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1. 发明授权

US06960652B2 Compositions and methods for modifying toxic effects of proteinaceous compounds 有权
标题翻译：用于改变蛋白质化合物毒性作用的组合物和方法
公开(公告)号：US06960652B2
公开(公告)日：2005-11-01
申请号：US10282935
申请日：2002-10-29
申请人： Ellen S. Vitetta , Victor F. Ghetie , Joan E. Smallshaw , Roxana G. Baluna
发明人： Ellen S. Vitetta , Victor F. Ghetie , Joan E. Smallshaw , Roxana G. Baluna
IPC分类号： A61K38/00 , A61K38/16 , A61K38/19 , A61K39/02 , A61K39/395 , C07K14/00 , C07K14/415 , C07K14/55 , C07K16/46 , C07K19/00 , G01N20060101
CPC分类号： C07K14/55 , A61K38/162 , A61K38/164 , A61K38/168 , A61K38/47 , A61K47/6813 , A61K47/6827 , A61K47/6849 , C07K16/2803 , C07K2319/00 , C07K2319/30 , C07K2319/55
摘要： The present invention provides methods to produce immunotoxins (ITs) and cytokines with a reduced ability to promote vascular leak syndrome (VLS). The invention also provides ITs and cytokines which have been mutated to lack amino acid sequences which induce VLS.
摘要翻译：本发明提供了产生具有降低的促进血管渗漏综合征（VLS）能力降低的免疫毒素（IT）和细胞因子的方法。本发明还提供已经突变以缺乏诱导VLS的氨基酸序列的IT和细胞因子。

2. 发明授权

US08658168B2 Compositions and methods for homoconjugates of antibodies which induce growth arrest of apoptosis of tumor cells 失效
标题翻译：诱导肿瘤细胞凋亡生长停滞的抗体的同种结合体的组合物和方法
公开(公告)号：US08658168B2
公开(公告)日：2014-02-25
申请号：US10118262
申请日：2002-04-08
申请人： Maria-Ana Ghetie , Jonathan W. Uhr , Ellen S. Vitetta
发明人： Maria-Ana Ghetie , Jonathan W. Uhr , Ellen S. Vitetta
IPC分类号： A61K39/395
CPC分类号： G01N33/574 , A61K38/00 , A61K47/68 , A61K2039/505 , C07K16/00 , C07K16/2803 , C07K16/2896 , C07K16/32 , C07K2317/31 , C07K2317/54 , C07K2317/55 , C07K2317/77
摘要： This invention discloses monoclonal antibodies (MAbs) which have little or no signaling activity as monomers become potent anti-tumor agents when they are converted into homoconjugates. The homoconjugates exert anti-growth activity by signaling G0/G1 arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and does not require an Fc portion. These conjugates are potent, anti-tumor agents.
摘要翻译：本发明公开了具有很少或没有信号传导活性的单克隆抗体（MAb），因为当它们被转化为同型缀合物时，单体成为有效的抗肿瘤剂。根据其结合的细胞表面分子，共轭体通过信号传导G0 / G1停滞或凋亡来发挥抗生长活性。该活动是特异性的，不需要Fc部分。这些缀合物是有效的抗肿瘤剂。

3. 发明授权

US5612185A Method for identifying tumor cells in cell cycle arrest 失效
标题翻译：确定细胞周期停滞中肿瘤细胞的方法
公开(公告)号：US5612185A
公开(公告)日：1997-03-18
申请号：US306525
申请日：1994-09-15
申请人： Jonathan W. Uhr , Ellen S. Vitetta , Louis J. Picker , Richard H. Scheuermann
发明人： Jonathan W. Uhr , Ellen S. Vitetta , Louis J. Picker , Richard H. Scheuermann
IPC分类号： A61K47/48 , C12Q1/68 , G01N33/48 , G01N33/574
CPC分类号： G01N33/57492 , A61K47/48569 , C12Q1/6886 , G01N33/48 , G01N33/5748 , C12Q2600/112 , C12Q2600/136 , Y10S435/973 , Y10S436/813
摘要： Disclosed are methods for the identification and characterization of tumor cell types present within malignant populations, and novel methods of cancer treatment. Tumor cells in cell cycle arrest have been identified, purified and characterized according to their size, altered morphology, surface phenotype and expression of oncogenes. Tumor cell cycle arrest can be induced in mice lacking an immune system solely upon administration of anti-idiotype antibodies. Methods of manipulating specific signals from the cell surface to alter the malignant phenotype of transformed cells are disclosed, as are methods for either eliminating or specifically maintaining tumor cells in cell cycle arrest.
摘要翻译：公开了用于鉴定和表征恶性群体中存在的肿瘤细胞类型的方法，以及新的癌症治疗方法。肿瘤细胞在细胞周期停滞中已被鉴定，纯化，并根据其大小，形态变化，表型表型和癌基因表达进行表征。仅在给予抗独特型抗体时，仅在缺乏免疫系统的小鼠中可诱导肿瘤细胞周期停滞。公开了从细胞表面操纵特异性信号以改变转化细胞的恶性表型的方法，以及在细胞周期停滞中消除或特异性维持肿瘤细胞的方法。

4. 发明授权

US07452971B2 Compositions and methods for modifying toxic effects of proteinaceous compounds 有权
标题翻译：用于改变蛋白质化合物毒性作用的组合物和方法
公开(公告)号：US07452971B2
公开(公告)日：2008-11-18
申请号：US11263537
申请日：2005-10-31
申请人： Ellen S. Vitetta , Victor F. Ghetie , Joan E. Smallshaw , Roxana G. Baluna
发明人： Ellen S. Vitetta , Victor F. Ghetie , Joan E. Smallshaw , Roxana G. Baluna
IPC分类号： A61K38/00 , C07K14/00
CPC分类号： C07K14/55 , A61K38/162 , A61K38/164 , A61K38/168 , A61K38/47 , A61K47/6813 , A61K47/6827 , A61K47/6849 , C07K16/2803 , C07K2319/00 , C07K2319/30 , C07K2319/55
摘要： The present invention provides methods to produce immunotoxins (ITs) and cytokines with a reduced ability to promote vascular leak syndrome (VLS). The invention also provides ITs and cytokines which have been mutated to lack amino acid sequences which induce VLS.
摘要翻译：本发明提供了产生具有降低的促进血管渗漏综合征（VLS）能力降低的免疫毒素（IT）和细胞因子的方法。本发明还提供已经突变以缺乏诱导VLS的氨基酸序列的IT和细胞因子。

5. 发明授权

US07175848B1 Ricin A chain mutants lacking enzymatic activity as vaccines to protect against aerosolized ricin 有权
标题翻译：蓖麻毒素A链突变体缺乏酶活性，作为防止雾化蓖麻毒蛋白的疫苗
公开(公告)号：US07175848B1
公开(公告)日：2007-02-13
申请号：US09698551
申请日：2000-10-26
申请人： Ellen S. Vitetta , Victor F. Ghetie , Joan E. Smallshaw , Roxana G. Baluna
发明人： Ellen S. Vitetta , Victor F. Ghetie , Joan E. Smallshaw , Roxana G. Baluna
IPC分类号： A61K38/16 , A61K39/00 , C07K14/195
CPC分类号： A61K39/00 , A61K38/168
摘要： The present invention provides methods to produce toxoid vaccines, such as ricin A chain vaccines, with reduced ability to promote vascular leak syndrome (VLS) and catalytic toxicity associated with various proteinaceous toxins, such as ribosome inactivating proteins. The invention also provides toxoids which have been mutated to lack amino acid sequences which induce VLS and toxic catalytic activity.
摘要翻译：本发明提供了生产类毒素疫苗的方法，例如蓖麻毒素A链疫苗，其具有降低的促进血管渗漏综合征（VLS）的能力以及与各种蛋白质毒素如核糖体失活蛋白质相关的催化毒性。本发明还提供已被突变以缺乏诱导VLS和毒性催化活性的氨基酸序列的类毒素。

6. 发明授权

US5045451A Methods for screening antibodies for use as immunotoxins 失效
标题翻译：用于筛选用作免疫毒素的抗体的方法
公开(公告)号：US5045451A
公开(公告)日：1991-09-03
申请号：US262974
申请日：1988-10-26
申请人： Jonathan W. Uhr , Ellen S. Vitetta
发明人： Jonathan W. Uhr , Ellen S. Vitetta
IPC分类号： G01N33/50 , G01N33/577
CPC分类号： G01N33/5008 , G01N33/577 , Y10S436/813
摘要： The present disclosure described an assay for screening monoclonal antibodies for their potential as highly cytotoxic immunotoxins. The assay involves treating cells with dilutions of the test antibody followed by a Fab fragment of a secondary antibody coupled to an A chain toxin ("indirect assay"). The cytotoxicity of the indirect assay is compared to that of the direct assay where the monoclonal antibody is coupled to an A chain toxin. Indirect and direct assays were carried out using 14 antibodies and a panel of 8 human and mouse cell types. The two assays showed virtually 100% correlation. The indirect assay, therefore, predicts the potency of a given monoclonal antibody to make an effective immunotoxin and should be useful in screening monoclonal antibodies for use as immunotoxins.
摘要翻译：本公开描述了用于筛选单克隆抗体作为高细胞毒性免疫毒素的潜力的测定法。该测定包括用稀释的测试抗体然后是与A链毒素偶联的二抗的Fab片段（“间接测定”）处理细胞。将间接测定的细胞毒性与单克隆抗体与A链毒素偶联的直接测定的细胞毒性进行比较。使用14种抗体和8种人和小鼠细胞类型进行间接和直接测定。这两种测定显示出几乎100％的相关性。因此，间接测定预测给定单克隆抗体产生有效免疫毒素的效力，并且可用于筛选用作免疫毒素的单克隆抗体。

7. 发明申请

US20120123097A1 RICIN A CHAIN MUTANTS LACKING ENZYMATIC ACTIVITY AS VACCINES TO PROTECT AGAINST AEROSOLIZED RICIN 有权
标题翻译： RICIN A链MUTANTS作为疫苗保护抗敏感RICIN的隐形酶活性
公开(公告)号：US20120123097A1
公开(公告)日：2012-05-17
申请号：US11673981
申请日：2007-02-12
申请人： Ellen S. Vitetta , Victor F. Ghetie , Joan E. Smallshaw , Roxana G. Baluna
发明人： Ellen S. Vitetta , Victor F. Ghetie , Joan E. Smallshaw , Roxana G. Baluna
IPC分类号： C07K14/42 , C07K14/21 , C07K14/415
CPC分类号： A61K39/00 , A61K38/168
摘要： The present invention provides methods to produce toxoid vaccines, such as ricin A chain vaccines, with reduced ability to promote vascular leak syndrome (VLS) and catalytic toxicity associated with various proteinaceous toxins, such as ribosome inactivating proteins. The invention also provides toxoids which have been mutated to lack amino acid sequences which induce VLS and toxic catalytic activity.
摘要翻译：本发明提供了生产类毒素疫苗的方法，例如蓖麻毒素A链疫苗，其具有降低的促进血管渗漏综合征（VLS）的能力以及与各种蛋白质毒素如核糖体失活蛋白质相关的催化毒性。本发明还提供已被突变以缺乏诱导VLS和毒性催化活性的氨基酸序列的类毒素。

8. 发明授权

US07668603B2 Medical composition employing nanostructures 失效
标题翻译：采用纳米结构的医学成分
公开(公告)号：US07668603B2
公开(公告)日：2010-02-23
申请号：US11343253
申请日：2006-01-26
申请人： Robert C Stirbl , Malcolm L Snead , Jimmy Xu , Ellen S Vitetta , Peter J Wilk
发明人： Robert C Stirbl , Malcolm L Snead , Jimmy Xu , Ellen S Vitetta , Peter J Wilk
IPC分类号： A61K9/16 , B01J13/00
CPC分类号： B82Y5/00 , A61K47/6923 , A61K47/6957 , A61N1/37205 , Y10S977/701
摘要： A composition of microscopic devices utilizable in a medical diagnostic or therapeutic procedure. Each microscopic device includes a nanostructure provided with a ligand for effectively coupling the nanostructure to a predetermined chemical or molecular site. A medical method in part comprises inserting the medical devices into a patient, attaching the nanostructures via the respective ligands to instances of a predetermined type of target structure inside the patient, and thereafter activating the nanostructures to perform a preselected medical diagnostic or therapeutic function.
摘要翻译：在医学诊断或治疗过程中可用的微观装置的组合物。每个微观器件包括具有用于有效地将纳米结构偶联到预定化学或分子部位的配体的纳米结构。医疗方法部分地包括将医疗装置插入患者体内，通过相应配体将纳米结构连接到患者体内的预定类型的靶结构的实例，然后激活纳米结构以执行预选的医学诊断或治疗功能。

9. 发明授权

US5767072A Therapeutic compositions comprising a CD4 peptide and methods of treatment of HIV infections 失效
标题翻译：包含CD4肽的治疗组合物和治疗HIV感染的方法
公开(公告)号：US5767072A
公开(公告)日：1998-06-16
申请号：US171206
申请日：1993-12-21
申请人： Ellen S. Vitetta , Jonathan W. Uhr
发明人： Ellen S. Vitetta , Jonathan W. Uhr
IPC分类号： A61K47/48 , A61K38/10 , A61K38/16
CPC分类号： A61K47/48276
摘要： Disclosed are methods and compositions for the treatment of HIV infections through the specific elimination of cells which express HIV env determinants such as gp120. The compositions of the invention include toxin conjugates composed of a CD4 derived gp120 binding ligand conjugated to a toxin A chain moiety such as ricin A chain or deglycosylated ricin A chain. Where a therapeutic composition is desired, the conjugates are formed by means of a cross linker which includes a disulfide bond. Disulfide linkages are not crucial where non-therapeutic uses, such as antibody generation, is intended. In preferred aspects of the invention, conjugates incorporating shorter CD4 peptides, such as those incorporating amino acids 41-57 or 41-84 of CD4, are disclosed. Therapeutic amounts of conjugates composed of soluble CD4 or a CD4 peptide cross-linked to deglycosylated A chain by means of as SMPT linker is administered to an HIV infected patient so as to specifically eliminate HIV infected cells without exerting significant toxicity against uninfected or class II cells.
摘要翻译：公开了通过特异性消除表达HIV环境因子如gp120的细胞来治疗HIV感染的方法和组合物。本发明的组合物包括由与CD4毒素A链部分（例如蓖麻毒素A链或去糖基化的蓖麻毒素A链）缀合的CD4衍生的gp120结合配体组成的毒素缀合物。当需要治疗组合物时，通过包含二硫键的交联剂形成缀合物。在非治疗用途，如产生抗体的情况下，二硫键不是至关重要的。在本发明的优选方面，公开了结合较短CD4肽的缀合物，例如掺入CD4的氨基酸41-57或41-84的那些。通过作为SMPT接头的可溶性CD4或与去糖基化A链交联的CD4肽组成的缀合物的治疗量被施用于HIV感染的患者，以特异性地消除HIV感染的细胞，而不对未感染或II类细胞产生显着的毒性。

10. 发明授权

US5578706A Methods and compositions concerning homogenous immunotoxin preparations 失效
标题翻译：关于均质免疫毒素制剂的方法和组成
公开(公告)号：US5578706A
公开(公告)日：1996-11-26
申请号：US147768
申请日：1993-11-04
申请人： Victor F. Ghetie , Jonathan W. Uhr , Ellen S. Vitetta
发明人： Victor F. Ghetie , Jonathan W. Uhr , Ellen S. Vitetta
IPC分类号： A61K47/48 , C07K16/28 , C07K16/46
CPC分类号： A61K47/48561 , A61K47/48476 , C07K16/2803
摘要： Immunotoxin preparations are described in which the preparations are enriched for a single species of immunotoxin. Also described are methods for the preparation of the substantially purified immunotoxins (ITs). Also disclosed are methods for determining the most effective species of immunotoxin conjugates for treated diseases and pharmaceutical preparations for such treatments.
摘要翻译：描述了免疫毒素制剂，其中制备物富集单种免疫毒素。还描述了制备基本纯化的免疫毒素（IT）的方法。还公开了用于确定治疗疾病的最有效种类的免疫毒素缀合物和用于这种治疗的药物制剂的方法。

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