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1. 发明授权

US5681731A Method for producing recombinant adeno-associated virus vectors 失效
标题翻译：重组腺相关病毒载体的制备方法
公开(公告)号：US5681731A
公开(公告)日：1997-10-28
申请号：US459049
申请日：1995-06-02
申请人： Jane S. Lebkowski , Maureen A. McNally , Thomas B. Okarma
发明人： Jane S. Lebkowski , Maureen A. McNally , Thomas B. Okarma
IPC分类号： C12N5/10 , C07K14/015 , C07K14/05 , C12N7/00 , C12N7/04 , C12N15/09 , C12N15/38 , C12N15/864 , C12N15/869 , C12R1/92 , C12N15/63 , C12N5/06 , C12N5/08 , C12N15/70
CPC分类号： C12N15/86 , C07K14/005 , C12N7/00 , C12N2710/16222 , C12N2710/16244 , C12N2710/16262 , C12N2750/14122 , C12N2750/14143
摘要： Simplified methods to produce recombinant adeno-associated virus (rAAV) vectors are described. The methods involve the use of chimeric plasmids which incorporate the Epstein Barr nuclear antigen (EBNA) gene, the latent origin of replication of Epstein Barr virus (oriP), and a rAAV genome. The chimeric plasmids themselves are also a part of the present invention. These plasmids are maintained as multicopy extra-chromosomal elements in cells, such as human 293 cells. Permanent cell lines carrying these EBV/AAV plasmids are induced to produce large amounts of rAAV upon addition of wild-type, adeno-associated virus helper functions. Vectors produced in this manner are capable of transducing exogenous genes into other human cell lines and exhibit the attributes of viral elements produced by conventional methods.
摘要翻译：描述了产生重组腺相关病毒（rAAV）载体的简化方法。该方法涉及使用掺入爱泼斯坦巴尔核抗原（EBNA）基因，爱泼斯坦巴尔病毒（oriP）的潜在复制起点）和rAAV基因组的嵌合质粒。嵌合质粒本身也是本发明的一部分。这些质粒作为细胞中的多拷贝染色体外元件维持，如人293细胞。携带这些EBV / AAV质粒的永久性细胞系在添加野生型腺相关病毒辅助功能后被诱导产生大量的rAAV。以这种方式产生的载体能够将外源基因转导到其他人细胞系中，并显示通过常规方法产生的病毒元件的属性。

2. 发明授权

US5730713A Removal of selected factors from whole blood or its components 失效
公开(公告)号：US5730713A
公开(公告)日：1998-03-24
申请号：US657239
申请日：1996-06-03
申请人： Thomas B. Okarma , John Blankenship , Abraham T. Lin , Mohammad A. Elkalay
发明人： Thomas B. Okarma , John Blankenship , Abraham T. Lin , Mohammad A. Elkalay
IPC分类号： A61K35/14 , A61M1/34 , A61M1/36 , A61M1/14 , A61M37/00
CPC分类号： A61M1/3679 , A61M1/3431 , A61M1/3621 , A61M1/3643 , Y10S530/811
摘要： This invention provides a composition, device and method for the removal of selected factors, such as cytokines or pharmaceuticals, from a substance such as whole blood or plasma. Advantageously, the invention provides for the treatment or prevention of septic shock syndrome or other conditions evidenced by the presence of cytokines in a patient by contacting the patient's whole blood with a composition comprising silica and a surface treatment material, such as heparin, but preferably human serum albumin (HSA). The treatment lowers the cytokine concentration of the blood. Pharmaceuticals can be removed from an individual's whole blood or plasma, such as for use in treating drug overdosage.

3. 发明授权

US5173414A Production of recombinant adeno-associated virus vectors 失效
标题翻译：重组腺病毒相关病毒载体的生产
公开(公告)号：US5173414A
公开(公告)日：1992-12-22
申请号：US605775
申请日：1990-10-30
申请人： Jane S. Lebkowski , Maureen A. McNally , Thomas B. Okarma
发明人： Jane S. Lebkowski , Maureen A. McNally , Thomas B. Okarma
IPC分类号： C12N5/10 , C07K14/015 , C07K14/05 , C12N7/00 , C12N7/04 , C12N15/09 , C12N15/38 , C12N15/864 , C12N15/869 , C12R1/92
CPC分类号： C12N15/86 , C07K14/005 , C12N7/00 , C12N2710/16222 , C12N2710/16244 , C12N2710/16262 , C12N2750/14122 , C12N2750/14143
摘要： A simplified method to produce recombinant adeno-associated virus (AAV) vectors is described. The procedure involves the use of chimeric plasmids which incorporate the Epstein Barr nuclear antigen (EBNA) gene, the latent origin of replication of Epstein Barr Virus (oriP), and a recombinant AAV genome. The chimeric plasmids themselves are also a part of the present invention. These EBV/AAV plasmids are maintained as multicopy extra-chromosomal elements in cells, such as human 293 cells. Permanent cell lines carrying these EBV/AAV plasmids are induced to produce large amounts of recombinant AAV virus upon addition of wild-type, adeno-associated virus helper functions. Recombinant AAV vectors produced in this manner are capable of transducing exogenous genes into other human cell lines and exhibit all of the attributes of viral elements produced by conventional methods.

4. 发明授权

US5437861A Removal of selected factors from whole blood or its components; and prevention and treatment of septic shock syndrome 失效
标题翻译：从全血或其组分中去除选定的因子; 并预防和治疗败血性休克综合征
公开(公告)号：US5437861A
公开(公告)日：1995-08-01
申请号：US32357
申请日：1993-03-16
申请人： Thomas B. Okarma , John Blankenship , Abraham T. Lin , Mohammad A. Elkalay
发明人： Thomas B. Okarma , John Blankenship , Abraham T. Lin , Mohammad A. Elkalay
IPC分类号： A61K35/14 , A61M1/34 , A61M1/36 , A61M1/14 , A01N59/00 , A61K31/74 , B01D15/00
CPC分类号： A61M1/3679 , A61M1/3431 , A61M1/3621 , A61M1/3643 , Y10S530/811
摘要： This invention provides a composition, device and method for the treatment or prevention of septic shock syndrome or other conditions evidenced by the presence of cytokines in a patient by contacting the patient's whole blood with a composition comprising silica and a surface treatment material, such as heparin, but preferably human serum albumin (HSA). The treatment lowers the cytokine concentration of the blood.
摘要翻译：本发明提供了一种用于治疗或预防败血性休克综合征或其他由病人存在细胞因子证明的条件的组合物，装置和方法，所述方法通过使患者的全血与包含二氧化硅和表面处理材料如肝素，但优选人血清白蛋白（HSA）。治疗降低血液的细胞因子浓度。

5. 发明授权

US5283034A Stabilization of sterilized surfaces for research and medical use 失效
标题翻译：用于研究和医疗用途的灭菌表面的稳定化
公开(公告)号：US5283034A
公开(公告)日：1994-02-01
申请号：US858125
申请日：1992-03-26
申请人： David A. Okrongly , Donald Lamons , Thomas B. Okarma
发明人： David A. Okrongly , Donald Lamons , Thomas B. Okarma
IPC分类号： A61K35/12 , A61K39/00 , C12N5/00 , C12N5/0783 , C12N7/02 , H61L2/00
CPC分类号： C12N7/00 , A61K35/12 , C12N5/0087 , C12N5/0636 , A61K2039/5158 , C12N2501/515 , C12N2740/16051
摘要： A method and composition which permits sterilization of surfaces coupled with biologically active moieties by ionizing radiation is described. The protecting composition contains a surface-stabilizing agent which adheres to the surface and has a molecular weight.gtoreq.5 kd, and an oxygen radical scavenger which is preferably a di- or polysaccharide or reduced form thereof. In the method of the invention, a surface which is coupled to a biologically active agent is protected with the invention composition, dried to a moisture content of less than 1%, and then sterilized by ionizing radiation under standard conditions. The sterilized surfaces of the invention are particularly useful in the production of medical devices intended for extracorporeal use, particularly in cell-separation techniques.
摘要翻译：描述了允许通过电离辐射与生物活性部分偶联的表面灭菌的方法和组合物。保护性组合物含有粘附到表面并具有≥5kd分子量的表面稳定剂，以及氧自由基清除剂，其优选为二糖或多糖或还原形式。在本发明的方法中，与本发明组合物一起保护与生物活性剂偶联的表面，干燥至含水量小于1％，然后在标准条件下通过电离辐射灭菌。本发明的灭菌表面特别可用于生产用于体外使用的医疗装置，特别是在细胞分离技术中。

6. 发明授权

US4963265A Plasma processing device with anaphylatoxin remover 失效
标题翻译：带过敏毒素去除剂的等离子体处理装置
公开(公告)号：US4963265A
公开(公告)日：1990-10-16
申请号：US191039
申请日：1988-05-06
申请人： Thomas B. Okarma , Brian R. Clark , L. Bernard Lerch , Chin-Hai Chang
发明人： Thomas B. Okarma , Brian R. Clark , L. Bernard Lerch , Chin-Hai Chang
IPC分类号： A61K35/16 , A61M1/36
CPC分类号： A61K35/16 , A61M1/3679 , Y10S210/908
摘要： Blood derived fluids are subjected to modification resulting in the production of anaphylatoxins. The anaphylatoxins may then be removed by passing the modified blood through silicic acid particles in an amount sufficient to substantially reduce the anaphylatoxins, while still retaining the other blood components and without affecting adversely the use of the blood for the patient.
摘要翻译：血液衍生的液体经过改变，导致过敏毒素的产生。然后可以通过使修饰的血液通过硅酸颗粒以足以大大减少过敏毒素的量，同时仍然保留其它血液成分并且不会不利地影响患者血液的使用而将经过过敏反应除去。

7. 发明授权

US06432653B1 Device and process for cell capture and recovery 失效
标题翻译：用于细胞捕获和恢复的装置和过程
公开(公告)号：US06432653B1
公开(公告)日：2002-08-13
申请号：US08291335
申请日：1994-08-17
申请人： Thomas B. Okarma
发明人： Thomas B. Okarma
IPC分类号： A61K3512
CPC分类号： C12N7/00 , A61K35/17 , A61K2039/5158 , C12N5/0087 , C12N5/0636 , C12N2501/515 , C12N2740/16051 , G01N33/545 , G01N33/56972 , Y10S436/824
摘要： Devices, processes and compositions are provided for effective separation of cells from a mixture of cells, where depletion or positive selection may be employed to provide a cellular population of interest. Of particular utility is the separation of cells from peripheral blood mononuclear cells, where members of the lymphoid or myeloid lineages may be isolated and used for research, diagnosis or therapy. Also of interest are cellular separation from bone marrow, tumor suspensions or lymphoid tissue suspensions, where cells can be isolated and used for a variety of purposes. The separated cells may be homogeneous, free of exogenous biologicals, viable, capable of replication and exhibit their full complement of biological activities. Multiple phenotypes can be captured simultaneously. Captured cells can be specifically activated with cytokines and antigens to provide cells which are MHC restricted and have antigen-specific effector functions.
摘要翻译：提供了装置，方法和组合物用于从细胞混合物中有效分离细胞，其中可以使用消耗或阳性选择来提供感兴趣的细胞群体。特别有用的是将细胞与外周血单核细胞分离，其中淋巴或骨髓谱系的成员可以被分离并用于研究，诊断或治疗。还有兴趣的是与骨髓，肿瘤悬浮液或淋巴组织悬浮液的细胞分离，其中细胞可以分离并用于各种目的。分离的细胞可以是均匀的，没有外源生物学，可行的，能够复制并表现出其完整的生物活性。可以同时捕获多种表型。捕获的细胞可以用细胞因子和抗原特异性活化，以提供MHC限制的细胞并具有抗原特异性效应子功能。

8. 发明授权

US6143508A Device and process for cell capture and recovery 失效
公开(公告)号：US6143508A
公开(公告)日：2000-11-07
申请号：US484559
申请日：1995-06-07
申请人： Thomas B. Okarma
发明人： Thomas B. Okarma
IPC分类号： A61K35/12 , A61K39/00 , C12N5/00 , C12N5/06 , C12N5/08 , A61K35/18 , C07K16/28
CPC分类号： C12N5/0087 , A61K2035/124 , A61K2039/5158 , C12M33/08 , C12M33/12 , C12N2501/515 , Y10S436/824
摘要： Devices, processes and compositions are provided for effective separation of cells from a mixture of cells, where depletion or positive selection may be employed to provide a cellular population of interest. Of particular utility is the separation of cells from peripheral blood mononuclear cells, where members of the lymphoid or myeloid lineages may be isolated and used for research, diagnosis or therapy. Also of interest are cellular separation from bone marrow, tumor suspensions or lymphoid tissue suspensions, where cells can be isolated and used for a variety of purposes. The separated cells may be homogeneous, free of exogenous biologicals, viable, capable of replication and exhibit their full complement of biological activities. Multiple phenotypes can be captured simultaneously. Captured cells can be specifically activated with cytokines and antigens to provide cells which are MHC restricted and have antigen-specific effector functions.

9. 发明授权

US5780280A Recombinant adeno-associated virus vectors 失效
标题翻译：重组腺相关病毒载体
公开(公告)号：US5780280A
公开(公告)日：1998-07-14
申请号：US459352
申请日：1995-06-02
申请人： Jane S. Lebkowski , Maureen A. McNally , Thomas B. Okarma
发明人： Jane S. Lebkowski , Maureen A. McNally , Thomas B. Okarma
IPC分类号： C12N5/10 , C07K14/015 , C07K14/05 , C12N7/00 , C12N7/04 , C12N15/09 , C12N15/38 , C12N15/864 , C12N15/869 , C12R1/92 , C12N15/64 , C12N15/86
CPC分类号： C12N15/86 , C07K14/005 , C12N7/00 , C12N2710/16222 , C12N2710/16244 , C12N2710/16262 , C12N2750/14122 , C12N2750/14143
摘要： Simplified methods to produce recombinant adeno-associated virus (rAAV) vectors are described. The methods involve the use of chimeric plasmids which incorporate the Epstein Barr nuclear antigen (EBNA) gene, the latent origin of replication of Epstein Barr virus (oriP), and a rAAV genome. The chimeric plasmids themselves are also a part of the present invention. These plasmids are maintained as multicopy extra-chromosomal elements in cells, such as human 293 cells. Permanent cell lines carrying these EBV/AAV plasmids are induced to produce large amounts of rAAV upon addition of wild-type, adeno-associated virus helper functions. Vectors produced in this manner are capable of transducing exogenous genes into other human cell lines and exhibit the attributes of viral elements produced by conventional methods.
摘要翻译：描述了产生重组腺相关病毒（rAAV）载体的简化方法。该方法涉及使用掺入爱泼斯坦巴尔核抗原（EBNA）基因，爱泼斯坦巴尔病毒（oriP）的潜在复制起点）和rAAV基因组的嵌合质粒。嵌合质粒本身也是本发明的一部分。这些质粒作为细胞中的多拷贝染色体外元件维持，如人293细胞。携带这些EBV / AAV质粒的永久性细胞系在添加野生型腺相关病毒辅助功能后被诱导产生大量的rAAV。以这种方式产生的载体能够将外源基因转导到其他人细胞系中，并显示通过常规方法产生的病毒元件的属性。

10. 发明授权

US5523096A Removal of selected factors from whole blood or its components 失效
标题翻译：从全血或其组分中去除所选择的因子
公开(公告)号：US5523096A
公开(公告)日：1996-06-04
申请号：US482315
申请日：1995-06-06
申请人： Thomas B. Okarma , John Blankenship , Abraham T. Lin , Mohammad A. Elkalay
发明人： Thomas B. Okarma , John Blankenship , Abraham T. Lin , Mohammad A. Elkalay
IPC分类号： A61K35/14 , A61M1/34 , A61M1/36 , B01J20/24 , A61M1/14 , A61M37/00
CPC分类号： A61M1/3679 , A61K35/14 , A61M1/3431 , A61M1/3621 , A61M1/3643
摘要： This invention provides a composition, device and method for the removal of selected factors, such as cytokines or pharmaceuticals, from a substance such as whole blood or plasma. Advantageously, the invention provides for the treatment or prevention of septic shock syndrome or other conditions evidenced by the presence of cytokines in a patient by contacting the patient's whole blood with a composition comprising silica and a surface treatment material, such as heparin, but preferably human serum albumin (HSA). The treatment lowers the cytokine concentration of the blood. Pharmaceuticals can be removed from an individual's whole blood or plasma, such as for use in treating drug overdosage.
摘要翻译：本发明提供了用于从诸如全血或血浆的物质中除去选定因子如细胞因子或药物的组合物，装置和方法。有利地，本发明提供了治疗或预防感染性休克综合征或其他由患者的细胞因子的存在所证实的条件，其通过使患者的全血与包含二氧化硅和表面处理材料（例如肝素，但优选人类）的组合物接触血清白蛋白（HSA）。治疗降低血液的细胞因子浓度。药物可以从个体的全血或血浆中除去，例如用于治疗药物过量。

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