JP2007521294A5 - - Google Patents
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- JP2007521294A5 JP2007521294A5 JP2006518692A JP2006518692A JP2007521294A5 JP 2007521294 A5 JP2007521294 A5 JP 2007521294A5 JP 2006518692 A JP2006518692 A JP 2006518692A JP 2006518692 A JP2006518692 A JP 2006518692A JP 2007521294 A5 JP2007521294 A5 JP 2007521294A5
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- 210000003324 RBC Anatomy 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 8
- 239000000969 carrier Substances 0.000 claims description 6
- 239000003146 anticoagulant agent Substances 0.000 claims description 5
- 230000002934 lysing Effects 0.000 claims description 2
- 210000003743 Erythrocytes Anatomy 0.000 claims 4
- 230000015271 coagulation Effects 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 238000005345 coagulation Methods 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 230000003449 preventive Effects 0.000 claims 2
- 210000004369 Blood Anatomy 0.000 claims 1
- 206010009802 Coagulopathy Diseases 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 230000035602 clotting Effects 0.000 claims 1
- 238000005755 formation reaction Methods 0.000 claims 1
- 230000002439 hemostatic Effects 0.000 claims 1
- 239000000546 pharmaceutic aid Substances 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 description 4
- 230000004059 degradation Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 229950003499 FIBRIN Drugs 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- NKCXQMYPWXSLIZ-PSRDDEIFSA-N (2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-m Chemical compound O=C([C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)[C@@H](C)O)[C@@H](C)O)C(C)C)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O NKCXQMYPWXSLIZ-PSRDDEIFSA-N 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 229940012952 Fibrinogen Drugs 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 229940019698 Fibrinogen containing hemostatics Drugs 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 210000004072 Lung Anatomy 0.000 description 1
- 210000002381 Plasma Anatomy 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 210000002966 Serum Anatomy 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 210000004027 cells Anatomy 0.000 description 1
- 230000000295 complement Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002949 hemolytic Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000001404 mediated Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
Description
ＲＢＣあたり６．５〜７．５×１０５のｔＰＡ分子を有するｂ１０ＲＢＣ／ＳＡ／ｂｔＰＡ錯体の活性を、Murcianoらにより開示されたように（Am. J. Physiol. Lung Cell Mol. Physiol 2002 282: L529-539）、125I−標識フィブリノゲンにトロンビンを添加することにより形成された、フィブリン塊中で試験した。ＲＢＣ／ｔＰＡを注入した凝血塊は、上清中に125ヨウ素を放出しながら分解された。同様の結果は、同一源のＲＢＣｓに連結するｔＰＡを用いた、ラット、マウスおよびヒト血しょうから形成された凝血塊でも観察された。新鮮血清中３７℃で２４時間の培養期間中、補体によるＲＢＣ／ｔＰＡの溶血反応は、コントロールＲＢＣｓに匹敵し、ｔＰＡの小画分のみがＲＢＣｓから分離した。フリーｔＰＡおよびＲＢＣ／ｔＰＡによる、先在する凝血塊対初期フィブリン塊の分解は、in vtroで最初に比較された。フリーｔＰＡは、初期凝血塊の９０％溶解に対し、先在するものの５０％分解を引き起こした（１．９倍の相違）。対照的に、ＲＢＣなどの、例えば３〜５ミクロンの大きさのキャリアに連結したｔＰＡは、初期凝血塊の８０％分解に対し、先在する塊の５％未満の分解を引き起こした（１７倍の相違）。従って、ＲＢＣなどの、例えば３〜５ミクロンの大きさのキャリアに連結した抗血栓剤を含む、本発明の組成物は、抗血栓剤単独より、初期凝血塊に対して１０倍以上大きな選択性を示す。
Claims (8)
- 大きさが赤血球に類似のキャリアに生体適合的に結合した治療薬を含む、組成物。
- キャリアが赤血球である、請求項１に記載の組成物。
- 治療薬が抗血栓剤である、請求項１に記載の組成物。
- 被験者に先在する止血塊を容認しながら、被験者の初期血管内凝血を選択的に溶解するための、請求項３に記載の組成物。
- 請求項３の組成物および薬学的に許容できる賦形剤を含む、血栓予防薬。
- 初期血管内凝血形成の予防のための、請求項５に記載の血栓予防薬。
- 大きさが赤血球に類似のキャリアに生体適合的に結合した抗血栓剤の、被験者に先在する止血塊を容認しながら、被験者の初期血管内凝血を選択的に溶解するための組成物の製造における使用。
- 大きさが赤血球に類似のキャリアに生体適合的に結合した抗血栓剤の、初期血管内凝血形成の予防のための組成物の製造における使用。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/611,723 US7041287B2 (en) | 1998-05-21 | 2003-07-01 | Compositions and methods for selective dissolution of nascent intravascular blood clots |
| PCT/US2004/020660 WO2005004804A2 (en) | 2003-07-01 | 2004-06-28 | Compositions and methods for selective dissolution of nascent intravascular blood clots |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007521294A JP2007521294A (ja) | 2007-08-02 |
| JP2007521294A5 true JP2007521294A5 (ja) | 2007-09-13 |
Family
ID=34062346
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006518692A Pending JP2007521294A (ja) | 2003-07-01 | 2004-06-28 | 初期血管内凝血を選択的に分解する組成物及び方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US7041287B2 (ja) |
| EP (1) | EP1648497A2 (ja) |
| JP (1) | JP2007521294A (ja) |
| AU (1) | AU2004255196B2 (ja) |
| CA (1) | CA2530529A1 (ja) |
| WO (1) | WO2005004804A2 (ja) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999059611A1 (en) * | 1998-05-21 | 1999-11-25 | The Trustees Of The University Of Pennsylvania | Compositions and methods for prevention and treatment of uncontrolled formation of intravascular fibrin clots |
| US7674466B2 (en) * | 1999-08-05 | 2010-03-09 | The Trustees Of The University Of Pennsylvania | Targeting and prolonging association of drugs to the luminal surface of the pulmonary vascular endothelial cells using antibodies that bind to ICAM-1 |
| US7405276B2 (en) * | 2000-11-01 | 2008-07-29 | Elusys Therapeutics, Inc. | Method of producing bispecific molecules by protein trans-splicing |
| EP1380290A1 (en) | 2002-07-09 | 2004-01-14 | Universitair Medisch Centrum Utrecht | Cross-beta structure pathway and its therapeutic relevance |
| US20070003552A1 (en) * | 2002-07-09 | 2007-01-04 | Gebbink Martijn F B | Cross-beta structure comprising amyloid binding proteins and methods for detection of the cross-beta structure, for modulating cross-beta structures fibril formation and for modulating cross-beta structure-mediated toxicity and method for interfering with blood coagulation |
| US20080317761A1 (en) * | 2004-04-28 | 2008-12-25 | The Trustees Of The University Of Pennsylvania | Peptide-Mediated Protein Transduction Into Cells of the Hematopoietic Lineage |
| US8119128B2 (en) * | 2004-10-29 | 2012-02-21 | The Regents Of The University Of Colorado, A Body Corporate | Antibodies that bind urokinase-type plasminogen activator and epitopes therefor |
| US20090202980A1 (en) * | 2005-03-21 | 2009-08-13 | Crossbeta Biosciences B.V. | Cross-Beta Structure Comprising Amyloid Binding Proteins and Methods for Detection of the Cross-Beta Structure, for Modulating Cross-Beta Structures Fibril Formation and for Modulating Cross-Beta Structure-Mediated Toxicity and Method for Interfering With Blood Coagulation |
| EP2386861A3 (en) * | 2005-07-13 | 2012-07-18 | Crossbeta Biosciences B.V. | Cross-ß structure binding compounds |
| US8114832B2 (en) * | 2005-07-13 | 2012-02-14 | Crossbeta Biosciences B.V. | Method for detecting and/or removing a protein comprising a cross-beta structure from a pharmaceutical composition |
| AU2006267177A1 (en) * | 2005-07-13 | 2007-01-18 | Crossbeta Biosciences B.V. | Methods for determining the effect of a treatment on the cross-beta structure content of a protein; selection of treatments and uses thereof |
| US20090130104A1 (en) * | 2005-10-05 | 2009-05-21 | The Trustees Of The University Of Pennsylvania | Fusion proteins for inhibition and dissolution of coagulation |
| WO2007108675A1 (en) * | 2006-03-17 | 2007-09-27 | Crossbeta Biosciences B.V. | Methods of binding of cross-beta structures by chaperones |
| AU2008257419B2 (en) * | 2007-05-23 | 2013-10-24 | The Trustees Of The University Of Pennsylvania | Targeted carriers for intracellular drug delivery |
| EP2058000A1 (en) * | 2007-11-08 | 2009-05-13 | Crossbeta Biosciences B.V. | Immunogenic compositions capable of activating T cells |
| EP2058001A1 (en) * | 2007-11-08 | 2009-05-13 | Crossbeta Biosciences B.V. | Enhancement of immunogenicity of antigens |
| WO2009086552A1 (en) * | 2008-01-02 | 2009-07-09 | The Trustees Of The University Of Pennsylvania | Targeting recombinant therapeutics to circulating red blood cells |
| CA2807942C (en) | 2010-08-10 | 2021-07-27 | Ecole Polytechnique Federale De Lausanne | Erythrocyte-binding therapeutics |
| US9517257B2 (en) | 2010-08-10 | 2016-12-13 | Ecole Polytechnique Federale De Lausanne (Epfl) | Erythrocyte-binding therapeutics |
| US9850296B2 (en) | 2010-08-10 | 2017-12-26 | Ecole Polytechnique Federale De Lausanne (Epfl) | Erythrocyte-binding therapeutics |
| US10946079B2 (en) | 2014-02-21 | 2021-03-16 | Ecole Polytechnique Federale De Lausanne | Glycotargeting therapeutics |
| US10953101B2 (en) | 2014-02-21 | 2021-03-23 | École Polytechnique Fédérale De Lausanne (Epfl) | Glycotargeting therapeutics |
| US10046056B2 (en) | 2014-02-21 | 2018-08-14 | École Polytechnique Fédérale De Lausanne (Epfl) | Glycotargeting therapeutics |
| MX2016010835A (es) | 2014-02-21 | 2017-07-11 | Anokion Sa | Terapeuticos dirigidos a la glucosa. |
| EP3638296A1 (en) | 2017-06-16 | 2020-04-22 | The University Of Chicago | Compositions and methods for inducing immune tolerance |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60200169A (ja) * | 1984-03-23 | 1985-10-09 | Green Cross Corp:The | 線維素溶解酵素前駆体測定用試薬 |
| WO1999059611A1 (en) * | 1998-05-21 | 1999-11-25 | The Trustees Of The University Of Pennsylvania | Compositions and methods for prevention and treatment of uncontrolled formation of intravascular fibrin clots |
-
2003
- 2003-07-01 US US10/611,723 patent/US7041287B2/en not_active Expired - Lifetime
-
2004
- 2004-06-28 JP JP2006518692A patent/JP2007521294A/ja active Pending
- 2004-06-28 WO PCT/US2004/020660 patent/WO2005004804A2/en active Search and Examination
- 2004-06-28 CA CA002530529A patent/CA2530529A1/en not_active Abandoned
- 2004-06-28 EP EP04777178A patent/EP1648497A2/en not_active Withdrawn
- 2004-06-28 AU AU2004255196A patent/AU2004255196B2/en not_active Ceased
-
2006
- 2006-02-13 US US11/352,720 patent/US20060140917A1/en active Pending
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