O)C=C1 LJCBAPRMNYSDOP-LVCYMWGESA-N 0.000 claims description 2
- GEHAEMCVKDPMKO-HXUWFJFHSA-N 1-[1-[(2s)-3-(6-chloronaphthalen-2-yl)sulfonyl-2-hydroxypropanoyl]piperidin-4-yl]-1,3-diazinan-2-one Chemical compound O=C([C@@H](CS(=O)(=O)C=1C=C2C=CC(Cl)=CC2=CC=1)O)N(CC1)CCC1N1CCCNC1=O GEHAEMCVKDPMKO-HXUWFJFHSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 101001024703 Homo sapiens Nck-associated protein 5 Proteins 0.000 claims description 2
- 102100036946 Nck-associated protein 5 Human genes 0.000 claims description 2
- 108090000190 Thrombin Proteins 0.000 claims description 2
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 claims description 2
- 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 description 2
- 230000001419 dependent effect Effects 0.000 claims description 2
- 229960000622 edoxaban Drugs 0.000 claims description 2
- 229960000610 enoxaparin Drugs 0.000 claims description 2
- 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 description 2
- KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical group 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 description 2
- 229960001318 fondaparinux Drugs 0.000 claims description 2
- 229940087051 fragmin Drugs 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 claims description 2
- 229960004072 thrombin Drugs 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 238000000034 method Methods 0.000 description 12
- 235000002639 sodium chloride Nutrition 0.000 description 10
- 239000012267 brine Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000000729 antidote Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22588709P | 2009-07-15 | 2009-07-15 | |
| US61/225,887 | 2009-07-15 | ||
| PCT/US2010/042015 WO2011008885A1 (en) | 2009-07-15 | 2010-07-14 | Unit dose formulation of antidotes for factor xa inhibitors and methods of using the same |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015158084A Division JP2015205933A (ja) | 2009-07-15 | 2015-08-10 | 第Ｘａ因子インヒビターの解毒剤の単位用量処方物およびその使用方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012533552A JP2012533552A (ja) | 2012-12-27 |
| JP2012533552A5 true JP2012533552A5 (enExample) | 2013-08-08 |
| JP6163304B2 JP6163304B2 (ja) | 2017-07-12 |
Family
ID=42989417
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012520756A Active JP6163304B2 (ja) | 2009-07-15 | 2010-07-14 | 第Ｘａ因子インヒビターの解毒剤の単位用量処方物およびその使用方法 |
| JP2015158084A Pending JP2015205933A (ja) | 2009-07-15 | 2015-08-10 | 第Ｘａ因子インヒビターの解毒剤の単位用量処方物およびその使用方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015158084A Pending JP2015205933A (ja) | 2009-07-15 | 2015-08-10 | 第Ｘａ因子インヒビターの解毒剤の単位用量処方物およびその使用方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (8) | US9056106B2 (enExample) |
| EP (1) | EP2453910B1 (enExample) |
| JP (2) | JP6163304B2 (enExample) |
| CN (1) | CN102625712B (enExample) |
| CA (1) | CA2767858C (enExample) |
| ES (1) | ES2605801T3 (enExample) |
| PT (1) | PT2453910T (enExample) |
| WO (1) | WO2011008885A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20090010098A (ko) | 2006-05-05 | 2009-01-28 | 밀레니엄 파머슈티컬스 인코퍼레이티드 | Ｘａ 인자 저해제 |
| PL2915564T3 (pl) * | 2007-09-28 | 2021-07-19 | Alexion Pharmaceuticals, Inc. | Antidota dla inhibitorów czynnika Xa i sposoby ich stosowania |
| EP3121271B1 (en) | 2009-03-30 | 2019-07-24 | Portola Pharmaceuticals, Inc. | Antidotes for factor xa inhibitors and methods of using the same |
| JP6163304B2 (ja) | 2009-07-15 | 2017-07-12 | ポートラ ファーマシューティカルズ， インコーポレイテッド | 第Ｘａ因子インヒビターの解毒剤の単位用量処方物およびその使用方法 |
| CA2784921A1 (en) | 2009-12-17 | 2011-07-14 | Millennium Pharmaceuticals, Inc. | Salts and crystalline forms of a factor xa inhibitor |
| US8742120B2 (en) * | 2009-12-17 | 2014-06-03 | Millennium Pharmaceuticals, Inc. | Methods of preparing factor xa inhibitors and salts thereof |
| CN104254603A (zh) * | 2012-02-14 | 2014-12-31 | 博尔托拉制药公司 | 用于制备xa因子抑制剂的重组解毒剂的方法 |
| HK1204964A1 (en) | 2012-02-16 | 2015-12-11 | Portola Pharmaceuticals, Inc. | Modulation of factor xa inhibitor mediated blood loss by partial and transient administration of antidote |
| BR112015001628A2 (pt) * | 2012-07-25 | 2017-11-07 | Catalyst Biosciences Inc | polipeptídeos de fator x modificados e uso dos mesmos |
| FR3000895B1 (fr) * | 2013-01-11 | 2017-02-24 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies Sa | Utilisation d'antidotes d'inhibiteurs de la coagulation indiques dans la prevention ou le traitement de pathologies thromboemboliques |
| SG10201705189XA (en) * | 2013-01-24 | 2017-07-28 | Portola Pharm Inc | INHIBITION OF TISSUE FACTOR PATHWAY INHIBITOR WITH FACTOR Xa DERIVATIVES |
| CN104994868A (zh) * | 2013-01-31 | 2015-10-21 | 辉瑞公司 | 用于抵消因子Xa抑制的组合物和方法 |
| PE20160877A1 (es) * | 2013-09-24 | 2016-09-11 | Pfizer | Composiciones que comprenden poblaciones heterogeneas de proteinas recombinantes humanas de factor xa de coagulacion |
| WO2015066606A2 (en) * | 2013-11-01 | 2015-05-07 | The Children's Hospital Of Philadelphia | Compositions and methods for increasing the half-life of factor xa |
| EP3096779B1 (en) * | 2014-01-24 | 2019-12-18 | Pfizer Inc | Compositions and methods for treating intracerebral hemorrhage |
| US9545383B2 (en) | 2014-04-01 | 2017-01-17 | Massachusetts Institute Of Technology | Blood clotting control |
| LT3149163T (lt) | 2014-05-26 | 2020-09-25 | Academisch Ziekenhuis Leiden | Prohemostatiniai baltymai, skirti kraujavimo gydymui |
| US10676731B2 (en) | 2014-08-19 | 2020-06-09 | The Children's Hospital Of Philadelphia | Compositions and methods for modulating factor IX function |
| EA036091B1 (ru) * | 2014-08-20 | 2020-09-25 | Портола Фармасьютикалз, Инк. | ВОДНЫЕ СОСТАВЫ АНТИДОТОВ ФАКТОРА Xa (fXa) ДЛЯ ПРЕДУПРЕЖДЕНИЯ ИЛИ УМЕНЬШЕНИЯ КРОВОТЕЧЕНИЯ И ИХ ПРИМЕНЕНИЕ |
| WO2017147522A1 (en) | 2016-02-24 | 2017-08-31 | Portola Pharmaceuticals, Inc. | Lyophilized formulations for factor xa antidote |
| TW201802121A (zh) | 2016-05-25 | 2018-01-16 | 諾華公司 | 抗因子XI/XIa抗體之逆轉結合劑及其用途 |
| CN110167575B (zh) | 2016-06-17 | 2024-03-15 | 阿雷克森制药公司 | 因子xa衍生物的制备 |
| AU2017383232B2 (en) | 2016-12-23 | 2024-09-12 | Novartis Ag | Factor XI antibodies and methods of use |
| JP7641903B2 (ja) * | 2019-02-07 | 2025-03-07 | 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 | 頭蓋内出血の治療方法及び効果の評価方法 |
| US12073926B2 (en) | 2020-09-21 | 2024-08-27 | Instrumentation Laboratory Company | Detecting and monitoring oral anticoagulants or intravenous direct thrombin inhibitors in a blood sample |
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| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| DE3546806C2 (enExample) | 1985-03-30 | 1991-03-28 | Marc Genf/Geneve Ch Ballivet | |
| US6492107B1 (en) | 1986-11-20 | 2002-12-10 | Stuart Kauffman | Process for obtaining DNA, RNA, peptides, polypeptides, or protein, by recombinant DNA technique |
| US5837249A (en) | 1985-04-19 | 1998-11-17 | The Wistar Institute | Method for generating an immunogenic T cell response protective against a virus |
| US4818700A (en) | 1985-10-25 | 1989-04-04 | Phillips Petroleum Company | Pichia pastoris argininosuccinate lyase gene and uses thereof |
| US5618920A (en) | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
| US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
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-
2010
- 2010-07-14 JP JP2012520756A patent/JP6163304B2/ja active Active
- 2010-07-14 ES ES10737699.8T patent/ES2605801T3/es active Active
- 2010-07-14 CN CN201080040105.XA patent/CN102625712B/zh active Active
- 2010-07-14 PT PT107376998T patent/PT2453910T/pt unknown
- 2010-07-14 WO PCT/US2010/042015 patent/WO2011008885A1/en not_active Ceased
- 2010-07-14 US US12/836,536 patent/US9056106B2/en active Active
- 2010-07-14 CA CA2767858A patent/CA2767858C/en active Active
- 2010-07-14 EP EP10737699.8A patent/EP2453910B1/en active Active
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2014
- 2014-06-30 US US14/320,199 patent/US20150025011A1/en not_active Abandoned
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2015
- 2015-08-10 JP JP2015158084A patent/JP2015205933A/ja active Pending
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2016
- 2016-07-15 US US15/212,105 patent/US20170014492A1/en not_active Abandoned
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2017
- 2017-12-06 US US15/833,520 patent/US10765726B2/en active Active
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2020
- 2020-07-30 US US16/943,933 patent/US20210085762A1/en not_active Abandoned
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2022
- 2022-01-05 US US17/569,402 patent/US20230000957A1/en not_active Abandoned
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2023
- 2023-07-14 US US18/352,637 patent/US20240189401A1/en not_active Abandoned
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2024
- 2024-10-08 US US18/909,369 patent/US20250186563A1/en active Pending
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