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1. 发明申请

US20130251761A1 ORGANIC COMPOUNDS 有权
公开(公告)号：US20130251761A1
公开(公告)日：2013-09-26
申请号：US13810587
申请日：2011-07-15
申请人： Barry S. Coller , Craig Thomas , Marta Filizola , Joshua Mccoy , Wenwei Huang , Min Shen
发明人： Barry S. Coller , Craig Thomas , Marta Filizola , Joshua Mccoy , Wenwei Huang , Min Shen
IPC分类号： A61K31/519 , A61K45/06 , C07D513/04
CPC分类号： A61K31/519 , A61K31/497 , A61K45/06 , C07D487/04 , C07D513/04 , A61K2300/00
摘要： The present invention relates to compounds and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.

2. 发明授权

US09066948B2 Oxadiazolo[3,2-a]pyrimidines and thiadiazolo[3,2-a]pyrimidines 有权
标题翻译：氧杂双环[3,2-a]嘧啶和噻二唑并[3,2-a]嘧啶
公开(公告)号：US09066948B2
公开(公告)日：2015-06-30
申请号：US13810587
申请日：2011-07-15
申请人： Barry S. Coller , Craig Thomas , Marta Filizola , Joshua McCoy , Wenwei Huang , Min Shen
发明人： Barry S. Coller , Craig Thomas , Marta Filizola , Joshua McCoy , Wenwei Huang , Min Shen
IPC分类号： A01N43/90 , A61K31/519 , C07D487/04 , A61K31/497 , A61K45/06 , C07D513/04
CPC分类号： A61K31/519 , A61K31/497 , A61K45/06 , C07D487/04 , C07D513/04 , A61K2300/00
摘要： The present invention relates to compounds of formula P-1 and related compounds and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The definitions of A, Y, R1, R2, Ra, Ra′, Rb, Rb′, Rc, Rc′, Rd, Rd′, Re, and Re′ are provided herein. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.
摘要翻译：本发明涉及式P-1化合物及其相关化合物和用于抑制和/或减少血小板沉积，粘附和/或聚集的组合物。本文提供了A，Y，R1，R2，Ra，Ra'，Rb，Rb'，Rc，Rc'，Rd，Rd'，Re和Re'的定义。本发明还涉及用于治疗或预防血栓形成障碍的方法，包括中风，心肌梗死，不稳定型心绞痛，外周血管疾病，血管成形术或支架放置后的突然闭合以及血管手术导致的血栓形成。

3. 发明申请

US20120190645A1 Organic compounds 有权
标题翻译：有机化合物
公开(公告)号：US20120190645A1
公开(公告)日：2012-07-26
申请号：US13441412
申请日：2012-04-06
申请人： Robert Blue , Barry S. Coller
发明人： Robert Blue , Barry S. Coller
IPC分类号： A61K31/727 , A61P7/02 , A61K31/519
CPC分类号： C07D513/04 , A61K31/519
摘要： The present invention relates to compounds and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The present invention also relates to methods for screening compounds and compositions useful for inhibiting or reducing platelet deposition, adhesion and/or aggregation. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.
摘要翻译：本发明涉及可用于抑制和/或减少血小板沉积，粘附和/或聚集的化合物和组合物。本发明还涉及用于筛选用于抑制或减少血小板沉积，粘附和/或聚集的化合物和组合物的方法。本发明还涉及用于治疗或预防血栓形成障碍的方法，包括中风，心肌梗死，不稳定型心绞痛，外周血管疾病，血管成形术或支架放置后的突然闭合以及血管手术导致的血栓形成。

4. 发明授权

US08173661B2 Alpha-IIB-beta-3 inhibitors and uses thereof 有权
标题翻译： α-IIB-β-3抑制剂及其用途
公开(公告)号：US08173661B2
公开(公告)日：2012-05-08
申请号：US12514286
申请日：2007-11-08
申请人： Robert Blue , Barry S. Coller
发明人： Robert Blue , Barry S. Coller
IPC分类号： A01N43/90 , A61K31/519 , C07D471/00 , C07D487/00 , C07D491/00
CPC分类号： C07D513/04 , A61K31/519
摘要： The present invention relates to compounds and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The present invention also relates to methods for screening compounds and compositions useful for inhibiting or reducing platelet deposition, adhesion and/or aggregation. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.
摘要翻译：本发明涉及可用于抑制和/或减少血小板沉积，粘附和/或聚集的化合物和组合物。本发明还涉及用于筛选用于抑制或减少血小板沉积，粘附和/或聚集的化合物和组合物的方法。本发明还涉及用于治疗或预防血栓形成障碍的方法，包括中风，心肌梗死，不稳定型心绞痛，外周血管疾病，血管成形术或支架放置后的突然闭合以及血管手术导致的血栓形成。

5. 发明授权

US5854005A Platelet blockade assay 失效
标题翻译：血小板阻断试验
公开(公告)号：US5854005A
公开(公告)日：1998-12-29
申请号：US754773
申请日：1996-11-20
申请人： Barry S. Coller
发明人： Barry S. Coller
IPC分类号： G01N33/50 , G01N33/86 , G01N33/546 , G01N33/552
CPC分类号： G01N33/86 , G01N33/5091 , Y10S435/975
摘要： The present invention is an assay for determining glycoprotein IIb/IIIa receptor blockade in whole blood. Agglutinization of small polymeric beads coated with a glycoprotein IIb/IIIa ligand such as fibrinogen results when the beads are contacted with whole blood containing platelets with glycoprotein IIb/IIIa receptors that are not blocked. Failure to agglutinate indicates that blockade of the GPIIb/IIIa receptors has been achieved. In a preferred embodiment, the addition of a thrombin receptor activator results in an assay that is rapid and convenient enough to be performed at the bedside and that results in agglutination of the small polymeric beads within a convenient, known period of time if the glycoprotein IIb/IIIa receptors are not blocked.
摘要翻译：本发明是用于测定全血中糖蛋白IIb / IIIa受体阻断的测定方法。当珠粒与含有未被阻断的糖蛋白IIb / IIIa受体的全血血小板接触时，会结合涂有糖蛋白IIb / IIIa配体如纤维蛋白原的小聚合物珠粒的凝集。未凝聚表明GPIIb / IIIa受体的阻断已经实现。在一个优选的实施方案中，加入凝血酶受体激活剂导致快速和方便的测定，足以在床边进行，并导致小聚合物珠粒在方便的已知时间段内凝集，如果糖蛋白IIb / IIIa受体不被阻断。

6. 发明授权

US5338725A Anti-aggregatory agents for platelets 失效
公开(公告)号：US5338725A
公开(公告)日：1994-08-16
申请号：US906525
申请日：1992-06-30
申请人： Iwao Ojima , Masakatsu Eguchi , Young-Im Oh , Barry S. Coller
发明人： Iwao Ojima , Masakatsu Eguchi , Young-Im Oh , Barry S. Coller
IPC分类号： A61K38/00 , C07K7/02 , C07K14/75 , A61K37/02 , C07K7/06 , C07K7/08
CPC分类号： C07K14/75 , C07K7/02 , A61K38/00
摘要： The present invention provides synthetic antiaggregatory agents for preventing inhibition of fibrinogen-platelet binding. These anti-aggregatory agents have the general formulas (1)-(5).H--[--(AA.sub.i).sub.i --R--G--D--(AA.sub.j).sub.j --].sub.n --Cx (1)[Ri--C(O)--R--G--D--(AA.sub.j).sub.j --].sub.n --CX (2)Cy--[--AA.sub.i).sub.i --R--G--D--(AA.sub.j).sub.i --].sub.n --Z (3)H--[--(AA.sub.i).sub.i --R--G--D--(AA.sub.j).sub.j --].sub.n --CZ--[--(AA.sub.k).sub.k --R--G--D--(AA.sub.l).sub.l --].sub.m --Z (4)[R.sub.1 --C(O)--R--G--D--(AA.sub.i).sub.i --].sub.n --CZ[--(AA.sub.j).sub.j ]--R--G--D--(AA.sub.k).sub.k --].sub.m --Z (5)in which: R=Arg; G=Gly; D=Asp; AA.sub.i, AA.sub.j, AA.sub.k and AA.sub.l = alpha-, beta- and omega-amino acid residues; (AA.sub.i).sub.i (AA.sub.j).sub.j =peptide chains having the same or different amino acid residues; (AA.sub.k).sub.k =peptide chains having the same or different amino acid residues; (AA.sub.l).sub.l =peptide chains having the same or different amino acid residues; i and j =integers 0-20; m =an integer 1-10; n=an integer 2-10; Cx =a conjugator bearing at least two amine residues in a molecule having 1-30 carbon atoms, i.e, diamines, triamines, tetramines, and polyamines, which can have other functional groups in the molecule; Cy =a conjugator bearing at least two carboxyl residues in a molecule having 1-30 carbon atoms, i.e., aliphatic, aromatic, heteroaromatic, cycloalkyl dicarboxylic acid, tricarboxylic acid, and polycarboxylic acid residues, which can have other functional groups in the molecule; Cz .sup.= a conjugator bearing at least one amine residue and one carboxyl residue in an aromatic or a cycloalkyl skeleton, having 1-30 carbon atoms, i.e., aromatic, heteroaromatic and cycloalkyl amino carboxylic acid, diamino carboxylic acid, diamino dicarboxylic acid, and ployamino polycarboxylic acid residues; R.sub.1 =an alkyl, aromatic, heteroaromatic, or cycloalkyl group having 1-30 carbons, which can have other functional groups in the molecule; and Z=carboxyl, amide, N-substituted amide, hydrazide, N-substituted hydrazide, or ester group.

7. 发明申请

US20100150913A1 ORGANIC COMPOUNDS 有权
标题翻译：有机化合物
公开(公告)号：US20100150913A1
公开(公告)日：2010-06-17
申请号：US12514286
申请日：2007-11-08
申请人： Robert Blue , Barry S. Coller
发明人： Robert Blue , Barry S. Coller
IPC分类号： A61K31/519 , C07D513/04 , A61P7/00 , A61P9/10 , A61K31/727 , A61K31/715 , A61K38/45 , A61K31/60 , A61K39/395 , G01N33/53 , A61F2/06
CPC分类号： C07D513/04 , A61K31/519
摘要： The present invention relates to compounds and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The present invention also relates to methods for screening compounds and compositions useful for inhibiting or reducing platelet deposition, adhesion and/or aggregation. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.
摘要翻译：本发明涉及可用于抑制和/或减少血小板沉积，粘附和/或聚集的化合物和组合物。本发明还涉及用于筛选用于抑制或减少血小板沉积，粘附和/或聚集的化合物和组合物的方法。本发明还涉及用于治疗或预防血栓形成障碍的方法，包括中风，心肌梗死，不稳定型心绞痛，外周血管疾病，血管成形术或支架放置后的突然闭合以及血管手术导致的血栓形成。

8. 发明授权

US5770198A Platelet-specific chimeric 7E3 immunoglobulin 失效
标题翻译：血小板特异性嵌合7E3免疫球蛋白
公开(公告)号：US5770198A
公开(公告)日：1998-06-23
申请号：US375074
申请日：1995-01-17
申请人： Barry S. Coller , David M. Knight
发明人： Barry S. Coller , David M. Knight
IPC分类号： A61K38/00 , A61P7/02 , C07K16/28 , C12N15/13 , A61K39/395
CPC分类号： C07K16/2848 , A61K38/00 , C07K2317/24 , C07K2317/55 , C07K2319/00 , C07K2319/30 , C07K2319/33
摘要： Platelet-specific, chimeric immunoglobulin and immunoglobulin fragments are described. The chimeric molecules are made up of a nonhuman antigen binding region and a human constant region. Preferred immunoglobulins are specific for glycoprotein IIb/IIIa receptor in its complexed form; they block ligand binding to the receptor and prevent platelet aggregation. The immunoglobulins are useful in anti-thrombotic therapy when administered alone or in conjunction with thrombolytic agents, as well as in thrombus imaging.
摘要翻译：描述血小板特异性，嵌合免疫球蛋白和免疫球蛋白片段。嵌合分子由非人抗原结合区和人恒定区组成。优选的免疫球蛋白对其复合形式的糖蛋白IIb / IIIa受体是特异性的; 它们阻断配体结合受体并防止血小板聚集。当单独或联合溶栓剂以及血栓成像时，免疫球蛋白可用于抗血栓形成治疗。

9. 发明授权

US5328840A Method for preparing targeted carrier erythrocytes 失效
标题翻译：靶向载体红细胞的制备方法
公开(公告)号：US5328840A
公开(公告)日：1994-07-12
申请号：US790851
申请日：1991-11-12
申请人： Barry S. Coller
发明人： Barry S. Coller
IPC分类号： A61K9/50 , A61K35/18 , A61K38/00 , C07K14/75 , C12N5/00 , C12N11/08 , A61K37/02 , A61K37/00
CPC分类号： A61K9/5068 , A61K35/18 , C07K14/75 , A61K38/00
摘要： The present invention provides new compounds and methods for promoting platelet aggregation, and controlling bleeding. The present invention is based on the surprising discovery that erythrocytes conjugated to certain peptides and polypeptides containing an R-G-D (Arg-Gly-Asp) sequence (collectively termed herein "RGD peptides") according to the invention, selectively bind to activated platelets but not to unactivated platelets. In recognition of the dual nature of the derivatized erythrocytes, they are termed herein "thrombo-erythrocytes". The thrombo-erythrocytes have no significant change in their rheological properties. In a preferred aspect, the thrombo-erythrocytes have the majority of RGD peptide cross-linked specifically to glycophorin A and glycophorin B on the surface of the erythrocyte. In the thrombo-erythrocytes of the invention, preferably, the N-terminal Arg of the R-G-D sequence should be spaced within 9-50 Angstroms, more preferably 10-40 Angstroms, and most preferably 11-25 Angstroms, from the erythrocyte protein to which the RGD peptide is conjugated. The invention is further directed to erthrocytes modified by replacement of their intracellular contents with a composition comprising a label or agent. Such modified erythrocytes are termed herein "carrier erythrocytes". The carrier erythrocytes have use in delivery of such labels or biologically active agents to specific tissues by conjugation to a targeting agent.
摘要翻译：本发明提供了促进血小板聚集和控制出血的新化合物和方法。本发明基于令人惊奇的发现，即与根据本发明的含有RGD（Arg-Gly-Asp）序列（统称为“RGD肽”）的某些肽和多肽缀合的红细胞选择性结合活化的血小板而不是未激活的血小板鉴于衍生化的红细胞的双重性质，它们在本文中称为“血小板红细胞”。血小板红细胞的流变特性没有明显变化。在优选的方面，血小板红细胞中大部分RGD肽与红细胞表面的血型糖蛋白A和血型糖蛋白B特异性交联。在本发明的血小板红细胞中，优选地，RGD序列的N-末端Arg应该从红细胞蛋白质的9-50埃，更优选10-40埃，最优选11-25埃， RGD肽共轭。本发明还涉及通过用包含标记或试剂的组合物置换其细胞内内容物而修饰的红细胞。这种修饰的红细胞在本文中称为“载体红细胞”。载体红细胞通过与靶向剂缀合而用于将这些标记物或生物活性剂递送至特定组织。

10. 发明授权

US09341637B2 Controlled platelet activation to monitor therapy of ADP antagonists 有权
公开(公告)号：US09341637B2
公开(公告)日：2016-05-17
申请号：US12943413
申请日：2010-11-10
申请人： Barry S. Coller , Dennis Durbin
发明人： Barry S. Coller , Dennis Durbin
IPC分类号： G01N33/86
CPC分类号： G01N33/86
摘要： A method is provided of determining whether an individual has reduced ability to form platelet thrombi due to inhibition of platelet activation initiation, signal transduction and/or GPIIb/IIIa blockade. A blood sample is obtained from the individual being assessed. The blood sample is mixed in combination with 1) an anticoagulant; 2) sufficient buffer to maintain the pH and salt concentration of the anticoagulated blood within a range suitable for platelet aggregation; 3) a platelet GPIIb/IIIa receptor ligand immobilized on a solid surface; 4) one or more agents to enhance a signal transduction pathway and 5) a receptor activator. The combination is incubated under conditions for agglutinating particles. Platelet-mediated agglutination is assessed in the agitated mixture. The absence of agglutination indicates that the individual has a reduced ability to form platelet thrombi.

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