公开(公告)号：US5658746A

公开(公告)日：1997-08-19

申请号：US552432

申请日：1995-11-03

申请人： Michael H. Coan ,  Cynthia J. Galloway ,  Vivian W. Lee

发明人： Michael H. Coan ,  Cynthia J. Galloway ,  Vivian W. Lee

IPC分类号： C12N15/09 ,  A61K47/48 ,  C12N15/02 ,  G01N33/554 ,  G01N33/566 ,  G01N33/68 ,  G01N33/567 ,  G01N33/53 ,  G01N33/531

CPC分类号： A61K47/48546 ,  A61K47/48369 ,  G01N33/554 ,  G01N33/566 ,  G01N33/6857 ,  G01N33/6863

摘要： A method of controlling the amount of a biologically active substance binding to a cell surface having both receptors to the substance and receptors for the Fc domain of an antibody that can complex with the substance or other antibodies that can complex with the substance. By exploiting the generally more numerous Fc receptor sites, substance binding can be increased and/or controlled. Method contemplates controlling amounts of substances such as cytokines, hormones, and growth factors that are associated with cells such as monocytes, macrophages, granulocytes, B cells, T cells, and platelets. Method is illustrated using conjugated antibodies to tissue necrosis factor (TNF) to increase the binding of TNF to monocytes.

摘要翻译： 控制与具有物质受体的细胞表面的结合的生物活性物质的量和与可与物质复合的物质或其它抗体复合的抗体Fc结构域的受体的量的方法。 通过利用通常更多的Fc受体位点，可以增加和/或控制物质结合。 方法考虑控制与诸如单核细胞，巨噬细胞，粒细胞，B细胞，T细胞和血小板等细胞相关的细胞因子，激素和生长因子的物质的量。 说明使用组织坏死因子（TNF）的结合抗体来增加TNF与单核细胞的结合的方法。

公开(公告)号：US4364861A

公开(公告)日：1982-12-21

申请号：US153341

申请日：1980-05-27

申请人： Gautam Mitra ,  Michael H. Coan ,  Shohachi Wada

发明人： Gautam Mitra ,  Michael H. Coan ,  Shohachi Wada

IPC分类号： A61K38/00 ,  C12N9/64 ,  A61K35/14 ,  A61K35/16 ,  A61K37/02 ,  C07G7/00

CPC分类号： C12N9/647 ,  A61K38/00 ,  Y10S530/831

摘要： Blood-coagulation-promoting products substantially free of thrombin are prepared from human blood plasma by contacting a human blood plasma fraction containing coagulation Factors II, VII, IX and X with an anion exchanger to adsorb the coagulation Factors, which are subsequently eluted from the anion exchanger. The eluate is treated to generate a substance having Factor VIII Inhibitor Bypassing Activity and being substantially free of thrombin, and activated Factor X.

摘要翻译： 通过将含有凝血因子II，VII，IX和X的人血浆级分与阴离子交换剂接触以吸附凝血因子，从人血浆中制备基本上不含凝血酶的促凝血产物，随后从阴离子 交换机。 处理洗脱液以产生具有因子VIII抑制剂旁路活性并且基本上不含凝血酶和活化因子X的物质。

公开(公告)号：US4391746A

公开(公告)日：1983-07-05

申请号：US374835

申请日：1982-05-05

申请人： Gautam Mitra ,  Michael H. Coan ,  Shohachi Wada

发明人： Gautam Mitra ,  Michael H. Coan ,  Shohachi Wada

IPC分类号： A61K38/00 ,  C12N9/64 ,  A61K35/14 ,  A61K35/16 ,  A61K37/02 ,  C07G7/00

CPC分类号： C12N9/644 ,  C12N9/647 ,  C12Y304/21022 ,  A61K38/00 ,  Y10S530/83 ,  Y10S530/831

摘要： Blood-coagulation-promoting products substantially free of thrombin are prepared from human blood plasma by contacting a human blood plasma fraction containing coagulation Factors II, VII, IX and X with an anion exchanger to adsorb the coagulation Factors, which are subsequently eluted from the anion exchanger. The eluate is treated to generate a substance having Factor VIII Inhibitor Bypassing Activity and being substantially free of thrombin, and activated Factor X.

公开(公告)号：US4229540A

公开(公告)日：1980-10-21

申请号：US54127

申请日：1979-07-02

申请人： Michael H. Coan

发明人： Michael H. Coan

IPC分类号： A61K38/00 ,  C12N9/48 ,  C12N9/64 ,  C12Q1/56 ,  C12N9/14 ,  C12N9/50

CPC分类号： C12Q1/56 ,  C12N9/48 ,  C12N9/6421 ,  A61K38/00

摘要： A previously undescribed hydrolytic enzyme has been successfully isolated from human plasma and purified to homogeneity. The enzyme has a molecular weight of about 70,000 daltons, has a Km for the substrate H-D-Phe-Pip-Arg-PNA of about 0.057 mM, a K.sub.I for benzamidine of about 1.1.times.10.sup.-5 M, is bindable to and elutable from insoluble barium salts, is inhibited by antithrombin III, especially in the presence of heparin, and, in vitro, has been found to activate and degrade human Factor VIII, activate human Factor V, and inhibit platelet aggregation induced by ADP, epinephrine, or collagen, thus providing a substance useful for antithrombotic studies.

摘要翻译： 已经成功地从人血浆中分离出先前未描述的水解酶，并纯化至均匀。 该酶具有约70,000道尔顿的分子量，对于底物，具有约0.057mM的底物HD-Phe-Pip-Arg-PNA的Km，约1.1×10-5M的苄脒的KI可结合并可溶于不溶性 钡盐被抗凝血酶III抑制，特别是在肝素存在下，体外已经发现活化和降解人因子VIII，激活人因子V，抑制ADP，肾上腺素或胶原诱导的血小板聚集， 从而提供一种可用于抗血栓形成研究的物质。

公开(公告)号：US4697003A

公开(公告)日：1987-09-29

申请号：US793807

申请日：1985-11-01

申请人： Michael H. Coan

发明人： Michael H. Coan

IPC分类号： A61K35/14 ,  A61K35/16 ,  A61K38/00 ,  A61K38/16 ,  A61K38/55 ,  A61P11/00 ,  C07K14/81 ,  C07G7/00

CPC分类号： C07K14/8125 ,  A61K38/00 ,  Y10S210/905 ,  Y10S530/831

摘要： There is disclosed a method for separating alpha-1-proteinase inhibitor (also known as alpha-1 antitrypsin) from an aqueous solution of plasma proteins, especially from Cohn Effluent II & III and Cohn Effluent I. The method includes the steps of first treating the aqueous solution to lower the concentration of salts therein and, optionally, its alcohol content, contacting the resulting solution with an anion exchange resin having selective affinity for alpha-1-proteinase inhibitor to selectively bind the alpha-1-proteinase inhibitor and allow unwanted plasma proteins to elute through the resin, displacing the alpha-1-proteinase inhibitor from the resin and recovering the same.

摘要翻译： 公开了一种从血浆蛋白质的水溶液中分离出α-1蛋白酶抑制剂（也称为α-1抗胰蛋白酶）的方法，特别是来自Cohn Effluent II＆III和Cohn流出液I.该方法包括以下步骤： 所述水溶液以降低其中的盐浓度和任选地其醇含量，使所得溶液与对α-1-蛋白酶抑制剂具有选择性亲和力的阴离子交换树脂接触以选择性结合α-1-蛋白酶抑制剂并允许不需要的 血浆蛋白质通过树脂洗脱，将α-1-蛋白酶抑制剂从树脂中取代并回收。

公开(公告)号：US4439358A

公开(公告)日：1984-03-27

申请号：US461422

申请日：1983-01-27

申请人： Michael H. Coan ,  William J. Brockway

发明人： Michael H. Coan ,  William J. Brockway

IPC分类号： A61K38/00 ,  C07K14/81 ,  C07G7/00

CPC分类号： C07K14/8125 ,  A61K38/00 ,  Y10S530/831

摘要： A method is disclosed for separating alpha-1-proteinase inhibitor from a blood plasma fraction particularly from the Cohn fractionation scheme. An aqueous solution of the blood plasma fraction is held at a pH of about 6.5-8.5, and a temperature of about 2.degree.-50.degree. C. for a period of about 0.2-24 hours and then mixed with a poly-condensed polyglycol. The mixture may be held at a temperature of about 2.degree.-10.degree. C. for a period of about 1-24 hours. Next, the pH of the mixture is adjusted to selectively precipitate unwanted proteins from the solution of alpha-1-proteinase inhibitor which is separated from the solution and purified further. The amount of poly-condensed polyglycol and the pH of the mixture are selected accordingly.

摘要翻译： 公开了一种从血浆级分分离特别是Cohn分馏方案分离α-1-蛋白酶抑制剂的方法。 将血浆级分的水溶液保持在约6.5-8.5的pH和约2°-50℃的温度下约0.2-24小时，然后与聚缩聚的聚乙二醇混合。 混合物可以在约2〜10℃的温度下保持约1-24小时。 接下来，调节混合物的pH以从α-1-蛋白酶抑制剂的溶液中选择性地沉淀不需要的蛋白质，该溶液与溶液分离并进一步纯化。 相应地选择聚缩合聚乙二醇的量和混合物的pH。

公开(公告)号：US4379087A

公开(公告)日：1983-04-05

申请号：US389202

申请日：1982-06-17

申请人： Michael H. Coan ,  William J. Brockway

发明人： Michael H. Coan ,  William J. Brockway

IPC分类号： A61K35/14 ,  A61K35/16 ,  A61K38/00 ,  A61K38/16 ,  A61K38/55 ,  C07K14/00 ,  C07K14/81 ,  C07G7/00

CPC分类号： C07K14/8125 ,  A61K38/00 ,  Y10S530/83 ,  Y10S530/831

摘要： A method is disclosed for separating alpha-1-proteinase inhibitor from a blood plasma fraction particularly from the Cohn fractionation scheme. An aqueous solution of the blood plasma fraction is held at a pH of about 6.5-8.5, and a temperature of about 2.degree.-50.degree. C. for a period of about 0.2-24 hours and then mixed with a poly-condensed polyglycol in a proportion of about 10-15 parts of polymer per 100 ml of aqueous solution containing the blood plasma fraction. The mixture may be held at a temperature of about 2.degree.-10.degree. C. for a period of about 1-24 hours. Next, the pH of the mixture is adjusted to about 4.6-5.7, to selectively precipitate unwanted proteins from the solution of alpha-1-proteinase inhibitor which is separated from the solution and purified further.

摘要翻译： 公开了一种从血浆级分分离特别是Cohn分馏方案分离α-1-蛋白酶抑制剂的方法。 将血浆级分的水溶液保持在约6.5-8.5的pH和约2°-50℃的温度下约0.2-24小时，然后与聚缩合的聚乙二醇混合 每100ml含有血浆级分的水溶液中约10-15份聚合物的比例。 混合物可以在约2〜10℃的温度下保持约1-24小时。 接下来，将混合物的pH调节至约4.6-5.7，以从溶液中分离出来从α-1-蛋白酶抑制剂的溶液中选择性地沉淀不想要的蛋白质，并进一步纯化。