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41. 发明申请

US20090170769A1 CELL SURFACE RECEPTOR ISOFORMS AND METHODS OF IDENTIFYING AND USING THE SAME 审中-公开
标题翻译：细胞表面受体的体积和鉴定方法和使用它们
公开(公告)号：US20090170769A1
公开(公告)日：2009-07-02
申请号：US12260961
申请日：2008-10-29
申请人： Pei JIN , H. Michael Shepard
发明人： Pei JIN , H. Michael Shepard
IPC分类号： A61K38/16 , C07K14/00 , C07H21/00 , C12N15/63 , C12N5/00 , A61P35/00 , A61P29/00
CPC分类号： C07K14/71
摘要： Isoforms of cell surface receptors, including isoforms of receptor tyrosine kinases, and pharmaceutical compositions containing the isoforms are provided. Chimeras of and conjugates containing the cell surface receptors that contain a portion, such as an extracellular domain, from one cell surface receptor, and a second portion, particularly an intron-encoded portion, from a second cell surface protein also are provided. The isoforms modulate the activity of a cell surface receptor. Methods for identifying and preparing isoforms of cell surface receptors including receptor tyrosine kinases are provided. Also provided are methods of treatment with the cell surface receptor isoforms.
摘要翻译：提供了细胞表面受体的同种型，包括受体酪氨酸激酶的同种型，以及含有同种型的药物组合物。还提供了含有来自第一细胞表面蛋白的含有来自一个细胞表面受体的一部分例如细胞外结构域和第二部分，特别是内含子编码部分的细胞表面受体的嵌合体和缀合物。异构体调节细胞表面受体的活性。提供了用于鉴定和制备包括受体酪氨酸激酶在内的细胞表面受体同种型的方法。还提供了用细胞表面受体同种型治疗的方法。

42. 发明授权

US07465734B2 Methods and compositions for overcoming resistance to biologic and chemotherapy 失效
标题翻译：克服生物和化疗抵抗力的方法和组合物
公开(公告)号：US07465734B2
公开(公告)日：2008-12-16
申请号：US09789226
申请日：2001-02-20
申请人： H. Michael Shepard
发明人： H. Michael Shepard
IPC分类号： A01N43/54 , A01N43/04 , A01N57/00 , C07D239/42 , C07D401/04 , A61K31/70 , A61K31/675
CPC分类号： C07H19/06 , A61K31/513 , A61K31/7068 , A61K31/7072 , C07H19/10 , C12Q1/48 , C12Q1/485 , G01N33/5011 , G01N2333/91011
摘要： This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.
摘要翻译：本发明提供了一种通过使靶细胞与候选治疗剂接触来鉴定潜在治疗剂的方法，所述候选治疗剂是细胞中的内源性细胞内酶的选择性底物，其作为通过生物或化疗选择的结果而增强其表达。本发明还提供了通过使细胞与作为内源性细胞内酶的选择性底物的前药接触来选择性杀死病理细胞的分子的方法和实施例。随后将前药转化为细胞毒素。本发明进一步提供的是通过向受试者施用作为内源性，过表达的细胞内酶的选择性底物并由酶转化成细胞的前体药物来治疗受试者中病理学，过度增殖细胞特征的病理学的方法毒素在过度增殖细胞中。

43. 发明授权

US06946259B2 Compositions and methods for treating cells having double minute DNA 失效
标题翻译：用于处理具有双分子DNA的细胞的组合物和方法
公开(公告)号：US06946259B2
公开(公告)日：2005-09-20
申请号：US09229229
申请日：1999-01-12
申请人： Geoffrey M. Wahl , Noriaki Shimizu , Teru Kanda , H. Michael Shepard
发明人： Geoffrey M. Wahl , Noriaki Shimizu , Teru Kanda , H. Michael Shepard
IPC分类号： A61K45/00 , A61K48/00 , A61K49/00 , A61P35/00 , A61P43/00 , C07K14/00 , C12N15/09 , C12Q1/02 , C12Q1/68 , G01N33/15 , G01N33/50 , G01N33/52 , G01N33/574 , G01N33/58 , G01N33/68
CPC分类号： C12Q1/68 , G01N33/5011 , G01N33/6875 , G01N2333/43595
摘要： This invention provides methods by which test substances can be screened for their ability to inhibit, enhance or eliminate double minute (DM) or extrachromosomal DNA by micronucleation in cells. This invention also provides a method for inducing maturation or death of a cell having the capacity to generate micronuclei. It also provides a method of treating a disease in a subject, the cells correlated with the disease having DM and extrachromosomal DNA as well as the capacity to generate micronuclei to capture them. Further provided is a method of detecting chromosomal and extrachromosomal DNA in a cell.
摘要翻译：本发明提供了通过细胞中微核来筛选测试物质以抑制，增强或消除双分钟（DM）或染色体外DNA的能力的方法。本发明还提供了诱导具有产生微核能力的细胞的成熟或死亡的方法。它还提供了治疗受试者疾病的方法，与具有DM和染色体外DNA的疾病相关的细胞以及产生微核以捕获它们的能力。还提供了检测细胞中染色体和染色体外DNA的方法。

44. 发明授权

US06495553B1 Methods and compositions for overcoming resistance to biologic and chemotherapy 有权
标题翻译：克服生物和化疗抵抗力的方法和组合物
公开(公告)号：US06495553B1
公开(公告)日：2002-12-17
申请号：US09130839
申请日：1998-08-07
申请人： H. Michael Shepard
发明人： H. Michael Shepard
IPC分类号： A61K31495
CPC分类号： C07H19/06 , A61K31/513 , A61K31/7068 , A61K31/7072 , C07H19/10 , C12Q1/48 , C12Q1/485 , G01N33/5011 , G01N2333/91011
摘要： This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.
摘要翻译：本发明提供了一种通过使靶细胞与候选治疗剂接触来鉴定潜在治疗剂的方法，所述候选治疗剂是细胞中的内源性细胞内酶的选择性底物，其作为通过生物或化疗选择的结果而增强其表达。本发明还提供了通过使细胞与作为内源性细胞内酶的选择性底物的前药接触来选择性杀死病理细胞的分子的方法和实施例。随后将前药转化为细胞毒素。本发明进一步提供的是通过向受试者施用作为内源性，过表达的细胞内酶的选择性底物并由酶转化成细胞的前体药物来治疗受试者中病理学，过度增殖细胞特征的病理学的方法毒素在过度增殖细胞中。

45. 发明授权

US06391884B1 Methods and compositions for overcoming resistance to biologic and chemotherapy 有权
公开(公告)号：US06391884B1
公开(公告)日：2002-05-21
申请号：US09130839
申请日：1998-08-07
申请人： H. Michael Shepard
发明人： H. Michael Shepard
IPC分类号： A61K31495
CPC分类号： C07H19/06 , A61K31/513 , A61K31/7068 , A61K31/7072 , C07H19/10 , C12Q1/48 , C12Q1/485 , G01N33/5011 , G01N2333/91011
摘要： This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.

46. 发明授权

US06348352B1 Methods for selectively transducing pathologic mammalian cells using a tumor suppressor gene 失效
标题翻译：使用肿瘤抑制基因选择性转导病理性哺乳动物细胞的方法
公开(公告)号：US06348352B1
公开(公告)日：2002-02-19
申请号：US08403797
申请日：1995-12-04
申请人： H. Michael Shepard , Nancy Kan
发明人： H. Michael Shepard , Nancy Kan
IPC分类号： C12N1588
CPC分类号： C07K14/4746 , A61K38/1709 , A61K48/00 , C07K14/47 , C12N2740/13043
摘要： A method for transducing a pathologic hyperproliferative mammalian cell is provided by this invention. This method requires contacting the cell with a suitable retroviral vector containing a nucleic acid encoding a gene product having a tumor suppressive function. Also provided by this invention is a method for treating a pathology in a subject caused by the absence of, or the presence of a pathologically mutated tumor suppressor gene.
摘要翻译：用于转导病理过度增殖的哺乳动物细胞的方法由本发明提供。该方法需要使细胞与含有编码具有肿瘤抑制功能的基因产物的核酸的合适的逆转录病毒载体接触。本发明还提供了一种用于治疗由于不存在或存在病理突变的肿瘤抑制基因导致的受试者病理学的方法。

47. 发明授权

US6165464A Monoclonal antibodies directed to the HER2 receptor 失效
公开(公告)号：US6165464A
公开(公告)日：2000-12-26
申请号：US044197
申请日：1998-03-17
申请人： Robert M. Hudziak , H. Michael Shepard , Axel Ullrich , Brian M. Fendly
发明人： Robert M. Hudziak , H. Michael Shepard , Axel Ullrich , Brian M. Fendly
IPC分类号： A61K31/00 , A61K31/365 , A61K31/366 , A61K31/40 , A61K31/407 , A61K31/505 , A61K31/519 , A61K31/529 , A61K31/70 , A61K31/7008 , A61K33/24 , A61K38/00 , A61K38/21 , A61K39/395 , A61K45/00 , A61K47/48 , A61P35/00 , A61P43/00 , C07K1/22 , C07K14/00 , C07K14/485 , C07K14/495 , C07K14/52 , C07K14/525 , C07K14/54 , C07K14/545 , C07K14/55 , C07K14/555 , C07K14/57 , C07K14/705 , C07K14/715 , C07K16/00 , C07K16/22 , C07K16/28 , C07K16/30 , C07K16/32 , C07K19/00 , C12N5/10 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/573 , G01N33/574 , G01N33/577 , C12N5/12
CPC分类号： C07K16/32 , A61K38/00 , A61K39/395 , A61K47/6843 , A61K47/6849 , A61K2039/505 , C07K16/22 , C07K16/30 , C07K16/3015 , C07K2317/73 , A61K2300/00 , A61K38/217 , A61K38/2013 , A61K38/2006 , A61K38/191
摘要： A method of inhibiting growth of tumor cells which overexpress a growth factor receptor or growth factor by treatment of the cells with antibodies which inhibit the growth factor receptor function, is disclosed. A method of treating tumor cells with antibodies which inhibit growth factor receptor function, and with cytotoxic factor(s) such as tumor necrosis factor, is also disclosed. By inhibiting growth factor receptor functions tumor cells are rendered more susceptible to cytotoxic factors.

48. 发明授权

US6015567A HER2 extracellular domain 失效
标题翻译： HER2细胞外结构域
公开(公告)号：US6015567A
公开(公告)日：2000-01-18
申请号：US422108
申请日：1995-04-14
申请人： Robert Michael Hudziak , H. Michael Shepard , Axel Ullrich
发明人： Robert Michael Hudziak , H. Michael Shepard , Axel Ullrich
IPC分类号： A61K39/00 , C07K14/71 , C12N1/19 , C12N1/21 , A61K38/00 , C07K14/705 , C07K19/00
CPC分类号： C07K14/71 , A61K39/00
摘要： A method of treating a human patient via active immunotherapy comprising administrating an effective amount of extracellular portion of human HER2 receptor to the patient wherein the method provokes a cell-mediated immune response to HER2 receptor in the patient treated therewith.
摘要翻译：一种通过主动免疫疗法治疗人类患者的方法，其包括向患者施用有效量的人HER2受体的细胞外部分，其中所述方法在用其治疗的患者中引发对HER2受体的细胞介导的免疫应答。

49. 发明授权

US5837520A Method of purification of viral vectors 失效
标题翻译：病毒载体的纯化方法
公开(公告)号：US5837520A
公开(公告)日：1998-11-17
申请号：US400793
申请日：1995-03-07
申请人： Paul W. Shabram , Bernard G. Huyghe , Xiaodong Liu , H. Michael Shepard
发明人： Paul W. Shabram , Bernard G. Huyghe , Xiaodong Liu , H. Michael Shepard
IPC分类号： C08L101/02 , A61K48/00 , C07K14/82 , C08F2/22 , C08F2/44 , C08F8/30 , C08F265/02 , C08L101/00 , C09D11/10 , C12N7/02 , C12N15/09 , C12N15/86 , C12Q1/00 , F23D14/20 , F23D14/48 , F23D14/70 , F23D14/84 , C12N7/00 , C12N15/00
CPC分类号： C12N7/00 , C07K14/82 , C08F265/02 , C09D11/106 , C12N15/86 , C12Q1/00 , A01K2217/05 , A61K48/00 , C12N2710/10343 , C12N2710/10351 , Y10S435/803
摘要： The invention provides a method for purifying viral vectors containing therapeutic genes for use in gene therapy. The invention comprises a method of purification from a cell lysate of a recombinant viral vector containing a therapeutic gene, which comprises: a) treating said lysate with an enzymatic agent that selectively degrades both unencapsulated DNA and RNA; b) chromatographing the treated lysate from step a) on a first resin; and c) chromatographing the eluant from step b) on a second resin; wherein one resin is an anion exchange resin and the other is an immobilized metal ion chromatography (IMAC) resin.
摘要翻译：本发明提供了一种用于纯化含有用于基因治疗的治疗基因的病毒载体的方法。本发明包括从包含治疗基因的重组病毒载体的细胞裂解物中纯化的方法，其包括：a）用选择性降解未包封的DNA和RNA的酶试剂处理所述裂解物; b）将经处理的来自步骤a）的裂解物色谱分离在第一树脂上; 和c）将来自步骤b）的洗脱液层析到第二树脂上; 其中一种树脂是阴离子交换树脂，另一种是固定金属离子色谱（IMAC）树脂。

50. 发明授权

US5772997A Monoclonal antibodies directed to the HER2 receptor 失效
标题翻译：针对HER2受体的单克隆抗体
公开(公告)号：US5772997A
公开(公告)日：1998-06-30
申请号：US447478
申请日：1995-05-23
申请人： Robert M. Hudziak , H. Michael Shepard , Axel Ullrich , Brian M. Fendly
发明人： Robert M. Hudziak , H. Michael Shepard , Axel Ullrich , Brian M. Fendly
IPC分类号： A61K31/00 , A61K31/365 , A61K31/366 , A61K31/40 , A61K31/407 , A61K31/505 , A61K31/519 , A61K31/529 , A61K31/70 , A61K31/7008 , A61K33/24 , A61K38/00 , A61K38/21 , A61K39/395 , A61K45/00 , A61K47/48 , A61P35/00 , A61P43/00 , C07K1/22 , C07K14/00 , C07K14/485 , C07K14/495 , C07K14/52 , C07K14/525 , C07K14/54 , C07K14/545 , C07K14/55 , C07K14/555 , C07K14/57 , C07K14/705 , C07K14/715 , C07K16/00 , C07K16/22 , C07K16/28 , C07K16/30 , C07K16/32 , C07K19/00 , C12N5/10 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/573 , G01N33/574 , G01N33/577 , C07K16/46
CPC分类号： C07K16/32 , A61K39/395 , A61K47/48538 , A61K47/48561 , C07K16/22 , C07K16/30 , C07K16/3015 , A61K2039/505 , A61K38/00 , C07K2317/73
摘要： A method of inhibiting growth of tumor cells which overexpress a growth factor receptor or growth factor by treatment of the cells with antibodies which inhibit the growth factor receptor function, is disclosed. A method of treatment tumor cells with antibodies which inhibit growth factor receptor function, and with cytotoxic factor(s) such as tumor necrosis factor, is also disclosed. By inhibiting growth factor receptor functions tumor cells are rendered more susceptible to cytotoxic factors.
摘要翻译：公开了通过用抑制生长因子受体功能的抗体处理细胞来抑制过表达生长因子受体或生长因子的肿瘤细胞生长的方法。还公开了用抑制生长因子受体功能的抗体和细胞毒性因子如肿瘤坏死因子治疗肿瘤细胞的方法。通过抑制生长因子受体功能，肿瘤细胞对细胞毒性因子的敏感性更高。

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