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1. 发明授权

US5075423A Purification of protein a by affinity chromatography followed by anion exchange 失效
标题翻译：通过亲和层析纯化蛋白质，然后进行阴离子交换
公开(公告)号：US5075423A
公开(公告)日：1991-12-24
申请号：US471014
申请日：1990-01-24
申请人： Joseph P. Balint, Jr.
发明人： Joseph P. Balint, Jr.
IPC分类号： C12P21/00 , A61K38/00 , A61P35/00 , A61P37/00 , C07K1/16 , C07K1/18 , C07K1/22 , C07K14/005 , C07K14/195 , C07K14/31 , C07K14/705 , C07K16/00 , C12P21/02 , C12R1/44
CPC分类号： C07K14/31
摘要： Affinity-purified protein A preparations are contacted with a suitable anionic exchange material in order to remove trace contamination. Staphylococcal enterotoxin B (SEB) and other proteinaceous contaminants are removed by passing such affinity-purified protein A preparations through a DEAE-cellulose column and thereafter selectively eluting the protein A to separate the contaminants. Very high purity protein A composition are thus obtained, typically having a contaminant concentration of about 5 weight % or below, with below about 0.001 weight % SEB.
摘要翻译：亲和纯化的蛋白A制剂与合适的阴离子交换材料接触以除去痕量污染物。通过使这种亲和纯化的蛋白A制剂通过DEAE-纤维素柱，然后选择性洗脱蛋白A以分离污染物，去除葡萄球菌肠毒素B（SEB）和其它蛋白质污染物。因此获得非常高纯度的蛋白质A组合物，通常具有约5重量％或更低的污染物浓度，低于约0.001重量％的SEB。

2. 发明授权

US4681870A Protein A-silica immunoadsorbent and process for its production 失效
标题翻译：蛋白A型硅胶免疫吸附剂及其生产工艺
公开(公告)号：US4681870A
公开(公告)日：1987-07-21
申请号：US690781
申请日：1985-01-11
申请人： Joseph P. Balint, Jr. , Richard E. Hargreaves
发明人： Joseph P. Balint, Jr. , Richard E. Hargreaves
IPC分类号： C07K1/22 , A61K39/00 , A61K39/395 , A61M1/36 , A61P35/00 , A61P37/00 , B01J20/26 , B01J20/32 , C07K1/16 , C07K17/14 , G01N33/552 , B01J20/22
CPC分类号： B01J20/3204 , B01J20/103 , B01J20/28004 , B01J20/3078 , B01J20/3085 , B01J20/3217 , B01J20/3219 , B01J20/3257 , B01J20/3263 , B01J20/3274 , G01N33/552 , A61M1/3679 , B01J2220/58 , Y10S128/03
摘要： An immunoadsorbent material for removing IgG and IgG-complexes from biological fluids is prepared by covalently binding protein A to a solid-phase silica matrix. It has been found that particularly stable, high-capacity immunoadsorbents are obtained by derivatizing the silica with amino and/or carboxyl groups, and reacting the protein A with a carbodiimide at a pH in the range from 3.5 to 4.5. Binding through free hydroxyl groups may be achieved with cyanogen halides at a pH in the range from 11.0 to 11.5. After acid washing (pH 2.0-2.5) to remove non-covalently bound protein A, the immunoadsorbent may be employed in a column for therapeutic treatment of various cancers and autoimmune disorders where IgG-complexes are implicated as suppressing factors in inhibiting a normal immune response.
摘要翻译：通过将蛋白A与固相二氧化硅基质共价结合来制备用于从生物流体中除去IgG和IgG-复合物的免疫吸附材料。已经发现，特别稳定的高容量免疫吸附剂通过用氨基和/或羧基衍生二氧化硅获得，并且使蛋白A与碳二亚胺在3.5至4.5的pH范围内反应。通过游离羟基的结合可以在pH为11.0至11.5范围内的氰卤化物达到。在酸洗（pH2.0-2.5）以除去非共价结合的蛋白A后，免疫吸附剂可用于治疗各种癌症和自身免疫疾病的柱，其中IgG-复合物被认为是抑制正常免疫应答的抑制因子。

3. 发明授权

US5733254A Method for treating patients suffering from immune thrombocytopenic purpura 失效
标题翻译：治疗患有免疫性血小板减少性紫癜的患者的方法
公开(公告)号：US5733254A
公开(公告)日：1998-03-31
申请号：US432036
申请日：1995-05-01
申请人： Frank R. Jones , Joseph P. Balint, Jr. , Harry W. Snyder
发明人： Frank R. Jones , Joseph P. Balint, Jr. , Harry W. Snyder
IPC分类号： A61M1/34 , A61M37/00
CPC分类号： A61M1/3472 , A61M1/3486
摘要： Immune thrombocytopenic purpura is treated by removal of IgG and circulating immune complexes from the patient's blood. Removal is accomplished by exposing the blood or blood plasma to an immunoadsorbent capable of removing IgG and its complexes. The immunoadsorbent comprises a suitable solid phase coupled to a receptor capable of binding IgG and its complexes, such as protein A. The IgG and its complexes are then removed by the extracorporeal exposure of the patient's blood to the immunoadsorbent, either in a continuous or discontinuous process. In the continuous process, the blood is removed in a steady flow from the patient, separated into its plasma and cellular components, the plasma treated, and the combined cellular components and treated plasma reinfused to the patient. In the discontinuous method, a small volume of blood is removed from the patient, the entire volume separated into plasma and cellular components, the plasma treated, and the entire volume of treated plasma returned to the patient, usually after the cellular components have been returned.
摘要翻译：免疫血小板减少性紫癜通过从患者血液中除去IgG和循环免疫复合物来治疗。通过将血液或血浆暴露于能够除去IgG及其复合物的免疫吸附剂来实现去除。免疫吸附剂包含与能够结合IgG及其复合物（例如蛋白A）的受体偶联的合适的固相。然后通过体外暴露患者的血液免疫IgG或其复合物，以免疫吸附剂将其连续或不连续处理。在连续过程中，以来自患者的稳定流动除去血液，分离成其等离子体和细胞组分，将血浆处理，并将组合的细胞组分和治疗的血浆重新灌注给患者。在不连续的方法中，从患者体内除去少量的血液，整个体积分离成等离子体和细胞组分，血浆处理，经处理的血浆的总体积返回到病人，通常在细胞组分被返回后。

4. 发明授权

US4865841A Methods and compositions for transient elimination of humoral immune antibodies 失效
标题翻译：用于瞬时消除体液免疫抗体的方法和组合物
公开(公告)号：US4865841A
公开(公告)日：1989-09-12
申请号：US112853
申请日：1987-10-23
申请人： Joseph P. Balint, Jr. , Sharon Cochran , Frank R. Jones , Harry W. Snyder
发明人： Joseph P. Balint, Jr. , Sharon Cochran , Frank R. Jones , Harry W. Snyder
IPC分类号： A61M1/36
CPC分类号： A61M1/3679
摘要： Antibody is removed from the blood of patients who are being treated or diagnosed with exogenous macromolecules, such as immunotoxins. As the immunotoxins are foreign antigens, the patient will develop an immune response. The antibodies produced by the immune response upon subsequent immunization with the immunotoxins will interfere with the desired function of the immunotoxins by preventing them from binding with their specific target site. By extracorporeally removing the antibodies, the activity of the immunotoxins can be enhanced.

5. 发明授权

US4801449A Method for treatment of Kaposi's sarcoma 失效
标题翻译：卡波西肉瘤治疗方法
公开(公告)号：US4801449A
公开(公告)日：1989-01-31
申请号：US948268
申请日：1986-12-31
申请人： Joseph P. Balint, Jr. , Frank R. Jones
发明人： Joseph P. Balint, Jr. , Frank R. Jones
IPC分类号： A61M1/36 , B01J20/32 , G01N33/552 , B01D15/08 , G01N33/543
CPC分类号： B01J20/3204 , B01J20/103 , B01J20/28004 , B01J20/3071 , B01J20/3078 , B01J20/3085 , B01J20/3092 , B01J20/3217 , B01J20/3219 , B01J20/3257 , B01J20/3263 , B01J20/3274 , G01N33/552 , A61M1/3679 , B01J2220/58 , B01J2220/62
摘要： An immunoadsorbent material for removing IgG and IgG-complexes from biological fluids is prepared by covalently binding protein A to a solid-phase silica matrix. It has been found that particularly stable, high-capacity immunoadsorbents are obtained by derivatizing the silica with amino and/or carboxyl groups, and reacting the protein A with a carbodiimide at a pH in the range from 3.5 to 4.5. Binding through free hydroxyl groups may be achieved with cyanogen halides at a pH in the range from 11.0 to 11.5. After acid washing (pH 2.0-2.5) to remove non-covalently bound protein A, the immunoadsorbent may be employed in a column for therapeutic treatment of various cancers and autoimmune disorders where IgG-complexes are implicated as suppressing factors in inhibiting a normal immune response. The column has been successfully employed in treating patients suffering from Kaposi's sarcoma.
摘要翻译：通过将蛋白A与固相二氧化硅基质共价结合来制备用于从生物流体中除去IgG和IgG-复合物的免疫吸附材料。已经发现，特别稳定的高容量免疫吸附剂通过用氨基和/或羧基衍生二氧化硅获得，并且使蛋白A与碳二亚胺在3.5至4.5的pH范围内反应。通过游离羟基的结合可以在pH为11.0至11.5范围内的氰卤化物达到。在酸洗（pH2.0-2.5）以除去非共价结合的蛋白A后，免疫吸附剂可用于治疗各种癌症和自身免疫疾病的柱，其中IgG-复合物被认为是抑制正常免疫应答的抑制因子。该柱已成功用于治疗患有卡波西氏肉瘤的患者。

6. 发明授权

US5782792A Method for treatment of rheumatoid arthritis 失效
标题翻译：治疗类风湿关节炎的方法
公开(公告)号：US5782792A
公开(公告)日：1998-07-21
申请号：US353946
申请日：1994-12-12
申请人： Frank R. Jones , Harry W. Snyder, Jr. , Joseph P. Balint, Jr.
发明人： Frank R. Jones , Harry W. Snyder, Jr. , Joseph P. Balint, Jr.
IPC分类号： A61M1/34 , A61M1/36 , A61M37/00
CPC分类号： A61M1/3679 , A61M1/3472 , A61M1/3486 , A61M1/3496 , A61M2202/0419
摘要： Rheumatoid arthritis is treated by the extra corporeal removal of IgG and IgG-containing circulating immune complexes from the patient's blood. Removal is preferably accomplished by exposing the blood or blood plasma to a protein A immunoadsorbent which binds to IgG-containing immune complexes with high affinity.
摘要翻译：类风湿关节炎是通过从患者血液中去除IgG和IgG的循环免疫复合物进行额外的体外处理。优选通过将血液或血浆暴露于以高亲和力结合含IgG免疫复合物的蛋白A免疫吸附剂来完成去除。

7. 发明授权

US5037649A Method for treatment of HIV-infected patients 失效
标题翻译：治疗艾滋病毒感染患者的方法
公开(公告)号：US5037649A
公开(公告)日：1991-08-06
申请号：US301214
申请日：1989-01-24
申请人： Joseph P. Balint, Jr. , Frank R. Jones
发明人： Joseph P. Balint, Jr. , Frank R. Jones
IPC分类号： A61M1/36 , B01J20/32 , G01N33/552
CPC分类号： B01J20/3217 , B01J20/3204 , B01J20/3219 , B01J20/3274 , G01N33/552 , A61M1/3679 , Y10S424/81
摘要： Patients suffering from HIV-1 infection, including both those who have and those who have not developed acquired immunodeficiency syndrome, are treated by extracorporeal removal of IgG and immune complexes. An immunoadsorbent material for removing IgG and IgG-complexes from biological fluids is prepared by covalently binding protein A to a solid-phase silica matrix. It has been found that particularly stable, high-capacity immunoadsorbents are obtained by derivatizing the silica with amino and/or carboxyl groups, and reacting the protein A with a carbodiimide at a pH in a range from 3.5 to 4.5. Binding through free hydroxyl groups may be achieved with cyanogen halides at a pH in the range from 11.0 to 11.5. After acid washing (pH 2.0-2.5) to remove non-covalently bound protein A, the immunoadsorbent may be employed in a column for therapeutic treatment of various cancers and autoimmune disorders where IgG-complexes are implicated as suppressing factors in inhibiting a normal immune response.
摘要翻译：患有HIV-1感染的患者，包括那些患有和未发展成熟的免疫缺陷综合征的患者，通过体外去除IgG和免疫复合物进行治疗。通过将蛋白A与固相二氧化硅基质共价结合来制备用于从生物流体中除去IgG和IgG-复合物的免疫吸附材料。已经发现，特别稳定的高容量免疫吸附剂通过用氨基和/或羧基衍生二氧化硅获得，并且使蛋白A与碳二亚胺在3.5至4.5的pH范围内反应。通过游离羟基的结合可以在pH为11.0至11.5范围内的氰卤化物达到。在酸洗（pH2.0-2.5）以除去非共价结合的蛋白A后，免疫吸附剂可用于治疗各种癌症和自身免疫疾病的柱，其中IgG-复合物被认为是抑制正常免疫应答的抑制因子。

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